Lifestyle Risk Score: handling missingness of individual lifestyle components in meta-analysis of gene-by-lifestyle interactions

Recent studies consider lifestyle risk score (LRS), an aggregation of multiple lifestyle exposures, in identifying association of gene-lifestyle interaction with disease traits. However, not all cohorts have data on all lifestyle factors, leading to increased heterogeneity in the environmental exposure in collaborative meta-analyses. We compared and evaluated four approaches (Naïve, Safe, Complete and Moderator Approaches) to handle the missingness in LRS-stratified meta-analyses under various scenarios. Compared to “benchmark” results with all lifestyle factors available for all cohorts, the Complete Approach, which included only cohorts with all lifestyle components, was underpowered due to lower sample size, and the Naïve Approach, which utilized all available data and ignored the missingness, was slightly inflated. The Safe Approach, which used all data in LRS-exposed group and only included cohorts with all lifestyle factors available in the LRS-unexposed group, and the Moderator Approach, which handled missingness via moderator meta-regression, were both slightly conservative and yielded almost identical p values. We also evaluated the performance of the Safe Approach under different scenarios. We observed that the larger the proportion of cohorts without missingness included, the more accurate the results compared to “benchmark” results. In conclusion, we generally recommend the Safe Approach, a straightforward and non-inflated approach, to handle heterogeneity among cohorts in the LRS based genome-wide interaction meta-analyses.Subject terms: Genetics, Risk factors     

骨髓间质干细胞体外分化为成骨细胞的实验研究

建立猪骨髓间质干细胞 (mesenchymalstemcells ,MSCs)体外分离培养方法。对猪MSCs体外分化为成骨细胞的能力进行研究。抽取猪骨髓 ,体外培养MSCs。取第二代MSCs ,以含有不同浓度的抗坏血酸、β -磷酸甘油、地塞米松及碱性成纤维细胞生长因子等条件培养基进行成骨细胞诱导分化。通过细胞形态变化 ,碱性磷酸酶染色及钙盐沉积对成骨细胞进行鉴定。结果表明MSC细胞形态由长梭形向多边形转变 ,ALP染色阳性 ,VonKossa染色阳性 ,经体外诱导分化后呈典型的成骨细胞样改变。猪骨髓MSCs可在体外长期、稳定培养 ,具有向成骨细胞分化的潜能 ,可以为骨组织工程研究提供较理想的细胞来源和动物模型。     

Molecular epidemiology of Vibrio cholerae O139 in China: polymorphism of ribotypes and CTX elements

Vibrio cholerae O139, the second etiological serogroup of cholera, triggered the first outbreak of O139 cholera in China in 1993. To analyze the clone polymorphism of O139 isolates in China, 117 strains of V. cholerae O139, isolated from different areas in China between 1993 and 1999, were selected to characterize the phylogenetic relationships by molecular techniques. Analysis of restriction fragment length polymorphism in the conserved 16S rRNA gene revealed seven different ribotypes within the 117 strains. Among these strains, there were eight that lacked the cholera toxin gene (ctxAB), zot, and the repetitive sequence (RS); these eight strains belonged to three individual ribotypes. Our results suggested that V. cholerae O139 strains in China had clone diversity in phylogeny. The results of our hybridization patterns for CTX genetic elements (ctxAB, zot, and RS) showed that CTXPhi genomes in most V. cholerae O139 strains had two or more copies and had extensive restriction patterns even for the strains which belong to the same ribotype. For 22 (20.1%) strains, the copies of ctxAB were different from those of zot, suggesting that a ctxAB-negative CTXPhi genome may exist in O139 strains. This ctxAB-negative CTXPhi genome may coexist with the intact CTXPhi genome in a strain. In addition, the dendrogram for I-CeuI-generated pulsed-field gel electrophoresis patterns showed that V. cholerae serogroup O139 has a closer relationship with one strain of serogroup O22 than with the strains of serogroup O1. The results of this study showed the clonal diversity and the distribution of O139 strains in China, suggesting multiple origins of the O139 cholera epidemic or sporadic events.     

