Background and purpose:In recent studies, the Notch-1 gene has been found to play an important role in the development of human glioblastoma.Short interfering RNA(siRNA) was used to silence the Notch-1 gene and block its expression.The objective was to determine whether siRNA targeting Notch-1 would inhibit the formation and growth of tumors in nude mice that modeled human glioblastoma.Methods:The human glioblastoma cell line TJ905 were first cultured and transfected with Notch-1 siRNA or nonsense siRNA by OligofectamineTM.The TJ905 cells were divided into 3 groups:the Notch-1 siRNA transfected group, nonsense siRNA transfected group and the control group.Each group's cells were subcutaneously injected into 5 nude mice.The nude mice(males, 3-4 weeks old) were given subcutaneous injections of either 0.2 mL of transfected siRNA or with normal TJ905 cells suspended at a 1?107 cells/mL concentration in a DMEM medium without serum.One week later, when the tumors were palpable, they were directly injected with the Notch-1 siRNA complex, nonsense siRNA complex, or PBS every 4 days for 20 days.Tumor sizes were measured every 3 days and calculated by the formula:volume(mm3) =1/2 length?(width)2.After a 20-day follow-up period, the mice were exterminated.Immunohistochemistry was used to determine the expression of Notch-1 gene.Results:The final tumor volume was less in nude mice injected with Notch-1 siRNA(1 203?206) mm3 compared mice injected with the nonsense siRNA injection(2 241?401) mm3, P

Objective Evaluation of efficacy and safety of combination of Yinxin Damo injection and low molecular heparin for deep venous thrombosis (DVT) in orthopedics operation.Methods Randomized controlled trials of combination of Yinxin Damo injection and low molecular heparin intervention study of DVT in orthopedics operation were searched from the Cochrane Library,clinicaltrials,gov,PubMed,EMBASE,CNKI,Wanfang database,VIP database,and Chinese biomedical database (CBM).According to the Cochrane Handbook 5.1,Meta analysis was performed by Revman 5.3 software.Results A total of 4 studies included 358 patients.The results of Meta-analysis showed that,compared with control group,incidence of DVT was significantly reduced (P =0.01),value of D-D significantly decreased (P ＜0.000 01) and value of PT increased (P =0.04),and increased value of APTT (P =0.07) in combined group.Heterogeneous sources of PT and APTT were analyzed,and the results after excluding literature 7,as compared with the control group,APTT and PT were significantly increased in combined group (P ＜ 0.000 1).Conclusion Based on the current clinical evidence,combination of Yinxin Damo injection and low molecular heparin treatment for DVT of orthopedics operation patients is effective and safe,but there is certain heterogeneity between the studies,therefore it is necessary to design a randomized controlled trial of high quality,large scale and multicenter to research.

A total of 192 patients with sepsis were tested by Montreal Cognitive Assessment (MoCA) for a preliminary diagnosis of whether or not there was sepsis associated encephalopathy (SAE) according to their test results.SAE was diagnosed or excluded after consultations and comprehensive analysis on the basis of clinical manifestations and auxiliary examination results.The scores of the patients in this group were (25.7 ± 3.3) points.The sensitivity of MoCA for screening SAE was 0.776 and its specificity 0.963.The rate of diagnostic coincidence between MoCA and comprehensive analysis for SAE was 0.880.The diagnostic concordance between two diagnostic methods of SAE was excellent (kappa value =0.753 ± 0.048,P =0.000).The area under the receiver operating characteristic (ROC) curve of MoCA for screening SAE was 0.929 ± 0.019 (P =0.000) ; the optimal cutoff value was 25.5 points; and its sensitivity was 0.779 and specificity 0.962.And negative correlations existed between score of MoCA and age,disease course and co-existing shock or multiple organ dysfunction syndrome (P ＜ 0.05).

Background::Heterotaxy (HTX) is a thoracoabdominal organ anomaly syndrome and commonly accompanied by congenital heart disease (CHD). The aim of this study was to analyze rare copy number variations (CNVs) in a HTX/CHD cohort and to examine the potential mechanisms contributing to HTX/CHD.Methods::Chromosome microarray analysis was used to identify rare CNVs in a cohort of 120 unrelated HTX/CHD patients, and available samples from parents were used to confirm the inheritance pattern. Potential candidate genes in CNVs region were prioritized via the DECIPHER database, and PNPLA4 was identified as the leading candidate gene. To validate, we generated PNPLA4-overexpressing human induced pluripotent stem cell lines as well as pnpla4-overexpressing zebrafish model, followed by a series of transcriptomic, biochemical and cellular analyses. Results::Seventeen rare CNVs were identified in 15 of the 120 HTX/CHD patients (12.5%). Xp22.31 duplication was one of the inherited CNVs identified in this HTX/CHD cohort, and PNPLA4 in the Xp22.31 was a candidate gene associated with HTX/CHD. PNPLA4 is expressed in the lateral plate mesoderm, which is known to be critical for left/right embryonic patterning as well as cardiomyocyte differentiation, and in the neural crest cell lineage. Through a series of in vivo and in vitro analyses at the molecular and cellular levels, we revealed that the biological function of PNPLA4 is importantly involved in the primary cilia formation and function via its regulation of energy metabolism and mitochondria-mediated ATP production. Conclusions::Our findings demonstrated a significant association between CNVs and HTX/CHD. Our data strongly suggested that an increased genetic dose of PNPLA4 due to Xp22.31 duplication is a disease-causing risk factor for HTX/CHD.