Objective To investigate the differences in the influencing factors for acute necrotizing pancreatitis (ANP) and infectious pancreatic necrosis (IPN) between Eastern and Western countries, and to provide a theoretical basis for the prediction and prevention of ANP. Methods Databases including PubMed, Embase, the Cochrane Library, and Web of Science were searched for articles on the influencing factors for ANP and IPN published up to January 21, 2021, and a Meta-analysis was performed. Results A total of 59 studies were included, with 22 studies from Eastern countries and 37 studies from Western countries.The Meta-analysis showed that in Eastern countries, male sex (odds ratio[ OR ]=1.51, 95% confidence interval[ CI ]: 1.18-1.91, P < 0.01), C-reactive protein (CRP)(standardized mean difference[ SMD ]=1.39, 95% CI : 1.06-1.71, P < 0.01), D-dimer ( SMD =0.44, 95% CI : 0.07-0.81, P =0.02), Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE-Ⅱ) score (mean difference[ MD ]=3.51, 95% CI : 1.38-5.64, P < 0.01), alcoholic etiology ( OR =3.57, 95% CI : 2.68-4.75, P < 0.01), and biliary etiology ( OR =0.60, 95% CI : 0.46-0.77, P < 0.01) were the influencing factors for ANP, and in Western countries, male sex ( OR =1.63, 95% CI : 1.30-2.05, P < 0.01), CRP ( SMD =2.09, 95% CI : 1.12-3.05, P < 0.01), APACHE-Ⅱ score ( MD =4.28, 95% CI : 2.73-5.83, P < 0.01), Ranson score ( MD =2.99, 95% CI : 2.50-3.47, P < 0.01), and organ failure ( OR =10.87, 95% CI : 2.62-45.04, P < 0.01) were the influencing factors for ANP.In Eastern countries, age ( MD =2.16, 95% CI : 0.43-3.89, P =0.01), body mass index (BMI)( MD =1.74, 95% CI : 1.23-2.25, P < 0.01), albumin level ( SMD =-0.43, 95% CI : -0.75 to-0.12, P < 0.01), CRP ( SMD =0.58, 95% CI : 0.04-1.11, P =0.03), procalcitonin ( SMD =0.80, 95% CI : 0.56-1.04, P < 0.01), D-dimer ( MD =0.23, 95% CI : 0.15-0.31, P < 0.01), APACHE-Ⅱ score ( MD =2.47, 95% CI : 0.73-4.22, P < 0.01), Ranson score ( MD =1.60, 95% CI : 1.46-1.73, P < 0.01), and extent of necrosis ≥30%( OR =2.52, 95% CI : 1.26-5.06, P < 0.01) were the influencing factors for IPN, while in Western countries, age ( MD =4.07, 95% CI : 1.82-6.31, P < 0.01), APACHE-Ⅱ score ( MD =3.28, 95% CI : 1.39-5.17, P < 0.01), Ranson score ( MD =2.18, 95% CI : 1.75-2.62, P < 0.01), SIRS score ( OR =3.88, 95% CI : 1.58-9.51, P < 0.01), alcoholic etiology ( OR =0.61, 95% CI : 0.42-0.87, P < 0.01), and organ failure ( OR =3.63, 95% CI : 1.11-11.92, P =0.03) were the influencing factors for IPN. Conclusion Current evidence shows that biliary etiology and alcoholic etiology are unique influencing factors for ANP in the Eastern population, while Ranson score is a unique influencing factor in the Western population.BMI and extent of necrosis ≥30% are unique influencing factors for IPN in the Eastern population, while alcoholic etiology is a unique influencing factor in the Western population.

