Objective:To investigate the value of early tight junction protein Claudin-5 levels in predicting the severity of acute pancreatitis (AP).Methods:A prospective observational study was conducted, including patients diagnosed with AP and admitted to the Northern Jiangsu People's Hospital from December 1, 2021 to November 30, 2022. Eligible healthy volunteers were randomly selected to serve as healthy controls during the same period. Patients were classified into mild acute pancreatitis (MAP) group, moderate-severe acute pancreatitis (MSAP) group, and severe acute pancreatitis (SAP) group based on the 2012 Atlanta classification criteria. Patients with SAP were then divided into three subgroups of 1, 3, and 7 days based on the duration of hospitalization. Baseline data, such as gender, age, underlying disease, and probable etiology, was collected from all enrolled individuals. The enzyme-linked immunosorbent assay (ELISA) was employed to detect serum Claudin-5 levels in each cohort of enrollees. Data on additional serologic indicators, including hematocrit (HCT), albumin (Alb), serum Ca 2+, C-reactive protein (CRP), and procalcitonin (PCT) levels, were obtained via the in-hospital test query system in each group of patients with AP. The modified Marshall score (mMarshall), modified CT severity index (mCTSI) score, bedside severity index of severity in acute pancreatitis (BISAP) score, and acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) were recorded for each group of patients with AP. Differences in the above indicators between groups were analyzed and compared. Spearman's correlation method was employed to examine the relationship between Claudin-5 levels and each influential factor. The receiver operator characteristic curve (ROC curve) was plotted to analyze the predictive value of each influencing factor on SAP. Ridge regression was used to screen for independent risk factors for SAP. Results:A total of 109 patients with AP were enrolled, comprising 66 in the MAP group, 15 in the MSAP group, and 28 in the SAP group. Additionally, 27 healthy volunteers were enrolled as the healthy control group. No statistically significant differences were observed in gender and age among the enrolled groups, and no statistically significant differences were identified among the three groups of patients with AP in terms of underlying disease and etiologic composition. As the disease progressed, serum Claudin-5 levels exhibited a notable increase across all AP patient groups, and they were all significantly higher than those in the healthy control group [ng/L: 888.58 (574.52, 1 141.59), 3 749.02 (2 784.93, 5 789.92), 4 667.81 (3 935.21, 7 315.66) vs. 291.13 (250.19, 314.75), all P < 0.05]. Subgroup analyses showed that as the disease duration prolonged, patients in the SAP group exhibited a notable decline in Claudin-5 levels at 3 days post-admission, compared with those at 1 day post-admission [ng/L: 2 052.59 (1 089.43, 4 006.47) vs. 4 667.81 (3 935.21, 7 315.66), P < 0.05]. Spearman correlation analysis showed that serum Claudin-5 levels in patients with AP were significantly positively correlated with CRP, PCT, HCT, and mMarshall, mCTSI, and BISAP scores ( r values were 0.570, 0.525, 0.323, 0.774, 0.670, 0.652, all P < 0.001), and significantly negatively correlated with Alb ( r = -0.394, P < 0.001). A significant trend was observed in patients with AP, with an increase of HCT levels and a decrease of Alb levels as the disease progressed (both P < 0.05). An improvement of aforementioned phenomena was observed in patients with SAP following treatment, indirectly indicating that serum Claudin-5 level was a positive indicator of vascular leakage. ROC curve analysis showed that serum Claudin-5 levels in patients with AP exhibited the highest accuracy for early prediction of SAP, with the area under the ROC curve (AUC) of 0.948. When serum Claudin-5 levels ≥2 997 ng/L, the sensitivity for early screening for SAP was 100% and the specificity was 88.89%. Multifactorial ridge regression analysis showed that serum Claudin-5 level, PCT and APACHEⅡscore could be used as independent risk factors for early prediction of SAP (all P < 0.05). Conclusion:Serum Claudin-5 levels facilitate early prediction of SAP and are strongly associated with inflammatory response and vascular leakage.

