BACKGROUND: Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI. METHODS: In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining and transmission electron microscopy. RESULTS: A low dose of ATO (0.75 μmol/L in vitro and 1 mg/kg in vivo ) significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitro  studies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent. CONCLUSION Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.
Animals ; Arsenic Trioxide ; Autophagy/physiology* ; Reperfusion Injury/prevention & control* ; Mice ; Male ; Proto-Oncogene Proteins c-akt/physiology* ; Arsenicals/therapeutic use* ; Oxides/therapeutic use* ; Liver/metabolism* ; Extracellular Signal-Regulated MAP Kinases/metabolism* ; Mice, Inbred C57BL

Carcinoma of pancreatic body and tail is a high invasive disease with a low resectability rate.It was once believed that celiac axis infiltration usually contraindicated resection.Distal pancreatectomy with en bloc celiac axis resection (DP-CAR) is described as a new treatment method of this disease.In recent years,more and more literatures have reported this operation,but they were case reports or small sample retrospective study,the results of which differed according to the different treatments and perioperative managements in different centers.The advantages and disadvantages of DP-CAR are still controversial.Research progress of DP-CAR is reviewed in this article.

Gastric resection can cause a multifactorial clinical manifestations of dyspepsia,such as flatulence,diarrhea,weight loss,and fat diarrhea.Exocrine pancreatic insufficiency (EPI) is one of the possible mechanisms of fat maldigestion following gastric surgery,the main causes may be related to rapid gastric emptying;asynchrony between gastric emptying and bilio-pancreatic secretion due to new tracts of various reconstructions;bacterial overgrowth after gastrectomy and so on.Oral pancreatic enzyme replacement therapy (PERT) is the mainstay of treatment for EPI,due to lack of available evidence so far,the efficacy and safety of pancreatic enzyme substitution in patients following gastric resection remains unclear and cannot be generally recommended.This review will sum up the revelant studies addressing EPI and PERT after gastric resection in recent years,and summarizes the mechanisms,clinical diagnostic methods and PERT treatment perscription of EPI after gastrectomy to improve the cognition of clinicans.