64排螺旋CT血管成像对2型糖尿病并冠心病的诊断价值

目的探讨64排螺旋CT血管成像（CTA）对2型糖尿病（T2DM）并冠心病（CAD）的冠状动脉病变的诊断价值。方法收集32例T2DM并CAD患者选择性冠状动脉造影（CAG）和CTA的影像资料,以CAG为金标准,以节段血管为评价单位,评估CTA诊断T2DM并CAD冠状动脉病变的准确性。结果CTA对T2DM并CAD患者冠状动脉病变的诊断敏感性为92.56%,特异性为93.56%,阳性预测值为82.96%,阴性预测值为97.38%,准确率为93.31%,能良好地反应T2DM并CAD患者冠状动脉病变的特点。T2DM并CAD患者冠状动脉钙化较严重,人均受累9.25个节段。随着钙化积分的增高,特异性在下降,但最低也达到87.39%,并且保持了良好的敏感性和阳性预测值。结论CTA是诊断T2DM并CAD冠状动脉病变较可靠、无创的检查方法。T2DM并CAD冠状动脉钙化广泛而严重,钙化对CTA结果判断的影响较小。     

非小细胞肺癌中HPV感染与EGFR、VEGF表达的相关性研究

目的:研究非小细胞肺癌(non-small cell lung cancer,NSCLC)中人乳头瘤病毒(human papillomavirus,HPV)感染与血管内皮生长因子(vascular endothelial growth factor,VEGF)和表皮生长因子受体(epidermal growth factor receptor,EGFR)表达的关系,探讨它们在肺癌发病中的作用。方法:采用PCR方法检测89例NSCLC和20例肺良性病变中HPV感染的情况;免疫组化SP法检测NSCLC的HPV( )组和HPV(-)组中VEGF、EGFR分别表达的情况。结果:NSCLC组中HPV感染率(35/89)明显高于肺良性病变组(1/20)(P=0.007)。HPV( )组VEGF和EGFR的表达均明显高于HPV(-)组,P值均<0.01。HPV( )、EGFR( )组和HPV( )、EGFR(-)组中VEGF的表达无明显差异。HPV感染与肺癌组织的分化程度、淋巴结转移明显相关,而与组织学类型、吸烟、性别和年龄无关;VEGF的表达与肺癌的淋巴结转移明显相关,而与其他临床病理特征无明显相关性;EGFR的表达与各临床病理特征均无明显相关性。结论:HPV的感染与NSCLC的发生存在一定的相关性,HPV的感染可能通过促进VEGF、EGFR的表达,使肺癌易发生淋巴管生成,导致肺癌易通过淋巴结转移,预防HPV的感染对降低肺癌的发生及减少肺癌的早期转移可能有着重要的意义。     

急性冠状动脉综合征患者血浆低密度脂蛋白免疫复合物的变化及意义

目的:探讨低密度脂蛋白免疫复合物(LDL-IC)在急性冠状动脉综合征(ACS)发生发展过程中的作用及其临床意义。方法:采用酶联免疫吸附法测定139例冠心病患者(ACS组76例,非ACS组63例)及111例正常对照组的血清LDL-IC浓度。根据冠状动脉造影结果将冠心病组分为多支病变组(病变≥2支)及单支病变组(1支病变)进行比较。结果:①ACS患者LDL-IC水平显著高于非ACS冠心病患者[(2.78±1.08)AU(相对单位)vs(1.74±0.45)AU,P<0.01]和正常对照组[(2.78±1.08)AUvs(1.55±0.71)AU,P<0.01]。②多支病变组LDL-IC水平高于单支病变组[(2.60±1.10)AUvs(1.82±0.50)AU,P<0.01]及正常对照组[(2.60±1.10)AUvs(1.55±0.71)AU,P<0.01]。③LDL-IC水平与氧化低密度脂蛋白(ox-LDL)水平呈显著正相关(r=0.348,P<0.01)。结论:LDL-IC与ACS的发生发展及冠状动脉病变程度之间可能存在一定的相关性。     

A Prediction Model of Tumor Progression and Survival in HER2-Positive Metastatic Gastric Cancer Patients Treated with Trastuzumab and Chemotherapy

The effects of different patient factors and dose levels of chemotherapeutic agents on clinical outcomes in advanced gastric cancer are not as yet fully characterized. We aimed at developing an integrative model that incorporates dose and covariate information to predict tumor growth and patient survival in advanced gastric cancer patients treated with trastuzumab (T), 5-FU(F)/capecitabine (X) (F or X), and cisplatin (P). Sixty-nine patients (training dataset) were used for model building and a separate 86 patients (test dataset) for model validation. A fraction of tumor cells sensitive to each drug was incorporated as a model parameter, and T was assumed as cytostatic and X/F and P as cytotoxic. Cox proportional hazards analyses were performed on model parameters and patient covariates. The model well described the time course of observed tumor size changes, and revealed that the pretreatment tumor growth rate constant k_g, which was formulated as a function of pretreatment disease duration and baseline tumor size, was positively correlated with baseline tumor size (p?=?0.0084) and histologic grade (p?=?0.034), and the efficacy of 5-FU with body weight (p?<?2e?16) and that of cisplatin with histologic grade (p?=?0.00013). Prior gastrectomy and Eastern Cooperative Oncology Group scores were significant prognostic factors for progression-free survival (PFS). For hazards analysis, a unit increase of k_g was associated with a relative risk of 3.19 for PFS (p?=?0.00055) and 4.45 for OS (p?=?2e?04) in the test dataset, with a similar trend observed in the training dataset. Dose-response simulations showed that, for small baseline tumor size or low histologic grade, a maximum cytotoxic effect was attainable with a dose smaller than the current recommended dose.     

