Karst grassland forage quality and its determinants in Guizhou Province of Southwest China.

Forage quality is a key property of grassland ecosystems. In this study, grassland forage qualities were measured at 373 sampling sites throughout Guizhou Province in the karst mountain region of Southwest China, and the factors affecting it were explored. The forage quality level of most plant species was categorized into four levels: (1) preferred forage species; (2) desirable forage species; (3) consumed but undesirable forage species; and (4) non-consumable or toxic forage species. High temperature and precipitation appeared to facilitate the growth of preferred forage species, but limited the growth of other plants. Increasing soil pH had a positive impact on the number and biomass of preferred forage plants, but a negative influence on other plants, especially non-consumable or toxic plants. Both GDP and population density had a positive correlation with the number and biomass of preferred forage species, while such correlations for other levels of forage species tended to be negative. Grazing could lead to a decrease in the preferred forage species. Therefore, it is suggested that by focusing on soil improvement in grassland and maintaining an appropriate grazing intensity, global warming and rapid economic growth in Guizhou Province will likely contribute to increase the forage quality of karst grasslands in Southwest China.

Performance of several simple, noninvasive models for assessing significant liver fibrosis in patients with chronic hepatitis B.

AIM: To compare the performance of several simple, noninvasive models comprising various serum markers in diagnosing significant liver fibrosis in the same sample of patients with chronic hepatitis B (CHB) with the same judgment standard. METHODS: A total of 308 patients with CHB who had undergone liver biopsy, laboratory tests, and liver stiffness measurement (LSM) at the Southwest Hospital, Chongqing, China between March 2010 and April 2014 were retrospectively studied. Receiver operating characteristic (ROC) curves and area under ROC curves (AUROCs) were used to analyze the results of the models, which incorporated age-platelet (PLT) index (API model), aspartate transaminase (AST) to alanine aminotransferase (ALT) ratio (AAR model), AST to PLT ratio index (APRI model), γ-glutamyl transpeptidase (GGT) to PLT ratio index (GPRI model), GGT-PLT-albumin index (S index model), age-AST-PLT-ALT index (FIB-4 model), and age-AST-PLT-ALT-international normalized ratio index (Fibro-Q model). RESULTS: The AUROCs of the S index, GPRI, FIB-4, APRI, API, Fibro-Q, AAR, and LSM for predicting significant liver fibrosis were 0.726 (P<0.001), 0.726 (P<0.001), 0.621 (P=0.001), 0.619 (P=0.001), 0.580 (P=0.033), 0.569 (P=0.066), 0.495 (P=0.886), and 0.757 (P<0.001), respectively. The S index and GPRI had the highest correlation with histopathological scores (r=0.373, P<0.001; r=0.372, P<0.001, respectively) and LSM values (r=0.516, P<0.001; r=0.513, P<0.001, respectively). When LSM was combined with S index and GPRI, the AUROCs were 0.753 (P<0.001) and 0.746 (P<0.001), respectively. CONCLUSION: S index and GPRI had the best diagnostic performance for significant liver fibrosis and were robust predictors of significant liver fibrosis in patients with CHB for whom transient elastography was unavailable.

Influence of Hepatic Inflammation on FibroScan Findings in Diagnosing Fibrosis in Patients with Chronic Hepatitis B.

Hepatic inflammation may affect the performance of FibroScan. This prospective study investigated the influence of hepatic inflammation on liver stiffness measurement (LSM) values by assessing FibroScan and liver biopsy findings in 325 patients with chronic hepatitis B. Liver fibrosis and inflammation were classified into five stages (S0-S4) and grades (G0-G4) according to the Scheuer scoring system. LSM values were correlated with fibrosis stage and inflammation grade (r = 0.479, p < 0.001, and r = 0.522, p < 0.001, respectively). Although LSM values increased in parallel with inflammation grade, no significant differences were found between patients with significant fibrosis (S2-S4) (p > 0.05). For inflammation grades G0, G1, G2 and G3, areas under receiver operating characteristic curves of FibroScan for significant fibrosis were 0.8267 (p < 0.001), 0.6956 (p < 0.001), 0.709 (p = 0.0012) and 0.6947 (p = 0.137), respectively. Inflammation has a significant influence on LSM values in patients with chronic hepatitis B with mild fibrosis, but not in those with significant fibrosis.

