Electro-acupuncture promotes gut motility and alleviates functional constipation by regulating gut microbiota and increasing butyric acid generation in mice.

OBJECTIVE: Abnormalities in the gut microbiota and intestinal short-chain fatty acid (SCFA) levels are implicated in the pathogenesis of functional constipation (FC). Electro-acupuncture (EA) has been shown to improve constipation-related symptoms and rebalance the gut microbiota. However, it is currently unknown whether the gut microbiota is a key mechanistic target for EA or how EA promotes gut motility by regulating the gut microbiota and SCFAs. Therefore, we assessed the effects of EA in FC mice and pseudo-germfree (PGF) mice to address these questions. METHODS: Forty female Kunming mice were randomly separated into a normal control group (n = 8), an FC group (n = 8), an FC + EA group (n = 8), a PGF group (n = 8) and a PGF + EA group (n = 8). The FC group and FC + EA group were treated with diphenoxylate to establish the FC model; the PGF group and PGF + EA group were given an antibiotic cocktail to initiate the PGF model. After maintaining the model for 14 d, mice in the FC + EA and PGF + EA groups received EA stimulation at the ST25 and ST37 acupoints, once a day, 5 times per week, for 2 weeks. Fecal parameters and intestinal transit rate were calculated to assess the efficacy of EA on constipation and gastrointestinal motility. Colonic contents were used to quantify gut microbial diversity using 16S rRNA sequencing, and measure SCFA concentrations using gas chromatography-mass spectrometry. RESULTS: EA significantly shortened the first black stool defecation time (P < 0.05) and increased the intestinal transit rate (P < 0.01), and fecal pellet number (P < 0.05), wet weight (P < 0.05) and water content (P < 0.01) over 8 h, compared with the FC group, showing that EA promoted gut motility and alleviated constipation. However, EA treatment did not reverse slow-transit colonic motility in PGF mice (P > 0.05), demonstrating that the gut microbiota may play a mechanistic role in the EA treatment of constipation. In addition, EA treatment restored the Firmicutes to Bacteroidetes ratio and significantly increased butyric acid generation in FC mice (P < 0.05), most likely due to the upregulation of Staphylococcaceae microorganisms (P < 0.01). CONCLUSION: EA-mediated resolution of constipation occurs through rebalancing the gut microbiota and promoting butyric acid generation. Please cite this article as: Xu MM, Guo Y, Chen Y, Zhang W, Wang L, Li Y. Electro-acupuncture promotes gut motility and alleviates functional constipation by regulating gut microbiota and increasing butyric acid generation in mice. J Integr Med. 2023; Epub ahead of print.

A Systematic Review and Meta-Analysis Protocol to Establish How Common Clinical Acupoint Stimulation-Related Therapies Should Be Used for Managing Insomnia.

Background: Many studies have now investigated the effects of common clinical acupoint stimulation-related therapies (ASRTs) following the meridian theory of traditional Chinese medicine for the management of insomnia. However, ASRT choice is currently based on personal clinical experience or patient preference. This study will review the common ASRTs reported in clinical trials and analyze their efficacy and safety for managing insomnia with or without co-morbidities. Methods: English and Chinese databases will be thoroughly searched, and other potentially eligible trials will be obtained by reviewing reference lists of identified studies and previous reviews. Only randomized controlled trials (RCTs) of common clinical ASRTs to manage insomnia published in peer-reviewed journals will be considered. Sleep quality questionnaires or indices will be considered as the main outcome, while the secondary outcomes will include sleep parameters, daytime dysfunction, quality of life, and adverse effects. Two reviewers will independently investigate eligible RCTs, extract information, analyze their methodological quality, and employ Grading of Recommendations, Assessment, Development and Evaluation (GRADE) criteria to evaluate the strength of the evidence. The treatment impact of various ASRTs will be calculated using meta-analysis techniques, and the degree of study heterogeneity will be assessed using Cochrane's Q and I-squared statistics. Subgroup and sensitivity analyses will be used to evaluate the reliability of the results. Results: Our systematic review and meta-analysis will present up-to-date evidence on: 1) which common clinical ASRTs are beneficial for the management of insomnia; and 2) whether the effects of common clinical ASRTs on insomnia vary depending on clinical, participant, and treatment characteristics. Conclusion: The results of our review should help decision-makers make educated choices regarding evidence-based non-pharmacological management options for insomnia. Study Registration: The International Platform of Registered Systematic Review and Meta-analysis (INPLASY), record INPLASY2021120137.

Comparative effectiveness of different acupuncture courses in functional constipation: A Bayesian network meta-analysis of clinical trials.

