Serum Exosomal Long Noncoding RNA Growth Arrest-Specific 5 Predicts 3-Month Mortality in Acute-on-Chronic Hepatitis B Liver Failure.

Background: Acute-on-chronic hepatitis B liver failure (ACHBLF) is a clinical syndrome with an extremely high mortality. In this study, we aim to evaluate the potential role of serum exosomal long noncoding RNA (lncRNA) growth arrest-specific 5 (GAS5) in ACHBLF and its predictive value for 3-month mortality. Methods: From December 2017 to June 2022, we enrolled 110 patients with ACHBLF and 42 healthy controls (HCs). Exosomes were isolated from the serum of the participants. Serum exosomal lncRNA GAS5 was detected using quantitative real-time polymerase chain reaction (qRT-PCR). The functional role of lncRNA GAS5 on hepatocyte phenotypes was investigated through loss-of-function and gain-of-function assays. Exosomal labeling and cell uptake assay were used to determine the exosomes-mediated transmission of lncRNA GAS5 in hepatocytes in vitro. Results: The serum exosomal lncRNA GAS5 was identified to be an independent predictor for 3-month mortality of ACHBLF. It yielded an area under the receiver operating characteristic curve (AUC) of 0.88, which was significantly higher than MELD score (AUC 0.73; P < 0.01). Further study found that lncRNA GAS5 could inhibit hepatocytes proliferation and increase hepatocytes apoptosis. Exosomes-mediated lncRNA GAS5 transfer promoted hepatocytes injury. The knocked down of lncRNA GAS5 weakened H2O2-induced hepatocytes injury. Conclusion: We revealed that serum exosomal lncRNA GAS5 might promote hepatocytes injury and showed high predictive value for 3-month mortality in ACHBLF.

Decreased GPX3 mRNA level in peripheral blood mononuclear cells is associated with HBV-related hepatocellular carcinoma.

BACKGROUND: Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) is one of the most common malignancies with increasing mortality. In this study, we aim to determine the alteration and diagnostic value of GXP3 expression for HBV-related HCC. METHODS: We recruited 243 subjects, including 132 HBV-related HCC patients, 78 chronic hepatitis B (CHB) patients and 33 healthy controls (HCs). The mRNA level of GPX3 in peripheral blood mononuclear cells (PBMCs) was assessed by quantitative real-time PCR. The GPX3 plasma level was detected by ELISA. RESULTS: The GPX3 mRNA level was significantly decreased in HBV-related HCC patients compared with in CHB patients and HCs (p<0.05). The plasma GPX3 level was significantly lower in patients with HBV-related HCC than in CHB patients and HCs (p<0.05). In the HCC subgroup, the GPX3 mRNA level was significantly lower in patients with positive HBeAg, ascites, advanced stage and poor differentiation compared with in the other groups (p<0.05). The receiver operating characteristic curve was constructed to estimate the diagnostic value of the GPX3 mRNA level for HBV-related HCC. The GPX3 mRNA level showed a significantly better diagnostic ability compared with alpha fetoprotein (AFP) (area under the curve 0.769 vs 0.658, p<0.001). CONCLUSIONS: A decreased GPX3 mRNA level might be a potential non-invasive biomarker for HBV-related HCC. It showed better diagnostic ability than AFP.

Early prediction model for prognosis of patients with hepatitis-B-virus-related acute-on-chronic liver failure received glucocorticoid therapy.

