TMUB1 expression is associated with the prognosis of colon cancer and immune cell infiltration.

Background: TMUB1 is a transmembrane protein involved in biological signaling and plays an important role in the stability and transcription of P53. However, its role in tumor remains unknown. Methods: Using R language, the expression level of 33 cancer spectrum TMUB1 was analyzed by the public database TCGA, GEO and HPA, the differential expressed gene (DEG) screening and protein interaction (PPI) network was constructed, and the differential genes of TMUB1 in colon cancer were identified. The relevant signaling pathways were identified by gene functional annotation and enrichment analysis. The ssGSEA algorithm in GSVA were used for immune infiltration analysis. The Kaplan-Meier analysis, univariate and multivariate Cox regression analysis, nomogram and calibration map analysis were constructed to evaluate the correlation between TMUB1 expression and clinical prognosis. The expression levels of TMUB1 in intestinal cancer cell lines as well as in 10 intestinal cancer tissues were verified by qPCR experiments. Results: Through the bioinformatics analysis of multiple databases and preliminary experimental studies, we found that the expression of TMUB1 was significantly increased in colon cancer tumors, and was correlated with the clinical N stage, pathological grade, lymphatic metastasis and BMI of colon cancer. TMUB1 may be involved in the regulation of the malignant progression of colon cancer. Meanwhile, patients with high expression of TMUB1 mRNA had worse OS and DSS, and TMUB1 expression was an independent prognostic factor for OS and DSS. It was further found that highly expressed TMUB1 tissues showed low levels of immune infiltration and stromal infiltration. Conclusion: We reported the expression level of TMUB1 in colon cancer and analyzed its potential prognostic value in colon cancer through the bioinformatics analysis and preliminary experimental studies. The high expression of TMUB1 is a negative prognostic factor for colon cancer patients. TMUB1 may be a potential target for colon cancer.

Interferon add-on therapy increased clinical cure significantly for interferon-experienced chronic hepatitis B patients with low HBsAg.

Currently, interferon add-on therapy brings hope for clinical cure of chronic hepatitis B patients with low HBsAg. However, in clinical practice patients with poor responses to their first interferon therapy were often switched to nucleos(t)ide analog therapy and then labeled as unsuitable patients for interferon therapy. Even if their HBsAg levels dropped to a low level, they were reluctant or not recommended to take interferon again, which caused them to miss out on interferon add-on therapy and clinical cure. Therefore, it is urgent to elucidate the effectiveness of interferon add-on therapy to get clinical cure for these interferon-experienced patients with low HBsAg. The purpose of this study was to investigate whether interferon-experienced patients could achieve the same HBsAg clearance and HBsAg seroconversion rates as interferon-naive patients. Also, the associated factor of HBsAg clearance and seroconversion were aimed to be clarified. 292 patients, including 85 interferon-experienced patients, were enrolled with HBsAg< 1500 IU/ml, HBeAg negative and HBV-DNA negative. And then, peg-interferon α-2b add-on therapy was performed. The results showed that the week 48 HBsAg clearance and seroconversion rates of all patients were 29.8% and 22.0%. There was no statistically significant difference between interferon-experienced and interferon-naive patients in week 48 HBsAg clearance and seroconversion rates, suggesting satisfactory clinical cure of the interferon add-on therapy for interferon-experienced patients. The age, baseline HBsAg, and week 12 HBsAg were negative correlated factors for week 48 HBsAg clearance and seroconversion. Furthermore, the age, baseline HBsAg and week 12 HBsAg for predicting the week 48 HBsAg clearance were cut off at 40.5 years, at 152.0 IU/ml and at 34.99 IU/ml, and for predicting seroconversion were cut off at 40.5 years, at 181.9 IU/ml and at 34.99 IU/ml, correspondingly. Significantly, interferon-experienced patients with low HBsAg were suggested with interferon add-on therapy to achieve clinical cure as soon as possible. This research provided evidences and cut-offs for the interferon add-on therapy against chronic hepatitis B.

Follow-Up of 108 Patients with Chronic Hepatitis B Virus Infection Treated with Polyethylene Glycol-Conjugated Derivatives of Interferon-Alpha and Monitoring of Off-Treatment Virological Relapse.