Objective:To investigate the function, mechanism and therapeutic potential of macrophages in non-alcoholic steatohepatitis (NASH).Methods:Eight-week-old male foz/ foz (Alms mutant) mice were fed with a high fat diet (HFD) for 6, 8 and 10 weeks and 8-week-old male C57BL/6 mice were fed with a methionine and choline-deficient (MCD) diet for 7 d, 3 weeks and 4 weeks to establish NASH models. The mice of control group were fed with normal diet or MCD control diet. The expression of F4/80 mRNA level in the livers of mice of NASH model group and control group was detected by fluorescence quantitative polymerase chain reaction. Macrophages in the livers of mice of NASH group and control group were determined by immunofluorescence staining. After transgenic lysM-Cre/DTR mice were fed with MCD diet for 5 weeks, they were divided into transgenic experimental group (ablation of macrophages induced by diphtheria-toxin (DTox) injection) and transgenic control group (phosphate buffer saline injection). The levels of triglyceride and lipid peroxide in the livers of transgenic experimental group and transgenic control group were detected, and the inflammation of the livers of the mice was scored. The mechanism of macrophages regulating inflammation in NASH was investigated by cytokine profiliny analysis and Western blotting. The interaction between hepatocytes and macrophages were determined by co-culturing the conditional medium of hepatocytes AML-12 and macrophages RAW264.7. Macrophages of mice of control group and NASH model group were depleted by liposomal clodronate to confirm its value in NASH prevention. Independent sample t-test was used for statistical analysis. Results:F4/80 mRNA level in the livers of NASH model foz/ foz mice fed with HFD for 6 weeks, 8 weeks and 10 weeks was higher than that of control group (1.49±0.19, 1.70±0.15 and 1.93±0.04 vs.1.05±0.22), and the differences were statistically significant ( t=3.06, 4.92 and 7.92, all P<0.05). The expression of F4/80 mRNA level of the livers of NASH model mice fed with MCD for 7 d and 3 weeks was higher than that of control group (2.70±0.99 and 3.08±1.71 vs.1.00±0.83), and the differences were statistically significant ( t=3.43 and 3.54, both P<0.01). The results of immunofluorescence demonstrated that compared with that of control group, the number of F4/80 + inducible nitric oxide synthase (iNOS) + M1 macrophages were significantly increased, while F4/80 + CD206 + M2 macrophages were significantly decreased in the livers of NASH model mice fed with MCD for 4 weeks. After macrophages depletion, the inflammation score, the levels of triglyceride and lipid peroxide in the liver of transgenic experimental mice were all lower than those of transgenic control mice (0.69±0.32 vs. 1.95±0.74, (43.97±13.24) g/mg vs. (63.09±14.85) g/mg, (24.84±6.21) nmol/mg vs.(37.91±8.91) nmol/mg), and the differences were statistically significant ( t =3.14, 2.72 and 2.41, all P<0.05). The results of cytokine profiling analysis showed that macrophage depletion could lower the levels of interleukin (IL)-12 and macrophages inflammatory protein-1α (the difference between multiples: -3.98, -2.74, both P<0.05). CCAAT/enhancer binding protein β was defected in the nuclear of transgenetic experimental mice. In vitro study showed that RAW264.7 macrophages conditional medium could promote lipid accumulation in AML-12 hepatocytes, while conditional medium from MCD medium-treated AML-12 hepatocytes could promote RAW264.7 macrophages to M1 polarization. After treated with liposomal clodronate, the levels of triglyceride and lipid peroxidation in the liver of control mice were both lower than those of MCD-induced NASH model mice((45.33±14.59) g/mg vs. (63.10±16.02) g/mg, (2.11±0.48) nmol/mg vs. (2.73±0.17) nmol/mg), and the differences were statistically significant ( t=2.84 and 2.73, both P<0.05). The results of Western blotting indicated that after treating with liposomal clodronate, the relative content of phosphorylated protein kinase R-like endoplasmic reticulum kinase, inositol requiring enzyme-1α, protein disulfide isomerase, glucose regulatory protein 78, phosphorylated eukaryotic initiation factor 2α in the liver of NASH model mice were all lower than those of NASH model mice without liposomal clodronate treatment (1.84±0.36 vs. 3.05±0.83, 1.50±0.84 vs. 6.65±1.47, 0.87±0.12 vs. 2.28±0.52, 1.68±0.43 vs. 4.76±1.13, 1.42±0.19 vs. 2.75±0.79), and the differences were statistically significant( t=2.32, 5.28, 4.56, 4.41 and 2.85, all P<0.05). Conclusions:Macrophages are polarized into M1 phenotype in NASH. M1 macrophages contributed to NASH progression by interacting with hepatocyets to promote the secretion of inflammatory cytokines, up-regulation of lipogenic factors, oxidative stress and endoplasmic reticulum stress, resulting in the progression of NASH. Macrophages depletion by liposomal clodronate is a potential noval approach for NASH prevention.

