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Objective To investigate the correlation between intracellular free calcium ion concentration and apoptosis in neurons induced by ammonia in Vitro, to explore the mechanism of ammonia intoxication. Methods Fetal rat neurons were cultured in vitro for 7 days, Neurons were assigned to the control group, low concentration of ammonia group, and high concentration of ammonia group. After treated for 24 h, Flow cytometry was used to count apoptosis cells, Flluo-3/Am was used to detect the variation of calcium in neurons. Results There was significant difference between control group and the low concentration of ammonia group. The difference was statistically significant between the low concentration of ammonia group and high concentration of ammonia group. Conclusion Ammonia might induce apoptosis of fetal rat neuron in vitro; there is striking correlation between intracellular free calcium ion concentration and neuronal apoptosis induced by ammonia. [ABSTRACT FROM AUTHOR]

Objective The purpose of this study was to analyze the clinical, serology, and histopathological characteristics in patients with autoimmune hepatitis-primary biliary cirrhosis(AIH-PBC) overlap syndrome, in order to facilitate cognition and therapy of the disease. Methods Clinical data, biochemistry, immunology and pathological findings of 36 patients were reviewed. Results AIH-PBC was mostly found in middle to oldaged women. Fatigue, pruritus and jaundice were the common symptoms, the patients, serum ALT, AST, GGT and ALP levels were elevated in patients with AIH-PBC overlap syndrome, and total bilirubin (TBIL), direct bilirubin (DBIL), serum IgG and IgM were elevated in some patients accompanied with positive of autoantibody. Liver biopsies in these patients revealed a hepatic lobule interface inflammation, lymphocytes infiltration in portal area accompanied by bile duct granulomatous inflammation and different bile duct lesions. Conclusion AIH-PBC is more common in middle to old aged women. It has the characteristics of both PBC and AIH in clinical and biochemistry, and both a hepatic lobule inflammation and bile duct lesions were revealed by liver biopsy. [ABSTRACT FROM AUTHOR]

Background and Aims: The hepatitis E virus (HEV) is a zoonotic disease, and infection with HEV in humans primarily causes acute infections and can progress to chronic manifestation in immunocompromised individuals. Over the past decade, guidelines for diagnosing and treating HEV infection have been developed. This study aimed to systematically assess the quality of current guidelines for diagnosing and treating HEV infection, and we analyzed the differences in guideline quality and primary recommendations and explored possible reasons for these differences., Methods: Guidelines published between 2013 and 2022 were searched, and studies were identified using selection criteria. The study assessed the quality of the included guidelines using the Appraisal of Guidelines for Research and Evaluation tool, extracted the primary recommendations in the guidelines, determined the highest level of evidence supporting the recommendations, and reclassified the evidence using the Oxford Centre for Evidence-Based Medicine grading system., Results: Seven guidelines were included in the final analysis. The quality of the guidelines varied widely. The discrepancies may have been caused by the lack of external experts, the failure to consider influencing factors in guideline application, and the lack of consideration of the public's opinion. Analysis of the heterogeneity in primary recommendations revealed differences in algorithms for managing chronic HEV infection, the dosage of ribavirin, and a low level of evidence supporting the primary recommendations., Conclusions: Guideline quality and primary recommendations vary considerably. Refinement by guideline developers and researchers would facilitate updating and applying guidelines for diagnosing and treating HEV infection., Competing Interests: The authors have no conflict of interest related to this publication., (© 2024 Authors.)