AIM: The purpose of this study was to examine the comparative effectiveness of different acupuncture courses for functional constipation (FC). BACKGROUND: There is a need to optimize the treatment course of acupuncture for FC to improve efficacy and save health resources. METHODS: We performed a systematic electronic search of eight databases from inception to April 2021. Randomized controlled trials comparing acupuncture treatment with sham acupuncture were included. The main outcome indicators were complete spontaneous bowel movement (CSBM), spontaneous bowel movement, Bristol Stool Form Scale (BSFS), responder rate and safety evaluation (SE). RESULTS: In this network meta-analysis, 19 studies with 1753 participants and 8 different acupuncture treatments were included. Using the consistency model via Monte Carlo simulation iterations, we found that the effect of acupuncture treatment at 3/4 weeks may be better in terms of CSBM and BSFS. The results of rank probability analysis showed that 6 weeks of treatment may be better for the responder rate, and 2 weeks of treatment may be better for SE. And, subgroup analysis found that, for patients with chronic severe functional constipation (CSFC), 8 weeks of acupuncture treatment may be the best for CSBM. CONCLUSIONS: By indirect comparison, 3/4 weeks of acupuncture treatment may be the optimal course of treatment for FC in terms of improving bowel frequency and stool shape. And for CSFC, 8 weeks of acupuncture treatment may be the best. However, there is still a lack of direct comparison and publication bias that affects the accuracy of research results.

Electroacupuncture Alleviates Functional Constipation in Mice by Activating Enteric Glial Cell Autophagy via PI3K/AKT/mTOR Signaling.

OBJECTIVE: To investigate autophagy-related mechanisms of electroacupuncture (EA) action in improving gastrointestinal motility in mice with functional constipation (FC). METHODS: According to a random number table, the Kunming mice were divided into the normal control, FC and EA groups in Experiment I. The autophagy inhibitor 3-methyladenine (3-MA) was used to observe whether it antagonized the effects of EA in Experiment II. An FC model was established by diphenoxylate gavage. Then the mice were treated with EA stimulation at Tianshu (ST 25) and Shangjuxu (ST 37) acupoints. The first black stool defecation time, the number, weight, and water content of 8-h feces, and intestinal transit rate were used to assess intestinal transit. Colonic tissues underwent histopathological assessment, and the expressions of autophagy markers microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1 were detected by immunohistochemical staining. The expressions of phosphoinositide 3-kinases (PI3K)-protein kinase B (AKT)-mammalian target of rapamycin (mTOR) signaling pathway members were investigated by Western blot and quantitative reverse transcription-polymerase chain reaction, respectively. The relationship between enteric glial cells (EGCs) and autophagy was observed by confocal immunofluorescence microscopy, localization analysis, and electron microscopy. RESULTS: EA treatment shortened the first black stool defecation time, increased the number, weight, and water content of 8-h feces, and improved the intestinal transit rate in FC mice (P<0.01). In terms of a putative autophagy mechanism, EA treatment promoted the expressions of LC3 and Beclin-1 proteins in the colonic tissue of FC mice (P<0.05), with glial fibrillary acidic protein (GFAP) and LC3 significantly colocalized. Furthermore, EA promoted colonic autophagy in FC mice by inhibiting PI3K/AKT/mTOR signaling (P<0.05 or P<0.01). The positive effect of EA on intestinal motility in FC mice was blocked by 3-MA. CONCLUSION: EA treatment can inhibit PI3K/AKT/mTOR signaling in the colonic tissues of FC mice, thereby promoting EGCs autophagy to improve intestinal motility.

Can acupuncture enhance therapeutic effectiveness of antidepressants and reduce adverse drug reactions in patients with depression? A systematic review and meta-analysis.

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.

Effectiveness and safety of acupuncture for treating functional constipation: An overview of systematic reviews.

