Hypoxia is a common physiological and pathological stimulus in many human diseases .The cellular oxygen sensors and the following activation of multiple cellular signal transduction pathways involved in hypoxia responses can regulate cell survival as well as respiration , blood circulation , metabolism and so forth .The cell response to hypoxia has a complex diversity .Hypoxia-induc-ible factor ( HIF) pathway in an oxygen dependent manner plays a central role during the hypoxia response .The HIF-independent path-ways are equally important under hypoxic conditions which can maintain the oxygen balance and metabolism balance .

Pulmonary fibrosis , an important cause of pulmonary diseases , has no effective protective and therapeutic meas-ures.Recent studies showed high mobility group protein B 1 (HMGB1) has an important role in the development of pulmonary fibrosis and many HMGB1 antagonists can alleviate pulmonary fibrosis in animal models .This paper summarizes the structure , function, intra-cellular signal transduction of HMGB1, the expression change of HMGB1 in pulmonary fibrosis and HMGB1 targeted therapy in pulmo-nary fibrosis in order to provide an effective basis for clinical treatment of pulmonary fibrosis .

Objective To evaluate the association between matrix metalloproteinase‐1 (MMP‐1)‐1 607 bp 1G/2G and matrix metalloproteinase‐3(MMP‐3)‐1 171 bp 5A/6A polymorphisms in promoter regions and susceptibility to ovarian cancer by Meta‐a‐nalysis .Methods Case‐control studies with regards of relationship between MMP‐1‐1 607 bp 1G/2G ,MMP‐3‐1 171 bp 5A/6A pol‐ymorphisms in promoter regions and susceptibility to ovarian cancer were searched in electronic databases .Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the association between polymorphisms and susceptibility .RevMan5 .0 software was applied for data analysis .Results Eight studies ,containing 5 studies for MMP‐1 and 3 studies for MMP‐3 ,were selected .For MMP‐1‐1 607 bp 1G/2G ,OR(95% CI)=0 .95 (0 .74-1 .21) ,P=0 .67 under 1G/1G :1G/2G+2G/2G model ,OR(95% CI)=0 .93 (0 .70-1 .23) ,P=0 .60 under 1G/1G :2G/2G model ,OR(95% CI)=0 .99 (0 .87-1 .14) ,P=0 .91 under 1G :2G model;for MMP‐3‐1 171 bp 5A/6A ,OR(95% CI)=0 .97(0 .68-1 .38) ,P=0 .85 under 5A/5A+5A/6A :6A/6A model .Overall ,there was statisti‐cal significance .Conclusion It is still not confirmed that significant association between the MMP‐1‐1 607 bp 1G/2G and MMP‐3‐1 171 bp 5A/6A polymorphisms in promoter regions and susceptibility to ovarian cancer exists in current literature .

Objective To study the correlation between symptomatic, radiological and etiological classification in acute ischemic stroke. Methods One hundred and twenty five patients with ischemic stroke within 48 hour of onset were prospectively studied with three step diagnosis: (1) symptomatic classification based on the Oxfordshire Community Stroke Project criteria (OCSP), (2) radiological classification(CT or MRI) and (3) etiological classification based on the Lausanne Stroke Registry criteria.Results Most of the patients with symptoms of total anterior circulation infarcts (TACI), partial anterior circulation infarcts (PACI) and posterior circulation infarcts (POCI) according to OCSP classification had corresponding lesions on CT or MRI, while only 67.3% of lacunar infarcts (LACI) patients had small subcortical infarction (SSI). More than 60% of patients with TACI were classified into cardioembolism (CE) in the third diagnosis, while the etiology of PACI was either CE or large artery atherosclerosis (LAA) in equal numbers. Only 57.7% of LACI patients were classified into small artery disease (SAD) and 28.8% of them into LAA, of which 80% patients had lesions other than SSI. The positive predictive value of SAD in the combination of LACI and SSI was 0.78. The etiology of POCI was variable.Conclusion Except for LACI, the symptomatic classification by OCSP corresponds well to the radiological classification. The etiological classification can be predicted in TACI and PACI, but it is hard to make in POCI, a number of LACI are due to LAA.