BACKGROUND: Early prediction for short-term prognosis is essential for the management of hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). In this study, we aim to establish a noninvasive model for predicting the 90-day mortality in patients with HBV-ACLF received glucocorticoid therapy. METHODS: Two hundred and eighty patients with HBV-ACLF were enrolled from July 2010 to June 2022. All patients received routine medicine treatment and 204 of them received additional glucocorticoid treatment. Then, the patients who received glucocorticoid treatment were randomly divided into a training cohort and a validation cohort. An early prediction model for 90-day mortality of HBV-ACLF was established in the training cohort and then validated in the validation cohort. RESULTS: HBV-ACLF patients received glucocorticoid treatment showed significantly better survival that those not (P < 0.01). In the training cohort, a noninvasive model was generated with hepatic encephalopathy grade, INR, total bilirubin, age and SIRS status, which was named HITAS score. It showed significantly better predictive value for 90-day mortality of HBV-ACLF than MELD score and Child-Turcotte-Pugh score in both the training cohort and validation cohort. Using the Kaplan-Meier analysis with cutoff points of 2.5 and 3.47, the HITAS score can classify HBV-ACLF patients into different groups with low, intermediate and high risk of death after glucocorticoid therapy. CONCLUSIONS: We proposed a HITAS score, which was an early prediction model for the prognosis of HBV-ACLF. It might be used to identify HBV-ACLF patients with favorable responses to glucocorticoid treatment.

Serum exosomal long noncoding RNA nuclear-enriched abundant transcript 1 predicts 90-day mortality in acute-on-chronic hepatitis B liver failure.

Objectives: Acute-on-chronic hepatitis B liver failure (ACHBLF) is characterized by high short-term mortality, calling for accurate prognostic biomarkers. This study aims to evaluate the predictive value of serum exosomal long noncoding RNA nuclear-enriched abundant transcript 1 (lncRNA NEAT1) for 90-day mortality of ACHBLF.Methods: This prospective study consisted of 113 ACHBLF patients from June 2013 to June 2017 as a training cohort and 72 ACHBLF patients from July 2017 to June 2020 as a validating cohort. LncRNA NEAT1 was detected using quantitative real-time polymerase chain reaction from serum exosomes.Results: LncRNA NEAT1 levels were higher in non-survivors than survivors (P< 0.01). In the training cohort, lncRNA NEAT1 (HR 1.049, 95%CI 1.023-1.075, P< 0.001) was an independent predictor for 90-day mortality of ACHBLF. Meanwhile, lncRNA NEAT1 showed significantly higher area under the curve of receiver operating characteristic (AUC) than MELD score in the training and validation cohort (P< 0.05, respectively). However, no significant difference was found in AUC between lncRNA NEAT1 and NEAT1 plus MELD score (P> 0.05). ACHBLF patients with lncRNA NEAT1 levels above 1.92 showed poorer survival condition than those below (P< 0.01).Conclusions: The serum exosomal lncRNA NEAT1 might be a better prognostic biomarker than MELD score for 90-day mortality of ACHBLF.

The impact of COVID-19 pandemic on transmission of monetary policy to financial markets.

This study uses event-study methodology to estimate the impact of the COVID-19 pandemic on the transmission of monetary policy to financial markets, based on a sample of 37 countries with severe pandemics. Financial markets include government bond, stock, exchange rate and credit default swap markets. The results suggest that the emergence of pandemic has weakened the transmission of monetary policy to financial markets to a more significant degree. During our sample period following the outbreak of pandemic, neither conventional nor unconventional monetary policies have significant effects on all four of the financial markets. Of course, the unconventional monetary policies are slightly more effective as they can affect the stock and exchange rate markets to some extent. Therefore, in the post-pandemic period, if the monetary policy is used to stimulate financial markets, stronger policy adjustments, or other macro policies such as fiscal policies, may be needed to achieve the desired effect.

[Characteristics of resting state functional magnetic resonance imaging in tinnitus patients with different degrees of affective disorder].

