Zhihui Huang

Functional constipation (FC) is a common functional gastrointestinal disorder thought to arise from the brain–gut axis dysfunction, yet direct human neurophysiological evidence is lacking. We recorded high-density electroencephalography (EEG) data in 21 FC patients and 37 healthy controls across resting, cognitive, and defecation-related tasks. We observed that FC patients displayed a consistent, task-dependent signature compared with healthy controls. At the regional level, FC patients exhibited increased alpha during both resting and defecation-related tasks, reduced temporal gamma during defecation-related tasks, as well as elevated temporal theta during the cognitive task. At the global level, we found altered network properties, such as global efficiency in the delta and beta band networks during resting and defecation-related tasks. These findings establish a direct neurophysiological link between specific, condition-dependent perturbations in cortical rhythm activity and FC pathophysiology. Our work implicates the brain–gut axis in symptom generation and opens a path toward EEG-based biomarkers and targeted neuromodulatory therapies.

INTRODUCTION: Slow colon transit and visceral hypersensitivity are recognized as major pathophysiological mechanisms in irritable bowel syndrome with constipation (IBS-C). However, there is a lack of therapies targeting both abdominal pain and colonic motility. This study was designed to investigate the long-term effects and possible mechanisms of transcutaneous electrical acustimulation (TEA) in patients with IBS-C. METHODS: Fifty-two patients with IBS-C were randomized into 2 groups: daily TEA for 4 weeks (n = 26) and daily sham-TEA for 4 weeks (n = 26). The number of complete spontaneous bowel movements per week (CSBMs/week, primary outcome), Irritable Bowel Syndrome Severity Scoring System, Patient Assessment of Constipation Quality of Life, visual analog scale (VAS) pain score, colonic transit time, and anorectal physiology were evaluated before treatment and at the end of the treatment. Colonic transit was assessed with radiopaque markers. Electrocardiograms were recorded for assessing autonomic functions. RESULTS: (i) TEA improved constipation and abdominal pain. After the treatment, the number of CSBMs/week during the last week in the TEA group was higher than that in the sham-TEA group (3.5 ± 1.6 vs 2.3 ± 0.6, P = 0.002). Similar effects were also noted in the visual analog scale pain score (P = 0.002) and Irritable Bowel Syndrome Severity Scoring System score (P = 0.025). In addition, there was a significant improvement in the quality of life of patients with constipation. The Patient Assessment of Constipation Quality of Life total score was significantly decreased in the TEA group (P = 0.004). (ii) Compared with sham-TEA, TEA improved colon transit (P = 0.002) and increased the threshold of rectal sensation (desire to defecate, P = 0.004; maximum tolerability, P < 0.001). (iii) TEA increased vagal activity, compared with sham-TEA (P < 0.05); at the end of the treatment, the vagal activity was significantly correlated with colon transit and the CSBMs/week. DISCUSSION: TEA improves constipation and symptoms of IBS by accelerating colon transit and reducing rectal sensation, possibly mediated by using the autonomic mechanisms.

HOXC10 indicates poor survival outcome in gastric cancer and promotes G1/S cell cycle transition through transcriptional repression of p21

Background: Alterations in intestinal permeability regulated by tight junctions (TJs) are associated with immune activation and visceral hypersensitivity in irritable bowel syndrome (IBS). Myosin light chain kinase (MLCK) is an important mediator of epithelial TJ. The aim of this study is to investigate the role of MLCK in the pathogenesis of IBS using a post infectious IBS (PI‐IBS) mouse model.Methods: Trichinella spiralis‐infected PI‐IBS mouse model was used. Urine lactulose/mannitol ratio was measured to assess intestinal epithelial permeability. Western blotting was used to evaluate intestinal TJ protein (zonula occludens‐1) and MLCK‐associated protein expressions. Immune profile was assessed by measuring Th (T helper) 1/Th2 cytokine expression. Visceral sensitivity was determined by abdominal withdrawal reflex in response to colorectal distension.Results: Eight weeks after inoculation with T. spiralis, PI‐IBS mice developed decreased pain and volume thresholds during colorectal distention, increased urine lactulose/mannitol ratio, elevated colonic Th1/Th2 cytokine ratio, and decreased zonula occludens‐1 expression compared to the control mice. MLCK expression was dramatically elevated in the colonic mucosa of PI‐IBS mice compared to the control mice, alongside increased pMLC/MLC and decreased MLCP expression. Administration of MLCK inhibitor and TJ blocker both reversed the increased intestinal permeability, visceral hypersensitivity, and Th1‐dominant immune profile in PI‐IBS mice.Conclusion: MLCK is a pivotal step in inducing increased intestinal permeability promoting low‐grade intestinal immune activation and visceral hypersensitivity in PI‐IBS mice. MLCK inhibitor may provide a potential therapeutic option in the treatment of IBS.