Human biology-based drug safety evaluation: scientific rationale,current status and future challenges

Introduction: Animal toxicity studies used to assess the safety of new candidate pharmaceuticals prior to their progression into human clinical trials are unable to assess the risk of non-pharmacologically mediated idiosyncratic adverse drug reactions (ADRs), the most frequent of which are drug-induced liver injury and cardiotoxicity. Idiosyncratic ADRs occur only infrequently and in certain susceptible humans, but are caused by many hundreds of different drugs and may lead to serious illness.

Areas covered: Idiosyncratic ADRs are initiated by drug-related chemical insults, which cause toxicity due to susceptibility factors that manifest only in certain patients. The chemical insults can be detected using in vitro assays. These enable useful discrimination between drugs that cause high versus low levels of idiosyncratic ADR concern. Especially promising assays, which have been described recently in peer-reviewed scientific literature, are highlighted.

Expert opinion: Effective interpretation of in vitro toxicity data requires integration of endpoints from multiple assays, which each address different mechanisms, and must also take account of human systemic and tissue drug exposure in vivo. Widespread acceptance and use of such assays has been hampered by the lack of correlation between idiosyncratic human ADR risk and toxicities observed in vivo in animals.     

基于增强图卷积神经网络的病毒形态识别方法研究

背景 透射电子显微镜（TEM）是检测病毒的重要手段,传统TEM检测常依靠专家手工观察,操作步骤繁琐,且已有机器学习方法易受到背景、噪声的影响,导致病毒检测方法准确率差、效率低且耗时长。 目的 探讨增强图卷积神经网络（EGCN）对TEM图像中的病毒形态自动识别问题,以提高TEM病毒检测的效率。 方法 EGCN模型利用卷积神经网络（CNN）提取像素间的局部特征信息,并结合样本特征之间的最近邻关系利用图卷积网络（GCN）进行图特征学习。在模型优化中联合优化群体超分类损失和分类交叉熵损失以提高EGCN模型对病毒类别信息特征的提取能力,较CNN对TEM病毒图像特征具备更强的特征提取能力。 结果 通过不同方法在15类TEM病毒图像数据集上开展实验,EGCN达到3.40%的top-1错误率、1.88%的top-2错误率、96.65%的精确度和96.60%的召回率,并通过一系列对比实验表明EGCN模型可以有效避免TEM图像中背景、噪声等的影响,提高对病毒识别的准确率。 结论 EGCN可以有效解决病毒形态识别任务,为病毒的诊断提供重要的参考价值。     

我院2年间骨科髋关节置换术预防性应用抗菌药物的临床评价

目的:评价我院骨科髋关节置换术预防性应用抗菌药物整治活动的效果,以期逐步扩大抗菌药物专项整治成效,建立长效管理机制。方法:随机抽取我院骨科行髋关节置换术患者182例,其中2010年4月-2011年4月(整治活动前组)90例,2011年11月-2012年11月(整治活动后组)92例。对患者的自然情况、抗菌药物使用品种、使用时机、使用疗程等进行汇总及评价,并将结果应用SPSS 18.0软件进行统计分析,比较两组患者预防性应用抗菌药物的合理性。结果:开展抗菌药物专项整治后,抗菌药物预防性应用主要药物由第3代头孢菌素(31.11%)变为第1代头孢菌素(54.35%),其他各类药物的使用率均有显著下降(P<0.01);预防用药时机由大于术前2 h(58.89%)变为切皮前0.5² h(88.04%);用药疗程由平均(11.91±3.87)d变为(4.07±2.32)d;抗菌药物平均总费用下降71.06%。经过整治活动后药物选择不合理、术前用药不合理、更换药物不合理以及联合用药不合理的情况均有显著下降(P<0.01)。结论:抗菌药物专项整治活动后,我院骨科髋关节置换术预防性应用抗菌药物合理性得到明显改善,抗菌药物合理应用的长效管理机制已逐步建立。     

Rapid prenatal diagnosis of beta thalassemia using DNA amplification and nonradioactive probes

We used in vitro DNA amplification by the polymerase chain reaction and nonradioactive probes for prenatal diagnosis of beta thalassemia in Chinese from the Guangdong province. Exact molecular diagnoses were made in all 20 fetuses studied over a 6-month period. We conclude that this method of prenatal diagnosis for beta thalassemia is a viable approach in many parts of the world where this disease is common.     

