In recent years,the basic research on liver fibrosis has been progressed rapidly.This article briefly reviews the cellular and molecular mechanisms of liver fibrosis,including the origin of myofibroblasts,immune regulation,autophagy,and epigenetic regulation,and introduces several new therapeutic targets.More and more evidences show that successful removal of causes is the most important antifibrotic therapy.At present,although the antifibrotic drugs acting on different targets have been emerging,most of them are still in the early stage of research and development,and well-designed clinical trials are needed to confirm their clinical efficacy.

This review article compared the antiviral therapies recommended by major international and national guidelines for management of chronic hepatitis B(CHB)issued by American Association for the Study of Liver Diseases, Asian-Pacific Association for the Study of the Liver,Chinese Society of Hepatology & Chinese Society of Infectious Diseases,China Medical Association,and World Health Organization in 2015. The essentials and highlights of guidelines were compared,focusing on goals of therapy,indications of therapy,choices of drugs,endpoints and duration of therapy, management of treatment failure,treatment of CHB in pregnancy.

Hepatitis B, Chronic ; Humans

BACKGROUND: There have been no effective means for clinical treatment of large regions of bone defects.Nano-hydroxyapatite/collagen(nHAC)composite would provide a new pathway for repair of bone defects owing to its similar structure to natural skeleton and better biocompatibility.OBJECTIVE: To investigate the role of nHAC composite co-cultured with bone marrow-derived mesenchymal stem cells(BMSCs)in repair of bone defects.METHODS: Following isolation and culture,human BMSCs were co-cultured with nHAC composite.Gross observation,histological analysis,and electron microscope observation were performed to analyze osteogenesis for repair of bone defects in the clinic.RESULTS AND CONCLUSION: Human nHAC could greatly proliferate in vitro.X-ray photography revealed that bone defects well healed after implantation of nHAC/BMSCs composite.These findings indicate that BMSCs exhibit osteogenic potential and nHAC is a satisfactory scaffold material for construction of tissue-engineered bone.

10.3969/j.issn.2095-4344.2013.23.006

During the course of the investigation of the antifungal metabolites against Peronophythora litchii from the fermentation broth of Streptomyces sp SC120, an antibiotics that exhibited the cytotoxicity to CNE 2 was isolated By spectral (UV, IR, HRMS, 1H NMR, 13 C NMR, 1H 1H COSY, HMQC and HMBC) analyses, its structure was identified as pimprinine The cytotoxicity of pimprinine to CNE 2 was reported for the first time

Objective: To observe influence of porphyromonas gingivalis (Pg, a main pathogenic bacterium of periodontal disease) on vascular intima adhesion factors and metalloproteinases. Methods: A total of 60 rats were randomly and equally divided into blank control group, Pg low dose group (Pg 2ml) and Pg high dose group (Pg 5ml) according to number table. The latter two groups respectively received intramuscular injection of corresponding dose Pg every three days without antibiotic intervention for 12 weeks. Then their venous blood was taken to measure levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), matrix metalloproteinase (MMP)-3 and MMP-9 in three groups. Results: Compared with blank control group, there were significant increase in contents of ICAM-1 [（175.79±14.30）ng/ml vs.（182.62±15.07）ng/ml, （189.39±14.93）ng/ml]、VCAM-1 [（256.49±37.17）ng/ml vs.（271.58±32.85）ng/ml , (286.66±30.66)ng/ml] 、 MMP-3 [（3.23±0.69）ng/ml vs.（3.61±0.82）ng/ml, (3.97±0.83)ng/ml]及 MMP-9 [（1.30±0.39）mg/L vs.（1.48±0.39）mg/L, 1.67±0.45）mg/L ]（P <0.05，or <0.01），Compared with Pg low dose group, there were significant increase in levels of above indexes in Pg high dose group (P<0.05). Conclusion: Porphyromonas gingivalis can significantly increase serum contents of vascular intima adhesion factors and metalloproteinases, aggravating pathological development of coronary heart disease.

