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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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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

Abstract141)   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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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

Abstract159)   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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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

Abstract579)   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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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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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

Abstract101)   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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Integrative medicine in the era of cancer immunotherapy: Challenges and opportunities
Ning Zhang, Xiao-he Xiao
Journal of Integrative Medicine    2021, 19 (4): 291-294.   DOI: 10.1016/j.joim.2021.03.005
Online available: 27 March 2021

Abstract76)   HTML    PDF      

Cancer immunotherapy has led to a new era of cancer treatment strategies, and transforming healthcare for cancer patients. Meanwhile, reports of immune-related adverse events have been increasing, greatly hindering the use of cancer immunotherapy. Traditional Chinese medicine (TCM), which has been widely used in Asian countries for thousands of years, is known to play a complementary role in the treatment of cancer. Taken in combined with conventional modern therapies, such as resection, ablation and radiotherapy, TCM exerts its main anti-cancer effects in two ways: health-strengthening (Fu-Zheng) and pathogen-eliminating (Qu-Xie). Theoretically, pathogen-eliminating TCM can promote the release of tumor-related antigens and should be able to increase the effect of immunotherapy, while health-strengthening TCM may have immune-enhancing mechanisms that overlap with immunotherapy. In the era of cancer immunotherapy, it is important to balance the use of TCM and immunotherapy, with the goal of enhancing immune efficacy and antagonizing immune toxicity. In this article, we discuss this issue by considering the mechanism of tumor immunotherapy, alongside the theoretical basis of TCM treatment of tumors, with the aim of bringing new insights to future research in this field.

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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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Can acupuncture enhance therapeutic effectiveness of antidepressants and reduce adverse drug reactions in patients with depression? A systematic review and meta-analysis
Ming-min Xu, Pei Guo, Qing-yu Ma, Xuan Zhou, Yu-long Wei, Lu Wang, Yue Chen, Yu Guo
Journal of Integrative Medicine    2022, 20 (4): 305-320.   DOI: 10.1016/j.joim.2022.05.002
Online available: 14 July 2022

Abstract44)   HTML    PDF      
Background
Some depressed patients receive acupuncture as an adjunct to their conventional medications.

Objective
This review aims to provide evidence on whether acupuncture can enhance the therapeutic effectiveness of antidepressants for treating depression, and explore whether acupuncture can reduce the adverse reactions associated with antidepressants.

Search strategy
English and Chinese databases were searched for randomized controlled trials (RCTs) published until December 1, 2021.

Inclusion criteria
RCTs with a modified Jadad scale score ≥ 4 were included if they compared a group of participants with depression that received acupuncture combined with antidepressants with a control group that received antidepressants alone.

Data extraction and analysis
Meta-analysis was performed, and statistical heterogeneity was assessed based on Cochran’s Q statistic and its related P-value. Primary outcomes were the reduction in the severity of depression and adverse reactions associated with antidepressants, while secondary outcomes included remission rate, treatment response, social functioning, and change in antidepressant dose. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework was used to evaluate the overall quality of evidence in the included studies.

Results
This review included 16 studies (with a total of 1958 participants). Most studies were at high risk of performance bias and at low or unclear risk of selection bias, detection bias, attrition bias, reporting bias, and other bias. Analysis of the 16 RCTs showed that, compared with antidepressants alone, acupuncture along with antidepressants reduced the Hamilton Depression Rating Scale-17 (HAMD-17) scores (standard mean difference [SMD] ?0.44, 95% confidence interval [CI] ?0.55 to ?0.33, P < 0.01; I2 = 14%), Self-rating Depression Scale (SDS) scores (SMD ?0.53, 95% CI ?0.84 to ?0.23, P < 0.01; I2 = 79%), and the Side Effect Rating Scale (SERS) scores (SMD ?1.11, 95% CI ?1.56 to ?0.66, P < 0.01; I2 = 89%). Compared with antidepressants alone, acupuncture along with antidepressants improved World Health Organization Quality of Life-BREF scores (SMD 0.31, 95% CI 0.18 to 0.44, P < 0.01; I2 = 15%), decreased the number of participants who increased their antidepressant dosages (relative risk [RR] 0.32, 95% CI 0.22 to 0.48, P < 0.01; I2 = 0%), and resulted in significantly higher remission rates (RR 1.52, 95% CI 1.26 to 1.83, P < 0.01; I2 = 0%) and treatment responses (RR 1.35, 95% CI 1.24 to 1.47, P < 0.01; I2 = 19%) in terms of HAMD-17 scores. The HAMD-17, SDS and SERS scores were assessed as low quality by GRADE and the other indices as being of moderate quality.

Conclusion
Acupuncture as an adjunct to antidepressants may enhance the therapeutic effectiveness and reduce the adverse drug reactions in patients receiving antidepressants. These findings must be interpreted with caution, as the evidence was of low or moderate quality and there was a lack of comparative data with a placebo control.

