Objective To investigate the correlation between RNF213 gene polymorphisms (rs112735431,rs138130613,and rs148731719) and the susceptibility of intracranial vascular stenosis disease.Methods The literature of studies on the correlation between RNF213 gene polymorphisms and intracranial vascular stenosis disease was collected according to the related databases.Using the Stata 12.0 software and selecting suitable genetic model,the heterogeneity was analyzed and the pooled odds ratio (OR) and its 95％ confidence interval (CI) were calculated.Results A total of 12 articles were included after screening.The result of meta-analysis showed that the rs112735431 polymorphism had a significant correlation with the susceptibility of moyamoya disease (MMD) in all genetic models,especially the most significant dominant model (AA + GA genotype vs.GG genotype:OR 101.46,95％ CI 59.41-173.27;P ＜0.001),at the same time,the polymorphism of this site also had significant correlation with the nonMMD intracranial large artery stenosis/occlusion (AA + GA genotype vs.GG genotype:OR 13.82,95％ CI 4.48-42.61;P＜ 0.001);the rs138130613 polymorphism had significant correlation with the susceptibility of MMD in Chinese population (OR 5.01,95％ CI 1.57-15.98;P=0.006);and no correlation between the rs148731719 polymorphism and the susceptibility of MMD was observed.Conclusions The RNF213 gene rs112735431 polymorphism is a susceptible factor of MMD,at the same time,the polymorphism of this site is also associated with the formation of non-MMD intracranial large artery stenosis.Systematic study on the molecular function of RNF213 may have important significance for diagnosis and treatment of such vascular stenosis diseases.

[Abstract ] Objective Bioinformatics provides a lot of valuable information for online prediction of new genes.In this study, we predicted the biological function of ubiquitin-conjugating enzyme 2S ( UBE2S) based on bioinformatics. Methods The UBE2S gene was screened and cloned from the cDNA library of human HepG2 cells.The relationship of the structure and function of UBE2S was explored based on the full-length cDNA library.MEGA5.05, CLUSTALW2 and SWISS-MODEL were used to study the phylogeny, conservation, and 3D structure of UBE2S. Results The UBE2S gene encoded a polypeptide of 241 residues with a predicted molec-ular weight of 23 770 and an isoelectric point of 8.81.The UBE2S protein contained no transmembrane locus and the probabilities of their functions of growth factors, cation channel and structural protein were 8.904, 0.313, and 0.291.The analysis of BLASTp showed that the isolated UBE2S had a 90-97%identity with the other species. Conclusion Analysis of the structure and function of the UBE2S protein can not only provide more information about its gene family but also pave the way for further experimental studies on the molecular mechanism of the consequent hepatocellular carcinoma.

Human acute premyeloid leukemia cell cDNA expression library was constructed to screen acute premyeloid leukemia tumor antigen. Total RNA and purified mRNA were extracted from human premyeloid cell line NB4. First and second strands of cDNA were synthesized by reverse transcription. After blunting, the cDNA fragments were ligated with EcoR I adapters. Then the cDNAs were digested with Xho I, and less than 400 bp cDNA fragment was removed by Sephacryl-S400 spin column, the remaining were ligated with lambdaZAP vector. The recombinants were packaged in vitro, and a small portion of packaged phage was used to infect E. coli XL1-Blue-MRF' for titration. The recombinants were examined by color selection. In order to evaluate the size of cDNA inserts and the diversity of library, the pBK-CMV phagemid was excised from the ZAP express vector by using ExAssist helper phage with XLOLR strain, and then the pBK-CMV phagemid was digested by Xho I and EcoR I. The results showed that the NB4 cell line cDNA library consisting of 1.65 x 10(6) recombinant bacteriophages was constructed with the recombinant ratio of 99.6%. The average length of the recombinant exogenous inserts was about 1.7 kb. It was concluded that the constructed cDNA library are deserved to screen target clones.
Bacteriophages/genetics ; DNA, Complementary/*biosynthesis ; *DNA, Neoplasm/biosynthesis ; DNA, Recombinant/biosynthesis ; *Gene Library ; Genetic Vectors ; Leukemia, Promyelocytic, Acute/*genetics ; Leukemia, Promyelocytic, Acute/metabolism ; Leukemia, Promyelocytic, Acute/pathology ; RNA-Directed DNA Polymerase/metabolism ; Transcription, Genetic/genetics

