A risk analysis based on a two-stage delayed diagnosis regression model with application to chronic disease progression

This paper presents a two-stage regression model for quantifying different stages of a disease progression with delayed diagnosis time and for identifying the risk factors associated with each stage. Conventional chronic disease progression studies reported replied on the assumption that the time of the confirmation of a disease state by diagnosis is the start time of this disease state. Clearly this will lead to biased estimates of progression since the disease state should have already occurred before the diagnosis, but the true occurrence time is unknown. This later confirmation is called the delayed diagnosis in this paper and a delay-time modelling procedure is developed for the identification of the unknown stages of progression. A hazard-based regression model is also proposed for a further risk analysis. We apply the developed methods to hepatitis C data and the analysis shows that considering the delayed diagnosis significantly improved the model fit in comparison with the conventional model. We also find that the risk factors associated with each stage are more significant, particularly in the second stage of progression, than those based on the conventional model. We conclude that such delayed phenomena in diagnosis should be taken into account when modelling the chronic disease progression process and conducting related risk analysis.     

乙型肝炎病毒表面抗原三维结构的同源模建及功能预测

结合生物信息学方法及分子模拟手段, 通过同源模建方法构建了乙型肝炎病毒表面抗原(HBsAg)Pres12的三维空间结构, 并结合生物实验在分子水平上探讨了乙型肝炎病毒表面抗原Pres12作为抗乙型肝炎病毒重要靶标的机理. 研究结果表明, HBsAg三维空间结构是由构型性的Pres1和线性的Pres2组成, 此结构由疏水氨基酸形成3个α-螺旋结构及Loop结构域, 并且N端由Pres1中残基构成了一个开裂, 形成了HBsAg可能的活性部位. 静电势分析结果证实, N端可能的活性部位具有较大的静电势分布, 因而具有与受体细胞蛋白相互作用的能力, 这为HBV病毒抑制剂药物分子的设计提供了有益帮助.     

HCV全基因组培养细胞的比较蛋白组学研究

利用比较蛋白质组技术研究了转染丙型肝炎病毒(Hepatitis C virus, HCV)全基因组的人肝癌细胞系Huh7细胞模型中蛋白质表达谱的变化, 建立了Huh7-HCV的双向凝胶电泳蛋白质表达图谱和数据库. 通过双向凝胶电泳分离和图像分析, 对表达差异2倍以上蛋白质点进行了胶内酶解和MALDI-TOF MS鉴定. 得到包括与细胞骨架蛋白、细胞周期、凋亡和信号转导等相关的14个蛋白质, 并且用Western blot验证了热休克蛋白70的蛋白质组研究结果. 利用HCV全基因组培养系统, 采用蛋白质组学技术, 为研究HCV病毒和宿主细胞相互作用提供了新的实验数据, 为深入研究HCV病毒复制和分子致病机理奠定了基础.     

A branch and bound algorithm for dynamic resource allocation in population disease management

We embed an approximate dynamic program into a branch-and-bound framework to solve sequential resource allocation problems in population disease management. The proposed algorithm is capable of providing an optimality guarantee and getting bounds on the optimality gap of healthcare interventions. A numerical study on screening and treatment policy implementation for chronic hepatitis C virus (HCV) infection provides useful insights regarding HCV elimination for baby boomers.     

复方绞股蓝液治疗HBV携带者160例疗效分析

用复方绞股蓝液治疗１６０例ＨＢＶ携带者（治疗组），用灭澳灵片、脾转移因子或聚肌胞针治疗１００例同期病例（对照组），总有效率：治疗组７７．５％，对照组６３．００％，Ｐ＜０．０５，治疗组明显优于对照组。     

新型免疫电极法测定乙型肝炎表面抗原

本文报道一种新型的乙型肝炎抗体膜片。测试时,仅需将25μl被检血清滴注于该膜上,经孵育与洗涤即可制得抗原与抗体复合物膜。用复合物膜组装成免疫电极,测定血清样品中乙型肝炎表面抗原含量。电极的线性范围是20～320ng/ml,方法的日间相对标准偏差为10.78％(n=4,m=5),对血清中可能存在的一些其它抗原具有较好的选择性。105例临床血清样本,本法与酶联免疫吸附分析法测定结果符合率为86％。乙肝抗体膜片系一次性使用,4℃可保存半年以上。     

对氟苯酚-H_2O_2-HRP体系酶联荧光免疫分析研究ⅢF~--Al-酸性铬蓝K荧光熄灭法测定人血清中乙肝E抗原

建立了一种检测人血清中乙肝Ｅ抗原的新荧光光度法．通过酶促反应：对氟苯酚＋Ｈ２Ｏ２ＨＲＰ→苯酚＋Ｆ－＋Ｈ２Ｏ与Ａｌ－酸性铬蓝Ｋ荧光体系相偶合，测定辣根过氧化物酶（ＨＲＰ）及其标记物．测定ＨＲＰ的线性范围为０．１９～３１ｍＵ／ｍＬ，检出限为０．０４ｍＵ／ｍＬ．     

丙肝电化学免疫传感器在血清检测中的应用

丙型肝炎病毒(hepatitis C virus,HCV)是丙肝的致病因子,该病毒自70年代发现以来,就一直困扰着人类。丙肝已成为近年来最为严重的传染病之一。目前临床诊断丙肝的主要方法有血清学非特异性检测[1]和特异性检测(酶联免疫分析方法、重组免疫印迹、聚合酶链反应[2]等)。血清学非特     

Highly sensitive electrochemical stripping detection of hepatitis B surface antigen based on copper-enhanced gold nanoparticle tags and magnetic nanoparticles

On the basis of copper-enhanced gold nanoparticle tags as an amplification approach, we introduced, in this paper, magnetic nanoparticles for further improving performance of electrochemical immunoassay by anodic stripping voltammetry (ASV) at a glassy-carbon electrode. Due to the use of antibody-immobilized magnetic nanoparticles, the immunoreaction between antibody and antigen takes place in a homogeneous bulk solution phase. Compared with traditional solid interface reaction, the proposed strategy can provide some advantages such as easy of separation, shorter analytical time, wider linear range, and lower detection limit. It was also successfully applied to HBsAg determination in a linear range of 0.1-1500 ng mL⁻¹ with a detection limit of 87 pg mL⁻¹. The proposed analytical strategy holds good selectivity, sensitivity and repeatability and also great promise for the extended application in the fields of clinical diagnosis, bio-affinity assay and environmental monitoring.