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 investigate the influencing factors for persistent inflammation, immunosuppression, and catabolism syndrome (PICS) in patients with severe acute pancreatitis(SAP), and to establish a predictive model. Methods A retrospective analysis was performed for the clinical data of 163 patients who were admitted to the intensive care unit and the emergency intensive care unit due to SAP in The First Affiliated Hospital of Guangxi Medical University from May 2012 to May 2022, and according to the diagnostic criteria for PICS, these patients were divided into PICS group (65 SAP patients with PICS) and non-PICS group (98 SAP patients without PICS). The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups. Variance inflation factor and correlation matrix heatmap were used to evaluate multicollinearity between variables, and Lasso regression and multivariate logistic regression were used to identify independent risk factors and establish a nomogram predictive model. The receiver operating characteristic (ROC) curve, the calibration curve, and the Hosmer-Lemeshow goodness-of-fit test were used for the internal validation of the model, and the decision curve was used to evaluate the clinical practicability of the model. Results The univariate analysis showed that there were significant differences between the PICS group and the non-PICS group in mean arterial pressure, hemoglobin, hematocrit (HCT), neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio (PLR), blood urea nitrogen, creatinine, Glasgow coma score, Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score, Sequential Organ Failure Assessment (SOFA) score, mechanical ventilation, acute respiratory distress syndrome, acute kidney injury (AKI), acute liver injury, hypovolemic shock, sepsis, intra-abdominal hypertension, intra-abdominal hemorrhage, and multiple organ dysfunction syndrome (all P < 0.05). The Lasso regression analysis showed that related predictive variables included PLR, HCT, APACHE Ⅱ, SOFA, mechanical ventilation, AKI, hypovolemic shock, and intra-abdominal hypertension, and the multivariate logistic regression analysis showed that PLR (odds ratio [ OR ]=1.006, P < 0.05), mechanical ventilation ( OR =4.324, P < 0.05), AKI ( OR =3.432, P < 0.05), and hypovolemic shock ( OR = 6.910, P < 0.05) were independent risk factors for PICS in patients with SAP. Model fitting was performed for the above factors, and bootstrap internal validation showed that the nomogram model had an area under the ROC curve of 0.874 (95% confidence interval: 0.822-0.925); the calibration curve of the model was close to the reference curve, and the Hosmer-Lemeshow goodness-of-fit test showed that the model was well fitted ( χ 2 =8.895, P =0.351). The decision curve analysis showed that the predictive model had good clinical practicability. Conclusion PLR, mechanical ventilation, AKI, and hypovolemic shock are independent risk factors for PICS in patients with SAP, and the nomogram model established has good discriminatory ability, calibration, and clinical practicability.

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.

Objective To investigate the relationship between visceral fat related index and the severity of acute pancreatitis (AP). Methods A total of 308 patients hospitalized with AP at the First Affiliated Hospital of Guangxi Medical University from September 2014 to October 2021 were included. They were divided into mild acute pancreatitis (MAP) ( n =186), moderate severe acute pancreatitis (MSAP) ( n =60) and severe acute pancreatitis (SAP) ( n =62) for comparison in age, hospitalization cost and days, scoring systems and body mass indexes. Comparison of normally distributed continuous data with homogeneity of variance between groups was made by one-way analysis of variance, and intergroup and intragroup pairwise comparison of data with heterogeneity of variance was made by the Kruskal-Wallis H test. The receiver operating characteristic curves (ROCs) for each index were constructed and area under the curve ( AUC ) was calculated to evaluate the performance of each index. Univariable and multivariable logistic regression analyses were used to identify the independent risk factors of MSAP and SAP. Results There were significant differences among the three groups in terms of hospitalization costs and durations, TG, HDL-C, NLR, WBC, Alb, Cr, BUN, scoring systems, CMI, LAP, WTI and CVAI. Further pairwise comparisons revealed that CMI, LAP, WTI and CVAI were significantly higher in the MAP group than in MSAP and SAP groups. We also found correlation between CMI and the severity of AP ( r =0.352, P < 0.001). By comparing the AUC s, CMI was found to be the most accurate in predicting the occurrence of MSAP and SAP. Univariable logistic regression analysis showed that CMI, LAP, WTI, CVAI and WC were the risk factors of MSAP and SAP. After adjusting for confounding factors, CMI and CVAI were identified as the independent risk factors of MSAP and SAP. The risk of MSAP and SAP with CMI ≥ 0.801 was 3.740 times that with CMI < 0.801 (95% CI : 1.983~7.056, P < 0.001). Conclusions Visceral fat is related to the severity of AP. Among the four visceral fat related indexes (CMI, LAP, WTI and CVAI), cardiometabolic index is the most valuable in predicting the severity of AP and they are positively correlated. CMI, an independent risk factor for MSAP and SAP, can be used to predict and assess the severity of AP.

