5-脂氧合酶抑制TNF-α诱导的胰腺癌细胞凋亡

目的:检测胰腺癌细胞中5-脂氧合酶(5-lipoxygenase,5-LOX)及其代谢产物的表达情况,分析高表达5-LOX及LTB4对胰腺癌细胞生长凋亡的影响.方法:体外培养人胰腺癌细胞株ASPC-1,PANC-1和SW1990,并构建5-LOX基因稳定转染细胞株.用RT-PCR和Western blot检测细胞5-LOX mRNA和蛋白的表达,ELISA检测细胞培养上清中LTB4的含量,采用流式细胞仪、Annexin V/PI双染法检测TNF-α诱导细胞的细胞凋亡.结果:三种胰腺癌细胞株均表达5-LOX mRNA和蛋白,细胞上清中也都检测到一定量LTB4分泌.5-LOX基因稳定转染细胞株表达5-LOX和LTB4的水平上升.TNF-α(20μg/L)处理野生型SW1990细胞,12和24 h后凋亡率分别为25.4%±3.65%和43.5%±5.23%,但该效应在高表达5-LOX的细胞株中明显减弱,分别为13.2%±2.01%和21.7%±3.65%.在野生型SW1990细胞培养中加入外源性LTB4(10 nmol/L)能抑制TNF-α诱导的细胞凋亡,野生型与处理组细胞24 h后凋亡率有显著性差异(47.6%±5.32%vs 18.5%±5.69%,P<0.01).用LTB4受体阻断剂处理5-LOX高表达细胞株,能恢复其对凋亡诱导的敏感性.结论:胰腺癌细胞均能表达5-LOX并产生LTB4,高表达5-LOX能抑制TNF-α诱导的胰腺癌细胞凋亡.     

SUMO4 and its role in type 1 diabetes pathogenesis

Susceptibility to type 1 diabetes (T1D) is determined by interactions of multiple genes with unknown environmental factors. Despite the characterization of over 20 susceptibility regions for T1D, identification of specific genes in these regions is still a formidable challenge. In 2004, we first reported the cloning of a novel, small ubiquitin-like modifier (SUMO) gene, SUMO4, in the IDDM5 interval on chromosome 6q25, and presented strong genetic and functional evidence suggesting that SUMO4 is a T1D susceptibility gene. Subsequent studies have consistently confirmed this association in multiple Asian populations despite controversial observations in Caucasians. In this review, we will update the genetic evidence supporting SUMO4 as a T1D susceptibility gene and discuss the possible explanations for the discrepant associations observed in Caucasians. We will then discuss the mechanisms through which SUMO4 contributes to the pathogenesis of T1D.     

Risk of Type 1 Diabetes Progression in Islet Autoantibody-Positive Children Can Be Further Stratified Using Expression Patterns of Multiple Genes Implicated in Peripheral Blood Lymphocyte Activation and Function

There is tremendous scientific and clinical value to further improving the predictive power of autoantibodies because autoantibody-positive (AbP) children have heterogeneous rates of progression to clinical diabetes. This study explored the potential of gene expression profiles as biomarkers for risk stratification among 104 AbP subjects from the Diabetes Autoimmunity Study in the Young (DAISY) using a discovery data set based on microarray and a validation data set based on real-time RT-PCR. The microarray data identified 454 candidate genes with expression levels associated with various type 1 diabetes (T1D) progression rates. RT-PCR analyses of the top-27 candidate genes confirmed 5 genes (BACH2, IGLL3, EIF3A, CDC20, and TXNDC5) associated with differential progression and implicated in lymphocyte activation and function. Multivariate analyses of these five genes in the discovery and validation data sets identified and confirmed four multigene models (BI, ICE, BICE, and BITE, with each letter representing a gene) that consistently stratify high- and low-risk subsets of AbP subjects with hazard ratios >6 (P < 0.01). The results suggest that these genes may be involved in T1D pathogenesis and potentially serve as excellent gene expression biomarkers to predict the risk of progression to clinical diabetes for AbP subjects.     

大鼠肾移植模型手术改良技巧探讨

目的探讨大鼠肾移植模型手术的改良方法。方法供体Sprague-Dawley(SD)大鼠21只,受体Wistar大鼠42只。采用双侧供肾。受体左肾切除后借助自制导管,行受体肾动脉与供体肾动脉、受体肾静脉与供体下腔静脉端端吻合,供体输尿管带膀胱瓣与受体膀胱吻合,最后切除右肾,腹腔内注入头孢米诺10 mg,关腹。记录手术时间,动、静脉吻合时间,冷、热缺血时间等手术数据;术后大鼠存活3 d认为模型建立成功,计算建模成功率,分析死亡原因。结果供体手术时间为(32.7±5.6)min,供肾修整时间为(4.2±1.1)min。受体手术时间为(42.3±4.9)min,其中动脉吻合时间为(10.1±3.2)min,静脉吻合时间为(13.9±2.5)min,尿路重建时间为(6.3±1.4)min。热缺血时间为(5.4±1.8)s,冷缺血时间为(56.2±7.3)min。42只受体大鼠中,建模成功40只,成功率为95%。另2只受体大鼠死亡,其中1只死于血管吻合口出血,1只死于尿瘘引致的腹膜炎。结论采用改良的血管端端吻合法建立大鼠肾移植模型具有操作简单、手术时间短、成功率高的特点。     

