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Acupuncture treatment for functional constipation (FC) is characterized by precise efficacy, rapid onset of action in the early stages, long-term stable effects, and overall regulation. This paper reviews recent literatures on acupuncture treatment for FC, indicating that acupuncture acts from multiple perspectives and pathways, including promoting intestinal motility, regulating intestinal microbiota, modulating the brain-gut axis, alleviating intestinal inflammation, and improving rectal hyposensitivity. Future research could delve into the mechanical sensation conduction mechanisms of acupuncture in improving rectal hyposensitivity, identify key intestinal microbiota genera and metabolic characteristics regulated by acupuncture, explore the network relationships among different mechanisms, and clarify the differential mechanisms of various acupuncture treatment protocols to optimize clinical therapy and enhance the clinical efficacy of acupuncture for FC.

Electroacupuncture Promotes Functional Recovery after Facial Nerve Injury in Rats by Regulating Autophagy via GDNF and PI3K/mTOR Signaling Pathway.

OBJECTIVE: To explore the mechanism of electroacupuncture (EA) in promoting recovery of the facial function with the involvement of autophagy, glial cell line-derived neurotrophic factor (GDNF), and phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway. METHODS: Seventy-two male Sprague-Dawley rats were randomly allocated into the control, sham-operated, facial nerve injury (FNI), EA, EA+3-methyladenine (3-MA), and EA+GDNF antagonist groups using a random number table, with 12 rats in each group. An FNI rat model was established with facial nerve crushing method. EA intervention was conducted at Dicang (ST 4), Jiache (ST 6), Yifeng (SJ 17), and Hegu (LI 4) acupoints for 2 weeks. The Simone's 10-Point Scale was utilized to monitor the recovery of facial function. The histopathological evaluation of facial nerves was performed using hematoxylin-eosin (HE) staining. The levels of Beclin-1, light chain 3 (LC3), and P62 were detected by immunohistochemistry (IHC), immunofluorescence, and reverse transcription-polymerase chain reaction, respectively. Additionally, IHC was also used to detect the levels of GDNF, Rai, PI3K, and mTOR. RESULTS: The facial functional scores were significantly increased in the EA group than the FNI group (P<0.05 or P<0.01). HE staining showed nerve axons and myelin sheaths, which were destroyed immediately after the injury, were recovered with EA treatment. The expressions of Beclin-1 and LC3 were significantly elevated and the expression of P62 was markedly reduced in FNI rats (P<0.01); however, EA treatment reversed these abnormal changes (P<0.01). Meanwhile, EA stimulation significantly increased the levels of GDNF, Rai, PI3K, and mTOR (P<0.01). After exogenous administration with autophagy inhibitor 3-MA or GDNF antagonist, the repair effect of EA on facial function was attenuated (P<0.05 or P<0.01). CONCLUSIONS: EA could promote the recovery of facial function and repair the facial nerve damages in a rat model of FNI. EA may exert this neuroreparative effect through mediating the release of GDNF, activating the PI3K/mTOR signaling pathway, and further regulating the autophagy of facial nerves.

Acupuncture as an adjunctive therapy for gastric ulcer: A modified Delphi consensus study.

BACKGROUND: Acupuncture is often used as an adjunctive therapy for gastric ulcer (GU). However, there is still a lack of evidence on the appropriate and optimal interventions for acupuncture. This study aimed to optimize the acupuncture treatment of gastric ulcers based on expert consensus for guiding acupuncturists in clinical practice. METHODS: To conduct this study, research evidence was gathered from databases in both Chinese and English. After discussion, preliminary clinical questions were developed. Following three rounds of multidisciplinary clinical expert consultation, the initial consensus questionnaire was formed after testing and modification by team members. A Delphi consensus was ultimately reached to answer the questionnaire and develop guidance for acupuncture treatment. A 9-point Likert-type scale was used to measure the agreement of expert consensus, where a score of 80% between 7 and 9 was defined as "agreement." RESULTS: After two rounds of Delphi voting, a total of 35 items reached an agreement. These items can be roughly divided into 6 domains. According to expert consensus, the application of acupuncture for gastric ulcer should follow a semistandardized approach. Based on the syndrome differentiation, the main acupoints recommended are Zusanli (ST36), Zhongwan (CV12), Neiguan (PC6), and Sanyinjiao (SP6), while the adjunct acupoints include Taichong (LR3), Guanyuan (CV4), Xuehai (SP10), and Taixi (KI3). In the experience of experts, adverse events associated with acupuncture are typically mild and often manifest as subcutaneous hematomas. CONCLUSION: There is a lack of definitive acupuncture guidelines that can effectively determine the optimal therapeutic approach for the treatment of gastric ulcer. This expert consensus provides recommendations for clinical research and practice of acupuncture, with a particular focus on the selection of acupoints. However, further exploration through rigorous studies is necessary due to the limited availability of clinical evidence.