ObjectiveTo investigate the value of early fluid resuscitation endpoints in evaluating blood volume in patients with acute pancreatitis. MethodsA retrospective analysis was performed for the clinical data of 445 previously untreated patients with acute pancreatitis who were admitted to The First Affiliated Hospital of Guangxi Medical University from 2003 to 2016 and had an onset time of less than 24 hours, and according the fluid resuscitation endpoints of mean arterial pressure (MAP), hematocrit (HCT), and blood urea nitrogen (BUN), the patients were divided into standard-reaching group (MAP ＞65 mm Hg, BUN ＜7.14 mmol/L, and HCT ≥0.35 and ≤044, n=219) and non-standard-reaching group (MAP ≤65 mm Hg or BUN ≥7.14 mmol/L or HCT ＞0.44 or ＜0.35, n=226). The standard-reaching group represented normal volume, while the non-standard-reaching group represented insufficient volume. The two groups were compared in terms of symptoms, signs, etiology, severity, complication, and prognosis. The chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups, and the Mann-Whitney U test was used for comparison of continuous data between two groups. ResultsCompared with the standard-reaching group, the non-standard-reaching group had significant increases in white blood cell count, BUN, and Computed Tomography Severity Index of the pancreas (Z=-2.85, -6.725, and -2.293, all P＜0.01). As for local complications, compared with the non-standard-reaching group, the standard-reaching group had significantly lower incidence rates of peripancreatic exudation (45.2% vs 54.9%, χ2=4.15, P＜0.05) and pancreatic necrosis (10.0% vs 186%, χ2=6.59, P＜0.05). As for systemic complications, compared with the non-standard-reaching group, the standard-reaching group had significantly lower incidence rates of acute respiratory distress syndrome (ARDS) (0.5% vs 4.4%, χ2=7.26, P＜0.05) and renal dysfunction (1.4% vs 6.6%, χ2=7.95, P＜0.05). The standard-reaching group had significantly lower proportion of patients with severe pancreatitis and hospital costs than the non-standard-reaching group (both P＜0.05). ConclusionFluid resuscitation endpoints can be used to evaluate the blood volume of patients with acute pancreatitis in the early stage after admission, and the patients not reaching the standard of fluid resuscitation tend to develop the complications such as peripancreatic exudation, pancreatic necrosis, ARDS, and renal dysfunction and may have higher hospital costs.

ObjectiveTo investigate the clinical features of severe acute hypertriglyceridemic pancreatitis (HTGP). MethodsA retrospective analysis was performed for the clinical data of 179 patients with moderate severe pancreatitis (MSAP) or severe acute pancreatitis (SAP) who were admitted to The First Affiliated Hospital of Guangxi Medical University from January 2013 to June 2016. According to the etiology, these patients were divided into severe biliogenic acute pancreatitis (biliogenic AP) group with 68 patients, severe alcoholic acute pancreatitis (alcoholic AP) group with 39 patients, severe acute HTGP group with 45 patients, and severe acute pancreatitis group with other causes (other group) with 27 patients. Related data of the patients with clear causes in the former three groups were recorded, including demographic data, blood triglyceride (TG) level on the first day of admission, cause, pancreatic necrosis, systemic complications ［acute respiratory distress syndrome (ARDS), acute renal injury, hypotension, and disseminated intravascular coagulation (DIC)］, and related clinical outcomes (admission to the intensive care unit, length of hospital stay, and mortality rate). In order to investigate the influence of TG concentration on the prognosis of AP patients, the patients were divided into normal blood lipid group with 82 patients, mild dyslipidemia group with 52 patients, moderate dyslipidemia group with 28 patients, and severe dyslipidemia group with 17 patients, according to the TG level on the first day of admission, and the incidence rates of systemic complications, pancreatic necrosis, and clinical outcomes were analyzed. The Kruskal-Wallis H test was used for comparison of continuous data between multiple groups, the chi-square test was used for comparison of categorical data between groups, and the Spearman rank correlation test was used for correlation analysis. ResultsBiliary tract disease remained the leading cause of SAP (38%), followed by hypertriglyceridemia (25%). As for systemic complications, the HTGP group had a significantly higher incidence rate of ARDS than the biliogenic AP group and the alcoholic AP group (P=0.014 and 0022). In the groups with different TG levels, the incidence rates of ARDS and acute renal injury were positively correlated with TG level (r=0.966 and 0.982, P=0.004 and 0.019). ConclusionThe HTGP group has a higher incidence rate of ARDS than the biliogenic AP group and the alcoholic AP group, and the risk of ARDS and acute renal injury tends to increase with the increasing TG level.

