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.

10.3969/j.issn.2095-4344.2013.23.006

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.

Hepatitis B, Chronic ; Humans

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

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.

Objective To investigate the protective and cure effects of dexamethasone on bleomycin-induced pulmonary fibrosis.Methods32 rats were randomly divided into the control group (C-group, n=8), injury group (I-group, n=12) and dexamethasone group (D-group, n=12). The acute pulmonary model was established by intratracheal injection of bleomycin with rats of the I-group and D-group; while rats of the C-group injected with distilled water. After that, rats of the D-group were injected with dexamethasone sodium phosphate in intraperitoneal every day, those of the C-group and I-group were injected with saline. The animals were killed on the 3rd, 7th, 14th, and 27th days after treatment, and tests of bronchoalveolar lavage fluid (BALF), total lung collagen content and lung tissue processing were performed.ResultsPathological evidence of the I-group rats demonstrated that the alveolar compartment companied with massive inflammatory cell invasion and a number of myofibroblast proliferation became more thick. However, lung injury in the D-group rats got better than that in the I-group. Neutrophil percentage achieved peak in both I-group and D-group on the 7th day. But the neutrophil ratio in the D-group was significantly lower than that of the I-group on the 7th day ( P<0.05) and the 14th day ( P<0.01). Total lung collagen content achieved peak on the 14th day both in I-group and D-group, but that of the I-group was significantly higher than that of the C-group ( P<0.01) and the D-group was significantly lower than the I-group ( P<0.01).ConclusionDexamethasone plays a protective and cure role in lung fibrosis by efficiently inhibiting the gather and invasion of neutropils and restraining the increase of collagen secreted by proliferous fibroblasts.

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 understand the nucleotide and amino acid differences of glycoprotein gene (G gene) between isolated rabies viruses in Henan Province and rabies vaccine strains used for human and animals. Methods G gene sequences of nine rabies viruses isolated from dogs in Xinyang city of Henan Province in December 2006 were amplified by reverse transcriptase (RT)-heminestedpolymerase chain reaction (PCR), and then were cloned and sequenced. The phylogenetic trees were constructed for analyzing the genetic characteristics of these rabies viruses. Results The homology of G gene among the nine isolates from Henan Province was 97.6% - 98.9% at nucleotide level and 99.2%-99.8% at amino acid level. The similarities between these isolates and CTN vaccine strain were 85.6%-93.0% and 91.9%-92.9% at nucleotide and amino acid level, respectively, which were higher than those between these isolates and other vaccine strains (80.4% - 83.3% and 87.7% - 92.5% at nucleotide and amino acid level, respectively). The nine isolates had several amino acid substitutions when compared to other genotype 1 rabies virus strains. Conclusions The nine rabies viruses strains isolated from Henan Province all belong to genotype 1. CTN may be an effective vaccine for preventing rabies in Henan Province.