Effects of acupuncture on gut microbiota and short-chain fatty acids in patients with functional constipation: a randomized placebo-controlled trial.

Objective: To comprehensively evaluate the effect of acupuncture on gut microbiota, identify specific microbes closely related to the clinical efficacy of acupuncture, and explored the role of short-chain fatty acids (SCFAs). Methods: A randomized placebo-controlled trial was conducted with 80 FC patients and 28 healthy controls (HCs). FC patients randomly received 16 acupuncture (n = 40) or sham acupuncture (n = 40) sessions over 4 weeks; HCs received no treatment. The change in the proportion of patients with mean weekly complete spontaneous bowel movements (CSBMs) was considered as the primary outcome measure. Moreover, the composition and the predictive metabolic function of the gut microbiota from feceal samples were analyzed by 16S rRNA gene sequencing, while feceal SCFAs were identified via gas chromatography-mass spectrometry (GC-MS). Results: Compared to sham acupuncture, acupuncture significantly increased the proportion of CSBM responders, and improved spontaneous bowel movements (SBMs), straining, stool consistency, and quality of life. Moreover, Sequencing of 16S rRNA genes revealed that acupuncture improved ß-diversity and restored the composition of gut microbiota. Specifically, the abundance of beneficial bacteria such as g_Lactobacillus increased while that of pathogenic bacteria such as g_Pseudomonas decreased after acupuncture, which were significantly correlated with alleviated symptoms. Moreover, ten microbes including g_Coprobacter, g_Lactobacillus, and g_Eubacterium_coprostanoligenes_group might be considered acupuncture-specific microbes, and formed a stable interaction network. Additionally, GC-MS analysis indicated that acupuncture increased the content of butyrate acid in the gut, which was positively correlated with an increase in defecation frequency and a decrease in acupuncture-related pathogens. Finally, acupuncture specific-microbes including g_Coprobacter, g_Lactobacillus, g_Pseudomonas, g_Eubacterium_coprostanoligenes_group, g_Erysipelotrichaceae_UCG.003, g_Prevotellaceae_UCG.001, and g_Rolstonia could accurately predict the clinical efficacy of acupuncture (AUC = 0.918). Conclusion: Acupuncture could effectively improve clinical symptoms in FC patients, and was associated with gut microbiota reshaping and increased butyrate acid levels. Moreover, key microbial genera such as g_Coprobacter and g_Lactobacillus was predictive of acupuncture efficacy in treating FC. Future studies are required to validate the causal relationship between key microbial genera and acupuncture clinical efficacy, and should explore further metabolic pathways for designing personalized treatment strategies. Clinical Trial Registration: http://www.chictr.org.cn, Identifier: ChiCTR2100048831.

Electroacupuncture for psychogenic erectile dysfunction: A resting-state functional magnetic resonance imaging study exploring the alteration of fractional amplitude of low frequency fluctuation.

Background: Psychogenic erectile dysfunction (PED) can seriously affect emotional and marital wellbeing. Electroacupuncture (EA) seems an effective method for treating PED. However, the central mechanisms underlying PED and the beneficial effects of EA treatment are unclear. The purpose of this study was to explore the central mechanisms of PED and to examine the impact of EA on erectile function. Methods: We recruited 14 PED patients and 14 matched normal controls (NCs). PED patients underwent twice rs-fMRI scans, respectively, pre- and post-treatment. The NCs only completed one rs-fMRI scan. We used the fractional amplitude of low frequency fluctuation (fALFF) to compare spontaneous neural activity between the PED patients and NCs, and to examine the differences between the pre- and post-EA treatment scans in the PED patients. Results: Scores on the IIEF5, QEQ, and SEAR improved after EA treatment. Compared with the NCs, PED patients showed increased fALFF in the right posterior cingulate cortex (PCC), right dorsolateral prefrontal cortex (DLPFC), right supplementary motor area (SMA), and left middle occipital gyrus. Most of these regions are closely implicated in sexual inhibition. The results of the correlation analysis results indicated that the fALFF of the right PCC was negatively correlated with IIEF5 scores. After treatment, fALFF values were substantially lower in the left triangular part of the inferior frontal gyrus, right DLPFC, right SMA, bilateral PCC and the orbital part of the middle frontal gyrus, and higher in the left middle temporal gyrus and left caudate nucleus. These regions mainly belong to the default mode network (DMN), executive control network and primary sensory motor network. The results of the correlation analysis indicated a positive association between the changes in IIEF5 score and changes in the fALFF value in the right PCC after EA treatment. Conclusion: In conclusion, our study highlights that PED patients have abnormal patterns of activity in the right PCC, right DLPFC, and right SMA mainly involved in the DMN, executive central network, and sensory motor network which could lead to a higher levels of sexual inhibition. EA might regulate the process of sexual inhibition to improve erection function in PED patients probably by modulating spontaneous brain activity in the DMN, executive central network, and sensory motor network.