Objective:To analyze the correlation of the degree of affective disorder and brain function changes by comparing the differences of resting-state functional Magnetic Resonance Imaging（rs-fMRI） between healthy volunteers without tinnitus and patients with tinnitus. Method:A analysis of 19 patients with tinnitus and 15 healthy volunteers without tinnitus. The patients were divided into mild group and severe group according to tinnitus handicap inventory（THI）. Rs-fMRI was collected and the regional homogeneity（ReHo） analysis, amplitude of low-frequency fluctuation（ALFF） analysis, and fractional amplitude of low frequency fluctuation（fALFF） analysis of rs-fMRI were performed by DPABI software. Two-sample t-test of the ReHo value, ALFF value and fALFF value between the mild group and the control group, the severe group and the control group, were performed respectively. Result:The fALFF value of the left occipital gyrus in the mild group was higher than that in the control group, the difference was statistically significant（P<0.05）, but there is no statistically significant difference of ALFF value and ReHo value between two groups. The ALFF value of the middle temporal gyrus（left）, superior frontal gyrus（right）, inferior frontal gyrus pars triangularis（left） and caudate nucleus（left） in the severe group were higher than those of the control group. But there was no significant difference in the fALFF value and the ReHo value. Conclusion:Different severity of affective disorder in patients with tinnitus have different areas of brain function abnormalities. Mild group was detected by fALFF analysis and the active brain area was the left middle occipital region. Severe group was detected by ALFF analysis. The active brain regions were left middle temporal gyrus, right superior frontal gyrus, left inferior frontal gyrus pars triangularis, and left caudate nucleus.

RIPK3 mRNA level acts as a diagnostic biomarker in hepatitis B virus-associated hepatocellular carcinoma.

HBV-associated hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide, and non-invasive early detection of HBV-associated HCC requires to be improved. To determine the alteration and clinical relevance of necroptosis and its key regulator receptor-interacting protein kinase 3 (RIPK3) in HBV-associated HCC, we detected the mRNA level of RIPK3 in peripheral blood mononuclear cells (PBMCs) and analyzed its correlation with clinical parameters. Here, we demonstrate that the expression of RIPK3 is elevated in patients with HBV-associated HCC compared to patients with chronic hepatitis B (CHB) and patients with HBV-related liver cirrhosis (LC). The mRNA level of RIPK3 is positively correlated with the severity of clinical manifestations and TNM stages. Moreover, the serum levels of RIPK3-asssocited cytokines are altered in consistent with the change of RIPK3 expression. The diagnostic accuracy of RIPK3 mRNA level is comparable to AFP test in discriminating HBV-associated HCC from LC and is better than AFP test in discriminating HBV-associated HCC from CHB. The combination of RIPK3 mRNA level and AFP test significantly improves the diagnosis of HBV-associated HCC. These data suggest that RIPK3 mRNA level is a biomarker in the onset and progression of HBV-associated HCC and may provide novel diagnostic strategies combined with the AFP test.

[Emission Characteristics and Risk Assessment of Volatile Organic Compounds from Typical Factories in Zhengzhou].

To understand the characteristics and potential hazards of volatile organic compounds (VOCs) emitted from different industrial factories in Zhengzhou, several representative factories have been selected for sample collection using canisters; the samples were subsequently analyzed by GC-MS/FID system, from which the composition and risk of VOCs are discussed in this study. It was found that OVOCs, especially ethyl acetate and isopropanol, were the most important species originating from printing factories, which accounted for more than 93.1% of total VOCs. The major components related to manufacturing industries, including automobile, furniture, and coating, were aromatics, mainly m/p-xylene, o-xylene, and ethylbenzene, which contributed 33.5%-90.0% to VOCs. Halogenated hydrocarbons made the largest contribution (52.3%) to VOCs in the food processing industry. The main components of VOCs were halogenoalkanes (25.5%) and alkanes (28.8%) in rubber factories. As for graphite carbon factories, the main components of VOCs were aromatics (28.5%) and alkanes (24.1%). Compared with previous studies, the VOC emission characteristics of factories involving solvent usage in Zhengzhou are consistent with those in other cities, but the compositional information of VOCs varies across different factories, even within the same industry, due to the different production processes and raw materials used. Risk assessment showed that the concentration of VOCs emitted from solvent factories are positively correlated with ozone formation potential (OFP) and the hazard index (HI). Specifically, benzene, toluene, ethylbenzene, xylene, and other C6-C8 aromatic hydrocarbons contributed significantly to OFP and HI. The HI values were 1.18 and 2.74 in automobile manufacturing factory NO.3 and wooden furniture factory NO.5, respectively, which were higher than the limits stated by EPA regulations because of the different production processes and raw materials, and the VOCs of the factories were mainly composed of aromatics; in particular, C6-C9 benzene series contributed significantly to HI and OFP. Therefore, it is necessary to control VOCs originating from industries involving solvent usage.

