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Effects of turmeric (Curcuma longa) and its constituent (curcumin) on the metabolic syndrome: An updated review
Zeinab Vafaeipour, Bibi Marjan Razavi, Hossein Hosseinzadeh
Journal of Integrative Medicine    2022, 20 (3): 193-203.   DOI: 10.1016/j.joim.2022.02.008
Online available: 09 March 2022

Abstract127)   HTML    PDF      
Metabolic syndrome (MS) involves people with the following risk factors: obesity, hypertension, high glucose level and hyperlipidemia. It can increase the risk of heart disease, stroke and type 2 diabetes mellitus. The prevalence of MS in the world’s adult population is about 20%–25%. Today, there is much care to use medicinal plants. Turmeric (Curcuma longa) as well as curcumin which is derived from the rhizome of the plant, has been shown beneficial effects on different components of MS. Thus, the purpose of this manuscript was to introduce different in vitroin vivo and human studies regarding the effect of turmeric and its constituent on MS. Moreover, different mechanisms of action by which this plant overcomes MS have been introduced. Based on studies, turmeric and its bioactive component, curcumin, due to their anti-inflammatory and antioxidant properties, have antidiabetic effects through increasing insulin release, antihyperlipidemic effects by increasing fatty acid uptake, anti-obesity effects by decreasing lipogenesis, and antihypertensive effects by increasing nitric oxide. According to several in vivoin vitro and human studies, it can be concluded that turmeric or curcumin has important values as a complementary therapy in MS. However, more clinical trials should be done to confirm these effects. 
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Core muscle functional strength training for reducing the risk of low-back pain in military recruits: An open-label randomized controlled trial
Xin Wang, Wen-juan Song, Yi Ruan, Bing-chu Li, Can Lü, Nian Huang, Fan-fu Fang, Wei Gu
Journal of Integrative Medicine    2022, 20 (2): 145-152.   DOI: 10.1016/j.joim.2021.12.002
Accepted: 26 August 2021
Online available: 22 December 2021

Abstract120)           

Background

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


Objective

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


Design, setting, participants and intervention

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


Main outcome measures

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

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


Trial registration

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

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Tanshinone IIA prevents acute lung injury by regulating macrophage polarization
Jia-yi Zhao, Jin Pu, Jian Fan, Xin-yu Feng, Jian-wen Xu, Rong Zhang, Yan Shang
Journal of Integrative Medicine    2022, 20 (3): 274-280.   DOI: 10.1016/j.joim.2022.01.006
Online available: 21 February 2022

Abstract114)   HTML    PDF      

Objective

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

Methods

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

Results

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

Conclusion

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

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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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Reporting and methodological quality of meta-analyses of acupuncture for patients with migraine: A methodological investigation with evidence map
Ting-ting Lu, Cun-cun Lu, Mei-xuan Li, Li-xin Ke, Hui Cai, Ke-hu Yang
Journal of Integrative Medicine    2022, 20 (3): 213-220.   DOI: 10.1016/j.joim.2022.02.003
Accepted: 10 January 2022
Online available: 23 February 2022

Abstract99)           
Background

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

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

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

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

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

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

Conclusion
Acupuncture is an effective and safe intervention for preventing and treating migraine, and could be considered as a good option for patients with migraine. However, the reporting and methodological quality of MAs included in this overview is suboptimal. In the future, AMSTAR 2 and PRISMA tools should be followed when making and reporting an SR with MA.
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Local vibration therapy promotes the recovery of nerve function in rats with sciatic nerve injury
Lu Yin, Yun An, Xiao Chen, Hui-xin Yan, Tao Zhang, Xin-gang Lu, Jun-tao Yan
Journal of Integrative Medicine    2022, 20 (3): 265-273.   DOI: 10.1016/j.joim.2022.02.001
Online available: 21 February 2022

Abstract99)   HTML    PDF      
Objective
It has been reported that local vibration therapy can benefit recovery after peripheral nerve injury, but the optimized parameters and effective mechanism were unclear. In the present study, we investigated the effect of local vibration therapy of different amplitudes on the recovery of nerve function in rats with sciatic nerve injury (SNI).
Methods
Adult male Sprague-Dawley rats were subjected to SNI and then randomly divided into 5 groups: sham group, SNI group, SNI + A-1 mm group, SNI + A-2 mm group, and SNI + A-4 mm group (A refers to the amplitude; n = 10 per group). Starting on the 7th day after model initiation, local vibration therapy was given for 21 consecutive days with a frequency of 10 Hz and an amplitude of 1, 2 or 4 mm for 5 min. The sciatic function index (SFI) was assessed before surgery and on the 7th, 14th, 21st and 28th days after surgery. Tissues were harvested on the 28th day after surgery for morphological, immunofluorescence and Western blot analysis.
Results
Compared with the SNI group, on the 28th day after surgery, the SFIs of the treatment groups were increased; the difference in the SNI + A-2 mm group was the most obvious (95% confidence interval [CI]: [5.86, 27.09], P < 0.001), and the cross-sectional areas of myocytes in all of the treatment groups were improved. The G-ratios in the SNI + A-1 mm group and SNI + A-2 mm group were reduced significantly (95% CI: [?0.12, ?0.02], P = 0.007; 95% CI: [?0.15, ?0.06], P < 0.001). In addition, the expressions of S100 and nerve growth factor proteins in the treatment groups were increased; the phosphorylation expressions of ERK1/2 protein in the SNI + A-2 mm group and SNI + A-4 mm group were upregulated (95% CI: [0.03, 0.96], P = 0.038; 95% CI: [0.01, 0.94], P = 0.047, respectively), and the phosphorylation expression of Akt in the SNI + A-1 mm group was upregulated (95% CI: [0.11, 2.07], P = 0.031).
Conclusion
Local vibration therapy, especially with medium amplitude, was able to promote the recovery of nerve function in rats with SNI; this result was linked to the proliferation of Schwann cells and the activation of the ERK1/2 and Akt signaling pathways.
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Functional connectivity changes during migraine treatment with electroacupuncture at Shuaigu (GB8)
Xiang-yu Wei, Shi-lei Luo, HuiChen, Shan-shan Liu, Zhi-gang Gong, Song-huaZhan
Journal of Integrative Medicine    2022, 20 (3): 237-243.   DOI: 10.1016/j.joim.2022.01.009
Accepted: 06 January 2022
Online available: 31 January 2022

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

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

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

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

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

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Shanghai expert consensus on clinical protocol for traditional Chinese medicine treatment of COVID-19 among the elderly population (second edition)
Xuan Chen, Chou-ping Han, Wei Zhang on behalf of Writing Group of the Shanghai Expert Consensus on Clinical Protocol for Traditional Chinese Medicine Treatment of COVID- among the Elderly Population (Second Edition)
Journal of Integrative Medicine    2022, 20 (5): 427-431.   DOI: 10.1016/j.joim.2022.06.001
Online available: 10 June 2022

Abstract90)   HTML    PDF      
This document is the revised edition of the previously issued Shanghai Expert Consensus on Clinical Protocol for Traditional Chinese Medicine Treatment of COVID-19 among the Elderly Population. Based on the clinical experience and the Protocol for Diagnosis and Treatment of COVID-19 (Trial 9th Edition), this revised edition provides treatment approaches and recommendations to proactively cope with Omicron variant and increase the therapeutic efficacy for coronavirus disease 2019 among the elderly population in Shanghai, China.
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Efficacy of the herbal formula of Foeniculum vulgare and Rosa damascena on elderly patients with functional constipation: A double-blind randomized controlled tria
Maryam Azimi, Hanieh Niayesh, Mahboobeh Raeiszadeh, Sedigheh Khodabandeh-shahraki
Journal of Integrative Medicine    2022, 20 (3): 230-236.   DOI: 10.1016/j.joim.2022.03.001
Accepted: 21 January 2022
Online available: 10 March 2022

Abstract90)   HTML    PDF      
Background
Constipation is a common chronic bowel disorder with an incidence of more than 50% in the elderly population. Complementary and alternative medicine is a cost-effective and satisfactory treatment for constipation used widely by the elderly.

Objective
This study evaluates the efficacy of an herbal formula made from Foeniculum vulgare Mill. and Rosa damascena for the treatment of constipation in an elderly population and consequent changes to their quality of life.

Design, setting, participants and intervention
This double-blind randomized active controlled clinical trial, with parallel group allocation ratio of 1:1, was conducted in a referral clinic in Afzalipour Hospital, affiliated to Kerman University of Medical Sciences in Kerman, Southeastern Iran. Individuals over 60 years of age, diagnosed with functional constipation (based on the Rome IV criteria), were included in this study. Participants received a sachet of 10 g F. vulgare and R. damascena (herbal formula group) or polyethylene glycol 4000 (PEG 4000 group) with a glass of warm water two times a day for 4 weeks and were followed up for 4 additional weeks.

Main outcome measures
Constipation severity, stool consistency, and the quality of life were used as the primary outcomes. Drug side effects were used as a secondary outcome. The outcomes were assessed using the Constipation Assessment Scale, the Bristol Stool Form Scale, and the Patient Assessment of Constipation Quality of Life questionnaire.

Results
A total of 25 participants in each group completed the four-week treatment cycle and the eight-week follow-up. At the end of the four-week treatment cycle, all clinical outcomes had significant improvements in both groups (P < 0.05). The analysis of constipation severity (P < 0.001), stool consistency (P < 0.001), and the quality of life (P < 0.001) showed significant improvements with fewer side effects (mild diarrhea) and a longer duration of symptom relief in the herbal formula group compared to the PEG 4000 group.

Conclusion
Although both interventions significantly improved the treatment outcomes, constipation severity, stool consistency and the quality of life were improved more effectively by the herbal formula than by PEG 4000; however, the mechanism of action is not yet understood.