钴合金和钛合金的细胞毒性研究

对植入材料磨损态的Co-29Cr-5Mo(CCM)和Ti-6Al-4V(Ti64)的细胞毒性进行研究。与固溶态相比,在完全培养液中,通过噻唑蓝(MTT)法研究两种合金在不同浸提浓度、不同浸提时间下的材料浸提液对小鼠成纤维细胞(L929)的毒性及影响机制。扫描电子显微镜(SEM)观察腐蚀前后材料表面的变化,ICP发射光谱仪(ICP-MS)检测CCM和Ti64合金中主要金属离子的释放,电化学工作站(CHI760E)表征两种磨损态合金在完全培养液中的腐蚀情况。MTT实验结果表明:磨损态的两种合金随材料浸提浓度和时间的增大,细胞的相对增殖率(RGR)均减小,其中CCM的RGR由98.36%减小至73.28%,细胞毒性由0级升至2级;Ti64的RGR减小至85.86%,细胞毒性升至1级。ICP-MS结果表明,磨损态合金有害离子的释放量随着浸提时间不断上升,浸提至168 h时,磨损态CCM合金Co和Cr释放量分别高达1 249.7和293.9 μg/L;磨损态Ti64合金Al和V释放量分别为30.7和19.7 μg/L。CCM的Tafel曲线和SEM分析表明,在完全培养液中,CCM表面化学位较高的棱、尖角以及微米级沟壑位置发生了缝隙腐蚀,造成金属离子的释放,并对L929细胞的生长和分裂产生抑制作用。     

Identification and molecular characterization of a single-stranded circular DNA virus with similarities to Sclerotinia sclerotiorum hypovirulence-associated DNA virus 1

A putative circular single-stranded DNA (ssDNA) virus was recovered from Hypericum japonicum collected in Vietnam. The viral isolate was tentatively named Hypericum japonicum-associated circular DNA virus (HJasCV). HJasCV shares 58.7-65.4% nucleotide sequence identity with Sclerotinia sclerotiorum hypovirulence-associated DNA virus 1 (SsHADV-1) and SsHADV-1-like viruses. Like this group of viruses, the genome of HJasCV (2 200 nt) has two large ORFs, one in the virion-sense and the other in the complementary-sense DNA. The proteins encoded in the virion-sense and complementary-sense ORFs share 39-46 % and 45-67 % amino acid sequence identity with the putative capsid and replication-associated proteins (Reps), respectively, of SsHADV-1 and SsHADV-1-like viruses. The putative Rep of HJasCV contains all of the motifs related to rolling-circle replication. Its 111-bp intergenic region (IR) contains a hairpin structure with a geminivirus-like nonanucleotide sequence, TAATGTTAT, at the apex of the loop. Phylogenetic analysis revealed that HJasCV forms a monophyletic clade with SsHADV-1 and SsHADV-1-like viruses.     

Influence of oxygen exposure on fermentation process and sensory qualities of Sichuan pickle (paocai)

The physicochemical and microbial changes, volatile profile, texture and appearance were investigated in three groups of Sichuan pickles differing in oxygen exposure during a 64 day fermentation process. At the beginning, all the Sichuan pickles displayed similar sensory and fermentation characteristics regarding lactic acid bacteria domination, sugar utilization, and lactate accumulation. Soon afterwards, continued exposure allowed premature pellicle formation and typical aerobic deterioration of Sichuan pickle, accompanied by texture destruction and an odorous stench characterized by arenes and aldehydes on the 32^nd day. Meanwhile, the facultative anaerobes including Lactobacillus (90 ± 2%), Pediococcus (4.7 ± 0.3%) and Lactococcus (1.2 ± 0.8%) were the dominant genera and probably associated with acetic acid production and arene enrichment under oxygen exposure conditions on the 32^nd day. Until the 48^th day, intermittent oxygen exposure resulted in pellicle formation and an unpleasant flavor characterized by ketones, esters and S-methyl thioacetate. In comparison, Sichuan pickle without oxygen exposure always maintained a relatively favorable fragrant scent and texture. Besides Lactobacillus, anaerobic genera were the main bacteria in Sichuan pickle under closed conditions and accounted for 50 ± 9% of the total bacteria on the 32^nd day. The study indicated the microbial and chemical characteristics of Sichuan pickles during practical production and provided a theoretical guidance for the industrial production of Sichuan pickle.

The physicochemical and microbial changes, volatile profile, texture and appearance were investigated in three groups of Sichuan pickles differing in oxygen exposure during a 64 day fermentation process.     

Radiotheranostic Targeting Cancer Stem Cells in Human Colorectal Cancer Xenografts

Molecular Imaging and Biology - The aim of this study was to perform radiotheranostics with radioiodinated monoclonal antibodies (mAbs) for targeting cancer stem cells (CSCs) in human colorectal...     

迷你临床演练评估方法在新护士第1年规范化培训中的应用

目的:观察迷你临床演练评估(Mini-CEX)方法提高毕业第1年新护士规范化培训的效果。方法:采用整群抽样法,以陆军军医大学新桥医院2017年入职的新护士91名为对照组,2018年入职的新护士120名为试验组。对照组采用常规培训方法。试验组在此基础上,将常规教学查房和操作训练改为每月1次Mini-CEX方法下的临床护理核心能力训练和临床护理操作技能培训,连续12次。采用配对样本t检验比较试验组第1次和第12次训练的Mini-CEX得分,采用独立样本t检验比较两组新护士理论和操作考核成绩。结果:试验组第12次的临床护理核心能力训练和临床护理操作技能训练的Mini-CEX得分分别为(6.27±0.46)、(6.73±1.10)分,均高于第1次得分,差异有统计学意义(t值分别为-8.48、-7.64;P<0.01);试验组新护士在1年规范化培训中,科室理论考核和操作考核成绩分别为(87.70±11.32)、(92.90±8.22)分,院级理论考核和操作考核成绩分别为(85.50±11.83)、(89.67±8.99)分,均高于对照组,差异有统计学意义(t值分别为-2.71、-2.09、-2.24、-3.22;P<0.05)。结论:Mini-CEX对提高毕业第1年新护士培训效果作用显著。