Dynamic change and significance of Mindin protein in chronic hepatitis B treated with PEG-IFNα-2b / 临床肝胆病杂志

ObjectiveTo investigate the change and potential role of Mindin protein in the treatment of chronic hepatitis B （CHB） with PEG-IFNα-2b. MethodsA total of 29 CHB patients who received the treatment with PEG-IFNα-2b in The Second Affiliated Hospital of Xi’an Jiaotong University from January 2018 to December 2019 were enrolled， and according to their clinical outcome， they were divided into cured group with 17 patients and uncured group with 12 patients. Peripheral blood samples were collected from both groups at baseline， 12 weeks， and 24 weeks to measure blood routine indices， liver function parameters， hepatitis B markers， and Mindin protein. HBsAg， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and Mindin protein at different time points were compared between the two groups. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； a Spearman correlation analysis was used to investigate correlation； a multiple linear regression analysis was used to investigate the influence of HBsAg and ALT on the content of Mindin protein. ResultsThe analysis of baseline data showed that there were significant differences in the levels of HBsAg， HBeAb， albumin， and albumin/globulin ratio between the cured group and the uncured group （all P<0.05）. The cured group tended to have a gradual increase in the level of Mindin， and the level of Mindin at 24 weeks was significantly higher than that at baseline （P<0.05）. The cured group had a significantly higher level of Mindin protein than the uncured group at 24 weeks （P=0.019）. The cured group had a significantly lower level of HBsAg than the uncured group （P<0.05）， with a significant change from baseline to each time point within the cured group （P<0.05）. In addition， the levels of ALT and AST in the cured group tended to first increase and then decrease， and the expression levels at 12 weeks were significantly higher than those at baseline （P<0.05）. At 12 weeks， there was a strong linear correlation between Mindin protein levels and ALT in the untreated group （r=0.760 8， P<0.05）， and further multiple linear regression analysis also demonstrated a linear relationship between the two （b=1.571， P=0.019）. ConclusionThere is a significant difference in the level of Mindin protein between the cured group and the non-cured group after 24 weeks of PEG-IFNα-2b antiviral treatment， and therefore， detecting the dynamic changes of Mindin protein can better predict the treatment outcome of CHB， which provides a reference for clinical practice.

Screening of key immune genes and pathways related to the ineffectiveness of interferon alpha treatment in patients with chronic hepatitis B based on GEO database / 西安交通大学学报(医学版)

【Objective】 To screen the differentially expressed immune genes between responders （Rs） and non-responders （NRs） in chronic hepatitis B patients receiving interferon alpha （IFN-α） treatment and to explore the molecular basis of IFN-α treatment failure. 【Methods】 The gene expression profile GSE27555 which contained 6 Rs and 7 NRs was obtained from the Gene Expression Omnibus （GEO） database； then differentially expressed genes between liver tissues of Rs and NRs were selected by the R software. The iconic immune gene set consisting of 1793 genes was downloaded from the immunology database and analysis portal （ImmPort）. The immune genes were extracted from the differentially expressed genes to obtain the differentially expressed immune genes. Subsequently， Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses of the differentially expressed immune genes were performed by the R software. Protein-protein interaction （PPI） network of the differentially expressed immune genes was constructed using the STRING online tool. The plugin CytoHubba of the Cytoscape software was applied to identify the top 10 genes by using Degree， MCC， MNC， and Closeness algorithms； then the intersection was taken to obtain the hub genes. 【Results】 A total of 88 differentially expressed immune genes， consisting of 13 upregulated and 75 downregulated genes， were identified between Rs and NRs. GO analysis showed that the differentially expressed immune genes were significantly enriched in T cell activation， cell chemotaxis， regulation of cell-cell adhesion， antigen processing and presentation. KEGG pathway analysis suggested that the differentially expressed immune genes were significantly enriched in cytokine-cytokine receptor interactions， Th cell differentiation， antigen processing and presentation， interactions between viral proteins and cytokines and cytokine receptors， chemokine signaling pathways， T cell receptor signaling pathway， IL-17 signaling pathway， natural killer cell-mediated cytotoxicity， Toll-like receptor signaling pathway， and other immune response signaling pathways. The top 7 hub genes， identified by the plugin cytoHubba of the Cytoscape software by using Degree， MCC， MNC and Closeness algorithms， were CD8A， IFNG， CCL2， CCL5， CXCL10， CCL4， and FCGR3A. 【Conclusion】 This study made a comprehensive analysis of the differentially expressed immune genes and signal pathways between Rs and NRs by bioinformatics， and identified 7 Hub genes related to the ineffectiveness of IFN-α treatment in CHB patients. These hub genes may serve as potential biomarkers for predicting the response of IFN-α treatment in CHB patients.