Objective To investigate the effect of Xuebijing injection on release of high mobility group box 1 (HMGB1) in endotoxin-induced cells. Methods HMGB1 concentration and mRNA expression were analyzed by enzyme-linked immunosorbent assay (ELISA) and RT-PCR, respectively. The effects of Xuebijing injection with 2, 10 and 50 mg/ml on HMGB 1 concentration in the culture medium of 200 ng/ml lipopolysaccharide-induced macrophage-like RAW 264.7 cells and BRL-3A hepatocytes, and HMGB1 mRNA expression in lipopolysaccharide-induced macrophages were observed. Results 50 mg/ml Xuebijing injection significantly decreased HMGB1 concentration in the culture medium of lipopolysaccharide-induced macrophages and hepatocytes(P< 0.01), and inhibited HMGB1 mRNA expression in macrophages. Conclusion Xuebijing injection inhibits endotoxin-induced release of HMGB1.

Objective High mobility group box 1 (HMGB1) mediates the inflammatory immune response as well as the prolif-eration, differentiation and migration of cells , neverthless, little study has been done on the changes of HMGB 1 expression in hepatoma tissues.The aim of the article was to investigate the changes of HMGB 1 mRNA and protein expression in hepatocellular carcinoma (HCC) tissues. Methods Real-time fluorescence quantitative PCR and Western blotting were applied to detect HMGB 1 mRNA and protein expression in HCC tissues and their paracancerous tissues of 13 cases.Immunofluorescence localization was used to analyze the changes of HMGB1 distribution in hepatic cells . Results The expression of HMGB1 mRNA and protein in HCC tissues (4.01 ±0.81) and (1.37 ±0.34) increased significantly in comparison with those in paracancerous tissues (5.76 ±1.28) and (0.52 ±0.12) ( P<0.01).Nucleo-cytoplasmic translocation of HMGB1 was observed in hepatocarcinoma cells . Conclusion There is increased expression of HMGB1 in HCC tissues, which shows HMGB1 mediates the carcinogenesis of HCC .

Objective To investigate the significance of determination for binding ratio of L-PHA(leukoagglutinating phytohemagglutinin) with serum alkaline phosphatase in the diagnosis of primary hepatic cancer.Methods The binding ratios of L-PHA with serum alkaline phosphatase in 50 healthy individuals,103 cases of primary hepatic cancer,22 cases of hepatocirrhosis,36 cases of chronic hepatitis,18 cases of acute hepatitis and 13 cases of digestive tract tumor were determined by lectin affinity chromatography.Results The binding ratio of L-PHA with serum alkaline phosphatase in primary hepatic cancer(16.01% 5.42%) were significantly increased as compared with the healthy control(7.50% 2.53%)(P 0.01).The binding ratios were positively correlated with the tumor size and AFP level.Conclusion The binding ratio of L-PHA with serum alkaline phosphatase is a potential parameter for the laboratory diagnosis of primary hepatic cancer.

Objective To evaluate the association of angiotensin (AGT ) gene M235T polymorphism with essential hypertension (EH) .Methods The literatures examining the association of the M 235T polymorphisms with EH were selected in electronic data-bases .Using RevMan5 .0 ,heterogeneity and pooled effect sizes were calculated .Results Totally ,29 articles ,with 5 971 cases and 6 443 controls were finally included in this study .The odds ratio (OR) value of TT+ TM∶MM genotype was 1 .13 (95% CI 1 .00-1 .25 ,P=0 .04) in worldwide populations .Subgroup analysis showed that the OR values of TT ∶MM genotype were 1 .13 (95% CI 0 .90-1 .42 ,P=0 .28) in subjects published before 2008 and 1 .29(95% CI 0 .94-1 .75 ,P=0 .11) in those after 2008(year of 2008 included) .The OR values of T ∶M in Han population was 1 .24 (95% CI 1 .01-1 .53 ,P=0 .04) .Conclusion TT+ TM genotype of the M235T polymorphisms is associated with EH in worldwide populations ,and T allele is also correlated with EH in Han popu-lation .

