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Effectiveness and safety of acupuncture for treating functional constipation: An overview of systematic reviews
Jun-peng Yao, Li-ping Chen, Xian-jun Xiao, Ting-hui Hou, Si-yuan Zhou, Ming-min Xu, Kai Wang, Yu-jun Hou, Lin Zhang, Ying Li
Journal of Integrative Medicine    2022, 20 (1): 13-25.   DOI: 10.1016/j.joim.2021.11.001
Online available: 16 November 2021

Abstract1254)   HTML    PDF      

Background

Functional constipation (FC) is one of the most prevalent functional gastrointestinal disorders. Dissatisfaction with medications prescribed to treat FC may lead patients to seek alternative treatments. Numerous systematic reviews (SRs) examining the use of acupuncture to treat FC have reported inconsistent results, and the quality of these studies has not been fully evaluated.

Objective

In this overview, we evaluated and summarized clinical evidence on the effectiveness and safety of acupuncture for treating FC and evaluated the quality and bias of the SRs we reviewed.

Search strategy

The search strategy was structured by medical subject headings and search terms such as “acupuncture therapy” and “functional constipation.” Electronic searches were conducted in eight databases from their inception to September 2020.

Inclusion criteria

SRs that investigated the effectiveness and safety of acupuncture for managing FC were included.

Data extraction and analysis

Two authors independently extracted information and appraised the methodology, reporting accuracy, quality of evidence, and risk of bias using the following critical appraisal tools: (1) A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2); (2) Risk of Bias in Systematic Reviews (ROBIS); (3) Preferred Reporting Items for Systematic Reviews and Meta-analyses for Acupuncture (PRISMA-A); and (4) the Grading of Recommendations, Assessment, Development and Evaluations (GRADE). A κ index was used to score the level of agreement between the 2 reviewers.

Results

Thirteen SRs that examined the clinical utility of acupuncture for treating FC were identified. Using the AMSTAR 2 tool, we rated 92.3% (12/13) of the SRs as “critically low” confidence and one study as “low” confidence. Using the ROBIS criteria, 38.5% (5/13) of the SRs were considered to have “low risk” of bias. Based on PRISMA-A, 76.9% (10/13) of the SRs had over 70% compliance with reporting standards. The inter-rater agreement was good for AMSTAR 2, ROBIS, and PRISMA-A. Using the GRADE tool, we classified 22.5% (9/40) of the measured outcomes as “moderate” quality, 57.5% (23/40) as “low” quality, and 20.0% (8/40) as “very low” quality. The inter-rater agreement was moderate when using GRADE. Descriptive analyses indicated that acupuncture was more efficacious than sham acupuncture for improving weekly complete spontaneous bowel movements (CSBMs) and for raising the Bristol Stool Form Scale (BSFS) score. Acupuncture appeared to be superior to anti-constipation drugs for improving weekly spontaneous bowel movements, the total effective rate, and the Patient Assessment of Constipation Quality of Life score. Although ten SRs mentioned the occurrence of adverse events, serious adverse events were not associated with acupuncture treatment.

Conclusion

Acupuncture may be more efficacious than sham acupuncture for improving CSBMs and BSFS scores and may be superior to anti-constipation drugs for improving bowel movement frequency, as well as quality of life. Limitations to current studies and inconsistent evidence suggest a need for more rigorous and methodologically sound SRs to draw definitive conclusions.

Systematic review registration

PROSPERO CRD42020189173.

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Rauwolfia vomitoria extract suppresses benign prostatic hyperplasia by reducing expression of androgen receptor and 5α-reductase in a rat model
Tian Fang, Ze-sheng Xue, Jia-xuan Li, Jia-kuan Liu, Di Wu, Mei-qian Li, Yu-ting Song, Shi-feng Yun, Jun Yan
Journal of Integrative Medicine    2021, 19 (3): 258-264.   DOI: 10.1016/j.joim.2020.12.002
Online available: 10 December 2020

Abstract586)   HTML    PDF      
Objective
Herbal medicine is an important therapeutic option for benign prostatic hyperplasia (BPH), a common disease in older men that can seriously affect their quality of life. Currently, it is crucial to develop agents with strong efficacy and few side effects. Herein we investigated the effects of the extract of Rauwolfia vomitoria, a shrub grown in West Africa, on BPH.
Methods
Rats with testosterone-induced BPH were treated with R. vomitoria. Prostates were histologically analyzed by hematoxylin and eosin staining. Proliferation index and the expression levels of androgen receptor and its associated proteins were quantified through immunohistochemistry and immunoblotting. Androgen receptor target genes were examined by quantitative real-time polymerase chain reaction. The sperm count and body weight of rats were also measured.
Results
The oral administration of R. vomitoria extract significantly reduced the prostate weight and prostate weight index in BPH rats, supported by the decreased thickness of the prostate epithelial layer and increased lumen size. Similar effects were observed in the BPH rats treated with the reference drug, finasteride. R. vomitoria extract significantly reduced the testosterone-induced proliferation markers, including proliferating cell nuclear antigen and cyclin D1, in the prostate glands of BPH rats; it also reduced levels of androgen receptor, its associated protein steroid 5α-reductase 1 and its downstream target genes (FK506-binding protein 5 and matrix metalloproteinase 2). Notably, compared with the finasteride group, R. vomitoria extract did not significantly reduce sperm count. 
Conclusion
R. vomitoria suppresses testosterone-induced BPH development. Due to its milder side effects, R. vomitoria could be a promising therapeutic agent for BPH.
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Using weighted blankets in an inpatient mental health hospital to decrease anxiety
Annette L. Becklund, Lisa Rapp-McCall, Jessica Nudo
Journal of Integrative Medicine    2021, 19 (2): 129-134.   DOI: 10.1016/j.joim.2020.11.004
Accepted: 13 October 2020
Online available: 28 November 2020

Abstract424)   HTML    PDF      
Objective
Patients who are involuntarily committed to a psychiatric facility often experience anxiety or increased anxiety in response to being placed in the institutional environment. The weighted blanket introduced a proactive treatment option. The purpose of this study was to evaluate patients' anxiety symptoms before and after weighted blanket, compared to a group that did not use a weighted blanket to control anxiety.

Methods
This study was conducted in an inpatient mental health facility from June 10, 2019, through November 7, 2019, with psychiatric patients who were not actively psychotic. Participants were offered the choice of weighted or unweighted blankets for a 20-minute intervention. The treatment group was comprised of individuals who had opted to use a 14-pound weighted blanket, 20-pound weighted blanket or 5-pound weighted lap pad. Participants in the comparison group had selected an un-weighted blanket. Before application of the blankets, pulse rate was measured using a pulse oximeter, and anxiety was measured using the Spielberger State-Trait Anxiety Inventory shortened form (STAI: Y-6). Both measures were taken again after the intervention. A two-way mixed analysis of variance (ANOVA) was run to examine the interaction effects between time (pre/post) and group (comparison/weighted blanket). Simple main effects were then further examined for the comparison/weighted blanket groups using a repeated measures ANOVA. Within the weighted blanket group, additional two-way mixed ANOVA was run to determine if gender or blanket weight made a statistically significant difference.

Results
There was a statistically significant difference (P < 0.05) among those who used weighted blankets (n = 61) and those who did not (n = 61) based on the pre/post data for both the STAI: Y-6 inventory and the patients’ pulse rates. The results of two-way ANOVA indicated a significant interaction effect between intervention time and group (P < 0.001). Repeated measures ANOVA indicated a change between pre/post for the weighted blanket group only, and showed significant reductions in both the STAI: Y-6 (P < 0.001) and pulse rates (P = 0.040). Within the weighted blanket group, additional two-way mixed ANOVA showed that neither gender nor blanket weight had significant difference for either the STAI: Y-6 or the pulse measures.

Conclusion
The use of weighted blankets is a safe and potentially effective way to help individuals in a psychiatric facility manage anxiety. This study found a statistically significant drop in anxiety for adults at an inpatient facility, as shown by the STAI: Y-6 scores and drop in pulse rates among patients using weighted blankets. This study suggests a possible alternative to medications, seclusion and physical restraints, which are not patient- centered or trauma-supported.
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Searching for the emotional roots of breast cancer: A cross-disciplinary analysis integrating psychology, Chinese medicine, and oncology biomarkers
Ofer Baranovitch, Meirav Wolff-Bar, Meora Feinmesser, Chen Sade-Zaltz, Ilan Tsarfaty, Victoria Neiman
Journal of Integrative Medicine    2022, 20 (1): 57-64.   DOI: 10.1016/j.joim.2021.11.005
Online available: 22 November 2021

Abstract359)   HTML    PDF      

Objective

We employed a multidisciplinary approach incorporating theoretical ideas, clinical experience, psychology, physiology, traditional Chinese medicine (CM), modern practice of CM, and oncology to explore the effect of patients’ repression of negative emotions and traumatic events on breast cancer (BC) pathogenesis.

Methods

BC female patients, older than 18 years of age, with available pathology reports who were treated at Rabin Medical Center were recruited. All participants completed questionnaires regarding medical history, behavioral tendencies, negative emotions, trauma, symptoms, and pathology (from a CM perspective). Data on tumor characteristics were collected from the pathology reports. The associations were examined using hierarchical binary logistic regressions. 

Results

A total of 155 BC patients were enrolled. The median age was 52 years, with a range of 26–79; 95% were mothers; 28% had estrogen receptor (ER)-negative BC, 52% had progesterone receptor (PR)-negative BC, 48% had human epidermal growth factor receptor 2-negative BC, and antigen Ki-67 ≥ 20% was reported for 52% of tumors. Statistically significant associations were found between the emotional markers (sense of motherhood failure, and lack of self-fulfillment), avoidance behavior, and physical symptoms that are related to emotional repression based on CM. Significant associations were also found between variables associated with physical symptoms of emotional repression, which involves the production and accumulation of non-substantial phlegm (i.e., “high-lipid Qi-like microscopic phlegm”), avoidance behavior which unconsciously uses “high-lipid Qi-like microscopic phlegm” in order to achieve emotional repression, and tumor parameters including tumor grade, PR status, and Ki-67. Patients with higher levels of “high-lipid Qi-like microscopic phlegm” were more likely to have tumors with worse prognosis (PR-negative, higher grade, and higher Ki-67). 

Conclusion

We demonstrated a relationship between emotional parameters, behavioral tendencies, CM parameters, and oncologic parameters in BC. Additional research is warranted to explore these associations and their relevance to clinical practice. 

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An overview of the anti-SARS-CoV-2 properties of Artemisia annua, its antiviral action, protein-associated mechanisms, and repurposing for COVID-19 treatment
Andréa D. Fuzimoto
Journal of Integrative Medicine    2021, 19 (5): 375-388.   DOI: 10.1016/j.joim.2021.07.003
Online available: 30 September 2021

Abstract317)   HTML    PDF      
Artemisia annua and its phytocompounds have a rich history in the research and treatment of malaria, rheumatoid arthritis, systemic lupus erythematosus, and other diseases. Currently, the World Health Organization recommends artemisinin-based combination therapy as the first-line treatment for multi-drug-resistant malaria. Due to the various research articles on the use of antimalarial drugs to treat coronaviruses, a question is raised: do A. annua and its compounds provide anti-severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) properties. PubMed/MEDLINE, Scopus, and Google Scholar were searched for peer-reviewed articles that investigated the antiviral effects and mechanisms of A. annua and its phytochemicals against SARS-CoVs. Particularly, articles that studied the herb’s role in inhibiting the coronavirus-host proteins were favored. Nineteen studies were retrieved. From these, fourteen in silico molecular docking studies demonstrated potential inhibitory properties of artemisinins against coronavirus-host proteins, including 3CLPRO, S protein, N protein, E protein, cathepsin-L, helicase protein, nsp3, nsp10, nsp14, nsp15, and GRP78 receptor. Collectively, A. annua constituents may impede the SARS-CoV-2 attachment, membrane fusion, and internalization into the host cells, and hinder the viral replication and transcription process. This is the first comprehensive overview of the application of compounds from A. annua against SARS-CoV-2/coronavirus disease 2019 (COVID-19) describing all target proteins. A. annua’s biological properties, the signaling pathways implicated in the COVID-19, and the advantages and disadvantages for repurposing of A. annuacompounds are discussed. The combination of A. annua’s biological properties, action on different signaling pathways and target proteins, and a multi-drug combined-therapy approach may synergistically inhibit SARS-CoV-2 and assist in the COVID-19 treatment. Also, A. annua may modulate the host immune response to better fight the infection. 
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Efficacy and safety of Shenyankangfu Tablet, a Chinese patent medicine, for primary glomerulonephritis: A multicenter randomized controlled trial
Jie Wu, Shu-wei Duan, Hong-tao Yang, Yue-yi Deng, Wei Li, Ya-ni He, Zhao-hui Ni, Yong-li Zhan, Shan Lin, Zhi-yong Guo, Jun Zhu, Jing-ai Fang, Xu-sheng Liu, Li-hua Wang, Rong Wang, Nian-song Wang, Xiao-hong Cheng, Li-qun He, Ping Luo, Shi-ren Sun s, Ji-feng Sun, Ai-ping Yin, Geng-ru Jiang, Hong-yu Chen, Wen-hu Liu, Hong-li Lin, Meng Liang, Lu Ma, Ming Chen, Li-qun Song, Jian Chen, Qing Zhu, Chang-ying Xing, Yun Li, Ji-ning Gao, Rong-shan Li, Ying Li, Hao Zhang, Ying Lu, Qiao-ling Zhou, Jun-zhou Fu, Qiang He, Guang-yan Cai, Xiang-mei Chen
Journal of Integrative Medicine    2021, 19 (2): 111-119.   DOI: 10.1016/j.joim.2021.01.009
Accepted: 16 December 2020
Online available: 30 January 2021

Abstract309)   HTML    PDF      
Background
Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease.

Objective
This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium.