BACKGROUND This single center study, which enrolled 108 patients with chronic hepatitis B virus infection treated with pegylated interferon-alpha (PEG-IFN-alpha), aimed to follow up and monitor off-treatment responses, including virological relapse, and analyze predictors of long-term efficacy of the PEG-IFN-alpha regimen. MATERIAL AND METHODS In total, 108 hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B who had completed the PEG-IFN-alpha regimen and achieved virological suppression were enrolled. The patients were followed up for 5 years to monitor off-treatment responses. Twenty-eight relevant factors, including the history of antiviral therapy and HBeAg seroconversion, were analyzed using the Cox proportional hazards regression model. RESULTS The cumulative rates of virological suppression were 75.70%, 68.68%, 65.25%, 63.91%, and 63.91% at 1, 2, 3, 4, and 5 years of the follow-up period, respectively. Compared with the rates of virological suppression, the cumulative rates of clinical suppression were 88.41%, 79.83%, 78.59%, 75.65%, and 75.65%, respectively, for the 5 years. Alanine aminotransferase (ALT) normalization at 24 weeks after off-therapy (relative risk [RR]=3.430, P=0.013) was a potential predictor for sustained virological suppression, and the history of anti-viral therapy (RR=0.164, P=0.004), quantitative value of hepatitis B virus surface antigen (HBsAg) at 48 weeks of anti-viral therapy (RR=2.697, P=0.039), and ALT normalization at 24 weeks after off-therapy (RR=5.467, P=0.004) were potential predictors for sustained clinical suppression. CONCLUSIONS Our results suggested that increased HBsAg levels at 48 weeks and normalization of ALT at 24 weeks after off-therapy might be predictive factors for long-term treatment efficacy.[color=red] [/color].

Alterations in intrinsic functional networks in Parkinson's disease patients with depression: A resting-state functional magnetic resonance imaging study.

AIMS: The aim of this research was to investigate the alterations in functional brain networks and to assess the relationship between depressive impairment and topological network changes in Parkinson's disease (PD) patients with depression (DPD). METHODS: Twenty-two DPD patients, 23 PD patients without depression (NDPD), and 25 matched healthy controls (HCs) were enrolled. All participants were examined by resting-state functional magnetic resonance imaging scans. Graph theoretical analysis and network-based statistic methods were used to analyze brain network topological properties and abnormal subnetworks, respectively. RESULTS: The DPD group showed significantly decreased local efficiency compared with the HC group (P = .008, FDR corrected). In nodal metrics analyses, the degree of the right inferior occipital gyrus (P = .0001, FDR corrected) was positively correlated with the Hamilton Depression Rating Scale scores in the DPD group. Meanwhile, the temporal visual cortex, including the bilateral middle temporal gyri and right inferior temporal gyrus in the HC and NDPD groups and the left posterior cingulate gyrus in the NDPD group, was defined as hub region, but not in the DPD group. Compared with the HC group, the DPD group had extensive weakening of connections between the temporal-occipital visual cortex and the prefrontal-limbic network. CONCLUSIONS: These results suggest that PD depression is associated with disruptions in the topological organization of functional brain networks, mainly involved the temporal-occipital visual cortex and the posterior cingulate gyrus and may advance our current understanding of the pathophysiological mechanisms underlying DPD.

Enhanced therapeutic effects of umbilical cord mesenchymal stem cells after prolonged treatment for HBV-related liver failure and liver cirrhosis.

