Evolution of gentamicin and arsenite resistance acquisition in Ralstonia pickettii water isolates

Ralstonia pickettii are ubiquitous in water environments. Members of this species are frequently, but not always, resistant to both gentamicin and arsenite. Gentamicin and arsenite co-resistance and the putative molecular mechanisms were investigated. A group of 37 R. pickettii strains isolated from drinking water and hospital wastewater were characterized for gentamicin and arsenite resistance phenotypes, the number and size of plasmids, and screened for genetic elements associated with arsenite tolerance, Integrative and Conjugative Elements (ICEs), among other. The genomes of three representative strains were compared.Most gentamicin resistant (GR) isolates (32/33) were resistant to arsenite, and harbored ICE- and ars operon-related genes. These genetic elements were not detected in any of the five arsenite susceptible strains, regardless of the GR (n = 1) or gentamicin susceptibility (GS) (n = 4) phenotype. The comparison of the genomes of two GR (one resistant and one susceptible to arsenite) and one GS strains suggested that these phenotypes correspond to three phylogroups, distinguished by presence of some genes only in GR isolates, in addition to point mutations in functional genes. The presence of ICEs and ars operon-related genes suggest that arsenite resistance might have been acquired by GR lineages.     

陕西省莱姆病自然疫源地调查研究

目的调查了解陕西省莱姆病自然疫源地。方法人群莱姆病螺旋体血清抗体检查,采用间接免疫荧光法(IFA);莱姆病患者,采用个案调查;蜱样,采用拖旗法采集;莱姆病螺旋体检测,采用巢式PCR法;莱姆病螺旋体基因分型,采用RFLP法。结果通过血清流行病学调查,陕西省富县张家湾镇、南郑县碑坝、陇县八渡镇3个农林地区人群莱姆病螺旋体自然感染率分别为8.33%(6/113)、8.88%(3/36)和7.51%(4/45)(P0.05),发现莱姆病患者14例,蜱类以嗜群血蜱和达吉克斯坦革蜱为优势种,检测蜱样1 116只。检测出阳性138只,总阳性率为12.35%。物种的阳性率分别为嗜群血蜱30.06%(107/356),达吉克斯坦革蜱3.88%(29/747),日本血蜱15.38%(2/13);检测出阳性蜱样138只,其中嗜群血蜱107只,84只为伽氏疏螺旋体基因型,23只为阿弗西尼疏螺旋体基因型;达吉克斯坦革蜱29只,24只为伽氏疏螺旋体基因型,5只为阿弗西尼疏螺旋体基因型;日本血蜱2只,均为伽氏疏螺旋体基因型。结论研究提示陕西省富县张家湾镇、南郑县碑坝、陇县八渡镇3个农林地区存在莱姆病自然疫源地。     

Isolated acute dysphagia due to varicella-zoster virus

We present a case of zoster sine herpete causing isolated acute dysphagia in an immunocompetent patient. The interest of this paper is the atypical presentation of varicella-zoster virus reactivation. A 77-year-old woman presented with a 3-day history of fever and worsening dysphagia for both liquid and solid foods. Cerebrospinal fluid examination revealed lymphocytic pleocytosis and PCR amplified varicella-zoster virus DNA with high antibody titers in both serum and cerebrospinal fluid. The panel was suggestive of a cranial neuritis due to varicella-zoster virus, involved cranial nerves, even in the absence of a cutaneous and mucosal rash. Varicella-zoster virus reactivation should be included in the differential diagnosis of isolated or multiple cranial nerve palsies, with or without zosteriform skin lesions. A prompt etiologic diagnosis can lead to early administration of antiviral therapy.     

海南省疟疾流行空间分布的环境影响因素初步分析

目的 分析海南省疟疾流行空间分布特征及其与自然环境因素的相关性,构建海南省疟疾流行空间分布预测模型.方法 获取2000年海南省雨季(5-10月)各县(市)疟疾发病资料以及气象、土地利用类型构成比、地表温度(LST)和各地平均高程等数据,分析发病率与上述各环境因素的相关性,应用负二项回归分析建立发病率的预测模型,并应用预测模型预测疟疾流行风险的空间分布.结果 海南省2000年雨季各市(县)疟疾发病率与各地的海拔高度、林地面积构成比、草地面积构成比呈显著正相关;与耕地面积构成比、城乡、工矿、居民用地面积构成比、LST呈显著负相关;与水域面积构成比、未利用土地面积构成比、平均气温、平均最高气温、平均最低气温、平均极温差、平均相对湿度及降雨量无明显相关性.负二项回归分析引入方程的因子为LST,回归方程为:Ⅰ(月发病率,单位:1/100万)=exp(-1.672-0.399×LST).结论 海南省疟疾流行空间分布与多种环境因素有关,可以利用遥感技术获取有关环境指标来预测疟疾流行风险的空间分布.     