Design, setting, participants and intervention
This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18–70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m2, and 24-hour proteinuria level of 0.5–3.0 g, were recruited in 41 hospitals across 19 provinces in China and were randomly divided into five groups: SYKFT, losartan potassium 50 mg or 100 mg, SYKFT plus losartan potassium 50 mg or 100 mg.

Main outcome measures
The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment.

Results
A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (= 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group.

Conclusion
SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone.

Trial registration number
NCT02063100 on ClinicalTrials.gov.
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Perioperative transcutaneous electrical acupoint stimulation for improving postoperative gastrointestinal function: A randomized controlled trial
Wen-jing Li, Chao Gao, Li-xin An, Yu-wei Ji, Fu-shan Xue, Yi Du
Journal of Integrative Medicine    2021, 19 (3): 211-218.   DOI: 10.1016/j.joim.2021.01.005
Accepted: 16 November 2020
Online available: 13 January 2021

Abstract210)   HTML    PDF      

Background 

Postoperative gastrointestinal dysfunction (PGD) is one of the most common complications in patients undergoing major abdominal surgery. Acupuncture has been used widely in gastrointestinal diseases due to its effectiveness and minimally invasive nature.


Objective

This study evaluated the efficacy of using transcutaneous electrical acupoint stimulation (TEAS) during the surgery and postoperative recovery in patients with gastric and colorectal surgery for improving postoperative gastrointestinal function.


Design, setting, participants and interventions

A total of 280 patients undergoing abdominal surgery were stratified by type of surgery (i.e., gastric or colorectal surgery) and randomly allocated into the TEAS group (group T) or the sham group (group S). Patients in group T received TEAS at LI4, PC6, ST36 and ST37. Patients in group S received pseudo-TEAS at sham acupoints. The stimulation was given from 30 min before anesthesia until the end of surgery. The same treatment was performed at 9 am on the 1st, 2nd and 3rd days after surgery, until the recovery of flatus in patients.


Main outcome measures

The primary outcome was the time to the first bowel motion, as detected by auscultation. The secondary outcomes included the first flatus and ambulation time, changes of perioperative substance P (SP), incidence of PGD, postoperative pain, postoperative nausea and vomiting (PONV) and some economic indicators.


Results

The time to first bowel motion, first flatus and first ambulation in group T was much shorter than that in group S (P < 0.01). In patients undergoing colorectal surgery, the concentration of SP was lower in group T than in group S on the third day after the operation (P < 0.05). The average incidence of PGD in all patients was 25%, and the frequency of PGD was significantly lower in group T than in in group S (18.6% vs. 31.4%, respectively; P < 0.05). TEAS treatment (odds ratio = 0.498; 95% confidence interval: 0.232–0.786) and type of surgery were relevant factors for the development of PGD. Postoperative pain score and PONV occurrence were significantly lower in group T (P < 0.01). Postoperative hospitalization days and the resulting cost to patients were greatly reduced in the TEAS group (P < 0.01).


Conclusion

Perioperative TEAS was able to promote the recovery of postoperative gastrointestinal function, reduce the incidence of PGD and PONV. The concentration of SP was decreased by TEAS treatment, which indicates that the brain-gut axis may play a role in how TEAS regulates gastrointestinal function.


Trial registration

Chinese Clinical Trial Registry, ChiCTR1900023263.

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Traditional Chinese medicine is a useful and promising alternative strategy for treatment of Sjogren's syndrome: A review
Shu-jun Wei, Qing-man He, Qing Zhang, Kang-hua Fu, Ruo-lan Li, Wei Peng, Yong-xiang Gao
Journal of Integrative Medicine    2021, 19 (3): 191-202.   DOI: 10.1016/j.joim.2021.01.008
Accepted: 11 November 2020
Online available: 14 January 2021

Abstract162)   HTML    PDF      
Primary Sjogren's syndrome (pSS) is a chronic autoimmune disease involving exocrine glands. Current studies have found that the occurrence of the disease is closely related to genetic, environmental and neuroendocrine factors, as well as abnormal activation of T and B lymphocytes. The etiology and pathogenesis of pSS is complex, and there is a lack of specific targeted drugs. Traditional Chinese medicines (TCMs) have been comprehensively investigated for their treatment effects on pSS. Through a systematic review of the literature, we summarized the TCMs used to treat pSS, and find that there are four major ways that TCMs are used, including upregulation of aquaporin proteins, suppression of cell apoptosis, suppression of the abnormal activation of B lymphocytes and suppression of the abnormal activation of T lymphocytes (balancing T helper type [Th]1/Th2 & Th17/Treg and suppressing follicular helper T [Tfh] cells). However, there are not enough data about the active constituents, quality control, pharmacokinetics, toxicity and modern preparations of these TCMs; therefore, more investigations are needed. This paper highlights the importance of TCMs for treating pSS and provides guidance for future investigations.
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Effects of traditional Chinese exercises and general aerobic exercises on older adults with sleep disorders: A systematic review and meta-analysis
Yang-hao-tian Wu, Wen-bo He, Yin-yan Gao, Xue-mei Han
Journal of Integrative Medicine    2021, 19 (6): 493-502.   DOI: 10.1016/j.joim.2021.09.007
Online available: 09 October 2021

Abstract159)           

Background

Sleep disorders are common in older adults and have a negative influence on their physical and mental health. General aerobic exercises (GAEs) have long been used in the treatment of sleep disorders as a non-pharmacological measure. However, there is no consensus on the efficacy of traditional Chinese exercises (TCEs) for treating sleep disorders in older adults and the difference between TCEs and GAEs.

Objective

This study assessed the effects of TCEs and GAEs on the sleep quality of older adults and the differences between these two interventions.

Search strategy

PubMed, Embase, Cochrane Library, Web of Science, China Biology Medicine disc, China National Knowledge Infrastructure, China Science Journal Database and Wanfang Data were searched from their inception to August 2020. 

Inclusion criteria

Randomized controlled trials (RCTs) that evaluated the effects of TCEs and GAEs on older adults with sleep disorders were included. 

Data extraction and analysis

Data were extracted by two researchers working independently. The risk bias of included studies was assessed using the Cochrane Handbook for Systematic Reviews of Interventions 5.1.0 and the quality of evidence was assessed using the Grades of Recommendation, Assessment, Development and Evaluation approach. The Pittsburgh Sleep Quality Index (PSQI) was used to estimate sleep quality. Meta-analyses were performed to assess the total PSQI score of the exercise intervention as the primary outcome, and the scores of subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, use of sleep medication and daytime dysfunction were assessed as secondary outcomes. Subgroup, sensitivity, and meta-regression analyses were conducted to assess the contribution of covariables to heterogeneity.

Results

A total of 22 RCTs (including 1747 participants) were included in the meta-analysis. The results indicated that TCEs (weighted mean difference [WMD] = –2.14, 95% confidence interval [CI] [–2.82, –1.46], P < 0.001; heterogeneity: P < 0.001, I2 = 82%; 15 studies, n = 1063) and GAEs (WMD = –2.88, 95% CI [–5.22, –0.55], P  < 0.001; heterogeneity: P  < 0.001, I2 = 98%; 5 studies, n = 500) significantly improved total sleep quality, having favorable effects on subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, use of sleep medication and daytime dysfunction. Subgroup analysis showed that TCEs demonstrated superiority after 12 weeks (WMD = –2.77, 95% CI [–4.26, –1.28], P  < 0.001; heterogeneity: P  < 0.001, I2 = 85%; 5 studies, n = 420) and Qigong had a greater intervention effect for improving the sleep quality of older adults than Tai Chi (WMD = –3.37, 95% CI [–4.38, –2.35], P  < 0.001; heterogeneity: P  = 0.04, I2 = 63%; 4 studies, n = 321). Meta-regression revealed that the year of publication, sample size, mean age of participants, and percentage of females in the primary studies did not account for the overall heterogeneity.

Conclusion

Current evidence shows that both TCEs and GAEs, as complementary and non-pharmacological approaches, help to improve the sleep quality in older adults with potentially clinical implications; however, there was not enough evidence to conclude the difference between them. More rigorous and high-quality RCTs are needed to arrive at reliable conclusions.

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Knowledge about, attitude and acceptance towards, and predictors of intention to receive the COVID-19 vaccine among cancer patients in Eastern China: A cross-sectional survey
Jing Hong, Xiao-wan Xu, Jing Yang, Jing Zheng, Shu-mei Dai, Ju Zhou, Qing-mei Zhang, Yi Ruan, Chang-quan Ling
Journal of Integrative Medicine    2022, 20 (1): 34-44.   DOI: 10.1016/j.joim.2021.10.004
Accepted: 11 October 2021
Online available: 26 October 2021

Abstract154)   HTML    PDF      
Objective
The coronavirus disease 2019 (COVID-19) pandemic has had a serious impact on health all over the world. Cancer patient, whose immunity is often compromised, faces a huge challenge. Currently, some COVID-19 vaccines are being developed and applied on general population; however, whether cancer patients should take COVID-19 vaccine remains unknown. Our study aimed to explore the knowledge, attitude, acceptance, and predictors of intention to receive the COVID-19 vaccine among cancer patients in Eastern China.

Methods
A cross-sectional study was conducted in Eastern China from June 17th to September 3rd, 2021. Patients were selected using a convenience sampling method. A self-report questionnaire was developed to assess knowledge about the COVID-19 vaccine, attitude towards the vaccine and acceptance of the vaccine; following a review of similar studies previously published in the scientific literature, multivariate logistic regression analysis was used to determine the predictors associated with COVID-19 vaccine acceptance.

Results
A total of 2158 cancer patients were enrolled in this study. The rate of vaccine hesitancy was 24.05% (519/2158); further, among the participants of vaccine acceptance, 767 had taken COVID-19 vaccine (35.54%), and 872 were willing to get vaccinated (40.01%). A total of 24 variables including demographic characteristics, clinical status of cancer, impact of COVID-19 pandemic on study participants, patients’ knowledge about the COVID-19 vaccine, and attitude towards the vaccine, had significant differences between the “vaccine hesitancy” population and “vaccine acceptance” population. Multivariate logistic regression analysis indicated that parameters including alcohol consumption (odds ratio [OR] = 1.849; 95% confidence interval [CI]: 1.375–2.488; P-Ref < 0.001 vs non-drinkers), income impacted by COVID-19 pandemic (OR = 1.930, 2.037 and 2.688 for mild, moderate, and severe impact, respectively; all P-Ref < 0.01 vs no impact), knowledge of how the vaccine was developed (OR = 1.616; 95% CI: 1.126–2.318; P-Ref = 0.009 vs unknown), believing in the safety of the vaccine (OR = 1.502; 95% CI: 1.024–2.203; P-Ref = 0.038 vs denying the safety of vaccine), willingness to pay for the vaccine (OR = 3.042; 95% CI: 2.376–3.894; P-Ref < 0.001 vs unwilling), and willingness to recommend families and friends to get vaccinated (OR = 2.744; 95% CI: 1.759–4.280; P-Ref < 0.001 vs do not recommend) were contributors to vaccine acceptance. While such as being retired (OR = 0.586; 95% CI: 0.438–0.784; P-Ref < 0.001 vs unemployed), undergoing multiple therapies of cancer (OR = 0.408; 95% CI: 0.221–0.753; P-Ref = 0.004 vs no ongoing treatment), and worrying that the vaccine might deteriorate the prognosis of cancer (OR = 0.393; 95% CI: 0.307–0.504; P-Ref < 0.001 vs might not) were contributors to vaccine hesitancy.

Conclusion
This study provided preliminary estimates of the rates of vaccine acceptance and vaccine hesitancy among cancer patients in Eastern China. The intention to receive the COVID-19 vaccine was impacted by factors such as patient occupation, alcohol consumption, and some parts of knowledge about and attitude towards COVID-19 vaccine. It is recommended to develop individualized vaccination plans that meet the healthcare needs of cancer patients.
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Effects of mild moxibustion on intestinal microbiome and NLRP3 inflammasome in rats with 5-fluorouracil-induced intestinal mucositis
Bing-rong Li, Shi-yun Shao, Long Yuan, Ru Jia, Jian Sun, Qing Ji, Hua Sui, Li-hong Zhou, Yi Zhang, Hui Liu, Qi Li, Yan Wang, Bi-meng Zhang
Journal of Integrative Medicine    2021, 19 (2): 144-157.   DOI: 10.1016/j.joim.2020.12.004
Online available: 13 December 2020

Abstract148)   HTML    PDF      
Objective
The present study investigated how mild moxibustion treatment affects the intestinal microbiome and expression of NLRP3-related immune factors in a rat model of intestinal mucositis (IM) induced with 5-fluorouracil (5-Fu).
Methods
Forty male Sprague-Dawley rats were randomly divided into control, chemotherapy, moxibustion and probiotics groups. The IM rat model was established by intraperitoneal injection of 5-Fu. Mild moxibustion treatment and intragastric probiotic administration were provided once daily for 15 days. Tissue morphology, serum levels of inflammatory factors and the expression levels of tight junction proteins, caspase-1, gasdermin D and NLRP3 were evaluated in colon tissue, through hematoxylin and eosin staining, electron microscopy, enzyme-linked immunosorbent assay, Western blotting, quantitative real-time reverse transcription polymerase chain reaction and immunofluorescence. Gut microbiome profiling was conducted through 16S rRNA amplicon sequencing.
Results
Moxibustion and probiotic treatments significantly increased the expression levels of tight junction proteins, reduced cell apoptosis and the expression levels of caspase-1, gasdermin D and NLRP3; they also decreased the serum levels of tumor necrosis factor-α, interleukin (IL)-6, IL-1β and IL-18, while increasing serum levels of IL-10. Moxibustion and probiotic treatments also corrected the reduction in α-diversity and β-diversity in IM rats, greatly increased the proportion of the dominant bacterial genus Lactobacillus and reduced the abundance of the genera Roseburia and Escherichia in chemotherapy-treated rats to levels observed in healthy animals. We also found that these dominant genera were firmly correlated with the regulation of pyroptosis-associated proteins and inflammatory factors. Finally, moxibustion and probiotic treatments elicited similar effects in regulating intestinal host-microbial homeostasis and the expression of NLRP3 inflammasome-related factors.
Conclusion
Moxibustion exerts its therapeutic effect on IM by ameliorating mucosal damage and reducing inflammation. Moreover, moxibustion modulates the gut microbiota, likely via decreasing the expression levels of the NLRP3 inflammasome.
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Therapeutic effects of herbal formula Huangqisan on metabolic disorders via SREBF1, SCD1 and AMPK signaling pathway
Ya-lei Liu, Zhen-yu Zhou, Min Gao, Guang Ji, Cheng Huang, Sheng-jie Fan
Journal of Integrative Medicine    2021, 19 (2): 167-176.   DOI: 10.1016/j.joim.2020.11.002
Accepted: 08 May 2020
Online available: 20 November 2020

Abstract142)   HTML    PDF      
Objective
Metabolic syndrome is a complex medical condition that has become an alarming epidemic, but an effective therapy for this disease is still lacking. The use of the herbal formula Huangqisan (HQS) to treat diabetes is documented in the Chinese medical literature as early as 1117 A.D.; however, its therapeutic effects and underlying mechanisms remain elusive.

