Novel fluoronucleoside analog NCC inhibits lamivudine-resistant hepatitis B virus in a hepatocyte model

ABSTRACT Antiviral drug resistance is the most important factor contributing to treatment failure using nucleos(t)ide analogs such as lamivudine for chronic infection with hepatitis B virus (HBV). Development of a system supporting efficient replication of clinically resistant HBV strains is imperative, and new antiviral drugs are needed urgently to prevent selection of drug-resistant HBV mutants. A novel fluorinated cytidine analog, NCC (N-cyclopropyl-4′-azido-2′-deoxy-2′-fluoro-β-d-cytidine), was recently shown to strongly inhibit human HBV in vitro and in vivo. This study was designed to evaluate the antiviral activity of NCC against lamivudine-resistant HBV. We generated a stable cell line encoding the major pattern of lamivudine-resistant mutations rtL180M/M204V and designated it "HepG2.RL1". Immuno-transmission electron microscopic examination and enzyme-linked immunosorbent assay were used to detect secretion of HBV-specific particles and antigens. Quantification of extracellular DNA and intracellular DNA of HepG2.RL1 cells by quantitative real-time polymerase chain reaction revealed >625-fold and >5556-fold increases in the 50% inhibitory concentration of lamivudine, respectively, compared with that for the wild-type virus. The results showed that NCC inhibited DNA replication and HBeAg production in wild-type or lamivudine-resistant HBV in a dose-dependent manner. In conclusion, screening for antiviral compounds active against lamivudine-resistant HBV can be carried out with relative ease using hepG2.RL1 cells. NCC is a potential antiviral agent against wild-type HBV and clinical lamivudine-resistant HBV and deserves evaluation for the treatment of HBV infection.

Practice of Optimizing Outpatient Service Process Using the Integrated Outpatient Self-service Platform / 医学信息学杂志

The paper conducts a case study of Yangzhou No.1 People′s Hospital, introduces the practice of outpatient process opti-mization based on informatization support platform, analyzes the operation status of self-service outpatient service platform and existing problems.Based on the M/M/s model in queuing theory, the queuing model of payment for outpatient service in the hospital is construc-ted, the characteristics of queuing payment problems for outpatient service are revealed, the relationship between the sharing rate of self-service terminals and the average length of the queue in service windows, the average waiting time of patients.

Clinical Effect Observation and Cost-effectiveness Analysis on Different Operation Types of Ring Mixed Hemorrhoids Treatment / 世界科学技术-中医药现代化

This study was aimed to compare clinical effect and safety of ring mixed hemorrhoids treatment with pro-cedure for prolapsed and hemorrhoids (PPH) and Milligan-Morgan (M-M) in order to evaluate their effects of health economics. Retrospective analysis was given on clinical data of 100 cases (including 48 cases in P group, 52 cases in M group) which met the inclusion criteria from June 2008 to June 2010 in the Affiliated Hospital of Luzhou Med-ical College. Statistical analysis was made on short- and long-term effect, patient satisfaction, perioperative and postoperative complications of two groups. The cost-effectiveness was analyzed with the effect of health economics methods. The results showed that there was no obvious difference on short-term effect between two groups. However, aspects such as surgery time, hospitalization time, back to work time, duration of pain, bleeding condition, postopera-tive pain and anal swelling in P group were significantly better than M group (P< 0.05); long-term effect and cost-effectiveness in M group were obviously better than P group (P < 0.05). There was no obvious difference on inci-dence rate of adverse reaction between two groups. It was concluded that the traditional external dissection and inter-nal ligation for circumferential mixed hemorrhoids had better clinical effect of both short- and long-term with better cost-effectiveness. It is still a better surgical treatment for circular mixed hemorrhoids.