Background and purpose:Regulation of MMR activity under hypoxia may play an important role in genetic instability of cancer,but the mechanism is still unclear.We investigated the expression of DNA mismatch repair genes MLH1 and MSH2 in human SCLC cell line H446 under hypoxic condition and explore the role of promoter methylation of genes in hypoxia.Methods:RT-PCR and Western blot were applied to detect MLH1 and MSH2 expression in human SCLC cell line H446 at the mRNA and the protein level,respectively,under either hypoxic condition or after 5-Aza-CdR treatment.Meanwhile,methylation-specific PCR(MSP)was used to determine promoter methylation of MLH1 and MSH2.Results:The expression of MLH1 and MSH2 in H446 cells significantly decreased both at the mRNA and the protein level under hypoxic condition.5-Aza-CdR treatment led to the restoration of MLH1 and MSH2 expression,while,both MLH1 and MSH2 were down-regulated again after removing 5-Aza-CdR.Conclusions:The promoter methylation of MLH1 and MSH2 may play an important role in its defective expression in H446 cells under hypoxic condition.And 5-Aza-CdR could restore MLH1 and MSH2 expression.

Objective To screen for clopidogrel metabolism related gene CYP2C19 in patients with coronary artery disease in Wuhan.Methods 316 patients,from Jan to Dec 2014,after cardiology percutaneous coronary interventional therapy (PCI) for the treatment of coronary artery disease were selected as research object.Clopidogrel metabolism related CYP2C19 geno-types (* 1,* 2,* 3)were detected by the gene chip,and for different types of metabolism of patients according to CYP2C19 gene type:strong metabolize type (*1/*1),intermediate metabolizer types (*1/*2,*1/*3),poor metaboli-zer types (*2/*2,*3/*3,*2/*3).Results According to the CYP2C19 gene polymorphism of metabolic function type, strong metabolic type carrying CYP2C19*1 (*1/*1)accounted was 43.4%,intermediate metabolizers carrying CYP2C19*2 or *3 (* 1/* 2 and * 1/* 3)and poor metabolizers (* 2/* 2,* 2/* 3 and * 3/* 3)accounted was 42.4% and 14.2%,respectively.Different gender had no statistical significance in CYP2C19 genotype differences.Conclusion Clopi-dogrel metabolism functional of CYP2C19 gene in patients with interventional coronary heart disease in Wuhan area had more deletion gene.

This work was carried out to investigate the effects of clonidine on some electrophysiological properties of the neurons of guinea-pig celiac ganglia in vitro, using the technique of intracellula.r recording. 54 neurons were examined, among which 18 neurons were found to be sensitive to clonidine. There were 3 reaction types in the sensitive cells, depolarization with decrease of membrane resistance, hyperpolarization with increase of membrane resistance and biphasic reaction ( depolarization followed by hyperpolarization ) . Clonidine depolarization was not blocked by low Ca^/high Mg2+ solution, pro-pranolol and yohimbine. However, it was reversibly blocked by prazo-sin. The experimental results show that clonidine has some! effects on the membrane potential and membrane resistance of the neurons of guinea-pig celiac ganglia,

OBJECTIVETo observe the morphological changes of photoreceptor cells in rats with retinitis pigmentosa (RP) induced by N-methyl-N-Nitrosourea (MNU) and the effects of acupuncture against it.

METHODSA total of 16 SD rats were treated with one-time intraperitoneal injection of MNU (50 mg/kg) to induce RP, and randomly divided into an acupuncture group and a model group, 8 rats in each one. In addition, 4 rats were selected as a control group. After model establishment, rats in the acupuncture group were treated with acupuncture at "Xinming-1" (Extra) and "Jingming" (BL 1) for 30 min, once a day for 7 days; rats in the model group and control group received no treatment, and the feeding conditions and fixation were identical as the acupuncture group. 2 h after the end of intervention, rats were sacrificed by cervical dislocation to observe the morphological changes of rhodopsin, rod terminals and rod bipolar cells.

RESULTSDue to the loss of retina photoreceptor cells induced by MNU in rats, in the model group the rhodopsin was stained in residual cell bodies, and there were sporadic rod terminals and little rod bipolar cells; outer segments, inter segments, cell bodies and cell terminals were all affected at different levels. The distribution of rhodopsin was also changed in the acupuncture group, showing more bodies of photoreceptor cells, and the residual rod terminals and rod bipolar cells were more than those in the model group; the injury of retina was less than that in the model group.

CONCLUSIONMNU could lead to a comprehensive injury to the morphology of photoreceptor cells, however, acupuncture is capable of inhibiting morphological changes of photoreceptor cells induced by MNU.