Methods
To investigate the beneficial effects of HQS on metabolic disorders, high-fat diet-induced obesity (DIO), leptin receptor dysfunction (db/db) and low-density lipoprotein receptor-knockout (LDLR-/-) mice were used. Obese mice were treated with either HQS or vehicle. Blood, liver tissue, white fat tissue and brown adipose tissue were harvested at the end of the treatment. Metabolic disease-related parameters were evaluated to test HQS’s effects against diabetes, obesity and hyperlipidemia. Aortic arches from LDLR-/- mice were analyzed to investigate the effects of HQS on atherosclerosis. RNA-sequence, quantitative real-time polymerase chain reaction and Western blot were performed to investigate the mechanisms of HQS against metabolic disorder.

Results
HQS lowered body weight, fasting blood glucose and serum lipid levels and improved glucose tolerance and insulin sensitivity in DIO mice and db/db mice (P < 0.05). HQS also blocked atherosclerotic plaque formation in LDLR-/- mice. HQS suppressed de novo lipid synthesis by reducing the expression of messenger RNA for sterol regulatory element-binding factor 1, stearyl coenzyme A desaturase 1 and fatty acid synthase, and enhancing adenosine 5'-monophosphate-activated protein kinase signaling in both in vivo and in vitro experiments, indicating potential mechanisms for HQS’s activity against diabetes.

Conclusion
HQS is effective for reversing metabolic disorder and has the potential to be used as therapy for metabolic syndrome.
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Consensus views on competencies and teaching methods for an interprofessional curriculum on complementary and integrative medicine: A Delphi study
Angelika Homberg, Katja Krug, Nadja Klafke, Katharina Glassen, Cornelia Mahler, Svetla Loukanova
Journal of Integrative Medicine    2021, 19 (3): 282-290.   DOI: 10.1016/j.joim.2021.03.001
Accepted: 03 February 2021
Online available: 11 March 2021

Abstract138)   HTML    PDF      
Objective
A collaborative team is necessary to help patients achieve their healthcare goals using complementary medicine. At present, healthcare professionals do not feel sufficiently qualified to provide this service. This study sought to identify competencies and teaching methods for interprofessional training on complementary and integrative medicine at medical schools.

Methods
Sixty-five German-speaking experts with various professional backgrounds were invited to take part in a three-round Delphi study. In the first round, predefined competencies were assessed on a seven-point Likert scale, and participants were invited to propose additional competencies that would be evaluated in the subsequent rounds. The competencies were ranked based on the participant assessments and were assigned to four relevance groups. In the second and third rounds, suitable teaching methods were identified using free-text fields and multiple-choice questions. In a final workshop, participants synthesized the outcomes of the previous sessions and derived key competencies that would be a benefit to undergraduate interprofessional training in complementary and integrative medicine at medical schools.

Results
The three rounds plus final worksop were attended by 50, 40, 36 and 11 experts. The competencies that these experts determined to be highly relevant to teaching complementary and integrative medicine emphasized, in particular, the respectful treatment of patients and the importance of taking a medical history. From these highly relevant competencies, three key targets were agreed upon in the final workshop: students are able to 1) classify and assess complementary medical terms and methods; 2) work collaboratively and integrate patients into the interprofessional team; 3) involve patients and their relatives respectfully and empathetically in all healthcare processes. To achieve these competency goals, the following teaching methods were highlighted: students discuss therapy options based on authentic patient cases with each other and practice empathic patient communication incorporating complementary medicine. Further, the theoretical background of complementary medicines could be provided as online-training, to use the class sessions for hands-on exercises and interprofessional exchange and discussion.

Conclusion
Despite the heterogeneous panel of experts, a consensus was reached on the competency orientation and teaching approaches. The results can promote the implementation of interprofessional training for complementary medicine in undergraduate education.
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Treatment of pulmonary fibrosis in one convalescent patient with corona virus disease 2019 by oral traditional Chinese medicine decoction: A case report
Na Zhi, Qian Mo, Shuo Yang, Yuan-xing Qin, Hao Chen, Zeng-guang Wu, Cai-hong Lan, Jun Zhang, Yin-long Li
Journal of Integrative Medicine    2021, 19 (2): 185-190.   DOI: 10.1016/j.joim.2020.11.005
Accepted: 30 September 2020
Online available: 18 November 2020

Abstract134)   HTML    PDF      
After one-month of oral treatment with traditional Chinese medicine decoction, without using other drugs, the lung inflammatory exudate, pulmonary fibrosis and quality of life of a 61-year-old female patient with corona virus disease 2019 (COVID-19) were significantly improved. No recurrence or deterioration of the patient’s condition was found within seven weeks of treatment and follow-up, and no adverse events occurred, indicating that oral Chinese medicine decoction was able to improve the pulmonary inflammation and fibrosis in a patient recovering from COVID-19, but further research is still needed.
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Carpobrotus edulis (L.) N.E.Br. extract as a skin preserving agent: from traditional medicine to scientific validation
Miriam Bazzicalupo, Laura Cornara, Bruno Burlando, Alberta Cascini, Marcella Denaro, Antonella Smeriglio, Domenico Trombetta
Journal of Integrative Medicine    2021, 19 (6): 526-536.   DOI: 10.1016/j.joim.2021.09.002
Online available: 30 September 2021

Abstract132)   HTML    PDF      

Objective

Carpobrotus edulis (L.) N.E.Br. is a succulent perennial plant native to South Africa and grows invasively in the Mediterranean basin. It is commonly used for the treatment of various diseases, including skin wound healing and regeneration, for which experimental validation is lacking. We therefore evaluated the skin healing properties of C. edulis by testing an C. edulis aqueous leaf extract (CAE) on cell cultures and in enzymatic assays.

Methods

Micro-morphological analysis of leaves was carried out using scanning electron microscopy and epifluorescence microscopy. Phytochemical features and antioxidant activity of CAE were evaluated by reversed-phase liquid chromatography coupled with diode array detection and electrospray ion trap mass spectrometry (RP-LC-DAD-ESI-MS), and in vitro cell-free assays. Biological activities were evaluated using keratinocytes and fibroblasts, as well as elastase, collagenase, and hyaluronidase.

Results

CAE showed high carbohydrates (28.59% ± 0.68%), total phenols ([101.9 ± 6.0] g gallic acid equivalents/kg dry extract [DE]), and flavonoids ([545.9 ± 26.0] g rutin equivalents/kg DE). RP-LC-DAD-ESI-MS revealed the predominant presence of hydroxycinnamic acids (51.96%), followed by tannins (14.82%) and flavonols (11.32%). The extract was not cytotoxic, had a strong and dose-dependent antioxidant activity, and inhibited collagenase (> 90% at 500 μg/mL) and hyaluronidase (100% at 1000 μg/mL). In cell culture experiments, CAE increased wound closure and collagen production, which was consistent with its high polyphenol content. 

Conclusion

Our data support the use of the C. edulis for skin care and the treatment of skin problems. Moreover, use of C. edulis for skin care purposes could be an eco-friendly solution to reduce its invasiveness in the environment.

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Use of complementary and alternative medicine in general population during COVID-19 outbreak: A survey in Iran
Mahlagha Dehghan, Alireza Ghanbari, Fatemeh Ghaedi Heidari, Parvin Mangalian, Mohammad Ali Zakerid
Journal of Integrative Medicine    2022, 20 (1): 45-51.   DOI: 10.1016/j.joim.2021.11.004
Accepted: 13 July 2021
Online available: 16 November 2021

Abstract132)   HTML    PDF      
Objective
Some epidemic diseases such as coronavirus disease 2019 (COVID-19) have caused many physical, psychological, and social challenges, despite the existence of treatment strategies. Many people are looking for complementary and alternative medicine (CAM) to prevent such diseases. The present study was performed to determine how some types of CAM were being used during the COVID-19 epidemic in Iran.

Methods
The present study had a cross-sectional descriptive correlational design. All Iranian residents above 17 years old were eligible to participate in the study. A total of 782 participants completed a demographic information questionnaire, a questionnaire about their use of CAMs and a questionnaire about their satisfaction with the CAMs they used. Web-based sampling was conducted from 20 April 2020 to 20 August 2020.

Results
Of the participants, 84% used at least one type of CAM during the COVID-19 outbreak. The most used CAMs were dietary supplements (61.3%), prayer (57.9%), and herbal medicines (48.8%). The majority of the participants (50%–66%) have used CAMs to prevent the transmission of COVID-19 or to reduce anxiety caused by the COVID-19 pandemic. CAM use was associated with sex, having children, place of residence, COVID-19 status, and source of gathering information about CAM (P < 0.05). All 32 participants who had been infected with COVID-19 used at least one type of CAM for treatment or alleviation of the disease symptoms.

Conclusion
During the COVID-19 outbreak, some types of CAM, particularly nutritional supplements, medicinal herbs, and prayer, were commonly used to prevent COVID-19 and reduce pandemic-related anxiety.
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Effects of turmeric (Curcuma longa) and its constituent (curcumin) on the metabolic syndrome: An updated review
Zeinab Vafaeipour, Bibi Marjan Razavi, Hossein Hosseinzadeh
Journal of Integrative Medicine    2022, 20 (3): 193-203.   DOI: 10.1016/j.joim.2022.02.008
Online available: 09 March 2022

Abstract127)   HTML    PDF      
Metabolic syndrome (MS) involves people with the following risk factors: obesity, hypertension, high glucose level and hyperlipidemia. It can increase the risk of heart disease, stroke and type 2 diabetes mellitus. The prevalence of MS in the world’s adult population is about 20%–25%. Today, there is much care to use medicinal plants. Turmeric (Curcuma longa) as well as curcumin which is derived from the rhizome of the plant, has been shown beneficial effects on different components of MS. Thus, the purpose of this manuscript was to introduce different in vitroin vivo and human studies regarding the effect of turmeric and its constituent on MS. Moreover, different mechanisms of action by which this plant overcomes MS have been introduced. Based on studies, turmeric and its bioactive component, curcumin, due to their anti-inflammatory and antioxidant properties, have antidiabetic effects through increasing insulin release, antihyperlipidemic effects by increasing fatty acid uptake, anti-obesity effects by decreasing lipogenesis, and antihypertensive effects by increasing nitric oxide. According to several in vivoin vitro and human studies, it can be concluded that turmeric or curcumin has important values as a complementary therapy in MS. However, more clinical trials should be done to confirm these effects. 
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Hypolipidemic and anti-atherosclerogenic effects of aqueous extract of Ipomoea batatas leaves in diet-induced hypercholesterolemic rats
Fidele Ntchapda, Fernand C. Tchatchouang, David Miaffo, Barthelemy Maidadi, Lorella Vecchio, Rodrigue E. Talla, Christian Bonabe, Paul F. Seke Etet, Theophile Dimo
Journal of Integrative Medicine    2021, 19 (4): 243-250.   DOI: 10.1016/j.joim.2021.02.002
Online available: 01 June 2021

Abstract126)      PDF      
Objective: Ipomoea batatas (L.) Lam. is a food plant used in African traditional medicine to treat cardiovascular diseases and related conditions. We assessed the hypolipidemic and anti-atherosclerogenic properties of the aqueous extract of I. batatas leaves in a rat model of diet-induced hypercholesterolemia.
Methods: Hypercholesterolemia was induced in male Wistar rats by exclusive feeding with a cholesterol-enriched (1%) standard diet for four weeks. Then, rats were treated once daily (per os) with I. batatas extract at doses of 400, 500 and 600 mg/kg or with atorvastatin (2 mg/kg), for four weeks. Following treatment, animals were observed for another four weeks and then sacrificed. Aortas were excised and processed for histopathological studies, and blood glucose level and lipid profile were measured.
Results: Hypercholesterolemic animals experienced a 21.5% faster increase in body weight, significant increases in blood glucose and blood lipids (148.94% triglycerides, 196.97% high-density lipoprotein cholesterol, 773.04% low-density lipoprotein cholesterol, 148.93% very low-density lipoprotein cholesterol and 210.42% total cholesterol), and increases in aorta thickness and atherosclerotic plaque sizes compared to rats fed standard diet. Treatment of hypercholesterolemic rats with the extract mitigated these alterations and restored blood glucose and blood lipid levels to normocholesterolemic values.
Conclusion: Our findings suggest that I. batatas leaves have hypolipidemic and anti-atherosclerogenic properties and justify their use in traditional medicine.
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Early therapeutic interventions of traditional Chinese medicine in COVID-19 patients: a retrospective cohort study
Miao-yan Shi, Shi-qi Sun, Wei Zhang, Xing Zhang, Gui-hua Xu, Xuan Chen, Zi-jian Su, Xiu-ming Song, Lu-jiong Liu, Yi-bao Zhang, Yi-le Zhang, Meng Sun, Qi Chen, Yan Xue, Hua Lü, Wei-an Yuan, Xiao-rong Chen, Yun-fei Lu
Journal of Integrative Medicine    2021, 19 (3): 226-231.   DOI: 10.1016/j.joim.2021.01.002
Accepted: 15 December 2020
Online available: 20 April 2021

Abstract123)   HTML    PDF      

Objective

To observe the early interventions of traditional Chinese Medicine (TCM) on the conversion time of nucleic acid in patients with coronavirus disease 2019 (COVID-19), and find possible underlying mechanisms of action.