Interaction of TLR-IFN and HLA polymorphisms on susceptibility of chronic HBV infection in Southwest Han Chinese.

BACKGROUND & AIMS: The toll-like receptor-interferon (TLR-IFN) signalling pathway plays a crucial role in HBV infection. Human leucocyte antigen (HLA) polymorphisms are associated with chronic HBV infection by genome wide association study (GWAS). We aimed to explore interaction between TLR-IFN and HLA gene polymorphisms in susceptibility of chronic HBV infection. METHODS: In the Chinese Southwest Han population, 1191 chronic HBV infection patients and 273 HBV clearance were selected. A total of 39 single nucleotide polymorphism loci in 23 genes of the TLR-IFN pathway and four HLA polymorphism loci associated with chronic HBV infection identified by GWAS were selected for genotyping. SNPStats, QVALUE, and multifactor dimensionality reduction were used for statistical analysis. RESULTS: A significant association was seen in several of the TLR-IFN pathway genes, TLR9 rs352140 (OR = 0.70, P = 0.0088), IL1B rs16944 (OR = 0.67, P = 0.016), IL12B rs3212227 (OR = 1.38, P = 0.021), IFNGR1 rs3799488 (OR = 1.48, P = 0.0048), IFNGR2 rs1059293 (OR = 0.27, P = 0.011), MX1 rs467960 (OR = 0.68, P = 0.022), as well as four loci in HLA, rs3077 (OR = 0.55, P < 0.0001), rs2856718 (OR = 0.60, P = 4e-04), rs9277535 (OR = 0.54, P < 0.0001) and rs7453920 (OR = 0.43, P < 0.0001). A synergistic relationship was seen between rs9277535 and rs16944 (0.13%), rs1143623 and rs6613 (0.10%). The combination of rs9277535 in HLA and rs16944 in IL1B was the best model to predict chronic HBV infection (testing accuracy = 0.6040, P = 0.0010, cross-validation consistency = 10/10). CONCLUSIONS: TLR-IFN pathway gene polymorphisms are associated with chronic HBV infection. Interactions with polymorphisms in these genes may be one mechanism by which HLA polymorphisms influence susceptibility to chronic HBV infection, as specific single nucleotide polymorphism combinations are highly predictive of chronic HBV infection.

Telbivudine prevents vertical transmission of hepatitis B virus from women with high viral loads: a prospective long-term study.

BACKGROUND & AIMS: Hepatitis B virus (HBV) infection is a leading cause of liver diseases. We investigated the efficacy and safety of telbivudine in preventing transmission of HBV from hepatitis B e antigen-positive pregnant women with high viral loads to their infants in an open-label study. METHODS: We performed a prospective study of 450 hepatitis B e antigen-positive pregnant women with HBV DNA levels greater than 10(6) IU/mL; 279 women received telbivudine (600 mg/d) during weeks 24 to 32 of gestation, and 171 women who were unwilling to take antiviral drugs participated as controls. All newborns were vaccinated with a recombinant HBV vaccine and hepatitis B immune globulin, according to a standard immunoprophylaxis procedure. Mother-to-child transmission of HBV was determined by detection of hepatitis B surface antigen and HBV DNA in the infant 6 months after birth. RESULTS: None of the infants whose mothers were given telbivudine tested positive for of hepatitis B surface antigen at 6 months, compared with 14.7% of infants in the control group (P = 5.317 × 10(-8)). Levels of HBV DNA also decreased among women given telbivudine; 40 of 172 (23.2%) women given telbivudine had undetectable HBV DNA levels before delivery, compared with none of the controls. A significantly higher proportion of women given telbivudine had undetectable levels of HBV DNA in cord blood (99.1%) than controls (61.5%; P = 1.195 × 10(-22)). No severe adverse events or complications were observed in women or infants. CONCLUSIONS: Telbivudine significantly reduces vertical transmission of HBV from pregnant women to their infants; it is safe and well tolerated by women and infants. Antiretroviral Pregnancy Registry Health Care Providers ID: 26592; Government number: Natural Science Foundation of China (NSFC) 30830090, 30972598; and Third Military Medical University Key Project for Clinical Research: 2012XLC05).