Trial registration
This trial was registered in the Iranian Registry of Clinical Trials (IRCTID: IRCT20200108046056N1).
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Aconitum heterophyllum Wall. ex Royle: A critically endangered medicinal herb with rich potential for use in medicine
Tareq A. Wani, Zahoor A. Kaloo, Nisar A. Dangroo
Journal of Integrative Medicine    2022, 20 (2): 104-113.   DOI: 10.1016/j.joim.2021.12.004
Online available: 28 December 2021

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

Abstract90)   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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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

Abstract89)   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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Antiplatelet and myocardial protective effect of shexiang tongxin dropping pill in patients undergoing percutaneous coronary intervention: A randomized controlled trial
Yan-jun Lin, Kun-li Jiao, Bo Liu, Lu Fang, Shu Meng
Journal of Integrative Medicine    2022, 20 (2): 126-134.   DOI: 10.1016/j.joim.2022.01.001
Accepted: 17 December 2021
Online available: 04 January 2022

Abstract88)   HTML    PDF      
Background
High on-clopidogrel platelet reactivity could be partially explained by loss-of-function alleles of CYP2C19, the enzyme that converts clopidogrel into its active form. Shexiang Tongxin Dropping Pill (STDP) is a traditional Chinese medicine to treat angina pectoris. STDP has been shown to improve blood flow in patients with slow coronary flow and attenuate atherosclerosis in apolipoprotein E-deficient mice. However, whether STDP can affect platelet function remains unknown.

Objective
The purpose of this study is to examine the potential effects of STDP on platelet function in patients undergoing percutaneous coronary intervention (PCI) for unstable angina. The interaction between the effects of STDP with polymorphisms of CYP2C19 was also investigated.

Design, participants and intervention
This was a single-center, randomized controlled trial in patients undergoing elective PCI for unstable angina. Eligible subjects were randomized to receive STDP (210 mg per day) plus dual antiplatelet therapy (DAPT) with clopidogrel and aspirin or DAPT alone.

Main outcome measures
The primary outcome was platelet function, reflected by adenosine diphosphate (ADP)-induced platelet aggregation and platelet microparticles (PMPs). The secondary outcomes were major adverse cardiovascular events (MACEs) including recurrent ischemia or myocardial infarction, repeat PCI and cardiac death; blood biomarkers for myocardial injury including creatine kinase-MB isoenzyme (CK-MB) and high-sensitive troponin I (hsTnI); and biomarkers for inflammation including intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1) and galectin-3.

Results
A total of 118 subjects (mean age: [66.8 ± 8.9] years; male: 59.8%) were included into analysis: 58 in the control group and 60 in the STDP group. CYP2C19 genotype distribution was comparable between the 2 groups. In comparison to the control group, the STDP group had significantly lower CK-MB (P < 0.05) but similar hsTnI (P > 0.05) at 24 h after PCI, lower ICAM-1, VCAM-1, MCP-1 and galectin-3 at 3 months (all P < 0.05) but not at 7 days after PCI (P > 0.05). At 3 months, the STDP group had lower PMP number ([42.9 ± 37.3] vs. [67.8 ± 53.1] counts/μL in the control group, P = 0.05). Subgroup analysis showed that STDP increased percentage inhibition of ADP-induced platelet aggregation only in slow metabolizers (66.0% ± 20.8% in STDP group vs. 36.0% ± 28.1% in the control group, P < 0.05), but not in intermediate or fast metabolizers. The rate of MACEs during the 3-month follow-up did not differ between the two groups.

Conclusion
STDP produced antiplatelet, anti-inflammatory and cardioprotective effects. Subgroup analysis indicated that STDP inhibited residual platelet reactivity in slow metabolizers only.
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Examining patterns of traditional chinese medicine use in pediatric oncology: A systematic review, meta-analysis and data-mining study
Chun Sing Lam, Li Wen Peng, Lok Sum Yang, Ho Wing Janessa Chou, Chi-Kong Li, Zhong Zuo, Ho-Kee Koon, Yin Ting Cheung
Journal of Integrative Medicine    2022, 20 (5): 402-415.   DOI: 10.1016/j.joim.2022.06.003
Accepted: 05 May 2022
Online available: 10 June 2022

Abstract85)   HTML    PDF      
Background
Traditional Chinese medicine (TCM) is becoming a popular complementary approach in pediatric oncology. However, few or no meta-analyses have focused on clinical studies of the use of TCM in pediatric oncology.

Objective
We explored the patterns of TCM use and its efficacy in children with cancer, using a systematic review, meta-analysis and data mining study.

Search strategy
We conducted a search of five English (Allied and Complementary Medicine Database, Embase, PubMed, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov) and four Chinese databases (Wanfang Data, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and VIP Chinese Science and Technology Periodicals Database) for clinical studies published before October 2021, using keywords related to “pediatric,” “cancer,” and “TCM.”

Inclusion criteria
We included studies which were randomized controlled trials (RCTs) or observational clinical studies, focused on patients aged < 19 years old who had been diagnosed with cancer, and included at least one group of subjects receiving TCM treatment.

Data extraction and analysis
The methodological quality of RCTs and observational studies was assessed using the six-item Jadad scale and the Effective Public Healthcare Panacea Project Quality Assessment Tool, respectively. Meta-analysis was used to evaluate the efficacy of combining TCM with chemotherapy. Study outcomes included the treatment response rate and occurrence of cancer-related symptoms. Association rule mining (ARM) was used to investigate the associations among medicinal herbs and patient symptoms.

Results
The fifty-four studies included in this analysis were comprised of RCTs (63.0%) and observational studies (37.0%). Most RCTs focused on hematological malignancies (41.2%). The study outcomes included chemotherapy-induced toxicities (76.5%), infection rate (35.3%), and response, survival or relapse rate (23.5%). The methodological quality of most of the RCTs (82.4%) and observational studies (80.0%) was rated as “moderate.” In studies of leukemia patients, adding TCM to conventional treatment significantly improved the clinical response rate (odds ratio [OR] = 2.55; 95% confidence interval [CI] = 1.49–4.36), lowered infection rate (OR = 0.23; 95% CI = 0.13–0.40), and reduced nausea and vomiting (OR = 0.13; 95% CI = 0.08–0.23). ARM showed that Radix Astragali, the most commonly used medicinal herb (58.0%), was associated with treating myelosuppression, gastrointestinal complications, and infection.

Conclusion
There is growing evidence that TCM is an effective adjuvant therapy for children with cancer. We proposed a checklist to improve the quality of TCM trials in pediatric oncology. Future work will examine the use of ARM techniques on real-world data to evaluate the efficacy of medicinal herbs and drug-herb interactions in children receiving TCM as a part of integrated cancer therapy.
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A "4D" systemic view on meridian essence: Substantial, functional, chronological and cultural attributes
Xiao Ye, Yu-lan Ren, Yun-hui Chen, Ji Chen, Xiao-jiao Tang, Zong-ming Zhang
Journal of Integrative Medicine    2022, 20 (2): 96-103.   DOI: 10.1016/j.joim.2021.11.006
Accepted: 22 October 2021
Online available: 27 November 2021

Abstract83)   HTML    PDF      
The term Jingluo, translated as meridian or channel, is a core component of traditional Chinese medicine (TCM) and has played a fundamental role in guiding the clinical practice of acupuncture for thousands of years. However, the essence of the meridian remains elusive and is a source of both confusion and debate for researchers. In this study, a “4D” systemic view on the essence of the meridian, namely substantial, functional, chronological, and cultural dimensions, was proposed based on a review of the ancient medical classics, recent research developments, and results from clinical practice. Previous studies have primarily focused on the substantial dimension of the meridian system, with scant interpretation about its functional domain. Neither systemic data nor evaluations have been adequately documented. Additionally, a limited but increasing number of studies have focused on the chronological and cultural dimensions. More investigations that embody the holistic concept of TCM and integrate the systemic modes and advanced techniques with dominant diseases of TCM need to be performed to obtain a more comprehensive understanding of the essence of meridians. The goal of this study is to yield useful information in understanding the essence of meridians and provide a reference and perspective for further research.
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Peperomia pellucida (L.) Kunth and eye diseases: A review on phytochemistry, pharmacology and toxicology
Keat Lam Ho, Phaik Har Yong, Chee Woon Wang, Umah Rani Kuppusamy, Chek Tung Ngo, Festo Massawe, Zhi Xiang Ng
Journal of Integrative Medicine    2022, 20 (4): 292-304.   DOI: 10.1016/j.joim.2022.02.002
Online available: 21 February 2022

Abstract80)   HTML    PDF      
Peperomia pellucida (L.) Kunth is a medicinal plant used to manage inflammatory illnesses such as conjunctivitis, and gastrointestinal and respiratory tract disorders in tropical and subtropical regions. However, little is known about its pharmacological mechanism of action against eye diseases. This review aims to critically discuss the phytochemistry, pharmacology and toxicology of P. pellucida as well as its roles in the treatment of cataract, glaucoma and diabetic retinopathy. Recent developments in the uses of P. pellucida for healthcare and nutraceutical products by the pharmaceutical industry are also covered in this review. For this review, a literature search was performed with PubMed, ScienceDirect, SciFinder Scholar and Scopus databases, using relevant keywords. Among the various phytochemicals identified from P. pellucida, β-caryophyllene, carotol, dillapiole, ellagic acid, pellucidin A, phytol and vitexin exhibit strong pharmacological activities within the mitogen-activated protein kinase and nuclear factor-κB signalling pathways in inflammatory eye diseases. The antihypertensive, anti-inflammatory, antioxidant, antihyperglycemic and anti-angiogenic activities displayed by P. pellucida extracts in many in vitroin vivo and clinical studies suggest its potential role in the management of inflammatory eye diseases. P. pellucida extract was non-toxic against normal cell lines but displayed mild toxicity in animal models. The growing public interest in P. pellucida has inspired the nutraceutical and pharmaceutical industries to process the plant into health products. Although the potential pharmacological mechanisms against eye diseases have been summarized, further studies of the interactions among constituent phytochemicals from P. pellucida within various signalling pathways shall support the use of the plant as an alternative therapeutic source.
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Low-level laser acupuncture reduces postoperative pain and morphine consumption in older patients with total knee arthroplasty: A randomized placebo-controlled trial
Chiung-Hui Huang, Mei-Ling Yeh, Fang-Pey Chen, Daphne Wu
Journal of Integrative Medicine    2022, 20 (4): 321-328.   DOI: 10.1016/j.joim.2022.04.002
Accepted: 24 January 2022
Online available: 09 April 2022

Abstract80)   HTML    PDF      
Background
Patients commonly develop postoperative pain after total knee arthroplasty (TKA). Acupuncture-related techniques and low-level laser therapy could be beneficial for pain management for older individuals.