Methods

A retrospective cohort study was conducted on 300 confirmed COVID-19 patients who were treated with TCM, at a designated hospital in China. The patients were categorized into three groups: TCM1, TCM2 and TCM3, who respectively received TCM interventions within 7, 8–14, and greater than 15 days of hospitalization. Different indicators such as the conversion time of pharyngeal swab nucleic acid, the conversion time of fecal nucleic acid, length of hospital stay, and inflammatory markers (leukocyte count, and lymphocyte count and percentage) were analyzed to observe the impact of early TCM interventions on these groups.

Results

The median conversion times of pharyngeal swab nucleic acid in the three groups were 5.5, 7 and 16 d (P < 0.001), with TCM1 and TCM2 being statistically different from TCM3 (P < 0.01). TCM1 (P < 0.05) and TCM3 (P < 0.01) were statistically different from TCM2. The median conversion times of fecal nucleic acid in the three groups were 7, 9 and 17 d (P < 0.001). Conversion times of fecal nucleic acid in TCM1 were statistically different from TCM3 and TCM2 (P < 0.01). The median lengths of hospital stay in the three groups were 13, 16 and 21 d (P < 0.001). TCM1 and TCM2 were statistically different from TCM3 (P < 0.01); TCM1 and TCM3 were statistically different from TCM2 (P < 0.01). Both leucocyte and lymphocyte counts increased gradually with an increase in the length of hospital stay in TCM1 group patients, with a statistically significant difference observed at each time point in the group (P < 0.001). Statistically significant differences in lymphocyte count and percentage in TCM2 (P < 0.001), and in leucocyte count (P = 0.043) and lymphocyte count (P = 0.038) in TCM3 were observed. The comparison among the three groups showed a statistically significant difference in lymphocyte percentage on the third day of admission (P = 0.044).

Conclusion

In this study, it was observed that in COVID-19 patients treated with a combination of Chinese and Western medicines, TCM intervention earlier in the hospital stay correlated with faster conversion time of pharyngeal swab and fecal nucleic acid, as well as shorter length of hospital stay, thus helping promote faster recovery of the patient. The underlying mechanism of action may be related to improving inflammation in patients with COVID-19.

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Core muscle functional strength training for reducing the risk of low-back pain in military recruits: An open-label randomized controlled trial
Xin Wang, Wen-juan Song, Yi Ruan, Bing-chu Li, Can Lü, Nian Huang, Fan-fu Fang, Wei Gu
Journal of Integrative Medicine    2022, 20 (2): 145-152.   DOI: 10.1016/j.joim.2021.12.002
Accepted: 26 August 2021
Online available: 22 December 2021

Abstract120)           

Background

Core muscle functional strength training (CMFST) has been reported to reduce injuries to the lower extremity. However, no study has confirmed whether CMFST can reduce the risk of low-back pain (LBP).


Objective

This study identified the effects of CMFST on the incidence of LBP in military recruits.


Design, setting, participants and intervention

We performed a prospective, open-label, randomized, controlled study in a population of young healthy male naval recruits from a Chinese basic combat training program. Participants were randomly assigned to either the core group or the control group. In additional to normal basic combat training, recruits in the core group underwent a CMFST program for 12 weeks, while recruits in the control group received no extra training.


Main outcome measures

At the beginning of the study and at the 12th week, the number of participants with LBP was counted, and lumbar muscle endurance was measured. In addition, when participants complained of LBP, they were assessed using the visual analog scale (VAS) and Roland Morris Disability Questionnaire (RMDQ).

Results: A total of 588 participants were included in the final analysis (295 in the core group and 293 in the control group). The incidence of LBP in the control group was about twice that of the core group over the 12-week study (20.8% vs 10.8%, odds ratio: 2.161–2.159, P < 0.001). The core group had better lumbar muscle endurance at 12 weeks than the control group ([200.80 ± 92.98] s vs [147.00 ± 84.51] s, P < 0.01). There was no significant difference in VAS score between groups, but the core group had a significantly lower RMDQ score at week 12 than the control group (3.33 ± 0.58 vs 5.47 ± 4.41, P < 0.05).
Conclusion: This study demonstrated that the CMFST effectively reduced the incidence of LBP, improved lumbar muscle endurance, and relieved the dysfunction of LBP during basic military training.


Trial registration

Chinese Clinical Trial Registry (ChiCTR-POC-14005550).

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Hepatic protective effects of Shenling Baizhu powder, a herbal compound, against inflammatory damage via TLR4/NLRP3 signalling pathway in rats with nonalcoholic fatty liver disease 
Mao-xing Pan, Chui-yang Zheng, Yuan-jun Deng, Kai-rui Tang, Huan Nie, Ji-qian Xie, Dong-dong Liu, Gui-fang Tu, Qin-he Yang, Yu-pei Zhang
Journal of Integrative Medicine    2021, 19 (5): 428-438.   DOI: 10.1016/j.joim.2021.07.004
Online available: 30 September 2021

Abstract115)   HTML    PDF      

Objective

High-fat diet (HFD) and inflammation are two key contributors to nonalcoholic fatty liver disease (NAFLD). Shenling Baizhu powder (SLBZP), a classical herbal compound, has been successfully used to alleviate NAFLD. However, its specific mechanisms are not fully understood. In this study, we assess the anti-NAFLD effect of SLBZP in vivo.

Methods

Rats were fed an HFD with or without SLBZP or with probiotics. At the end of week 16, an echo magnetic resonance imaging (EchoMRI) body composition analyser was used to quantitatively analyse body composition; a micro-computed tomography (micro-CT) imaging system was used to evaluate whole body and liver fat; and the Moor full-field laser perfusion imager 2 was used to assess liver microcirculation, after which, all rats were sacrificed. Then, biochemical indicators in the blood and the ultrastructure of rat livers were evaluated. Protein expression related to the liver Toll-like receptor 4 (TLR4)/Nod-like receptor family pyrin domain-containing 3 (NLRP3) signalling pathway was assessed using Western blot analysis. Further, high-throughput screening of 29 related inflammatory factors in liver tissue was performed using a cytokine array. 

Results

SLBZP supplementation reduced body weight, serum free fatty acid, and insulin resistance index (P < 0.05). It also ameliorated liver microcirculation and ultrastructural abnormalities. EchoMRI and micro-CT quantitative analyses showed that treatment with SLBZP reduced fat mass and visceral fat (P < 0.05 and P < 0.01, respectively). In addition, SLBZP decreased the expression of lipopolysaccharide (LPS)-activated TLR4/NLRP3 signalling pathway-related proteins and altered the expression levels of some inflammatory cytokines in liver tissues.

Conclusion

SLBZP can inhibit NLRP3 inflammasome activation and interleukin-1β release by suppressing LPS-induced TLR4 expression in rats with HFD-induced NAFLD. Thus, SLBZP may be beneficial for the prevention and treatment of inflammatory damage and associated diseases. 

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The knowledge, attitude, practice and predictors of complementary and alternative medicine use among type 2 diabetes mellitus patients in Indonesia
Yunita Sari, Akhyarul Anam, Annas Sumeru, Eman Sutrisna
Journal of Integrative Medicine    2021, 19 (4): 347-353.   DOI: 10.1016/j.joim.2021.04.001
Accepted: 15 March 2021
Online available: 23 April 2021

Abstract115)   HTML    PDF      
Objective
The prevalence of complementary and alternative medicine (CAM) usage among patients with type 2 diabetes mellitus (T2DM) in Indonesia is high. However, to date, little is known about why Indonesian T2DM patients choose CAM therapies, how their knowledge, attitude and practice (KAP) of CAM affects their choices, or how demographics correlate with patient choices. Therefore, this study aimed to investigate the KAP and predictors of CAM usage in T2DM patients in Indonesia.

Methods
This was an observational, cross-sectional study. Patients were interviewed using a questionnaire. Chi-square tests or Fisher’s exact tests were used to compare demographic and clinical data, as well as KAP assessments, between T2DM patients who use and do not use CAM. Multivariate logistic regression analyses were used to investigate predictors of CAM usage.

Results
A total of 628 T2DM patients were enrolled in the study. CAM therapies were used by 341 patients (54.3%). The most common therapies were herbs and spiritual healing, used by 100.0% and 68.3% of CAM-using patients, respectively. CAM therapies were frequently recommended by family members (91.5%), and CAM users had significantly more knowledge and more positive attitudes toward CAM therapies than nonusers. Among users, 66% said they would not follow their healthcare providers’ instructions to not use CAM therapies, and 69.5% said they would not disclose their plan to use CAM therapies with their healthcare provider. Neither demographic nor clinical characteristics were associated with CAM use. The factors that best predicted the use of CAM therapies were their availability and low cost (odds ratio [OR] = 4.59; 95% confidence interval [CI]: 3.01–7.01), the belief that CAM therapies were safe (OR = 2.04; 95% CI: 1.40–2.95), the belief that CAM therapies could help with diabetes control (OR = 1.75; 95% CI: 1.15–2.66), and the belief that CAM therapies could help maintain physical health (OR = 1.68; 95% CI: 1.13–2.49).

Conclusion
CAM therapy users were more knowledgeable and had more positive attitudes toward CAM, but most of them chose not to disclose their CAM use to their healthcare providers. CAM use in Indonesia was associated with its accessibility, affordability, safety and effectivity, but not with any demographic or clinical characteristics. This study provided new evidence and insights for nurses and physicians in Indonesia that will help to design educational programs about the safety and efficacy of CAM therapies.
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Stevens-Johnson syndrome/toxic epidermal necrolysis successfully treated with Chinese herbal medicine Pi-Yan-Ning: A case report
Shu-yi Chen, Qun-wei Chen, Liu-mei Shou, Hong Pan, Shan-ming Ruan, Zhe-hao Liang, Qi-jin Shu
Journal of Integrative Medicine    2021, 19 (6): 555-560.   DOI: 10.1016/j.joim.2021.10.001
Online available: 18 October 2021

Abstract115)   HTML    PDF      
Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a rare adverse cutaneous reaction with a low incidence and high mortality. Despite posing a serious threat to patients’ health and lives, there is no high-quality evidence for a standard treatment regimen. Here we report the case of a 62-year-old man with stage IV pancreatic cancer who experienced immunotherapy-induced SJS/TEN. After consensus-based regular treatments at a local hospital, his symptoms became worse. Thus, he consented to receive Chinese herbal medicine (CHM) therapy. The affected parts of the patient were treated with the CHM Pi-Yan-Ning which was applied externally for 20 min twice a day. After 7 days of treatment, the dead skin began peeling away from the former lesions that had covered his hands, feet, and lips, indicating that skin had regenerated. After 12 days of treatment, the patient’s skin was completely recovered. In this case, SJS/TEN was successfully treated with Pi-Yan-Ning, suggesting that there might be tremendous potential for the use of Pi-Yan-Ning in the treatment of severe skin reactions to drug treatments. Further basic investigations and clinical trials to explore the mechanism and efficacy are needed.
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Tanshinone IIA prevents acute lung injury by regulating macrophage polarization
Jia-yi Zhao, Jin Pu, Jian Fan, Xin-yu Feng, Jian-wen Xu, Rong Zhang, Yan Shang
Journal of Integrative Medicine    2022, 20 (3): 274-280.   DOI: 10.1016/j.joim.2022.01.006
Online available: 21 February 2022

Abstract114)   HTML    PDF      

Objective

Acute lung injury (ALI) is a serious respiratory dysfunction caused by pathogen or physical invasion. The strong induced inflammation often causes death. Tanshinone IIA (Tan-IIA) is the major constituent of Salvia miltiorrhiza Bunge and has been shown to display anti-inflammatory effects. The aim of the current study was to investigate the effects of Tan-IIA on ALI.

Methods

A murine model of lipopolysaccharide (LPS)-induced ALI was used. The lungs and serum samples of mice were extracted at 3 days after treatment. ALI-induced inflammatory damages were confirmed from cytokine detections and histomorphology observations. Effects of Tan-IIA were investigated using in vivo and in vitro ALI models. Tan-IIA mechanisms were investigated by performing Western blot and flow cytometry experiments. A wound-healing assay was performed to confirm the Tan-IIA function.

Results

The cytokine storm induced by LPS treatment was detected at 3 days after LPS treatment, and alveolar epithelial damage and lymphocyte aggregation were observed. Tan-IIA treatment attenuated the LPS-induced inflammation and reduced the levels of inflammatory cytokines released not only by inhibiting neutrophils, but also by macrophage. Moreover, we found that macrophage activation and polarization after LPS treatment were abrogated after applying the Tan-IIA treatment. An in vitro assay also confirmed that including the Tan-IIA supplement increased the relative amount of the M2 subtype and decreased that of M1. Rebalanced macrophages and Tan-IIA inhibited activations of the nuclear factor κB and hypoxia-inducible factor pathways. Including Tan-IIA and macrophages also improved alveolar epithelial repair by regulating macrophage polarization. 

Conclusion

This study found that while an LPS-induced cytokine storm exacerbated ALI, including Tan-IIA could prevent ALI-induced inflammation and improve the alveolar epithelial repair, and do so by regulating macrophage polarization.