BACKGROUND: Functional constipation (FC) is one of the most prevalent functional gastrointestinal disorders. Dissatisfaction with medications prescribed to treat FC may lead patients to seek alternative treatments. Numerous systematic reviews (SRs) examining the use of acupuncture to treat FC have reported inconsistent results, and the quality of these studies has not been fully evaluated. OBJECTIVE: In this overview, we evaluated and summarized clinical evidence on the effectiveness and safety of acupuncture for treating FC and evaluated the quality and bias of the SRs we reviewed. SEARCH STRATEGY: The search strategy was structured by medical subject headings and search terms such as "acupuncture therapy" and "functional constipation." Electronic searches were conducted in eight databases from their inception to September 2020. INCLUSION CRITERIA: SRs that investigated the effectiveness and safety of acupuncture for managing FC were included. DATA EXTRACTION AND ANALYSIS: Two authors independently extracted information and appraised the methodology, reporting accuracy, quality of evidence, and risk of bias using the following critical appraisal tools: (1) A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2); (2) Risk of Bias in Systematic Reviews (ROBIS); (3) Preferred Reporting Items for Systematic Reviews and Meta-analyses for Acupuncture (PRISMA-A); and (4) the Grading of Recommendations, Assessment, Development and Evaluations (GRADE). A κ index was used to score the level of agreement between the 2 reviewers. RESULTS: Thirteen SRs that examined the clinical utility of acupuncture for treating FC were identified. Using the AMSTAR 2 tool, we rated 92.3% (12/13) of the SRs as "critically low" confidence and one study as "low" confidence. Using the ROBIS criteria, 38.5% (5/13) of the SRs were considered to have "low risk" of bias. Based on PRISMA-A, 76.9% (10/13) of the SRs had over 70% compliance with reporting standards. The inter-rater agreement was good for AMSTAR 2, ROBIS, and PRISMA-A. Using the GRADE tool, we classified 22.5% (9/40) of the measured outcomes as "moderate" quality, 57.5% (23/40) as "low" quality, and 20.0% (8/40) as "very low" quality. The inter-rater agreement was moderate when using GRADE. Descriptive analyses indicated that acupuncture was more efficacious than sham acupuncture for improving weekly complete spontaneous bowel movements (CSBMs) and for raising the Bristol Stool Form Scale (BSFS) score. Acupuncture appeared to be superior to anti-constipation drugs for improving weekly spontaneous bowel movements, the total effective rate, and the Patient Assessment of Constipation Quality of Life score. Although ten SRs mentioned the occurrence of adverse events, serious adverse events were not associated with acupuncture treatment. CONCLUSION: Acupuncture may be more efficacious than sham acupuncture for improving CSBMs and BSFS scores and may be superior to anti-constipation drugs for improving bowel movement frequency, as well as quality of life. Limitations to current studies and inconsistent evidence suggest a need for more rigorous and methodologically sound SRs to draw definitive conclusions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020189173.

Corrigendum to "Positive Effect of Electro-Acupuncture Treatment on Gut Motility in Constipated Mice Is Related to Rebalancing the Gut Microbiota".

[This corrects the article DOI: 10.1155/2021/6652017.].

The Effectiveness of Acupuncture in Management of Functional Constipation: A Systematic Review and Meta-Analysis.

OBJECTIVE: The purpose of this study was to assess the effectiveness and safety of acupuncture for functional constipation (FC). METHODS: A rigorous literature search was performed in English (PubMed, Web of Science, the Cochrane Library, and EMBASE) and Chinese (China National Knowledge Infrastructure (CNKI), Chinese Biological Medical (CBM), Wanfang database, and China Science and Technology Journal (VIP)) electronic databases from their inception to October 2019. Included randomized controlled trials (RCTs) compared acupuncture therapy with sham acupuncture or pharmacological therapies. The outcome measures were evaluated, including the primary outcome of complete spontaneous bowel movement (CSBM) and secondary outcomes of Bristol Stool Form Scale (BSFS), constipation symptoms scores (CSS), responder rate, the Patient Assessment of Constipation Quality of Life (PAC-QOL) questionnaire, and safety evaluation. Meta-analysis was performed by using RevMan5.3. RESULTS: The merged data of 28 RCTs with 3525 participants indicated that acupuncture may be efficient for FC by increasing CSBMs (p < 0.00001; MD = 0.84 [95% CI, 0.65 to 1.03]; I 2 = 0%) and improving constipation symptoms (p=0.03; SMD = -0.4 [95% CI, -0.78 to -0.03]; I 2 = 74%), stool formation (p < 0.00001; MD = 0.24 [95% CI, 0.15 to 0.34]; I 2 = 0%), quality of life (p < 0.00001; N = 1, MD = -0.33 [95% CI, -0.45 to -0.21]), and responder rates (p=0.02; RR = 2.16; [95% CI, 1.1 to 4.24]; I 2 = 69%) compared with the effects of sham treatment. No increased risk of adverse events was observed (p=0.44; RR = 1.18; [95% CI, 0.77 to 1.81]; I 2 = 0%). With regard to medication comparisons, the pooled data indicated that acupuncture was more effective in increasing CSBMs (p=0.004; MD = 0.53 [95% CI, 0.17 to 0.88]; I 2 = 88%) and improving patients' quality of life (p < 0.00001; SMD = -0.73 [95% CI, -1.02 to -0.44]; I 2 = 64%), with high heterogeneity. However, there were no significant differences in responder rate (p=0.12; RR = 1.31; [95% CI, 0.94 to 1.82]; I 2 = 53%), BSFS (p=0.5; MD = 0.17 [95% CI, -0.33 to 0.68]; I 2 = 93%), or CSS (p=0.05; SMD = -0.62 [95% CI, -1.23 to -0.01]; I 2 = 89%). Regarding safety evaluation, acupuncture was safer than medications (p < 0.0001; RR = 0.3; [95% CI, 0.18 to 0.52]; I 2 = 30%). CONCLUSIONS: Current evidence suggests that acupuncture is an efficient and safe treatment for FC. Acupuncture increased stool frequency, improved stool formation, alleviated constipation symptoms, and improved quality of life. However, the evidence quality was relatively low and the relationship between acupuncture and drugs is not clear. More high-quality trials are recommended in the future. PROSPERO registration number: CRD42019143347.