Objective
To examine the effect of low-level laser acupuncture (LA) in reducing postoperative pain, pain-related interference in daily life, morphine consumption, and morphine-related side effects in older patients with knee osteoarthritis who underwent TKA.

Design, setting, participants and intervention
A single-blind randomized placebo-controlled trial was conducted. Patients (N = 82) were recruited and randomly assigned via a computer-generated list to the LA group or a placebo group. The LA group received low-level laser therapy at Sanyinjiao (SP6), Taixi (KI3), Kunlun (BL60), Fengshi (GB31), Futu (ST32) and Neiguan (PC6) after TKA, while the placebo acupuncture group received the same treatment procedure without laser energy output.

Main outcome measures
The primary outcome was postoperative pain intensity, and it was measured at baseline and hours 2, 6, 10, 24, 48 and 72 after TKA. The secondary outcomes, including relative pain, postoperative pain-related interference in daily life and morphine consumption, were measured at hours 24, 48 and 72 after TKA.

Results
Generalized estimating equations revealed significant between-group differences in pain intensity (P = 0.01), and trend differences in pain intensity for the LA group starting at hours 10 to 72 (P < 0.05) and morphine consumption at hours 48 and 72 (P < 0.05). The changes in pain-related interference in daily life were significant (P < 0.05) at 72 h, with the exception of the parameters for worst pain, mood, and sleep. Nausea and vomiting side effects from morphine had significant between-group differences at hours 10 and 24 (P < 0.05).

Conclusion

Low-level LA gradually reduced older patients’ postoperative pain intensity and morphine consumption within the first 72 h after their TKA for osteoarthritis. Low-level LA may have benefits as an adjuvant pain management technique for clinical care.


Trial registration

ClinicalTrials.gov registration number NCT03995446.

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Therapeutic effects of the extract of Sancao Formula, a Chinese herbal compound, on imiquimod-induced psoriasis via cysteine-rich protein 61
Wan-jun Guo, Yi Wang, Yu Deng, Lin-yan Cheng, Xin Liu, Ruo-fan Xi, Sheng-jie Zhu, Xin-yi Feng, Liang Hua, Kan Ze, Jian-yong Zhu, Dong-jie Guo, Fu-lun Li
Journal of Integrative Medicine    2022, 20 (4): 376-384.   DOI: 10.1016/j.joim.2022.04.004
Online available: 26 April 2022

Abstract79)   HTML    PDF      

Objective

Psoriasis is a common chronic inflammatory skin disease that is prone to recurrence, and the proinflammatory factor, cysteine-rich protein 61 (Cyr61), is important in its pathophysiology. Long-term clinical practice has shown that Sancao Formula (SC), a Chinese herbal compound, is effective in the treatment of psoriasis, but the precise mechanism remains unknown. In this study, we investigate the mechanism by which SC extract alleviates imiquimod (IMQ)-induced psoriasis.

Methods

The expression of Cyr61 in psoriatic lesions and normal healthy skin was detected using immunohistochemical analysis to investigate the biological role of Cyr61 in models of psoriatic inflammation. A psoriatic mouse model was established by topical application of IMQ, and the effect of topical application of SC extract was evaluated using the psoriasis area and severity index (PASI) score, hematoxylin-eosin staining, and histopathological features of the skin. Next, a HaCaT cell inflammation model was established using interferon-γ (IFN-γ), and the effect of SC extract on the mRNA and protein levels of Cyr61 and intercellular cell adhesion molecule-1 (ICAM-1) was confirmed using Western blot and quantitative real-time polymerase chain reaction analyses.

Results

Immunohistochemical staining showed that the expression of Cyr61 in psoriatic lesions was higher than that in normal skin samples (78.26% vs 41.18%, P < 0.05), and the number of Cyr61-positive cells in psoriatic lesions was also significantly higher than in normal skin (18.66 ± 2.51 vs 4.33 ± 1.52, P < 0.05). Treatment in mice with IMQ-induced psoriasis showed that SC extract could significantly improve the inflammatory phenotype, PASI score (10.875 ± 0.744 vs 3.875 ± 0 .582, P < 0.05), and pathological features compared with those in IMQ model group; SC treatment was also associated with decreased levels of Cyr61 and ICAM-1. In the IFN-γ-induced inflammatory cell model, the mRNA and protein levels of Cyr61 and ICAM-1 were upregulated, while the SC extract downregulated the levels of Cyr61 and ICAM-1.

Conclusion

The results provide a theoretical basis for the involvement of Cyr61 in the pathogenesis of psoriasis, and suggest that SC should be used to target Cyr61 for the prevention of psoriasis recurrence.

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Potential effects of propolis and honey in COVID-19 prevention and treatment: A systematic review of in silico and clinical studies
Witoo Dilokthornsakul, Ramanya Kosiyaporn, Rattanamanee Wuttipongwaragon, Piyameth Dilokthornsakul
Journal of Integrative Medicine    2022, 20 (2): 114-125.   DOI: 10.1016/j.joim.2022.01.008
Accepted: 10 January 2022
Online available: 26 February 2022

Abstract75)           
Background
Propolis and honey have been studied as alternative treatments for patients with coronavirus disease 2019 (COVID-19). However, no study has yet summarized the full body of evidence for the use of propolis and honey in COVID-19 prevention and treatment.

Objective
This study systematically reviews the mechanisms of propolis and honey against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and current evidence for the use of propolis and honey in COVID-19 prevention and treatment.

Search strategy
A systematic search was conducted of electronic databases including PubMed, Scopus, ScienceDirect, and Cochrane Library from their inceptions to April 2021.

Inclusion criteria
Studies that evaluated the effect of propolis or bee products against SARS-CoV-2 using in silico methods, clinical studies, case reports and case series were included.

Data extraction and analysis
A standardized data extraction form was used, and data were extracted by two independent reviewers. Narrative synthesis was used to summarize study results concerning the use of propolis or honey in COVID-19 prevention and treatment and their potential mechanisms of action against SARS-CoV-2.

Results
A total of 15 studies were included. Nine studies were in silico studies, two studies were case reports, one study was a case series, and three studies were randomized controlled trials (RCTs). In silico studies, using molecular docking methods, showed that compounds in propolis could interact with several target proteins of SARS-CoV-2, including angiotensin-converting enzyme 2, the main protease enzyme, RNA-dependent RNA polymerase, and spike protein. Propolis may have a positive effect for clinical improvement in mild and moderate-to-severe COVID-19 patients, according to case reports and case series. The included RCTs indicated that propolis or honey could probably improve clinical symptoms and decrease viral clearance time when they were used as adjuvant therapy to standard of care.

Conclusion
In silico studies showed that compounds from propolis could interact with target proteins of SARS-CoV-2, interfering with viral entry and viral RNA replication, while clinical studies revealed that propolis and honey could probably improve clinical COVID-19 symptoms and decrease viral clearance time. However, clinical evidence is limited by the small number of studies and small sample sizes. Future clinical studies are warranted.

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Combining electroacupuncture and transcranial direct current stimulation as an adjuvant therapy enhances spontaneous conversation and naming in subacute vascular aphasia: A retrospective analysis
Samwel Sylvester Msigwa, Yan Li, Xiang-lin Cheng, Fen Cao
Journal of Integrative Medicine    2022, 20 (3): 244-251.   DOI: 10.1016/j.joim.2022.03.002
Accepted: 21 January 2022
Online available: 12 March 2022

Abstract74)   HTML    PDF      
Objective
Emerging evidence shows the effectiveness of speech and language therapy (SLT); however, precise therapeutic parameters remain unclear. Evidence for the use of adjunctive transcranial direct current stimulation (tDCS) to treat post-stroke aphasia (PSA) is promising; however, the utility of combining tDCS and electroacupuncture (EA) has not yet been analyzed. This study assessed the therapeutic consequences of EA and tDCS coupled with SLT in subacute PSA patients who were also undergoing hyperbaric oxygen therapy (HBOT).

Methods
A retrospective analysis was conducted on subacute (<?6 months) PSA patients who were divided into three groups: patients who received EA plus tDCS (acupuncture group), patients who underwent tDCS (tDCS group), and patients who experienced conventional therapy (HBOT + SLT). All subjects underwent 21 days of treatment and also received conventional treatment. The aphasia battery of Chinese (ABC) was used to score pre- and post-intervention status.

Results
The analysis comprised 238 patients. Cerebral infarction was the most frequent stroke type (137 [57.6%]), while motor (66 [27.7%]) and global aphasia (60 [25.2%]) were the most common types of aphasia. After 21 days of intervention, the ABC scores of all patients were improved. The acupuncture group had the highest ABC scores, but only repetition, naming, and spontaneous speech were statistically improved (P < 0.01). Post-hoc tests revealed significant improvement in word retrieval in the acupuncture and tDCS groups (P < 0.01, P = 0.037), while the acupuncture group had additional significant improvement in spontaneous conversation (P < 0.01).