BACKGROUND:Contraction of three-dimensional collagen gels has been used as a model for the contraction which characterizes both normal wound healing and the development of fibrosis in the tissue. Several factors and cytokines,such as tumor necrosis factor alpha (TNF-α), interleukin-1, prostaglandin E2 and insulin have been proved to play important roles in collagen remodeling in vitro as well as serum extravasation during the fibrotic progress.OBJECTIVE: To observe extracellular collagen matrix contraction and apoptosis of fetal lung fibroblasts in TNF-α,interleukin-1, insulin, prostaglandin E2, albumin and globum under three-dimensional culture, and investigate the effects of cytokines, insuin, serum and serum protein on the remodeling and fibrotic formation of lung tissue.DESIGN: A randomized controlled experiment.SETTING: Department of Respiratory Medicine, Lanzhou General Hospital of Lanzhou Military Area Command of Chinese PLA.MATERIALS: The experiment was carried out The experiments were carried out in the respiratory laboratory of Lanzhou General Hospital of Lanzhou Military Area Command of Chinese PLA from August 2005 to January 2006. Human fetal lung fibroblasts (American Type Culture Collection), Dulbecco's modified Eagle's medium (DMEM) and fetal bovine serum, insulin, transforming growth factor (TGF) (R&D), prostaglandin E2, type Ⅰ collagen was extracted from rat-tail tendons.METHODS: In order to investigate the effect of initial collagen concentration in the gels on the contractility of fibroblasts,the appropriate amount of collagen was mixed with distilled water, four fold-concentrated DMEM, and cells were suspended so that the mass concentration was 0.75-2.0 g/L, with a physiological ionic strength and the desired cell concentration. In order to investigate the effect of cell number in the gels on the contraction, the cellular concentration fibroblasts in the gels were prepared to 0.2×107-4×107 L-1. The areas of floating gels were measured daily and the contraction was calculated by contrasting the initial size (％ of initial area). Different serum concentrations (0.01％-0.5％)in the medium were prepared, the serum albumin (0.1％) or globulin (0.1％) were added to the serum-free culture medium to observe the gel contraction. TGF (10 mg/L), interleukin-1 (10 mg/L), insulin (1 mg/L) and prostaglandin E2 (0.1 μmol/L) were added to observe the effects of cytokines and insulin on fibroblasts-mediated collagen gel contraction.The DNA content and cellular survivability in gels in collagen were determined.MAIN OUTCOME MEASURES: Effect of lung fibroblasts on collagen contraction with or without the presence of cytokines in three-dimensional culture; Effect of collagen with different concentration on the proliferation and apoptosis.RESULTS: ① Collagen gel contraction showed a dependence on the number of fibroblasts. ② Collagen gel contraction was augmented by increasing serum concentration in culture medium, and albumin increased the contraction dramatically. ③TGF and insulin significantly increased the contraction, whereas prostaglandin E2 and interleukin-1 significantly inhibited the gel contraction. ④ The lower the initial collagen concentration was, the more gel contracted and smaller final size were observed, and cell apoptosis increased.CONCLUSION: During the fibrotic process, fibroblast population migrated into the injured lung tissue may play an important role in the development of pulmonary fibrosis and serum infiltrating into injury lung tissue may play an role in stimulating the fibrotic progress. Infiltrating fluids and edema result in the dilution of the collagen concentration in the pulmonary interstitial which may lead to stronger contraction and serious fibrosis. In the dense fibrosis area, cells were hard to survive. In consequence, the final structure of fibrotic lung could not been changed and lung fibrosis progressed.

Objective To investigate whether antihypertensive treatment is beneficial to patients with diabetes mellitus when their blood pressure (BP) is below 140/90 mm Hg(1 mm Hg =0.133 kPa).Methods MEDLINE,EMBASE,IPA database and secondary resources were searched with terms including blood pressure,hypertension and anti-hypertension drug.Inclusion criteria:random control study; subjects were patients with diabetes mellitus or impaired glucose tolerance; endpoint BP ≤ 140/90 mm Hg; endpoint BP between two groups had significant differences.There were 16 studies meet inclusive criteria with a total of 51 470 patients.RR and 95％ CI were used as index to judge the difference of clinical outcomes between aggressive antihypertensive treatment group and standard antihypertensive treatment group.RevMan5.0 software was used for statistical analysis.Results When BP of patients with diabetes mellitus were below 140/90 mm Hg,anti-hypertensive treatment could reduce incidence rate of cardiovascular event (RR 0.91,95％ CI 0.87-0.96,P =0.0004) and stroke (RR 0.75,95 ％ CI 0.63-0.88,P =0.0005),and increased incidence rate of symptomatic hypotension (RR 3.57,95％ CI 1.41-11.20,P =0.03) and hyperpotassemia (RR 1.57,95％ CI 1.05-2.33,P =0.03).There were no significant differences in all-cause mortality (RR 0.94,95％ CI 0.87-1.01,P =0.08),cardiovascular mortality (RR 0.95,95％ CI 0.85-1.08,P =0.05),myocardial infarction (RR 0.93,95％ CI 0.82-1.05,P =0.26),heart failure (RR 0.90,95％ CI 0.76-1.06,P =0.21) between the aggressive antihypertensive treatment group and standard antihypertensive treatment group.Conclusions When blood pressure of patients with diabetes mellitus was below 140 mm Hg,there was little benefit from aggressive antihypertensive treatment,and the risk of serious adverse events even increased.

Objective To predict and identify the linear B-cell epitopes in the major group 3 allergen derived from Derma-tophagoides farina(Der f 3). Methods The linear B-cell epitopes of Der f 3 allergen were analyzed based on the physicochemi-cal properties of amino acids including antigenicity,surface accessibility,flexibility,hydrophilicity,beta-turn by online bioinfor-matics softwares. The eight predicted peptides of linear B-cell epitopes were artificially synthesized and incubated with three aller-gic serum pools(4 serum samples in each),which were consisted of total 12 serum samples from the allergic individuals,and the strong positive epitopes were selected. Results Eight B-cell epitopes from Der f 3 were predicted successfully. Five of eight B-cell epitopes were identified with strong IgE-binding abilities followed by specific IgE assay. The amino acid sequences of them were following:33KAKAGDCP40, 86HASGGEKIQVAEIYQHENYDSMTID110, 118LKTPMTLDQTNAKPVPLPPQGSDVKVG144, 156QEGSYSLP163 and 199DVANGGVDSCQGDSGGPVVD218. Conclusions Five linear B-cell epitopes of Der f 3 allergen have been identified successfully. This result might provide a basis of the diagnosis and treatment for asthma.