Systematic review registration: INPLASY202150008.
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Allium tuberosum alleviates pulmonary inflammation by inhibiting activation of innate lymphoid cells and modulating intestinal microbiota in asthmatic mice
Hao-cheng Zheng, Zi-rui Liu, Ya-lan Li, Yong-an Wang, Jing-wei Kong, Dong-yu Ge, Gui-ying Peng
Journal of Integrative Medicine    2021, 19 (2): 158-166.   DOI: 10.1016/j.joim.2020.11.003
Accepted: 11 July 2020
Online available: 02 December 2020

Abstract76)   HTML    PDF      
Objective
This study tests whether long-term intake of Allium tuberosum (AT) can alleviate pulmonary inflammation in ovalbumin (OVA)-induced asthmatic mice and evaluates its effect on the intestinal microbiota and innate lymphoid cells (ILCs).

Methods
BALB/c mice were divided into three groups: phosphate buffer saline, OVA and OVA + AT. The asthmatic murine model was established by sensitization and challenge of OVA in the OVA and OVA + AT groups. AT was given to the OVA + AT group by oral gavage from day 0 to day 27. On day 28, mice were sacrificed. Histopathological evaluation of lung tissue was performed using hematoxylin and eosin, and periodic acid-Schiff staining. The levels of IgE in serum, interleukin-5 (IL-5) and IL-13 from bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay. The ILCs from the lung and gut were detected by flow cytometry. 16S ribosomal DNA sequencing was used to analyze the differences in colon microbiota among treatment groups.

Results
We found that long-term intake of AT decreased the number of inflammatory cells from BALF, reduced the levels of IL-5 and IL-13 in BALF, and IgE level in serum, and rescued pulmonary histopathology with less mucus secretion in asthmatic mice. 16S ribosomal DNA sequencing results showed that AT strongly affected the colonic bacteria community structure in asthmatic mice, although it had no significant effect on the abundance and diversity of the microbiota. Ruminococcaceae and Desulfovibrionaceae were identified as two biomarkers of the treatment effect of AT. Moreover, AT decreased the numbers of ILCs in both the lung and gut of asthmatic mice.

Conclusion
The results indicate that AT inhibits pulmonary inflammation, possibly by impeding the activation of ILCs and adjusting the homeostasis of gut microbiota in asthmatic mice.
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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

Abstract147)   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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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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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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Can eastern wisdom resolve western epidemics? Traditional chinese medicine therapies and the opioid crisis
Thomas Efferth, An-long Xu, Roxana Damiescu, Mita Banerjee, Norbert W. Paul, David Y.W. Lee
Journal of Integrative Medicine    2021, 19 (4): 295-299.   DOI: 10.1016/j.joim.2021.03.006
Accepted: 02 February 2021
Online available: 26 March 2021

Abstract57)   HTML    PDF      
The widespread use of opioids to treat chronic pain led to a nation-wide crisis in the United States. Tens of thousands of deaths annually occur mainly due to respiratory depression, the most dangerous side effect of opioids. Non-opioid drugs and non-pharmacological treatments without addictive potential are urgently required. Traditional Chinese medicine (TCM) is based on a completely different medical theory than academic Western medicine. The scientific basis of acupuncture and herbal treatments as main TCM practices has been considerably improved during the past two decades, and large meta-analyses with thousands of patients provide evidence for their efficacy. Furthermore, opinion leaders in the United States favour non-pharmacological techniques including TCM for pain management to fight the opioid crisis. We advocate TCM as therapeutic option without addictive potential and without life-threatening side effects (e.g., respiratory depression) to treat chronic pain patients suffering from opioid misuse. The evidence suggests that: (1) opioid misuse cannot be satisfactorily managed with standard medication; (2) opinion leaders in the United States favour to consider non-opioid and non-pharmacological treatment strategies including those from TCM to treat acute and chronic pain conditions; (3) large meta-analyses provide scientific evidence for the clinical activity of acupuncture and herbal TCM remedies in the treatment of chronic pain. Future clinical trials should demonstrate the safety of TCM treatments if combined with Western medical practices to exclude negative interactions between both modalities.
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Antioxidant and antiaging effect of traditional Thai rejuvenation medicines in Caenorhabditis elegans 
Sutticha Ruangchuay, Qiang-qiang Wang, Liang-yi Wang, Jing Lin, Yong-chao Wang, Guo-huan Zhong, Katesarin Maneenoon, Ze-bo Huang, Sasitorn Chusri
Journal of Integrative Medicine    2021, 19 (4): 362-373.   DOI: https://doi.org/10.1016/j.joim.2021.03.004
Online available: 24 March 2021

Abstract32)   HTML    PDF      

Objective

This study explored the rejuvenation mechanisms of Thai polyherbal medicines using different approaches, including in vitro methods, as well as a well-defined nematode model, Caenorhabditis elegans.

