Background:High-fat diet leads to intestinal mucosa barrier dysfunction,but the mechanism is not clear. High-fat diet can induce increase of bile acid. Aims:To investigate whether the high bile acid induced by high-fat diet could act on intestinal stem cell to disrupt stem cell differentiation and imparing the intestinal mucosa. Methods:Twenty-four rats were divided into 3 groups:fed with regular diet,high-fat diet and high-fat diet + cholestyramine,respectively,for 2 weeks. Serum bile acid was detected by ELISA. Ileal diameter was measured and HE staining was performed to observe histology of intestinal mucosa. Expression of Lgr5 gene was determined by RT-qPCR. Ileal tissue fed with regular diet was cultured with deoxycholic acid(DCA)or DCA + cholestyramine for 24 hours in vitro,expression of Lgr5 gene was determined by RT-qPCR. Results:Compared with control group,serum bile acid was significantly increased(P < 0. 05),ileal diameter was significantly decreased,height of intestinal crypts and villus was significantly decreased(P < 0. 05),and expression of Lgr5 gene was significantly decreased in high-fat diet group(P < 0. 01). All the above-mentioned indices were significantly ameliorated in high-fat diet + cholestyramine group(P < 0. 05). In vitro study showed that expression of Lgr5 gene was significantly decreased in DCA group than in control group(P < 0. 01),and cholestyramine could significantly increase expression of Lgr5 gene(P < 0. 05). Conclusions:High-fat diet induced increasing of circulatory bile acid can cause injury of intestinal mucosa by inhibiting stem cell function,which can be ameliorated by cholestyramine.

Objective To evaluate the therapeutic effect of endoscopy for patients with anastomotic or nonanastomotic biliary strictures after liver transplantation.Methods Clinical and follow-up data of 56 patients,38 (67.9％) with anastomotic strictures (AS),and 18 (32.1％) with nonanastomotic strictures (NAS) after liver transplantation,who underwent endoscopic therapy were collected and analyzed.Results Compared to AS patients,NAS patients showed shorter time from liver transplantation to initial presentation (4.45 ± 1.47 vs.8.00 ±2.31 months,P =0.000),underwent more ERCP procedures (6.20 ±1.28 vs.4.11 ± 1.51,P =0.000) and received more stents (10.20 ±3.59 vs.7.53 ±2.12,P =0.001).Although the success rate was not statistically different,patients with NAS needed longer treatment duration and had higher recurrence rate (50.0％ vs.18.2％,P =0.033) as well as shorter duration from treatment to recurrence.Among patients with AS,the treatment failure group had longer stricture length (13.00 ±3.61 vs.6.63 ±2.09,P =0.000) than the success group and the patients who experienced recurrence had longer stricture length (10.48 ± 1.07 vs.5.86 ± 1.55,P =0.000) and narrower stricture diameter (1.52 ± 0.38 vs.1.94 ± 0.32,P =0.001).Among NAS patients,the multiple biliary strictures group had lower success rate and higher recurrence rate,but with no statistical significance (62.5％ vs.90.0％,P =0.275 and 66.7％ vs.37.5％,P =0.592,recpectively).Conclusion NAS patients have lower response to endoscopic treatment than AS patients.The length and diameter of biliary stricture in AS as well as the number of stricture in NAS may influent the effect of endoscopic treatment.

Objective To evaluate the effect of small endoscopic sphincterotomy and endoscopic balloon dilatation in the treatment of common duct stones (CDS) in patients with atypical papillae (combined with diverticula; after surgical operation; combined with abnormal duodenal lumen with no definite cause).MethodsOne hundred and three patients with CDS and with atypical papillae treated from July 2007 to March 2010 were randomly divided into three groups.Thirty-four patients received endoscopic sphincterotomy (EST group),34 patients received endoscopic balloon dilatation (EBD group) and the remaining 35 patients received small endoscopic sphincterotomy and endoscopic balloon dilatation (EST+EBD group).The general state of the patients in the 3 groups showed no significant difference (P＞0.05).We tried to remove all CDS using baskets and/or balloons after the procedures on the papillae.In some patients the stones were crushed by using a basket mechanical lithotriptor (BML).In some patients with huge stones,we could only placed in a plastic stent because of the high risk of removing the stones in a single procedure.ResultsSuccessful endoscopic retrograde cholangiopancreatography (ERCP) was carried out in 96 patients.Patients in the EST+ EBD group had less complications,especially hemorrhage,when compared with the EST group (P＜0.05).Also,the EST+EBD group had a significantly higher success rate of complete stone removal (P＜0.05),decreased use of BML (P＜0.05) and decreased rate of acute pancreatitis when compared with the EBD group (P＜0.05).ConclusionsThe success rate of ERCP in managing patients with CDS with atypical papillae remained high.Small endoscopic sphincterotomy and endoscopic balloon dilatation had a higher success rate of removing stones at the first attempt and a decreased rate of complications.

