摘要：Liver injury is a common cause of drug approval withdrawal during drug development,pre-clinical research,and clinical *** not properly treated,patients with severe liver injury can suffer from acute liver failure or even ***,utilization of the convenient in vitro hepatotoxicity assessment model for early detection of drug-induced hepatotoxicity is vital for drug development and safe personalized ***(e.g.,hydrogels,nanofibers,decellularized liver matrix)and bioengineering technologies(e.g.,microarrays,micropatterns,3D printing,and microfluidics)have been applied for in vitro hepatotoxicity assessment *** review summarizes the structure and functions of the liver as well as the components of in vitro hepatotoxicity assessment *** addition,it highlights the latest advances in developing hepatotoxicity models with the ultimate goal of further clinical translation.

摘要：The global increase in the prevalence of drug-resistant bacteria has necessitated the development of alternative treatments that do not rely on conventional antimicrobial *** bacteriophage-derived lytic enzymes in antibacterial therapy shows promise;however,a thorough comparison and evaluation of their bactericidal efficacy are *** study aimed to compare and investigate the bactericidal activity and spectrum of such lytic enzymes,with the goal of harnessing them for antibacterial ***,we examined the bactericidal activity of spanins,endolysins,and holins derived from 2 Escherichia coli model phages,T1 and *** these,T1-spanin exhibited the highest bactericidal activity against ***,we expressed T1-spanin within bacterial cells and assessed its bactericidal activity.T1-spanin showed potent bactericidal activity against all clinical isolates tested,including bacterial strains of 111 ***,2 Acinetobacter spp.,3 Klebsiella spp.,and 3 Pseudomonas *** contrast,T1 phage-derived endolysin showed bactericidal activity against *** and ***,yet its efficacy against other bacteria was inferior to that of ***,we developed a phage-based technology to introduce the T1-spanin gene into target *** synthesized non-proliferative phage exhibited strong antibacterial activity against the targeted *** potent bactericidal activity exhibited by spanins,combined with the novel phage synthetic technology,holds promise for the development of innovative antimicrobial agents.

摘要：In vaccine development,broadly or cross-type neutralizing antibodies(bnAbs or cnAbs)are frequently targeted to enhance *** immunodominant antibodies could help fine-tune vaccine immunogenicity and augment the precision of immunization ***,the methodologies to capitalize on the attributes of bnAbs in vaccine design have not been clearly *** this study,we discovered a cross-type neutralizing monoclonal antibody,13H5,against human papillomavirus 6(HPV6)and *** nAb exhibited a marked preference for HPV6,demonstrating superior binding activity to virus-like particles(VLPs)and significantly higher prevalence in anti-HPV6 human serum as compared to HPV11 antiserum(90%vs.31%).Through co-crystal structural analysis of the HPV6 L1 pentamer:13H5 complex,we delineated the epitope as spanning four segments of amino acids(Phe42-Ala47,Gly172-Asp173,Glu255-Val275,and Val337-Tyr351)on the L1 surface *** interaction analysis and site-directed mutagenesis revealed that the Ser341 residue in the HPV6 HI loop plays a critical role in the interaction between 13H5 and *** Ser341 with alanine,which is the residue type present in HPV11 L1,almost completely abolished binding activity to *** swapping amino acids in the HPV11 HI loop with corresponding residues in HPV6 L1(Ser341,Thr338,and Thr339),we engineered chimeric HPV11-6HI ***,the chimeric HPV11-6HI VLPs shifted the high immunodominance of 13H5 from HPV6 to the engineered VLPs and yielded comparable neutralization titers for both HPV6 and HPV11 in mice and non-human *** approach paves the way for the design of broadly protective vaccines from antibodies within the main immunization reservoir.

摘要：许多研究已在其结核分枝杆菌分离株共享DNA指纹的基础上定义了患者簇。成簇相当于最近的传播,并且对伴随结核分枝杆菌正在高度传播人群亚组来说,与成簇有关的因素已作为指标被找出。在进行和解释这些研究中值得考虑的提醒应予以注意。例如,根据标志物的稳定性和长时间在人群中的菌株数量,某些并非近期传播的原因使菌株组可能完全相同。如果病例对特定人群是新移民或在研究中不是所有人群中的病例都被包括的话,确定由近期传播引发的病例可能不作为成簇被见到。所见的成簇数量将根据研究持续的时间。 在研究的设计、所包括病例的比例、补充和所使用成簇的界定上,研究应给出精确的资料。成簇的数据应至少被年龄、性别和移民状况分开。为了最大的获得信息,研究应涉及一个人群中所有病例的高比例、与传统的流行病学接触调查结合进行(如果可能的话)、并且提供人群中结核病发病资料和患者的年龄、性别、人类免疫缺损病毒状况、耐药性及社会和种族组资料。关键词:结核病;分子流行病学;DNA指纹;RFLP;传播;