Methods

THP-R-SR012 decoction was selected from 23 polyherbal medicines, based on metal-chelating and chain-breaking antioxidant capacities. The influences of this extract on the survival and some stress biomarkers of C. elegans under paraquat-induced oxidative stress were evaluated. Furthermore, lifespan analysis and levels of lipofuscin accumulation were examined in senescent nematodes. The phytochemical profile of THP-R-SR012 was analyzed. 

Results

Supplementation with THP-R-SR012 decoction significantly increased the mean lifespan and reduced the oxidative damage to C. elegans under oxidative stress conditions. Further, THP-R-SR012 supplementation slightly influenced the lifespan and the level of lipofuscin accumulation during adulthood. Antioxidant-related phytochemical constituents of THP-R-SR012 decoction were rutin, naringenin, 3,4-dihydroxybenzoic acid, gallic acid, glycyrrhizic acid, demethoxycurcumin and 18α-glycyrrhetinic acid.

Conclusion

The antioxidant potential of THP-R-SR012 was due to its scavenging properties, its enhancement of antioxidant-related enzyme activities, and the presence of the antioxidant-related compound. These results support the traditional use of THP-R-SR012 decoction as a tonic for nourishing and strengthening the whole body.

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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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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

Abstract121)   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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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

Abstract106)   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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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

Abstract1248)   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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Salvadora persica extract attenuates cyclophosphamide-induced hepatorenal damage by modulating oxidative stress, inflammation and apoptosis in rats
Talat Albukhari, Bassem Refaat, El-Sayed Bakr, Sameh Baz, Bodour Rajab, Hossam Gadalla, Mohamed El-Boshy
Journal of Integrative Medicine    2022, 20 (4): 348-354.   DOI: 10.1016/j.joim.2022.05.001
Accepted: 11 November 2021
Online available: 15 July 2022

Abstract37)           
Objective: Salvadora persica (SP) is used as a food additive and is a common ingredient in folk medicine. This study investigates the antioxidant, anti-inflammatory, and beneficial effects of SP against cyclophosphamide (CYP) toxicity in rats.
Methods: In a 10-day study, 32 male rats were equally allocated into 4 groups (8 rats/group) as follows: the normal control (NC group), normal rats that only received oral aqueous extract of SP (100 mg/[kg·d]; SP group), animals treated with intraperitoneal CYP injections (30 mg/[kg·d]; CYP group), and the CYP + SP group that concurrently received CYP with SP aqueous extract. Serum samples were collected to measure the liver and renal biochemical profiles, as well as antioxidant and oxidative stress markers and the concentrations of interleukin-1β (IL-1β), IL-6, IL-10, tumor necrosis factor-α (TNF-α), nuclear factor-κB (NF-κB) and adenosine 5’-monophosphate-activated protein kinase (AMPK). Hepatic and renal tissues were also harvested for histopathology and to measure apoptosis using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling technique, alongside tissue levels of oxidative stress markers.
Results: Liver enzymes, total bilirubin, creatinine and urea, as well as serum IL-1β, IL-6, TNF-α and NF-κB increased significantly, whilst total protein, albumin, calcium, IL-10 and AMPK declined in serum of the CYP group relative to the NC group. The hepatorenal concentrations of glutathione, glutathione peroxidase and catalase declined markedly in the CYP group, whereas malondialdehyde, protein adducts, and apoptosis index increased compared with the NC group. By contrast, the hepatorenal biochemistry and apoptosis index of the SP group were comparable to the NC group. Interestingly, the CYP + SP group had significant improvements in the liver and renal biochemical parameters, enhanced anti-oxidative and anti-inflammatory effects, and marked declines in hepatic and renal apoptosis relative to the CYP group. Moreover, all monitored parameters were statistically indistinguishable between the CYP + SP group and the NC group.
Conclusion: This study suggests that the aqueous extract of SP could be a potential remedy against CYP-induced hepatorenal damage and may act by modulating the AMPK/NF-κB signaling pathway and promoting anti-oxidative and anti-inflammatory activities.
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Is the N-of-1 method applicable in bodywork research? Lessons learned using a trial as a methodological pilot
Stergios Tsiormpatzis
Journal of Integrative Medicine    2021, 19 (3): 203-210.   DOI: 10.1016/j.joim.2021.01.010
Accepted: 08 January 2021
Online available: 02 February 2021