Efficacy and safety of moxibustion for patients with functional constipation: A protocol for systematic review and meta analysis.

INTRODUCTION: The objective of this review is to assess the efficacy and safety of moxibustion for treating patients with functional constipation (FC). METHODS AND ANALYSIS: We will electronically search the following databases: OVID MEDLINE, EMBASE, PubMed, Web of Science, the Cochrane Central Register of Controlled Trials, Cochrane library, CINAHL, AMED, China Network Knowledge Infrastructure, Wan-fang Database, China Biomedical Literature Database, and other resources from inception to October 2019, without any language restrictions. Randomised-controlled trials will be included. The primary outcome is the improvement in mean complete spontaneous bowel movements and stool form (utilize the Bristol Stool Form Scale [BSFS]). Secondary outcomes involve the degree of difficulty in defecation, proportion of responders, mean transit time, health-related quality of life, and adverse events rate. The methodological quality will be assessed using the Cochrane risk of bias tool. RESULTS: This work will summarize clinical evidence to assess the effectiveness and safety of moxibustion treatment for FC patients. CONCLUSION: This systematic review and meta-analysis will provide current evidence of the efficacy and safety of moxibustion treating FC. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42020157955.

Effectiveness of different acupuncture courses for functional constipation: A protocol for systematic review and network meta-analysis.

BACKGROUND: This study will evaluate the effectiveness of different acupuncture courses for functional constipation (FC) through network meta-analysis. METHODS: Eight database (PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials (Central), China National Knowledge Infrastructure (CNKI), China Biomedical Literature Database (CBM) and Wanfang Database) will be searched from inception to October 2019. Only randomized controlled trials comparing different acupuncture courses or acupuncture versus sham acupuncture or placebo will be included. The outcomes involved weekly stool frequency, Bristol Fecal score, responder rate and safety evaluation. The risk of bias assessment and quality of evidence will be appraised using the Cochrane Risk of Bias Tool and the Grading of Recommendations, Assessment, Development and Evaluation guidelines. RevMan 5.3 software, STATA V.14.0 and GeMTC software will be used to perform the network meta-analysis. RESULTS: This work will compare and arrange the comparative efficacy of different acupuncture treatments for FC by summarizing the current evidences. The results will be submitted in the form of a journal publication. CONCLUSION: The results of this network meta-analysis may help doctors determine the best treatments for patients to manage FC. PROSPERO REGISTRATION NUMBER: CRD42020153801.

The effect and safety of acupuncture on patients with functional constipation: Protocol for a systematic review and meta-analysis of high quality RCTs.

BACKGROUND: Functional constipation (FC) is a prevalent clinical disease that affects a considerable proportion of the population of all ages. Persistent FC significantly reduces quality of life and influences physical and emotional well-being, as well as consumes many substantial healthcare resources. Acupuncture originates from Traditional Chinese Medicine (TCM), and emerging evidence of several randomized controlled trials (RCTs) published suggest that acupuncture has positive effects for FC. Since 2019, several new results of high quality RCTs about acupuncture treatment for FC have been published. Thus a systematic review will be designed to appraise the effectiveness and safety of acupuncture for improvement of FC in patients based on high quality RCTs. METHODS: We carried out a rigorous literature search in English and Chinese electronic database from inception to present. Two reviewers will identify relevant studies, extract and manage trial information, and then assess the risk of bias in included studies by the Cochrane risk of bias assessment tool. Only high quality RCTs will be included. Data will be synthesized by either fixed-effects or random-effects model regarding to a heterogeneity test. The primary outcome measurement will be the change from baseline in mean complete spontaneous bowel movements and stool form. The secondary outcomes involved disappearance rate of symptoms, proportion of responders, mean transit time, health-related quality of life, and safety of intervention. Meta-analysis will be performed by using Cochrane's RevMan software. RESULTS: This systematic review will summarize high quality clinical evidence to assess and appraise the effectiveness and safety of acupuncture treatment for FC patient. EXPECTED CONCLUSION: This systematic review and meta-analysis will provide evidence to determine whether acupuncture treatment is an effective and safe therapy for the prevention and treatment of FC compared with medication treatment.