Conclusion
Combining acupuncture and tDCS as an adjuvant therapy for subacute PSA led to significant spontaneous speech and word retrieval improvements. Future prospective, multi-ethnic, multi-center trials are warranted.
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Fructus Zanthoxyli extract improves glycolipid metabolism disorder of type 2 diabetes mellitus via activation of AMPK/PI3K/Akt pathway: Network pharmacology and experimental validation
Ting Zhang, Qing Zhang, Wei Zheng, Ting Tao, Ruo-lan Li, Li-yu Wang, Wei Peng, Chun-jie Wu
Journal of Integrative Medicine    2022, 20 (6): 543-560.   DOI: 10.1016/j.joim.2022.07.004
Accepted: 13 May 2022
Online available: 05 August 2022

Abstract73)           
Objective: This study investigated the potential mechanisms behind the beneficial effects of Fructus Zanthoxyli (FZ) against type 2 diabetes mellitus (T2DM) based on network pharmacology and experimental validation.
Methods: Ultra-high-performance liquid chromatography coupled with hybrid quadrupole-orbitrap high-resolution mass spectrometry, and gas chromatography-mass spectrometry were used to identify the constituents of FZ. Next, the differentially expressed genes linked to the treatment of diabetes with FZ were screened using online databases (including Gene Expression Omnibus database and Swiss Target Prediction online database), and the overlapping genes and their enrichment were analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG). Finally, the pathway was verified by in vitro experiments, and cell staining with oil red and Nile red showed that the extract of FZ had a therapeutic effect on T2DM.
Results: A total of 43 components were identified from FZ, and 39 differentially expressed overlapping genes were screened as the possible targets of FZ in T2DM. The dug component-target network indicated that PPARA, PPARG, PIK3R3, JAK2 and GPR88 might be the core genes targeted by FZ in the treatment of T2DM. Interestingly, the enrichment analysis of KEGG showed that effects of FZ against T2DM were closely correlated with the adenosine monophosphate-activated protein kinase (AMPK) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathways. In vitro experiments further confirmed that FZ significantly inhibited palmitic acid-induced lipid formation in HepG2 cells. Moreover, FZ treatment was able to promote the AMPK and PI3K/Akt expressions in HepG2 cells.
Conclusion: Network pharmacology combined with experimental validation revealed that FZ extract can improve the glycolipid metabolism disorder of T2DM via activation of the AMPK/PI3K/Akt pathway.
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Homeopathy for COVID-19 in primary care: A randomized, double-blind, placebo-controlled trial (COVID-Simile study)
Ubiratan Cardinalli Adler, Maristela Schiabel Adler, Ana Elisa Madureira Padula, Livia Mitchiguian Hotta, Amarilysde Toledo Cesar, José Nelson Martins Diniz, Helen de Freitas Santos, Edson Zangiacomi Martinez
Journal of Integrative Medicine    2022, 20 (3): 221-229.   DOI: 10.1016/j.joim.2022.03.003
Accepted: 21 February 2022
Online available: 12 March 2022

Abstract73)   HTML    PDF      
Background
Different homeopathic approaches have been used as supportive care for coronavirus disease 2019 (COVID-19) cases, but none has been tested in a clinical trial.

Objectives
To investigate the effectiveness and safety of the homeopathic medicine, Natrum muriaticum LM2, for mild cases of COVID-19.

Design, setting, participants, and interventions
A randomized, double-blind, two‐armed, parallel, single-center, placebo-controlled clinical trial was conducted from June 2020 to April 2021 in S?o-Carlos, Brazil. Participants aged > 18 years, with influenza-like symptoms and positive result from a real-time polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2 were recruited and randomized (1:1) into two groups that received different treatments during a period of at-home-isolation. One group received the homeopathic medicine Natrum muriaticum, prepared with the second degree of the fifty-millesimal dynamization (LM2; Natrum muriaticum LM2), while the other group received a placebo.

Outcome measures
The primary endpoint was time until recovery from COVID-19 influenza-like symptoms. Secondary measures included a survival analysis of the number and severity of COVID-19 symptoms (influenza-like symptoms plus anosmia and ageusia) from a symptom grading scale that was informed by the participant, hospital admissions, and adverse events. Kaplan-Meier curves were used to estimate time-to-event (survival) measures.

Results
Data from 86 participants were analyzed (homeopathy, n = 42; placebo, n = 44). There was no difference in time to recovery between two groups among participants who were reporting influenza-like symptoms at the beginning of monitoring (homeopathy, n = 41; placebo, n = 41; P = 0.56), nor in a sub-group that had at least 5 moderate to severe influenza-like symptoms at the beginning of monitoring (homeopathy, n = 15; placebo, n = 17; P = 0.06). Secondary outcomes indicated that a 50% reduction in symptom score was achieved significantly earlier in the homeopathy group (homeopathy, n = 24; placebo, n = 25; P = 0.04), among the participants with a basal symptom score ≥ 5. Moreover, values of restricted mean survival time indicated that patients receiving homeopathy might have improved 0.9 days faster during the first five days of follow-up (P = 0.022). Hospitalization rates were 2.4% in the homeopathy group and 6.8% in the placebo group (P = 0.62). Participants reported 3 adverse events in the homeopathy group and 6 in the placebo group.

Conclusion
Results showed that Natrum muriaticum LM2 was safe to use for COVID-19, but there was no statistically significant difference in the primary endpoints of Natrum muriaticum LM2 and placebo for mild COVID-19 cases. Although some secondary measures do not support the null hypothesis, the wide confidence intervals suggest that further studies with larger sample sizes and more symptomatic participants are needed to test the effectiveness of homeopathic Natrum muriaticum LM2 for COVID-19.

Trial registration
UMIN Clinical Trials Registry ID: JPRN-UMIN000040602.
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Antiglycation and antioxidant activities of the crude extract and saponin fraction of Tribulus terrestris before and after microcapsules release
Célia Cristina Malaguti Figueiredo, Amanda da Costa Gomes, Filipe Oliveira Granero, João Luiz Bronzel Junior, Luciana Pereira Silva, Valdecir Farias Ximenes, Regildo Márcio Gonçalves da Silva
Journal of Integrative Medicine    2022, 20 (2): 153-162.   DOI: 10.1016/j.joim.2021.12.003
Online available: 28 December 2021

Abstract71)   HTML    PDF      

Objective

The present study investigated antiglycation and antioxidant activities of crude dry extract and saponin fraction of Tribulus terrestris. It also developed a method of microencapsulation and evaluated antiglycation and antioxidant activities of crude dry extract and saponin fraction before and after microcapsules release. 

Methods

Antiglycation activity was determined by relative electrophoretic mobility (REM), free amino groups and inhibition of advanced glycation end-product (AGE) formation. Antioxidant activity was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric ion reducing antioxidant power (FRAP), nitric oxide (NO) and thiobarbituric acid reactive species (TBARS) tests. Microcapsules were prepared using maltodextrin as wall material and freeze-drying as encapsulation technique. Morphological characterization of microcapsules was evaluated by scanning electron microscopy, and encapsulation efficiency and microcapsules release were determined by total saponins released. Antiglycation and antioxidant assays were performed using crude dry extract and saponin fraction of T. terrestris before and after release.

Results

Saponin fraction showed an increase of 32.8% total saponins. High-performance liquid chromatography-mass spectrometry analysis showed the presence of saponins in the obtained fraction. Antiglycation evaluation by REM demonstrated that samples before and after release present antiglycation activity similar to bovine serum albumin treated with aminoguanidine. Additionally, samples inhibited AGEs formation, highlighting treatment with saponins fraction after release (89.89%). Antioxidant tests demonstrated antioxidant activity of the samples. Crude dry extract before encapsulation presented the highest activities in DPPH (92.00%) and TBARS (32.49%) assays. Saponins fraction before encapsulation in FRAP test (499 μmol Trolox equivalent per gram of dry sample) and NO test (15.13 μmol nitrite formed per gram of extract) presented the highest activities. 

Conclusion

This study presented antiglycation activity of crude dry extract and saponins fraction of T. terrestris, besides it demonstrated promising antioxidant properties. It also showed that the encapsulation method was efficient and maintained biological activity of bioactive compounds after microcapsules release. These results provide information for further studies on antidiabetic and antiaging potential, and data for new herbal medicine and food supplement formulations containing microcapsules with crude extract and/or saponins fraction of T. terrestris.

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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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Progress in the design and quality control of placeboes for clinical trials of traditional Chinese medicine 
Ning Guo, Fei Wu, Mei Wu, Yuan Wang, Qing Lang, Xiao Lin, Yi Feng
Journal of Integrative Medicine    2022, 20 (3): 204-212.   DOI: 10.1016/j.joim.2022.02.005
Online available: 09 March 2022

Abstract67)   HTML    PDF      
In recent years, new preparations of traditional Chinese medicines (TCMs) have been developed, increasing the need for their clinical trials. Using placeboes rather than control drugs is increasingly popular in clinical trials of TCMs, as the therapeutic effects of the tested TCMs can be more properly judged. The basic attributes of TCM placeboes include similarity, safety, applicability and controllability. In particular, it is necessary to have similarities in appearance, color, smell and taste between the tested TCMs and placeboes. This is quite difficult for some TCMs due to their distinctive smell and taste. On the other hand, according to the TCM theory on homology of medicine and food, many foods also have certain bioactivities, potentially further complicating the selection of materials for TCM placeboes. In this review, firstly, studies on the special smell and taste of TCMs were introduced. Then, the preparation quality evaluation processes for TCM placeboes were summarized and discussed, based on the relevant literature published in recent years and the research results from our own lab. This review will facilitate the further research and development of TCM placeboes.
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Biotechnical system based on fuzzy logic prediction for surgical risk classification using analysis of current-voltage characteristics of acupuncture points
Sergey Filist, Riad Taha Al-Kasasbeh, Olga Shatalova, Nikolay Korenevskiy, Ashraf Shaqadan, Zeinab Protasova, Maksim Ilyash, Mikhail Lukashov
Journal of Integrative Medicine    2022, 20 (3): 252-264.   DOI: 10.1016/j.joim.2022.02.007
Accepted: 26 January 2022
Online available: 26 February 2022

Abstract67)   HTML    PDF      
Objective
This study aimed to develop expert fuzzy logic model to assist physicians in the prediction of postoperative complications of prostatic hyperplasia before surgery.

Methods
A method for classification of surgical risks was developed. The effect of rotation of the current-voltage characteristics at biologically active points (acupuncture points) was used for the formation of classifier descriptors. The effect determined reversible and non-reversible changes in electrical resistance at acupuncture points with periodic exposure to a sawtooth probe current. Then, the developed method was tested on the prediction of the success of surgical treatment of benign prostatic hyperplasia.

Results
Input descriptors were obtained from collected data including current-voltage characteristics of 5 acupuncture points and composed of 27 arrays feeding in the model. The maximum diagnostic sensitivity of the classifier for the success of a surgical operation in the control sample was 88% and for testing data set prediction accuracy was 97%.