Abstract44)   HTML    PDF      
N-of-1 trial designs have rarely been used in bodywork research. Using a recent trial as a methodological pilot, critical issues related to the applicability of N-of-1 trials to bodywork are discussed. These include the issues of carry-over effects, bias-controlling approaches and statistical analysis. The discussion highlights the importance of mixed methods and draws some suggestions for a future research program. N-of-1 trials could be used to provide insights about some essential elements of bodywork modalities and their effectiveness.
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Pingchan granule for depressive symptoms in Parkinson’s disease: A randomized, double-blind, placebo-controlled trial
Si-chun Gu, Jie Zhou, Qing Ye, Can-xing Yuan
Journal of Integrative Medicine    2021, 19 (2): 120-128.   DOI: 10.1016/j.joim.2020.12.006
Online available: 22 January 2021

Abstract73)   HTML    PDF      

Background

Depression in patients with Parkinson’s disease (dPD) is related closely to quality of life. Current studies have suggested that Pingchan granule (PCG) might be effective for treating dPD.

Objective

This study determines the efficacy of PCG for depressive symptoms in Parkinson’s disease (PD).

Design, setting, participants and interventions

This was a randomized, double-blind, placebo-controlled trial, conducted in Longhua Hospital, Shanghai, China. Patients diagnosed with idiopathic PD and clinically significant depressive symptoms (defined by a 24-item Hamilton Rating Scale for Depression [HAM-D] score ≥ 8) were included in this study, followed for 24 weeks and randomly assigned to PCG or placebo treatment groups in a 1:1 ratio.

Main outcome measures

The primary outcome was the change from baseline to week 24 in HAM-D score among the set of patients who completed the study following the treatment protocol (per-protocol set). Secondary outcomes included changes in scores on the Unified Parkinson’s Disease Rating Scale (UPDRS) part 2 (UPDRS-II), UPDRS part 3 (UPDRS-III), Parkinson’s Disease Sleep Scale (PDSS) and Hamilton Rating Scale for Anxiety (HAM-A), between baseline and week 24.

Results

Eighty-six patients were enrolled, and 85 patients were included in the per-protocol set. HAM-D scores decreased by an adjusted mean of 11.77 (standard error [SE] 0.25) in the PCG group and 3.86 (SE 0.25) in the placebo group (between-group difference = 7.91, 95% confidence interval [7.22, 8.80], P < 0.001), in the multivariable linear regression. Improvements in scores on the UPDRS-II, UPDRS-III, PDSS, and HAM-A scales were also observed.

Conclusion

Treatment with PCG was well tolerated and improved depressive symptoms and motor and other non-motor symptoms in PD.

Trial registration

Chinese Clinical Trial Register, ChiCTR-INR-17011949.

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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

Abstract85)   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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An overview on the chemistry, pharmacology and anticancer properties of tetrandrine and fangchinoline (alkaloids) from Stephania tetrandra roots
Eric Wei Chiang Chan, Siu Kuin Wong, Hung Tuck Chan
Journal of Integrative Medicine    2021, 19 (4): 311-316.   DOI: 10.1016/j.joim.2021.01.001
Online available: 07 February 2021

Abstract66)   HTML    PDF      
Tetrandrine (TET) and fangchinoline (FAN) are dominant bisbenzylisoquinoline (BBIQ) alkaloids from the roots of Stephania tetrandra of the family Menispermaceae. BBIQ alkaloids comprise two benzylisoquinoline units linked by oxygen bridges. The molecular structures of TET and FAN are exactly the same, except that TET has a methoxy (?OCH3) group, while FAN has a hydroxyl (?OH) group at C7. In this overview, the current knowledge on the chemistry, pharmacology and anticancer properties of TET and FAN have been updated. The focus is on colon and breast cancer cells, because they are most susceptible to TET and FAN, respectively. Against colon cancer cells, TET inhibits cell proliferation and tumor growth by inducing apoptosis and G1 cell cycle arrest, and suppresses adhesion, migration and invasion of cells. Against breast cancer cells, FAN inhibits cell proliferation by inducing apoptosis, G1-phase cell cycle arrest and inhibits cell migration. The processes involve various molecular mechanisms and signaling pathways. Some insights on the ability of TET and FAN to reverse multi-drug resistance in cancer cells and suggestions for future research are provided. 
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Antifertility and profertility effects of the leaves and seeds of fluted pumpkin: Sperm quality, hormonal effects and histomorphological changes in the testes of experimental animal models
Rex-Clovis C. Njoku, Sunny O. Abarikwu
Journal of Integrative Medicine    2021, 19 (2): 104-110.   DOI: 10.1016/j.joim.2021.01.007
Online available: 24 January 2021

