An intelligent hybrid approach for hepatitis disease diagnosis: Combining enhanced k‐means clustering and improved ensemble learning

In real world, the automatic detection of liver disease is a challenging problem among medical practitioners. The intent of this work is to propose an intelligent hybrid approach for the diagnosis of hepatitis disease. The diagnosis is performed with the combination of k‐means clustering and improved ensemble‐driven learning. To avoid clinical experience and to reduce the evaluation time, ensemble learning is deployed, which constructs a set of hypotheses by using multiple learners to solve a liver disease problem. The performance analysis of the proposed integrated hybrid system is compared in terms of accuracy, true positive rate, precision, f‐measure, kappa statistic, mean absolute error, and root mean squared error. Simulation results showed that the enhanced k‐means clustering and improved ensemble learning with enhanced adaptive boosting, bagged decision tree, and J48 decision tree‐based intelligent hybrid approach achieved better prediction outcomes than other existing individual and integrated methods.     

应用免疫斑点法检测不同工艺灭活的乙肝血源疫苗中的前S_1和S_2蛋白

作者应用前 S_1、前 S_2和 HBsAg/a 单克隆抗体,用免疫斑点法(Immuno-spot)检测同一批的乙肝表面抗原分别经加热灭活和三步化学灭活后的前 S_1和前 S_2蛋白保留情况,比较了两种工艺对前 S_1和前 S_2蛋白的影响。结果表明;加热灭活可保留前 S_1和前 S_2蛋白,三步化学灭活使前 S_1和前 S_2蛋白丢失,从抗原组成上看,加热灭活后的抗原更接近自然抗原。首次报告了含有前 S_1蛋白的乙肝疫苗,并对前 S_1和前 S_2蛋白在乙肝血源疫苗中的可能作用进行了讨论。     

CpG-ODN对乙肝核酸疫苗及重组疫苗免疫效果的影响

目的研究CpG寡聚脱氧核苷酸(CpGODN)对乙肝核酸疫苗及重组(CHO细胞)疫苗免疫效果的影响。方法核酸疫苗实验组用CpGODN与乙肝核酸疫苗联合免疫BALBc小鼠,阳性对照组注射核酸疫苗,阴性对照组注射质粒pVAX1;重组疫苗分4个实验组,用CpGODN与不同剂量的重组疫苗配伍后分别免疫BALBc小鼠,阳性对照组注射重组疫苗,阴性对照组注射生理盐水。应用ELISA检测小鼠血清中的抗HBs水平。结果CpG与乙肝核酸疫苗组抗体阳转率比阳性对照组提高3倍,抗体水平提高2倍。CpG与重组疫苗组的阳转率和阳转时间均高于或早于CpG与核酸疫苗实验组。加入CpGODN后,即使重组疫苗用量减少3倍,诱导抗体水平和阳转率均无明显改变。结论CpGODN可提高乙肝核酸疫苗和重组疫苗的免疫效果,并使抗体产生的时间提前。     

丙型肝炎负链RNA的检测及意义

检测HCV（－）RNA是了解HCV复制的有效手段。本研究采用HCV负链RNA检测法检查5例慢性活动性丙型肝炎病人的肝组织及10例慢性活动性肝炎病人的血浆及淋巴－单核细胞。HCV负链RNA在前者均被检出，但在后者未被检出。将一份HCV负链RNA阳性的肝组织提取液作10－2稀释后仍可测得阳性结果，说明肝脏为HCV复制的主要器官；该方法可用于疑难病人肝穿刺标本的检测及其它研究。     

联苯双酯中间体的合成

为考查联苯双酯中间体2-溴-3,4-亚甲二氧基-5-甲氧基苯甲酸甲酯的合成方法,采用先环合后溴代的合成路线．以没食子酸为原料,经甲酯化、甲醚化、二氯甲烷环合和溴代得2-溴-3,4-亚甲二氧基-5-甲氧基苯甲酸甲酯,总收率约37％,经IR和^1HNMR确证了结构．此合成工艺具有生产应用价值．     

Cytotoxic T Cell Expression of Leukocyte-Associated Immunoglobulin-Like Receptor-1 (LAIR-1) in Viral Hepatitis C-Mediated Hepatocellular Carcinoma

