ObjectiveTo investigate the effect of mitochondrial calcium uniporter （MCU） on the cytoskeleton of pancreatic ductal epithelial cells in a mouse model of acute pancreatitis （AP） induced by caerulein （CAE）， to analyze the role of MCU in the development of AP， and to provide a theoretical basis for clinical treatment. MethodsIn the in vivo experiment， wild-type male C57BL6/J mice， aged 4 weeks， were randomly divided into control group and AP group， with 6 mice in each group. The mice in the AP group were given intraperitoneal injection of CAE to establish a model of AP， and those in the control group were given intraperitoneal injection of an equal volume of normal saline. Serum and pancreatic tissue samples were collected after 24 hours of modeling. HE staining was used to observe pancreatic histopathological changes； Western Blot was used to measure the expression levels of MCU， glutathione peroxidase 4 （GPX4）， and acyl-CoA synthetase long chain family member 4 （ASCL4）； kits were used to measure the serum level of amylase. In the in vitro experiment， the human pancreatic ductal epithelial cell line HPDE6-C7 was co-cultured with CAE for 24 hours to establish an in vitro AP model， and the cells were divided into control group， CAE group， RR （an MCU activity inhibitor） group， CAE+RR group， Fer-1 （an ferroptosis inhibitor） group， CAE+Fer-1 group， Erastin （an ferroptosis inducer） group， and CAE+Erastin group. CCK-8 assay was used to observe the influence of different agents on cell viability； Western Blot was used to measure the expression levels of MCU， GPX4， and ASCL4； immunofluorescence assay was used to measure reactive oxygen species （ROS）， actin cytoskeleton， and monolayer permeability； kits were used to measure the concentrations of malondialdehyde （MDA）， glutathione （GSH）， Fe²⁺， and total iron. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for comparison between two groups. ResultsIn the in vivo experiment， compared with the control group， the AP group had significant increases in pancreatic histopathological score， the serum level of amylase， and the expression levels of MCU and ASCL4， as well as a significant reduction in the expression of GPX4 （all P<0.05）. In the in vitro experiment， compared with the control group， the CAE group had significant increases in the expression levels of MCU and ASCL4， a significant reduction in the expression of GPX4， and significant increases in the concentrations of Fe²⁺， total iron， and MDA， the green fluorescence intensity of ROS， and monolayer permeability， as well as a significant reduction in the concentration of GSH （all P<0.05）， with the presence of actin cytoskeleton disruption. Compared with the CAE group， the CAE+RR group had a significant increase in the expression level of GPX4， a significant reduction in the expression level of ASCL4， and significant reductions in the concentrations of Fe²⁺， total iron， and MDA， the green fluorescence intensity of ROS， and monolayer permeability and a significant increase in the concentration of GSH （all P<0.05）， with alleviation of actin cytoskeleton disruption. Compared with the CAE group， the CAE+Fer-1 group had significant reductions in the concentrations of Fe²⁺， total iron， and MDA， the green fluorescence intensity of ROS， and monolayer permeability and a significant increase in the concentration of GSH （all P<0.05）， with alleviation of actin cytoskeleton disruption. Compared with the CAE group， the CAE+Erastin group had significant increases in the concentrations of Fe²⁺， total iron， and MDA， the green fluorescence intensity of ROS， and monolayer permeability and a significant reduction in the concentration of GSH （all P<0.05）， with aggravation of actin cytoskeleton disruption. ConclusionDuring the onset of AP， MCU mediates oxidative stress-induced ferroptosis and leads to the disruption of the pancreatic ductal epithelial barrier， which may be one of the possible pathogeneses of AP.

Objective To explore the efficacy and safety of endoscopic ligation in treatment of gastric submucosal tumors(diameter≤1 cm).Methods Clinical data of 177 patients with gastric submucosal tumors who received endoscopic therapy from October 2020 to July 2022 were retrospectively analyzed.Patients were divided into endoscopic submucosal dissection(ESD)group(n = 142)and endoscopic ligation group(n = 35)according to different endoscopic treatment methods,and the operation time,intraoperative complications,postoperative hospital stay,surgical cost,complete lesion resection,postoperative complications and pathology of the two groups were compared.Results The operative time of the ESD group was(33.23±8.55)min,which was significantly longer than that of the endoscopic ligation group(24.85±5.96)min.The intraoperative bleeding was ERB-c1 and no ERB-c2 of the ESD group,which was better than that of the endoscopic ligation group,and the operative cost was(24 615.08±5 678.32)yuan,significantly more than that of the endoscopic ligation group(21 319.26±7 235.95)yuan,the differences were statistically significant(P＜0.05).There was no significant difference in the intraoperative perforation rate,postoperative hospitalization time and postoperative follow-up time between the two groups(P＞0.05).No surgical transfer,serious infection,delayed hemorrhage and perioperative death occurred in both groups,and no tumor recurrence,metastasis and death were found.Conclusion Endoscopic ligation has the advantages of relatively safe,efficient,less blood loss and low cost,but it has the risk of bleeding which is difficult to predict.Therefore,it is particularly important to select appropriate treatment after adequate evaluation.

