治疗性疫苗的研究进展

治疗性疫苗可克服机体的免疫耐受 ,提高机体的特异性免疫反应 ,对一些目前尚无有效治疗药物的传染性疾病及肿瘤等起到治疗作用。介绍了治疗性疫苗的概况、机理和临床研究的最新进展。     

Genetic Characterization and Role in Virulence of the Ribonucleotide Reductases of Streptococcus sanguinis

Streptococcus sanguinis is a cause of infective endocarditis and has been shown to require a manganese transporter called SsaB for virulence and O₂ tolerance. Like certain other pathogens, S. sanguinis possesses aerobic class Ib (NrdEF) and anaerobic class III (NrdDG) ribonucleotide reductases (RNRs) that perform the essential function of reducing ribonucleotides to deoxyribonucleotides. The accompanying paper (Makhlynets, O., Boal, A. K., Rhodes, D. V., Kitten, T., Rosenzweig, A. C., and Stubbe, J. (2014) J. Biol. Chem. 289, 6259–6272) indicates that in the presence of O₂, the S. sanguinis class Ib RNR self-assembles an essential diferric-tyrosyl radical (Fe^III₂-Y^•) in vitro, whereas assembly of a dimanganese-tyrosyl radical (Mn^III₂-Y^•) cofactor requires NrdI, and Mn^III₂-Y^• is more active than Fe^III₂-Y^• with the endogenous reducing system of NrdH and thioredoxin reductase (TrxR1). In this study, we have shown that deletion of either nrdHEKF or nrdI completely abolishes virulence in an animal model of endocarditis, whereas nrdD mutation has no effect. The nrdHEKF, nrdI, and trxR1 mutants fail to grow aerobically, whereas anaerobic growth requires nrdD. The nrdJ gene encoding an O₂-independent adenosylcobalamin-cofactored RNR was introduced into the nrdHEKF, nrdI, and trxR1 mutants. Growth of the nrdHEKF and nrdI mutants in the presence of O₂ was partially restored. The combined results suggest that Mn^III₂-Y^•-cofactored NrdF is required for growth under aerobic conditions and in animals. This could explain in part why manganese is necessary for virulence and O₂ tolerance in many bacterial pathogens possessing a class Ib RNR and suggests NrdF and NrdI may serve as promising new antimicrobial targets.     

感染性心内膜炎患者致病菌分布及死亡因素分析

目的探讨感染性心内膜炎(IE)患者致病菌分布、致病菌耐药性及患者死亡因素。方法回顾性分析我院2014年11月至2018年3月收治的80例感染性心内膜炎患者的临床资料。根据是否发生死亡将患者分成存活组(75例)与病死组(5例)。采集两组患者血液标本进行细菌培养、鉴定及药敏试验,并对患者死亡因素进行统计。结果 80例IE患者共检测出96株病原菌,其中革兰阳性菌63株,占65.63%;革兰阴性菌27株,占28.13%;真菌6株,占6.25%。药敏试验显示链球菌属及金黄色葡萄球菌对青霉素耐药率最高,分别为90.32%和93.33%;其次为红霉素,分别为70.97%和73.33%。单因素分析结果显示,肝脏肿大、血红蛋白(90 g/L)及抗生素的使用与IE患者的死亡有关(均P0.05)。结论 IE患者病原菌以革兰阳性菌为主,其主要菌属对青霉素耐药率最高,要加强对肝脏肿大、血红蛋白及抗生素相关因素的防治,降低IE患者的病死率。     

Implementation of the 2015 European Society of Cardiology guidelines for the management of infective endocarditis in the Netherlands

Because the occurrence of infective endocarditis (IE) continues to be associated with high mortality, a working group was created by the Dutch Society of Cardiology to examine how the most recent European Society of Cardiology (ESC) guidelines for IE management could be implemented most effectively in the Netherlands. In order to investigate current Dutch IE practices, the working group conducted a country-wide survey. Based on the results obtained, it was concluded that most ESC recommendations could be endorsed, albeit with some adjustments. For instance, the suggested pre-operative screening and treatment of nasal carriers of Staphylococcus aureus as formulated in the ESC guideline was found to be dissimilar to current Dutch practice, and was therefore made less restrictive. The recently adapted ESC diagnostic criteria for IE were endorsed, while the practical employment of the relevant diagnostic techniques was simplified in an adapted flowchart. In addition, the presence of a multidisciplinary, so-called ‘endocarditis team’ in tertiary centres was proposed as a quality indicator. An adapted flowchart specifically tailored to Dutch practice for microbiological diagnostic purposes was constructed. Lastly, the working group recommended the Stichting Werkgroep Antibioticabeleid (SWAB; Dutch Working Party on Antibiotic Policy) guidelines for IE treatment instead of the antibiotic regimens proposed by the ESC.

