BackgroundThe effect of antiviral therapy in chronic hepatitis B (CHB) on reducing the risk of long-term complications (LTCs) remains unclear so far. To study whether long-term nucleos(t)ide analogues therapy can reduce the risk of long-term complications.MethodsWe searched MEDLINE, EMBASE, OVID, the Cochrane Central Register of Controlled Trials. Relative risks (RRs) of long-term complications with or without treatment were studied. Also subgroup analyses including the status of drug-resistance, HBeAg and pre-existing compensated cirrhosis were done using relative risks of long-term complications either with or without treatment or among nucleos(t)ide analogues treatment groups.ResultsSix eligible studies (3644 patients in all) were included. Data showed the incidence of long-term complications in treatment groups was induced by 74%(RR:0.26, 95% CI: 0.15-0.47) compared with no treatment. Whether drug-resistant happened or not during the long-term therapy, the incidence of long-term complications was still significantly induced respectively by 45%(RR: 0.55,95%CI:0.40-0.76) and 78% (RR:0.22, 95%CI: 0.13-0.36). For both different status of HBeAg and pre-existing compensated cirrhosis, there was significant lower incidence of long-term complications in treatment groups compared with no treatment, too. Moreover, among the NA treatment groups, patients with drug-resistance had 2.64 times (RR:2.64, 95%CI: 1.58-4.41) higher chance of developing to long-term complications, and patients with pre-existing compensated cirrhosis also had 3.07 times (RR:3.07, 95%CI: 1.04-9.11) higher chance of developing to long-term complications.ConclusionsLong-term nucleos(t)ide analogue therapy for adults with CHB prevents or delays the development of long-term complications including decompensated cirrhosis, CHB-related death or CHB-related HCC in patients with CHB. The patients who need take antiviral drugs should receive the antiviral therapy as soon as possible.
Multi-drug resistance (MDR) is a major obstacle towards a successful treatment of hepatocellular carcinoma (HCC). The mechanisms of MDR are intricate and have not been fully understood. Therefore, we employed a cell-line model consisting of the 5-fluorouracil (5-FU) resistant BEL7402/5-FU cell line and its parental BEL7402 cell line. Using relative and absolute quantification (iTRAQ)-coupled 2D LC-MS/MS, a successfully exploited high-throughput proteomic technology, in total, 660 unique proteins were identified and 52 proteins showed to be differentially expressed in BEL7402/5-FU compared with BEL7402. Several differentially expressed proteins were further validated by Western blot and real-time quantitative RT-PCR analysis. Furthermore, the association of MDR with ANXA3, one of the highly expressed proteins in BEL7402/5-FU, was verified. Our study represents the first successful application of iTRAQ technology for MDR mechanisms analysis in HCC. Many of the differentially expressed proteins identified had not been linked to MDR in HCC before, which provide valuable information for further understanding of MDR.
High-performance osmotic energy conversion requires both large ionic throughput and high ionic selectivity, which can be significantly promoted by exterior surface charges simultaneously, especially for short nanopores. Here, we investigate the enhancement of ionic diffusion by charged exterior surfaces under various conditions and explore corresponding effective charged areas. From simulations, ionic diffusion is promoted more significantly by exterior surface charges through nanopores with a shorter length, wider diameter, and larger surface charge density, or under higher salt gradients. Effective widths of the charged ring regions near nanopores are reversely proportional to the pore length and linearly dependent on the pore diameter, salt gradient, and surface charge density. Due to the important role of effective charged areas in the propagation of ionic diffusion through single nanopores to cases with porous membranes, our results may provide useful guidance to the design and fabrication of porous membranes for practical high-performance osmotic energy harvesting.
Hepatitis B virus (HBV) is the most common of the hepatitis viruses that cause chronic liver infections in humans and it is considered a major global health problem. However, the mechanisms of HBV replication are complex and not yet fully understood. In this study, the HBV DNA-transfected HepG2.2.15 cell line and its parental HepG2 cell line were analyzed by isobaric tags for relative and absolute quantitation (iTRAQ)-coupled two-dimensional liquid chromatography tandem mass-spectrophotometry (2D LC-MS/MS), a successfully exploited high-throughput proteomic technology. In total, 2,028 unique proteins were identified and 170 proteins were differentially expressed in HepG2.2.15 cells as compared with that in HepG2. Several differentially expressed proteins were further validated by Western blot and real-time quantitative reverse transcription-PCR. Furthermore, the association of HBV replication with heat shock protein B1, one of the highly expressed proteins in HepG2.2.15 cells, was verified. HSPB1 functions as a anti-viral protein during HBV infection by specifically inducing type interferon and some downstream antiviral effectors. This study is the first to report the application of iTRAQ technology to analyze the underlying mechanisms of HBV replication. Many of the differentially expressed proteins identified have not been linked to HBV replication before, and may provide valuable novel insights into HBV replication.
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