ObjectiveTo investigate the value of albumin-bilirubin (ALBI) score in predicting the prognosis of cirrhotic patients with esophagogastric variceal bleeding, and to identify risk stratification and increase clinical applicability. MethodsA retrospective analysis was performed for the clinical data of 273 cirrhotic patients with esophagogastric variceal bleeding who were hospitalized in Subei People’s Hospital of Jiangsu from October 2012 to August 2018, and all patients received standard management after admission. Survival status was obtained through electronic medical records and telephone follow-up, and according to the prognosis in August 2020, the patients were divided into death group with 109 patients and survival group with 164 patients. General data were compared between the two groups. The Mann-Whitney U test was used for comparison of continuous variables between two groups, and the chi-square test or the Fisher’s exact test was used for comparison of categorical variables between two groups; univariate and multivariate Cox regression analyses were used to identify independent risk factors for prognosis. The Kaplan-Meier curve was used to analyze the survival rates of patients with different ALBI grades, and the log-rank test was used for comparison between groups; the receiver operating characteristic (ROC) curve was plotted to compare the ability of ALBI score, Child-Turcotte-Pugh (CTP) score, and Model for End-Stage Liver Disease (MELD) score in predicting short-term (6 weeks) and long-term prognoses. ResultsDuring follow-up, 109 patients (39.9%) died, and the death group had a significantly higher ALBI score than the survival group ［-1.49 (-1.82 to -1.11) vs -1.79 (-2.22 to -1.49), Z=5.630, P＜0.001］. The univariate analysis showed that age ≥55 years, hemoglobin ≤100 g/L, neutrophil count ≥3.4×109/L, platelet count ≤42×109/L, albumin ≤28 g/L, total bilirubin ≥21 μmol/L, alanine aminotransferase ≥42 U/L or aspartate aminotransferase ≥48 U/L, creatinine ≥94 μmol/L, serum sodium ≤137 mmol/L, international normalized ratio of prothrombin ≥1.5, ascites, and hepatic encephalopathy were risk factors for death in cirrhotic patients with esophagogastric variceal bleeding, and the patients with ALBI grade 3 had a significantly higher risk of death than those with ALBI grade 1 or 2; prophylactic ligation was a protective factor for survival improvement in cirrhotic patients with esophagogastric variceal bleeding (all P＜0.05). The multivariate analysis showed that age ≥55 years (hazard ratio ［HR］=2.531, 95% confidence interval ［CI］: 1.624-3.946, P＜0.001), creatinine ≥94 μmol/L (HR=1.935, 95% CI: 1.208-3.100, P=0.006), serum sodium ≤137 mmol/L ［HR=1.519, 95% CI: 1.015-2.274, P=0.042］, ascites (HR=1.641, 95% CI: 1.041-2.585, P=0.033), hepatic encephalopathy (HR=9.972, 95% CI: 3.961-25.106, P＜0.001), and ALBI grade 3 (HR=1591, 95% CI: 1.007-2.515, P=0.047) were independent risk factors for death. The patients with ALBI grade 3 had a significantly lower survival rate than those with ALBI grade 1 (χ2=18.691, P＜0.001) and ALBI grade 2 (χ2=21.364, P＜0.001), and the patients with ALBI grade 1 had a significantly higher survival rate than those with ALBI grade 2 (χ2=6513, P=0.011). The ROC curve analysis showed that ALBI score, CTP score, and MELD score had an area under the ROC curve (AUC) of 0770, 0.730, and 0.706, respectively, in predicting short-term (6 weeks) prognosis, and they had an AUC of 0.701, 0685, and 0659, respectively, in predicting long-term prognosis. ConclusionALBI score has a good value in predicting short-term (6 weeks) and long-term prognoses of cirrhotic patients with esophagogastric variceal bleeding, and the risk of death increases with ALBI grade. ALBI score can be used as an objective and simple model in clinical practice.

Nonalcoholic fatty liver disease (NAFLD) is a type of metabolic disorder syndrome of abnormal lipid deposition in hepatocytes, and with the improvement of living standards, the incidence rate of NAFLD has reached a worrying level. Several anthropometric indicators, including waist circumference, waist-hip ratio, and waist-height ratio, have been used in the evaluation of obesity and the correlation study of various metabolic diseases. This article introduces the association between NAFLD and various anthropometric indicators for obesity and points out that anthropometric indicators for obesity can be used for the prevention and control of NAFLD.