摘要：单位:日本东京市新宿区。目的:通过对新宿区的结核分枝杆菌的传染状况的评估,以便有效合理地分配卫生资源,从而成功地实施结核控制规划。设计:将结核分枝杆菌的基因型资料和结核患者资料结合起来的观察描述性研究。结果:男性、年龄小于40岁的患者和无家可归者的基因型成簇率显著较高,他们的调整比值比和95%可信区间分别是(aOR 1.94,95%CI 1.04—3.65,P=0.038),(aOR 2.09,95%CI 1.17—3.71,P=0.012),(aOR 2.72,95%CI 1.42—5.20,P=0.002),而国外出生患者的基因型成簇率却较低(aOR 0.21,95%CI 0.06—0.76,P= 0.017)。在152例结核患者的45个基因型簇中, 102(67.1%)例患者的26个簇是由无家可归者和非无家可归混合而成,其中一个混合簇包括1个在日本出生的8个月的婴儿。结论:此研究显示结核分枝杆菌在无家可归人群的传播要比在非无家可归人群中更常发生。然而,偶然的接触也会引起结核分枝杆菌在无家可归者和普通人群之间的传播。

摘要：目的比较四药联用(四联)和三药联用(三联)的抗逆转录病毒疗法作为HIV感染者一线治疗的疗效和安全性,并探讨现有的临床试验对临床实践及未来研究的启示。研究设计随机对照试验的系统综述和meta分析。数据来源系统检索了PubMed、EMBASE、CENTRAL、Web of Science及Allied Health Literature数据库2001年3月至2016年12月期间发表的研究(其中PubMed和EMBASE的检索更新至2018年6月),以及合格研究和相关综述的参考文献。入选标准比较四联与三联抗逆转录病毒疗法作为HIV感染者一线治疗的作用,并评价了至少一种疗效或安全性结局的随机对照试验。分析方法对检测不到的HIV-1 RNA、CD4 T细胞计数、病毒学失败、新发艾滋病事件、死亡和严重不良反应等结局的资料采用随机效应模型进行meta分析。结果共找到12项合格研究,包括4251例HIV感染者。四联和三联抗逆转录病毒疗法对各个疗效和安全性结局的影响均类似,且没有一个总体效应估计值的点值落在支持四联疗法的一侧。与三联疗法相比,四联疗法组出现不同结局的相对危险度及其95%可信区间如下:检测不到的HIV-1 RNA,0.99(0.93~1.05);病毒学失败,1.00(0.90~1.11);新发艾滋病事件,1.17(0.84~1.63);死亡,1.23(0.74~2.05);严重不良反应,1.09(0.89~1.33)。两组CD4 T细胞计数增加的平均差值为-19.55个细胞/μl(-43.02~3.92)。无论联合抗逆转录病毒疗法的具体方案如何,上述2组比较的结果大体不变,且在所有亚组和敏感性分析中均变化不大。结论在HIV感染者的一线治疗中,四联抗逆转录病毒疗法的效果并不优于三联疗法。这一发现为当前推荐三联疗法作为一线治疗的指南提供了支持。除非对现有证据的系统综述显示确有必要,否则不应该再开展新的临床试验去比较四联与三联疗法。当然,本系统综述并不排除当有新的抗逆转录病毒药物种类出现时包含该类药物的四联疗法比三联疗法更好的可能性。

摘要：目的:评估左氧氟沙星、加替沙星及莫西沙星等新氟喹诺酮类药物对肺结核患者的早期杀菌活性及延长早期杀菌活性。设计:随机开放临床试验。40例成年新诊断的涂阳肺结核患者(每组10例)分别每日单一接受异烟肼300mg,或左氧氟沙星1000mg,或加替沙星400mg,或莫西沙星400mg的7天治疗。治疗前2天及单药治疗7天期间,每日收集痰液进行定量培养。计量单药治疗开始的头2天(0-2天)及治疗后5天(2-7天)的菌量下降情况,以评估各药的早期及延长早期杀菌活性。对实验室工作人员关于病人治疗分组信息采用单盲法。结果:异烟肼的早期杀菌活性为0.67log10cfu/毫升/天,高于莫西沙星(0.33log10cfu/毫升/天)及加替沙星(0.35log10cfu/毫升/天)。与每日1000mg左氧氟沙星的早期杀菌活性(0.45log10cfu/毫升/天)相比,无统计学差异(P=0.14)。3种氟喹诺酮类药物的早期杀菌活性(0-2天)与延长早期杀菌活性(2-7天)相似。总体说来,氟喹诺酮类药物的延长早期杀菌活性高于异烟肼。结论:莫西沙星、加替沙星及高剂量左氧氟沙星,虽然略低于异烟肼,但均有良好的早期杀菌活性,并具有较高的延长早期杀菌活性。有理由对这些药物敏感的结核病人进行进一步的治疗研究。

摘要：目的 若亲代患妊娠剧吐，评估其子代妊娠剧吐的复发风险。设计 基于人群的队列研究。资料 来自挪威的注册数据。研究对象 1967--2006年挪威医学出生登记的生育链接数据资料：544087对母女及399777对母子：主要观察指标在患妊娠剧吐妇女的母亲及其女儿以及婆媳间妊娠剧吐风险。