ObjectiveTo establish an analytical method with high sensitivity and wide range in biotin-avidin and time-resolved fluoroimmunoassay system for the quantitative detection of antinuclear antibody (ANA)-Ig (GAM).MethodsANA in standard preparation or sample was combined with solid nuclear antigen,biotinylation antibody and the europium(Eu3+)-labelled avidin to form the compounds of solid nuclear antigen-antibody-biotinylation antibody-SA-Eu3+.The fluorescence enhancement fluid was added to dis-sociate the Eu3+,the content of ANA was directly proportional to fluorescence intensity,the BAS-TRFLA was established for the quantitative detection of ANA-Ig (GAM).The sensitivity,specificity,reliability and range of detection were evaluated.Semm of 50 blood donor,105 patients with systemic lupus erythematosus (SLE),109 patients with rheumatoid arthritis(RA),25 patients with PBC,29 patients with Sj(o)gren's syndrome (SS),23 patients with scleroderma,25 patients with MCTD were included in this study.The positive rate was calculated.ResultsThe inner-group difference between high,medium and low densities mixture serum was 3.13％,3.74％ and 5.76％ and the inter-group precision rate was 5.31％,6.25％ and 7.46％ in BAS-TRFLA.The sensitivity of TRFIA was better than that of the ELISA method.The low detection limit was 2.24 U/ml.The mean recovery rate was 100.74％.The results measured by the TRFIA and ELISA methods were closely correlated(R2=0.978).The positive rate of blood donor,and patient with SLE,RA,PBC,SS,scleroderma and MCTD were 0,100％,23％,96％,38％,91％,92％ respectively.When compared with ELISA,the detection range of TRFIA was wider,and stability was better.ConclusionBAS-TRFIA is a stable method for detection of ANA with high sensitive and wide range of detection.It is important for the early diagnosis of autoimmune disease and monitoring the treatment efficacy of autoimmune disease.And this method may be widely used in clinical laboratories in the future.

Objective To investigate the distribution of hepatitis B virus (HBV) genotypes in patients with chronic HBV infections and the correlations of genotypes with liver fibrosis and hepatocellular carcinoma (HCC).Methods Serological,virological and pathological data of 190 patients with chronic HBV infections admitted to Hangzhou First People's Hospital during June 2007 and June 2012 were retrospectively analyzed.The series included 62 cases of chronic hepatitis B (CHB),60 cases of liver cirrhosis and 68 cases of HCC.HBV was genotyped by multiplex PCR,and subgenotyped by restriction fragment length polymorphism (RFLP).SPSS 11.0 was used for statistical analysis.Results Among 190 patients,61 were HBV genotype B (32.1％),126 were genotype C (66.3％),and 3 were B + C hybrid.HBV B2 (61/61,100.0％) and C2 (123/126,97.6％) were the major subgenotypes.HBV genotype B was more prevalent in CHB patients (46.8％,29/62) than in liver cirrhosis (20.0％,12/60) and in HCC patients (29.4％,20/68) (x2 =8.73 and 4.16,P＜0.01 or P＜0.05),whereas the prevalence of genotype C was higher in liver cirrhosis and HCC than that in CHB (x2 =9.54 and 4.17,P ＜0.01 or P ＜ 0.05).Patients with genotype C2 had higher serum hyaluronic acid level than with genotype B2 in 3 groups (t =2.685,2.433 and 2.015,P ＜ 0.01 or P ＜ 0.05).CHB patients with C2 infections had higher liver fibrosis grade than those with B2 (x2 =6.726,P =0.010),while there was no statistical difference in liver inflammation grade (x2 =0.601,P ＞ 0.05).HCC patients with B2 infection tended to have larger tumor diameter (≥5 cm) (x2 =7.231,P ＜ 0.01) and those with C2 infection were prone to be more serious cirrhosis (x2 =4.910,P ＜ 0.05).Conclusions HBV genotypes C2 and B2 are predominant in patients with chronic HBV infections in Hangzhou.HCC patients infected with HBV C2 may be complicated with more severe liver fibrosis,and those with HBV B2 infections may tend to have larger liver tumor.