Influencing factors for the short-term prognosis of patients with HBV-related acute-on-chronic liver failure / 临床肝胆病杂志

ObjectiveTo investigate the influencing factors for the short-term prognosis of patients with HBV-related acute-on-chronic liver failure (HBV-ACLF). MethodsClinical data were collected from 240 HBV-ACLF patients without liver transplantation who were admitted To The Second Affiliated Hospital of Xi’an Jiaotong University from January 2009 to December 2019, and the patients were divided into groups according to survival on days 28 and 90 after admission (28-day survival group with 164 patients and 28-day death group with 76 patients; 90-day survival group with 140 patients and 90-day death group with 100 patients). The data collected included predisposing factors, liver function parameters, Model for End-Stage Liver Disease (MELD) score, MELD combined with serum sodium concentration (MELD-Na) score, and complications. The Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The receiver operating characteristic (ROC) curve was plotted to calculate the area under the ROC curve (AUC), and a multivariate logistic regression analysis was used to investigate the risk factors for the short-term prognosis of HBV-ACLF. ResultsThe main predisposing factors of HBV-ACLF included spontaneous activation of HBV (55.6%) and HBV activation caused by the withdrawal of or resistance to nucleoside analogues (25.2%). There were significant differences in age, prothrombin time activity (PTA), neutrophil-lymphocyte ratio (NLR), serum sodium, MELD score, MELD-Na score, and total bilirubin (TBil) at baseline between the 28-day survival group and the 28-day death group (Z=-2.400,-6.015, -5.070, -5.103, -5.044, -7.430, and -6.637, all P＜0.05), and there were also significant differences in age, PTA, NLR, serum sodium, MELD score, MELD-Na, TBil, and cholesterol at baseline between the 90-day survival group and the 90-day death group (Z=-2.205, -7.728, -3.335, -4.015, -6.053, -7.908, -6.655, and -3.607, all P＜0.05). The multivariate logistic regression analysis showed that TBil ＞260.20 mmol/L (odds ratio ［OR］=4.572, 95% confidence interval ［CI］: 1.321-15823, P＜0.05), PTA ＜24.8% (OR=8.934, 95%CI: 3.026-26.374, P＜0.05), NLR＞5.63 (OR=2.632, 95%CI: 1.126-6.152, P＜0.05), serum sodium ＜130.8 mmol/L (OR=27.467, 95%CI: 6.113-123.423, P＜0.05), MELD score ＞17.84 (OR=4.303, 95%CI: 1.048-17.663, P＜0.05), and MELD-Na score ＞25.1 (OR=3.453, 95%CI: 1.614-7.387, P＜0.05) were independent risk factors for 28-day survival; TBil＞260.20 mmol/L (OR=5.148, 95%CI: 1.918-13.822, P＜0.05), PTA ＜25.5% (OR=15.718, 95%CI: 5.161-47.866, P＜0.05), serum sodium ＜135.3 mmol/L (OR=10.080, 95%CI: 3.244-31.323, P＜005), MELD score ＞17.84 (OR=11.157, 95%CI: 2.580-48.254, P＜0.05), MELD-Na score ＞25.1 (OR=4.391, 95%CI: 2057-9.372, P＜0.05) were independent risk factors for 90-day survival. Among the 240 patients, 160 (66.7%) experienced infection within 90 days, among whom 140 had bacterial infection, 12 had viral infection, and 8 had fungal infection. The 160 patients with infection had a significantly higher 90-day mortality rate than the patients without infection (46.3% vs 32.5%, χ2=6.720, P=0.010). Of all 240 patients, 176 had ascites, 44 had pleural effusion, 36 had acute renal injury, 60 had hepatic encephalopathy, and 12 had gastrointestinal bleeding within 28 days, and there were significant differences in the proportion of patients with acute renal injury, grade Ⅲ-Ⅳ hepatic encephalopathy, or gastrointestinal bleeding between the 28-day survival group and the 28-day death group (χ2=64.088，29811，7.797，all P＜0.05). ConclusionTBil, PTA, serum sodium, MELD score, and MELD-Na score at baseline are independent risk factors for the 28- and 90-day prognosis of HBV-ACLF. Liver inflammation and necrosis caused by HBV activation may be the initiating factor for ACLF, and infection, acute renal injury, hepatic encephalopathy, and gastrointestinal bleeding are the main complications affecting the prognosis of patients.