Background/aims: Previous studies have found that the injection of rat bone marrow mesenchymal stem cells (rBMSCs) in a mouse model of acute hepatic failure significantly relieves intestinal damage and endotoxemia. However, the mechanism of this process remains unknown. This study demonstrated the differentiation of rBMSCs into enterocyte-like cells and possible molecular mechanisms for this with the aim of finding a new treatment for intestinal epithelial injury and endotoxemia during liver failure., Materials and Methods: rBMSCs were isolated from rat femurs and tibias. Differentiation was induced by co-culturing rBMSCs with rat intestinal epithelial cells (mIEC-6) using Transwell plates; after three, seven, and ten days of induction, expression of specific differentiation molecules were quantified. To inhibit the activity of the Mitogen-activated protein kinase 1/2 (ERK1/2) signaling pathway, an inhibitor of Mitogen-activated protein kinase kinase 1/2 (MEK1/2) was added to the co-culture medium, and western blot analysis was performed after 36 or 72 h to evaluate the expression of ERK1/2 signaling pathway markers (p-MEK1/2 and p-ERK1/2)., Results: The rBMSCs differentiated into enterocyte-like cells when co-cultured with mIEC-6 cells. Inhibition of ERK1/2 signaling abrogated the activity of MEK1/2, but MEK increased after 72 h, and the epithelioid differentiation of rBMSCs was consistent with the change in MEK expression., Conclusion: rBMSCs differentiate into intestinal epithelium after co-culture with mIEC-6 by regulation of the ERK1/2 signaling pathway. Further research is needed to elucidate the network of mechanisms.

Angiogenesis induced by vascular endothelial growth factor A (VEGF-A) plays a critical role in tumor growth and metastasis. The study aimed to evaluate the expression of VEGF-A in gastric adenocarcinoma and investigate its correlations with tumor clinicopathological features and prognostic significance. VEGF-A expression was detected by immunohistochemistry on a tissue microarray containing 90 pairs of human gastric adenocarcinoma and paracancerous tissues. Levels of VEGF-A in gastric adenocarcinoma were significantly higher than those in paracancerous tissues ( P =0.018). Furthermore, the result was coincident with that of human gastric adenocarcinoma xenografts in nude-mice ( P <0.01). In addition, the VEGF-A expression was positive correlation with TNM stage ( P =0.047), tumor size ( P =0.028), positive lymph nodes ( P =0.002) and lymphovascular invasion ( P =0.001). Finally, Kaplan-Meier survival analysis showed that VEGF-A up-regulation indicated a poor prognosis for overall survival ( P =0.039). In conclusions, VEGF-A may be used as a biomarker for evaluating both the biological behavior of tumor and the prognosis in patients with gastric adenocarcinoma., Competing Interests: None., (IJCEP Copyright © 2017.)

Inflammatory transport through the gut-liver axis may facilitate liver cirrhosis. Cyclooxygenase-2 (COX-2) has been considered as one of the important molecules that regulates intestinal epithelial barrier function. This study was aimed to test the hypothesis that inhibition of COX-2 by celecoxib might alleviate liver cirrhosis via reduction of intestinal inflammatory transport in thiacetamide (TAA) rat model. COX-2/prostaglandin E2 (PGE2)/EP-2/p-ERK integrated signal pathways regulated the expressions of intestinal zonula occludens-1 (ZO-1) and E-cadherin, which maintain the function of intestinal epithelial barrier. Celecoxib not only decreased the intestinal permeability to a 4-kDa FITC-dextran but also significantly increased expressions of ZO-1 and E-cadherin. When celecoxib greatly decreased intestinal levels of LPS, TNF-α, and IL-6, it significantly enhanced T cell subsets reduced by TAA. As a result, liver fibrosis induced by TAA was significantly alleviated in the celecoxib group. These data indicated that celecoxib improved the integrity of intestinal epithelial barrier, blocked inflammatory transport through the dysfunctional gut-liver axis, and ameliorated the progress of liver cirrhosis., (Copyright © 2016 the American Physiological Society.)