Abstract38)   HTML    PDF      
Fluted pumpkin (FP; Telfairia occidentalis) is an edible vegetable, grown in West Africa, that is used in traditional medicine for its regulatory effects on the male gonads. Scientific articles concerning the effects of FP were identified by searching PubMed, PubChem, Scopus, Springer, ResearchGate, Google Scholar and Web of Science; this literature was to better understand the effects of FP seed (FPS) and leaf (FPL) extracts on the testes. Data showed that in experimental animals extracts of FPL and FPS at 1/100 of the lethal dose promoted testis regeneration and improved testosterone concentration and sperm quality, while at higher doses they had antifertility effects. Several extracts of FPS and FPL, including ethanol, aqueous, methanol and hydroethanolic, had protective effects on the testes of study animals at lower doses (≥ 50 mg/kg body weight), but at higher doses (≥ 200 mg/kg body weight) they inhibited hormone synthesis, sperm quality and histomorphological structure, under both normal and disease conditions. The posttreatment effects of FPS on the gonads were reversible in young mature rats and FPS had slight systemic toxic effects. Although, there are inconsistencies in some of the published results, the current evidence suggests that FPS and FPL have both profertility and reversible antifertility effects in experimental animals. 
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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

Abstract308)   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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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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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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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

Abstract107)   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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Association of complementary and integrative therapy use and symptoms among Turkish patients with familial Mediterranean fever
Sibel Şentürk, Dilek Efe Arslan, Adil Çetinkaya
Journal of Integrative Medicine    2021, 19 (4): 340-346.   DOI: 10.1016/j.joim.2021.01.003
Accepted: 18 September 2020
Online available: 13 January 2021

Abstract65)   HTML    PDF      
Objective
This study explored the correlations between the use of complementary and integrative therapies (CITs) and symptoms among Turkish patients with familial Mediterranean fever (FMF).

Methods
This is a cross-sectional and descriptive study. The study was conducted with 1119 FMF patients who were registered to the social networking site for Behcet’s and the FMF Patients Association (Befemder) in Turkey, between January 2018 and February 2019. Data were collected using an online survey, for which a three‐part questionnaire was created using a Google form. Descriptive statistics, chi-square test and logistic regression analysis were used to analyze the data.

Results
It was determined that 53.2% of the individuals who participated in the research used various forms of CITs and that 32.8% used vitamin and mineral supplements (calcium, iron, and vitamin B12, C and D), 25.0% used nutritional supplements (fish oil and honey), and 24.6% used oral herbs (ginger, turmeric, green tea and rosemary) and mind-body methods (relaxation, respiration exercise and meditation). It was determined that the percentage of participants that used CITs was higher among women (odds ratio [OR] = 1.825; 95% confidence interval [CI] 1.421–2.344), those with joint pain (OR = 1.385; 95% CI 1.047–1.832), those with difficulty breathing (OR = 1.323; 95% CI 1.031–1.697), those with gastrointestinal symptoms (OR=1.405; 95% CI 1.089–1.814) and those who had a family member with FMF (OR = 1.437; 95% CI 1.115–1.851).

Conclusion
More than half of the individuals used at least one type of CIT for symptom control.
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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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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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Genome-wide analysis of hippocampal transfer RNA-derived small RNAs identifies new potential therapeutic targets of Bushen Tiansui formula against Alzheimer’s disease
Zhe-yu Zhang, Chun-hu Zhang, Jing-jing Yang, Pan-pan Xu, Peng-ji Yi, Mu-li Hu, Wen-jun Peng
Journal of Integrative Medicine    2021, 19 (2): 135-143.   DOI: 10.1016/j.joim.2020.12.005
Online available: 12 December 2020

Abstract80)   HTML    PDF      

Objective

Bushen Tiansui formula (BSTSF), a traditional Chinese medicine prescription, has been widely used to treat Alzheimer’s disease (AD). However, the mechanisms underlying its effects remain largely unknown. In this study, a rat AD model was used to study the effects of BSTSF on cognitive performance and expression of transfer RNA-derived small RNAs (tsRNAs) in the hippocampus, to determine whether treatment of AD with BSTSF could regulate the expression of tsRNAs, a novel small non-coding RNA.

Methods

To generate a validated AD model, oligomeric amyloid-β1-42 (Aβ1-42) was injected intracerebroventricularly into rats. The Morris water maze (MWM) test was used to evaluate rat cognitive performance, and tsRNA-sequencing was conducted to examine tsRNA expression in the rat hippocampus. Potential targets were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Bioinformatic analyses were conducted to investigate the biological function of candidate tsRNAs.

Results

The learning and memory deficits of Aβ1–42-induced AD rats, assessed by MWM tests, were clearly ameliorated by BSTSF treatment. A total of 387 tsRNAs were detected in the rat hippocampus. Among them, 13 were significantly dysregulated in AD rats compared with sham control rats, while 57 were markedly altered by BSTSF treatment, relative to untreated AD rats (fold change ≥ 2 and P < 0.05). Moreover, six BSTSF treatment-related tsRNAs were identified and validated by qRT-PCR. Bioinformatic analyses indicated that the six treatment-related tsRNAs had potential therapeutic roles, via multiple signaling pathways and Gene Ontology biological functions, including cyclic adenosine monophosphate and retrograde endocannabinoid signaling.