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.

[Study on the mechanism of electroacupuncture repairing intestinal barrier via regulating mast cell in rats with diarrhea-predominant irritable bowel syndrome].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on mast cell activation-related substances and intestinal barrier function in diarrhea-predominant irritable bowel syndrome (IBS-D) model rats, so as to explore its underlying mechanisms. METHODS: Thirty female SD rats were randomly divided into control group, model group and EA group, with 10 rats in each group. IBS-D model was established by chronic unpredictable mild stress combined with senna solution gavage. Rats in the EA group received EA treatment (2 Hz/15 Hz，0.1-1.0 mA) at "Zusanli" (ST36), "Taichong"(LR3) and "Tianshu"(ST25), 20 min per day, for a total of 14 days, with sides alternated daily. Visceral pain threshold was used to evaluate visceral hypersensitivity, diarrhea index was used to evaluate diarrhea degree. After all treatments, the pathological scores of colon were recorded after HE staining, the contents of cholecystokinin (CCK), substance P (SP), tryptase (TPS) and adenosine triphosphate (ATP) in colon were detected by ELISA, and the expressions of colonic tight junction protein ZO-1 and occludin were detected by Western blot. RESULTS: Compared with the control group, the visceral pain threshold, the expression levels of colonic ZO-1 and occludin proteins decreased (P<0.01), while the diarrhea index, the contents of colonic CCK, SP, TPS and ATP were significantly increased (P<0.01) in the model group. After intervention, in comparison with the model group, the visceral pain thre-shold, the protein expression levels of colonic ZO-1 and occludin protein increased (P<0.01), while the diarrhea index, the contents of colonic CCK, SP, TPS and ATP were significantly decreased (P<0.01) in the EA group. CONCLUSION: EA can significantly alleviate the symptoms of visceral hypersensitivity and diarrhea in IBS-D rats. Its mechanism may be related to down-regulating colonic CCK, SP, TPS and ATP, inhibiting mast cell activation and degranulation, and up-regulating colonic barrier tight junction proteins.

Electroacupuncture induces weight loss by regulating tuberous sclerosis complex 1-mammalian target of rapamycin methylation and hypothalamic autophagy in high-fat diet-induced obese rats.

Background: Obesity can be caused by abnormalities of hypothalamic autophagy, which is closely regulated by the epigenetic modification of TSC1-mTOR. However, whether the weight-reducing effect of EA may relate to the modification of TSC1-mTOR methylation and hypothalamic autophagy remain unclear. This study was conducted to reveal the possible mechanism by which EA reduces BW by measuring the levels of TSC1-mTOR methylation and hypothalamic autophagy-related components. Methods: The weight-reducing effect of EA was investigated in high-fat diet (HFD)-induced obese (DIO) rats by monitoring the BW, food consumption, and epididymal white adipose tissue (eWAT)/BW ratio. Hematoxylin and eosin staining was performed for morphological evaluation of eWAT. Immunofluorescence was utilized to observe the localization of LC3 in the hypothalamus. The expressions of autophagy components (Beclin-1, LC3, and p62) and mTOR signaling (mTOR, p-mTOR, p70S6K, and p-p70S6K) were assessed by western blot. The methylation rate of the TSC1 promoter was detected by bisulfite genomic sequencing. Results: Treatment with EA significantly reduced the BW, food consumption, and eWAT/BW ratio; attenuated the morphological alternations in the adipocytes of DIO rats. While HFD downregulated the expression levels of Beclin-1 and LC3 and upregulated those of p62, these changes were normalized by EA treatment. EA markedly decreased the methylation rate of the TSC1 gene promoter and suppressed the protein expressions of mTOR, p-mTOR, p70S6K, and p-p70S6K in the hypothalamus. Conclusion: EA could reduce BW and fat accumulation in DIO rats. This ameliorative effect of EA may be associated with its demethylation effect on TSC1-mTOR and regulation of autophagy in the hypothalamus.