Objective:To study the signaling pathway of the up-regulation of claudin-5 expression by Xuebijing injection.Methods:Animal and cell models of acute respiratory distress syndrome (ARDS) were induced by lipopolysaccharide (LPS). ① In vivo study, 20 male Sprague-Dawley (SD) rats were randomly divided into 4 groups: control group, LPS group (LPS injection 10 mg/kg for 12 hours), Xuebijing control group (Xuebijing injection 1 mg/kg, twice a day, for 3 days), and Xuebijing intervention group (LPS injection after pretreatment of Xuebijing injection), according to random number method with 5 rats in each group. The lung tissues were taken to detect lung dry/wet weight ratio (W/D) and the morphological changes in each group. Claudin-5, phosphorylated forkhead box transcription factor O1 (p-FOXO1), total FOXO1 (t-FOXO1), phosphorylated Akt (p-Akt) and total Akt (t-Akt) in lung tissues were detected by immunohistochemical staining (IHC) and Western blotting. ② In vitro study, human pulmonary microvascular endothelial cells (HPMECs) were divided into 6 groups (5 holes in each group): control group, Xubijing control group (incubated with 2 g/L Xubijing for 24 hours), phosphoinositide 3-kinases (PI3K) signaling pathway LY294002 control group (incubated with 10 μmol/L LY294002 for 1 hour), LPS group (incubated with 1 mg/L LPS for 12 hours), Xubijing intervention group (incubated with 2 g/L Xuebijing for 24 hours, then with 1 mg/L LPS for 12 hours) and LY294002 intervention group (incubated with 10 μmol/L LY294002 for 1 hour, then with 2 g/L and Xubijing for 24 hours, and then with 1 mg/L LPS for 12 hours). The expression levels of claudin-5, p-FOXO1, t-FOXO1, p-Akt and t-Akt of HPMECs in each group were assessed by Western blotting. Results:In vivo study: ① Compared with the control group, the lung W/D ratio increased significantly in LPS group (6.79±0.42 vs. 4.19±0.13), and decreased significantly after the intervention of Xuebijing (4.92±0.38 vs. 6.79±0.42, P < 0.01). ② Morphological changes of lung tissue: compared with the control group, the injury of lung tissue in LPS group was more serious, which was significantly improved after Xuebijing intervention. ③ Expression levels of claudin-5, p-Akt/t-Akt and p-FOXO1/t-FOXO1: the expression levels of claudin-5, p-Akt/t-Akt and p-FOXO1/t-FOXO1 in LPS group were significantly decreased as compared with the control group (claudin-5/GAPDH: 0.33±0.03 vs. 1.03±0.07, p-Akt/t-Akt: 0.18±0.02 vs. 1.01±0.13, p-FOXO1/t-FOXO1: 0.16±0.06 vs. 1.00±0.19, all P < 0.01). After the intervention of Xuebijing, the expression levels were significantly increased as compared with the LPS group (claudin-5/GAPDH: 0.53±0.05 vs. 0.33±0.03, p-Akt/t-Akt: 0.56±0.12 vs. 0.18±0.02, p-FOXO1/t-FOXO1: 0.68±0.10 vs. 0.16±0.06, all P < 0.01). In vitro study: compared with the control group, the expression level of claudin-5 in the LPS group was significantly decreased (claudin-5/β-actin: 0.45±0.03 vs. 1.01±0.15, P < 0.01), and the expression level of claudin-5 in Xuebijing intervention group was also significantly decreased (claudin-5/β-actin: 0.80±0.08 vs. 1.01±0.15, P < 0.01). After the intervention of LY294002, the expression of claudin-5 was significantly decreased as compared with the Xubijing intervention group (claudin-5/β-actin: 0.41±0.02 vs. 0.80±0.08, P < 0.01). Conclusion:Xuebijing injection improve pulmonary vascular barrier function in rats with ARDS by up-regulating claudin-5 expression through PI3K/Akt/FOXO1 signaling pathway.

With the improvement in people's awareness of diseases and the level of diagnosis and treatment, the incidence rates of immunoglobulin G4-related disease (IgG4-RD) and autoimmune liver disease (AILD) are constantly increasing, and IgG4-related sclerosing cholangitis is the overlapping part of the disease spectrum of IgG4-RD and AILD, while the association between IgG4-related autoimmune hepatitis (IgG4-AIH) and these two diseases remains unclear. This article reviews the hepatic manifestation of IgG4-RD, summarizes the clinical features of IgG4-AIH, and analyzes whether IgG4-AIH is a subtype of AIH or a hepatic involvement of IgG4-RD. It is believed that IgG4-AIH has similar but different clinical manifestations and histopathological features from classical AIH, and IgG4-AIH may be classified as two types, i.e., a subtype of AIH and the liver manifestation of IgG4-RD. The research on the pathogenesis, clinical features, and clinical diagnosis and treatment of IgG4-AIH should be taken seriously in future.

Clinical data of 113 patients with non-alcoholic fat liver disease (NAFLD) diagnosed by liver biopsy from January 2015 to January 2017 in Taizhou People's Hospital were retrospectively reviewed . Patients all underwent transient elastographic ( TE) examination and the values of fat attenuation index (FAI) were obtained.The hepatocyt fatty changes in pathological examination were scored as 0 (＜5%, n＝40), 1 (5%-33%,n ＝27), 2 (34% -66%,n ＝28) and 3 (＞66%, n ＝18).There were significant differences in AST , Glu, TC and FAI among patients with hepatocyte fatty change scores 0, 1, 2 and 3, and the FAI was significantly correlated with the degree of fatty liver disease .The areas under the ROC curve (AUCs) of FAI in patients with hepatocyte fatty change scores 1, 2 and 3 were 0.78, 0.90 and 0.96, respectively.Logistic regression analysis showed that FAI was correlated with TG , TC and BMI.The results suggest that FAI in TE can be a non-invasive, rapid and objective evaluation method for patients with NAFLD.