Research advances in immune tolerance in chronic hepatitis B virus infection / 临床肝胆病杂志

Immune tolerance refers to the specific non-response or negative response of T and B lymphocytes to antigens.According to the period of formation,immune tolerance can be classified into central tolerance and peripheral tolerance.Immune tolerance to hepatitis B virus (HBV) after HBV infection is considered a major cause of chronic HBV infection.This article briefly reviews the roles of HBeAg,functional defects of dendritic cells,low response of cytotoxic T lymphocytes,T helper cells and cytokines,variations of HBV genotype and genome,and host gene polymorphisms in the development of immune tolerance in chronic HBV infection,as well as related research advances.

Research on the Relationship between Hospital Service Culture and Employee Satisfaction / 现代医院

Objective To explore the relationship between hospital service culture model and the satisfaction degree of employees.Methods To build a hospital service culture model through qualitative and quantitative research and make it into the hospital service culture questionnaire and use the satisfaction scale to investigate and analyze the sample.Results The hospital service culture model conforms to the standard modeling, which consists of a sense of belonging, sense of achievement, ability development, self-reconciliation, humanization, effective communication, effective performances and win-win.These eight factors have significant positive correlations with the employee satisfaction (P<0.01).Regression analysis showed that the 8 factors on employee satisfaction prediction coefficient was between 0.062~0.241 (P<0.05 or P<0.01, P<0.001).Conclusion The sense of belonging, sense of achievement, development ability, self-congruity, humanity, effective communication, efficiency and win-win in hospital service culture have become positive predictors in different degree and range of employee satisfaction.

Effect of PLTP on CSE-induced IL-8 production in human bronchial epithelial cells / 中国免疫学杂志

Objective:To investigate the effect of PLTP gene on CSE-induced IL-8 production in human bronchial epithelial cell line (HBECs). Methods:Wistar rats were exposed to air or cigarette smoke for 6 hours/day on 3 consecutive days,then the lungs were sectioned and examined. The number of total white blood cell and differential white blood cells in BALF were counted. The different concentrations of CSE co-cultured with HBECs for 24 hours. Cells growth was detected by MTT assay. Expression levels of PLTP mRNA and IL-8 mRNA were examined by RT-PCR,protein of PLTP was investigated by Western blot,and production of IL-8 ex-amined by ELISA. Results:The number of white blood cells in BALF was significantly increased compared with controls. Enhanced ex-pression level of PLTP and IL-8 were observed in CS-exposure group. Proliferation of HBECs tends to decrease at high concentrations of CSE(2. 0% CSE and 4. 0% CSE). The results suggested that the production of IL-8 induced by CSE in a time- and concentration-dependent manner,while the expression of PLTP induced by CSE in a dose-dependent manner. Furthermore,expression levels of IL-8 significantly increased after silence PLTP gene. Conclusion:PLTP siRNA could increase CSE-induced IL-8 production in HBECs.