Nonalcoholic fatty liver disease (NAFLD) includes a series of diseases affected by various complex factors. Mitochondrial dysfunction often occurs in NAFLD and may lead to the progression of hepatitis and liver fibrosis. This article reviews the important role of mitochondrial oxidative stress, respiration, energy metabolism, quality control, and mitochondrial DNA in NAFLD and summarizes the current status of mitochondria-targeted therapy for NAFLD, hoping to provide a new direction for the research and clinical treatment of NAFLD.

OBJECTIVETo investigate the role of TGF-beta1 and STAT3 signaling in liver fibrosis using a rat model system and to determine the therapeutic mechanism of AG490 in relation to this signaling pathway.

METHODSRats were randomly divided into a control group and DENA-induced liver fibrosis model group, and then subdivided into AG490 treatment groups. During fibrosis development, liver tissue samples were collected at different time points (0, 4 and 8 weeks) and evaluated according to the Scheuer scoring system. Expression of STAT3, TGFbeta1, alpha-SMA, E-cadherin, MMP2 and TIMP1 was measured by PCR (mRNA) and immunohistochemistry and western blotting (protein).

RESULTSIncreasing degrees of inflammation and fibrosis were observed in liver tissues of DENA-treated rats throughout model establishment. The mRNA expression of TGFbeta1 and STAT3 was significantly increased in DENA-induced rats with advanced fibrosis (AF) compared to those with early fibrosis (EF) (P = 0.034 and P = 0.012 respectively). The protein expression of TGF-beta1, phospho-Smad2, alpha-SMA, E-cadherin, STAT3 and phospho-STAT3 was significantly increased in DENA-induced rats with AF compared to the unmodeled control group (P = 0.048, P = 0.003, P = 0.002, P = 0.028, P = 0.009 and P = 0.039). The protein expression of E-cadherin was lower in the DENA-induced rats with AF than in those with EF (P = 0.026). STAT3 and TGF-beta1 co-expression was detected in AF tissues. DENA-induced AG490-treated rats with AF showed substantially lower protein expression of STAT3, TGF-beta1, MMP2 and TIMP1 compared to DENA-induced untreated rats with AF (P = 0.006, P = 0.018, P = 0.010 and P = 0.005); in addition, the degrees of fibrosis and inflammation were also greatly reduced in the DENA-induced AG490-treated rats with AF compared to DENA-induced untreated rats with AF (P = 0.042 and P = 0.021). Conclusions STAT3 signal transduction may regulate the TGF-beta1 pathway and affect liver fibrosis, especially in the advanced phase. AG490 can inhibit TGFbeta1-STAT3 signaling, resulting in reversal of liver fibrosis.

Animals ; Disease Models, Animal ; Liver Cirrhosis ; chemically induced ; metabolism ; Rats ; Rats, Sprague-Dawley ; STAT3 Transcription Factor ; metabolism ; Signal Transduction ; Transforming Growth Factor beta1 ; metabolism ; Tyrphostins ; pharmacology

