Nutrition is a necessary condition for cell proliferation, including pancreatic β cells; however, over-nutrition, and the resulting obesity and glucolipotoxicity, is a risk factor for the development of Type 2 diabetes mellitus (DM), and causes inhibition of pancreatic β-cells proliferation and their loss of compensation for insulin resistance. Here, we showed that Retinoic acid (RA)-inducible gene I (RIG-I) responds to nutrient signals and induces loss of β cell mass through G1 cell cycle arrest. Risk factors for type 2 diabetes (e.g., glucolipotoxicity, TNF-α and LPS) activate Src in pancreatic β cells. Elevated RIG-I modulated the interaction of activated Src and STAT3 by competitive binding to STAT3. Elevated RIG-I downregulated the transcription of SKP2, and increased the stability and abundance of P27 protein in a STAT3-dependent manner, which was associated with inhibition of β cell growth elicited by Src. These results supported a role for RIG-I in β cell mass loss under conditions of metabolic surplus and suggested that RIG-I-induced blocking of Src/STAT3 signalling might be involved in G1 phase cycle arrest through the Skp2/P27 pathway in pancreatic β cells.

This study aimed to assess the clinical value of transprepancreatic septotomy indwelling guide wire or pancreatic duct stent in intractable endoscopic retrograde cholangiopancreatography (ERCP) for bile duct cannulation.Of the 2107 patients treated by ERCP, a total of 81 cases with difficult bile duct cannulation underwent transprebiliopancreatic septotomy (referred to as the septotomy group, 37 cases) and transprepancreatic septotomy with pancreatic duct stent (modified septotomy group, 44 cases). Success rates of cannulation and postoperative complications for both methods were compared.Among them, 77 cases were successfully administered bile duct cannulation. The success rates of the septotomy and modified septotomy groups were 91.89% and 97.73%, respectively, with no significant difference (P = .489). Of the 77 patients, 12 cases had complications. The septotomy group included 7 acute pancreatitis, 1 bleeding, and 1 biliary tract infection cases; while in the modified septotomy group, there were 1 acute pancreatitis, 1 bleeding, and 1 biliary tract infection cases. The occurrence rate of acute pancreatitis in the modified septotomy group was lower than that of the septotomy group (2.33% vs 20.59%) with a significant difference (P = .026).These findings indicate that transprepancreatic septotomy with pancreatic duct stent seems to be a safe and feasible operation with reducing complication rates.

ThE present work focused on exploring Girdin expression within gastric cancer (GC), examining the effect of Girdin on the cell phenotype of GC, and clarifying the underlying mechanisms. Girdin expression in GC samples was identified by immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR) assays. Girdin-targeting siRNAs were transfected into GC cells; later, we examined GC cell proliferation, migration, invasion, and apoptosis, respectively. Additionally, the protein expression was examined through Western blotting assay. Moreover, the tumor implantation experiment was conducted for examining Girdin knockdown in vivo. The results showed that Girdin expression elevated within GC samples, which was associated with the dismal prognostic outcome. Girdin knockdown suppressed GC cell proliferation, migration, and invasion, and enhanced apoptosis and cell cycle arrest. Girdin promoted the phosphorylation of AKT, GSK3β, and β-catenin. Moreover, Girdin inhibited the phosphorylation of β-catenin. Girdin suppressed cell apoptosis and stimulated cell migration and invasion, while AKT inhibitor (MK2206) treatment reversed the effect of Girdin overexpression, and GSK3β inhibitor (CHIR99021) treatment enhanced the effect of Girdin overexpression on GC cells. Besides, Girdin delayed tumor growth in vivo. In conclusion, Girdin was abnormally expressed in GC samples, which promoted the development of GC by regulating AKT/GSK3β/β-catenin signaling.