BACKGROUND: Umbilical cord mesenchymal stem cells (UCMSCs) have been demonstrated to have good therapeutic effects in the treatment of HBV-related liver diseases. However, the therapeutic effect of UCMSCs on HBV-related liver failure and liver cirrhosis and the variations in the efficacy of UCMSCs after different treatment courses remain poorly understood. Therefore, this study was designed to answer these two questions. METHODS: This was an observational study that retrospectively considered a 3-year period during which 513 patients who received stem cell infusion and met the criteria of hepatic failure and liver cirrhosis were identified from the databases of the Third Affiliated Hospital of Sun Yat-sen University. The eligible patients were categorized into the liver failure group and liver cirrhosis group. The two groups were divided into different subgroups according to the duration of stem cell therapy. In the liver failure group, group A received more than 4 weeks and group B received less than 4 weeks of stem cell therapy. In the liver cirrhosis group, patients who received more than 4 weeks of stem cell therapy belonged to group C, and the patients in group D received less than 4 weeks of stem cell therapy. The patients were followed up for 24 weeks. The demographics, clinical characteristics, biochemical factors, and model for end-stage liver disease (MELD) scores were recorded and compared among different groups. RESULTS: A total of 64 patients met the criteria for liver failure, and 59 patients met the criteria for liver cirrhosis. After UCMSC treatment, the levels of alanine aminotransferase (ALT), glutamic-oxaloacetic transaminase (AST), and total bilirubin (TBIL) at all postbaseline time points were significantly lower than those at baseline in the liver failure group and liver cirrhosis group; the prothrombin activity (PTA) and MELD scores gradually improved in only the liver failure group. Four weeks after UCMSC treatment, patients who received prolonged treatment with UCMSCs had a larger decrease in TBIL levels than patients who terminated treatment with UCMSCs. After more than 4 weeks of UCMSC treatment, there were no statistically significant differences in the changes in ALT, AST, TBIL, and PTA values and MELD scores between patients with liver failure who received prolonged treatment with UCMSCs and patients with liver cirrhosis who received prolonged treatment with UCMSCs at any time point. However, the median decrease and cumulative decrease in the TBIL level of patients with liver failure with a standard 4-week treatment course were larger than those of patients with liver cirrhosis with a standard 4-week treatment course. CONCLUSION: Peripheral infusion of UCMSCs showed good therapeutic effects for HBV-related liver failure and liver cirrhosis. Prolonging the treatment course can increase the curative effect of UCMSCs for end-stage liver disease, especially for patients with cirrhosis.

HBV promotes the recruitment of IL-17 secreting T cells via chemokines CCL22 and CCL17.

BACKGROUND AND AIMS: Little is known about the mechanisms of IL-17 secreting T cells accumulation in HBV-transfected livers. Here, we investigated the role of the chemokines CCL17, CCL20 and CCL22 in this process. METHODS: Peripheral blood and liver tissues were obtained from 30 chronic hepatitis B (CHB) patients and 15 healthy volunteers and were evaluated by flow cytometric analysis and immunohistochemistry. Chemokine production by monocyte-derived dendritic cells (MoDCs) cocultured with HBV-transfected or untransfected Huh7 cells was measured by quantitative real-time PCR and enzyme-linked immunosorbent assay. The chemotactic activity of the culture supernatants was also tested. RESULTS: The proportions of IL-17 secreting CD4 (Th17) and CD8 (Tc17) T cells were both increased in liver and peripheral blood mononuclear cells of CHB patients compared to those in HVs. CHB patients showed higher intrahepatic levels of CCL17 mRNA, CCL22 mRNA, CCR6 mRNA and CCR4 mRNA than HVs. The expression of CCR6 and CCR4 on the surface of Th17 and Tc17 cells in CHB patients was also significantly higher than that in HVs. Significant correlations existed between the CCR4/CCR6 levels and both the alanine transaminase levels and HBV DNA loads. Contact between MoDCs and pBlue-HBV-transfected Huh7 cells induced the expression of CCL17 and CCL22 dependent on the dose of HBV DNA. However, CCL20 expression was lower in CHB patients than in HVs. Transwell experiments showed that upregulation of CCL17 and CCL22 enhanced the migration of IL-17 secreting T cells. CONCLUSIONS: Contact of HBV-transfected cells with MoDCs induces CCL17 and CCL22 chemokine production, which may favour the recruitment of Th17 and Tc17 cells to liver tissue in CHB. Our results reveal the mechanism of IL-17 secreting T cells recruitment to liver tissue and thus provide new immunotherapy targets for CHB patients.

The association between fasting plasma glucose and all-cause and cause-specific mortality by gender: The rural Chinese cohort study.