Hypomethylation of the cyclin D1 promoter in hepatitis B virus-associated hepatocellular carcinoma.

The hypomethylation of the Cyclin D1 (CCND1) promoter induced by excess oxidative stress likely promotes the development of hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC). We aimed to evaluate methylation status of the CCND1 promoter as a new plasma marker for the detection of HBV-HCC.We consecutively recruited 191 participants, including 105 patients with HBV-HCC, 54 patients with chronic hepatitis B (CHB), and 32 healthy controls (HCs). Using methylation-specific polymerase chain reaction, we identified the methylation status of the CCND1 promoter in plasma samples. We analyzed the expression levels of the CCND1 mRNA in peripheral blood mononuclear cells by using quantitative real-time PCR. We assessed the plasma levels of superoxide dismutase, 8-hydroxydeoxyguanosine and malondialdehyde by using enzyme-linked immunosorbent assays.Patients with HBV-HCC (23.81%) presented a reduced methylation frequency compared with patients with CHB (64.81%) or HCs (78.13%) (P < .001). When receiver operating characteristic curves were plotted for patients with HBV-HCC versus CHB, the methylation status of the CCND1 promoter yielded diagnostic parameter values for the area under the curve of 0.705, sensitivity of 76.19%, and specificity of 64.81%, thus outperforming serum alpha-fetoprotein (AFP), which had an area under the curve of 0.531, sensitivity of 36.19%, and specificity of 90.74%. Methylation of the CCND1 promoter represents a prospective diagnostic marker for patients with AFP-negative HBV-HCC and AFP-positive CHB. The expression levels of CCND1 mRNA was increased in patients with HBV-HCC compared with patients with CHB (Z = -4.946, P < .001) and HCs (Z = -6.819, P < .001). Both the extent of oxidative injury and antioxidant capacity indicated by the superoxide dismutase, 8-hydroxydeoxyguanosine and malondialdehyde levels were increased in patients with HBV-HCC. Clinical follow up of patients with HBV-HCC revealed a worse overall survival (P = .012, log-rank test) and a decreased progression-free survival (HR = 0.109, 95%CI: 0.031-0.384) for the unmethylated CCND1 group than methylated CCND1 group.Our study confirms that oxidative stress appears to correlate with plasma levels of CCND1 promoter methylation, and the methylation status of the CCND1 promoter represents a prospective biomarker with better diagnostic performance than serum AFP levels.

Nexus of FDI, population, energy production, and water resources in South Asia: a fresh insight from dynamic common correlated effects (DCCE).

The purpose of this study is to explore the empirical relationship between foreign direct investment (FDI), population, energy production, and water resources in South Asia. The newly developed approach dynamic common correlated effects (DCCE) by Chudik and Pesaran (Journal of Econometrics 188:393-420, 2015a) for measuring co-integration has been applied in the present study. This procedure provides significant robust outcomes in the presence of cross-sectional dependence among the cross-sectional units. The findings confirmed that earlier models, such as mean group (MG), pooled mean group (PMG), and augmented mean group (AMG), which have been used in the literature for long data, provide misleading results in the presence of cross-sectional dependence among the cross-sectional units. A statistically significant and negative result has been observed between FDI, population, energy production, and water resources in South Asia. The governments of South Asian economies must encourage green FDI initiatives for water management, ensuring water security, securing natural resources for enhancing the sustainable development of regional economies.

Receptor-Interacting Protein Kinase 3 (RIPK3) mRNA Levels Are Elevated in Blood Mononuclear Cells of Patients with Poor Prognosis of Acute-on-Chronic Hepatitis B Liver Failure.