全髋关节置换术均衡双下肢长度的探讨

目的探讨全髋关节置换术均衡双下肢长度的临床意义和手术设计。方法回顾分析2000-2004年获得随访的单侧全髋关节置换手术病例48例,采用骨水泥型假体12髋,混合型假体36髋,术前双下肢等长30例(含股骨颈骨折患者),10例患肢长度短缩1.0-2.0cm,6例短缩2.0-4.0cm,2例短缩4.0-6.0cm。通过术前肢体长度测量及X片测量制定手术方案,选择假体、预估颈长和截骨平面;术中正确磨削髋臼,寻找最佳旋转中心,结合透视及特殊试验修正截骨平面,调节假体颈长,达到均衡双下肢长度的目的。结果全部病例采用Harris评分,优30例,良12例,中4例,差2例。术前等长30例巾术后出现5例手术侧延长1.0-2.0cm,1例延长2.5cm。术前不等长的18例中,术后恢复等长10例,6例手术侧延长1.0-2.0cm,2例术前重度短缩的先天性髋关节发育不良病人术后仍然短缩2.0-3.0cm。术后肢体等长35例Harris评分平均92.3分,术后肢体不等长13例Harris评分平均88.6分。结论全髋关节置换术的手术设计。手术技巧以及假体设计等诸多因素影响下肢长度,术后肢体不等长降低了患者的满意度。应重视术前测量及术中综合评价方法的运用,重视软组织平衡技术和肢长调节,掌握全髋置换术中均衡下肢长度的手术技术,进一步改善手术效果。     

腭部恶性肿瘤的CT诊断

探讨腭部恶性肿瘤的CT表现及其诊断价值。回顾性分析32例经病理证实的腭部恶性肿瘤的CT表现,其中男27例,女5例。所有病例均行横断增强扫描,其中8例同时行平扫,2例加冠状位扫描。腭部恶性肿瘤的CT表现为:(1)腭部肿块(26例)、腭部软组织增厚(6例)和腭骨质破坏(6例),其中病变位于软腭(22例)、硬腭(4例)、软硬腭交界处(3例);(2)邻近结构受累及(27例);(3)颈部淋巴结转移(17例)。CT是一种优良的检查技术,能显示腭部恶性肿瘤的大体病理改变以及侵犯途径,为临床治疗和预后提供重要信息。     

Age-dependent and iron-independent expression of two mRNA isoforms of divalent metal transporter 1 in rat brain

The DMT1(Nramp2/DCT1) is a newly discovered proton-coupled metal-ion transport protein. The cellular localization and functional characterization of DMT1 suggest that it might play a role in physiological iron transport in the brain. In the study, we evaluated effects of dietary iron and age on iron content and DMT1 expression in four brain regions: cortex, hippocampus, striatum, substantia nigra. Total iron content in all regions was significantly lower in the low-iron diet rats and higher in the high-iron diet rats than that in the control animals, showing that dietary iron treatment for 6-weeks can alter brain iron levels. Contrary to our expectation, there was no significant alternation in DMT1(+IRE) and (-IRE) mRNA expression and protein content in all brain regions examined in spite of the existence of the altered iron levels in these regions after 6-weeks' diet treatment although TfR mRNA expression and protein level were affected significantly, as was expected. The data demonstrates that expression of DMT1(+IRE) and (-IRE) was not regulated by iron in these regions of adult rats. The lack of response of DMT1 to iron status in the brain suggests that the IRE of brain DMT1 mRNA might be not really iron-responsive and that DMT1-mediated iron transport might be not the rate-limiting step in brain iron uptake in adult rats. Our findings also showed that development can significantly affect brain iron and DMT1(+IRE) and (-IRE) expression but the effect varies in different brain regions, indicating a regionally specific regulation in the brain.     

