Immune response- and viral control-related pathways in the progression of chronic hepatitis B.

BACKGROUND: Chronic hepatitis B (CHB) is a complicated and dynamic course, and is associated with advanced liver disease. Host immune response against viral infection plays a pivotal role in the progression of CHB. However, it is still uncharted that how the hepatic transcriptomes in patients with CHB are correlated with the clinical phases. OBJECTIVE: This study aimed to identify the specific sub-networks across various phases of CHB and infer potential pathways for phenotypic outcome prediction. METHODS: In this study, we performed the pairwise comparisons of the hepatic transcriptomes of CHB patients under different phases, and constructed the differential co-expression networks (DCNs). We firstly identified the critical genes from each DCN according to the adjacency matrix of the network. Then, the specific sub-networks were digged by iteratively affiliating genes that can increase the classification accuracy, using a snow-ball sampling strategy. Permutation test was implemented to determine the statistical significance of these sub-networks. Finally, each sub-network was given a most significant functional pathway. RESULTS: We constructed 3 DCNs by pairwise comparing the hepatic transcriptomes among three CHB phases, and systemically tracked 1, 1 and 2 specific sub-networks and pathways, respectively. Relative to immune tolerant phase, TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) pathway was significantly changed in the immune clearance phase, and nuclear receptor transcription pathway and adenylate cyclase activating pathway were altered in inactive carrier state. The host genes related to DNA strand elongation showed significant difference between the immune clearance phase and inactive carrier state. CONCLUSIONS: By pairwise comparing the hepatic transcriptomes of CHB patients under a network view, several immune- and viral control-related pathways were identified in this study. These results might serve as a foundation for characterizing the host transcriptomes responded to CHB infection, and hold clues for the development of potential targets for disease control.

STM study of electrical transport properties of one dimensional contacts between MnSi(~1.7) nanowires and Si(111) and (110) substrates.

We demonstrate the formation of contact barriers at the interfaces between MnSi1.7 nanowires (NWs) and Si substrates by the current-voltage (I-V) curves measured by scanning tunneling microscope with the tip contacting the NWs. The NWs on Si(110) exhibit linear reverse bias I-V curves, which suggests a parallel Ohmic surface state conductance of the Si(110) surface. The NWs on Si(111) exhibit nonlinear reverse bias I-V behavior, which indicates a considerable amount of minority carrier recombination-generation current. The NW length-dependence study of the forward bias current clearly shows that the quantitative change in NW length leads to a qualitative change in electrical transport properties. We derive a characteristic length LC ≈ 200 nm and the corresponding aspect ratio of ∼12-18 for MnSi1.7 NWs according to the variation of current density with the NW length.

An-Luo-Hua-Xian Pill Improves the Regression of Liver Fibrosis in Chronic Hepatitis B Patients Treated with Entecavir.

Background and Aims: Chronic hepatitis B (CHB) can cause liver fibrosis and lead to cirrhosis and cancer. As the effectiveness of antiviral therapy to reverse liver fibrosis is limited, We aimed to evaluate the effect of An-Luo-Hua-Xian pill (ALHX) on fibrosis regression in CHB patients treated with entecavir (ETV). Methods: Treatment-naïve patients with CHB were randomly treated with ETV alone or combined with ALHX (ETV+ALHX) between October 1, 2013 and December 31, 2020. Demographic, laboratory, and liver histology data before and after 78 weeks of treatment were collected. The Ishak fibrosis score (F) was used and fibrosis regression required a decrease in F of ≥1 after treatment. Results: A total of 780 patients were enrolled, and 394 with a second liver biopsy after treatment were included in the per-protocol population, 132 in ETV group and 262 in ETV+ALHX group. After 78 weeks of treatment, the fibrosis regression rate in the ETV+ALHX group was significantly higher than that of the ETV group at baseline F≥3 patients: 124/211 (58.8%) vs. 45/98 (45.9%), p=0.035. The percentage of patients with a decreased liver stiffness measurement (LSM) was higher in the ETV+ALHX group: 156/211 (73.9%) vs. 62/98 (63.%), p=0.056. Logistic regression analysis showed that ETV combined with ALHX was associated with fibrosis regression [odds ratio (OR)=1.94, p=0.018], and a family history of hepatocellular carcinoma was on the contrary. (OR=0.41, p=0.031). Conclusions: ETV combined with ALHX increased liver fibrosis regression in CHB patients.

Increased frequency of circulating Th17 cells in acute-on-chronic hepatitis B liver failure.