Acupuncture and weight loss in Asians: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: Acupuncture is effective for reducing body weight; however, evidence in Asian populations is lacking. We performed a systematic review and meta-analysis to evaluate the efficacy of acupuncture for body weight reduction in Asians. METHODS: The Medline, Embase, Cochrane library, and Chinese databases were searched for relevant studies through October 20, 2018. Publications describing randomized controlled trials (RCTs) comparing acupuncture with other treatments for the reduction of body weight were compiled. Reviewers assessed bias and collected data on trial characteristics and outcomes. The study was conducted based on the reporting items of the guidelines for systematic evaluation and meta-analysis (PRISMA). Review Manager 5.2 software was used to calculate weight mean difference (WMD) and 95% confidence intervals (CIs). RESULTS: Twelve RCTs involving 1151 subjects were included. Compared with the control groups, the acupuncture groups exhibited significantly greater reductions of body mass index (BMI)(WMD -1.20kg/m2; 95% CI -1.91, -0.48)and waist circumference (WMD -1.85 cm; 95% CI -3.20, -0.49) In the subgroup analyses, significant differences in the reduction of BMI was observed between the acupuncture and sham acupuncture groups, the acupuncture plus diet and exercise, and the diet and exercise groups, and the acupuncture and no intervention groups, but not between the acupuncture plus exercise and exercise groups [corrected]. CONCLUSIONS: Our study demonstrates that acupuncture is effective in the intervention of overweight/obesity in Asians; however, compared with exercise alone, acupuncture combined with exercise had no effect on the BMI or waist circumstance in the short term. Long-term studies are needed to evaluate the efficacy of acupuncture in weight reduction in Asians.

Systematic reviews of pharmacological and nonpharmacological treatments for patients with chronic urticaria: An umbrella systematic review.

A wide range of pharmacological and nonpharmacological interventions for chronic urticaria (CU) have been evaluated in systematic reviews (SRs). We conducted an umbrella review of SRs of the effectiveness and safety of pharmacological and nonpharmacological interventions for CU, which allow the findings of separate reviews to be compared and contrasted and thereby provide decision makers in healthcare with the evidence they need.We included SRs evaluating pharmacological and nonpharmacological interventions for CU. Comprehensive searches were conducted in 7 bibliographic databases, relevant journals up to July 2018. Two reviewers independently assessed the studies' relevance and quality. The assessment of multiple systematic reviews tool and grading of recommendations assessment, development and evaluation method was used to assess the methodological quality of the SRs and classify the quality of the outcomes.In total, 41 SRs were included. Thirty-seven reviews performed quantitative research syntheses, and 4 reviews performed qualitative research syntheses. The majority of SRs evaluated interventions based on combination therapies, antihistamines, traditional Chinese medicines, autohemotherapy, omalizumab, acupuncture, cyclosporine, and leukotriene receptor antagonist. Positive intervention outcomes were reported in the majority (75.32%) of the reviews. However, the methodological quality and evidence quality of the reviews were generally poor.There is some evidence to support a variety of interventions for CU. However, there was much heterogeneity in evidence quality among SRs. Many of the SRs had methodological weaknesses that make them vulnerable to bias. Moreover, there remained little information on the relative effectiveness of one intervention compared with another. Therefore, further SRs that adherence to strict scientific methods are necessary, and primary studies make comparisons between the different treatment options directly.

[Effect of Acupuncture Intervention on Depression Behavior and Expression of ERK 1/2 and BDNF in Prefrontal Cortex in Chronic Unpredictable Mild Stress Induced Depression Rats].