Necroptosis refers to a programmed form of necrosis, which involves the receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like protein (MLKL). In this study, to investigate the role of necroptosis in the pathogenesis of acute-on-chronic hepatitis B liver failure (ACHBLF), we retrospectively analyzed 122 patients with ACHBLF, 131 patients with chronic hepatitis B (CHB), and 35 healthy controls (HCs). Using quantitative real-time polymerase chain reaction (RT-qPCR), we measured RIPK3 mRNA levels in peripheral blood mononuclear cells (PBMCs). ELISA was performed to measure the serum levels of MLKL, TNF-α and caspase-8. We found that RIPK3 mRNA levels were significantly higher in patients with ACHBLF than those with CHB or HCs. RIPK3 mRNA levels in patients with ACHBLF were positively correlated with serum levels of TNF-α or MLKL and negatively correlated with caspase-8 levels. Univariate and multivariate analysis revealed that RIPK3 mRNA level was predictive of 3-month mortality of ACHBLF. The area under receiver operating characteristic curve (AUC) of RIPK3 mRNA levels was 0.810 (95% CI: 0.729-0.876), which was higher than that of MELD scores (0.766, 95% CI: 0.681-0.838). The optimal cut-off point of 8.81 was determined for RIPK3 mRNA levels, which showed a sensitivity of 80.7% and a negative predictive value of 80.4%. These results indicate that elevated RIPK3 mRNA levels in PBMCs are associated with poor prognosis of ACHBLF. We thus propose that necroptosis may play an important role in pathogenesis of ACHBLF.

Does Income Diversification Benefit the Sustainable Development of Chinese Listed Banks? Analysis Based on Entropy and the Herfindahl-Hirschman Index.

We collected data pertaining to Chinese listed commercial banks from 2008 to 2016 and found that the competition between banks is becoming increasingly fierce. Commercial banks have actively carried out diversification strategies for greater returns, and the financial reports show that profits are increasingly coming from the non-interest income benefits of diversification strategies. However, diversification comes with risk. We built a panel threshold model and investigated the effect of income diversification on a bank's profitability and risk. Diversification was first measured by the Herfindahl-Hirschman index (HHI), and the results show that there is a nonlinear relationship between diversification and profitability or risk does exist. We introduced an interesting index based on the entropy to test the robustness of our model and found that a threshold effect exists in both our models, which is statistically significant. We believe the combination of the entropy index (ENTI) and the HHI enables more efficient study of the relationship between diversification and profitability or risk more efficiently. Bankers and their customers have increasingly been interested in income diversification, and they value risk as well. We suggest that banks of different sizes should adopt the corresponding diversification strategy to achieve sustainable development.

Stock Net Entropy: Evidence from the Chinese Growth Enterprise Market.

By introducing net entropy into a stock network, this paper focuses on investigating the impact of network entropy on market returns and trading in the Chinese Growth Enterprise Market (GEM). In this paper, indices of Wu structure entropy (WSE) and SD structure entropy (SDSE) are considered as indicators of network heterogeneity to present market diversification. A series of dynamic financial networks consisting of 1066 daily nets is constructed by applying the dynamic conditional correlation multivariate GARCH (DCC-MV-GARCH) model with a threshold adjustment. Then, we evaluate the quantitative relationships between network entropy indices and market trading-variables and their bilateral information spillover effects by applying the bivariate EGARCH model. There are two main findings in the paper. Firstly, the evidence significantly ensures that both market returns and trading volumes associate negatively with the network entropy indices, which indicates that stock heterogeneity, which is negative with the value of network entropy indices by definition, can help to improve market returns and increase market trading volumes. Secondly, results show significant information transmission between the indicators of network entropy and stock market trading variables.

Hypomethylated Ubiquitin-Conjugating Enzyme2 Q1 (UBE2Q1) Gene Promoter in the Serum Is a Promising Biomarker for Hepatitis B Virus-Associated Hepatocellular Carcinoma.