Objective To determine the predictive factors for antiviral therapy in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B virus (HBV) infection [HBeAg(-) CHBI] patients with HBV DNA＜4.3 lg IU/mL.Methods A total of 179 HBeAg (-) CHBI patients were retrospective analyzed.Histology activity index (HAI) and fibrosis (S) were scored according to the Knodell HAI scoring system,and HAI＞3 and/or S≥3 was adopted as indications for treatment.Univariate and multiple regression analysis were used to assess factors associated with treatment indications.Receiver operating curves (ROC) and area under curve (AUC) were used to determine the predictive value of relevant factors.Results There were 81 cases with HAI＞3 (45.3％) and 72 with S≥3 (40.22％),and the proportion of patients with indications for treatment was 54.7 ％.Multiple regression analysis showed that age,γ-glutamyl transpeptadase (γ-GT),platelet (PLT) and albumin (Alb) were the predictive factors for the severity of liver damage and indication for treatment (all P＜0.05).The AUC for age,PLT,γ-GT and Alb were 0.655,0.657,0.726 and 0.65,respectively,and the corresponding Yoden index for age,PLT,γ-GT,and Alb were 0.297,0.426,0.03 and 0.012,respectively,the sensitivities of predicting HBeAg (-CHBI for treatment indications were 0.643,0.842,0.705 and 0.653,respectively.Conclusions This study shows that 54.7％ of HBeAg(-)CHBI patients with HBV DNA＜4.3 lg IU/ml have significant liver histological changes and require antiviral treatment.Older age,higher γ-GT,lower PLT and lower Alb levels are the predictive factors for treatment.

Objective To investigate the clinical manifestation,curative effect and prognosis of patients with EB viral hepatitis.Methods Clinical data of 40 hospitalized patients with EB viral hepatitis was retrospectively analyzed.The patients were divided into single EB viral hepatitis group (n =18) and EB viral hepatitis complicated with other liver damage group (n =22).The clinical characteristics were summarized.Results The main clinical manifestations of patients with EB viral hepatitis were fatigue,anorexia,jaundice,hepatosplenomegaly,and different degrees of damage.Levels of serum total bilirubin (TBIL),alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in EB viral hepatitis complicated with other liver damage group were significantly higher than those in single EB viral hepatitis group (P ＜ 0.05).Conclusion EB virus infection is one of the causes of liver function damage.

Objective To investigate the clinical manifestation,curative effect and prognosis of patients with EB viral hepatitis.Methods Clinical data of 40 hospitalized patients with EB viral hepatitis was retrospectively analyzed.The patients were divided into single EB viral hepatitis group (n =18) and EB viral hepatitis complicated with other liver damage group (n =22).The clinical characteristics were summarized.Results The main clinical manifestations of patients with EB viral hepatitis were fatigue,anorexia,jaundice,hepatosplenomegaly,and different degrees of damage.Levels of serum total bilirubin (TBIL),alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in EB viral hepatitis complicated with other liver damage group were significantly higher than those in single EB viral hepatitis group (P ＜ 0.05).Conclusion EB virus infection is one of the causes of liver function damage.

Traditionally regarded as a vitamin regulating calcium and phosphorus homeostasis, vitamin D is now discovered as a highly versatile molecule involved in immunity, cancer, infectious diseases, fibrosis, fatty liver diseases, and alcoholic liver diseases.In several studies, lower vitamin D status has been found to be associated with increased risk and unfavorable outcome of acute infections.This paper reviews the research progress of the roles played by vitamin D in various inflammatory diseases and its mechanisms.

Objective To compare the efficacy and safety of tenofovir (TDF) and entecavir (ETV) in patients with chronic hepatitis B (CHB) .Methods Studies that compared the treatment efficacy and safety between TDF and ETV in CHB patients were searched through electronic databases before Mar 2015 .Alanine aminotransferase (ALT) normalization rate ,hepatitis B virus (HBV) DNA suppression rate ,hepatitis B e antigen (HBeAg ) seroconversion rate ,drug resistance rate and safety profile were reviewed .RevMan 5 .2 was used for analysis .Results A total of 13 studies met inclusion criteria and 1 934 patients were analyzed ,including 884 patients treated with TDF and 1 050 with ETV .The HBV DNA suppression rate of TDF was superior to ETV at week 48 (OR=1 .36 ,95% CI:1 .05 -1 .76 ,P=0 .02) .The ALT normalization rate of ETV was superior to TDF at week 24 (OR= 0 .68 ,95% CI:0 .48-0 .96 ,P= 0 .03) .The virological response at week 24 ,ALT normalization rate at week 48 and serological response at week 24 and 48 were not significantly different between patients treated with TDF and ETV (all P>0 .05) .The resistance rate was not significantly different between patients treated with TDF and ETV 24 months after treatment (P=0 .51) .And the safety profiles of these two drugs were similar (P>0 .05) .Conclusions TDF has better virological response compared with ETV .The drug resistance rate and safety profile are similar between TDF and ETV .

MicroRNAs (miRNAs) are small non-coding RNAs that regulate both mRNA and protein expression of target genes and play important roles in proliferation,differentiation,development and metabolism of cells.This paper reviews the research progress on miRNAs involvement in liver diseases,including viral hepatitis,fatty liver,drug induced liver disease,primary biliary cirrhosis and primary hepatocellular carcinoma.