Conclusion
The use of tuples of current-voltage characteristic descriptors of acupuncture points in the classifiers could be used to predict the success of surgical treatment with satisfactory accuracy. The model can be a valuable tool to support physicians' diagnosis.
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Remission of type 2 diabetes depends on prompt comprehensive lifestyle changes upon diagnosis: How can this “Road to Damascus” experience be supported?
Theocharis Koufakis, Kalliopi Kotsa, Nikolaos Papanas
Journal of Integrative Medicine    2022, 20 (4): 288-291.   DOI: 10.1016/j.joim.2022.04.001
Online available: 12 April 2022

Abstract65)   HTML    PDF      
Theoretically, a new diagnosis of type 2 diabetes mellitus (T2DM) requires a dramatic change in an individual’s way of life. Weight loss and physical activity can lead to remission of diabetes, which has been associated with a lower risk of developing complications. Today, the importance of a healthy lifestyle is further highlighted by data showing that obesity and diabetes increase the risk of severe complications from coronavirus disease 2019. However, remission rarely occurs in reality, probably due to the inability of people with T2DM to adhere to the intensive lifestyle interventions that are necessary. The complexity of contributing factors may explain why making these changes is so challenging and underscore the fact that there is no magical solution for T2DM. Instead, hard work from both patients and health care providers is needed for the conversion to be achieved. This article calls for more research on the underlying reasons why adhering to a healthy way of life is so difficult for people with diabetes and obesity. Clearly defining these barriers would facilitate the planning of effective policies to promote the adoption of appropriate lifestyle changes early in the course of the disease.
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Analysis of mechanisms of Shenhuang Granule in treating severe COVID-19 based on network pharmacology and molecular docking
Xiang-ru Xu, Wen Zhang, Xin-xin Wu, Hong-qiang Yang, Yu-ting Sun, Yu-ting Pu, Bei Wang, Wei Peng, Li-hua Sun, Quan Guo, Shuang Zhou, Bang-jiang Fang
Journal of Integrative Medicine    2022, 20 (6): 561-574.   DOI: 10.1016/j.joim.2022.07.005
Accepted: 15 June 2022
Online available: 05 August 2022

Abstract64)           
Objective: Severe cases of coronavirus disease 2019 (COVID-19) are expected to have a worse prognosis than mild cases. Shenhuang Granule (SHG) has been shown to be a safe and effective treatment for severe COVID-19 in a previous randomized clinical trial, but the active chemical constituents and underlying mechanisms of action remain unknown. The goal of this study is to explore the chemical basis and mechanisms of SHG in the treatment of severe COVID-19, using network pharmacology.
Methods: Ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry was employed to screen chemical constituents of SHG. Putative therapeutic targets were predicted by searching traditional Chinese medicine system pharmacology database and analysis platform, SwissTargetPrediction, and Gene Expression Omnibus (GEO) databases. The target protein-protein interaction network and enrichment analysis were performed to investigate the hub genes and presumptive mechanisms. Molecular docking and molecular dynamics simulations were used to verify the stability and interaction between the key chemical constituents of SHG and COVID-19 protein targets.
Results: Forty-five chemical constituents of SHG were identified along with 131 corresponding therapeutic targets, including hub genes such as HSP90AA1, MMP9, CXCL8, PTGS2, IFNG, DNMT1, TYMS, MDM2, HDAC3 and ABCB1. Functional enrichment analysis indicated that SHG mainly acted on the neuroactive ligand-receptor interaction, calcium signaling pathway and cAMP signaling pathway. Molecular docking showed that the key constituents had a good affinity with the severe acute respiratory syndrome coronavirus 2 protein targets. Molecular dynamics simulations indicated that ginsenoside Rg4 formed a stable protein-ligand complex with helicase.
Conclusion: Multiple components of SHG regulated multiple targets to inhibit virus invasion and cytokine storm through several signaling pathways; this provides a scientific basis for clinical applications and further experiments.
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Addressing the need for personalizing music therapy in integrative oncology
Tara Rajendran
Journal of Integrative Medicine    2022, 20 (4): 281-283.   DOI: 10.1016/j.joim.2022.01.005
Accepted: 15 December 2021
Online available: 17 January 2022

Abstract64)   HTML    PDF      
Music therapy is an integrative oncology practice that has been rapidly emerging, over the past two decades, as a field of its own, clinically and academically. The randomized controlled trials that evaluate the clinical impact of music therapy are growing in number, and at the same time, there has been progress in understanding the neurobiological mechanisms that underly the beneficial effects of music therapy. Cultural background and autobiographical memories may uniquely influence music perception and cognition. It is vital to personalize music therapy because music preferences are unique; one size does not fit all. Cognitive music science studies and clinical music therapy trials that study individualized music choices will serve as a vital step forward in providing patient-directed personalized integrative cancer care. The field of music therapy is advancing, and its ability to improve a patient’s quality of life can be understood only through robust, personalized, evidence-based initiatives that focus on research, advocacy, education, and delivery of care.
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Stress reduction via neuro-emotional technique to achieve the simultaneous resolution of chronic low back pain with multiple inflammatory and biobehavioural indicators: A randomized, double-blinded, placebo-controlled trial
Peter Bablis, Henry Pollard, Anthony L. Rosner
Journal of Integrative Medicine    2022, 20 (2): 135-144.   DOI: 10.1016/j.joim.2021.12.001
Online available: 28 December 2021

Abstract61)   HTML    PDF      

Background

Beginning with the concepts of stress developed by Selye, an approach to stress and pain management, known as neuro-emotional technique (NET), has been developed. It is a treatment approach based on the principle that the stressor effects of dormant and/or current unresolved issues or trauma are what determine one’s bodily responses. These responses are relatively personalized to the conditioned, experiential and emotional reality of the individual.

Objective

To determine the effect of NET on patients with chronic low back pain (CLBP) over time. 

Design, setting, participants, and interventions

In a randomized, double-blinded, placebo-controlled study conducted in a single clinic, NET or control treatments were given twice weekly for 4 weeks in a population of 112 patients. 

Main outcome measures

Outcome measures, including Oswestry Disability Index, Quadruple Visual Analogue Scale, the psychoneuroimmunology markers of blood serum levels of C-reactive protein, tumour necrosis factor-α, interleukin-1 (IL-1), IL-6, and IL-10, and 10 dimensions of the Short Form Health Survey scale, were assessed at baseline and at 1, 3 and 6 months following the intervention period.

Results

Compared to placebo, NET produced clinical and statistical significance (P < 0.001) via declines of virtually all physiological, pain and disability markers, accompanied by gains in quality-of-life indicators at 0 (baseline), 1, 3 and 6 months. Reductions of the percentages of patients whose 5 biomarkers lay outside the normative range were achieved at 1, 3 and 6 months by NET but not control interventions. 

Conclusion

A randomized, controlled trial of CLBP patients indicated that 8 NET interventions, compared to placebo, produced clinically and statistically significant reductions in pain, disability and inflammatory biomarkers, and improvements in quality-of-life measures.

Trial Registration

The trial was registered with the Australian and New Zealand Clinical Trials Registry (No. ACTRN12608000002381).

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Safety of acupotomy in a real-world setting: A prospective pilot and feasibility study
Sang-Hoon Yoon, Chan-Young Kwon, Hee-Geun Jo, Jae-Uk Sul, Hyangsook Lee, Jiyoon Won, Su Jin Jeong, Jun-Hwan Lee, Jungtae Leem
Journal of Integrative Medicine    2022, 20 (6): 514-523.   DOI: 10.1016/j.joim.2022.08.003
Accepted: 09 July 2021
Online available: 17 August 2022

Abstract61)   HTML    PDF      
Objective
Acupotomy is a modern acupuncture method that includes modern surgical methods. Since acupotomy is relatively more invasive than filiform acupuncture treatment, it is important to establish the safety profile of this practice. To justify further large-scale prospective observational studies, this preliminary study was performed to assess the feasibility of the approach and investigate the safety profile and factors potentially associated with adverse events (AEs).

Methods
This was a prospective pilot study that assessed the feasibility of a large-scale forthcoming safety study on acupotomy treatment in a real-world setting. The feasibility (call response rate, drop-out rate, response rate for each variable and recruitment per month) and safety profile (incidence, type, severity and causality of AEs, and factors potentially associated with AEs) were measured.

Results
A total of 28 participants joined the study from January to May 2018. A follow-up assessment was achieved in 258 (1185 treatment points) out of 261 sessions (1214 treatment points). The response rate via telephone on the day after treatment was 87.3%. There were 8 systemic AEs in all the sessions (8/258; 3.11%) and 27 local AEs on the total points treated (27/1185; 2.28%). Severe AEs did not occur. Total AE and local AE occurrence were associated with blade width and the number of needle stimulations per treatment point.

Conclusion
The findings suggest that it could be feasible to analyze the safety of acupotomy in a real-world setting. Moreover, the primary data on some relevant AEs could be determined. We are planning large-scale prospective studies based on these findings.
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Effects of bioactive compounds from Pleurotus mushrooms on COVID-19 risk factors associated with the cardiovascular system
Eduardo Echer dos Reis, Paulo Cavalheiro Schenkel, Marli Camassola
Journal of Integrative Medicine    2022, 20 (5): 385-395.   DOI: 10.1016/j.joim.2022.07.002
Accepted: 14 December 2021
Online available: 30 August 2022

Abstract59)           
Mushrooms are a group of fungi with great diversity and ultra-accelerated metabolism. As a consequence, mushrooms have developed a protective mechanism consisting of high concentrations of antioxidants such as selenium, polyphenols, β-glucans, ergothioneine, various vitamins and other bioactive metabolites. The mushrooms of the Pleurotus genus have generated scientific interest due to their therapeutic properties, especially related to risk factors connected to the severity of coronavirus disease 2019 (COVID-19). In this report, we highlight the therapeutic properties of Pleurotus mushrooms that may be associated with a reduction in the severity of COVID-19: antihypertensive, antihyperlipidemic, antiatherogenic, anticholesterolemic, antioxidant, anti-inflammatory and antihyperglycemic properties. These properties may interact significantly with risk factors for COVID-19 severity, and the therapeutic potential of these mushrooms for the treatment or prevention of this disease is evident. Besides this, studies show that regular consumption of Pleurotus species mushrooms or components isolated from their tissues is beneficial for immune health. Pleurotus species mushrooms may have a role in the prevention or treatment of infectious diseases either as food supplements or as sources for pharmacological agents.
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Moxibustion alleviates decreased ovarian reserve in rats by restoring the PI3K/AKT signaling pathway
Hong-xiao Li, Ling Shi, Shang-jie Liang Chen-chen Fang, Qian-qian Xu, Ge Lu, Qian Wang, Jie Cheng, Jie Shen, Mei-hong Shen
Journal of Integrative Medicine    2022, 20 (2): 163-172.   DOI: 10.1016/j.joim.2022.01.007
Online available: 27 February 2022

Abstract59)   HTML    PDF      

Objective

Moxibustion, a common therapy in traditional Chinese medicine, has potential benefits for treating decreased ovarian reserve (DOR). The present study investigates the protective effect of moxibustion in a rat model of DOR and explores the possible mechanisms.