Efficacy and MicroRNA-Gut Microbiota Regulatory Mechanisms of Acupuncture for Severe Chronic Constipation: Study Protocol for a Randomized Controlled Trial.

Background: Severe chronic constipation (SCC) is a common functional gastrointestinal (GI) disorder associated with disruptions in GI motility. Abnormalities between gut microbiota and microRNAs (miRNAs) are implicated in the pathogenesis of GI motility in SCC. Acupuncture has been shown to improve constipation-related symptoms and rebalance the gut microbiota. This protocol proposed a plan to explore the hypothesis that the efficacy of acupuncture is associated with the crosstalk between gut microbes and miRNAs in patients with SCC. Methods: This trial is designed as a randomized, sham-controlled trial involving 80 patients and 40 healthy volunteers. A total of 80 patients with SCC (≤2 mean spontaneous, complete bowel movements per week [CSBMs]) will be randomly allocated to receive either 16-session acupuncture at true acupoints or non-penetrating sham acupuncture at non-acupoints for 4 weeks. The primary outcome will be the proportion of patients with ≥3 mean weekly CSBMs over weeks 1-4 and 5-8. Secondary efficacy endpoints include bowel movements, stool consistency, degree of straining, and the quality of life. Healthy volunteers will not receive any clinical intervention. Fasting plasma and fecal samples will be analyzed by 16S rRNA third-generation sequencing and miRNA high-throughput sequencing technologies. Finally, a tripartite network analysis will be used to investigate the interactions among clinical efficacy, miRNAs, and intestinal microbiota. Discussion: From the perspective of microRNA-gut microbiota regulatory mechanisms, our results will partially illuminate the crucial role of fecal miRNAs and intestinal microbiota to understand how acupuncture exerts its anti-constipation role. Trial registration: This trial is registered with ChiCTR2100048831, registered 18 July 2021; ethical approval has been obtained from the Sichuan Regional Ethics Review of Committee on Traditional Chinese Medicine, approval ID: 2021KL-023.

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.

Acupuncture methods for functional constipation: protocol for a systematic review and network meta-analysis.

BACKGROUND: Functional constipation (FC) is one of the most prevalent functional gastrointestinal disorders, with the most significant negative impact on health-related quality of life. Despite that multiple systematic reviews and clinical trials have suggested that acupuncture could be effective for FC treatment, the comparative effectiveness among various acupuncture approaches has remained unknown. This protocol proposed a plan to assess and rank the effectiveness and safety of different acupuncture methods for patients with FC. METHODS: We will search 8 bibliographic databases from their inception to 30 June 2021, including the Cochrane Central Register of Controlled Trials, MEDLINE (via PubMed), EMBASE, Allied and Complementary Medicine Database, the Chinese Biomedical Literature Database (CBM), Wanfang Database, VIP Database, and China National Knowledge Infrastructure (CNKI). Randomized controlled trials (RCT) examining acupuncture methods for FC will be considered. The primary outcome is a measurement of the weekly stool frequency [including bowel movement (BM), spontaneous bowel movement (SBM), and complete SBM]. There will be at least 2 reviewers in charge of study selection, data extraction, risk of bias assessment. Bayesian network meta-analysis will be conducted using ADDIS (Aggregate Data Drug Information System) V.1.16.8. Meta-regression and subgroup analyses will also be performed, if feasible, to address the potential causes of inconsistency and heterogeneity. Furthermore, the strength of evidence will be appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. DISCUSSION: In this study, we will provide evidence-based hierarchies for the effectiveness and safety of acupuncture therapies to manage constipated patients, assisting healthcare providers, physicians, and patients in making more informed treatment decisions. TRIAL REGISTRATION: This study has been registered at PROSPERO (https://www.crd.york.ac.uk/prospero/) with a registration number CRD42021227920.