Conclusion

This study identified a previously uncharacterized mechanism underlying the effects of BSTSF in alleviating the learning and memory deficits in Aβ1–42-induced AD rats, demonstrating that tsRNAs are potential therapeutic targets of BSTSF in the treatment of AD.

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Improving the health and treatment success rates of in vitro fertilization patients with traditional chinese medicine: need for more robust evidence and innovative approaches
Marisa Casal
Journal of Integrative Medicine    2022, 20 (3): 187-192.   DOI: 10.1016/j.joim.2022.02.004
Online available: 21 February 2022

Abstract87)   HTML    PDF      
Maximising access to and the success of fertility treatments should be a priority for global reproductive health, as should overall patient well-being. The demand for in vitro fertilization (IVF) and other assisted fertility treatments has increased over the past decade and is likely to further increase in years to come. Nevertheless, there is still considerable unmet demand for infertility support worldwide. Moreover, the high emotional, physical and financial burden experienced by individuals undergoing IVF cycles can be a risk for their mental and physical health, which in turn can influence treatment continuation and the likelihood of IVF success. Studies from various parts of the world show that most individuals undergoing IVF also use adjunct alternative medicines and procedures, the most common being traditional Chinese medicine (TCM). The complementary and synergistic role of TCM for individuals undergoing IVF is an area that merits further attention and research, both for its potential positive effects on IVF success rates and for its broader physical and mental health benefits. However, much of the existing evidence is not sufficiently robust or consistent for findings to be adopted with confidence. This commentary argues that much work must be done to understand the efficacy and clinical best practices for these integrated approaches. This can be achieved in part by developing more robust and clinically relevant randomized controlled trial protocols, collecting and triangulating evidence through a variety of study designs and methods, and strengthening the collection and pooling of clinic-level data.
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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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Ziyin Huatan Recipe, a Chinese herbal compound, inhibits migration and invasion of gastric cancer by upregulating RUNX3 expression
Shang-jin Song, Xuan Liu, Qing Ji, Da-zhi Sun, Li-juan Xiu, Jing-yu Xu, Xiao-qiang Yue
Journal of Integrative Medicine    2022, 20 (4): 355-364.   DOI: 10.1016/j.joim.2022.02.006
Online available: 27 February 2022

Abstract87)   HTML    PDF      

Objectives

Ziyin Huatan recipe (ZYHT), a traditional Chinese medicine comprised of Lilii Bulbus, Pinelliae Rhizoma, and Hedyotis Diffusa, has shown promise in treating gastric cancer (GC) in the clinic. However, its potential mechanism in treating GC has not yet been clearly addressed. This study aimed to predict targets and molecular mechanisms of ZYHT by network pharmacology analysis and to explore the role of ZYHT in GC both in vitro and in vivo.

Methods

Targets and molecular mechanisms of ZYHT were predicted via network pharmacology analysis. The effects of ZYHT on the expression of metastasis-associated targets were further validated by western blot and quantitative real-time polymerase chain reaction. To explore the specific molecular mechanisms of ZYHT on migration and invasion, the runt-related transcription factor 3 (RUNX3) gene was knocked out by clustered regularly interspaced short palindromic repeats/Cas9, and lentiviral vectors were transfected into SGC-7901 cells. Then lung metastasis model of gastric cancer in nude mice was established to explore the anti-metastasis effect of ZYHT. Western blot and immunohistochemistry were used to explore the impact of ZYHT on the expression of metastasis-related proteins with or without RUNX3 gene.

Results

The network pharmacology analysis showed that ZYHT might inhibit focal adhesion, and migration, invasion and metastasis of GC. ZYHT inhibited the proliferation, migration and invasion of GC cells in vitro via regulating the expression of metastasis-associated targets. Knocking out RUNX3 almost completely reversed the cell phenotypes (migration and invasion) and protein expression levels elicited by ZYHT. In vivo studies showed that ZYHT inhibited the metastasis of GC cells to the lung and prolonged the survival time of nude mice. Knocking out RUNX3 partly reversed the metastasis of GC cells to the lung and the protein expression levels elicited by ZYHT.

Conclusion

ZYHT can e?ectively inhibit the invasion and migration of GC in vitro and in vivo, and its molecular mechanism may relate to the upregulation of RUNX3 expression.