Methods

Sixty-four female Sprague-Dawley rats were randomly divided into four groups: control, DOR, moxibustion (MOX), and hormone replacement therapy (HRT). The DOR rat model was established by intragastric administration of 50 mg/kg Tripterygium glycoside suspension (TGS), once daily for 14 days. MOX and HRT treatments were given from the day TGS administration was initiated. The ovarian reserve function was evaluated by monitoring the estrus cycle, morphological changes in ovaries, levels of serum estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and anti-Mullerian hormone (AMH), pregnancy rate and embryo numbers. Terminal-deoxynucleotidyl transferase-mediated nick-end-labeling staining was used to identify ovarian granulosa cell apoptosis, while the protein and mRNA expressions of Bax, B-cell lymphoma-2 (Bcl-2), phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) in ovarian tissues were examined by immunohistochemistry, Western blot and quantitative reverse transcription-polymerase chain reaction.

Results

Compared with the DOR group, MOX improved the disordered estrous cycle, promoted follicular growth, reduced the number of atresia follicles, increased the concentrations of serum E2 and AMH, and decreased serum FSH and LH concentrations. More importantly, the pregnancy rate and embryo numbers in DOR rats were both upregulated in the MOX treatment group, compared to the untreated DOR model. Further, we found that the MOX group had reduced apoptosis of ovarian granulosa cells, increased Bcl-2 expression and reduced expression of Bax. Furthermore, the PI3K/AKT signaling pathway was triggered by the moxibustion treatment.

Conclusion

Moxibustion improved ovarian function and suppressed apoptosis of ovarian granulosa cells in a rat model of DOR induced by TGS, and the mechanism may involve the PI3K/AKT signaling pathway.


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Apoptotic and autophagic death union by Thuja occidentalis homeopathic drug in cervical cancer cells with thujone as the bioactive principle
Asmita Pal, Sucharita Das, Soumalee Basu, Rita Kundu
Journal of Integrative Medicine    2022, 20 (5): 463-472.   DOI: 10.1016/j.joim.2022.06.004
Online available: 17 June 2022

Abstract57)   HTML    PDF      

Objective

‘Multi-targeting’ drugs can prove fruitful to combat drug-resistance of multifactorial disease—cervical cancer. This study envisioned to reveal if Thuja homeopathic mother tincture (MT) and its bioactive component could combat human papillomavirus (HPV)-16-infected SiHa cervical cancer cells since it is globally acclaimed for HPV-mediated warts.

Methods

Thuja MT was studied for its antiproliferative and antimigratory properties in SiHa cells followed by microscopic determination of reactive oxygen species (ROS) generation by 2’,7’-dichlorodihydrofluorescein diacetate (DCFDA) staining and loss in mitochondrial membrane potential (MMP) by rhodamine (Rh) 123 staining. Apoptosis and autophagy inductions were studied by acridine orange (AO) ethidium bromide (EB) staining and immunoblot analyses of marker proteins. The bioactive component of Thuja MT detected by gas chromatography-mass spectrometry was studied for antiproliferative and antimigratory properties along with in silico prediction of its cellular targets by molecular docking and oral drug forming competency.

Results 

Thuja MT showed significant antiproliferative and antimigratory potential in SiHa cells at a 50% inhibitory concentration (IC50) dosage of 17.3 μL/mL. An increase in DCFDA fluorescence and loss in Rh123 fluorescence prove that Thuja MT acted through the burst of ROS and loss in MMP respectively. AO/EB-stained cells under the microscope and immunoblot analyses supported Thuja-induced cellular demise via dual pathways—apoptosis and autophagy. Immunoblots showed cleavage of caspase-3 and poly adenosine diphosphate-ribose polymerase-1 (PARP-1) along with upregulation of Beclin-1, microtubule-associated protein 1 light chain 3B (LC3B)-II, and p62 proteins. Hence, the apoptotic cascade followed a caspase-3-dependent pathway supported by PARP-1 cleavage, while autophagic death was Beclin-1-dependent and mediated by accumulation of LC3BII and p62 proteins. Thujone, detected as the bioactive principle of Thuja MT showed greater anti-proliferative and anti-migratory potential at an IC50 77 μg/mL along with excellent oral drug competency with the ability for gastrointestinal absorption and blood-brain-barrier permeation with nil toxicity. Molecular docking depicted thujone with the strongest affinity for mammalian target of rapamycin, phosphoinositide 3-kinase, and protein kinase B followed by B-cell lymphoma 2, murine double minute 2 and adenosine monophosphate-activated protein kinase, which might act as upstream triggers of apoptotic-autophagic crosstalk. 

Conclusion

Robust ‘multi-targeting’ anticancer potential of Thuja drug and thujone for HPV-infected cervical cancer ascertain its therapeutic efficacy for HPV infections. 


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Effects of different courses of moxibustion treatment on intestinal flora and inflammation of a rat model of knee osteoarthritis
Ye-juan Jia, Tian-yu Li, Peng Han, Yu Chen, Li-jia Pan, Chun-sheng Jia
Journal of Integrative Medicine    DOI: 10.1016/j.joim.2022.01.004
Online available: 30 March 2022

The use of melittin to enhance transgene expression mediated by recombinant adeno-associated virus serotype 2 vectors both in vitro and in vivo
Yi-lin Xie, Ji-yao Wang, Yun He, Xiao-min Yu, Qing-yun Zheng, Chen Ling, Xi-lin Feng, Li-qing Zhu
Journal of Integrative Medicine    2023, 21 (1): 106-115.   DOI: 10.1016/j.joim.2022.10.003
Accepted: 26 June 2022
Online available: 14 October 2022

Abstract56)           
Objective: Melittin, a cell-penetrating peptide, improves the efficiency of many non-viral gene delivery vectors, yet its application in viral vectors has not been well studied. The non-pathogenic recombinant adeno-associated virus (rAAV) vector is an ideal in vivo gene delivery vector. However, its full potential will only be achieved after improvement of its transduction efficiency. To improve the transduction efficiency of rAAV2 vectors, we attempted to develop a melittin-based rAAV2 vector delivery strategy.
Methods: The melittin peptide was inserted into the rAAV2 capsid either in the loop VIII of all viral proteins (VPs) or at the N terminus of VP2. Various rAAV2-gfp or -fluc vectors were subjected to quantitative real-time polymerase chain reaction and Western blot assays to determine their titers and integrity of capsid proteins, respectively. Alternatively, the vectors based on wild-type capsid were pre-incubated with melittin, followed by transduction of cultured cells or tail vein administration of the mixture to C57BL/6 and BALB/c nude mice. In vivo bioluminescence imaging was performed to evaluate the transgene expression.
Results: rAAV2 vectors with melittin peptide inserted in the loop VIII of VPs had low transduction efficiency, probably due to dramatically reduced ability to bind to the target cells. Fusing the melittin peptide at the N-terminus of VP2 produced vectors without the VP2 subunit. Interestingly, among the commonly used rAAV vectors, pre-incubation of rAAV2 and rAAV6 vectors with melittin significantly enhanced their transduction efficiency in HEK293 and Huh7 cells in vitro. Melittin also had the ability to increase the rAAV2-mediated transgene expression in mouse liver in vivo. Mechanistically, melittin did not change the vector-receptor interaction. Moreover, cell counting kit-8 assays of cultured cells and serum transaminase levels indicated melittin had little cytotoxicity.
Conclusion: Pre-incubation with melittin, but not insertion of melittin into the rAAV2 capsid, significantly enhanced rAAV2-mediated transgene expression. Although further in vivo evaluations are required, this research not only expands the pharmacological potential of melittin, but also provides a new strategy to improve gene therapy mediated by rAAV vectors.
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Liver injury and dietary supplements: Does hydroxycitric acid trigger hepatotoxicity?
AndreaZovi, Roberto Langella, Andrea Nisic, Antonio Vitiello, Umberto M. Musazzi
Journal of Integrative Medicine    2022, 20 (5): 473-475.   DOI: 10.1016/j.joim.2022.05.003
Accepted: 11 May 2022
Online available: 30 May 2022

Abstract55)   HTML    PDF      
Rising rates of obesity has increased the global use of herbal supplements intended to control weight. However, taking these preparations without appropriate medical supervision could increase the risk of manifestation of side effects, especially at the hepatic level. In literature, different cases of acute liver injury consequent to the use of food supplements containing Garcinia cambogia and hydroxycitric acid are reported. This letter aims to review the most recent literature that analysed the herb-induced liver disease due to the use of hydroxycitric acid, from the first alert coming from the European Food and Drug Administration in 2009, to the last recent European food alerts from 2020 to 2021. It is noteworthy that in some cases it demonstrated the relationship between hydroxycitric acid and hepatotoxicity. Therefore, there is a need to draw more attention to the relationship between a safe use and a more awareness in the intake of these supplements, to preserve the safety of the consumers who increasingly purchase food supplements, products that have only nutritive properties and are never curative.
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Traditional Chinese medicine treatment for COVID-19: An overview of systematic reviews and meta-analyses
Han-ting Wu, Cong-hua Ji, Rong-chen Dai, Pei-jie Hei, Juan Liang, Xia-qiu Wu, Qiu-shuang Li, Jun-chao Yang, Wei Maob, Qing Guo
Journal of Integrative Medicine    2022, 20 (5): 416-426.   DOI: 10.1016/j.joim.2022.06.006
Accepted: 06 May 2022
Online available: 05 August 2022