[Involvement of Pirt /TRPV1 signaling in acupuncture-induced reduction of visceral hypersensitivity in diarrhea-predominant irritable bowel syndrome rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on the expression of Pirt (a regulator of TRPV1) in the dorsal root ganglia (DRG) and transient receptor potential vanilloid 1 (TRPV1, a molecular sensor of noxious heat and capsaicin) in the colonic mucosa in rats suffering from diarrhea-predominant irritable bowel syndrome (IBS-D), so as to explore its mechanisms underlying alleviation of visceral hypersensitivity of IBS-D. METHODS: Forty SD rats (half male and half female) were randomly assigned to control, model, EA, and medication groups by lottery, with 10 rats in each group. The IBS-D model was established by chronic unpredictable mild stress (CUMS) and gavage of senna soaking fluid. Rats in the EA group received EA (2 Hz/15 Hz,0.1-1 mA) stimulation of unilateral "Tianshu"(ST25), "Zusanli" (ST36), "Sanyinjiao"(SP6) and "Taichong"(LR3) for 15 min once a day for 14 days, and rats of the medication group received intragastric administration of pinave-rium bromide (10 mL/kg, 2.7 mg/mL) once daily for 14 days. The visceral pain threshold (VPT) was measured by using abdominal wall withdrawal reflex (AWR) test. The diarrhea index （loose stool rate ［total number of loose stool/total number of defecation］ X mean loose degree ［0-4 grades according to the filter paper stain diameter］ in 6 h/d） was used to assess the severity of diarrhea. The expression of Pirt in the DRG and TRPV1 in the colonic mucosa tissue was detected using immunohistochemistry. RESULTS: After modeling, the VPT was obviously reduced (P<0.01), while the diarrhea index, mean optical density of Pirt and TRPV1 were remarkably increased in the model group relevant to the control group (P<0.01). After the interventions, the VPT was obviously increased while the diarrhea index, and the mean optical density of Pirt and TRPV1 was noticeably decreased in both EA and the medicine groups in contrast to the model group (P<0.01). No significant differences were found between the EA and medicine groups in up-regulating VPT and down-regulating the diarrhea index, and Pirt and TRPV1 expression (P>0.05). CONCLUSION: EA can effectively alleviate visceral hypersensitivity in IBS-D rats, which may be related to its effect in down-regulating the expression level of DRG Pirt and colonic TRPV1.

Comparison of efficacy and safety of Chinese patent medicine in the treatment of postmenopausal osteoporosis: A protocol for systematic review and network meta-analysis.

BACKGROUND: Postmenopausal osteoporosis (PMOP) is the focus and difficult problem in the world at present, and we found that Chinese patent medicine(CPM) shown a more miraculous effect. Many kinds of Chinese patent medicine have been proved to be effective in the treatment of this disease, but it is still unclear which kind of Chinese patent medicine has the best effect. Therefore, we propose a network meta-analysis (NMA) protocol to observe the efficacy of various CPM for this disease and provide guidance for clinical practice. METHODS: We will use the NMA method to complete this study. First, all the randomized controlled trials of CPM or CPM combined with western medicine in the treatment of PMOP were collected by searching all online Chinese and English databases. The information time limit is from the establishment of the database to August 30, 2020. Then 2 staff members will sift through all the literature and analyze the data using Stata and Winbugs. RESULTS: Through this analysis, we will observe and rank the clinical effects of different CPM for PMOP. The main evaluation indexes include: New fracture, Quality of life, Severe side effects, Death from all causes. Secondary outcome indicators include Bone Mineral density, clinical efficiency, and some laboratory indicators, such as estradiol, serum calcium, serum, etc. CONCLUSION:: This study will rank the therapeutic effects of various proprietary Chinese medicines in the treatment of PMOP, which will be helpful in improving the PMOP treatment regimen.INPLASY registration number: INPLASY202090047.

Acupuncture for patients with chronic pruritus: protocol of a systematic review and meta-analysis.