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Berberine mitigates nonalcoholic hepatic steatosis by downregulating SIRT1-FoxO1-SREBP2 pathway for cholesterol synthesis
Meng-ya Shan, Ying Dai, Xiao-dan Ren, Jing Zheng, Ke-bin Zhang, Bin Chen, Jun Yan, Zi-hui Xu
Journal of Integrative Medicine    2021, 19 (6): 545-554.   DOI: 10.1016/j.joim.2021.09.003
Online available: 13 October 2021

Abstract112)   HTML    PDF      

Objective

To investigate effects of berberine (BBR) on cholesterol synthesis in HepG2 cells with free fatty acid (FFA)-induced steatosis and to explore the underlying mechanisms.

Methods

A steatosis cell model was induced in HepG2 cell line fed with FFA (0.5 mmol/L, oleic acid:palmitic acid = 2:1), and then treated with three concentrations of BBR; cell viability was assessed with cell counting kit-8 assays. Lipid accumulation in cells was observed through oil red O staining and total cholesterol (TC) content was detected by TC assay. The effects of BBR on cholesterol synthesis mediators were assessed by Western blotting and quantitative polymerase chain reaction. In addition, both silent information regulator 1 (SIRT1) and forkhead box transcription factor O1 (FoxO1) inhibitors were employed for validation. 

Results

FFA-induced steatosis was successfully established in HepG2 cells. Lipid accumulation and TC content in BBR groups were significantly lower (P < 0.05, P < 0.01), associated with significantly higher mRNA and protein levels of SIRT1(P < 0.05, P < 0.01), significantly lower sterol regulatory element-binding protein 2 (SREBP2) and 3-hydroxy 3-methylglutaryl-CoA reductase levels (P < 0.05, P < 0.01), as well as higher Acetyl-FoxO1 protein level (P < 0.05, P < 0.01) compared to the FFA only group. Both SIRT1 inhibitor SIRT1-IN-1 and FoxO1 inhibitor AS1842856 blocked the BBR-mediated therapeutic effects. Immunofluorescence showed that the increased SIRT1 expression increased FoxO1 deacetylation, and promoted its nuclear translocation.

Conclusion

BBR can mitigate FFA-induced steatosis in HepG2 cells by activating SIRT1-FoxO1-SREBP2 signal pathway. BBR may emerge as a potential drug candidate for treating nonalcoholic hepatic steatosis. 

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The safety, efficacy and pharmaceutical quality of male enhancement nutraceuticals bought online: Truth versus claim
Mohamed Ismail Nounou, Heba A. Eassa, Nada A. Helal, Khaled Aboul Fotouh, Ihab Mansoor, Isabel K. Latz, Cindy Zheng, Hadeer A. Eassa, Dina Mohamed, Diana M. Huynh, Abigail R. Wiss, Jessica Sweeney, Monica T. Oakes, Mark M. Mikhail, Nadine Amine, Harshvir Kaur, Natalia Echeverry, Kamila Orzechowski, Doreen Szollosi
Journal of Integrative Medicine    2021, 19 (3): 232-242.   DOI: 10.1016/j.joim.2021.02.003
Accepted: 09 March 2021
Online available: 09 March 2021

Abstract111)   HTML    PDF      

Objective

Nutraceutical products are widely used for their claimed therapeutic benefits. However, falsified or adulterated nutraceuticals present a major health threat to consumers. This study investigates the pharmaceutical quality, safety and anti-inflammatory effects of six male enhancement nutraceuticals that claim to be 100% natural.

Methods

Three batches of six male enhancement products were tested to detect the presence and levels of adulterants via high-performance liquid chromatography (HPLC). The pharmaceutical quality of the selected nutraceuticals was tested with near infrared spectroscopy (NIR) and SeDeM. The cytotoxic effects of these products on HepG2 cells were determined through cell proliferation (XTT) and lactate dehydrogenase (LDH) cytotoxicity assays. Lastly, the in vitro inflammatory effects of these products were investigated using murine J774 macrophages through cytokine release analysis.

Results

HPLC analysis detected the presence of sildenafil citrate, a vasodilator, and the active ingredient in Viagra and Revatio, in all batches of the products we analyzed. Amount of sildenafil citrate ranged from 0.45 mg to 51.85 mg among different batches. NIR assessment showed inter- and intra-batch heterogeneity in product composition. Results of the XTT and LDH assays showed significant cytotoxic effects of the analyzed products. XTT analysis revealed that the viability of HepG2 treated with tested products varied from 27.57% to 41.43%. Interestingly, the male enhancement products also showed anti-inflammatory effects.

Conclusion

Despite their labeling as 100% natural, all products tested in this study contained levels of sildenafil citrate, which was not reported on the packaging. There was a lack of pharmaceutical uniformity among products of the same batch and across different batches. Additionally, the products we tested had cytotoxic effects. These study findings highlight the adulteration, poor quality and hazard of these nutraceuticals. Therefore, strict regulation of these products and standardization of the definition of nutraceuticals are urgently needed. Further, these falsely advertised products should be withdrawn from the market due to potential adverse effects on the health of their consumers.

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Impact of the COVID-19 pandemic on intention to use traditional Chinese medicine: A cross-sectional study based on the theory of planned behavior
Yi Xia, Lu-shao-bo Shi, Jing-hui Chang, Hua-zhang Miao, Dong Wang
Journal of Integrative Medicine    2021, 19 (3): 219-225.   DOI: 10.1016/j.joim.2021.01.013
Accepted: 11 December 2020
Online available: 01 June 2021

Abstract111)   HTML    PDF      
Objective
Coronavirus disease 2019 (COVID-19) has become an increasingly severe public health emergency. Although traditional Chinese medicine (TCM) has helped to combat COVID-19, public perception of TCM remains controversial. We used the theory of planned behavior (TPB) to identify factors that affect the intention to use TCM.

Methods
A cross-sectional web-based survey of 10,824 individuals from the general public was conducted between March 16 and April 2, 2020. The participants were recruited using a snowball sampling method. Data were collected using a self-administered questionnaire, based on the TPB. The questionnaire consisted of demographic characteristics and TPB structures. Structural equation modeling was used to identify predictors of intention.

Results
The results indicated the model explained 77.5% and 71.9% of intention and attitude variance. Intention to use TCM had the strongest relationship with attitude (P < 0.001), followed by past behavior (P < 0.001), subjective norms (P < 0.001) and perceived behavioral control (P < 0.001). Attitudes toward TCM were significantly affected by perceived behavioral control (P < 0.001), subjective norms (P < 0.001) and cognition of TCM (P < 0.001).

Conclusion
Attitude is a key factor in determining the intention to use TCM, followed by past behaviors, subjective norms and perceived behavioral control. Our results offer important implications for health policy makers to promote the use of TCM.
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Filiform needle acupuncture for allergic rhinitis: A systematic review and meta-analysis
Shi-Hao Du, Wei Guo, Chao Yang, Sheng Chen, Sheng-Nan Guo, Shuo Du, Zhong-Ming Du, Yu-Tong Fei, Ji-Ping Zhao
Journal of Integrative Medicine    2022, 20 (6): 497-513.   DOI: 10.1016/j.joim.2022.08.004
Accepted: 07 May 2022
Online available: 05 August 2022

Abstract111)           

Background

Filiform needle acupuncture (FNA), the most classical and widely applied acupuncture method based on traditional Chinese medicine theory, has shown a promising effect in the treatment of allergic rhinitis (AR).

Objective

We aim to comprehensively evaluate the efficacy, safety, cost-effectiveness, and patient preference of FNA in the treatment of AR by comparing FNA with sham acupuncture, no treatment, and conventional medication.

Search strategy

Eight electronic databases were systematically searched from inception to October 14, 2021. Additional studies were acquired from clinical trial registration platforms and reference lists.

Inclusion criteria

RCTs were included if they compared FNA with either sham acupuncture, no treatment, or conventional medications for AR.

Data extraction and analysis

Two researchers extracted data independently of each other using a predesigned data acquisition form, and results were cross-checked after completion. The primary outcome was symptom score (Total Nasal Symptom Score or Visual Analog Scale), and the secondary outcomes were the AR control questionnaire, quality of life (QoL) score (Different versions of Rhinoconjunctivitis Quality of Life Questionnaires), medication score (use of rescue medication), mental health score, total IgE, adverse event rate, clinical economic indicators, and patient satisfaction score. Standardized mean difference (SMD) or mean difference (MD) with 95% confidence intervals (CIs) was used to calculate the effect size for continuous data, while risk ratio with 95% Cis was used for dichotomous data.

Results

Thirty studies were included in this review. Compared with sham acupuncture, FNA significantly reduced the symptom score (SMD: –0.29 [–0.43, –0.15]), AR’s impact on QoL (SMD: –0.23 [–0.37, –0.08]) and medication score (SMD: –0.3 [–0.49, –0.11]). Compared with no treatment, FNA dramatically reduced the symptom score (SMD: –0.8 [–1.2, –0.39]) and AR’s impact on QoL (SMD: –0.82 [–1.13, –0.52]). There were no increased rates of adverse event with FNA compared to sham acupuncture and no treatment. FNA increased patient satisfaction and may be cost-effective. Most pieces of evidence from the above two comparisons were of high confidence. Moreover, FNA significantly outperformed conventional medication in reducing the symptom score (SMD: –0.48 [–0.85, –0.1]) and displayed a lower rate of adverse events, but the quality of evidence was very low.

Conclusion

FNA is an effective and safe intervention for AR and can help with symptom relief, QoL improvement, reducing medication usage, and increasing patient satisfaction. Further studies are needed to verify its cost-effectiveness and superiority over conventional medication and the best therapeutic strategies.

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Impact of socioeconomic and health-related factors on consumption of homeopathic and natural remedies in Spain in 2006, 2011 and 2017
Jose Antonio Castilla-Jimena, Isabel Ruiz-Pérez, Jesús Henares-Montiel
Journal of Integrative Medicine    2022, 20 (1): 52-56.   DOI: 10.1016/j.joim.2021.10.003
Online available: 22 October 2021

Abstract110)   HTML    PDF      

Objective

Complementary and alternative medicine use and type of use may be influenced by sociodemographic and economic determinants through which we could identify characteristics of patients with greater trend to use it. This paper aims to describe the changes in the consumption of homeopathic and natural remedies in Spain for three time points in order to discern changes in rate of consumption, associated factors and whether their use has been affected by a period of economic recession. 

Methods

This study utilized 2006, 2011 and 2017 cross-sectional data from the Spanish National Health Survey, a nationally representative survey of the population aged more than 15 years old and resident in Spain. Independent bivariate and multivariate descriptive analyses for each of the 3 years studied were performed.

Results

The rate of consumption of both homeopathic and natural remedies has decreased over the periods studied. In spite of this decrease, the consumer profile appears to remain stable over the three periods. The sociodemographic factors associated with their consumption were being female, being 30–64 years old, being separated/divorced, having higher education qualifications, being employed and belonging to a higher social class. Psychiatric morbidity, chronic health problems such as pain, mental health problems or malignant tumors, and absence of major cardiovascular events were the clinical factors associated. 

Conclusion

It can be concluded that beyond the economic situation, the use of homeopathic and natural remedies obeys to the needs of the patients related to their state of health and the response they receive from the health system. It may be that women have different needs and expectations of the healthcare system and, given this breach of expectations, seek remedy to alleviate their needs outside the system and conventional medicine.

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Metabolomic characteristics of spontaneously hypertensive rats under chronic stress and the treatment effect of Danzhi Xiaoyao Powder, a traditional Chinese medicine formula
Shuai Chen, Jin Hu, Deng-cheng Lu, Hong-yi Liu, Shan-shan Wei
Journal of Integrative Medicine    2022, 20 (1): 73-82.   DOI: 10.1016/j.joim.2021.11.007
Accepted: 05 August 2021
Online available: 22 December 2021

Abstract110)           

Objective

Numerous studies have demonstrated the close relationship between chronic stress and blood pressure (BP). Hypertensive subjects exhibit exaggerated reactions to stress, especially higher BP. The mechanisms by which stress affects pre-existing hypertension still need to be explored. Danzhi Xiaoyao Powder (DP), a historical traditional Chinese medicine formula, is a promising treatment for BP control in hypertensive patients under stress. The present study investigated the metabolomic disruption caused by chronic stress and the treatment effect and mechanism of DP.


Methods

Spontaneously hypertensive rats (SHRs) were subjected to chronic restraint stress (CRS) for 4 weeks. BP was measured via the tail-cuff method, and anxiety-like behavior was quantified using the elevated-plus-maze test. Meanwhile, DP was administered intragastrically, and its effects were observed. Global metabolomic analysis was performed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, followed by multivariate statistical analysis to detect differential metabolites and pathways.


Results

DP alleviated the CRS-induced increase in BP and anxiety-like behavior. Systematic metabolic di?erences were found among the three study groups. A total of 29 differential plasma metabolites were identified in both positive- and negative-ion modes. These metabolites were involved in triglyceride metabolism, amino acid (phenylalanine, tryptophan, and glycine) metabolism, and steroid hormone pathways.


