Research progress on mechanism of acupuncture in treating functional constipation. / é’ˆåˆºæ²»ç–—åŠŸèƒ½æ€§ä¾¿ç§˜çš„æœºåˆ¶ç ”ç©¶è¿›å±•.

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.

The gut microbiome and metabolites are altered and interrelated in patients with functional constipation.

Introduction: Gut microbiota and metabolites have been identified to contribute to the pathogenesis of functional constipation (FC); however, the underlying mechanism(s) have not been elucidated, and the relationship between the gut microbiota and metabolites in FC has received limited attention in the literature. Methods: 16S rDNA sequencing and non-targeted metabolomic detection based on liquid chromatography-mass spectrometry (LC-MS/MS) technologies were combined to analyze the altered gut microbiome and metabolic profile of fecal samples from FC patients and healthy individuals (healthy control; HC). Results: The richness and diversity of gut microbiota significantly (p < 0.01) increased in FC patients. Compared to the HC group, 18 genera, including Intestinibacter, Klebsiella, and Akkermansia, exhibited statistically significant changes (p < 0.05). Metabolic analysis showed that metabolic profiles were also markedly altered with 79 metabolites, such as (-)-caryophyllene oxide, chenodeoxycholic acid, and biliverdin, indicating significant inter-group differences (p < 0.05). Besides, the primary bile acid biosynthesis, as well as the metabolic profile of porphyrin and chlorophyll, were the most dominant enriched pathways (FDR < 0.01), in which chenodeoxycholic acid and biliverdin were significantly enriched, respectively. Correlation analysis demonstrated a strong relationship between 10 genera and 19 metabolites (r > 0.6, FDR < 0.05), and notably, Intestinibacter showed a negative correlation with biliverdin (FDR < 0.001), which highlighted the interplay of the gut microbiota and metabolites in the pathogenesis of FC. Conclusion: Our research describes the characteristics of the gut microbiota and metabolic profiles and the correlation between the gut microbiota and metabolites in FC patients. This may contribute to the understanding of the underlying mechanisms involved in FC pathogenesis and may provide novel insights into therapeutic interventions.

Effect of electroacupuncture on enteric neuronal autophagy in functional constipation mice. / ç”µé’ˆå¯¹åŠŸèƒ½æ€§ä¾¿ç§˜å°é¼ è‚ é“ç¥žç»å ƒè‡ªå™¬æ°´å¹³çš„å½±å“.

OBJECTIVES: To explore the effect mechanism of electroacupuncture (EA) on functional constipation (FC) at the combined lower he-sea and front-mu points of large intestine based on enteric neuronal autophagy. METHODS: A total of 40 SPF Kunming mice were randomly divided into 5 groups (n = 8), i.e. a control group, a model group, an acupuncture group, a 3-methyl adenine (3-MA) group, and a 3-MA + acupuncture group. Except the control group, the FC model was established by gavage with compound diphenoxylate suspension for 14 days in the other 4 groups. After successful modeling, the mice of the acupuncture group and the 3-MA + acupuncture group received EA at bilateral "Tianshu" (ST 25) and "Shangjuxu" (ST 37), stimulated for 30 min with disperse-dense wave, 2 Hz/15 Hz of frequency, 1 mA of intensity. EA was delivered once daily. One course of treatment was composed of 5 days and 2 courses were needed, with an interval of 2 days. An intraperitoneal injection of 3-MA (15 mg/kg) was administered 30 min before EA in the mice of the 3-MA group and the 3-MA + acupuncture group, once daily. Before and after intervention, the time of the first black stool defecation and defecation behaviors in 6 h were observed in each group. After intervention, in every group, the small intestine propulsion rate was calculated, the colon tissue morphology was observed using HE staining, the ultrastructure of enteric neuronal autophagy was observed under transmission electron microscope, and the expressions of microtubule-associated protein 1 light chain 3 (LC3), Beclin-1 and neuronal nuclear antigen protein (NeuN) in neurons of colonic muscularis were determined by immunohistochemistry. RESULTS: Before intervention, when compared with those in the control group, the time of the first black stool defecation was prolonged (P<0.01, P<0.05), and numbers (P<0.01), wet weight (P<0.01, P<0.05) and water content (P<0.05, P<0.01) of stool in 6 h were reduced in the model, acupuncture, 3-MA and 3-MA + acupuncture groups. After intervention, compared with those in the control group, the time of the first black stool defecation was longer (P<0.05), and numbers (P<0.01), wet weight (P<0.01) and water content (P<0.01) of stool in 6 h were decreased in the model group. The time of the first black stool defecation was shortened (P<0.01), and numbers (P<0.01), wet weight (P<0.01) and water content (P<0.01) of stool in 6 h were increased in the acupuncture group when compared with those in the model group. The time of the first black stool defecation was extended (P<0.01), and numbers (P<0.01), wet weight (P<0.01) and water content (P<0.01) of stool in 6 h were declined in the 3-MA + acupuncture group in comparison with those in the acupuncture group. All layers of colon tissue were normal and intact in each group. When compared with the control group, the small intestine propulsion rate and the average optical density (OD) values of LC3, Beclin-1 and NeuN in neurons of colonic muscularis were decreased (P<0.01), and autophagosomes were dropped in the model group. In the acupuncture group, the small intestine propulsion rate and the average OD values of NeuN, LC3 and Beclin-1 in neurons of colonic muscularis increased (P<0.01,P<0.05), and autophagosomes were elevated when compared with those in the model group. The small intestine propulsion rate and the average OD values of NeuN, LC3 and Beclin-1 in neurons of colonic muscularis were dropped (P<0.05,P<0.01) in the 3-MA + acupuncture group in comparison with those in the acupuncture group. CONCLUSIONS: Electroacupuncture may promote enteric neuronal autophagy and increase the number of neurons so that the intestinal motility can be improved and constipation symptoms can be relieved in FC mice.