Virus-related hepatocellular carcinoma (HCC) pathogenesis involves liver inflammation, therefore, despite successful treatment, hepatitis C virus (HCV) may progress to HCC from initiated liver cirrhosis. Cytotoxic T cells (Tcs) are known to be involved in HCV-related cirrhotic complications and HCC pathogenesis. The inhibitory checkpoint leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is expressed on Tcs. Therefore, we aimed to determine whether the Tc expression level of LAIR-1 is associated with HCC progression and to evaluate LAIR-1 expression as a noninvasive biomarker for HCC progression in the context of liver cirrhosis related to HCV genotype 4 (G4) in Egyptian patients’ peripheral venous blood liquid biopsy. A total of 64 patients with HCC and 37 patients with liver cirrhosis were enrolled in this case-controlled study, and their LAIR-1 expression on Tc related to the progression of liver cirrhosis was examined and compared to that of the apparently healthy control group (n = 20). LAIR-1 expression was analyzed using flow cytometry. Results: The HCC group had significantly higher LAIR-1 expression on Tc and percentage of Tc positive for LAIR-1 (LAIR-1+Tc%) than the HCV G4-related liver cirrhosis group. LAIR-1+Tc% was correlated with the HCC surrogate tumor marker AFP (r = 0.367, p = 0.001) and insulin resistance and inflammation prognostic ratios/indices. A receiver operating characteristic (ROC) curve revealed that adding LAIR-1+Tc% to AFP can distinguish HCC transformation in the Egyptian patients’ cohort. Upregulated LAIR-1 expression on Tc could be a potential screening noninvasive molecular marker for chronic inflammatory HCV G4 related liver cirrhosis. Moreover, LAIR-1 expression on Tc may be one of the players involved in the progression of liver cirrhosis to HCC.     

Development and Use of a Kinetical and Real-Time Monitoring System to Analyze the Replication of Hepatitis C Virus

In microbiological research, it is important to understand the time course of each step in a pathogen’s lifecycle and changes in the host cell environment induced by infection. This study is the first to develop a real-time monitoring system that kinetically detects luminescence reporter activity over time without sampling cells or culture supernatants for analyzing the virus replication. Subgenomic replicon experiments with hepatitis C virus (HCV) showed that transient translation and genome replication can be detected separately, with the first peak of translation observed at 3–4 h and replication beginning around 20 h after viral RNA introduction into cells. From the bioluminescence data set measured every 30 min (48 measurements per day), the initial rates of translation and replication were calculated, and their capacity levels were expressed as the sums of the measured signals in each process, which correspond to the areas on the kinetics graphs. The comparison of various HuH-7-derived cell lines showed that the bioluminescence profile differs among cell lines, suggesting that both translation and replication capacities potentially influence differences in HCV susceptibility. The effects of RNA mutations within the 5′ UTR of the replicon on viral translation and replication were further analyzed in the system developed, confirming that mutations to the miR-122 binding sites primarily reduce replication activity rather than translation. The newly developed real-time monitoring system should be applied to the studies of various viruses and contribute to the analysis of transitions and progression of each process of their life cycle.     

Hepatotoxicity of Drugs Used in Multiple Sclerosis,Diagnostic Challenge,and the Role of HLA Genotype Susceptibility

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system and the association with other autoimmune diseases is well-documented. There are many therapeutic options for the treatment of MS. Most of the available drugs cause drug-induced liver injury (DILI) to variable extents with heterogeneous clinical and biological manifestations, including liver injury with or without signs of hypersensitivity and autoimmunity. The diagnosis of DILI may be particularly difficult because MS is frequently associated with idiopathic autoimmune hepatitis. Recent advances suggest that MS and immune-mediated DILI could be promoted by genetic factors, including HLA genotype. In addition, some of these drugs may promote hepatitis B virus reactivation. This review explores the potential hepatotoxicity of drugs used to treat MS and the criteria to distinguish DILI from idiopathic autoimmune hepatitis associated with MS. The role of susceptible genes both promoting MS and causing the hepatotoxicity of the drug used for MS treatment is also discussed.     

BAY41-4109对乙肝病毒衣壳组装的影响

乙肝病毒衣壳蛋白成功组装成衣壳二十面体的过程是病毒前基因组RNA逆转录形成成熟DNA的必要步骤。衣壳结构的轻微改变或破坏能对病毒子代传播产生巨大影响。应用透射电子显微镜研究发现小分子抗病毒化合物（heteroaryldihvdropyrimidine,HAP）BAY41．4109在与衣壳蛋白二聚体摩尔浓度比达到1：2时,能干扰乙肝病毒衣壳蛋白组装成衣壳二十面体。在BAY41—4109的作用下,衣壳蛋白发生错误组装,形成不规则球体、平面片状结构和管状结构。应用图像处理技术对管状结构进行分析,发现它是衣壳蛋白重新装配形成的具有螺旋对称性的规则组装体,衣壳蛋白按六角晶格方式排列,其最小组成单位是衣壳蛋白的二聚体。