Objective To evaluate the therapeutic effect of endoscopic management of plastic stents of post-liver transplantation anastomotic biliary stricture. Methods From January 2010 to October 2015, clinical data of patients with post-liver transplantation anastomotic biliary stricture and received endoscopic retrograde cholangiopancreatog﹣raphy and plastic stents management was collected. The technical success rate, ERCP-related complications, clinical remission rate and long-term complications were main outcome measurements to compare the efficacy and safety of different number of stents in managing post-liver transplantation anastomotic biliary stricture. Results Among the 18 patients (0.5 ~ 60.0 months) with post-liver transplantation ABSs, seven patients received less plastic stents treat﹣ment (< 3 stents), nine patients with persistent anastomotic or recurrent stricture received multiple plastic stents treatment (≥ 3 stents), two patients received multiple plastic stents treatment once suffered with post-liver trans﹣plantation ABSs. The endoscopic technical success rate was seventy-six over eighty (95.0 %). Among the seven pa﹣tients received less plastic stents treatment, one loss to follow-up, two were still under treatment, one died of acute hepatic failure, one died of septic stock, one combined with biliary fistula resulted in treatment failure, one achieved clinical remission, the clinical remission rate was one third (33.3 %). Among the eleven patients received multiple plastic stents treatment, two loss to follow-up, one was still under treatment, two received surgery because of failed treatment, six achieved clinical remission, the clinical remission rate was 75.0 % (6/8). The average diameters and stent durations of management of 1 stent, 2 stents, 3 stents, 4 stents, 5 stents, 7 stents were 8.5 F, 17.0 F, 24.0 F, 28.0 F, 36.0 F, 50.0 F. Among the six early postoperative complications, five cases occurred in less stent manage﹣ment and one occurred in MPSs management, the early postoperative complication rate was 7.5 %(6/80). No severe ERCP-related complications and procedure-related deaths. Conclusions Endoscopic management of plastic stents is safe and effective for post-liver transplantation ABSs. Providing larger biliary support, the multiple plastic stents treatment was superior to less plastic stents treatment in view of clinical remission rate, especially for refractory one. Multiple plastic stents did not increase the incidence of complications, it could be used as the first-line treatment of post-liver transplantation duct-to-duct biliary anastomosis for its safety and effectivity.

Objective To explore the expression and function of myosin light streptokinase (MLCK) in small intestine mucosa of acute necrotizing pancreatitis (ANP) rats.Methods Fifty-six male SD rats were randomly assigned to control group and ANP group.A rat model of ANP was reproduced by retrograde injection of 4％ sodium taurocholate into the biliopancreatic duct,while the control group underwent a sham operation.The rats were sacrificed at 6th,12th,24th,48th hour after ANP induction.Serum amylase、TNF α,IL 1β,diamine oxidase (DAO) were measured.The pathological scores in the pancreas and small intestine were observed.The ultrastructure and tight junction (TJ) changes in the small intestine mucosa were observed with an electron microscope.The localization and expression of MLCK in small intestine mucosa was determined by immunohistochemistry method.Results Compared to the control group,the serum amylase,TNF-α,IL-1 β,DAO level,in the ANP group were all significantly increased;[(4 978 ± 1 574) U/L vs (1 176 ± 124))U/L,(47.88 ± 15.85) μg/L vs (17.24 ± 1.99) μg/L,(132.48 ± 68.54) μg/L vs (23.51 ± 6.44) μg/L,(95.96 ± 30.84)μg/L vs (38.06 ± 17.73)U/L at 12 h],and the pathology scores of pancreas and small intestine were both significantly elevated [12 h:(12.2 ± 1.80) vs (4.68 ± 0.35),(2.58 ± 0.52) vs (0.58 ±0.26)] (P ＜0.05);the MLCK protein expression in small intestine mucosa was significantly increased in ANP group (12 h:0.1863 ± 0.0230 vs 0.1636 ± 0.0049),and the difference was statistically significant (P ＜0.05).The small intestine ultrastructure was seriously damaged and TJ was widened significantly in ANP Group.Conclusions The increased serum TNF alpha and IL-1β concentration and DAO activity and up-regulated MLCK protein expression in small intestine mucosa may damage the integrity of tight junction of intestinal epithelial cell and cause intestine mucosa barrier dysfunction.