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.

Global trends in research on miRNA-microbiome interaction from 2011 to 2021: A bibliometric analysis.

An increasing number of research suggests that the microRNA (miRNA)-microbiome interaction plays an essential role in host health and diseases. This bibliometric analysis aimed to identify the status of global scientific output, research hotspots, and frontiers regarding the study of miRNA-microbiome interaction over the past decade. We retrieved miRNA-microbiome-related studies published from 2011 to 2021 from the Web of Science Core Collection database; the R package bibliometrix was used to analyze bibliometric indicators, and VOSviewer was used to visualize the field status, hotspots, and research trends of miRNA-microbiome interplay. In total, 590 articles and reviews were collected. A visual analysis of the results showed that significant increase in the number of publications over time. China produced the most papers, and the United States contributed the highest number of citations. Shanghai Jiaotong University and the University of California Davis were the most active institutions in the field. Most publications were published in the areas of biochemistry and molecular biology. Yu Aiming was the most prolific writer, as indicated by the h-index and m-index, and Liu Shirong was the most commonly co-cited author. A paper published in the International Journal of Molecular Sciences in 2017 had the highest number of citations. The keywords "expression" and "gut microbiota" appeared most frequently, and the top three groups of diseases that appeared among keywords were cancer (colorectal, et al.), inflammatory bowel disease (Crohn's disease and ulcerative colitis), and neurological disorders (anxiety, Parkinson's disease, et al.). This bibliometric study revealed that most studies have focused on miRNAs (e.g., miR-21, miR-155, and miR-146a), gut microbes (e.g., Escherichia coli, Bifidobacterium, and Fusobacterium nucleatum), and gut bacteria metabolites (e.g., butyric acid), which have the potential to improve the diagnosis, treatment, and prognosis of diseases. We found that therapeutic strategies targeting the miRNA-microbiome axis focus on miRNA drugs produced in vitro; however, some studies suggest that in vivo fermentation can greatly increase the stability and reduce the degradation of miRNA. Therefore, this method is worthy of further research.

Manual Therapy and Related Interventions for Carpal Tunnel Syndrome: A Systematic Review and Meta-Analysis.

Objective: Systematic review and meta-analysis to assess the efficacy of Manual therapy and related interventions in the treatment of carpal tunnel syndrome (CTS) based on Boston carpal tunnel questionnaire. Design: Systematic review and meta-analysis. Subjects: Carpal tunnel syndrome. Interventions: Manual therapy and related interventions versus other therapies or manual therapy and related interventions plus other therapies versus other therapies. Outcomes measures: Boston carpal tunnel questionnaire. Results: A total of 6 studies were included, including 211 cases in the manual therapy group and 211 cases in the control group. The quality of the included articles was high, and the results of meta-analysis showed that manual therapy and related interventions were superior in terms of improving the Boston carpal tunnel questionnaire Symptom Severity score in patients with CTS (standardised mean difference [SMD] -1.13, 95% CI -1.40 to -0.87), were superior to control groups in terms of improving the Boston carpal tunnel questionnaire functional capacity scale in patients with CTS (SMD -1.01,95% CI -1.24 to -0.77). Conclusion: The results of this meta-analysis suggested that manual therapy and related interventions were better than control groups in treating CTS. Manual therapy and related interventions could relieve the symptoms of patients with CTS and promote the recovery of hand function. Manual therapy and related interventions should be considered clinically effective methods for treating CTS. Registration: The protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO; No. CRD 42020201389). Contribution of the Article: Manual therapy and related interventions could relieve the symptoms of patients with CTS and promote the recovery of hand function. Manual therapy and related interventions should be considered clinically effective methods for treating CTS.

Profiles analysis reveals circular RNAs involving zebrafish physiological development.

Recent studies have found that known functions of circular RNAs (circRNAs) include sequestration of microRNAs (miRNAs) or proteins, modulation of transcription and interference with splicing, and even translation to produce polypeptides. The zebrafish model is also demonstrably similar to humans in many studies. To explore the changes in circRNAs during embryonic development and to further research the mechanism of action of circRNAs in development-related diseases, Zebrafish embryos at the blastula period, gastrula period, segmentation period, throat stage, and incubation period were collected. Illumina deep-sequencing technology and CircRNA Identifier (CIRI) algorithm were used to detect circRNAs. In total, we identified 1,028 circRNAs (junction reads ≥5 and p < 0.05). Considering that the function of circRNAs is related to host genes, a bioinformatics analysis revealed these differentially expressed host genes are involved in NOTCH signaling pathways, cardiovascular system development, retinal ganglion cell axon guidance, and so on. Moreover, circRNAs can participate in biological regulation through the function of miRNA sponges. TargetScan and miRanda were used to predict 73 miRNAs binding to circRNAs such as miR-19b, miR-124, and so on. Some miRNAs play important roles in embryogenesis. The peak expression of circRNAs is distributed at different time points, suggesting that it may be involved in embryogenesis at different stages. Our study provides a foundation for understanding the dynamic regulation of circRNA transcriptomes during embryogenesis and identifies novel key circRNAs that might control embryonic development in a zebrafish model.