It has been nearly 20 years from the discovery of hepatitis C virus (HCV)and clinical diagnosis of hepatitis C to antiviral therapy with interferon,and significant progress has been made.Substantial changes have taken place in both the concept and strategy for antiviral treatment of hepatitis C,with more and more direct-acting antiviral agents emerging in recent years;these changes are as follows:from the control of HCV to clinical cure,from a sustained virologic response (SVR)rate around 30%with conventional interferon therapy to an SVR rate of 70%-80% with standard therapy with pegylated interferon and ribavirin,and from evaluating the difficulty of treatment based on genotypes and viral load to determining the treatment strategy according to host IL28B genotypes and response patterns (rapid virologic re-sponse and complete early virologic response).The progress in antiviral therapy strategies for hepatitis C is systematically reviewed for re-understanding of refractory hepatitis C.

Different subtypes of chronic hepatitis B virus(HBV)infection occurred clinically because of the status of virus’s interaction with immune system. In patients with immune tolerance,high level of HBV DNA was found,serum hepatitis B e antigen(HBeAg)was positive,and serum level of alanine aminotransferase(ALT)was normal with only mild or no inflammation in liver tissue. However,not all the patients with normal ALT were in immune tolerance status,the disease could progress insidiously and develop into liver cirrhosis. Whether these patients need anti-viral therapy has always been a hotspot of study. This article reviewed the correlation between immune status and HBV infection,the identification of patients with normal ALT but not in immune tolerance status,and the indication of anti-viral therapy for these patients.

Carcinoma, Hepatocellular ; therapy ; Catheter Ablation ; Chemoembolization, Therapeutic ; Combined Modality Therapy ; Humans ; Liver Neoplasms ; therapy ; Liver Transplantation

OBJECTIVE:To establish a method for content determination of schisandrin and schisandrin B in compound wurenchun capsule by RP-HPLC.METHODS:Column lichrosphere C18 was used,mobile phase of water and MeOH(gradient elution)was set up,the flow rate was 1.0mL?min-1,the column temperature was 30℃and the detection wavelength was 254nm.RESULTS:The linear ranges of schizandrin and schisandrin B were within 0.182 4～1.641 6?g(r=1.000 3)and 0.189 6～ 1.706 4?g(r=0 .999 9),respectively.The average recoveries were 98.32%(RSD=1.02%)and 97.22 %(RSD=0.94%),respectively.CONCLUSION:The established method is convenient,accurate and highly specific,and it can be used for the quality control of compound wurenchun capsule.

Isoliquiritigenin (ISL) is a flavonoid compound isolated from licorice. It possesses excellent antioxidant and anti-diabetic activities. This study aims to investigate the molecular mechanism underlying the alleviatory effect of ISL on energy metabolism imbalance caused by type 2 diabetes mellitus (T2DM). 8-week-old male C57BL/6J mice were used in in vivo experiments. The high-fat-high-glucose diet combined with intraperitoneal injection of streptozotocin was applied to establish T2DM animal model. All animal experiments were performed in accordance with the Institutional Guidelines of Laboratory Animal Administration issued by the Committee of Ethics at Beijing University of Chinese Medicine. HepG2 cells were used in in vitro experiments. Enzyme-linked immunosorbent assay (ELISA) and real-time quantitative polymerase chain reaction (RT-qPCR) were used to examine the protein and mRNA levels of mitochondrial function-related targets. The levels of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) in HepG2 cells were measured by the flow cytometry. Additionally, the molecular docking of ISL and key target proteins was analyzed. It was found that ISL significantly inhibited the activity of mitochondrial respiratory chain complex I and increased the protein levels of uncoupling protein 2 (UCP2) in the livers of mice and HepG2 cells. It also obviously decreased the ROS levels and increased the MMP levels in cultured HepG2 cells. In addition, ISL promoted mitochondrial biogenesis by activating proliferator-activated receptor gamma co-activator 1α (PGC-1α) and enhanced mitophagy by upregulating Parkin. It also improved mitochondrial fusion by increasing the mRNA and protein levels of mitofusin 2 (MFN2). In conclusion, ISL alleviates energy metabolism imbalance caused by T2DM through suppression of excessive mitochondrial oxidative phosphorylation and promotion of mitochondrial biogenesis, mitophagy, and fusion.

Isoliquiritigenin (ISL) is an active chalcone compound isolated from licorice. It possesses anti-inflammatory and anti-oxidative activities. In our previous study, we uncovered a great potential of ISL in treatment of type 2 diabetes mellitus (T2DM). Therefore, this study aims to reveal the mechanism underlying the alleviatory effects of ISL on T2DM-induced glycolipid metabolism disorder. High-fat-high-sugar diet (HFD) combined with intraperitoneal injection of streptozotocin (STZ) were used to establish T2DM mice model. All animal experiments were carried out with approval of the Committee of Ethics at Beijing University of Chinese Medicine. HepG2 cells were used in in vitro experiments, and sodium palmitate (SP) was applied to establish insulin resistance (IR) model cells. The effects of ISL on body weight, fasting blood glucose levels, and pathological changes in the livers of mice were examined. Enzyme-linked immune sorbent assay (ELISA) and real-time quantitative PCR (RT-qPCR) were applied to detect the regulatory effects of ISL on key targets involved in glucolipid metabolism. Additionally, molecular docking and analytical dynamics simulation methods were used to analyze the interaction between ISL and key target protein. The results indicate that ISL significantly downregulates the transcriptional levels and inhibits the activities of key enzymes involved in gluconeogenesis, including pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK), and fructose-1, 6-bisphosphatase (FBP). It also downregulates the transcriptional and protein levels of hepatocyte nuclear factor 4α (HNF4α) and cAMP response element binding protein (CREB), the two transcriptional factors involved in gluconeogenesis. Thus, ISL inhibits hepatic gluconeogenesis in T2DM mice. In addition, ISL reduces total cholesterol (TC) and triglyceride (TG) levels in the livers of T2DM mice. Moreover, ISL downregulates the mRNA levels of lipogenesis genes and upregulates those of genes involved in fatty acid oxidation, lipid uptake, and lipid export. In conclusion, ISL suppresses hepatic gluconeogenesis, promotes lipolysis, and restrains lipogenesis in T2DM mice, thereby improving the abnormal glycolipid metabolism caused by T2DM.

