Analysis of hypermutation of the 5’ noncoding region in the BC L-6 gene

Objective To investigate BCL-6 gene mutations in Chinese populations with B-cell non- Hodgkin’s lymphoma.Methods Polymerase chain reaction (PCR), denaturing gradient gel electrophoresis (DGGE) and direct DNA sequencing were used to identify mutations in the 5’ noncoding re gion of the BCL-6 gene in a total of 40 cases of diffuse large-cell lymphoma ( DLCL) and follicular lymphoma (FL).Results Nine cases were found to have base substitutions.The incidence of BCL-6 gene mutation and the frequency of single-base changes were approximately 25.7% an d (0.56-1.10)×10(-2)/bp, respectively.Conclusions The 5’ regulatory region of the BCL-6 gene undergoes frequent somatic hypermuta tion during lymphomagenesis and the identification of BCL-6 gene hypermutations provides a molecular marker for confirmatory diagnosis of B-NHL.     

Sustained Release of Metformin via Red Blood Cell Accumulated Sulfenamide Prodrug

Metformin is a first-line antidiabetic drug to treat type 2 diabetes. It is rapidly eliminated from plasma but also accumulated into red blood cells (RBCs) from which it is slowly released back into plasma. The aim of the study was to evaluate whether the amount of metformin in the RBCs could be increased by a sulfenamide prodrug approach, which could provide longer duration of metformin in systemic circulation. Pharmacokinetic properties of metformin and its cyclohexyl sulfenamide prodrug were evaluated in plasma and in whole blood after intravenous and oral administration in rats. Once the sulfenamide prodrug reached the bloodstream, it was rapidly and efficiently accumulated into the RBCs, where it was converted to metformin by free thiols. The RBC–whole blood ratio of metformin was increased approximately from 42% to 96% when metformin was administered intravenously as its sulfenamide prodrug, and the proportion of metformin in the RBCs was found to be concentration and time independent. Because metformin was slowly liberated into plasma, the prodrug showed a sustained-release pharmacokinetic profile and longer plasma half-life for metformin after oral administration. Therefore, this sulfenamide prodrug has great potential to improve metformin therapy as the daily doses could be reduced.     

恒温湿化氧疗在气管切开患者中的效果观察

目的：探讨恒温湿化氧气吸入对气管切开患者氧疗效果的影响。方法将60例气管切开吸氧患者随机分为实验组和对照组,所有患者在气管切开前均无肺部感染、无肺部慢性疾病、APACHE Ⅱ评分8分以上。实验组采用恒温湿化氧疗,对照组采用湿化瓶吸氧＋间歇湿化法,比较两组患者呼吸频率、氧饱和度、氧分压、二氧化碳分压、气道湿化效果、痰痂形成、呼吸道刺激症状、呼吸道粘膜出血及肺部感染率等方面的差异。结果实验组心率、氧饱和度、动脉血氧分压、二氧化碳分压以及湿化满意度均优于对照组,差异有统计学意义（P＜0.05）。结论气管切开病人采用恒温湿化氧疗湿化效果较好。     

甲状腺手术行喉返神经解剖显露的临床分析

目的探讨甲状腺术中喉返神经的解剖及显露的临床意义,以减少喉返神经损伤。方法回顾性分析965例甲状腺手术患者的临床资料,所有手术均在全嘛下进行并常规显露喉返神经,手术切除范围由病变情况决定,并对喉返神经解剖特点、损伤情况进行分析。结果共解剖显露喉返神经1052条,其中右侧721条,左侧331条,包括双侧87条;采用上方入路解剖86条,侧方661条,下方305条;右侧喉返神经位于气管食管沟内走行者461条,偏离者260条;左侧位于气管食管沟内走行者285条,偏离者46条;喉返神经入喉前有分支者687条（65．3％）,未分支直接人喉者365条（34．7％）;喉不返神经2条;解剖神经平均用时（6．7±0．54）min;术后神经暂时性损伤11例,永久性损伤2例,均于6个月后对侧声带代偿,嘶哑改善。结论熟悉喉返神经的解剖,灵活运用不同的解剖入路,常规解剖显露神经,是避免喉返神经损伤的有效方法。     

Investigation of microRNA expression signatures in HCC via microRNA Gene Chip and bioinformatics analysis

BackgroundDysregulation of miRNAs is closely involved with hepatocellular carcinoma (HCC) progression, oncogenesis and signalling pathways. The aim of this study was to investigate differences in expression of miRNAs in HCC tissue in comparison to healthy liver tissue, as well as to explore the key miRNA-targeted genes.MethodsGene Chip microarray analysis was used to analyse differentially expressed miRNAs (DEMs) in tissues, and qRT-PCR was performed to validate the top 9 downregulated miRNAs. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed for target genes using the DAVID database. A protein-protein interaction (PPI) network of the target genes was created by STRING and visualised using Cytoscape. Three online miRNA databases were utilised to aid in the prediction of genes targeted by the top 10 significantly altered DEMs.ResultsIn total, 153 upregulated and 206 downregulated miRNAs were identified in HCC tissue. The genes targeted by the top 10 increased and decreased miRNAs were 6 and 1060, respectively. Moreover, FOXO1 was projected to be regulated by all twenty miRNAs. A PPI network was constructed that consisted of 956 nodes and 1298 edges. Four significant modules, consisting of 66 hub genes, were detected from the PPI system via MCODE. Functional enrichment demonstrated that miRNAs have a vital function in cancer development and advancement.ConclusionIn summary, our study identified DEMs in HCC tissue, major target genes and possible molecular mechanisms that underlie HCC, providing novel insights for treatment approaches.     

索拉非尼联合TACE术治疗中晚期肝细胞癌30例临床观察

目的观察索拉菲尼联合经导管肝动脉化疗栓塞术（TACE）对中晚期肝细胞癌的疗效以及血清血管内皮生长因子的变化。方法将2007年12月至2009年4月入住我院无法手术切除的中晚期肝细胞癌患者60例随机分为两组,每组各30例。治疗组：索拉菲尼＋TACE术。对照组：单纯行TACE术。索拉菲尼于TACE术后5d开始口服。400mgbid,至少服用3个月,每位患者行TACE术不少于两次,并检测TACE术前1周及术后2周血清VEGF水平。结果治疗组有效率为50.0%,对照组36.7%,组间比较差异无统计学意义（P〉0.05）;治疗组疾病控制率为83.3%,对照组53.3%,组间比较差异有统计学意义（P〈0.05）;治疗组中位肿瘤进展时间为6.2个月,对照组中位TTP为3.1个月,组间比较差异有统计学意义（P〈0.001）;治疗组1年生存率为83.3%,对照组为56.7%,组间比较差异有统计学意义（P〈0.05）;治疗组血清VEGF下降显著（P〈0.05）,对照组治疗前后血清VEGF水平对比,差异无统计学意义（P〉0.05）。治疗组及对照组毒副反应均为Ⅰ-Ⅲ度,经对症处理后症状可缓解。治疗组腹泻、手足综合征、皮疹、高血压等症状与对照组比较,差异有统计学意义。结论索拉菲尼联合TACE术能改善不能手术中晚期肝癌患者的疾病控制率,并降低血清VEGF水平,可延长患者生存期且其毒副作用可以耐受。