Does the microbiome play a causal role in spondyloarthritis?

The purpose of this study is to review the potential causal role of the microbiome in the pathogenesis of spondyloarthritis. The method used for the study is literature review. The microbiome plays a major role in educating the immune response. The microbiome is strongly implicated in inflammatory bowel disease which has clinical and genetic overlap with spondyloarthritis. The microbiome also plays a causal role in bowel and joint disease in HLA B27/human beta 2 microglobulin transgenic rats. The mechanism(s) by which HLA B27 could influence the microbiome is unknown but theories include an immune response gene selectivity, an effect on dendritic cell function, or a mucosal immunodeficiency. Bacteria are strongly implicated in the pathogenesis of spondyloarthritis. Studies to understand how HLA B27 affects bacterial ecosystems should be encouraged.     

鞍山市铁东区公共场所使用化妆品存在的主要卫生问题及对策

目的了解鞍山市铁东区公共场所使用化妆品卫生问题,保障使用者身体健康。方法对2013年度鞍山市铁东区卫生防疫站辖区内监管的公共场所随机抽检化妆品,对公共场所使用化妆品单位数及比例,化妆品标签标识卫生问题等进行描述。结果住宿业化妆品使用情况为56%,其他三种场所100%使用。化妆品标签标识检查住宿业合格率最低,仅为50%。国产特殊用途化妆品持有效证件率仅为65%,普通的仅为62%。标签标识问题突出,进货渠道复杂。化妆品抽检合格率低。结论公共场所的化妆品卫生质量令人担忧。     

鞍山市铁东区公共场所卫生基层问题及解决建议

笔者作为基层卫生监督工作人员经过十多年的公共场所卫生监督工作,通过对鞍山市铁东区公共场所卫生监督情况进行分析。发现当前存在许多公共场所卫生监督执法困难和难题,主要表现为卫生监督队伍薄弱,新兴公共场所剧增,公共场所执法依据不确定性（无法可依）等问题。笔者提出相应的解决建议,应转变卫生监督观念,提高监督管理质量。     

肝细胞生长因子对人脐带间充质干细胞增殖、黏附及迁移影响的体外研究

目的：探讨肝细胞生长因子( HGF)对人脐带间充质干细胞( hUCMSCs)增殖、黏附及迁移能力的影响。方法按照不同腺病毒感染 hUCMSCs 分为实验组( Ad-GFP-HGF )和对照组( Ad-GFP )。以最佳感染复数转染hUCMSCs,观察细胞形态变化以及GFP蛋白的表达。比较各组细胞增殖能力、黏附能力及迁移能力。 Western Bolt检测各组细胞HGF的表达水平。结果对照组和实验组均出现了GFP的表达,实验组hUCMSCs的增殖、黏附及迁移能力均较对照组增强(P<0．05)。实验组细胞HGF的表达水平显著高于对照组(P<0．05)。结论 HGF的高表达能明显促进hUCMSCs的增殖、黏附和迁移。     

UBQLN2 mutations are not a frequent cause of amyotrophic lateral sclerosis in Ireland

Mutations in UBQLN2 have been shown to be a cause of dominant X-linked amyotrophic lateral sclerosis (ALS). Occurrences of mutations in this gene vary across ALS populations. We screened UBQLN2 for mutations in a final cohort of 150 Irish ALS patients. Individuals who were from families with male-to-male transmission or who carried pathogenic hexanucleotide repeat expansions in C9orf72 were excluded. Apart from common synonymous variation, no sequence variants in UBQLN2 were observed. Mutations in UBQLN2 are therefore not a frequent cause of ALS in the Irish population.