OBJECTIVE: To investigate the effect of acupuncture intervention on the depression behavior and expression of extracellular signal-regulated protein kinases (ERK 1/2), p-ERK 1/2 and brain-derived neurotrophic factor (BDNF) in the prefrontal cortex of chronic unpredictable mild stress (CUMS) induced depression rats, so as to explore its antidepressant mechanism. METHODS: Sixty-four male SD rats were randomly divided into control, model, acupuncture, Fluoxetine, model ＋ Dimethyl sulfoxide (DMSO), model ＋ PD 98059(an ERK pathway inhibitor), acupuncture ＋ PD 98059 and Fluoxetine ＋ PD 98059 groups (n＝8 rats in each). The CUMS depression model was established by using chronic mild and unpredictable stress methods for 21 days. Manual acupuncture stimulation was applied to "Baihui" (GV 20) and "Yintang" (GV 29) for 10 min before modeling, once daily for 21 days. Fluoxetine hydrochloride suspension (1.8 mg•kg－1•d－1) was given to rats of the Fluoxetine group and Fluo-xetine ＋ PD 98059 group by gavage 30 min before CUMS. PD 98059 (dissolved in DMSO, 10 µL) was administered to rats of model ＋ PD 98059 group, acupuncture ＋ PD 98059 and Fluoxetine ＋ PD 98059 group, and DMSO (10 µL) to rats of model ＋ DMSO group by intracerebroventricular injection 1 h before CUMS. Sucrose consumption test was carried out to evaluate the depressive behavior. Western blot was performed to detect the expression of ERK 1/2, p-ERK 1/2 and BDNF of prefrontal cortex. RESULTS: Compared with the control group, the sucrose consumption and the expression levels of p-ERK 1/2 and BDNF protein in the prefrontal cortex were significantly reduced in the model and model＋DMSO group (P<0. 01). After the intervention, modeling induced decrease of the sucrose consumption, and p-ERK 1/2 and BDNF expression was significantly up-regulated in both acupuncture and Fluoxetine groups (P<0.01, P<0.05), but not in the model＋PD 98059, Fluoxetine ＋PD 98059 and acupuncture＋PD 98059 groups (P>0.05). No significant differences were found among the model＋PD 98059, Fluoxetine ＋PD 98059 and acupuncture＋PD 98059 groups in the sucrose consumption, and ERK 1/2, p-ERK 1/2 and BDNF expression levels (P>0.05), and in the expression levels of ERK 1/2 protein among the 8 groups (P>0.05). CONCLUSION: Acupuncture intervention has an anti-depressive role in CUMS induced depression rats, which may be related to its effects in up-regulating the expression of p-ERK 1/2 and BDNF in the prefrontal cortex tissue.

Beneficial Effects of Qigong Wuqinxi in the Improvement of Health Condition, Prevention, and Treatment of Chronic Diseases: Evidence from a Systematic Review.

PURPOSE: Qigong is a modality of traditional Chinese mind-body medicine that has been used to prevent and cure ailments, to improve health in China for thousands of years. Wuqinxi, a Chinese traditional Qigong that focuses on mind-body integration, is thought to be an effective exercise in promoting physical and mental wellbeing. Thus, we summarized the evidence and aim to unravel effects of Wuqinxi on health outcomes. METHODS: We performed a systematic review of Wuqinxi studies published in English or Chinese since 1979. Relevant English and Chinese language electronic data bases were used for literature search. The selection of studies, data extraction, and validation were performed independently by two reviewers. RESULTS: A total of 28 eligible studies were included in this review, among which three are 3 in English and 25 in Chinese. The studies included in this review involve three different experimental designs: (1) 16 RCTs; (2) 2 historical cohort studies; and (3) 10 pretest and posttest studies (PPS). Participants in this review are categorized as either healthy or clinical populations. The results from this systematic review support the notion that Wuqinxi may be effective as an adjunctive rehabilitation method for improving psychological and physiological wellbeing among different age of healthy populations in addition to alleviating and treating diseases among various clinical populations. CONCLUSION: The results indicated that Wuqinxi has been thought to be beneficial to improve health and treat chronic diseases. However, the methodological problems in the majority of included studies make it difficult to draw firm conclusive statements. More methodologically rigorous designed large-scale RCTs with a long-term follow-up assessment should be further conducted to examine the effects of Wuqixi on health-related parameters and disease-specific measures in different health conditions. This systematic review lends insight for future studies on Wuqinxi and its potential application in preventive and rehabilitation medicine.

Safety of Qigong: Protocol for an overview of systematic reviews.