OBJECTIVETo observe the effect of N-acetylcysteine (NAC) on intestine injury induced by cardiopulmonary bypass (CPB) in rats.

METHODSThirty-two rats were randomly divided into sham-operated group, NAC control group, CPB model group, and CPB plus NAC treatment group (n=8). In the latter two groups, the rats were subjected to CPB for 1 h. The rats received intraperitoneal injections of normal saline or NAC (0.5 g/kg) as appropriate for 3 successive days prior to CPB, and those in CPB plus NAC group were given NAC (100 mg/kg) in CPB prime followed by infusion at 20 mgsol;(kg·h) until the cessation of CPB. Intestinal and blood samples were collected 2 h after CPB for pathological analysis and measurement of intestinal concentrations of malondialdehyde (MDA), tumor necrosis factor (TNF)-α, interlukin (IL)-6 and activity of superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-Px) and serum levels of diamine oxidase (DAO).

RESULTSEvident oxidative stress and pathological damages of the intestines were observed in rats after CPB. NAC treatment obviously alleviated intestinal damages induced by CPB, decreased the levels of intestinal MDA, TNF-α, IL-6 and serum DAO and increased activity of SOD, GSH, and GSH-Px in the intestines.

CONCLUSIONPerioperative NAC treatment can alleviate intestinal injury induced by CPB in rats by suppressing oxidative stress and inflammatory response.

Acetylcysteine ; pharmacology ; Animals ; Cardiopulmonary Bypass ; adverse effects ; Glutathione ; metabolism ; Glutathione Peroxidase ; metabolism ; Inflammation ; drug therapy ; Interleukin-6 ; metabolism ; Intestines ; drug effects ; physiopathology ; Malondialdehyde ; metabolism ; Oxidative Stress ; drug effects ; Rats ; Superoxide Dismutase ; metabolism ; Tumor Necrosis Factor-alpha

Objective To investigate the clinical value of the Classification of acute pancreatitis2012.Methods Medical records and clinical data of patients with acute pancreatitis (AP) who were admitted to First Affiliated Hospital of Guangxi Medical University between October 2009 and September 2012 were retrospectively reviewed and analyzed.Patients were divided into mild acute pancreatitis (MAP),moderately severe acute pancreatitis (MSAP),and severe acute pancreatitis (SAP) groups according to the Classification of acute pancreatitis-2012.The number of improved and cured patients,length of hospital stay,hospitalization costs,rate of ICU admission,length of ICU stay,incidence of SIRS,and length of SIRS continue,Ranson scores,APACHE Ⅱ scores,computed tomographic severity index (CTSI) scores among the 3 groups were compared.Results One hundred and sixty-six patients with AP (119 males and 47 females) were included,and 76 were MAP,65 MSAP and 25 SAP.The average interval between AP onset and hospital admission was (2.27 ± 1.46) d.The number of improved and cured patients,length of hospital stay,hospitalization costs,rate of ICU admission,length of ICU stay,incidence of SIRS,and length of SIRS continue,Ranson scores,APACHE Ⅱ scores,CTSI scores increased with the severity of AP.The corresponding values in SAP group were 21 cases (84.0％),(23.8 ± 13.6) d,(53900 ± 30260) Yuan,48.0％ (12/25) and (5.76 ± 13.8) d,96.0％ (24/25) and (5.00 ± 2.40) d,(3.76 ± 1.30) score,(8.52 ± 4.24) score,(5.44 ± 3.48) score.Seventy-nine patients developed local complications,among them 34 was acute peripancreatic fluid collection,45 was acute necrosis collection.The incidence of acute necrosis collection in SAP group was significantly higher than that in MSAP group (68.0％ vs 44.6％,P =0.047),but the incidence of acute peripancreatic fluid collection in SAP group was significantly lower than that in MSAP group (16.0％ vs 46.2％,P =0.016).Organ failure occurred in 42 patients,among them 35 cases were respiratory failure,2 cases were renal failure,and 5 cases were respiratary and renal failure.The incidence of organ failure in SAP and MSAP group was 100％ and 26.2％,the difference between the two groups was statistically significant (P ＜ 0.05).Conclusions Classification of acute pancreatitis-2012 is a simple and convenient system,which can predict the severity of AP and appropriate for clinical application.