Evaluating the effectiveness and cost-effectiveness of free influenza vaccination policy for older adults in Yinzhou,China: Study protocol of a real-world analyses

BackgroundInfluenza causes excessive morbidity and mortality among older adults. While influenza vaccine provides protection against its infection, the vaccination coverage in China among older adults has been very low. Previous evidence on the cost-effectiveness of government-sponsored free influenza vaccination programs in China was primarily based on literature data, which might not always reflect real-world patient populations. The Yinzhou Health Information System (YHIS) is a regional database that captures electronic health records, insurance claims data, etc. for all residents in Yinzhou district, Zhejiang province, China. We will use YHIS to study the effectiveness, influenza-related direct medical cost and cost-effectiveness analysis (CEA) of the free influenza vaccination program for older adults. In this paper, we describe the study design and innovations in detail.MethodsWe will establish a retrospective cohort of permanent older residents aged 65 and over, using YHIS between 2016 and 2021. We will estimate the vaccine coverage rate, influenza incidence rate and influenza-related direct medical cost from 2016 to 2021. Regression discontinuity will be used to estimate vaccine effectiveness for the 2020/2021 season. We will build a decision tree model to compare the cost-effectiveness of three influenza vaccination options (free trivalent influenza vaccine, free quadrivalent influenza vaccine, and no policy) from both societal and health system perspectives. Parameter inputs will be gathered from both YHIS and published literature. We will calculate the incremental cost-effectiveness ratio with cost and quality-adjusted life years (QALYs) discounted at 5 % annually.DiscussionOur CEA solidifies multiple sources including regional real-world data and literature for a rigorous evaluation of the government-sponsored free influenza vaccination program. The results will provide real-world evidence from real-world data on the cost-effectiveness of a real-world policy. Our findings are expected to support evidence-based policy making and to promote health for older adults.     

仙灵骨葆相关肝损伤的临床病例分析及拆方实验研究

仙灵骨葆为骨科常用药,临床疗效好,但近年来发现有致肝损伤风险。本研究通过对文献不良反应报告和重点医院病例进行分析,发现文献检索到的仙灵骨葆肝损伤病例存在较大比例的报告信息不完整,难以准确判断其因果关系。重点医院药物性肝损伤(DILI)病例中,筛选出仙灵骨葆相关肝损伤患者6例,其中2例经整合证据链法评价达到了“临床诊断”标准。进一步对区域全人群健康大数据进行分析,估算其粗发生率为0.034%,属于罕见水平,具有显著的个体差异和特异质属性,仙灵骨葆相关肝损伤总体发生水平低于其他骨病用药。基于免疫应激介导的特异质肝损伤模型,通过拆方研究发现,方中淫羊藿和补骨脂是引起肝损伤的相关药味,全方的肝损伤严重程度弱于淫羊藿和补骨脂,提示方中另外4味药(续断、知母、地黄、丹参)有减轻二者引起的肝损伤作用。进一步进行拆方研究,发现4味药均有减轻淫羊藿和补骨脂所致肝损伤作用,其中丹参的配伍减毒效果最好。综上,仙灵骨葆可能在极少数易感个体引起特异质肝损伤,但发生风险低于其他常用骨病药物。临床应用仙灵骨葆要注意避免在免疫应激患者应用。仙灵骨葆引起肝损伤的主要药味为补骨脂、淫羊藿,且丹参在全方中起到配伍减毒作用。本研究可为仙灵骨葆临床合理用药提供参考。     

中国医疗机构工作人员流感疫苗预防接种指南

为了加强中国医疗机构工作人员流感疫苗的接种, 中华预防医学会医院感染控制分会联合中国临床实践指南联盟制定了《中国医疗机构工作人员流感疫苗预防接种指南》。本指南结合国内外研究进展和专家意见, 主要关注了7个临床相关问题, 并根据牛津循证医学中心2011版证据质量评估表对研究进行证据评级, 最终形成推荐意见。指南强调了医疗机构工作人员接种流感疫苗的重要性, 降低自身流感患病率可有效减少医院传播风险。本指南建议: 如无禁忌证, 医疗机构工作人员均应积极接种流感疫苗。推荐对感染传播风险极高的工作人员、高危人群和孕妇优先接种流感疫苗。另外, 指南还提供了疫苗的选择、接种时间及接种频次的建议。鉴于目前我国医疗机构工作人员流感疫苗接种率偏低且地区差异明显, 本指南建议进一步加强关于流感疫苗接种的健康教育, 根据各个省市区具体情况, 采取"多元化"方法, 积极开展有组织的接种活动。     

Silencing acpP gene via antisense oligonucleotide-niosome complex in clinical Pseudomonas aeruginosa isolates

Pseudomonas aeruginosa, an opportunistic Gram-negative pathogen, is one of the major causes of nosocomial infections. In addition to its physiological adaptation capacity, it can develop resistance to disinfectants and antibiotics through various mechanisms. Recently, new eradication methods are gaining attention. Therefore, in this study, an LNA-2′-O-methyl hybrid antisense oligonucleotide targeting the acyl carrier protein P (acpP) gene was introduced into P. aeruginosa isolates. The design was determined through sequence analysis and prediction of the secondary structure of mRNA by software. Niosomes were used for enhancing cellular uptake. The control of the binding and transfection ability of the sequence was determined fluorometrically by labeling with 6-Fam. The effects were determined with broth microdilution method and qPCR studies. Eight different formulations were prepared. Among these, one formulation has shown to have ASO complexation ability whose composition was 312 μl Span 80 + 69.5 mg Cholesterol+ 36.4 mg CTAB+1 ml Chloroform and 5 ml dH₂O. Thus this formulation was determined as the delivery system for the next stages. Significant gene inhibition was detected at the six isolates. Results of this study suggested that niosomes can be used as a delivery system for cellular uptake of ASO and could eliminate bacterial growth.     

Tightly controlled response to oxidative stress; an important factor in the tolerance of Bacteroides fragilis

The exposure of Bacteroides fragilis to highly oxygenated tissues induces an oxidative stress due to a shift from the reduced condition of the gastrointestinal tract to an aerobic environment of host tissues. The potent and effective responses to reactive oxygen species (ROS) make the B. fragilis tolerant to atmospheric oxygen for several days. The response to oxidative stress in B. fragilis is a complicated event that is induced and regulated by different agents. In this review, we will focus on the B. fragilis response to oxidative stress and present an overview of the regulators of responses to oxidative stress in this bacterium.