Conclusion

These findings expose the metabolomic disturbances induced by chronic stress in SHRs and suggest an innovative treatment for this disorder.
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Methods for development of a core outcome set for clinical trials integrating traditional Chinese medicine and Western medicine
Rui-jin Qiu, Min Li, Jia-yuan Hu, Jing Chen, Hong-cai Shang
Journal of Integrative Medicine    2021, 19 (5): 389-394.   DOI: 10.1016/j.joim.2021.07.001
Accepted: 23 June 2021
Online available: 28 July 2021

Abstract108)   HTML    PDF      
Clinical trial outcome reporting differs between studies integrating traditional Chinese medicine (TCM) and Western medicine, so that some clinical trials are not eligible for inclusion in a systematic review. The excluded studies are therefore less widely disseminated, and even valid studies are less likely to yield impact. This problem may be addressed by developing core outcome sets (COSs) for integrative medicine in specific healthcare areas. The first stage of development is to define the scope of the COS for integrative medicine, the second stage is to establish the need for such a COS, and the third stage is to develop a protocol and register the COS. The final stage involves three steps: (i) development of a comprehensive list of outcomes (including efficacy outcomes and safety outcomes and TCM syndromes) using systematic review, qualitative or cross-sectional research, and reviews of package inserts and medical records; (ii) merging and grouping of outcomes within domains; (iii) conducting two rounds of Delphi survey and consensus meetings with a range of stakeholders. The final COS will include a general COS and core TCM syndromes set. Development of COSs for clinical trials of integrative medicine may help to standardize outcome reporting and reduce publication bias in the future.
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Antitumor effects of different Ganoderma lucidum spore powder in cell- and zebrafish-based bioassays
Yue-jiao Shi, Hua-xian Zheng, Zhu-ping Hong, Han-bo Wang, Ying Wang, Ming-yan Li, Zhen-hao Li
Journal of Integrative Medicine    2021, 19 (2): 177-184.   DOI: 10.1016/j.joim.2021.01.004
Accepted: 17 November 2020
Online available: 20 April 2021

Abstract108)   HTML    PDF      

Objective

Ganoderma lucidum spore (GLS) is gaining recognition as a medicinal part of G. lucidum and has been reported to possess various pharmacological properties, such as antitumor activity. In this work, wall-broken GLS powder (BGLSP) and wall-removed GLS powder (RGLSP), two kinds of GLS powder with different manufacturing techniques, were compared in terms of contents of active constituents and in vivo and in vitro antitumor effects.

Methods

The ultraviolet and visible spectrophotometry method was used to determine the contents of polysaccharides and total triterpenoids in BGLSP and RGLSP. Seventeen individual triterpenoids were further quantified using ultra-high-performance liquid chromatography and quantitative analysis of multi-components by single marker. The antitumor effects of BGLSP and RGLSP were evaluated using in vitrocell viability assay against human gastric carcinoma SGC-7901, lung carcinoma A549 and lymphoma Ramos and further validated by in vivo zebrafish xenograft models with transplanted SGC-7901, A549 and Ramos.

Results

The results showed that the contents of polysaccharides, total triterpenoids and individual triterpenoids of RGLSP were significantly higher than those of BGLSP. Although both BGLSP and RGLSP inhibited the three tumor cell lines in vitro in a dose-dependent manner, the inhibitory effects of RGLSP were much better than those of BGLSP. In the in vivo zebrafish assay, RGLSP exhibited more potent inhibitory activities against tumors transplanted into the zebrafish compared with BGLSP, and the inhibition rates of RGLSP reached approximately 78%, 31% and 83% on SGC-7901, A549 and Ramos, respectively. 

Conclusion

The results indicated that the antitumor effects of GLS were positively correlated with the contents of the polysaccharides and triterpenoids and demonstrated that the wall-removing manufacturing technique could significantly improve the levels of active constituents, and thereby enhance the antitumor activity.

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Serum metabolic profiling of traditional Chinese medicine syndromes in patients with diarrhea-predominant irritable bowel syndrome
Si-qi Tang, Yun-liang Wang, Zi-ye Xie, Yang Zhang, Yi Guo, Kang-li Gao, Tang-you Mao, Chun-e Xie, Jun-xiang Li, Xiao-yan Gao
Journal of Integrative Medicine    2021, 19 (3): 274-281.   DOI: 10.1016/j.joim.2021.03.002
Accepted: 06 January 2021
Online available: 16 March 2021

Abstract107)   HTML    PDF      
Objective
The clinical symptoms of diarrhea-predominant irritable bowel syndrome (IBS-D) can be effectively improved by traditional Chinese medicine (TCM) treatment, based on the usage of specific therapies for different TCM syndromes. However, in the stage of diagnosis, the standard criteria for the classification of TCM syndrome were still deficient. Through serum metabolic profiling, this study aimed to explore potential biomarkers in IBS-D patients with different TCM syndromes, which can assist in diagnosis of the disease.

Methods
Serum samples were collected from healthy controls (30 cases), IBS-D patients with Liver-Stagnation and Spleen-Deficiency syndrome (LSSD, 30 cases), Yang Deficiency of Spleen and Kidney syndrome (YDSK, 11 cases) and Damp Abundance due to Spleen-Deficiency syndrome (DASD, 22 cases). Serum metabolic profiling was conducted by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The potential biomarkers were screened by orthogonal partial least square-discriminate analysis, while metabolic pathways undergoing alterations were identified by pathway enrichment analysis in MetaboAnalyst 4.0.

Results
Overall, 34 potential biomarkers were identified in LSSD group, 36 in YDSK group and 31 in DASD group. And the 13 metabolites shared by three groups were determined as the potential biomarkers of IBS-D. Glycerophospholipid metabolism was disturbed significantly in IBS-D patients, which may play a role in IBS-D through inflammation. What’s more, three TCM syndromes have the specific potential biomarkers in glycerophospholipid metabolism.

Conclusion
The serum metabolomics revealed that different TCM syndrome types in IBS-D may have different metabolic patterns during disease progression and glycerophospholipid metabolism was one of the pathways, whose metabolism was disturbed differently among three TCM syndromes in IBS-D. Therefore, the specific potential biomarkers in glycerophospholipid metabolism of three TCM syndromes in IBS-D can serve as the objective indicators, which can facilitate the TCM-syndrome objective classification of IBS-D.
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Application of an extreme learning machine network with particle swarm optimization in syndrome classification of primary liver cancer
Liang Ding, Xin-you Zhang, Di-yao Wu, Meng-ling Liu
Journal of Integrative Medicine    2021, 19 (5): 395-407.   DOI: 10.1016/j.joim.2021.08.001
Online available: 30 September 2021

Abstract104)   HTML    PDF      

Objective

By optimizing the extreme learning machine network with particle swarm optimization, we established a syndrome classification and prediction model for primary liver cancer (PLC), classified and predicted the syndrome diagnosis of medical record data for PLC and compared and analyzed the prediction results with different algorithms and the clinical diagnosis results. This paper provides modern technical support for clinical diagnosis and treatment, and improves the objectivity, accuracy and rigor of the classification of traditional Chinese medicine (TCM) syndromes.

Methods

From three top-level TCM hospitals in Nanchang, 10,602 electronic medical records from patients with PLC were collected, dating from January 2009 to May 2020. We removed the electronic medical records of 542 cases of syndromes and adopted the cross-validation method in the remaining 10,060 electronic medical records, which were randomly divided into a training set and a test set. Based on fuzzy mathematics theory, we quantified the syndrome-related factors of TCM symptoms and signs, and information from the TCM four diagnostic methods. Next, using an extreme learning machine network with particle swarm optimization, we constructed a neural network syndrome classification and prediction model that used “TCM symptoms + signs + tongue diagnosis information + pulse diagnosis information” as input, and PLC syndrome as output. This approach was used to mine the nonlinear relationship between clinical data in electronic medical records and different syndrome types. The accuracy rate of classification was used to compare this model to other machine learning classification models.

Results

The classification accuracy rate of the model developed here was 86.26%. The classification accuracy rates of models using support vector machine and Bayesian networks were 82.79% and 85.84%, respectively. The classification accuracy rates of the models for all syndromes in this paper were between 82.15% and 93.82%.

Conclusion

Compared with the case of data processed using traditional binary inputs, the experiment shows that the medical record data processed by fuzzy mathematics was more accurate, and closer to clinical findings. In addition, the model developed here was more refined, more accurate, and quicker than other classification models. This model provides reliable diagnosis for clinical treatment of PLC and a method to study of the rules of syndrome differentiation and treatment in TCM.

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Processing methods and mechanisms for alkaloid-rich Chinese herbal medicines: A review
Ruo-lan Li, Qing Zhang, Jia Liu, Li-ying He, Qin-wan Huang, Wei Peng, Chun-jie Wu
Journal of Integrative Medicine    2021, 19 (2): 89-103.   DOI: 10.1016/j.joim.2020.12.003
Online available: 12 December 2020

Abstract102)   HTML    PDF      
The processing of Chinese herbal medicine is a form of pharmaceutical technology developed over thousands of years, in order to increase efficiency and decrease toxicity of herbs in traditional Chinese medicine (TCM). Herbal processing is essential for safe and effective application of TCM in clinical practice, as it alters the active chemical components and therefore the functions of herbal medicines. Alkaloid-rich herbal medicines in TCM are commonly processed by cleansing, cutting, processing by dry stir-frying, stir-frying with liquid adjuvants, and processing by water decoction. In addition, commonly used adjuvants for processing alkaloid-rich herbal medicines are river sand, wine, vinegar, brine, honey and herbal juice. For alkaloid-rich herbal medicines, the main chemical reactions that occur during processing include hydrolysis, oxidation, replacement, decomposition and condensation. This paper aimed to summarize the processing methods and mechanisms for alkaloid-rich Chinese herbal medicines, and provide much-needed theoretical support and scientific evidence for understanding those mechanisms and effects. Information on processing methods for alkaloid-rich herbal medicines was collected from classic books of herbal medicine, PhD and MSc dissertations, online scientific databases including PubMed, SciFinder, Scopus, Web of Science, Baidu Scholar and Google Scholar. This paper should help to advance our knowledge of the processing mechanisms and aid in the development of processing methods for alkaloid-rich Chinese herbal medicines.
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A novel supplement with yeast β-glucan, prebiotic, minerals and Silybum marianum synergistically modulates metabolic and inflammatory pathways and improves steatosis in obese mice
Victor Abou Nehmi Filho, Gilson Masahiro Murata, Ruan Carlos Macêdo de Moraes, Gabriely Cristina Alves Lima, Danielle Araujo de Miranda, Katrin Radloff, Raquel Galvão Figuerêdo Costa, Joyce de Cassia Rosa de Jesus, Jéssica Alves De Freitas, Nayara Izabel Viana, Ruan Pimenta, Katia Ramos Moreira Leite, José Pinhata Otoch, Ana Flávia Marçal Pessoa
Journal of Integrative Medicine    2021, 19 (5): 439-450.   DOI: 10.1016/j.joim.2021.05.002
Accepted: 06 March 2021
Online available: 04 June 2021

Abstract102)   HTML    PDF      
Objective
To evaluate the synergic effects of a novel oral supplement formulation, containing prebiotics, yeast β-glucans, minerals and silymarin (Silybum marianum), on lipid metabolism and inflammatory and mitochondrial proteins of the liver, in control and high-fat diet-induced obese mice.

Methods
After an acclimation period, 32 male C57BL/6 mice were divided into the following groups: nonfat diet (NFD) vehicle, NFD supplemented, high-fat diet (HFD) vehicle and HFD supplemented. The vehicle and experimental formulation were administered orally by gavage once a day during the last four weeks of the diet (28 consecutive days). We then evaluated energy homeostasis, inflammation, and mitochondrial protein expression in these groups of mice.

Results
After four weeks of supplementation, study groups experienced reduced glycemia, dyslipidemia, fat, and hepatic fibrosis levels. Additionally, proliferator-activated receptor-α, AMP-activated protein kinase-1α, peroxisome proliferator-activated receptor γ co-activator 1-α, and mitochondrial transcription factor A expression levels were augmented; however, levels of IκB kinase α and p65 nuclear factor-κB expression, and oxidative markers were reduced. Notably, the cortisol/C-reactive protein ratio, a well-characterized marker of the hypothalamic-pituitary-adrenal axis immune interface status, was found to be modulated by the supplement.

Conclusion
We found that the novel supplement modified different antioxidant, metabolic and inflammatory pathways, improved energy homeostasis and the inflammatory state, and consequently alleviated hepatic steatosis.
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Effects of lavender and Citrus aurantium on pain of conscious intensive care unit patients: A parallel randomized placebo-controlled trial
Zahra Karimzadeh, Mansooreh Azizzadeh Forouzi, Haleh Tajadini, Mehdi Ahmadinejad, Callista Roy, Mahlagha Dehghan
Journal of Integrative Medicine    2021, 19 (4): 333-339.   DOI: 10.1016/j.joim.2021.01.006
Accepted: 29 December 2020
Online available: 20 April 2021

Abstract102)   HTML    PDF      

Background

Conscious patients admitted to intensive care units (ICUs) suffer from pain for various reasons, which can affect their recovery process. 

Objective

The present study compared the effects of aromatherapy with Citrus aurantium and lavender essential oils against placebo for reducing pain in conscious intensive care patients.

Design, setting, participants and interventions

This study was a parallel randomized placebo-controlled trial. The ICUs of two educational hospitals in Kerman in Southeastern Iran were the study setting. One hundred and fifty conscious intensive care patients were randomly divided into three groups using a stratified block randomization method. Two groups received aromatherapy with essential oils: one with lavender and the other with C. aurantium; these patients received a 30-minute therapy session using their assigned essential oil on the second day of their intensive care stay. The placebo group used 5 drops of normal saline instead of essential oil during their session. 

Main outcome measures

Patient’s pain was assessed using a visual analog scale before the aromatherapy intervention, as well as immediately after and one and three hours after intervention. 

Results

The mean pain score of the lavender group was 40.01 before the aromatherapy intervention and fell to 39.40, 30.60 and 23.68 immediately after the intervention, and at hour one and three post-intervention, respectively. The mean pain score of the C. aurantium group was 45.48 before the intervention and was reduced to 32.34 at three hours after the intervention. The mean pain of the placebo group decreased from 42.80 before the intervention to 35.20 at three hours after the intervention. Pain scores of all groups decreased during the study (P < 0.001). The mean pain of the lavender group was significantly lower than that of the placebo group at three hours after the intervention. 

Conclusion

The results of this study showed that aromatherapy with lavender essential oil reduced pain in conscious ICU patients. Our data could not justify the use of C. aurantium for reducing pain in this population.

Trial registration

No. IRCT20170116031972N9 (https://en.irct.ir/trial/40827).