Human acute premyeloid leukemia cell cDNA expression library was constructed to screen acute premyeloid leukemia tumor antigen. Total RNA and purified mRNA were extracted from human premyeloid cell line NB4. First and second strands of cDNA were synthesized by reverse transcription. After blunting, the cDNA fragments were ligated with EcoR I adapters. Then the cDNAs were digested with Xho I, and less than 400 bp cDNA fragment was removed by Sephacryl-S400 spin column, the remaining were ligated with lambdaZAP vector. The recombinants were packaged in vitro, and a small portion of packaged phage was used to infect E. coli XL1-Blue-MRF' for titration. The recombinants were examined by color selection. In order to evaluate the size of cDNA inserts and the diversity of library, the pBK-CMV phagemid was excised from the ZAP express vector by using ExAssist helper phage with XLOLR strain, and then the pBK-CMV phagemid was digested by Xho I and EcoR I. The results showed that the NB4 cell line cDNA library consisting of 1.65 x 10(6) recombinant bacteriophages was constructed with the recombinant ratio of 99.6%. The average length of the recombinant exogenous inserts was about 1.7 kb. It was concluded that the constructed cDNA library are deserved to screen target clones.
Bacteriophages ; genetics ; DNA, Complementary ; biosynthesis ; DNA, Neoplasm ; biosynthesis ; DNA, Recombinant ; biosynthesis ; Gene Library ; Genetic Vectors ; Humans ; Leukemia, Promyelocytic, Acute ; genetics ; metabolism ; pathology ; RNA-Directed DNA Polymerase ; metabolism ; Transcription, Genetic ; genetics

T-Vec（talimogene laherparepvec）是由Ⅰ型单纯疱疹病毒（HSV-1）改造而来的一种溶瘤病毒，能够选择性地在恶性肿 瘤细胞中复制而不伤及其他正常细胞。T-Vec在治疗晚期黑色素瘤患者的Ⅲ期临床试验中显示出良好的安全性和肿瘤治疗效 果，已于2015年经美国FDA批准用于治疗晚期黑色素瘤。为了提高T-Vec的疗效，扩大其应用范围，T-Vec联合其他抗肿瘤疗法 以及应用于其他肿瘤的临床试验仍在陆续开展。近期，T-Vec联合免疫检查点抑制剂在治疗晚期黑色素瘤的临床试验中取得新 进展，临床数据显示T-Vec联合疗法具有更强的抗肿瘤活性。此外，T-Vec在治疗头颈癌、胰腺癌、肝癌等肿瘤的临床研究中也取 得了一定进展。本文对近年来T-Vec治疗肿瘤的临床试验的相关研究进展做一综述。

Extracellular vesicles (EVs) have recently received much attention about the application of drug carriers due to their desirable properties such as nano-size, biocompatibility, and high stability. Herein, we demonstrate orange-derived extracellular vesicles (OEV) nanodrugs (DN@OEV) by modifying cRGD-targeted doxorubicin (DOX) nanoparticles (DN) onto the surface of OEV, enabling significantly enhancing tumor accumulation and penetration, thereby efficiently inhibiting the growth of ovarian cancer. The obtained DN@OEV enabled to inducement of greater transcytosis capability in ovarian cancer cells, which presented the average above 10-fold transcytosis effect compared with individual DN. It was found that DN@OEV could trigger receptor-mediated endocytosis to promote early endosome/recycling endosomes pathway for exocytosis and simultaneously reduce degradation in the early endosomes-late endosomes-lysosome pathway, thereby inducing the enhanced transcytosis. In particular, the zombie mouse model bearing orthotopic ovarian cancer further validated DN@OEV presented high accumulation and penetration in tumor tissue by the transcytosis process. Our study indicated the strategy in enhancing transcytosis has significant implications for improving the therapeutic efficacy of the drug delivery system.