Objective: To evaluate the clinical features of patients with primary biliary cirrhosis (PBC) and positive expression of sp100 autoantibody in order to generate a clinical screening profile that may help to increase early diagnosis and timely initiation of therapy., Methods: The clinical data of 70 patients who were diagnosed with PBC by liver biopsy between January 2006 to December 2009 at the Second Affiliated Hospital of Kunming Medical University of Hepatobiliary and Pancreatic Medicine were retrospectively collected for analysis. The patients were divided according to expression of anti-sp100: positive patients, n = 12; negative patients, n = 58. The groups were comparatively analyzed for differences in clinical, biochemical, immunological, and histopathological parameters. Normally distributed data was compared by t-test, and non-normally data was compared by rank-sum test., Results: There was no significant difference in age among the sp100-positive and sp100-negative patients (51.6 +/- 9.5 vs. 50.0 +/- 14.7 years, P more than 0.05). The sp100-positive group had significantly more women (80.0% vs. 61.9%, X2 = 0.32, P more than 0.05) and more patients with atypical symptoms (18.2% vs. 13.8%) but the difference of the latter did not reach statistical significance. The sp100-positive group had significantly higher levels of alkaline phosphatase (ALP; 466 vs. 163 U/L, Z = 3.71), gamma-glutamyl-transpeptidase (GGT; 728 vs. 154 U/L, Z = 3.38), and immunoglobulin M (IgM; 4.25 +/- 2.86 vs. 2.81 +/- 2.15, t = 2.06, P less than 0.05). Forty of the total patients tested negative for antimitochondrial (AMA)-M2 antibodies, and eight of those were sp100-positive (20.0%) while 18 were antinuclear (ANA) antibody-positive (45.0%). There were significantly more AMA-M2-negative/ANA-positive patients than sp100-positive patients (P = 0.021). Anti-sp100 expression was not associated with the pathological stage of PBC (R1 = 5.500, P more than 0.05)., Conclusion: SP100-positive PBC may show a bias towards the female sex, and may be characterized by enhanced serum levels of ALP, GGT, and IgM. Further clinical differences may manifest as the disease progresses, and changes in autoantibodies' expression and liver function markers should be carefully monitored in follow-up.

Aim: To study the association between host immunity and hepatitis B virus (HBV) recurrence after liver transplantation., Methods: Peripheral blood mononuclear cells (PBMC) were isolated from 40 patients with hepatitis B and underwent orthotopic liver transplantation (OLT) before and 2, 4, 8 wk after surgery. After being cultured in vitro for 72 h, the levels of INF-gamma and TNF-alpha in culture supernatants were detected with ELISA. At the same time, the quantities of HBV DNA in serum and PBMCs were measured by real time PCR., Results: The levels of INF-gamma and TNF-alpha in PBMC culture supernatants decreased before and 2, 4 wk after surgery in turns (INF-gamma 155.52+/-72.32 ng/L vs 14.76+/-9.88 ng/L vs 13.22+/-10.35 ng/L, F = 6.946, P = 0.027 < 0.05; TNF-alpha 80.839+/-46.75 ng/L vs 18.59+/-17.29 ng/L vs 9.758+/-7.96 ng/L, F = 22.61, P = 0.0001 < 0.05). The levels of INF-gamma and TNF-alpha were higher in groups with phytohemagglutinin (PHA) than in those without PHA before surgery. However, the difference disappeared following OLT. Furthermore, INF-gamma and TNF-alpha could not be detected in most patients at wk 4 and none at wk 8 after OLT. The HBV detection rate and virus load in PBMC before and 2, 4 wk after surgery were fluctuated (HBV detected rate: 51.4%, 13.3%, 50% respectively; HBV DNA: 3.55+/-0.674 log10 copies/mL vs 3.00+/-0.329 log10 copies/mL vs 4.608+/-1.344 log10 copies/mL, F = 7.582, P = 0.002 < 0.05). HBV DNA in serum was 4.48+/-1.463 log10 copies/mL before surgery and <10(3) copies/mL after OLT except for one with 5.72 x 10(6) copies/mL 4 wk after OLT who was diagnosed as HBV recurrence. The levels of INF-gamma and TNF-alpha were lower in patients with a high HBV load than in those with a low HBV load (HBV DNA detected/undetected in PBMCs: IFN-gamma 138.08+/-72.44 ng/L vs 164.24+/-72.07 ng/L, t = 1.065, P = 0.297 > 0.05, TNF-alpha 80.75+/-47.30 ng/L vs 74.10+/-49.70 ng/L, t = 0.407, P = 0.686 > 0.05; HBV DNA positive/negative: IFN-gamma 136.77+/-70.04 ng/L vs 175.27+/-71.50 ng/L, t = 1.702, P = 0.097 > 0.05; TNF-alpha 75.37+/-43.02 ng/L vs 81.53+/-52.46 ng/L, t = 0.402, P = 0.690 > 0.05)., Conclusion: The yielding of INF-gamma and TNF-alpha from PBMCs is inhibited significantly by immunosuppressive agents following OLT with HBV load increased, indicating that the impaired immunity of host is associated with HBV recurrence after OLT.