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Evaluating the methodology of studies conducted during the global COVID-19 pandemic: A systematic review of randomized controlled trials
Meng-zhu Zhao, Chen Zhao, Shuang-shuang Tu, Xu-xu Wei, Hong-cai Shang
Journal of Integrative Medicine    2021, 19 (4): 317-326.   DOI: 10.1016/j.joim.2021.03.003
Online available: 29 March 2021

Abstract101)   HTML    PDF      
Background
The therapeutic evidence collected from well-designed studies is needed to help manage the global pandemic of the coronavirus disease 2019 (COVID-19). Evaluating the quality of therapeutic data collected during this most recent pandemic is important for improving future clinical research under similar circumstances.

Objective
To assess the methodological quality and variability in implementation of randomized controlled trials (RCTs) for treating COVID-19, and to analyze the support that should be provided to improve data collected during an urgent pandemic situation.

Search strategy
PubMed, Excerpta Medica Database, China National Knowledge Infrastructure, Wanfang, and Chongqing VIP, and the preprint repositories including Social Science Research Network and MedRxiv were systematically searched, up to September 30, 2020, using the keywords “coronavirus disease 2019 (COVID-19),” “2019 novel coronavirus (2019-nCoV),” “severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2),” “novel coronavirus pneumonia (NCP),” “randomized controlled trial (RCT)” and “random.”

Inclusion criteria
RCTs studying the treatment of COVID-19 were eligible for inclusion. 

Data extraction and analysis
Screening of published RCTs for inclusion and data extraction were each conducted by two researchers. Analysis of general information on COVID-19 RCTs was done using descriptive statistics. Methodological quality was assessed using the risk-of-bias tools in the Cochrane Handbook for Systematic Reviews of Interventions (Version 5.1.0). Variability in implementation was assessed by comparing consistency between RCT reports and registration information. 

Results
A total of 5886 COVID-19 RCTs were identified. Eighty-one RCTs were finally included, of which, 45 had registration information. Methodological quality of the RTCs was not optimal due to deficiencies in five main domains: allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, and selective reporting. Comparisons of consistency between published protocols and registration information showed that the 45 RCTs with registration information had common deviations in seven items: inclusion and exclusion criteria, sample size, outcomes, research sites of recruitment, interventions, and blinding.

Conclusion
The methodological quality of COVID-19 RCTs conducted in early to mid 2020 was consistently low and variability in implementation was common. More support for implementing high-quality methodology is needed to obtain the quality of therapeutic evidence needed to provide positive guidance for clinical care. We make an urgent appeal for accelerating the construction of a collaborative sharing platform and preparing multidisciplinary talent and professional teams to conduct excellent clinical research when faced with epidemic diseases of the future. Further, variability in RCT implementation should be clearly reported and interpreted to improve the utility of data resulting from those trials.
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Local vibration therapy promotes the recovery of nerve function in rats with sciatic nerve injury
Lu Yin, Yun An, Xiao Chen, Hui-xin Yan, Tao Zhang, Xin-gang Lu, Jun-tao Yan
Journal of Integrative Medicine    2022, 20 (3): 265-273.   DOI: 10.1016/j.joim.2022.02.001
Online available: 21 February 2022

Abstract99)   HTML    PDF      
Objective
It has been reported that local vibration therapy can benefit recovery after peripheral nerve injury, but the optimized parameters and effective mechanism were unclear. In the present study, we investigated the effect of local vibration therapy of different amplitudes on the recovery of nerve function in rats with sciatic nerve injury (SNI).
Methods
Adult male Sprague-Dawley rats were subjected to SNI and then randomly divided into 5 groups: sham group, SNI group, SNI + A-1 mm group, SNI + A-2 mm group, and SNI + A-4 mm group (A refers to the amplitude; n = 10 per group). Starting on the 7th day after model initiation, local vibration therapy was given for 21 consecutive days with a frequency of 10 Hz and an amplitude of 1, 2 or 4 mm for 5 min. The sciatic function index (SFI) was assessed before surgery and on the 7th, 14th, 21st and 28th days after surgery. Tissues were harvested on the 28th day after surgery for morphological, immunofluorescence and Western blot analysis.
Results
Compared with the SNI group, on the 28th day after surgery, the SFIs of the treatment groups were increased; the difference in the SNI + A-2 mm group was the most obvious (95% confidence interval [CI]: [5.86, 27.09], P < 0.001), and the cross-sectional areas of myocytes in all of the treatment groups were improved. The G-ratios in the SNI + A-1 mm group and SNI + A-2 mm group were reduced significantly (95% CI: [?0.12, ?0.02], P = 0.007; 95% CI: [?0.15, ?0.06], P < 0.001). In addition, the expressions of S100 and nerve growth factor proteins in the treatment groups were increased; the phosphorylation expressions of ERK1/2 protein in the SNI + A-2 mm group and SNI + A-4 mm group were upregulated (95% CI: [0.03, 0.96], P = 0.038; 95% CI: [0.01, 0.94], P = 0.047, respectively), and the phosphorylation expression of Akt in the SNI + A-1 mm group was upregulated (95% CI: [0.11, 2.07], P = 0.031).
Conclusion
Local vibration therapy, especially with medium amplitude, was able to promote the recovery of nerve function in rats with SNI; this result was linked to the proliferation of Schwann cells and the activation of the ERK1/2 and Akt signaling pathways.
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Reporting and methodological quality of meta-analyses of acupuncture for patients with migraine: A methodological investigation with evidence map
Ting-ting Lu, Cun-cun Lu, Mei-xuan Li, Li-xin Ke, Hui Cai, Ke-hu Yang
Journal of Integrative Medicine    2022, 20 (3): 213-220.   DOI: 10.1016/j.joim.2022.02.003
Accepted: 10 January 2022
Online available: 23 February 2022

Abstract99)           
Background

Acupuncture has been widely used to relieve migraine-related symptoms. However, the findings of previous systematic reviews (SRs) and meta-analyses (MAs) are still not completely consistent. Their quality is also unknown, so a comprehensive study is needed.

Objective
To evaluate the reporting and methodological quality of these MAs concerning acupuncture for migraine, and summarize evidence about the efficacy and safety of acupuncture for migraine.

Search strategy
PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese Biomedical Databases, Wanfang Data, and VIP databases were searched from inception to September 2020, with a comprehensive search strategy.

Inclusion criteria
The pairwise MAs of randomized controlled trials (RCTs) concerning migraine treated by acupuncture or acupuncture-based therapies, with a control group that received sham acupuncture, medication, no treatment, or acupuncture at different acupoints were included.

Data extraction and analysis
Two independent investigators screened studies, extracted relevant data, and assessed reporting and methodological quality using PRISMA 2009 and AMSTAR 2, then all results were cross-checked. Spearman correlation test was used to evaluate the correlation between reporting and methodological quality scores.

Results
A total of 20 MAs were included in this study. The included MAs indicated that acupuncture was efficacious and safe in preventing and treating migraine when compared with control intervention. There was a high correlation between reporting and methodological quality scores (rs = 0.87, P < 0.001). The quality of the included SRs needs to be improved mainly with regard to protocol and prospective registration, using a comprehensive search strategy, summarizing the strength of evidence body for key outcomes, a full list of excluded studies with reasons for exclusion, reporting of RCTs’ funding sources, and assessing the potential impact of risk of bias in RCTs on MA results.

Conclusion
Acupuncture is an effective and safe intervention for preventing and treating migraine, and could be considered as a good option for patients with migraine. However, the reporting and methodological quality of MAs included in this overview is suboptimal. In the future, AMSTAR 2 and PRISMA tools should be followed when making and reporting an SR with MA.
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Aerobic exercise suppresses hepatocellular carcinoma by downregulating dynamin-related protein 1 through PI3K/AKT pathway
Tong Zhao, Bing-jie Guo, Chu-lan Xiao, Jiao-jiao Chen, Can Lü, Fan-fu Fang, Bai Li
Journal of Integrative Medicine    2021, 19 (5): 418-427.   DOI: 10.1016/j.joim.2021.08.003
Online available: 30 September 2021

Abstract97)   HTML    PDF      
Objective
Exercise, as a common non-drug intervention, is one of several lifestyle choices known to reduce the risk of cancer. Mitochondrial division has been reported to play a key role in the occurrence and transformation of hepatocellular carcinoma (HCC). This study investigated whether exercise could regulate the occurrence and development of HCC through mitosis.
Methods
Bioinformatics technology was used to analyze the expression level of dynamin-related protein 1 (DRP1), a key protein of mitochondrial division. The effects of DRP1 and DRP1 inhibitor (mdivi-1) on the proliferation and migration of liver cancer cells BEL-7402 were observed using cell counting kit-8, plate colony formation, transwell cell migration, and scratch experiments. Enzyme-linked immunosorbent assay, Western blot and real-time polymerase chain reaction were used to detect the expression of DRP1 and its downstream phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway. A treadmill exercise intervention was tested in a nude mouse human liver cancer subcutaneous tumor model expressing different levels of DRP1. The size and weight of subcutaneous tumors in mice were detected before and after exercise.
Results
The expression of DRP1 in liver cancer tissues was significantly upregulated compared with normal liver tissues (P < 0.001). The proliferation rate and the migration of BEL-7402 cells in the DRP1 over-expression group were higher than that in the control group. The mdivi-1 group showed an inhibitory effect on the proliferation and migration of BEL-7402 cells at 50 μmol/L. Aerobic exercise was able to inhibit the expression of DRP1 and decrease the size and weight of subcutaneous tumors. Moreover, the expression of phosphorylated PI3K (p-PI3K) and phosphorylated AKT (p-AKT) decreased in the exercise group. However, exercise could not change p-PI3K and p-AKT levels after knocking down DRP1 or using mdivi-1 on subcutaneous tumor.
Conclusion
Aerobic exercise can suppress the development of tumors partially by regulating DRP1 through PI3K/AKT pathway.

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Functional connectivity changes during migraine treatment with electroacupuncture at Shuaigu (GB8)
Xiang-yu Wei, Shi-lei Luo, HuiChen, Shan-shan Liu, Zhi-gang Gong, Song-huaZhan
Journal of Integrative Medicine    2022, 20 (3): 237-243.   DOI: 10.1016/j.joim.2022.01.009
Accepted: 06 January 2022
Online available: 31 January 2022

Abstract97)           
Objective
To investigate the changes in the functional connectivity (FC) in the right insula between migraine without aura (MWoA) and healthy controls by using resting-state functional magnetic resonance imaging (rs-fMRI), and to observe the instant alteration of FC in MWoA during electroacupuncture (EA) stimulation at Shuaigu (GB8).

Methods
A total of 30 patients with MWoA (PM group) and 30 healthy controls (HC group) underwent rs-fMRI scans. The PM group underwent a second rs-fMRI scan while receiving EA at GB8. The right insula subregions, including the ventral anterior insula (vAI), dorsal anterior insula (dAI) and posterior insula (PI), were selected as the seed points for FC analysis.

Results
Aberrant FC, including dAI with right postcentral gyrus, PI with left precuneus, was found among PM before EA (PMa), PM during EA (PMb) and HC. Meanwhile, decreased FC between dAI and the right postcentral gyrus was found in the PMa compared to the HC and PMb. Increased FC between the PI and left precuneus was found in the PMa compared to the HC and PMb. Correlation analysis showed that the FC value of the right postcentral gyrus in PMa was negatively correlated with the scores of Hamilton Rating Scale for Depression and Hamilton Rating Scale for Anxiety. The FC value of the left precuneus in PMa was positively correlated with the visual analogue scale score.

Conclusion
The alteration of FC between the right insula subregions and multiple brain regions may be an important index for MWoA. EA at GB8 was able to adjust the FC between the right insula subregions and parietal lobe, namely, the right dAI and right postcentral gyrus, and the right PI and left precuneus, thereby rendering an instant effect in the management of MWoA.
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Why the “sugars” in traditional Unani formulations are a pivotal component: A viewpoint perspective
Mohammad Fazil, Sadia Nikhat
Journal of Integrative Medicine    2022, 20 (2): 91-95.   DOI: 10.1016/j.joim.2022.01.002
Online available: 18 January 2022

Abstract94)   HTML    PDF      
Traditional medicine systems around the globe, like Unani, Ayurveda and traditional Chinese medicine, include a number of sugar-based formulations, which contain a large amount of saccharide-containing sweetener, such as honey, sucrose or jaggery. With pervasive lifestyle disorders throughout the world, there have been discussions to consider alternative sweetening agents. Here, from the perspective of Unani medicine, we discuss how the saccharide-based sweeteners may be an essential component of these traditional preparations, like electuaries, which may be deprived of their bioactivities without these saccharides. With contemporary researches, it is known that apart from their own therapeutic effects, saccharides also form deep eutectic solvents which help in enhancing the bioactivity of other ingredients present in crude drugs. In addition, they provide energy for fermentation which is essential for biotransformation of compounds. Interestingly, the sugars also increase the shelf-life of these compound drugs and act as natural preservatives. On the basis of this review, we strongly believe that saccharide-based sweeteners are an essential component of traditional medicines and not merely an excipient.

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Efficacy of the herbal pair, Radix Achyranthis Bidentatae and Eucommiae Cortex, in preventing glucocorticoid-induced osteoporosis in the zebrafish model
Joon-ho Lee, Yuan-ji Wei, Zhong-yan Zhou, Yu-ming Hou, Cheng-long Wang, Li-bo Wang, Hong-jin Wu, Yu Zhang, Wei-wei Dai
Journal of Integrative Medicine    2022, 20 (1): 83-90.   DOI: 10.1016/j.joim.2021.11.003
Accepted: 23 August 2021
Online available: 22 December 2021

Abstract93)           

Objective

In traditional Chinese medicine, the herbal pair, Radix Achyranthis Bidentatae (RAB) and Eucommiae Cortex (EC), is widely used to treat osteoporosis. Herein, we determined whether this herbal pair can be used to ameliorate glucocorticoid (GC)-induced osteoporosis (GIOP) and find its optimal dosage in zebrafish.