Objective To investigate the mechanism of occurrence and development of zinc-alpha-2-glycoprotein (AZGP1) in the activated hepatic stellate cells (HSCs) and liver fibrosis.Methods The activated human hepatic stellate cell line LX2 was induced by the stimulation of transforming growth factor-β1 to construct carbon tetrachloride liver fibrosis mice model.The situation expression of AZGP1 in liver cells and tissues were observed.Plasmid transfection method was used to detect the activation,proliferation,apoptotic functions and changes in related factors of LX2 cells,respectively,after the overexpression and inhibition of AZGP1expression.Univariate analysis of variance was used for multiple group comparison.Results The results of immunofluorescence staining showed that AZGP1 protein was decreased and α-smooth muscle actin was increased in the activated LX2 cells,and the two were negatively correlated.AZGP1 gene and protein were significantly under-expressed in activated LX2 cells and liver tissues of mice with carbon tetrachloride liver fibrosis.Collagen I,matrix metalloproteinase-2,and α-smooth muscle actin genes and proteins were significantly down-regulated in LX2 cells after over-expression of AZGP 1.Cell fluorescence showed that AZGP 1-overexpressing cells were activated and α-smooth muscle actin protein was reduced.In addition,the proliferative activity and G1/S-specific cyclin D1 protein of LX2 cells were significantly reduced after overexpression of AZGP1,while cell cycle experiments showed that the proportion of cells overexpressing AZGP1 was significantly increased in the G0/G1 phase,and the proportion of S phase was significantly reduced.AZGP1 had no significant effect on the apoptosis of LX2 cells.Conclusion AZGP1 can reverse liver fibrosis by inhibiting the activation and proliferation of hepatic stellate cells,and thereby overexpression of AZGP1 is expected to become a new target for liver fibrosis treatment.

Objective:To explore the value of 5G-based robotic remote ultrasound diagnosis system in musculoskeletal joint injuries.Methods:From March to December 2020, 58 volunteers at a training base who felt musculoskeletal pain or paresthesia were selected and performed both robotic remote ultrasound (remote ultrasound group) and conventional ultrasound (portable ultrasound group). The two types of examinations were compared, the consistency of the two diagnosis results was analyzed by the Kappa test, and the the difference of the diagnosis results was compared by McNemar test.Results:Among the 58 volunteers, 40 cases were positive by both methods and 11 volunteers had 2-3 positive results. There were 59 positive results in the remote ultrasound group and 64 positive results in the portable ultrasound group. The positive rate of the examination sites from high to low was knee joint>foot and ankle joint >hand and wrist joint >shoulder joint>elbow joint, calf and hip. The diagnosis results of the two groups were in good consistency (Kappa=0.782, P<0.001), and there was no statistically significant difference in the diagnosis results between the two groups (χ 2=3.2, P=0.063). Five more diseases with positive results were detected in the portable ultrasound group: 1 meniscus injury, 1 medial collateral ligament injury, 1 soft tissue injury around the metatarsal, 1 biceps tendinitis with effusion and 1 cubital ulnar nerve subluxation. Conclusions:The 5G-based robotic remote ultrasound system has good consistency with conventional ultrasound in the diagnosis of musculoskeletal injures. It can be applied to the ultrasound diagnosis of musculoskeletal joint injuries in remote areas.

Background: Unintended intraoperative hypothermia is a common complication of general anesthesia surgery, which can cause pain, coagulation dysfunction, wound infection, delayed recovery, and other adverse consequences. There are few studies related to intraoperative hypothermia during endoscopic retrograde cholangiopancreatography (ERCP). Aims: To analyze the risk factors of intraoperative hypothermia during ERCP under general anesthesia and establish a predictive model. Methods: A total of 121 patients underwent ERCP under general anesthesia from September 2021 to November 2021 at Shanghai General Hospital were recruited, and relevant clinical data were collected. Logistic regression analysis was used to screen risk factors, and a predictive model was constructed. The model was externally validated by independent datasets with ROC curve and Hosmer⁃Lemeshow goodness of fit test. Results: A total of 114 patients were enrolled in modeling group. The incidence of intraoperative hypothermia was 11.40% (13/114). There were more women in the hypothermia group (P<0.05). The temperature of entering the operating room and operating room temperature were relatively lower in the hypothermia group (P<0.05). Gender was an independent risk factor for intraoperative hypothermia in ERCP under general anesthesia (P<0.05). The predictive model constructed by using gender and temperature of entering the operating room screened by Logistic regression analysis had a good discrimination and calibration, area under the ROC curve by external validation was 0.78. Conclusions: Gender and temperature of entering the operating room can effectively predict the occurrence of intraoperative hypothermia and assist perioperative monitoring and management.