Objective To investigate the operation timing of laparoscopic cholecystectomy (LC)after endoscopic sphincterotomy (EST).Methods A total of 240 patients with cholecystolithiasis and choledocholithiasis received EST combined with LC.They were divided into 3 groups by random digits table method with 80 cases each:3 days after EST(group A),7 days after EST(group B),and 30 days after EST (group C).Intraoperative and postoperative clinical data were compared among three groups.Results The operation time of LC in group B [(52.5 ± 6.4) min] was longer than that in group A and group C [(35.8 ± 5.7),(34.6 ± 2.6) min],and there was significant difference (P ＜ 0.01).The intraoperative conversion rate in group B [10.0 ％ (8/80)] was higher than that in group A and group C [1.3 ％ (1/80),1.3 ％ (1/80)],and there was significant difference (P ＜ 0.05).The amount of bleeding in group B [(51.7 ± 4.8) ml] was larger than that in group A and group C [(27.9 ± 6.4),(28.2 ± 3.6) ml],and there was significant difference (P ＜ 0.01).The cost of hospitalization in group C [(15 361.2 ± 1 007.8) yuan] was more than that in group A and group B [(10 085.1 ± 695.4),(10 632.4 ± 855.9) yuan],and there was significant difference (P＜ 0.01).Conclusion LC performed 3 days after EST can reduce the operation difficulty and conversion rate,and shorten the operation time,and this modality is safe and effective.

Objective To observe the application of dysphagia ventilation swallowing and speaking valve inchildren with swallowing disorder after tracheostomy.Methods Four children with tracheostomy done and swallowing disorders(3 with brainstem encephalitis caused by hand,foot and mouth disease and 1 post-surgery case of cerebellar astrocytoma)were observed.Videofluoroscopic swallowing studies(VFSS)showed cricopharyngeal achalasia and silent aspiration.After VFSS assessments,ventilation swallowing and speaking valves(Passy-Muir,USA,PMVs)were applied to the 4 children.After that they received comprehensive swallowing trainings including balloon dilatation,breathing exercises,sensory stimulation and electrical stimulation.Results Four children could pronounce with PMVs immediately.After(36.50 ± 35.63)d of comprehensive intervention,all of them could live without tracheostomy tube or nasal feeding tube,their swallowing function improved obviously and could take food per os.Conclusions The application of PMVs combining with swallowing training is effective for children with swallowing disorder and dysphonia after tracheostomy.It is helpful to decrease the risk of aspiration,to open the cricopharyngeus muscle and to restore pronunciation.

Objective To identify the drug-induced constituents in rat serum containing drug of Compound Wurenchun Capsula and determine the content of these constituents. Methods Identification of the drug-induced constituents in serum has been carried out by combinative method of HPLC-DAD and UPLC-MS/MS. The content of four lignans in serum has been detected by HPLC-UV. Results Seven of eight original form compounds in serum have been identified as schisandrin,gomisin J,schisandrol B,deoxyschizandrin,gomisin N,schisandrin B,and schisandrin C. The UV spectrogram of five metabolites showed the absorption character of dibenzocyclooctadiene lignans. Eight lignans were identified by UPLC-MS/MS,besides schisantherin,there are seven lignan-like ones detected by HPLC-DAD. The content of schisandrin,schisandrol B,deoxyschizandrin,and schisandrin B in serum was (8.145 3?1.020 2),(6.604 5?1.341 4),(0.560 1?0.137 5),and (5.933 0?0.966 6) ?g/mL,respectively. ConclusionLignans and their metabolites are composed of the main drug-induced constituents in rat serum.

Objective To determine schisandrin,schisandrol B,deoxyschizandrin,and schisandrin B in serum containing drug of Compound Wurenchun Capsula.Methods An HPLC method was set up.Li-chrosphere C18 column(250 mm ?4.6 mm,5 ?m) and Phenomenex Description C18(4.0 mm?3.0 mm)protective column were used.Acetonitrile-water was used as gradient mobile phase.The flow rate was 1.0 mL/min.The column temperature was 30 ℃ and the detection wavelength was 210 nm.Results The linear ranges of schisandrin,schisandrol B,deoxyschizandrin,and schisandrin B were within 0.051 2-0.768 0 ?g(r=0.999 5),0.054 0-0.810 0 ?g(r=0.999 6),0.012 3-0.184 5 ?g(r=0.999 8),and 0.039 8-0.597 0 ?g(r=0.999 6),respectively.The average concentration of these four lignans in serum containing drug were 8.021 1,6.231 0,0.530 8,and 5.851 0 ?g/mL,respectively.Conclusion This method is easy,sensitive,specific,and accurate for the assaying of the four lignans in serum containing drug of Compound Wurenchun Capsula.