Acupuncture Therapy ; Animals ; Humans ; Male ; Photoreceptor Cells ; cytology ; Rats ; Rats, Sprague-Dawley ; Retinitis Pigmentosa ; physiopathology ; therapy

Objective To study the expression of WWOX gene in non-small cell lung cancer and its significance. Methods WWOX protein expression was evaluated by immunohistochemistry in 81 NSCLC patients(50 squamous cell carcinomas,31 adenocarcinomas and 20 adjacent normal lung tissues),and correlation with histopathologic(histotype,grade,tumor-node-metastasis,stage) and clinical characteristics was studied. Results WWOX expression was absent/reduced in 72.8% of NSCLC,whereas it was normal in 80.0% of adjacent normal lung tissues.WWOX expression was strongly associated with tumor histology and histologic grade(P

OBJECTIVE:Study on the efficiency of azithromycin sustained-release vaginal suppository in inhibiting ureaplasma urealyticum(Uu)in vitro.METHODS:The method of microdilution was used to determine the minimal inhibitory concentration(MIC)for Uu that azithromycin sustained-release vaginal suppository campared with azithromycin dried suspension. RESULTS:The MIC for Uu that both azithromycin sustained-release vaginal suppository and azithromycin dried suspension is lower than 0.125?g?mL~(-1).CONCLUSION:Azithromycin sustained release vaginal suppository has significant inhibitive effects on Uu under the experiment condition.

Objective To investigate the role of methylated DNA mismatch repair gene MLH1 and MSH2 in the acquired multidrug-resistance of human small cell lung cancer cells H446.Methods The reverse transcription polymerase chain reaction(RT-PCR)and Western blot were applied to measure MLH1 and MSH2 mRNA and protein expressions of the multidrug-resistant cells H446/DDP and its parental cells H446.The promoter methylation status of the genes was assessed by methylation-specific PCR(MSP).Results The expressions of MLH1 and MSH2 significantly decreased both in mRNA level and protein level.Promoter methylation of MLH1 was observed in H446/DDP cells but not in H446 cells.Promoter semi-methylation of MSH2 in H446 cells was transformed to methylation in H446/DDP cells.Conclusion The downregulation of DNA mismatch repair gene MLH1 and MSH2 induced by its promoter methylation may play an important role in the acquired multidrug resistance of human small cell lung cancer.

Objective To investigate the effect of hypoxic preconditioning on hepatocytes early growth response factor 1 ( EGR-1 ) in a rat liver autotransplantation. Methods The rat portal vein perfusion model was established for donor liver autotransplantation. Rats were then divided into group A:hypoxic preconditioning was done before transplantation; group B: rats undergoing liver transplantation without preconditioning; group C: Normal control group of rats. Liver histopathological changes, the mRNA expression of HIF-1, TNF-1 and the WB results of EGR-1 were compared between groups. Results The expression of HIF-1 α RNA determined in group A was more obvious than in group B and group C. Six hours after surgery, the expression in group A was significantly higher than that in group B (t =9. 601, df= 10, 2-tailed Sig = 0. 000, P<0. 05 ) ; Egr-1 protein expression in group A and group B increased after surgery,with that in group A being significantly lower than that in group B. The RT-PCR expression of TNF-α RNA in group B compared with group A and group C was more obvious. Six hours after operation, the expression of TNF in group B was significantly higher than that in group A ( t = -12. 067, df = 10, 2-tailed Sig =0. 000, P<0. 05 ). The expression of Egr-1 was positively correlated with that of TNF. A liver cell pathology showed less severe injury in structure of hepatic lobule, mild swelling of liver cells, no significant changes in liver tissue. Conclusions Hypoxic preconditioning adaptation in rat liver transplantation generates modest increase in EGR-1, and reduces the production of TNF and other inflammatory factors.

CDISC standard has become a set of global data standards that can be used in clinical study, covering the full life cycle of clinical researches. After nearly 20 years of development and continuous version upgrades, CDISC standard can improve the quality and efficiency of clinical research and drug review, and to facilitate all stakeholders involved in researches to exchange the study data and communicate the outcomes. CDISC standard has been or is to be adopted as standard format in data submission by multiple regulatory authorities, and more widely implemented by the global pharmaceutical community. CDISC standard is gradually adopted in China. The feasibility and roadmap of CDISC standard as the Chinese data submission format requirements are undergoing exploration and piloting further.

OBJECTIVE:To investigate the characteristics of cecum and colon-specific drug delivery system of 4-aminosalicyl-ic acid-maltoside (4-ASA-Mal) in vitro. METHODS:With the cumulative release rate of 4-ASA as the index,HPLC was em-ployed to observe the delivery of 4-ASA-Mal (equivalent to 250 μg/ml 4-ASA) in the buffer solutions of different pH (1.2,6.8 and 7.4)and in the aqueous contents in different parts(stomach,small intestine,cecum and colon)of normal rats and the rat mod-els of ulcerative colitis. RESULTS:4-ASA-Mal was hardly released in the buffer solutions of different pH. 12 h cumulative release rates were less than 8% in the aqueous contents in the stomachs and small intestines of normal rats and rat models,and were 55%and 81% in the aqueous contents in the cecum and colons of normal rats,and 55% and 74% in the aqueous contents in the cecum and colons of model rats with ulcerative colitis. CONCLUSIONS:4-ASA-Mal can release a lot of 4-ASA in aqueous contents in ce-cum and colon,targeting cecum and colon in vitro.