Population PK-PD Model of Pegylated Interferon Alfa-2a in Healthy Korean Men

Pegylated interferon alfa-2a (PEG-IFN alfa-2a), which was developed to overcome the disadvantages of conventional formulations, is widely prescribed for hepatitis B or C virus infection. It is characterized by pharmacokinetic (PK) and pharmacodynamic (PD) properties much different from those of conventional forms. The present study developed a population PK-PD model of subcutaneous PEG-IFN alfa-2a in a Korean population. For PK, IFN alfa-2a concentrations were described by a 1-compartment model with first-order absorption, preceded by skin-to-depot first-order input. For PD, serum 2’-5’ oligoadenylsynthetase activity was described by an effect compartment model incorporating a tolerance compartment. The baseline serum 2’-5’ oligoadenylsynthetase level was found to have an inverse relationship with sensitivity to tolerance, leading to high tolerance at low baseline. The model revealed that subjects with low baselines experienced time delay, while those with high baselines showed tolerance in their concentration-effect relationships. The developed models matched well with data and simulation results, and the model showed that the optimal dose decreases with the baseline, with no dose effective for a baseline >250 pmol/dL. Our results can serve as a basis for improving dosing regimens of PEG-IFN alfa-2a in adult patients with chronic hepatitis B or C infection.     

不同冠根比的后牙种植义齿5年临床疗效评价

目的:评价不同冠根比的后牙区种植义齿的临床效果。方法:选择2007年1月—2012年1月来诊接受后牙区种植的119例患者,共植入208颗ITI种植体并完成贵金属烤瓷冠修复。修复完成后,根据临床冠根比(crown-to-implant ratio,C/I)分为以下3组:C/I≤1,11.5。随访6～66个月,分别记录3组修复体机械并发症的发生情况。拍摄X线片,测量种植义齿的临床牙冠及牙根长度,计算C/I值及种植体周围骨吸收量。应用寿命表法计算C/I≤1及C/I>1的所有种植义齿的5年累积存留率,采用SPSS 13.0软件包对数据进行统计学分析。结果:所有种植体的平均临床冠根比为1.07±0.24,C/I最小0.6,最大1.8,机械并发症为9.6%。3组不同冠根比种植义齿的机械并发症发生几率及年均骨吸收量均无显著差异(P>0.05)。C/I>1的种植义齿5年累积存留率为97.6%,C/I≤1的5年累积存留率为98.8%。结论:种植义齿的冠根比与种植体周围骨吸收程度及机械并发症的发生几率无相关性,冠根比>1的种植义齿修复效果较好。     

The Iron-Sensing Fur Regulator Controls Expression Timing and Levels of Salmonella Pathogenicity Island 2 Genes in the Course of Environmental Acidification

In order to survive inside macrophages, Salmonella produces a series of proteins encoded by genes within Salmonella pathogenicity island 2 (SPI-2). In the present study, we report that Fur, a central regulator of iron utilization, negatively controls the expression of SPI-2 genes. Time course analysis of SPI-2 expression after the entry of Salmonella into macrophages revealed that SPI-2 genes are induced earlier and at higher levels in the absence of the Fur regulator. It was hypothesized that Fur repressed the SPI-2 expression that was activated during acidification of the phagosome. Indeed, as pH was lowered from pH 7.0 to pH 5.5, the lack of Fur enabled SPI-2 gene expression to be induced at higher pH and to be expressed at higher levels. Fur controlled SPI-2 genes via repression of the SsrB response regulator, a primary activator of SPI-2 expression. Fur repressed ssrB expression both inside macrophages and under acidic conditions, which we ascribe to the direct binding of Fur to the ssrB promoter. Our study suggests that Salmonella could employ iron inside the phagosome to precisely control the timing and levels of SPI-2 expression inside macrophages.     

具有高效降解地塞米松能力的伯克霍尔德菌CQ001株的分离及功能基因组学分析

目的 研究细菌对地塞米松类甾体激素的降解作用及其分子机制,为构建清除水环境医源性地塞米松类药物污染的工程菌奠定基础.方法 采用富集培养法从医院废水中分离降解地塞米松的细菌,采用固相萃取-高效液相色谱(HPLC)法检测细菌对地塞米松的降解效能,通过16S rDNA序列测定进行鉴定.用Illumina Hiseq4000结合第三代测序技术对降解菌的全基因组测序,并进行序列组装、注释和分析,对降解地塞米松相关基因进行RT-qPCR验证.结果 分离到1株对地塞米松有较高降解作用的细菌,经鉴定属于伯克霍尔德菌属(Burkholderia),命名为Burkholderia sp.CQ001.该菌对地塞米松磷酸钠及地塞米松的降解率分别为84.8％和77.11％.全基因组测序表明Burkholderia sp.CQ001包含2条染色体和4个巨型质粒,与代谢相关基因大部分集中在2号染色体上,共3 260 157 bp.生物信息学分析表明,该菌含有甾体代谢通路中许多重要酶类的编码基因,其中与地塞米松降解相关的有ABC转运子,3-甾酮-9 α-脱氢酶等,这些基因在以地塞米松磷酸钠为碳源的培养条件下表达量不同程度地高于以蔗糖为碳源的培养条件.结论 Burkholderia sp.CQ001是一株具有强大的代谢功能和代谢途径丰富的细菌,具有降解地塞米松类甾体激素的性能,该菌株为后续研究甾体激素的降解机制和构建清除水环境医源性地塞米松类药物污染的工程菌提供了菌种.