BackgroundNeural-immune-endocrine network mechanism has attracted increased attention in diarrhoea-predominant irritable bowel syndrome (IBS-D). Pre-clinical evidence indicates that nerve growth factor (NGF) mediates visceral hypersensitivity and gut barrier dysfunction, via interactions with mast cells and sensory nerve fibres. AimTo explore the role of nerve growth factor, as well as mast cell-nerve growth factor-nerve interaction in IBS-D pathophysiology. MethodsIn this cross-sectional study, IBS-D patients and healthy controls first underwent clinical and psychological assessments. Visceral sensitivity to rectal distension was tested. As gut barrier function markers, serum diamine oxidase and D-lactate were detected. Rectosigmoid biopsies were taken for the analyses of nerve growth factor expression, mast cell count and activation, and sensory nerve fibres expressing transient receptor potential vanilloid 1 and calcitonin gene-related peptide. Correlations between these parameters were examined in patients. ResultsThirty-eight IBS-D patients (28 males, 10 females; average age 30.2 years) and 20 healthy controls (12 males, 8 females; average age 26.8 years) participated in the study. The patients presented increased psychological symptoms, visceral hypersensitivity and impaired gut barrier function. NGF gene expression, mast cell count and sensory nerve fibres were significantly increased in the patients (P < 0.05). In correlation analysis, NGF expression was positively correlated with the disease severity, anxiety and serum diamine oxidase; visceral sensitivity thresholds were negatively associated with NGF expression (Bonferroni corrected P < 0.0029). ConclusionsElevated mucosal NGF may interact with mast cells and sensory nerve fibres, contributing to visceral hypersensitivity and impaired gut barrier function in IBS-D.

Summary Aims The purpose of this study was to examine the effectiveness of beinaglutide on body weight, glycated haemoglobin (HbA 1c ), blood pressure and lipid profiles in patients with type 2 diabetes mellitus (T2DM) in a real‐world setting in China. Materials and methods This was a multicentre, observational, retrospective, open‐label study conducted in China. Data were collected from T2DM patients who started treatment with beinaglutide between 2017 and 2018. Results A total of 314 patients were included in the study. After 3 months of treatment with beinaglutide, there were significant reductions in body weight (−10.05 kg [95% confidence interval −9.29 to −10.80]), HbA 1c (−2.87% [−2.62 to −3.11]), 2‐h postprandial plasma glucose (−5.46 mmol L −1 [−4.96 to −5.95]) and fasting plasma glucose (−3.04 mmol L −1 [−2.78 to −3.31]) (all p < 0.0001). In addition, 84.96% and 72.18% of the patients achieved weight loss of ≥5% and ≥10%, respectively. Subgroup analyses showed that weight loss was significantly greater in patients with ≥28 kg m −2 of baseline body mass index and 0.60 mg of beinaglutide doses ( p = 0.007 and p < 0.0001, respectively). HbA 1c reductions were significantly greater in patients with ≥9.0% baseline HbA 1c and in those administered 0.40–0.48 mg of beinaglutide doses (all p < 0.0001). Weight loss at 3 months was positively correlated with baseline BMI and the dose of beinaglutide. Positive determinants for HbA 1c reduction after 3 months were baseline HbA 1c and the dose of beinaglutide. Conclusions These observational results confirmed the benefits of beinaglutide in weight loss and glycaemic control and support the use of beinaglutide as an effective treatment for T2DM.