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Natural antioxidants in the management of Parkinson’s disease: review of evidence from cell line and animal models
Reem Abdul-Latif, Ieva Stupans, Ayman Allahham, Benu Adhikari, Thilini Thrimawithana
Journal of Integrative Medicine    2021, 19 (4): 300-310.   DOI: 10.1016/j.joim.2021.03.007
Online available: 07 April 2021

Abstract87)   HTML    PDF      
Parkinson’s disease (PD) is a chronic progressive neurodegenerative disease. It results from the death of dopaminergic neurons. The pathophysiological mechanisms in idiopathic PD include the production of α-synuclein and mitochondrial respiratory function-affecting complex I, caused by reactive oxygen species. Therefore, the use of natural antioxidants in PD may provide an alternative therapy that prevents oxidative stress and reduces disease progression. In this review, the effects of hydroxytyrosol, Ginkgo biloba, Withania somnifera, curcumin, green tea, and Hypericum perforatum in PD animal and cell line models are compared and discussed. The reviewed antioxidants show evidence of protecting neural cells from oxidative stress in animal 
and cell models of PD. However, the clinical efficacy of these phytochemicals needs to be optimised and further investigated.
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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

Abstract90)   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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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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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

Abstract155)           

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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Polyherbal formula SC-E3 inhibits rheumatoid arthritis activity in a mouse model of type-II collagen-induced arthritis
Ju-Yeon Park, Young-Won Kwon, Sun-Ah Kim, Sun-Dong Park, Chang-Hyun Kim, Jin-Hee Kim, Ju-Hee Lee
Journal of Integrative Medicine    2021, 19 (3): 265-273.   DOI: 10.1016/j.joim.2020.12.001
Online available: 01 June 2021

Abstract56)   HTML    PDF      

Objective

SC-E3 is a polyherbal formula that contains five medicinal herbs used frequently in traditional herbal medicine. In our previous study, we demonstrated the antioxidant and anti-inflammatory effects of SC-E3. The present study examined the effects of SC-E3 in a mouse model of type-II collagen-induced arthritis (CIA).

Methods

In vivo, male DBA/1J mice were immunized by intradermal injection of bovine type-II collagen and complete or incomplete Freund’s adjuvant, to induce arthritis. SC-E3 was orally administered daily for 23 days. In vitro, bone marrow-derived macrophages (BMMs) were treated with macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL) in the absence or presence of SC-E3.

Results

Administrations of SC-E3 were found to have anti-arthritic effects in the joints of CIA mice, as evidenced by reduced paw swelling, bone erosion and deformation, inflammatory cell infiltration, and inflammation in synovial membrane. SC-E3 also reduced serum levels of tumor necrosis factor-α, interleukin-1β, aspartate aminotransferase and alanine aminotransferase. Furthermore, tartrate-resistant acid phosphatase-positive osteoclast numbers in the joints were significantly lower in SC-E3-treated CIA mice than in CIA mice. In addition, the differentiations of BMMs to multinucleated osteoclasts induced by M-CSF and RANKL stimulation were dose-dependently reduced by SC-E3.

Conclusion

These results suggest that SC-E3 possesses substantial anti-arthritic activity because it inhibits pro-inflammatory cytokines and osteoclastogenesis, and that SC-E3 has potential therapeutic use for the treatment of rheumatoid arthritis.


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Recovery of a patient with severe COVID-19 by acupuncture and Chinese herbal medicine adjuvant to standard care
Xin Yin, Shu-bin Cai, Lan-ting Tao, Lu-ming Chen, Zhong-de Zhang, Su-hong Xiao, Arthur Yin Fan, Xu Zou
Journal of Integrative Medicine    2021, 19 (5): 460-466.   DOI: 10.1016/j.joim.2021.06.001
Accepted: 06 June 2021
Online available: 28 June 2021

Abstract55)   HTML    PDF      
There is currently no drug or therapy that can cure the coronavirus disease 2019 (COVID-19), which is highly contagious and can be life-threatening in severe cases. Therefore, seeking potential effective therapies is an urgent task. An older female at the Leishenshan Hospital in Wuhan, China, with a severe case of COVID-19 with significant shortness of breath and decrease in peripheral oxygen saturation (SpO2), was treated using manual acupuncture and Chinese herbal medicine granule formula Fuzheng Rescue Lung with Xuebijing Injection in addition to standard care. The patient’s breath rate, SpO2, heart rate, ratio of neutrophil/lymphocyte (NLR), ratio of monocyte/lymphocyte (MLR), C-reactive protein (CRP), and chest computed tomography were monitored. Acupuncture significantly improved the patient’s breathing function, increased SpO2, and decreased her heart rate. Chinese herbal medicine might make the effect of acupuncture more stable; the use of herbal medicine also seemed to accelerate the absorption of lung infection lesions when its dosage was increased. The combination of acupuncture and herbs decreased NLR from 14.14 to 5.83, MLR from 1.15 to 0.33 and CRP from 15.25 to 6.01 mg/L. These results indicate that acupuncture and Chinese herbal medicine, as adjuvants to standard care, might achieve better results in treating severe cases of COVID-19.
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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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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