     

周期型马来丝虫感染期幼虫在人卵巢癌细胞系中的体外培养

周期型马来丝虫感染期幼虫(L_3)在三种含人卵巢粘液性囊腺癌细胞系(OMC_(685))的RPMI1640培养系统中均能蜕皮发育为L_4,幼虫最长存活66天,蜕皮率和完成蜕皮率可分别达57.1％和89.3％。在不含细胞系的培养液中,幼虫最长存活14天,基本上不蜕皮。本实验结果提示OMC_(685)细胞系可能产生某些有利于周期型马来丝虫L_3体外生存和发育的物质。     

Platelet aggregation by oral streptococci

One proposed mechanism in the pathogenesis of infective endocarditis is the direct aggregation of platelets by the bacteria causing the disease. Some, but not all, strains of Streptococcus sanguis have been reported to aggregate platelets but the taxonomy of this and related taxa has changed recently. The ability to aggregate platelets by 24 genetically grouped laboratory stock strains was studied along with 8 recent isolates from cases of endocarditis. Strains belonging to S. sanguis could aggregate platelets, but not S. gordonii, "S. parasanguis", S. mitis, S. oralis or related taxa. Also, preliminary data indicate that certain biotypes of S. sanguis lack the ability to aggregate platelets. Of the recent clinical isolates, only 4 aggregated platelets and each of these showed phenotypes typical of S. sanguis. These data suggest that the ability to aggregate platelets is not essential for an organism to be able to cause endocarditis, although it may be a significant virulence factor.     

感染性心内膜炎与肠道菌群的相关性研究

目的探讨感染性心内膜炎与肠道乳杆菌、双歧杆菌和大肠埃希菌的临床相关性。方法选择2008年4月至2016年4月湖州市第一人民医院心内科病房收治的单纯感染性心内膜炎患者67例为观察组,选择同期来院体检结果正常者65例为对照组。分别收集观察组患者治疗前1天、治疗第3天和治疗1周后3个不同时间节点的粪便标本,同时收集对照组的粪便标本,通过FISH实验检测粪便中双歧杆菌和乳杆菌的含量差异,同时通过16SrRNA/DNA荧光定量PCR技术进一步明确观察组患者3个时期肠道双歧杆菌、大肠埃希菌和乳杆菌与对照组的数量差异。结果观察组患者治疗前1天双歧杆菌值为6.2%±0.56%,治疗第3天为4.3%±0.34%,治疗1周后为8.7%±0.56%,对照组双歧杆菌值为9.4%±0.98%。观察组患者治疗前1天乳杆菌值为5.4%±0.86%,治疗第3天为4.9%±0.24%,治疗1周后为6.1%±0.72%,对照组乳杆菌值为8.3%±0.51%。治疗前1天与治疗1周后,观察组患者双歧杆菌和乳杆菌值与对照组相比,差异均有统计学意义(P0.05)。16SrRNA/DNA荧光定量PCR检测表明,观察组患者在3个治疗时期中肠道乳杆菌、双歧杆菌和大肠埃希菌数量的对数值与对照组比较差异均有统计学意义(P0.05)。其中观察组患者双歧杆菌和乳杆菌数量在治疗第3天较低,1周后有所回升;大肠埃希菌数量在治疗第3天亦较低,但1周后没有明显回升。结论感染性心内膜炎患者肠道菌群数量与健康人相比有所下降,肠道乳杆菌、大肠埃希菌和双歧杆菌失调可能影响其发病和转归。     

静脉毒瘾者金黄色葡萄球菌性感染性右心内膜炎(附2例报告及文献复习)

本文在国内首次报道２例静脉毒瘾者金黄色葡萄球菌性感染性右心内膜炎（ＳＩＲＥＤ）,其临床特点：①常合并有肝炎病毒感染;②确诊有赖于心脏超声检查发现三尖瓣赘生物、细菌的毒血症状及血培养的结果;③治疗应根据药敏结果选择２至３种敏感的抗生素联用,其剂量应比常规量大２至３倍,疗程６至８周或更长;④有效治疗后,该病预后良好