Abstract52)           
Background: Coronavirus disease 2019 (COVID-19) is a rapidly spreading disease that has caused an extensive burden to the world. Consequently, a large number of clinical trials have examined the efficacy of traditional Chinese medicine (TCM) for treating and preventing COVID-19, with coinciding proliferation of reviews summarizing these studies.
Objective: This study aimed to evaluate the methodological quality and evidence quality of systematic reviews and meta-analyses on the efficacy of TCM.
Search strategy: Seven electronic databases, including PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chongqing VIP, Wanfang Data and SinoMed, were searched for systematic reviews and meta-analyses in October 2021. Search terms such as “Chinese medicine,” “Lianhua Qingwen” and “COVID-19” were used.
Inclusion criteria: Systematic reviews and meta-analyses of randomized controlled trials that evaluated the efficacy of TCM treatment of COVID-19 were included.
Data extraction and analysis: A Measurement Tool to Assess Systematic Reviews Version 2.0 (AMSTAR 2) was used to evaluate the methodological quality. The quality of evidence was graded using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Data extraction and analysis were performed by two reviewers independently.
Results: There were 17 meta-analyses included in our overview. The intervention group was defined as TCM combined with Western medicine, while the control group was Western medicine alone. The methodological quality of all the included studies was moderate to poor. A total of 89 outcome indicators were evaluated, of which, 8 were rated as moderate quality, 39 as low quality, and 41 as very low quality. Only one outcome measure was graded as being of high quality. The moderate quality of evidence indicated that, for the treatment of COVID-19, the clinical efficacy of TCM in combination with Western medicine was better, in terms of lung recovery, rate of conversion to severe/critical cases, symptom scores, duration of symptoms, mortality, and length of hospital stay.
Conclusion: Evidence from the included studies shows that, compared with conventional Western medical therapy alone, the addition of TCM to COVID-19 treatment may improve clinical outcomes. Overall, the quality of evidence of TCM for COVID-19 was moderate to poor. Meta-analyses of the use of TCM in the treatment of COVID-19 can be used for clinical decision making by accounting for the experiences of clinical experts, medical policies, and other factors.
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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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Methodology of network pharmacology for research on Chinese herbal medicine against COVID-19: A review
Yi-xuan Wang, Zhen Yang, Wen-xiao Wang, Yu-xi Huang, Qiao Zhang, Jia-jia Li, Yu-ping Tang, Shi-jun Yue
Journal of Integrative Medicine    2022, 20 (6): 477-487.   DOI: 10.1016/j.joim.2022.09.004
Accepted: 15 August 2022
Online available: 22 September 2022

Abstract50)   HTML    PDF      
Traditional Chinese medicine, as a complementary and alternative medicine, has been practiced for thousands of years in China and possesses remarkable clinical efficacy. Thus, systematic analysis and examination of the mechanistic links between Chinese herbal medicine (CHM) and the complex human body can benefit contemporary understandings by carrying out qualitative and quantitative analysis. With increasing attention, the approach of network pharmacology has begun to unveil the mystery of CHM by constructing the heterogeneous network relationship of “herb-compound-target-pathway,” which corresponds to the holistic mechanisms of CHM. By integrating computational techniques into network pharmacology, the efficiency and accuracy of active compound screening and target fishing have been improved at an unprecedented pace. This review dissects the core innovations to the network pharmacology approach that were developed in the years since 2015 and highlights how this tool has been applied to understanding the coronavirus disease 2019 and refining the clinical use of CHM to combat it.
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Using a consensus acupoints regimen to explore the relationship between acupuncture sensation and lumbar spinal postoperative analgesia: A retrospective analysis of prospective clinical cooperation
Yen-Lin Chao, Yi-Ai Rau, Hong-Sheng Shiue, Jiun-Lin Yan, Yuan-Yun Tang, Shao-Wen Yu, Bo-Yan Yeh, Yen-Lung Chen, Tsung-Hsien Yang, Shu-Chen Cheng, Yi-Wen Hsieh, Hsin-Chia Huang, Fu-Kuang Tsai, Yu-Sheng Chen, Geng-Hao Liu
Journal of Integrative Medicine    2022, 20 (4): 329-337.   DOI: 10.1016/j.joim.2022.04.003
Accepted: 31 January 2022
Online available: 12 April 2022

Abstract49)   HTML    PDF      
Objective
This study evaluated the effectiveness of acupuncture treatment on postoperative pain in patients with degenerative lumbar spine disease, and explored the relationship between the postoperative analgesic effect of acupuncture and the sensation of acupuncture experienced by the patients.

Methods
This retrospective study analyzed the medical records of 97 patients who had undergone an operation by the same surgeon due to degenerative lumbar disease. These patients were divided into acupuncture group (n = 32), patient-controlled analgesia (PCA) group (n = 27), and oral analgesia group (n = 38) according to the different postoperative analgesic methods. During their hospitalization, patients completed daily evaluations of their pain using a visual analogue scale (VAS), and injection times of supplemental meperidine were recorded. Also, the Chinese version of the Massachusetts General Hospital Acupuncture Sensation Scale (C-MASS) was used in the acupuncture group.

Results
Each of the three treatment groups showed significant reductions in postoperative pain, as shown by reduced VAS scores. The acupuncture group, however, had less rebound pain (P < 0.05) than the other two groups. Both the acupuncture and PCA groups experienced acute analgesic effects that were superior to those in the oral analgesia group. In addition, the higher the C-MASS index on the second day after surgery, the lower the VAS score on the fourth day after surgery. There was also a significant difference in the “dull pain” in the acupuncture sensation.

Conclusion
The results demonstrated that acupuncture was beneficial for postoperative pain and discomfort after simple surgery for degenerative spinal disease. It is worth noting that there was a disproportionate relevance between the patient’s acupuncture sensation and the improvement of pain VAS score.

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Xiaoyao San, a Chinese herbal formula, ameliorates depression-like behavior in mice through the AdipoR1/AMPK/ACC pathway in hypothalamus
Kai-rui Tang, Xiao-wei Mo, Xing-yi Zhou, Yue-yue Chen, Dong-dong Liu, Liang-liang He, Qing-yu Ma, Xiao-juan Li, Jia-xu Chen
Journal of Integrative Medicine    2022, 20 (5): 442-452.   DOI: 10.1016/j.joim.2022.07.003
Abstract48)   HTML    PDF      

Objective

Depression and metabolic disorders have overlapping psychosocial and pathophysiological causes. Current research is focused on the possible role of adiponectin in regulating common biological mechanisms. Xiaoyao San (XYS), a classic Chinese medicine compound, has been widely used in the treatment of depression and can alleviate metabolic disorders such as lipid or glucose metabolism disorders. However, the ability of XYS to ameliorate depression-like behavior as well as metabolic dysfunction in mice and the underlying mechanisms are unclear.

Methods

An in vivo animal model of depression was established by chronic social defeat stress (CSDS). XYS and fluoxetine were administered by gavage to the drug intervention group. Depression-like behaviors were analyzed by the social interaction test, open field test, forced swim test, and elevated plus maze test. Glucose levels were measured using the oral glucose tolerance test. The involvement of certain molecules was validated by immunofluorescence, histopathology, and Western blotting. In vitro, hypothalamic primary neurons were exposed to high glucose to induce neuronal damage, and the neuroprotective effect of XYS was evaluated by cell counting kit-8 assay. Immunofluorescence and Western blotting were used to evaluate the influences of XYS on adiponectin receptor 1 (AdipoR1), adenosine 5’-monophosphate-activated protein kinase (AMPK), acetyl-coenzyme A carboxylase (ACC) and other related proteins.

Results

XYS ameliorated CSDS-induced depression-like behaviors and glucose tolerance impairment in mice and increased the level of serum adiponectin. XYS also restored Nissl bodies in hypothalamic neurons in mice that exhibited depression-like behaviors and decreased the degree of neuronal morphological damage. In vivo and in vitro studies indicated that XYS increased the expression of AdipoR1 in hypothalamic neurons.

Conclusion

Adiponectin may be a key regulator linking depression and metabolic disorders;  regulation of the hypothalamic AdipoR1/AMPK/ACC pathway plays an important role in treatment of depression by XYS.