Objective To investigate the roles of toll like receptor7 (TLR7) and toll like receptor 9 (TLR9) in the pathogenesis of acute pancreatitis.Methods AR42J cells were treated by lipopolysaccharide at different dosages (0,1,10,100 mg/L),and cell model of acute pancreatitis in vitro was established.AR42J cells without lipopolysaccharide treatment were as control.Cells and culture supernatant were collected after 24 hours cultivation.TLR7,TLR9 mRNA and protein expressions were detected by RT-PCR and Western Blot,and levels of TNF-α,IL-10 in culture supernatant were measured by ELISA.Results The TLR 7 mRNA expression levels in control group,1,10,100 mg/L lipopolysaccharide group were 0.12 ± 0.09,0.28 ± 0.06,0.49 ± 0.04,0.78 ± 0.04,and the TLR9 mRNA expression levels were 0.06 ± 0.02,0.32 ± 0.03,0.56 ± 0.14,0.84 ± 0.12; the TLR7 protein expression levels were 0.04 ± 0.01,0.26 ± 0.05,0.49 ±0.04,0.77 ±0.16,and the TLR9 protein expression levels were 0.10 ±0.14,0.62 ±0.23,1.21 ± 0.26,1.75 ± 0.13 ; the TNF-α levels in culture supernatant were (8.01 ± 5.32),(25.64 ± 8.71),(49.06 ± 10.23),(75.83 ± 6.65) ng/L,and the IL-10 levels were (155.54 ± 25.47),(105.16 ± 10.49),(69.36 ± 8.19),(14.07 ± 9.06)ng/L.The expression levels of TLR7 and TLR9's mRNA,protein in cell,as well as the levels of TNF-α in culture supernatant increased with the lipopolysaccharide concentration,while the levels of IL-10 in culture supernatant decreased with the lipopolysaccharide concentration,and the difference among these groups was statistically significant (P ＜ 0.01).Conclusions The expressions of TLR7 and TLR9 in AR42J cells treated by using lipolysaccharide are obviously up-regulated,and it suggests that TLR7 and TLR9 may be vital in the pathogenesis of acute pancreatitis.

Objective To observe the expression of adrenomedullin (ADM) mRNA in hepatic tissue of rats with acute necrotizing pancreatitis (ANP) complicated with hepatic injury.Methods Sixty-four SD rats were randomly divided into control group and ANP group with 32 rats in each group.In ANP group,ANP model was induced by retrograde injection of 5％ sodium taurocholate into biliopancreatic duct of rats.Rats in control group only received sham operation and pancreas manipulation.All the rats were sacrificed at 3,6,12,24 h after the operation.The serum levels of amylase,alanine aminotransferase (ALT),aspartate aminotransferase (AST) and ADM were detected.Pathological changes in pancreatic and hepatic tissue were examined.The expressions of ADM mRNA in hepatic tissue were evaluated by fluorescence quantitative PCR.Results The serum concentrations of amylase,ALT,AST were (7229 ±968),(174.2 ±28.0),(657.7 ± 139.0) U/L,which were significantly higher than those in control group [(2036 ± 292),(104.3 ± 22.1),(419.7 ± 86.3) U/L],and the difference between the two groups was statistically significant (P ＜ 0.05 or P ＜0.01).Pathological injury of pancreas and liver tissue in ANP gradually aggravated with time,and the pathological scores at 12 h were (11.60 ± 1.51),(2.60 ± 0.89),which were significantly higher than those in control group (1.20 ± 0.77,0),and the difference between the two groups was statistically significant (P＜0.01).The serum concentrations of ADM in ANP group increased at 3 h after ANP induction,and reached (38.53 ± 6.25)pg/ml at 12 h,which was significantly higher than that in control group [(28.99 ±3.92)pg/ml] ; the concentrations of ADM in liver tissue increased at 3 h after ANP induction,and reached (3.00 ± 1.49) at 6 h,which was significantly higher than that in control group (1.04 ± 0.20),and the difference between the two groups was statistically significant (P＜0.05 or P＜0.01).Conclusions The expression of ADM mRNA in rat 's hepatic tissue increases in the early stage of ANP,and the serum concentration of ADM also increases.