INTRODUCTION: Chronic pruritus (CP) frequently occurs in many skin and systemic diseases, and adversely affects quality of life. This systematic review aims to evaluate treatment effects of acupuncture on CP. METHODS AND ANALYSIS: An electronic and manual search will be conducted for all acupuncture treatments for CP, from the inception date of predefined database up to 28 February 2020. Databases include PubMed, Embase, Springer, Web of Science, the Cochrane Library, the World Health Organization International Clinical Trial Registration Platform, the Chinese Medicine Database, the China National Knowledge Infrastructure, the Chinese Biomedical Literature Database, the China Science Journal Database and the Wanfang Database. Other sources, including existing systematic reviews, conference proceedings and reference lists of identified publications will also be searched. Additionally, any clinical randomised controlled trials related to acupuncture treatment for CP, regardless of the publication status and language limitations, will be included. Study selection, data extraction and research quality assessments will be conducted independently by two researchers. The primary outcome measures include the Visual Analogue Scale, Urdu 5D-Itch Scale or other validated scales implemented after at least 2 weeks of treatment. Secondary outcomes include the effective rate, Quality of Life Scale (eg, the EQ-5D third level, the Dermatology Life Quality Index, etc.), Pittsburgh Sleep Quality Index, recurrence rate during the follow-up period and adverse events. If possible, meta-analyses will be performed using RevMan V.5.3 statistical software; otherwise, a descriptive analysis or subgroup analysis will be conducted. The results will be presented as the risk ratio of the binary data and the mean difference (MD) or standardised MD of the continuous data. ETHICS AND DISSEMINATION: This systematic review protocol does not require formal ethical approval because the data are not personalised. It will be published in peer-reviewed journals and presented at international academic conferences. PROSPERO REGISTRATION NUMBER: CRD42019136727.

Cupping therapy for patients with chronic urticaria: A systematic review and meta-analysis.

BACKGROUND: Chronic urticaria (CU) is a common skin disease, which has a negative effect on quality of life. Current treatments do not fully control the symptoms of urticaria for many CU patients, thus effective and safe treatments for CU are still needed. OBJECTIVE: This review aims to evaluate the effectiveness and safety of cupping therapy in patients with CU. SEARCH STRATEGY: The search strategy looked for the presence of related keywords, such as "chronic urticaria" and "cupping therapy," in the title and abstract of research articles indexed in major databases. Randomized controlled trials (RCTs) were selected after querying nine electronic databases from their inception to May 2019 with the above search terms. INCLUSION CRITERIA: RCTs were included if they recruited patients with CU who were intervened with dry or wet cupping. Publications could be written in Chinese or English. DATA EXTRACTION AND ANALYSIS: Data were extracted, and the studies were assessed for the quality of their methodological design and risk of bias. Meta-analyses of the RCT data were conducted to assess the total effective rate of the treatment as the primary outcome. Skin disease quality of life index score, recurrence rate, and adverse events were assessed as secondary outcomes. Subgroup analyses were conducted based on different interventions. RESULTS: Thirteen comparisons from 12 RCTs involving 842 participants were included. There were no significant differences between wet cupping and medications in total effective rate (n = 372; risk ratio [RR] = 1.10, 95% confidence interval [CI] 0.97 to 1.25; P = 0.14) or recurrence rate (n = 240; RR = 0.56, 95% CI 0.23 to 1.36; P = 0.20). Cupping therapy, in combination with antihistamine treatment was more efficacious than antihistamines alone, with a greater total effective rate (n = 342; RR = 1.18, 95% CI 1.01 to 1.39; P = 0.03) and lower recurrence rate (n = 342; RR = 0.52, 95% CI 0.32 to 0.84; P = 0.007). Cupping therapy combined with acupuncture was more effective than acupuncture alone (n = 156; RR = 1.25, 95% CI 1.07 to 1.46; P = 0.006). No serious adverse events were reported. CONCLUSION: Wet cupping may be as effective as treatment with antihistamines. When cupping therapy is used as an adjuvant therapy to antihistamines or acupuncture, it may enhance the efficacy. Results drawn from these studies should be interpreted with caution and applied with care to clinical practice, because of the poor quality among the studies that were reviewed. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42019137451.