Autoimmune hepatitis is a type of autoimmune disease and has known pathogenesis at present, which is believed to be associated with immune imbalance in the body. In inflammatory diseases, regulatory B cells (Bregs) inhibits the differentiation of CD4+ T lymphocytes into T helper 1 cells and T helper 17 cells by secreting interleukin-10 (IL-10) to inhibit inflammatory response. Patients with autoimmune hepatitis have reductions in the level of IL-10 in peripheral blood and the number and function of Bregs, which leads to the fact that Bregs cannot effectively inhibit inflammatory response, suggesting that Bregs play a certain role in the pathogenesis of autoimmune hepatitis. This article reviews the mechanism of action of Breg subsets in autoimmune hepatitis.

ObjectiveTo investigate the expression and clinical significance of OX40/OX40L (CD134/CD134L) in CD4+ T cells, CD8+ T cells, monocytes, and B lymphocytes in peripheral blood of patients with autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and their overlap syndrome before and after standardized treatment. MethodsA total of 74 patients with AIH, PBC, and their overlap syndrome who were diagnosed in Subei People’s Hospital of Jiangsu from August 2015 to August 2019 were enrolled, and according to related diagnostic criteria, they were divided into AIH group (group A) with 29 patients, PBC group (group P) with 26 patients, and overlap syndrome group (group C) with 19 patients. A healthy control group with 30 individuals was also established. Peripheral blood samples were collected before and after standardized treatment to measure the expression of OX40/OX40L on the surface of peripheral blood cells by immunofluorescence flow cytometry, and the expression of OX40/OX40L was compared before and after treatment and between the three groups and the healthy control group to investigate its clinical significance. A one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between two groups; the paired t-test was used for comparison of paired samples between two groups. ResultsThere were no significant differences in sex composition and age composition between the three groups (P＞0.05). Before treatment, the positive rate of OX40 in peripheral blood CD4+ T cells gradually increased in groups A, P, and C, and groups A, P, and C had a significantly higher positive rate of OX40 than the control group (14.80%±4.99%/17.11%±2.71%/25.18%±5.55% vs 6.67%±2.26%, F=14.823, P＜0.001); groups A, P, and C had a significantly higher positive rate of OX40 in CD8+ T cells than the control group (4.86%±1.54%/6.40%±1.88%/7.33%±2.12% vs 4.09%±2.69%, F=5.486, P＜0.001); the positive rate of OX40L in CD14+ monocytes was 19.84%±6.11% in group A, 21.17%±4.35% in group P, 29.13%±6.32% in group C, and 4.86%±2.34% in the control group, and there was a significant difference between groups (F=17004, P＜0.001); the positive rate of OX40L in CD19+ B cells was 17.62%±3.86% in group A, 14.75%±4.32% in group P, 1013%±2.56% in group C, and 4.50%±1.38% in the control group, showing a trend of gradual reduction, and groups A, P, and C had a significantly higher positive rate than the control group (F=12.221, P＜0.001). After treatment, the positive rate of OX40 in CD8+ T cells decreased significantly to a similar level as the control group, and there was no significant difference between groups (F=0731, P=0.538). For the other three types of cells, although there were varying degrees of reduction in the positive rate of OX40/OX40L after treatment, groups A, P, and C still had a significantly higher positive rate than the control group; in CD4+ T cells, the positive rate of OX40 was 11.00%±1.98% in group A, 13.72%±1.03% in group P, 19.72%±3.47% in group C, and 6.67%±2.26% in the control group, and groups A, P, and C had a significantly higher positive rate than the control group (F=11.365, P＜0.001); in CD14+ monocytes, the positive rate of OX40L was 11.82%±2.23% in group A, 15.19%±4.42% in group P, 24.51%±4.09% in group C, and 4.86%±2.34% in the control group, and groups A, P, and C had a significantly higher positive rate than the control group (F=13748, P＜0.001); in CD19+ B cells, the positive rate of OX40L was 9.09%±3.25% in group A, 6.81%±2.20% in group P, 748%±2.85% in group C, and 4.50%±1.38% in the control group, and groups A, P, and C had a significantly higher positive rate than the control group (F=8.052, P＜0.001). Groups A, P, and C had significant reductions in the expression of OX40/OX40L in peripheral blood CD4+ T cells, CD8+ T cells, CD14+ monocytes, and CD19+ B lymphocytes after treatment (all P＜0.05). ConclusionThe expression of OX40/OX40L in peripheral blood increases in patients with AIH, PBC, and their overlap syndrome and decreases after treatment, indicating that the OX40/OX40L pathway is involved in the pathogenesis of the above diseases, and the role of OX40 on the surface of CD8+ T cells may better reflect the treatment outcome.