[Meta-analysis of magnesium isoglycyrrhizinate combined with nucleoside analogues in patients with chronic hepatitis B].

OBJECTIVE: To evaluate the efficacy and safety of the magnesium isoglycyrrhizinate plus nucleoside analogues (MGL + NA) combination therapy in patients with chronic hepatitis B using a meta-analysis approach. METHODS: The Chinese Biochemical literature on Disc (CBMDisc) and the Chinese Scientific Journal database, CNKI, were searched for randomized controlled trials (RCTs) of MGL+NA in patients with chronic hepatitis B published between 1995 and 2013. Data related to treatment type (combination therapy vs. mono-therapy) and outcome (markers of efficacy and safety, including levels of hepatitis B virus (HBV) DNA, hepatitis B e antigen (HBeAg), alanine aminotransferase (ALT) and aspartate aminotransferase (AST)). Weighted mean differences (WMD) were calculated and the Peto method was used to determine the relative risk (RR), both with 95% confidence intervals (CIs). RESULTS: Meta-analysis of the six included RCTs of MGL + NA, representing a 704 patients with chronic hepatitis B, showed WMDs for ALT of -12.98 (95% CI: -18.24 to -7.71, P less than 0.01) and for AST of -9.49 (95% CI: -14.53 to -4.45, P = 0.0002) and RRs for HBeAg of 1.79 (95% CI: 1.17 to 2.76, P = 0.008) and for HBV DNA of 1.35 (95% CI: 1.05 to 1.74, P = 0.02). The therapeutic efficacy of MGL+NA combination therapy was better than that of NA mono-therapy (P less than 0.01). CONCLUSION: For patients with chronic hepatitis B, MGL combination therapy may enhance the antiviral efficacy of NA treatment and help to improve liver function during treatment.

Clinical implications of hepatitis B surface antigen quantitation in the natural history of chronic hepatitis B virus infection.

BACKGROUND: HBsAg quantitation may be useful for managing patients with hepatitis B virus (HBV) infection. OBJECTIVES: We explored the clinical implications of HBsAg quantitation for patients with HBsAg levels >250IU/ml (Abbott Diagnostics). STUDY DESIGN: Two hundred and thirty-three HBV-infected patients comprising 29 immune tolerance cases, 49 treatment-naïve HBeAg-positive chronic hepatitis B (CHB) cases, 91 inactive HBV carrier cases, and 64 treatment-naïve HBeAg-negative CHB cases were analyzed. HBsAg was quantified by the Architect HBsAg assay (Abbott Diagnostics) after a 1:500 automated dilution. RESULTS AND CONCLUSIONS: HBsAg (log10IU/ml) was established for immune tolerance (4.50±0.43), HBeAg-positive CHB (4.17±0.66), inactive HBV carrier (3.32±0.44), and HBeAg-negative CHB (3.23±0.40); (p=4.92×10(-35)). No significant difference was observed between inactive HBV carrier and HBeAg-negative CHB (p=0.247). The proportions of HBsAg <2000IU/ml for inactive HBV carrier and HBeAg-negative CHB were 51.6% and 59.3%, respectively (p=0.341). Positive correlations between HBsAg and HBV DNA were observed for immune tolerance (p=1.23×10(-4)) and HBeAg-positive CHB (p=0.003), but not for HBeAg-negative CHB (p=0.432). A negative correlation between HBsAg and age was observed for immune tolerance (p=0.030), HBeAg-positive CHB (p=0.016), and inactive HBV carrier (p=0.001), but not in HBeAg-negative CHB (p=0.249). No significant differences between HBsAg and ALT for HBeAg-positive (p=0.338) or HBeAg-negative CHB (p=0.564) were observed. For patients with HBsAg quantitation >250IU/ml, HBsAg may reflect HBV DNA replication for HBeAg-positive cases. HBsAg is not a suitable marker for evaluating hepatitis activity and distinguishing between cases of HBeAg-negative CHB and inactive HBV carrier state.

Long-term outcomes after nucleos(t)ide analogues discontinuation in chronic hepatitis B patients with HBeAg-negative.