[Effect of electroacupuncture on intestinal epithelial mucosal barrier function in rats with diarrhea-predominant irritable bowel syndrome].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on intestinal epithelial mucosal barrier function in diarrhea-predominant irritable bowel syndrome(IBS-D) rats, so as to explore its mechanisms underlying improvement of IBS-D. METHODS: Forty SD rats (half male and half female) were randomly divided into control, model, EA and medication (Pinaverium Bromide, PB) groups, with 10 rats in each group. The IBS-D model was established by chronic unpredictable mild stress combined with gavage of Senna-leaf solution. EA (2 Hz/15 Hz，0.1-1 mA) was applied to unilateral "Zusanli"(ST36),"Tianshu" (ST25), "Sanyinjiao"(SP6) and "Taichong"(LR3) alternatively for 15 min, once daily for 14 days. Rats of the medication group was treated by gavage of PB (10 mL·kg-1·d-1) for 14 days. The visceral sensitivity (pain) was assessed by using the pressure threshold which the inserted rectal balloon catheter air-inflation (connected to a blood pressure gauge) induced stronger abdominal muscular contraction to force the rat's abdomen to lift the experimental stand surface. The diarrhea index was used to evaluate loose stool grade. The expression of Claudin-1 and Occludin (intestinal epithelial tight junction proteins) of colon tissue was detected by immunohistochemistry. The activity of plasma diamine oxidase (DAO) was assayed by using spectrophotometry. RESULTS: Compared with the control group, the diarrhea index and plasma DAO activity in the model group were significantly increased (P<0.01), while the visceral pain threshold, expression of Claudin-1 and Occludin in the model group were significantly decreased (P<0.01). After the treatment, the diarrhea index and plasma DAO activity were significantly lower in both EA and medication groups than that in the model group (P<0.01), and the visceral pain threshold and expression levels of Claudin-1 and Occludin were obviously increased (P<0.05, P<0.01). No significant differences were found between the EA and medication groups in all the above-mentioned indexes (P>0.05). CONCLUSION: Electroacupuncture can significantly improve abdominal pain and diarrhea in IBS-D model rats, which may be closely associated with its effects in up-regulating the expression of intestinal epithelial tight junction proteins Claudin-1 and Occludin to restore the function of intestinal epithelial mucosal barrier.

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.

Effect of auriculotherapy and intervention types on weight control: A systematic review and meta-analysis protocol.

BACKGROUND: Overweight and obesity characterized by abnormal or excessive fat accumulation, can cause many complications. Auriculotherapy, as the traditional Chinese technique, is widely applied in clinical trials for the management of body weight. The program aims to evaluate the effect and safety of auriculotherapy therapy and intervention types on weight control. METHODS: All randomized controlled trials related to auriculotherapy targeting overweight and obesity will be searched in online databases, such as Medline, EMbase, Cochrane Central Register of Controlled Trials, AMED, CBM, Wanfang Data, and other databases from their inception to July 2019. The primary outcome is the difference in BMI from baseline to the end of studies. Secondary outcomes include the change of weight, percentage of body fat, waist circumference, serum lipid before and after treatment. Study selection, data extraction, and assessment of risk of bias will be performed independently by 2 reviewers. Comprehensive Meta-Analysis software (Version 3; Biostat Inc.) will be used for data synthesis. RESULTS: This study will provide a comprehensive review of the available evidence for the treatment of obesity with auriculotherapy. CONCLUSION: The conclusion of this study will provide evidence to judge whether auriculotherapy is an effective therapeutic intervention for obesity. PROSPERO REGISTRATION NUMBER: CRD42019136827.

Optimal dietary alcoholic extract of lotus leaf improved growth performance and health status of grass carp (Ctenopharyngodon idellus).

Grass carp (Ctenopharyngodon idellus) is one of the most important aquaculture fish in China. This study tried to explore the effects of dietary alcoholic extract of lotus leaf (AELL) addition on the growth performance and health status of grass carp by feeding juvenile fish (average weight: 34 ±â€¯1 g) with four different experimental diets: control, AELL7, AELL14 and AELL21 for 8 weeks. At the end of the growth trial, the highest values of final body weight (FBW), weight gain rate (WGR), specific growth rate (SGR) and feed intake (FI) all occurred in group AELL14 (P < 0.05). Compared to control, the crude lipid content of whole-body and the serum malondialdehyde (MDA) in the three experimental groups decreased, while the serum superoxide dismutase (SOD), glutathione peroxidase (GSH) and total antioxidant capacity (T-AOC) values almost all increased in the three experimental groups. The highest serum immunoglobulin M (IgM) concentration occurred in AELL14 group (P < 0.05). In AELL14 and AELL21 groups, both the serum complement 3 (C3) concentration and lysozyme (LYS) activity were significantly higher, whereas the final cumulative mortality in challenge test was significantly lower, when compared to those in control group (P < 0.05). The AELL exerted dose-dependent beneficial effects on grass carp health through up-regulating related gene expressions and enzyme activity. In conclusion, the optimal dietary AELL level is 0.14% for juvenile grass carp.