Nonalcoholic fatty liver disease is a group of diseases with unclear pathophysiological mechanism and is closely associated with metabolic syndrome. Bacterial components and metabolites produced by gut microbiota can regulate glucose and lipid metabolism, inflammatory response, and oxidative stress, and bile acids regulate immune function, energy metabolism, and material metabolism through various signaling pathways after activating their receptors. Gut microbiota and bile acids interact with each other through enterohepatic circulation, and the changes of their structure and function are involved in the development and progression of nonalcoholic fatty liver disease. This article reviews the effect of the homeostatic dysregulation of gut microbiota and bile acids and their interactions on nonalcoholic fatty liver disease.

Autoimmune hepatitis (AIH) is a chronic autoimmune disease in the liver, with major clinical manifestations of positive autoantibody, abnormal elevation of aminotransferases, and hypergammaglobulinemia. Current studies have shown that regulatory T (Treg)/T helper 17 (Th17) and T helper 1 (Th1)/T helper 2 (Th2) imbalance is one of the mechanisms of the development and progression of AIH. OX40 (also known as CD134, TNFRSF4, or ACT35) and its ligand OX40L are members of the tumor necrosis factor family, and they participate in immune response as co-stimulators of T cell activation and can regulate Treg/Th17 and Th1/Th2 balance, thus affecting the progression of various autoimmune diseases. However, there are few reports on the role of OX40 and OX40L in AIH. With reference to related articles, this article reviews the role of Treg/Th17 and Th1/Th2 balance in AIH and the potential association between OX40/OX40L (new targets for immunological diagnosis and treatment) and AIH.

ObjectiveTo investigate the clinical value of ultrasound-guided percutaneous drainage in the treatment of liver abscess from the aspects of laboratory markers and size of abscess. MethodsA total of 79 patients with liver abscess who underwent ultrasound-guided percutaneous drainage in Department of Gastroenterology in Northern Jiangsu People’s Hospital from January 2013 to August 2018 were enrolled, among whom 36 patients who were lost or transferred, abandoned treatment, had an age pf ＜18 years, or were not followed up in the outpatient service were excluded. A total of 43 patients were finally included in the retrospective study. The t-test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups. ResultsAll 43 patients achieved a one-time success of puncture and placement of drainage tube. Of all 43 patients, 36 had fear of cold and pyrexia, among whom 31 (86.1%) had a normal body temperature on day 3 after surgery, and there were significant changes in leukocyte count, percentage of neutrophils, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase after surgery (t=6.668, 6.255, 2337, 3.001, and 5.198, all P＜0.05). There was a significant reduction in the diameter of abscess after surgery (74±31 mm vs 31±28 mm, t=18.517, P＜0.05). The average length of hospital stay was 19.84±9.37 days. Of all 43 patients, 19(44.2%) were cured and 24(55.8%) had response to treatment. Of all 43 patients, 38 had positive results of liver abscess culture, among whom 25(65.8%) had Klebsiella pneumoniae infection, suggesting that Klebsiella pneumoniae was the most common pathogenic bacteria. ConclusionUltrasound-guided percutaneous drainage has a high success rate, few complications, and reliable clinical efficacy in the treatment of liver abscess. Therefore, it is recommended as the first choice for the clinical treatment of liver abscess.

Nonalcoholic fatty liver disease (NAFLD) is closely associated with insulin resistance and genetic susceptibility and is one of the chronic liver diseases that threaten human health .Under certain conditions, Th17 cells and regulatory T (Treg) cells can be transformed to each other to maintain immune homeostasis.In recent years, more and more studies have been performed on the involvement of Th 17 and Treg cells in the development and progression of liver diseases .Th17 cells, Treg cells, and their balance may become the new targets for the treatment of NAFLD.This article reviews the latest research advances in the association of Th 17 and Treg cells with NAFLD and the role of Th17/Treg balance in the development and progression of NAFLD .