Objective: To detect the rule of hepatocyte-function change with 1 week following liver transplantation and to select useful parameter to forecast prognosis, we investigated the function of hepatocytes dynamically of patients within 1 week following surgery., Methods: A retrospective study was undertaken. Data was collected form 149 patients in our hospital from December 1994 to August 2003. AST, ALT, total bilirubin (TB), direct bilirubin (DB), prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen (FIB) were examined in the day before operation, 1, 3 and 7 d following surgery., Results: Single peak of all values occurred with 1 week in patients who lived more than 1 month following surgery. The level of FIB, PT and APTT, AST and ALT descended to normal level in 1, 3 and 7 d after liver transplantation respectively. However, double peaks of bilirubin and altered peak of APTT and PT were observed in patients lived less than 1 month after surgery. Furthermore, descents of these values were delayed. Compared with the reversion of patients received classic liver transplantation, that of patients who received piggy back-on liver transplantation showed a slow recovery trend in earlier period after surgery. However, at 7 d following surgery, both can went near to normal level. The level of AST 7 d, DB 1 d and 3 d, PT 1 d following surgery and TB were related closely to the prognosis of patients who underwent liver transplantation., Conclusions: The levels of ALT, AST, TB, DB, PT, APTT and FIB become normal on the whole within 1 week after liver transplantation. During this period, Single peak of all values occur. Alteration of the hump indicated the occurrence of complications. The shape of hepatic function hump and the level of AST, DB and PT and TB postoperation were useful value to forecast prognosis.

Objective: To study the changes of HBV markers and HBV DNA and the perioperative factors influencing them after orthotopic liver transplantation (OLT)., Methods: A retrospective study was undertaken. Data was collected from 97 patients in the First Affiliated Hospital of Sun Yat-sen University from March 1999 to October 2003. Patients were investigated on the 7-14, 14-30, 30-90, 90-180, 180-360 and 360- days after OLT. All the patients who received OLT were serum HBV positive before their operations., Results: Kinetic expressions of HBV serum marker and HBV DNA were established. A few patient's HBeAg was negative (8%) before their operation. Within 7 day following surgery, no patient was HBeAg positive. However, the rate of HBeAg positive increased on the 90-180 day following surgery. The postoperation time of taking lamivudine was different between patients with HBeAg seroconversion and of those without (U = 88.5). Peaks occurred within 14 d of HBsAg negative and 14-30 d of anti-HBs positive after operation. Then they decreased and minimized at 90-180 day after liver transplantation. Patients who suffered more bleeding during the operation were more likely to be anti-HBs positive (3800ml vs. 3000ml, U = 8193.0) and HBsAg negative in serum within 2 week (5200ml vs. 4200ml, U = 1648.5) after OLT. While patient's who received more blood transfusion (1000ml vs. 1600ml, U = 9796.0) during operation were not likely to be anti-HBs positive in serum after surgery. Furthermore, the time of infusing HBIg did not affect the state of anti-HBs (U = 1252.5). At the same time, there were no correlations between the change of HBsAg in serum and in the method of operation (chi2 = 0.042). During this process, presentation of anti-HBc changed a little., Conclusion: The advantages brought on by operative factors become blunt 7-14 d following OLT. More attention should be taken to avoid reinfection of HBV 90-180 day after OLT. Tyrosine-methionine-aspartic acid-aspartic acid (YMDD) mutation of HBV is more likely to occur when taking lamivudine longer. Then, HBV DNA should be monitored and a liver biopsy should be scheduled regularly after OLT.