BACKGROUND: Qigong, as one of the essential elements of Traditional Chinese exercises, has been used to improve physical and psychological health and combat diseases in China for thousands of years. In recent years, the beneficial effects of Qigong on different medical conditions are becoming more accepted by both patients and health care providers. Although it is a common impression that Qigong and related therapies are generally safe procedures, but the current understanding of its adverse events is fragmented. Thus, we conducted this overview to synthesize comprehensively existing systematic reviews on adverse events associated with Qigong and related therapies, and our findings can be used to informing clinicians, Qigong practitioner, and patients alike on applying such treatments or interventions in clinical treatment and daily life training mindful manner, and provide a guideline for researchers in future. METHODS: A systematic review of reviews will be performed. A literature search strategy designed by a number of specialists in the fields of Traditional Chinese Medicine (TCM), sports medicine, health information, and Qigong training will be carried out in relevant English and Chinese electronic database. The date range of search will start from inception to the search date. Two reviewers will identify relevant studies, extract data information, and then assess the methodical quality by Assessment of Multiple Systematic Reviews (AMSTAR) tool. Any types of systematic review that summarized adverse effects related to Qigong and related therapies in human will be included. Any safety-related outcomes will be considered as the primary outcomes of this overview. Where objectives from 2 or more reviews overlap, we will assess the causes of any noted discrepancies between reviews. An overall summary of results will be performed using tabular and graphical approaches and will be supplemented by narrative description. RESULTS: This overview will identify any adverse events associated with nonstandardized Qigong and related therapies procedures based on current relevant literature evidence of safety for Qigong. CONCLUSION: Our overview will provide evidence to help synthesize the broad degree of information available on furthering the knowledge, safety, and application of Qigong. ETHICS AND DISSEMINATION: Formal ethical approval is not required, as this study is an overview based on the published systematic reviews. The result of this overview of systematic reviews will be published in a peer-reviewed journal or disseminated at national and international conferences. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42018109409.

The effect of Imaginary Working Qigong on the psychological well-being of college students: Study protocol for a randomized controlled trial.

INTRODUCTION: College students are special populations that are particularly prone to have significantly high level of psychological distress than their community peers. Apparently, the best way to manage stress and mental state is through self-care. The characteristic of Qigong is self-directed and self-healing, which is a traditional Chinese mind-body exercise, which has the potential as a stress management intervention. Imaginary Working Qigong, as a kind of static Qigong, is more perception-oriented and can bring about benign sensations of mind and body so as to eliminate stress completely and induce physiological and mental relaxation. In this study protocol, we will systematically examine the feasibility and acceptability of Imaginary Working Qigong on psychological outcomes of the college students and deeply explore molecular biological mechanisms underlying the effects of mind adjustment induced Imaginary Working Qigong. METHODS/DESIGNS: We will conduct a randomized, assessor and statistician-blinded, parallel-controlled trial exploring the beneficial mind adjustment of Imaginary Working Qigong in college students.A total of 80 eligible college students from Beijing University of Chinese Medicine will be recruited and randomly allocated into Imaginary Working Qigong training or unaltered lifestyle control group according 1:1 allocation ratio with allocation concealment. Imaginary Working Qigong training will last 8 weeks. The study period is 12 weeks including a 4-week supervised training, 4-week independence training, and a 4-week follow-up. Relevant psychological outcomes measurement will take place at baseline, 5 weeks (at the end of supervised training), 9 weeks (at the end of independence training), and 13 weeks (after the 4-week follow-up period) by blinded independent outcome assessors. CONCLUSION: This is the first randomized controlled trial protocol from the perspective of Qigong connotation to systematically evaluate the effects and relevant molecular mechanism of Imaginary Working Qigong for the mental health of a college student population. If our study demonstrates a significant intervention effect, this would provide preliminary higher-quality evidence and establish a further guidance for the application of Imaginary Working Qigong program among a college student population. ETHICS AND DISSEMINATION: The study protocol and consent forms have been approved by the medical and animal experiment ethic committee of BUCM (approval number: BJZYYDX-LL2014005).

Effect of Liuzijue Qigong on patients with chronic obstructive pulmonary disease: Protocol for a systematic review and meta-analysis.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide with a substantial and increasing social and economic burden. Liuzijue Qigong is a kind of traditional Chinese Qigong exercises that Traditional Chinese Medicine practitioners prescribe to individuals with COPD to strengthen the internal organs' function. Liuzijue Qigong was recommended for use in COPD rehabilitation, and some clinical trials indicate that Liuzijue Qigong would produce better functional capacity and quality of life of individuals with COPD. The objective of this study is to conduct a systematic review of the existing studies to assess effectiveness and safety of Liuzijue Qigong for the prevention or treatment of COPD in patients. METHODS: We will perform the comprehensive literature search in English and Chinese electronic database. The publication period will be from inception to the search date. In addition, the clinical trial registries, dissertations, informal publication, grey literature, reference lists of studies, systematic reviews, and conference abstracts will also be collected. Two reviewers will identify relevant studies, extract data information, and then assess the methodical quality by the Cochrane risk of bias assessment tool. Only randomized controlled trials comparing Liuzijue Qigong against other intervention or nonintervention will be included. Data will be synthesized by either fixed-effect or random-effect model regarding to a heterogeneity test. The routine lung function, arterial blood gas tensions, partial pressure of carbon dioxide, functional capacity, 30 seconds sit-to-stand test, respiratory function, maximal inspiration pressure, maximal expiratory pressure, airway resistance, and specific airway conductance will be assessed as primary outcomes. The secondary outcomes involved dyspnea, and fatigue levels, respiratory muscle strength, upper and lower limb muscle strength, handgrip strength test, and health-related quality of life and safety. Meta-analysis will be performed by using Cochrane's Review Manager software (version 5.3.5). RESULTS: This systematic review and meta-analysis will provide a high-quality synthesis and evaluate the efficacy and safety based on current relevant literature evidence of Liuzijue Qigong intervention for COPD patient. CONCLUSION: Our systematic review will provide evidence to determine whether Liuzijue Qigong is an effective and safe approach to prevention and treatment of COPD patients.