Aberrant DNA methylation, which can be detected in circulating cell-free DNA (cfDNA), is one of the major epigenetic alterations in hepatocellular carcinoma (HCC). UBE2Q1, a putative member of the ubiquitin-conjugating enzyme family, might play substantial roles in tumorigenesis. However, the methylation status of the UBE2Q1 gene in HCC remains unknown. We aimed to determine the methylation status of the UBE2Q1 gene promoter and to evaluate its potential clinical significance for HCC detection. The methylation-specific polymerase chain reaction (MSP) assay was used to detect the UBE2Q1 gene methylation status in serum samples from 80 patients with hepatitis B virus (HBV)-related HCC, 40 patients with liver cirrhosis (LC), 40 patients with chronic hepatitis B (CHB), and 20 healthy controls (HCs). Significantly lower methylation frequencies were detected in HCC patients (33.75%) compared with LC patients (55.00%, p = 0.026) and CHB patients (60.00%, p = 0.006) and HCs (65.00%, p = 0.011). Hypomethylation of the UBE2Q1 gene was negatively associated with the tumor node metastasis stage (rs = -0.30, p = 0.008). The UBE2Q1 gene methylation status combined with alpha fetoprotein using cut-off points of 20, 200 and 400 ng/ml showed sensitivity and specificity values of 58.8% and 75.0%, 53.8% and 87.5%, and 37.5% and 88.7%, respectively, and yielded a significantly increased area under the ROC curve (0.720, 0.760 and 0.694, respectively) for discriminating HCC from LC and CHB. Our study results suggest that hypomethylation of the UBE2Q1 gene promoter is a potential biomarker for detecting HBV-associated HCC.

A noninvasive model to predict liver histology in HBeAg-positive chronic hepatitis B with alanine aminotransferase ≤ 2upper limit of normal.

BACKGROUND AND AIM: Liver biopsy remains the gold standard to evaluate liver histology. However, it has several limitations. This study aims to construct a noninvasive model to predict liver histology for commencing antiviral therapy in HBeAg-positive chronic hepatitis B (CHB) with aminotransferase (ALT) ≤ 2 upper limit of normal (ULN). METHODS: Two hundred and ninety-eight patients with HBeAg-positive CHB, ALT ≤ 2ULN and HBV-DNA ≥20 000 IU/ml were enrolled and randomly divided into a training group and a validation group. A noninvasive model was constructed in the training group to predict significant liver histological change [necroinflammatory activity grade (G) ≥ 2 or fibrosis stage (S) ≥ 2] and then validated in the validation group. RESULTS: Aspartate aminotransferase, HBsAg, platelet, and albumin were identified as independent predictors. A model was constructed by them. It had an area under the receiver operating characteristic curve of 0.875 in the training group, 0.858 in the validation group and 0.868 in the entire cohort. Using a cut-off point of -0.96, it showed 93% sensitivity, 90% negative predictive value (NPV) in the training group and 95% sensitivity, 94% NPV in the validation group. Using a cut-off point of 0.96, it showed 95% specificity, 91% positive predictive value (PPV) in the training group and 89% specificity, 80% PPV in the validation group. CONCLUSIONS: This study constructed a noninvasive model to predict liver histology in HBeAg-positive CHB with ALT ≤ 2ULN, which might reduce the clinical need for liver biopsy.

Overexpression of serum sST2 is associated with poor prognosis in acute-on-chronic hepatitis B liver failure.