BACKGROUND: To evaluate the association between fasting plasma glucose (FPG) and mortality by gender. METHODS: A total of 17 248 eligible participants from a rural Chinese prospective cohort population were included. The same questionnaire interview and anthropometric and laboratory measurements were performed at both baseline (2007-2008) and follow-up (2013-2014). Participants were classified according to baseline FPG and diabetic status by sex. Restricted cubic splines and Cox proportional-hazards regression models, estimating hazard ratio (HR) and 95% confidence interval (CI), were used to assess the FPG-mortality relation. RESULTS: During the 6-year follow-up, 618 men and 489 women died. The FPG-mortality relation was J shaped for both sexes. For men, risk of all-cause and noncardiovascular disease (CVD)/noncancer mortality was greater with low fasting glucose (LFG) than with normal fasting glucose (adjusted HR [aHR] 1.60; 95% CI, 1.05-2.43; and aHR 2.16; 95% CI, 1.15-4.05). Men with diabetes mellitus (DM) showed increased risk of all-cause (aHR 2.04; 95% CI, 1.60-2.60), CVD (aHR 1.98; 95% CI, 1.36-2.89), and non-CVD/noncancer mortality (aHR 2.62; 95% CI, 1.76-3.91). Men with impaired fasting glucose (IFG) had borderline risk of CVD mortality (aHR 1.34; 95% CI, 1.00-1.79). Women with LFG had increased risk of non-CVD/noncancer mortality (aHR 2.27; 95% CI, 1.04-4.95), and women with DM had increased risk of all-cause (aHR 1.73; 95% CI, 1.35-2.23), CVD (aHR 1.76; 95% CI, 1.24-2.50), and non-CVD/noncancer mortality (aHR 1.97; 95% CI, 1.27-3.08). CONCLUSIONS: LFG is positively associated with all-cause mortality risk in rural Chinese men but not in women.

MFGE8 polymorphisms are significantly associated with metabolism-related indicators rather than metabolic syndrome in Chinese people: A nested case-control study.

BACKGROUND: The correlation between single nucleotide polymorphisms (SNPs) of milk fat globule-epidermal growth factor 8 (MFGE8) and metabolic syndrome (MetS) and metabolism-related indicators are limited. The present study explored the relation in Chinese adults. METHODS: We conducted a nested case-control study based on the Rural Chinese Cohort Study including 408 people with MetS and 408 controls matched by baseline sex, age (±2 years), marital status, and residence village. Four polymorphisms were selected and genotyped by using the SNPscan Genotyping system. Conditional logistic regression was used to estimate the association of MFGE8 polymorphisms with MetS incidence, and linear regression was used to assess the association with metabolism-related indicators in controls. RESULTS: We found no significant association of MFGE8 SNPs with MetS incidence or systolic blood pressure, or triglycerides level, or fasting plasma glucose (P > 0.05). However, MFGE8 rs4932450 was negatively associated with high-density lipoprotein cholesterol (HDL-C) level under the dominant model (ß = -0.0218, P = 0.007) and the additive model (ß = -0.0175, P = 0.012) and positively associated with diastolic blood pressure (DBP) under the recessive model (ß = 4.8848, P = 0.011). The rs3784751 SNP was associated with increased waist circumference (WC) in controls (ß = 0.0307, P = 0.028). CONCLUSIONS: MFGE8 polymorphisms were not associated with MetS but were related to DBP, HDL-C level, and WC in Chinese adults.

CD36 gene variants is associated with type 2 diabetes mellitus through the interaction of obesity in rural Chinese adults.

BACKGROUND: Evidences show that cluster determinant 36 (CD36) protein plays a role in lipid metabolism and insulin resistance, and the expression of CD36 is inducible in obesity. The present study evaluated the association of CD36 variants and the interaction with obesity on type 2 diabetes mellitus (T2DM) risk. METHODS: We performed a case-control study nested in the Rural Chinese Cohort Study. We included 546 incident T2DM cases matched with non-T2DM controls in a 1:1 ratio by sex, age (within 2 years), marital status, and residence village. Four loci in CD36 (rs1194197, rs2151916, rs3211956, and rs7755) were genotyped by SNPscanTM Genotyping system. RESULTS: After adjusting for potential confounding, we observed no statistically significant association between the CD36 polymorphisms and T2DM risk. Compared to wild-type homozygous carriers with normal weight, overweight/obesity participants carrying the mutational allele rs7755 showed increased risk of T2DM, by 114% (OR = 2.14, 95% CI: 1.33-3.46; Pinteraction = 0.007); abdominal obesity participants carrying the mutational allele rs7755 showed increased risk of T2DM, by 133% (OR = 2.33, 95% CI: 1.48-3.66; Pinteraction = 0.002). Furthermore, rs2151916 polymorphism was associated with triglycerides level (P = 0.019), and the rs1194197 variant was related to systolic blood pressure (P = 0.023) within the group of controls. CONCLUSIONS: CD36 genotypes were not associated with the progression to T2DM independently. However, our results suggested a positive interaction between the CD36 variants and obesity on T2DM susceptibility, which might be through a cardiometabolic disorder.