BACKGROUND: T helper (Th) 17 cells participate in the pathogenesis of liver diseases but their exact role in acute-on-chronic hepatitis B liver failure (ACHBLF) still remains obscure. AIMS: This present study was aimed to characterize the circulating Th17 cells and to analyze their association with disease progression in ACHBLF. METHODS: This retrospective study consisted of 40 ACHBLF patients, 40 chronic hepatitis B (CHB) patients and 20 healthy controls. The frequency of peripheral Th17 cells and IL-17 mRNA level in peripheral blood mononuclear cells (PBMCs) were estimated by flow cytometry and relative quantitative real-time polymerase chain reaction. RESULTS: We found that the frequency of peripheral Th17 cells, as well as the level of IL-17 mRNA in PBMCs, was significantly increased in ACHBLF patients compared with CHB patients and healthy controls. In ACHBLF patients, the frequency of Th17 cells was positively correlated with serum total bilirubin (r = 0.392, P = 0.012) and model for end-stage liver disease scores (r = 0.383, P = 0.015), but negatively correlated with prothrombin activity (r = -0.317, P = 0.046). The same trend was observed as for relative expression of IL-17. Furthermore, the frequency of Th17 cells and IL-17 mRNA level were significantly elevated in non-survivors compared with survivors in ACHBLF patients. CONCLUSIONS: These results suggested that Th17 cells as well as IL-17 might be related with disease severity and prognosis in ACHBLF patients.

Oseltamivir compared with the Chinese traditional therapy maxingshigan-yinqiaosan in the treatment of H1N1 influenza: a randomized trial.

BACKGROUND: Observational studies from Asia suggest that maxingshigan-yinqiaosan may be effective in the treatment of acute H1N1 influenza. OBJECTIVE: To compare the efficacy and safety of oseltamivir and maxingshigan-yinqiaosan in treating uncomplicated H1N1 influenza. DESIGN: Prospective, nonblinded, randomized, controlled trial. (ClinicalTrials.gov registration number: NCT00935194) SETTING: Eleven hospitals from 4 provinces in China. PATIENTS: 410 persons [corrected] aged 15 to 69 [corrected] years with laboratory-confirmed H1N1 influenza. INTERVENTION: Oseltamivir, 75 mg twice daily; maxingshigan-yinqiaosan decoction (composed of 12 Chinese herbal medicines, including honey-fried Herba Ephedrae), 200 mL 4 times daily; oseltamivir plus maxingshigan-yinqiaosan; or no intervention (control). Interventions and control were given for 5 days. MEASUREMENTS: Primary outcome was time to fever resolution. Secondary outcomes included symptom scores and viral shedding determined by using real-time reverse transcriptase polymerase chain reaction. RESULTS: Significant reductions in the estimated median time to fever resolution compared with the control group (26.0 hours [95% CI, 24.0 to 33.0 hours]) were seen with oseltamivir (34% [95% CI, 20% to 46%]; P < 0.001), maxingshigan-yinqiaosan (37% [CI, 23% to 49%]; P < 0.001), and oseltamivir plus maxingshigan-yinqiaosan (47% [CI, 35% to 56%]; P < 0.001). Time to fever resolution was reduced by 19% (CI, 0.3% to 34%; P = 0.05) with oseltamivir plus maxingshigan-yinqiaosan compared with oseltamivir. The interventions and control did not differ in terms of decrease in symptom scores (P = 0.38). Two patients who received maxingshigan-yinqiaosan reported nausea and vomiting. LIMITATIONS: Participants were young and had mild H1N1 influenza virus infection. Missing viral data precluded definitive conclusions about viral shedding. CONCLUSION: Oseltamivir and maxingshigan-yinqiaosan, alone and in combination, reduced time to fever resolution in patients with H1N1 influenza virus infection. These data suggest that maxingshigan-yinqiaosan may be used as an alternative treatment of H1N1 influenza virus infection. PRIMARY FUNDING SOURCE: Beijing Science and Technology Project and Beijing Nova Program.

Methylation of the glutathione-S-transferase M3 gene promoter is associated with oxidative stress in acute-on-chronic hepatitis B liver failure.

Chronic hepatitis B (CHB) is a major cause for liver disease worldwide, ranking as the first cause for liver cirrhosis and hepatocellular carcinoma. Acute-on-chronic hepatitis B liver failure (ACHBLF) is most commonly caused by acute severe exacerbation during CHB virus infection. The pathophysiology of ACHBLF is still poorly understood. Glutathione-S-transferase (GST) M3 belongs to GSTs superfamily and it has been demonstrated to contribute to oxidative stress-mediated liver damage. The present study was aimed to determine the potential association between GSTM3 promoter methylation and oxidative stress in ACHBLF patients. Thirty ACHBLF patients, 30 CHB patients and 10 healthy controls were included in this study. Methylation of GSTM3 promoter was determined using methylation-specific PCR (MSP) method. Plasma biomarkers for oxidative stress including malondialdehyde (MDA) and GST were detected by enzyme-linked immunosorbent assay (ELISA). Model for end-stage liver disease (MELD) scoring system was used for predicting the severity and prognosis of liver failure. ACHBLF patients had significant higher GSTM3 promoter methylation rate than CHB patients (30% versus 6.7%, χ(2) = 5.455, P = 0.020). Plasma MDA and GST levels were significantly increased in ACHBLF patients compared with CHB patients. Meanwhile, MDA, MELD scores and mortality rate were significantly higher in methylated group than those in unmethylated group of ACHBLF patients. Furthermore, plasma MDA levels were positively correlated with MELD scores of ACHBLF (r = 0.588, P = 0.001). In conclusion, the methylation of GSTM3 promoter may contribute to oxidative stress-associated liver damage and correlate with the disease severity in ACHBLF.