BACKGROUND: Hepatitis B e Antigen (HBeAg)-negative chronic hepatitis B (CHB) patients have an active liver disease with a high risk of progression to decompensated cirrhosis and hepatocellular carcinoma. The management strategy for HBeAg-negative CHB patients treated with nucleos(t)ide analogues (NUCs) is a topic of concern. To observe the outcomes for this population after NUCs withdrawal, HBeAg-negative CHB patients with loss of hepatitis B surface antigen (HBsAg) or sustained undetectable HBV DNA levels who had discontinued NUCs therapy were included in the study. METHODS: A total of 66 patients (2 patients with HBsAg loss and 64 patients with sustained undetectable HBV DNA levels) were examined. HBV DNA levels and alanine aminotransferase (ALT) levels were monitored regularly after discontinuation of NUCs therapy. Relapse was defined as HBV DNA levels >2,000 IU/mL while off therapy in at least two determinations more than 4 weeks apart. RESULTS: The time to achieve undetectable HBV DNA levels was 14 weeks (interquartile range (IQR): 12-24 weeks). The time until consolidation therapy was 144 weeks (IQR: 96-168 weeks). No relapses occurred in either of the HBsAg loss patients. Among the 64 patients with undetectable HBV DNA levels, 19 (29.7%) patients demonstrated evidence of relapse. All the relapses occurred within 96 weeks after discontinuation. The median duration of relapse was 36 weeks (IQR: 12-48 weeks). Elevation of HBV DNA and ALT levels over baseline was only observed in 10% of the relapse patients. There were no significant differences among the baseline characteristics (sex, HBV genotype, age, or ALT level) or the time until consolidation therapy between relapse and sustained-response patients. CONCLUSIONS: NUC discontinuation is feasible after achieving undetectable HBV DNA levels in HBeAg-negative CHB patients. Prolonging the time until consolidation therapy may be a good strategy to decrease the rate of relapse. More than 96 weeks of sustained response is a predictive marker of long-term sustained response.

Expression pattern of serum cytokines in hepatitis B virus infected patients with persistently normal alanine aminotransferase levels.

PURPOSE: About 60-80 % of chronic hepatitis B virus (HBV) carriers are characterized with persistently normal alanine transaminase (ALT). Differences of cytokine expression are associated with the prognosis of HBV infection. We investigated the expression pattern of 30 cytokines associated with anti-HBV immunity in patients with normal ALT. METHODS: Four patient groups (immune tolerance, inactive hepatitis B surface antigen carriers, resolved hepatitis B, and control; 10 subjects per group) were assigned. Thirty cytokines, including IFN-γ, IL-1ß, IL-2, IL-4, IL-6, IL-7, IL-9, IL-10, IL-12p40, IL-12p70, IL-15, IL-17A, IL-17C, IL-21, IL-22, IL-23p19, IL-28A, IL-29, CCL5, CCL16, CCL20, CCL22, CXCL9, CXCL10, CXCL11, TNFRSF8, TNFRSF18, IL-6R, gp130, and TGF-ß1, were measured using a human cytokine antibody array. Signal intensities were obtained by laser scanner. Protein-protein interactions were analyzed by STRING (Search Tool for the Retrieval of Interacting Genes/Proteins). RESULTS: Significant differences of signal intensities were observed for IL-2, IL-4, IL-6, IL-7, IL-9, IL-10, IL-12p40, IL-12p70, IL-15, IL-21, IL-23p19, IL-28A, and IL-29. The lowest intensity was in controls. Among three HBV infection groups, significant differences were observed in IL-2, IL-4, IL-12p70, IL-15, IL-21, IL-23p19, and IL-29. The highest intensity was in the inactive group. All cytokines with significant differences were involved JAK-STAT signaling that up-regulate FOXP3, SOCS3 and MX1. CONCLUSION: Differential expression of cytokines in JAK-STAT signaling is an important factor associated with prognosis of HBV infection. The elevation of γC cytokines, IL-12p70, IL-23p19, and IL-29 may promote spontaneous HBeAg seroconversion and HBV clearance.

Epidemiological and clinical features of Plasmodium falciparum malaria in united nations personnel in Western Bahr el Ghazal State, South Sudan.

