Objective: Necrotizing enterocolitis (NEC) is a gastrointestinal emergency with a severe inflammation storm, intestinal necrosis, and perforation. MicroRNA-146a-5p (miR-146a-5p) has been reported to be a valuable anti-inflammatory factor in various intestinal inflammatory disorders. However, the role of miR-146a-5p in NEC, its effects on nucleotide-binding domain and leucine-rich repeat-containing protein 3 (NLRP3) inflammasome, and its downstream inflammatory factors remain unknown. This study aimed to investigate the role of miR-146a-5p and NLRP3 inflammasome and its downstream inflammatory factors in NEC development.Methods: The expression levels of miR-146a and NLRP3 inflammasome were investigated in intestinal tissues. Next, the mechanism by which miR-146a-5p regulates NLRP3 inflammasome activation was explored in vitro in THP-1 cells. Finally, to identify the effects of miR-146a-5p on NEC in vivo, NEC mice were transinfected with miR-146a-5p overexpression adenovirus before the occurrence of NEC.Results: NLRP3 inflammasome enzymatic protein caspase-1 and its downstream inflammatory factors increased in NEC intestinal samples in both humans and mice, and miR-146a-5p expression level was increased and mainly expressed in the macrophages of the affected intestine. In vitro, only miR-146a-5p mimic inhibited NLRP3 inflammasome downstream inflammatory factors and its upstream protein chloride intracellular channel protein 4 (CLIC4) expression in cellular membrane in the THP-1 cell line, and this only occurred under mild/moderate LPS concentration. MiR-146a-5p overexpression adenovirus transfection reduced CLIC4 cellular membrane expression and inhibited NLRP3 downstream factors increasing in vivo. After the transfection of miR-146a-5p adenovirus, the survival rate of NEC mice was increased, and intestinal injury was ameliorated.Conclusion: MiR-146a-5p inhibited NLRP3 inflammasome downstream inflammatory factors and CLIC4 membrane expression in NEC. Additionally, miR-146a-5p could attenuate inflammation and intestinal injury in the NEC-affected intestine.

Background and Objectives:Laparoscopic common bile duct exploration (LCBDE) has been verified to be an effective technique in treating choledocholithiasis, and T-tube insertion has been widely performed after LCBDE. With growing doubts regarding the effectiveness and safety of T-tube drainage (TTD), it has been suggested to replace such with primary duct closure (PDC). This meta-analysis aimed to evaluate the short- and long-term effectiveness and safety of PDC compared with TTD after LCBDE.Methods:The PubMed, Science Citation Index, and Cochrane Central Register of Controlled Trials databases were used to accomplish a systematic literature search for randomized controlled trials and pro-/retrospective cohort studies that compared PDC alone or PDC combined with biliary drainage stenting (PDC+BD) with TTD after LCBDE. A subgroup analysis was established to compare PDC+BD with TTD. RevMan 5.3 was used for the statistical analysis.Results:A total of 2552 patients from 26 studies were included. The pooled odds ratio supported PDC, which yielded lower postoperative overall morbidity and incidence of bile leak and bile peritonitis and shorter surgical time and postoperative hospital stay when compared with TTD. In the subgroup analysis, PDC+BD showed significantly better results in terms of postoperative overall morbidity, incidence of bile leak and bile peritonitis, surgical time, and postoperative hospital stay than did TTD. PDC and PDC+BD showed no difference in the incidence of recurrent stones and biliary stricture during the long-term follow-up period compared with TTD.Conclusion:PDC alone or PDC+BD is superior to TTD as a duct-closure method after LCBDE.

Background Intestinal dysbiosis is believed to be one of the factors inducing neonatal necrotizing enterocolitis (NEC). Probiotics have been employed to treat NEC in a number of animal experiments and clinical trials, and some significant benefits of utilizing probiotics for the prevention or alleviation of NEC have been confirmed. However, the mechanism underlying the efficacy of probiotics in treating NEC has not been elucidated. Results Impairment of the intestinal barrier, which was characterized by the decreased expression of tight junction components, was observed in the pathogenesis of NEC. The probiotic mixture alleviated this intestinal damage by enhancing the function of the barrier. Meanwhile, the probiotics remodeled the composition of the intestinal microbiota in NEC mice. Furthermore, increased expression of the pregnane X receptor (PXR) was observed after treatment with the probiotic mixture, and PXR overexpression in Caco-2 cells protected the barrier from lipopolysaccharide (LPS) damage. Further research showed that PXR could inhibit the phosphorylation of c-Jun N-terminal kinase (JNK) and could increase the expression of tight junction components. Conclusions Our study confirmed that probiotics could ameliorate intestinal lesions by enhancing the function of the mucosal barrier. Specifically, probiotics may target PXR, which may subsequently enhance the expression of tight junction components by inhibiting the phosphorylation of JNK and enhance the function of the barrier.