失血性休克对大鼠血管平滑肌BKCa通道酪氨酸磷酸化水平的影响

目的:探讨失血性休克对大鼠肠系膜上动脉血管平滑肌BK_Ca通道酪氨酸磷酸化的影响以及NO对BK_Ca通道酪氨酸磷酸化的调控。方法:建立大鼠失血性休克模型[(35±5)mmHg]并提取肠系膜上动脉总裂解蛋白,采用免疫沉淀及免疫印迹技术,观察休克血管平滑肌BK_Ca通道酪氨酸磷酸化的变化情况;采用原代培养的大鼠肠系膜上动脉血管平滑肌细胞,观察NO对BK_Ca通道酪氨酸磷酸化的调控及其时-效、量-效关系。结果:失血性休克2 h及4 h后大鼠肠系膜上动脉血管平滑肌BK_Ca通道α亚基酪氨酸磷酸化明显增强 (P＜0.01 );L-精氨酸(5×10^-5-5×10^-4 mol/L)孵育30 min即可诱导培养血管平滑肌细胞BK_Ca通道α亚基酪氨酸磷酸化增强,2 h内无明显下降;且L-精氨酸诱导BK_Ca通道α亚基酪氨酸磷酸化具有剂量依赖性。结论:重症失血性休克可增强血管平滑肌BK_Ca 通道酪氨酸磷酸化,且NO参与了该调控过程。     

个体化出院指导应用于高血压病患者的效果分析

目的：探讨个体化出院指导对高血压患者依从性的影响。方法：将80例患者随机分为实验组和对照组，分别给予个体化出院指导联合一般性出院指导和单用一般性出院指导，出院三个月和六个月时跟踪随访。结果：实验组的依从性明显好于对照组，出院后随访病情复发率明显降低（P〈0.05〉。结论：个体化出院指导可提高高血压患者依从性，改善患者的社会适应能力，降低复发率。     

Rapid identification and susceptibility testing using the VITEK(R) 2 system using culture fluids from positive BacT/ALERT(R) blood cultures

BACKGROUND AND PURPOSE: In order to reduce the turnaround time for laboratory diagnosis of bacteremia, the efficacy of identification and antimicrobial susceptibility testing using samples taken directly from positive BacT/ALERT(R) standard aerobic and standard anaerobic blood culture bottles was evaluated. METHODS: 160 positive blood culture bottles were examined and incubated at 35 degrees C in 5% carbon dioxide for 4-24 h, and an aliquot of the culture fluid was Gram stained. Samples containing Gram-negative bacilli were inoculated on VITEK(R) 2 ID-GNB (identification-Gram-negative bacilli) and AST (antimicrobial susceptibility testing)-GN04 cards, and those containing Gram-positive cocci were inoculated on ID-GPC (identification-Gram-positive cocci) and AST-P526 cards. The same samples were also examined by the standard method, involving subculture from positive BacT/ALERT standard blood culture bottles. RESULTS: Eighty seven of 97 Gram-negative bacilli (89.7%) and 21 of 63 Gram-positive cocci (33.3%) were correctly identified to the species level. For antimicrobial susceptibility testing, the direct method had an overall error rate of 5.4% for Gram-negative bacilli, with 0.9% very major, 0.9% major, and 3.6% minor discrepancies compared to the standard method. The overall error rate in antimicrobial susceptibility testing for the 13 Staphylococcus spp. was 10.3%, with 6.0% very major, 2.6% major, and 1.7% minor discrepancies. CONCLUSION: These data suggest that VITEK 2 cards inoculated with samples taken directly from positive Bact/ALERT blood culture bottles would provide acceptable identification and antimicrobial susceptibility testing results for Gram-negative bacilli, but not for Gram-positive cocci. Compared to the standard method, the direct method would reduce turnaround time by at least 24 h.