Western Bahr el Ghazal State is located in northwestern South Sudan, which is a tropical area subject to Plasmodium falciparum malaria epidemics. The aim of this study is to explore the epidemiological and clinical features of Plasmodium falciparum malaria in United Nations personnel stationed in this area. From July 2006 to June 2009, epidemiological data and medical records of 678 patients with Plasmodium falciparum malaria at the U.N. level 2 hospital were analyzed. The U.N. personnel were divided into individuals not immune to Plasmodium falciparum and individuals semi-immune to Plasmodium falciparum. The patients were divided into a chemoprophylaxis group (non-immune individuals who complied with the chemoprophylaxis regimen, 582 cases) and a no/incomplete chemoprophylaxis group (non-immune individuals who either did not fully comply with chemoprophylaxis or did not use it at all and semi-immune individuals who did not use chemoprophylaxis, 96 cases). Overall morbidity was about 11.3%. There was a significant difference in the morbidity of semi-immune and non-immune individuals (1.3% vs. 15.1%, P<0.001). Out of the total, 82.9% of cases occurred during the rainy season. The incidence of fever in the chemoprophylaxis group was significantly lower than in the no/incomplete chemoprophylaxis group (36.8% vs. 96.9%, P<0.001). Significant differences were observed between the two groups with respect to all other malaria-like symptoms except gastrointestinal symptoms, serum glucose level, platelet count, and alanine aminotransferase level. The incidence of complications was 1.2% (chemoprophylaxis group) and 44.8% (no/incomplete chemoprophylaxis group).The most common complication was thrombocytopenia, which was seen in 40.6% of the no/incomplete chemoprophylaxis group. In summary, Plasmodium falciparum malaria mainly occurred in rainy season. Gastrointestinal symptoms are an important precursor of malaria. Blood smears and rapid diagnostic tests should be performed after the onset of gastrointestinal symptoms. Appropriate chemoprophylaxis is necessary for reducing the severity of malaria.

Treatment with exogenous hydrogen sulfide attenuates hyperoxia-induced acute lung injury in mice.

The aim of this work was to test the effect of treatment with hydrogen sulfide (H2S) on hyperoxia-induced acute lung injury in mice. Mice were exposed to room air or 95 % O2, and treated with NaHS (intraperitoneal injection of 0.1 ml/kg/day of 0.56 mol/l NaHS). Treatment with H2S partly restored the reduced H2S levels in plasma and lungs of mice exposed to hyperoxia. Treatment with H2S attenuated hyperoxia-induced acute lung injury marked by reduced ratio of lung weight to body weight, ratio of lung wet weight to dry weight, and cell numbers and protein content in bronchoalveolar lavage (BAL) and decreased apoptosis. Treatment with H2S markedly prolonged the survival of mice under oxygen exposure. Treatment with H2S abated hyperoxia-induced oxidative stress marked by reduced malondialdehyde and peroxynitrite formation, reduced NADPH oxidase activity, enhanced translocation of nuclear factor E2-related factor (Nrf2) into nucleus and increased activity of HO-1. Treatment with H2S decreased IL-1ß, MCP-1, and MIP-2, and increased IL-10 expression in lungs of mice exposed to hyperoxia. Treatment with H2S decreased NFκB activity and iNOS expression in lungs, and reduced NOx content in BAL of mice exposed to hyperoxia. Treatment with H2S reduced lung permeability and suppressed VEGF release and VEGFR2 expression in lungs of mice under oxygen exposure. Treatment with exogenous H2S attenuated hyperoxia-induced acute lung injury through abating oxidative stress, suppressing inflammation, and reducing lung permeability in mice.

Serum levels of interleukin-12 in various clinical states with hepatitis B virus infection.

Hepatitis B virus (HBV) infection involves various clinical states. Interleukin-12 (IL-12) has been identified as a crucial cytokine in the development of cellular immunity. But the association between HBV infection clinical states and cellular immunity response remains unclear. The aim was to explore the association by investigating serum levels of IL-12. Observed in acute hepatitis B, the highest serum levels of IL-12 was accompanied by HBeAg seroconversion. Serum levels of IL-12 was associated with alanine transaminase (ALT) levels and significant more in chronic hepatitis B patients with ALT over five times upper limit of normal and a minority of immune-tolerance patients than controls. Serum levels of IL-12 may be an available marker to evaluate cellular immunity for HBV infection. Elevation in IL-12 levels may be a factor to promote HBeAg seroconversion and an opportunity to be given antivirus treatment for immune-tolerance carriers.