CONSORT: Effects of adding adefovirdipivoxil to peginterferon alfa-2a at different time points on HBeAg-positivepatients: A prospective, randomized study.

BACKGROUND: The aims of this study were to compare the efficacy and safety of the addition of adefovir dipivoxil (ADV) (started at different time points) to pegylated interferon alpha-2a (PEG-INF-α2a) and PEG-INF-α2a monotherapy. This prospective, randomized study sought to evaluate the safety and efficacy of the combination of PEG-INF-α2a and ADV at different time points.120 patients were randomized into groups that received PEG-INF-α2a as monotherapy (group A) or in combination with ADV started at week 0 (group B), 12 (group C), or 24 (group D). All patients were followed for 48 weeks. Efficacy and safety analyses were performed. METHODS: Patients in group a received 135 µg of PEG-INF-α2a by subcutaneous injection once weekly for 48 weeks. Patients in the ADV add-on group received 135 µg of PEG-INF-α2a subcutaneously once weekly and received 10 mg of ADV administered once daily for 48 weeks. HBV DNA, HBsAg, HBeAg, and hepatitis B e antibody levels were determined. Responses were determined at week 12 (ADV add-on), the end of treatment for PEG-INF-α2a (48weeks) and ADV (EOT) and at the end of 96 weeks of follow-up (EOF). RESULTS: The rate of HBV DNA loss were higher in the combination groups than group A at the week 12, week 48, the EOT and EOF (P < 0.05). The rates of HBeAg seroconversion and HBsAg loss were similar among the treatment groups (P>0.05). The alanineaminotransferase (ALT) normalization rate was higher in the combination group than group A only at the EOT (P = 0.007). By the EOF, the patients with ADV added at week 12 achieved higher rates of HBV DNA loss (71.9%), HBeAg seroconversion (50.0%), HBsAg loss (15.6%), and ALT normalization (78.1%). CONCLUSIONS: PEG-INF-α2a plus ADV combination therapy is safe and superior to PEG-INF-α2amonotherapyfor decreasing serum HBV DNA and normalizing the ALT level but has no significant impact on the rate of HBeAg seroconversion and HBsAg loss. Adding ADV at week 12 may be an optimal combination strategy.

TIMP-1 expression induced by IL-32 is mediated through activation of AP-1 signal pathway.

Hepatic fibrosis is a necessarily stage from the progression of chronic liver diseases to cirrhosis, even hepatocellular carcinoma (HCC). Hepatic fibrosis is characterized by the progressive accumulation of extracellular matrix (ECM). The balance between ECM production and degradation is mediated by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). TIMP-1 is an important regulator in the synthesis and degradation of ECM. IL-32, a multi-function cytokine, could induce IL-1ß, IL-6, IL-8 and other cytokine expressions by activating AP-1, NF-κß, p38MAPK signal pathways. IL-32 expression is increased in liver tissues of hepatic fibrosis. However, the role of IL-32 in the pathogenesis of liver fibrosis is not thoroughly clear. Recently, it is demonstrated that TIMP-1 expression is induced by the activation of AP-1 signal pathway. So we assayed the effect of IL-32 on TIMP-1 expression by LX-2 cells (one of HSCs cell lines) in the present study. We found that IL-32 could induce TIMP-1 expression by LX-2 cells at a dose-dependent manner. IL-32 could increase TIMP-1 promoter activity and induce TIMP-1 expression by activating AP-1 signal pathway. Moreover, the increase of TIMP-1 expression could promote the migration of LX-2 cells. In conclusion, we believe that IL-32 might be involved in the pathogenesis of hepatic fibrosis by inducing TIMP-1 expression.

Human hepatocytes express absent in melanoma 2 and respond to hepatitis B virus with interleukin-18 expression.