The effect of Three-Circle Post Standing (Zhanzhuang) Qigong on the physical and psychological well-being of college students: Study protocol for a randomized controlled trial.

BACKGROUND: The physical and mental health of college students tends to continuously decline around the world due to lifestyle or behavior habits changes, and pervasive presence of the Internet. Thus it is urgent to improve their health in college life. As a traditional Qigong form is practiced mainly in a standing posture. Three-Circle Post Standing Qigong (TCPSQ) is suitable for regular practicing and has beneficial effects on improving the physiological function and psychological emotion by adjusting body, breathing, and mind. The aim of the 3 adjustments is to achieve a state of harmonious unity-integrating these adjustments into "one." In this study protocol article, we will systematically explore the effectiveness and safety, feasibility of TCPSQ on physical and psychological outcomes of the college students and deeply understand the state of harmonious unity-integrating adjustments of body, breath, and mind into "one." METHOD/DESIGN: We will conduct a randomized, assessor, and statistician blinded, parallel-controlled trial comparing the beneficial effect of TCPSQ in college students. A total of 80 eligible college students from the Beijing University of Chinese Medicine (BUCM) will be recruited and randomly allocated into TCPSQ training or unaltered lifestyle control group according 1:1 allocation ratio with allocation concealment. TCPSQ intervention will last 10 weeks. The study period is 18 weeks including a 10-week supervised intervention and a 8-week follow-up. The relevant physical and psychological outcomes, adverse events, and safety will be evaluated at baseline, 6 weeks (at the mid-point of intervention), 11 weeks (at the end of intervention), and 19 weeks (after the 8-week follow-up period) by blinded independent outcome assessors. DISCUSSION: This is the first randomized controlled trial protocol from the perspective of Qigong connotation to systematically investigate the effect of TCPSQ for the physical and mental health of a college student population. If the results in our study prove a significant intervention effect, this would provide preliminary higher-quality evidence and establish an optimal guidance for the application of TCPSQ exercise program among a college student population. ETHICS AND DISSEMINATION: The study was approved by the ethics committee of the Beijing University of Chinese Medicine (approval number: 2018BZHYLL0109). A SPIRIT checklist is available for this protocol. The trial was registered in Chinese Clinical Trial Registry (WHO ICTRP member). Registration number: ChiCTR-BON-17010840.

Mechanisms Underlying the Antidepressant Response of Acupuncture via PKA/CREB Signaling Pathway.

Protein kinase A (PKA)/cAMP response element-binding (CREB) protein signaling pathway, contributing to impaired neurogenesis parallel to depressive-like behaviors, has been identified as the crucial factor involved in the antidepressant response of acupuncture. However, the molecular mechanisms associated with antidepressant response of acupuncture, neurogenesis, and depressive-like behaviors ameliorating remain unexplored. The objective was to identify the mechanisms underlying the antidepressant response of acupuncture through PKA signaling pathway in depression rats by employing the PKA signaling pathway inhibitor H89 in in vivo experiments. Our results indicated that the expression of hippocampal PKA-α and p-CREB was significantly downregulated by chronic unpredicted mild stress (CUMS) procedures. Importantly, acupuncture reversed the downregulation of PKA-α and p-CREB. The expression of PKA-α was upregulated by fluoxetine, but not p-CREB. No significant difference was found between Acu and FLX groups on the expression of PKA-α and p-CREB. Interestingly, H89 inhibited the effects of acupuncture or fluoxetine on upregulating the expression of p-CREB, but not PKA-α. There was no significant difference in expression of CREB among the groups. Conclusively, our findings further support the hypothesis that acupuncture could ameliorate depressive-like behaviors by regulating PKA/CREB signaling pathway, which might be mainly mediated by regulating the phosphorylation level of CREB.