BACKGROUND AND OBJECTIVE: Interleukin-33 (IL-33) and soluble ST2 (sST2) have been demonstrated to be involved in liver injury. The present study aims to evaluate serum IL-33 and sST2 level in acute-on-chronic hepatitis B liver failure (ACHBLF) and determine their predictive value for prognosis. METHODS: Serum IL-33 and sST2 level in patients with ACHBLF, chronic hepatitis B (CHB) and healthy controls (HCs) were determined by enzyme-linked immunosorbent assay (ELISA). Clinical and laboratory parameters were obtained. RESULTS: Serum IL-33 was significantly higher in patients with ACHBLF (313.10±419.97pg/ml) than those with CHB (97.25±174.67pg/ml, P<0.01) and HCs (28.39±6.53pg/ml, P<0.01). Serum sST2 was significantly higher in patients with ACHBLF (1545.87±1135.70pg/ml) than those with CHB (152.55±93.28pg/ml, P<0.01) and HCs (149.27±104.90pg/ml, P<0.01). In all participants, serum IL-33 was significantly correlated with sST2 (r=0.43, P<0.01). In patients with ACHBLF, serum IL-33 was significantly correlated with alanine aminotransferase (ALT; r=0.26, P=0.04). Serum sST2 was significantly correlated with total bilirubin (TBIL; r=0.59, P<0.01), Log10 [HBV DNA] (r=-0.47, P<0.01) and model for end-stage liver diseases (MELD; r=0.28, P=0.03). Serum sST2 had an area under the receiver operating characteristic curve (AUC) of 0.81 in predicting 3-month mortality of ACHBLF. Patients with ACHBLF who had sST2 >1507pg/ml showed significantly poorer survival than those who had sST2 ≤1507pg/ml (P<0.01). Moreover, measurement of sST2 and MELD together significantly improved the diagnostic value of MELD alone (P<0.05). CONCLUSIONS: Our study showed that serum IL-33 and sST2 were overexpressed in ACHBLF and sST2 might potentially serve as a prognostic marker for it.

Aberrant DNA methylation of G-protein-coupled bile acid receptor Gpbar1 (TGR5) is a potential biomarker for hepatitis B Virus associated hepatocellular carcinoma.

BACKGROUND: G-protein-coupled bile acid receptor Gpbar1 (TGR5) is a newly identified liver tumor suppressor in carcinogenesis. This present study was therefore to determine the potential value of serum TGR5 promoter methylation in identifying hepatocellular carcinoma (HCC) from chronic hepatitis B (CHB) patients. METHODS: The circulating cell-free DNA (cfDNA) was extracted from a retrospective dataset including 160 HCC, 88 CHB and 45 healthy controls (HCs). Methylation status of TGR5 promoter was examined by methylation-specific polymerase chain reaction (MSP). RESULTS: Hypermethylation of the TGR5 promoter occurred significantly more frequent in HCC (77/160, 48.13%) than CHB (12/88, 13.64%; p<0.01) and HCs (2/45, 4.44%; p<0.01). The methylation rate of TGR5 in HCC patients ≥60 years old was significantly higher than those <60 years old (p<0.05). Alpha fetoprotein (AFP) had sensitivity of 58.13%, 30.63% and 24.38% at cut-off points of 20, 200 and 400ng/ml respectively; while TGR5 methylation combined AFP had sensitivity of 81.25%, 68.13% and 65%. AFP had specificity of 47.73%, 92.05% and 98.86% at cut-off points of 20, 200 and 400ng/ml respectively; while TGR5 methylation combined AFP had specificity of 38.64%, 78.41% and 85.23%. AFP had Youden index of 0.06, 0.23 and 0.23 at cut-off points of 20, 200 and 400ng/ml respectively; while TGR5 methylation combined AFP had Youden index of 0.20, 0.47 and 0.50. CONCLUSIONS: Our findings strongly suggested the combination of serum TGR5 promoter methylation and AFP enhanced the diagnostic value of AFP alone in discriminating HCC from CHB patients.

Alteration of interferon-α/ß receptors in chronic hepatitis B patients.

BACKGROUND: The present study determined type I interferon (IFN) receptor (interferon-α/ß receptor (IFNAR)) and its predicable role in interferon-α2b treatment in chronic hepatitis B (CHB) patients. METHODS: Expression of IFN-α/ßR-1 and IFN-α/ßR-2 in peripheral blood mononuclear cells and in liver tissue was measured by flow cytometry, immunofluorescence, immunohistochemistry and RT-PCR. RESULTS: IFN-α/ßR-1 and IFN-α/ßR-2 in monocytes and lymphocytes increased in CHB patients. Expression of IFNAR-1 and IFNAR-2 in liver had positive correlation with HBV-DNA in liver tissue. Expression of IFN-α/ßR in lymphocytes and monocytes increased in the first month, but then decreased during the subsequent interferon-α2b treatment, patients who had higher levels of IFN-α/ßR-2 in monocytes prior to therapy showed better viral response than those with lower levels. CONCLUSIONS: Expression of IFN-α/ßR-2 in monocytes can be used as a predictable parameter to evaluate the effect of IFN-α treatment in CHB patients.