Absent in melanoma 2 (AIM2) is a recently recognized cytoplasmic receptor which could sense cytoplasmic double-stranded DNA (dsDNA). After AIM2 detects the presence of parasitic nucleic acids (dsDNA) derived from invasive bacteria or viral genomes (for example, vaccinia virus and cytomegalovirus) within infected cells, AIM2 inflammasome could be formed. The formed AIM2 inflammasome could induce innate immune response and increase expressions of IL-1ß and IL-18. Hepatitis B virus (HBV) is a hepatotropic, non-cytopathic double-stranded DNA virus. The immune response to viral antigens or virus is thought to be responsible for both liver damage and viral clearance in patients with HBV infection. However, there are no reports about whether AIM2 inflammasome exists in hepatocytes. In the present study, we investigated the presence and activity of AIM2 inflammasome in human hepatocytes. We found that AIM2 was expressed in cytoplasm of hepatocytes, and IL-18 expression was increased after AIM2 sensed HBV in hepatocytes in vitro. These results showed that AIM2 inflammasome was active in hepatocytes. We also found that hepatic AIM2 expression of chronic hepatitis B (CHB) patients was higher than that of controls. Hepatic AIM2 expression levels were positively correlated to the severity of liver inflammation. IL-18 is already considered to be associated with hepatic injury during HBV infection. In conclusion, we, therefore, believe that AIM2 inflammasome in hepatocytes might play an important role in the development and maintenance of HBV-related hepatitis.

[ROG,GATA3 and T-bet mRNA levels in peripheral blood mononuclear cells in patients with chronic hepatitis B].

OBJECTIVE: To investigate the role of ROG, GATA3 and T-bet in the progression of chronic hepatitis B (CHB). METHODS: The mRNA levels of ROG, GATA3 and T-bet in peripheral blood mononuclear cells (PBMCs) from 135 patients with CHB (including 45 mild cases, 42 moderate cases, and 48 severe cases) and 15 healthy control subjects were detected by real-time quantitative PCR. RESULTS: The levels of T-bet mRNA in the PBMCs were significantly higher in CHB patients than in the healthy controls (P<0.05), and also differed significantly between the 3 groups of CHB patients (P<0.05). ROG mRNA levels were significantly higher in severe cases of CHB than in the healthy controls and mild and moderate CHB cases (P<0.05), but were similar among the latter 3 groups (P>0.05). The mRNA level of GATA3 in the PBMCs were significantly higher in moderate and severe CHB cases than in the healthy controls and mild CHB cases (P<0.05). The T-bet/GATA3 ratio was significantly greater in the 3 CHB groups than in the control group (P<0.05) but comparable between the 3 CHB groups (P>0.05). ROG levels were not correlated with GATA3 levels or T-bet/GATA3 ratio in the CHB cases. CONCLUSIONS: The mRNA levels of ROG, GATA3 and T-bet in the PBMCs are obviously up-regulated in CHB patients and these 3 genes may participate in the progression of CHB. ROG plays an important role in correcting and maintaining the new balance of Th1/Th2.

[Deep sequencing of the T cell receptor Vb CDR3 repertoire of peripheral CD4+T cells in primary biliary cirrhosis].

OBJECTIVE: To determine the immune repertoires of peripheral CD4+T cell receptor (TCR) Vb CDR3 in primary biliary cirrhosis (PBC) and analyze TCR diversity and preferred usage at sequence-level resolution. METHODS: ARM-PCR and high-throughput sequencing were used to obtain millions of TCR Vb CDR3 sequences from peripheral CD4+T cells isolated from 7 patients with PBC and healthy volunteers. All sequencing data were analyzed, together with corresponding clinical information, by bioinformatic software. The Mann-Whitney U test was used for statistical analysis. RESULTS: The PBC patients showed a lower level of diversity among the peripheral CD4+TCR Vb CDR3 than the healthy volunteers, and patients with higher level progression of the disease showed a greater lack of diversity. In addition, 4 specific preferred-usage amino acid sequences were discovered for the PBC patients: ASSFTGGPVEQY, ASSLISSGNNEQF, ATSRDTLAGGPGDTQY, and SASLEGNTEAF; these sequences were also found in higher frequencies in patients with later stages of PBC. CONCLUSIONS: Decreased TCR Vb CDR3 diversities and specific preferred usage of TCR CDR3 sequences in peripheral CD4+T lymphocytes in PBC suggest that clonal expansion of a large number of CD4+T cells may be an important factor for PBC progression. These data provide a better understanding about the general characteristics of CD4+T cells in PBC patients and related to pathogenesis of the disease, and may provide useful insights into potential targets for immunotherapy.

Influence of chronic HBV infection on superimposed acute hepatitis E.