Abstract353)   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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Successfully treated recalcitrant atopic eczema with acupoint autohemotherapy: A case report and hypothesized mechanism of the therapy
Bin Zhao, Yong Chen, Shi-min Liao, Jian-ying Zheng, Shi-hua Yan, Dong-shu Zhang
Journal of Integrative Medicine    2022, 20 (2): 182-186.   DOI: 10.1016/j.joim.2022.01.003
Accepted: 07 December 2021
Online available: 13 January 2022

Abstract68)   HTML    PDF      
Acupoint autohemotherapy at bilateral Zusanli (ST36) and Xuehai (SP10) was used to treat a 26-year-old female patient who had suffered from recalcitrant atopic eczema (AE) for five years. The treatment was applied at a frequency of once per week for the first month, followed by a three-month period of once every other week. At the end of treatment, the patient's AE symptoms were entirely resolved, and by the end of a six-month follow-up her immunoglobulin E level had returned to the normal range. Further, there was no relapse of AE symptoms during the six-month follow-up. Therefore, we hypothesized that after the repeated treatments the local inflammatory reaction induced by autologous blood injection triggered a local immune response, followed by a systemic immune response after the repeated treatment, finally leading to the anti-inflammation and immunomodulation effects. This case suggests that acupoint autohemotherapy could be used as an effective complementary treatment for recalcitrant AE, especially in cases where other treatments have failed. Further comparative studies are needed to corroborate the value and mechanisms of this therapy.
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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

Abstract109)   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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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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Parkinson's disease, heart disease and propolis consumption
Fulvio A. Scorza, Antonio-Carlos G. de Almeida, Carla A. Scorza, Ana C. Fiorini, Josef Finsterer
Journal of Integrative Medicine    2021, 19 (5): 467-468.   DOI: 10.1016/j.joim.2021.07.002
Accepted: 02 July 2021
Online available: 22 July 2021

Abstract60)   HTML    PDF      
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Qili Qiangxin, a compound herbal medicine formula, alleviates hypoxia-reoxygenation-induced apoptotic and autophagic cell death via suppression of ROS/AMPK/mTOR pathway in vitro
Cai-lian Fana, Wan-jun Caib, Meng-nan Ye, Miao Chen, Yi Dai
Journal of Integrative Medicine    2022, 20 (4): 365-375.   DOI: 10.1016/j.joim.2022.04.005
Accepted: 07 February 2022
Online available: 15 July 2022

Abstract50)           
Objective: Qili Qiangxin (QLQX), a compound herbal medicine formula, is used effectively to treat congestive heart failure in China. However, the molecular mechanisms of the cardioprotective effect are still unclear. This study explores the cardioprotective effect and mechanism of QLQX using the hypoxia-reoxygenation (H/R)-induced myocardial injury model.
Methods: The main chemical constituents of QLQX were analyzed using high-performance liquid chromatography-evaporative light-scattering detection. The model of H/R-induced myocardial injury in H9c2 cells was developed to simulate myocardial ischemia-reperfusion injury. Apoptosis, autophagy, and generation of reactive oxygen species (ROS) were measured to assess the protective effect of QLQX. Proteins related to autophagy, apoptosis and signalling pathways were detected using Western blotting.
Results: Apoptosis, autophagy and the excessive production of ROS induced by H/R were significantly reduced after treating the H9c2 cells with QLQX. QLQX treatment at concentrations of 50 and 250 μg/mL caused significant reduction in the levels of LC3II and p62 degradation (P < 0.05), and also suppressed the AMPK/mTOR signalling pathway. Furthermore, the AMPK inhibitor Compound C (at 0.5 μmol/L), and QLQX (250 μg/mL) significantly inhibited H/R-induced autophagy and apoptosis (P < 0.01), while AICAR (an AMPK activator, at 0.5 mmol/L) increased cardiomyocyte apoptosis and autophagy and abolished the anti-apoptotic effect of QLQX. Similar phenomena were also observed on the expressions of apoptotic and autophagic proteins, demonstrating that QLQX reduced the apoptosis and auotophagy in the H/R-induced injury model via inhibiting the AMPK/mTOR pathway. Moreover, ROS scavenger, N-Acetyl-L-cysteine (NAC, at 2.5 mmol/L), significantly reduced H/R-triggered cell apoptosis and autophagy (P < 0.01). Meanwhile, NAC treatment down-regulated the ratio of phosphorylation of AMPK/AMPK (P < 0.01), which showed a similar effect to QLQX.
Conclusion: QLQX plays a cardioprotective role by alleviating apoptotic and autophagic cell death through inhibition of the ROS/AMPK/mTOR signalling pathway.
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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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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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