[Hypomethylation of TNF-alpha gene promoter in the patients with acute-on-chronic hepatitis B liver failure].

OBJECTIVE: The present study was designed to investigate the possible epigenetic alteration in the promoter of TNF-alpha in the patients with acute-on-chronic hepatitis B liver failure (ACHBLF). METHODS: The methylation of TNF-alpha promoter in peripheral blood mononuclear cells (PBMCs) was measured by methylation specific PCR (MSP). The level of serum TNF-alpha was determined by enzyme-linked immunosorbent assay (ELISA). Model for End-stage Liver Disease (MELD) was performed for the evaluation of liver failure. RESULTS: The serum level of TNF-alpha in patients with ACHBLF(44.9260 +/- 26.48523) was higher than that in CHB (18.92505 +/- 9.04461) and healthy controls (11.9172 +/- 5.04612) (P < 0.05). Moreover, the serum TNF-alpha level was significantly decreased in methylation group as compared to unmethylaiton group in patients with ACHBLF (P < 0.05). MELD was not significantly different between methylated and unmethylated group of ACHBLF patients (P > 0.05). In addition, the serum level of TNF-alpha was found to be positively correlated with serum total bilirubin (r = 0.891, P < 0.01) and MELD score (r = 0.792, P < 0.01), but to be negatively correlated with prothrombin activity (r = - 0.511, P < 0.05) in patients with ACHBLF. CONCLUSION: The TNF-alpha methylation patten is stable for the liver failure, suggesting the effect of environment on methylation.

[Study of oxidative stress in chronic hepatitis B patients with elevated serum total bilirubin].

OBJECTIVE: To investigate oxidative stress in chronic hepatitis B (CHB) patients with elevated serum total bilirubin (TBIL). METHODS: 75 CHB patients with elevated serum TBIL were enrolled in the present study. A, B, C, D and E group were defined. Serum Malondialdehyde (MDA), Xanthine Oxidase (XOD), Vitamin C (V(C)) and Vitamin E (V(E)) were determined. The control group contained 11 healthy donors and the carrier group contained 16 Hepatitis B surface antigen (HBsAg) carriers. RESULTS: The concentrations of MDA and XOD were significantly higher in each group of patients than in the control (P < 0.05), while V(C) and V(E) were significantly lower (P < 0.05). The concentration of XOD was significantly higher in the carrier group than in the control (P < 0.05), while MDA, V(C) and V(E) were not significantly different (P > 0.05). The concentrations of MDA and XOD were significantly positively correlated with TBIL (r = 0.670, P < 0.01; r = 0.737, P < 0.01, respectively) in the patients, while V(C) and V(E) were significantly negatively correlated with TBIL (r = -0.463, P < 0.01; r = -0.247, P < 0.05, respectively). The concentration of MDA was significantly different among all the groups in the patients except the comparison between group A and group B. The concentration of XOD was significantly different between group A, B, C and group D, E (P < 0.05). The concentration of V(C) was significantly different between group A and group D, E and between group B, C, D and group E (P < 0.05). The concentration of V(E) was significantly different between group A, B and group E (P < 0.05). CONCLUSION: There was a disturbance between oxidative stress and anti-oxidative ability in CHB patients with elevated serum TBIL. Oxidative stress became more serious along with the increasing of serum TBIL. In HBsAg carriers, oxidative stress level was low. The results suggest antioxidant treatment for CHB patients with elevated serum TBIL may help to improve the effect of therapy.