Effect of PLTP on CSE-induced IL-8 production in A549 cells / 中国免疫学杂志

Objective:To investigate the effect of PLTP gene on CSE-induced IL-8 production in human alveolar Type Ⅱcells ( Adenocarcinomic human alveolar epithelial cells , A549 ) .Methods: The different concentrations of CSE co-cultured with human alveolar epithelial cell line ( A549 ) for 24 hours.MTT assay was performed to study the effect of CSE on human alveolar epithelial cell line(A549) growth.Expression levels of PLTP mRNA and IL-8 mRNA were examined by RT-PCR,protein of PLTP were examined by Western blot ,and protein of IL-8 was examined by ELISA .Results: MTT assay showed that the proliferation of A 549 cell line were stimulated by the 0.125%CSE,while the proliferation of A549 cell tends to decrease at high concentrations of CSE (2.0% CSE and 4.0%CSE),and in this middle concentrations of CSE (0.25%CSE ,0.5%CSE and 1.0%CSE),the proliferation of A549 cell was not significantly affected .Our studys suggested that PLTP and IL-8 release were induced by CSE in a concentration-dependent and time-dependent manner ,and expression levels of IL-8 obviously increased after silence PLTP gene .Conclusion:PLTP siRNA can increased CSE-induced IL-8 production in human alveolar epithelial cells (A549).

Role of phospholipid transfer protein in cigarette smoke-induced apoptosis of RLE-6TN cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the role of phospholipid transfer protein (PLTP) in cigarette smoke extract (CSE)-induced apoptosis of rat alveolar type II cells (RLE-6TN) in vitro.</p><p><b>METHODS</b>Rat alveolar epithelial cell line RLE-6TN were transfected with a small interfering RNA (siRNA) targeting PLTP prior to exposure to different concentrations of CSE for 24 or 48 h. The morphological changes of the apoptotic cells were observed by fluorescence microscopy with Hochest staining, and the cell apoptosis rate was measured with flow cytometry. The expression level of PLTP and caspase-3 activity in the cells were examined with Western blotting.</p><p><b>RESULTS</b>Exposure to CSE significantly increased the cell apoptosis rate from (1.68∓0.098)% to (18.663∓0.964)% (P<0.001). Hoechst staining revealed distinct apoptotic changes in CSE-treated cells, which showed increased PLTP expression and caspase-3 activity. PLTP knockdown with the specific siRNA partly suppressed the SCE-induced enhancement of caspase-3 activity in the cells.</p><p><b>CONCLUSION</b>PLTP may play a role in CSE-induced apoptosis of rat alveolar cells in vitro.</p>

Cyclophosphamide intervention in vivo increases the ABCG2 expression in adrenocortical carcinoma cells / 医学研究生学报

Objective High expression of multi-resistant transporter ATP-binding cassette super family G member 2 (ABCG2) is a major cause of drug resistance and chemotherapeutic failure of cancer .This study was to investigate the significance of ABCG2 expression in adrenocortical cancer cells after cyclophosphamide ( CTX) intervention in vivo . Methods Ten male and fe-male BALB/C-nu mice were randomly divided into a cyclophosphamide ( CTX) group and a control of equal number .SW-13 cells were subcutaneously injected into the nude mice to establish a model of subcutaneous transplantation tumor , followed by intraperitoneal injec-tion of CTX and isotonic saline solution into the two groups of mice , respectively .Then the expression of ABCG 2 in tumor tissue and primarily cultured cells was detected by immunohistochemistry and flow cytometry . Results The expression of ABCG 2 in the tumor tissue was significantly higher in the CTX than in the control group ([69.1 ±1.83]%vs [53.4 ±1.65]%, P<0.05), and so was that in the primarily cultured cells ([97.89 ±1.36]% vs [81.88 ±8.31]%, P<0.05). Conclusion The ABCG2 gene is in-volved in the drug resistance of adrenocortical carcinoma and may be a therapeutic target of the malignancy .