AIM: To investigate the influence of chronic hepatitis B virus (HBV) infection [based on the status of hepatitis B e antigen (HBeAg), HBV DNA, and cirrhosis] on superimposed acute hepatitis E. METHODS: A total of 294 patients were recruited from the Department of Infectious Diseases of the Third Affiliated Hospital, Sun Yat-sen University, from January 2003 to January 2012. The patients were classified into two groups: an HBV + hepatitis E virus (HEV) group (a group with chronic HBV infection that was superinfected with acute hepatitis E, n = 118) and an HEV group (a group with acute hepatitis E, n = 176). We retrospectively analyzed and compared the clinical features of the two groups. Statistical analyses were performed using the χ(2) test or Fisher's exact test for categorical variables and the Student's t test for continuous variables. A P value < 0.05 was considered statistically significant. RESULTS: The peak values of prothrombin time, serum total bilirubin, and Model for End-Stage Liver Disease scores were significantly higher in the HBV + HEV group. More patients in the HBV + HEV group had complications (39.8% vs 16.5%, P = 0.000) and developed liver failure (35.6% vs 8.5%, P = 0.000). Additionally, the mortality of the HBV + HEV group was significantly higher (20.3% vs 7.4%, P = 0.002). Further analysis of the HBV + HEV group showed that there were no significant differences in complication occurrence, liver failure incidence, or mortality between patients with different HBeAg and HBV DNA statuses. However, in patients with underlying cirrhosis, complication occurrence and liver failure incidence significantly increased. In total, 12.7% of the patients in the HBV + HEV group received anti-HBV treatment, but this therapy failed to reduce mortality in patients who developed liver failure. CONCLUSION: The presence of underlying cirrhosis in chronic HBV infection results in more severe clinical outcomes with superimposed acute hepatitis E. Anti-HBV treatment cannot improve the prognosis of liver failure caused by HBV-HEV superinfection.

[Construction and expression of non-structural protein gene 3-4b of HCV 1b based on the adenoassociated virus vector].

OBJECTIVE: To clone 1b type of HCV NS3-4b Gene and express in HEK 293 cells, lay the foundation for further study of the HCV NS3-4b recombinant adeno-associated virus vaccine and its dendritic cell vaccine. METHODS: HCV 1b patients' serum was collected, and full length NS3-4b segment was amplified by RT-PCR and cloned into adeno-associated virus' expression vector pAAV. CMV. EGFP in order to express in HEK 293 cells. At last, it was validated whether express or not by Western Blot. RESULTS: The 1b type gene NS3-4b were amplified and consistent to the expected size (2838 bp), the recombinant plasmid has been confirmed its successful restructured by double enzyme and sequencing, at last, Western Blot map can see objective protein expression after it transfect HEK 293 cells. CONCLUSION: The adeno-associsted virus recombination HCV NS3-4b plasmid have successfully constructed and it can express in eukaryotic cells.

Relapse rate and associated-factor of recurrence after stopping NUCs therapy with different prolonged consolidation therapy in HBeAg positive CHB patients.

BACKGROUND: Many chronic hepatitis B (CHB) patients recur after off-therapy and have to accept prolonged consolidation therapy with NUCs. We investigated the rate of HBV relapse after stopping NUCs therapy with different time period of prolonged consolidation therapy in HBeAg positive CHB patients, and analyzed the associated-factor of recurrence. METHODS: We recruited 162 HBeAg-positive CHB patients who met the standard of stopping NUCs therapy recommended by the 2005 APASL. Patients in group A, without the prolonged consolidation therapy, were as controls. Patients in group B were divided into 3 subgroups (group B1, 7 (range 3-11) months of the prolonged consolidation therapy; group B2, 17 (range 13-20) months of the prolonged consolidation therapy; group B3, 28 (range 25-34) months of the prolonged consolidation therapy). Virologic relapse was defined as an increase in serum HBV DNA to >10(3)copies/ml after off-therapy. RESULTS: One hundred and thirty-six patients (group A, 40 patients; group B1, 54 patients; group B2, 23 patients; group B3, 19 patients) were eligible for this study. The cumulative rates of relapse in group B at 6 months and 48 months were 29.2%, 41.7% after off-therapy, respectively. The cumulative rates of relapse in group B were statistically lower than that in group A at the same time periods. The cumulative rate of relapse in group B3 or group B2 was statistically lower than that in group B1, respectively. On multivariate analysis by Cox's proportional hazard model, age at off-therapy, baseline ALT and the different time period of the prolonged consolidation therapy were associated with the relapse of HBV after off-therapy. CONCLUSIONS: Consolidation therapy with NUCs after HBeAg seroconversion should be further prolonged. Age at off-therapy, ALT at baseline and the time period of the prolonged consolidation therapy could provide information to direct anti-viral therapy.