Methods

The characteristics of the aqueous extract of RAB and EC were separately characterized using high-performance liquid chromatography. Osteoporosis was induced in 5-day post-fertilization zebrafish larvae by exposing them to 10 μmol/L dexamethasone (Dex) for 96 h. Seven combinations of different ratios of RAB and EC were co-administered. Treatment efficacy was determined by calculating zebrafish vertebral area and sum brightness, via alizarin red staining, and by detecting alkaline phosphatase (ALP) activity. Multiple regression analysis was conducted to test the optimal dosage ratio.


Results

According to the Chinese Pharmacopoeia (2015), β-ecdysone (β-Ecd) is a major bioactive marker in RAB extract, while pinoresinol diglucoside (PDG) is the major marker in EC extract. Both of β-Ecd and PDG content values aligned with the Chinese Pharmacopoeia standards. Treatment with 10 μmol/L Dex reduced zebrafish vertebral area, sum brightness, and ALP activity, but RAB and EC attenuated these effects. Combining 50 μg/mL RAB and 50 μg/mL EC was optimal for preventing GIOP in zebrafish. Reverse transcription-quantitative polymerase chain reaction was used to evaluate the mRNA expression of osteogenesis-related genes. A treatment of 10 μmol/L Dex decreased runt-related transcription factor 2 (Runx2), osteogenic protein-1 (OP-1), bone γ-carboxyglutamic acid-containing protein (BGLAP), and β-catenin levels. This effect was counteracted by RAB and EC co-treatment (P < 0.05). Additionally, the effect of using the two herbal extracts together was better than single-herb treatments separately. These results demonstrated that RAB and EC preserve osteoblast function in the presence of GC. The best mass ratio was 1:1.


Conclusion

RAB and EC herbal pair could ameliorate GC-induced effects in zebrafish, with 1:1 as the optimal dosage ratio.

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Angiotensin-converting enzyme inhibitors from plants: A review of their diversity, modes of action, prospects, and concerns in the management of diabetes-centric complications
Rakhi Chakraborty, Swarnendu Roy
Journal of Integrative Medicine    2021, 19 (6): 478-492.   DOI: 10.1016/j.joim.2021.09.006
Online available: 09 October 2021

Abstract91)           
Angiotensin-converting enzyme (ACE) inhibitors are antihypertensive medications often used in the treatment of diabetes-related complications. Synthetic ACE inhibitors are known to cause serious side effects like hypotension, renal insufficiency, and hyperkalaemia. Therefore, there has been an intensifying search for natural ACE inhibitors. Many plants or plant-based extracts are known to possess ACE-inhibitory activity. In this review, articles focusing on the natural ACE inhibitors extracted from plants were retrieved from databases like Google Scholar, PubMed, Scopus, and Web of Science. We have found more than 50 plant species with ACE-inhibitory activity. Among them, Angelica keiskeiMomordica charantiaMuntingia calaburaPrunus domestica, and Peperomia pellucida were the most potent, showing comparatively lower half-maximal inhibitory concentration values. Among the bioactive metabolites, peptides (e.g., Tyr-Glu-Pro, Met-Arg-Trp, and Gln-Phe-Tyr-Ala-Val), phenolics (e.g., cyanidin-3-O-sambubioside and delphinidin-3-O-sambubioside), flavonoids ([-]-epicatechin, astilbin, and eupatorin), terpenoids (ursolic acid and oleanolic acid) and alkaloids (berberine and harmaline) isolated from several plant and fungi species were found to possess significant ACE-inhibitory activity. These were also known to possess promising antioxidant, antidiabetic, antihyperlipidemic and anti-inflammatory activities. Considering the minimal side effects and lower toxicity of herbal compounds, development of antihypertensive drugs from these plant extracts or phytocompounds for the treatment of diabetes-associated complications is an important endeavour. This review, therefore, focuses on the ACE inhibitors extracted from different plant sources, their possible mechanisms of action, present status, and any safety concerns.
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Design of dual targeting immunomicelles loaded with bufalin and study of their anti-tumor effect on liver cancer
Hao Gou, Ruo-chen Huang, Yong-hua Su, Wei Li
Journal of Integrative Medicine    2021, 19 (5): 408-417.   DOI: 10.1016/j.joim.2021.05.001
Online available: 08 June 2021

Abstract91)   HTML    PDF      

Objective

Bufalin is an effective drug for the treatment of liver cancer. But its high toxicity, poor water-solubility, fast metabolism and short elimination half-life limit its use in tumor treatment. How to make the drug accumulate in the tumor and reduce side effects while maintaining its efficacy are urgent problems to be solved. The goal of this study is to solve these problems.

Methods

A copolymer with tunable poly-N-isopropylacrylamide and polylactic acid was designed and synthesized. The corresponding dual targeting immunomicelles (DTIs) loaded with bufalin (DTIs-BF) were synthesized by copolymer self-assembly in an aqueous solution. The size and structure of DTIs-BF were determined by ZetaSizer Nano-ZS and transmission electron microscopy. Then, its temperature sensitivity, serum stability, critical micelle concentration (CMC), entrapment efficiency (EE), drug release and non-cytotoxicity of blank block copolymer micelles (BCMs) were evaluated. Next, the effects of DTIs-BF on cellular uptake, cytotoxicity, and tumor cell inhibition were evaluated. Finally, the accumulation of DTIs-fluorescein isothiocyanate (FITC) and the in vivo anti-tumor effect were observed using an interactive video information system. 

Results

DTIs-BF had a small size, spherical shape, good temperature sensitivity, high serum stability, low CMC, high EE, and slow drug release. The blank BCMs had very low cytotoxicity. Compared with free bufalin, the in vitro cellular internalization and cytotoxicity of DTIs-BF against SMMC-7721 cells were significantly enhanced, and the effects were obviously better at 40 ℃ than 37 ℃. In addition, the therapeutic effect on SMMC-7721 cells was further enhanced by the programmed cell death specifically caused by bufalin. When DTIs-FITC were injected intravenously in BALB/c nude mice bearing liver cancer, the accumulation of FITC was significantly increased in tumors.

Conclusion

DTIs-BF is a potentially effective nano-formulation and has broad prospects in the clinical treatment of liver cancer.


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A model to standardize safety and quality of care for cupping therapy
Riska Siregar, Aris Setyawan, Syahruramdhani Syahruramdhani
Journal of Integrative Medicine    2021, 19 (4): 327-332.   DOI: 10.1016/j.joim.2021.01.011
Accepted: 08 January 2020
Online available: 02 February 2021

Abstract91)   HTML    PDF      
Cupping therapy has historical, traditional and religious value. It is increasingly popular in the field of complementary, alternative and integrative medicine. However, standards for safety and quality of service are absent. Although it is generally considered safe, cupping therapy can cause adverse events. Most of these events are predictable and preventable. A comprehensive approach to patient eligibility and therapist selection, along with compliance with standard operational procedures is essential to regulate the safety of the practice. Here we discuss a model framework for standardizing safety and quality of care. We recommend that this model be used routinely by cupping therapists and their associations on a nation-wide scale.
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Meta-analysis on the effect of combining Lianhua Qingwen with Western medicine to treat coronavirus disease 2019
Deng-chao Wang, Miao Yu, Wen-xian Xie, Li-yan Huang, Jian Wei, Yue-hua Lei
Journal of Integrative Medicine    2022, 20 (1): 26-33.   DOI: 10.1016/j.joim.2021.10.005
Online available: 05 November 2021

Abstract91)   HTML    PDF      

Background

Coronavirus disease 2019 (COVID-19) has become a worldwide life-threatening pandemic. Lianhua Qingwen is believed to possess the ability to treat or significantly improve the symptoms of COVID-19. These claims make it important to systematically evaluate the effects of using Lianhua Qingwen with Western medicine to treat COVID-19.

Objective

To evaluate the safety and efficacy of combination therapy, employing Lianhua Qingwen with Western medicine, to treat COVID-19, using a meta-analysis approach.

Search strategy

China National Knowledge Infrastructure, Wanfang Database, VIP Database, PubMed, Embase, and Cochrane Library databases were searched for studies evaluating the effect of Lianhua Qingwen-Western medicine combination therapy in the treatment of COVID-19.

Inclusion criteria

(1) Research object: hospitalized patients meeting the diagnostic criteria of COVID-19 were included. (2) Intervention measures: patients in the treatment group received Lianhua Qingwen treatment combined with Western medicine, while the control group received either Western medicine or Chinese medicine treatment. (3) Research type: randomized controlled trials and retrospective study were included.

Data extraction and analysis

Two researchers extracted the first author, the proportion of males and females, age, body temperature, course of treatment, rate of disappearance of main symptoms, duration of fever, adverse reactions, and total effectiveness from the literature. Odds ratio (OR) and 95% confidence interval (CI) were used as the effect value for count data, and mean difference (MD) and 95% CI were used as the effect value for measurement data.

Results

Six articles met the inclusion criteria, including a total of 856 COVID-19 patients. The meta-analysis showed that Lianhua Qingwen combination therapy achieved higher rates of fever reduction (OR = 3.43, 95% CI [1.78, 6.59], P = 0.0002), cough reduction (OR = 3.39, 95% CI [1.85, 6.23], P < 0.0001), recovery from shortness of breath (OR = 10.62, 95% CI [3.71, 30.40], P < 0.0001) and recovery from fatigue (OR = 2.82, 95% CI [1.44, 5.53], P = 0.003), higher total effectiveness rate (OR = 2.51, 95% CI [1.73, 3.64], P< 0.00001), and shorter time to recovery from fever (MD = –1.00, 95% CI [–1.04, 0.96], P < 0.00001), and did not increase the adverse reaction rate (OR = 0.65, 95% CI [0.42, 1.01], P = 0.06), compared to the single medication control. 

Conclusion

The Lianhua Qingwen and Western medicine combination therapy is highly effective for COVID-19 patients and has good clinical safety. As only a small number of studies and patients were included in this review, more high-quality, multicenter, large-sample-size, randomized, double-blind, controlled trials are still needed for verification.

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Green-synthetized selenium nanoparticles using berberine as a promising anticancer agent#br#
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Mohamed S. Othman, Sofian T. Obeidat, Amal H. Al-Bagawi, Mohamed A. Fareid, Alaa Fehaid, Ahmed E. Abdel Moneim
Journal of Integrative Medicine    2022, 20 (1): 65-72.   DOI: 10.1016/j.joim.2021.11.002
Online available: 16 December 2021

Abstract90)   HTML    PDF      

Objective

The chemo-preventative and therapeutic properties of selenium nanoparticles (SeNPs) have been documented over recent decades and suggest the potential uses of SeNPs in medicine. Biogenic SeNPs have higher biocompatibility and stability than chemically synthesized nanoparticles, which enhances their medical applications, especially in the field of cancer therapy. This study evaluated the potential of green-synthetized SeNPs by using berberine (Ber) as an antitumor agent and elucidated the mechanism by which these molecules combat Ehrlich solid tumors (ESTs).

Methods

SeNPs containing Ber (SeNPs-Ber) were synthesized using Ber and Na2SeO3 and characterized with Fourier transform infrared spectroscopy. Sixty male Swiss albino mice were then acclimatized for one week, injected with Ehrlich ascites tumor cells, and divided into four groups: EST, EST + cisplatin (5 mg/kg), EST + Ber (20 mg/kg), and EST+ SeNPs-Ber (0.5 mg/kg). At the end of a 16-day observation period, 12 mice from each group were euthanized to analyze differences in the body weight, tumor size, gene expression, and oxidative stress markers in the four groups. Three mice from each group were kept alive to compare the survival rates.

Results

Treatment with SeNPs-Ber significantly improved the survival rate and decreased the body weight and tumor size, compared to the EST group. SeNPs-Ber reduced oxidative stress in tumor tissue, as indicated by a decrease in the lipid peroxidation and nitric oxide levels and an increase in the glutathione levels. Moreover, SeNPs-Ber activated an apoptotic cascade in the tumor cells by upregulating the Bcl-2-associated X protein and caspase-3 expression rates and downregulating the B-cell lymphoma 2 expression rate. SeNPs-Ber also considerably improved the histopathological alterations in the developed tumor tissue, compared to the EST group. 

Conclusion

Our study provides a new insight into the potential role of green-synthesized SeNPs by using Ber as a promising anticancer agent, these molecules could be used alone or as supplementary medication during chemotherapy.

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Aconitum heterophyllum Wall. ex Royle: A critically endangered medicinal herb with rich potential for use in medicine
Tareq A. Wani, Zahoor A. Kaloo, Nisar A. Dangroo
Journal of Integrative Medicine    2022, 20 (2): 104-113.   DOI: 10.1016/j.joim.2021.12.004
Online available: 28 December 2021

Abstract90)   HTML    PDF      
Aconitum heterophyllum (Patrees) is a critically endangered medicinal herb of the northwestern Himalayas and has enormous pharmacological potential. It is the only nonpoisonous member of the genus Aconitum, and has been used as a medicinal herb since ancient times. A. heterophyllum is an important ingredient in many traditional systems of medicine. Mostly, it is harvested for its roots, and its medicinal properties are due to the presence of diverse bioactive secondary metabolites, commonly known as aconites. Our understanding of the pharmacological properties of this intriguing genus is continuously growing due to its broad chemical diversity. The therapeutic uses identified by traditional medicinal practice are receiving extensive study. Multiple in vitro experimental investigations of A. heterophyllum have reported the analgesic, anti-inflammatory, antiarrhythmic, antiparasitic and anticancer properties, as well as its effects on the central nervous system. In this review, we highlight the classification, distribution, commerce, traditional uses, phytochemistry, pharmacology and conservation measures relevant to this species. Additionally, this review includes the biosynthetic pathways of A. heterophyllum’s key constituents, which could be targeted to enhance the expression levels of desired metabolites via genetic interventions. Studying the genomics, transcriptomics, proteomics and metabolomic aspects of this species would be helpful in developing highly designed genotypes and chemotypes of this species to be used in commercial production.
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ISSN 2095-4964
CN 31-2083/R

Editors-in-Chief:
Lixing Lao, Virginia, USA
Frequency: 6 issues per year
Publisher: Science Press, China

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