Enhanced demethylation of interferon-γ gene promoter in peripheral blood mononuclear cells is associated with acute-on-chronic hepatitis B liver failure.

Acute-on-chronic hepatitis B liver failure (ACHBLF) refers to liver failure occurring in patients with chronic hepatitis B (CHB) related liver diseases. Interferon-γ (IFN-γ) plays an important role in the exacerbation of liver function. However, the exact mechanism, by which IFN-γ mediates ACHBLF, is not fully understood. Forty patients with ACHBLF, fifteen patients with CHB and ten healthy controls were included in this present study. ELISA was performed to measure the level of serum IFN-γ. The methylation status of IFN-γ promoter in peripheral blood mononuclear cells (PBMCs) was determined using methylation-specific PCR. Model for End-stage Liver Disease (MELD) scoring was performed for evaluating the severity of liver failure. The serum level of IFN-γ in patients with ACHBLF or CHB was significantly lower than that in healthy controls, while the serum IFN-γ level in ACHBLF patients was significantly higher than that in CHB patients. In ACHBLF patients, the level of IFN-γ was positively correlated with total bilirubin and MELD score, but negatively correlated with prothrombin time activity. These results suggest the involvement of IFN-γ in the pathogenesis of ACHBLF. Importantly, the degree of methylation of the IFN-γ gene promoter in ACHBLF patients (60%, 24/40) was significantly lower than that in CHB patients (93%, 14/15), but was higher than that in the control group (20%, 2/10). Furthermore, in ACHBLF patients, the serum IFN-γ level was significantly higher in unmethylation group than that in methylation group. In conclusion, enhanced demethylation of IFN-γ gene promoter in PBMCs may be associated with the onset of ACHBLF.

Gpc-3 is a notable diagnostic, prognostic and a latent targeted therapy marker in hepatocellular carcinoma.

BACKGROUND/AIMS: To describe the features of the Gpc-3, explore the significance and value about the role of Gpc-3 in pathological diagnosis and prognostic evaluation of hepatocellular carcinoma. METHODOLOGY: Take an overview of Gpc-3 expression in hepatocellular carcinoma and its expression of the relationship between the clinicopathological features of hepatocellular carcinoma, analysis the expression of Gpc-3 in liver cell adenoma, heterosexual hyperplasia and hepatitis C. RESULTS: The expression of GPC-3 has a certain amount of specificity and sensitivity in hepatocellular carcinoma. CONCLUSIONS: Gpc-3 is not only a diagnostic and prognostic marker in hepatocellular carcinoma, but also is expected to be an ideal target for the therapy of hepatocellular carcinoma.

Formation of manganese silicide nanowires on Si(111) surfaces by the reactive epitaxy method.

Manganese silicide nanowires (NWs) with a large length/width ratio have been predominantly formed on Si(111)- 7 x 7 surfaces with the reactive epitaxy method by a delicate control of growth parameters. The supply of free Si atoms per unit time plays a crucial role in the formation of the NWs. High growth temperature and low Mn deposition rate are favorable for the growth of long NWs with a large length/width ratio and the formation of islands with other shapes can be greatly restrained under these conditions. The formation of NWs is driven by the minimization of the strain energy caused by the lattice mismatch between the silicide and substrate. Scanning tunneling spectroscopy measurements show that the NWs exhibit a semiconducting character with a band gap of approximately 0.8 eV, which is consistent with that of bulk MnSi(1.7).

Simultaneous soot combustion and nitrogen oxides storage on potassium-promoted hydrotalcite-based CoMgAlO catalysts.

A series of potassium-promoted hydrotalcite-based CoMgAlO mixed oxide catalysts used for simultaneous soot combustion and nitrogen oxides storage were prepared by impregnation method. The techniques of TG/DTA, XRD, H2-TPR and in situ DRIFTS were employed for catalyst characterization. Over the catalyst containing 7.5% or 10% K, the soot ignition temperature (Ti=260 degrees C) and total removal temperature (Tf=390 degrees C) are decreased by 180 degrees C and 273 degrees C, respectively, as compared with the uncatalyzed reaction. The results of kinetic calculation show that the presence of K-promoted catalysts decreases the activation energy of soot combustion from 207kJ/mol to about 160kJ/mol. When 400ppm NO is introduced, lower characteristic temperatures or higher reaction rate for soot oxidation is achieved. Simultaneously, relatively larger nitrogen oxides storage capacity is obtained. It is revealed by H2-TPR that the addition of K increases the amount of active Co sites and the mobility of bulk lattice oxygen due to the low melting point of K-containing compounds, the low valence of K+ and the strong interaction between K and Mg(Al). For nitrogen oxides storage, different routes via chelating bidentate nitrates, monodentate nitrates and ionic nitrates are confirmed by in situ DRIFTS over the CoMgAlO catalysts with potassium loadings of 0, 1.5 and 7.5%, respectively.