Relationship between MIF-173 G/C polymorphism and susceptibility to chronic hepatitis B and HBV-induced liver cirrhosis.

Macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine, played an important role in immune-mediated diseases. The promoter region of MIF, which had functional polymorphisms, controlled MIF expression. MIF polymorphism was associated with many inflammatory diseases. But the association of MIF polymorphism with chronic hepatitis B (CHB) or HBV-induced liver cirrhosis (HC) had not yet been reported. In present study, polymorphism of MIF-173 was genotyped in 95 CHB patients, 73 HC patients and 90 healthy controls in southern China. The frequency of MIF-173 C/C genotype in patients with CHB or HC was statistically significantly higher than that in healthy controls, respectively. Moreover, difference in the distribution of MIF-173 C allele between CHB patients and healthy controls was statistically significant. However, there was no statistical relationship between MIF-173 genotype and clinical features in patients with CHB or HC. Our results suggest that MIF-173 C/C polymorphism might be associated with increased risk of CHB or HC in Chinese southern population.

[Comparative study on the clinical characteristics of HBV infection patients with different pathologic inflammation grade].

OBJECTIVE: The aim of this study was to compare the biochemical and virological characteristics among patients infected with hepatitis B virus (HBV) according to pathologic inflammation grade. METHODS: 428 patients with chronic HBV infection accept liver biopsy, liver function test, HBeAg detection and HBV DNA levels detection. They were studied and subdivided into four groups according to pathologic inflammation grade. The biochemical and virological characteristics were studied. Univariate analysis was performed with the SPSS 16.0. RESULTS: In different inflammation grading group, mean age and sex composition were no difference. Serum levels of ALT was highest in group G3 and lowet in group G0-1, there was statistically significant among groups (P = 0.005); AST and TBil were all highest in group G4 and lowest in group G0-1, statistically significant also found among groups (P = 0.000 & 0.004). Serum levels of ALB and PTA were all highest in group G0-1 and lowest in group G4, had statistically significant among groups (P = 0.000 & 0.000). There was no difference of HBV DNA level and percentage of HBeAg (+) among four groups (P = 0.565 & 0.065). CONCLUSIONS: The serum AST, TBil, ALB and PTA were different and can partly reflect the inflammation degree of liver damage in patients with HBV infection. ALT and PTA can reflect the inflammation degree of G0-1, G2 and G3; AST, TBil, ALB and PTA reflect the G3 and G4. HBV DNA level and HBeAg status can not indicate the inflammation degree in HBV infection patients.

[Genetic variation of IL-28B is associated with treatment response of patients with chronic hepatitis C].

OBJECTIVE: To explore the effect of IL-28B variation on the response of patients with chronic hepatitis C virus (HCV) infection to therapy. METHODS: A total of 220 patients with chronic hepatitis C (CHC) were prospectively treated with pegilated interferon (peg-IFN) in combination with ribavirin (RBV) for 48 weeks. After completing the therapy, the patients were followed-up for 24 weeks and the therapeutic effectiveness was evaluated. The rs8099917 was identified from each cohort. The IL28B genotype was compared in hepatitis C patients to assess the effect of single nucleotide polymorphism (SNP) on different treatment response. RESULT: The proportion of the rs8099917 TT, TG, and GG genotypes was 71.4%, 25.0%, and 3.6% in sustained viral response (SVR) group; 15.8%, 60.5%, 23.7% in null response (NR) group; 38.1%, 52.3%, 9.6% in relapse (RP) group. There was a statistically significant difference in the genotype among SVR, NR and RP groups (P < 0.001, Chi-square test). NR vs. SVR (TG vs. TT: OR = 7.67, 95% CI: 2.91-20.56, P < 0.001). RP vs. SVR (TG vs. TT: OR = 3.10, 95% CI: 1.14-6.36, P < 0.01). CONCLUSIONS: The genotypes of IL-28 B (rs8099917) is closely related to the effectiveness of peg-IFN-alpha/RBV therapy, and it is an important predictive factor before treatment in patients with chronic hepatitis C.