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Influence of electroacupuncture on ghrelin and the phosphoinositide 3-kinase/protein kinase B/endothelial nitric oxide synthase signaling pathway in spontaneously hypertensive rats
Yue Zhang, Dong-ling Zhong, Ya-ling Zheng, Yu-xi Li, Yi-jie Huang, Yi-jing Jiang, Rong-jiang Jin, Juan Li
Journal of Integrative Medicine    2022, 20 (5): 432-441.   DOI: 10.1016/j.joim.2022.06.007
Abstract48)   HTML    PDF      
Objective
To investigate the influence of electroacupuncture (EA) on ghrelin and the phosphoinositide 3-kinase/protein kinase B/endothelial nitric oxide synthase (PI3K/Akt/eNOS) signaling pathway in spontaneously hypertensive rats (SHRs).
Methods
Eight Wistar-Kyoto rats were used as the healthy blood pressure (BP) control (normal group), and 32 SHRs were randomized into model group, EA group, EA plus ghrelin group (EA + G group), and EA plus PF04628935 group (a potent ghrelin receptor blocker; EA + P group) using a random number table. Rats in the normal group and model group did not receive treatment, but were immobilized for 20 min per day, 5 times a week, for 4 continuous weeks. SHRs in the EA group, EA + G group and EA + P group were immobilized and given EA treatment in 20 min sessions, 5 times per week, for 4 weeks. Additionally, 1 h before EA, SHRs in the EA + G group and EA + P group were intraperitoneally injected with ghrelin or PF04628935, respectively, for 4 weeks. The tail-cuff method was used to measure BP. After the 4-week intervention, the rats were sacrificed by cervical dislocation, and pathological morphology of the abdominal aorta was observed using hematoxylin-eosin (HE) staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of ghrelin, nitric oxide (NO), endothelin-1 (ET-1) and thromboxane A2 (TXA2) in the serum. Isolated thoracic aortic ring experiment was performed to evaluate vasorelaxation. Western blot was used to measure the expression of PI3K, Akt, phosphorylated Akt (p-Akt) and eNOS proteins in the abdominal aorta. Further, quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to measure the relative levels of mRNA expression for PI3K, Akt and eNOS in the abdominal aorta.
Results
EA significantly reduced the systolic BP (SBP) and diastolic BP (DBP) (P < 0.05). HE staining showed that EA improved the morphology of the vascular endothelium to some extent. Results of ELISA indicated that higher concentrations of ghrelin and NO, and lower concentrations of ET-1 and TXA2 were present in the EA group (P < 0.05). The isolated thoracic aortic ring experiment demonstrated that the vasodilation capacity of the thoracic aorta increased in the EA group. Results of Western blot and qRT-PCR showed that EA increased the abundance of PI3K, p-Akt/Akt and eNOS proteins, as well as expression levels of PI3K, Akt and eNOS mRNAs (P < 0.05). In the EA + G group, SBP and DBP decreased (P < 0.05), ghrelin concentrations increased (P < 0.05), and the concentrations of ET-1 and TXA2 decreased (P < 0.05), relative to the EA group. In addition, the levels of PI3K and eNOS proteins, the p-Akt/Akt ratio, and the expression of PI3K, Akt and eNOS mRNAs increased significantly in the EA + G group (P < 0.05), while PF04628935 reversed these effects.
Conclusion
EA effectively reduced BP and protected the vascular endothelium, and these effects may be linked to promoting the release of ghrelin and activation of the PI3K/Akt/eNOS signaling pathway.
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Pharmacological action of quercetin against testicular dysfunction: A mini review
Damilare E. Rotimi, Tomilola D. Olaolu, Oluyomi S. Adeyemi
Journal of Integrative Medicine    2022, 20 (5): 396-401.   DOI: 10.1016/j.joim.2022.07.001
Accepted: 10 May 2022
Online available: 05 August 2022

Abstract47)           
The testis is an immune-privileged organ susceptible to oxidative stress and inflammation, two major factors implicated in male infertility. A reduction in the concentration and activities of testicular function biomarkers has been shown to correlate with impaired hypothalamic-pituitary-testicular axis and oxidative stress. However, the use of natural products to ameliorate these oxidative stress-induced changes may be essential to improving male reproductive function. Quercetin possesses several pharmacological activities that may help to combat cellular reproduction-related assaults, such as altered sperm function and reproductive hormone dysfunction, and dysregulated testicular apoptosis, oxidative stress, and inflammation. Studies have shown that quercetin ameliorates testicular toxicity, largely by inhibiting the generation of reactive oxygen species, with the aid of the two antioxidant pharmacophores present in its ring structure. The radical-scavenging property of quercetin may alter signal transduction of oxidative stress-induced apoptosis, prevent inflammation, and increase sperm quality in relation to the hormonal concentration. In this review, the therapeutic potential of quercetin in mediating male reproductive health is discussed.
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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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To “tell or not to tell”—Exploring disclosure about medicine use by people living with sleep disorders
Vibha Malhotra, Joanna Harnett, Erica McIntyre, Amie Steel, Keith Wong, Bandana Saini
Journal of Integrative Medicine    2022, 20 (4): 338-347.   DOI: 10.1016/j.joim.2022.03.004
Online available: 12 April 2022

Abstract43)   HTML    PDF      
Objective: To explore the difference in rates and reasons for disclosure of either conventional or complementary medicine (CM) to healthcare practitioners between people living with sleep disorders (SDs) and those without SDs.
Methods: A cross-sectional survey (N = 2019 adults) that measured sociodemographic characteristics, health status, health service utilisation, health literacy and health communication (medicine disclosure) of a representative sample of Australians was conducted. Data from participants reporting an SD (n = 265) were compared to those not reporting an SD to assess measures of health communication and disclosure about medicine use.
Results: Overall, rates of medicine disclosure to both conventional and CM practitioners were high, in respondents with (70%) and without an SD (57%). Those reporting an SD had higher expectations of their conventional health practitioner’s knowledge of CM, associated clinical decision-making skills, and approval of CM use, and held a higher degree of concern about drug interactions (P < 0.05). The main reasons cited for disclosing CM use to conventional health practitioners and conventional medicine use to CM practitioners were “I want them to fully understand my health status” and “I was concerned about drug interactions with the CMs used.”
Conclusion: The high rate of medicine use disclosure by people with SDs is driven by an intention to inform their healthcare practitioner about their health status and concerns about potential medicine interactions. Therefore, research about the expectations that people with an SD have of their conventional healthcare practitioners’ knowledge of CM and CM-drug interactions requires further examination. Likewise, further examination of CM practitioner’s conventional medicine knowledge is encouraged.
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Moxibustion regulates T-regulatory/T-helper 17 cell balance by modulating the microRNA-221/suppressor of cytokine signaling 3 axis in a mouse model of rheumatoid arthritis
Chuang Zhao, Xiao-yan Li, Zun-yuan Li, Miao Li, Zhi-dan Liu
Journal of Integrative Medicine    2022, 20 (5): 453-462.   DOI: 10.1016/j.joim.2022.06.002
Online available: 15 June 2022

Abstract43)   HTML    PDF      

Objective

Rheumatoid arthritis (RA) progression is associated with the balance of T-regulatory (Treg) and T-helper 17 (Th17) cells, while the role of microRNAs (miRs) in regulating Treg/Th17 cell balance has not been clarified. This study aimed to assess whether moxibustion could regulate Treg/Th17 cell balance by modulating the miR-221/suppressor of cytokine signaling 3 (SOCS3) axis in the RA mouse model.

Methods

A mouse model of collagen-induced arthritis (CIA) was established in male DBA/1J mice. Twenty-two days after CIA induction, the mice received daily treatment with moxibustion for 12 times. Pathological scores were assessed according to the levels of synovial hyperplasia. The expression levels of cytokines interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), IL-17 and IL-10 were analyzed in serum by enzyme-linked immunosorbent assay. The cluster of differentiation 4 (CD4+) splenocytes was analyzed by fluorescence-activated cell sorting. The expression levels of RA-related miRs and target genes were subsequently detected, and the target of miR-221 was confirmed by the dual-luciferase reporter assay.

Results

It was revealed that moxibustion treatment decreased the pathological scores and downregulated the expression levels of IL-1β, IL-6, TNF-α, IFN-γ and IL-17, while upregulated the expression level of IL-10. The Treg/Th17 cell balance was regulated by moxibustion treatment. The expression level of miR-221 was suppressed by moxibustion treatment. Furthermore, SOCS3 was found as the direct target of miR-221, which mediated the function of moxibustion by regulating the Treg/Th17 cell balance.

Conclusion

Moxibustion therapy regulated the Treg/Th17 cell balance by modulating the miR-221/SOCS3 axis in the RA mouse model.

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Integrated therapeutic plasma exchange and traditional Chinese medicine treatment in a patient with severe COVID-19: A case report
Chia-Wei Lin, Wei-Chen Hsu, Chien-Lu Lu, Su-Hsing Cheng, Cheng-Pin Chen, Yu-Chang Hou
Journal of Integrative Medicine    2022, 20 (6): 575-580.   DOI: 10.1016/j.joim.2022.09.001
Accepted: 06 February 2022
Online available: 22 November 2022

Abstract42)           
This report presents the case of a 59-year-old man with severe COVID-19 that gradually progressed to cytokine release syndrome and then acute respiratory distress syndrome; he was successfully treated via integration of therapeutic plasma exchange and traditional Chinese medicine. The patient initially presented with a sore throat, severe muscle aches, productive cough and fever. On the worsening of symptoms, remdesivir was administered. However, as the symptoms continued to worsen and a cytokine release syndrome was suspected, oxygen was provided through a high-flow nasal cannula (50 L/min) and therapeutic plasma exchange was performed to prevent worsening of the acute respiratory distress syndrome. On the same day, a course of traditional Chinese medicine was introduced in consultation with the infectious house staff. The patient’s symptoms gradually improved; the levels of C-reactive protein and D-dimers reduced, and the patient was weaned to a simple oxygen mask and eventually to room air. This is the first reported case of the integration of these treatments. Together, they prevented the patient from requiring intubation, played a role in cytokine management, and also improved the clinical symptoms, including productive purulent sputum, cough, frequent stool passage and intermittent fever, with no adverse effects. As a result, the patient was discharged within two weeks of the integration of these treatments. Therefore, the integration of therapeutic plasma exchange and traditional Chinese medicine is an effective therapy for patients with severe COVID-19.
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The scope and potential of music therapy in stroke rehabilitation
Tara Rajendran, Martha Summa-Chadwick
Journal of Integrative Medicine    2022, 20 (4): 284-287.   DOI: 10.1016/j.joim.2022.04.006
Accepted: 24 April 2022
Online available: 14 July 2022

Abstract39)   HTML    PDF      
There is a growing interest in the use of music therapy in neurological rehabilitation. Of all the major neurological illnesses, stroke rehabilitation has been observed to have some of the strongest potential for music therapy’s beneficial effect. The current burden of stroke has raised the need to embrace novel, cost-effective, rehabilitation designs that will enhance the existing physical, occupation, and speech therapies. Music therapy addresses a broad spectrum of motor, speech, and cognitive deficits, as well as behavioral and emotional issues. Several music therapy designs have focused on gait, cognitive, and speech rehabilitation, but most of the existing randomized controlled trials based on these interventions have a high risk of bias and are statistically insignificant. More randomized controlled trials with greater number of participants are required to strengthen the current data. Fostering an open and informed dialogue between patients, healthcare providers, and music therapists may help increase quality of life, dispel fallacies, and guide patients to specific musical interventions.
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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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