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Inhibitory glycinergic transmission in adult spinal cord is primarily mediated by glycine receptors (GlyRs) containing the α1 subunit. Here, we found that α1ins, a longer α1 variant with 8 amino acids inserted into the intracellular large loop (IL) between transmembrane (TM)3 and TM4 domains, was expressed in the dorsal horn of the spinal cord, distributed at inhibitory synapses, and engaged in negative control over nociceptive signal transduction. Activation of metabotropic glutamate receptor 5 (mGluR5) specifically suppressed α1ins-mediated glycinergic transmission and evoked pain sensitization. Extracellular signal-regulated kinase (ERK) was critical for mGluR5 to inhibit α1ins. By binding to a D-docking site created by the 8-amino–acid insert within the TM3–TM4 loop of α1ins, the active ERK catalyzed α1ins phosphorylation at Ser380, which favored α1ins ubiquitination at Lys379 and led to α1ins endocytosis. Disruption of ERK interaction with α1ins blocked Ser380 phosphorylation, potentiated glycinergic synaptic currents, and alleviated inflammatory and neuropathic pain. These data thus unraveled a novel, to our knowledge, mechanism for the activity-dependent regulation of glycinergic neurotransmission. [ABSTRACT FROM AUTHOR]

Objective: To systematically evaluate the efficacy and safety of Modified Tongxie Yaofang (M-TXYF) for the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D). Method: Electronic databases including PubMed, Springer Link, EMBASE, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature (CBM), Wanfang, and Chinese Scientific Journals Database (VIP) were conducted from their inception through May 11, 2017 without language restrictions. Primary and secondary outcomes were estimated by 95% confidence intervals (CI). RevMan 5.3 and the Cochrane Collaboration’s risk of bias tool were analyzed for this meta-analysis. Results: Twenty-three literatures with a total of 1972 patients were included for the meta-analysis. The overall risk of bias evaluation was low. The pooled odds ratio showed that M-TXYF was significantly superior to routine pharmacotherapies (RP) in clinical therapeutic efficacy (OR 4.04, 95% CI 3.09, 5.27, P < 0.00001, therapeutic gain = 17.6%, number needed to treat (NNT) = 5.7). Moreover, compared with RP, M-TXYF showed that it can significantly reduce the scores of abdominal pain (standardized mean difference (SMD) -1.27; 95% CI -1.99, -0.56; P = 0.0005), abdominal distention (SMD -0.37; 95% CI -0.73, -0.01; P = 0.09), diarrhea (SMD -1.10; 95% CI -1.95, -0.25; P = 0.01), and frequency of defecation (SMD -1.42; 95% CI -2.19, -0.65; P = 0.0003). The differences of the adverse events between experiment and control groups had no statistical significance. Conclusion: This meta-analysis indicated that M-TXYF could be a promising Chinese herbal formula in treating IBS-D. However, considering the lack of higher quality of randomized controlled trials (RCTs), highly believable evidences should be required. [ABSTRACT FROM AUTHOR]

Aim: This meta-analysis analyzed the efficacy and safety of traditional Chinese medicine (TCM) for the treatment of irritable bowel syndrome with constipation (IBS-C). Methods: We searched seven electronic databases for randomized controlled trials investigating the efficacy of TCM in the treatment of IBS-C. The search period was from inception to June 1, 2017. Eligible RCTs compared TCM with cisapride and mosapride. Article quality was evaluated with the Cochrane Risk Bias Tool in the Cochrane Handbook by two independent reviewers. Begg’s test was performed to evaluate publication bias. Review Manager 5.3 and Stata 12.0 were used for analyses. Results: Eleven eligible studies comprising a total of 906 participants were identified. In the primary outcome, TCM showed significant improvement in overall clinical efficacy compared with cisapride and mosapride (odds ratio [OR] = 4.00; 95% confidence interval [CI]: 2.74,5.84; P < 0.00001). In terms of secondary outcomes, TCM significantly alleviated abdominal pain (OR = 5.69; 95% CI: 2.35, 13.78; P = 0.0001), defecation frequency (OR = 4.38; 95% CI: 1.93, 9.93. P = 0.0004), and stool form (OR = 4.96; 95% CI: 2.11, 11.65; P = 0.0002) in the treatment group as compared to the control group. A lower recurrence rate was associated with TCM as compared to cisapride and mosapride (OR = 0.15; 95% CI: 0.08, 0.27; P < 0.00001). No adverse effects were observed during TCM treatment. Conclusions: TCM showed greater improvement in terms of clinical efficacy in the treatment of IBS-C than cisapride and mosapride, although it was not possible to draw a definitive conclusion due to the small sample size, high risk, and low quality of the studies. Large multi-center and long-term high-quality randomized control trials are needed. [ABSTRACT FROM AUTHOR]

Jianpi Yiqi therapy (JYT) is a classical therapy in treating chronic atrophic gastritis (CAG), but the clinical effects of it are still contentious. The purpose of this article is to evaluate the efficacy and safety of JYT for CAG. Seven electronic databases including PubMed, Embase, Springer Link, CNKI (China National Knowledge Infrastructure), VIP (Chinese Scientific Journals Database), Wan-fang database, and CBM (Chinese Biomedicine Database) were searched from their inception to November 1, 2016. 13 randomized controlled trials (RCTs) with a total of 1119 participants were identified for analysis. Meta-analyses demonstrated that both JYT (RR 1.41; 95% CI 1.27, 1.57; P < 0.00001) and JYT + western medicine (RR 1.27; 95% CI 1.17, 1.38; P < 0.00001) were more efficacious than only western medicine. Furthermore, JYT had potential improvement on traditional Chinese medicine (TCM) symptoms scores such as stomachache, stomach distention, belching, fatigue, et al. In addition, no serious adverse events were reported in the selected trials. The Cochrane Collaboration’s risk of bias tool was evaluated for the weaknesses of methodological quality, while the quality level of Grades of Recommendations Assessment Development and Evaluation (GRADE) evidence classification indicated “Very low”. This meta-analysis indicates that JYT may have potential effects on the treatment of patients with CAG. However, due to limitations of methodological quality and small sample size of the included studies, further standardized research of rigorous design should be needed. [ABSTRACT FROM AUTHOR]