阴道分泌物常规检测结果分析

了解女性生殖道健康状况及常见阴道病分布情况。方法:采用阴道分泌物常规检测对315例体检女职工阴道分泌物标本进行检查。结果:阴道清洁度在Ⅰ~Ⅱ度227例(72.1%);清洁度在Ⅲ~Ⅳ度88例(27.9%);细菌性阴道炎(BV)65例(20.6%);霉菌性阴道炎(MV)29例(9.2%);滴虫性阴道炎(TV)5例(1.5%)。结论:阴道分泌物常规检查能及时发现女性生殖系统常见病,多发病,值得临床借鉴。     

女性患者阴道分泌物及宫颈支原体与衣原体检测结果分析

目的分析阴道分泌物及宫颈支原体与衣原体的检测结果,为临床治疗提供依据。方法选择2015年1月~2016年12月我院妇科门诊患者500进行研究,对患者阴道分泌物、宫颈衣原体和支原体检测结果进行统计分析。结果 500例患者中,确诊为外阴阴道假丝酵母菌病86例,检出率为17.2%;细菌性阴道病108例,检出率为21.6%;滴虫性阴道炎6例,检出率为1.2%;宫颈衣原体感染38例,检出率为7.6%;支原体感染123例,检出率为24.6%。不同年龄患者阴道性疾病检出率比较,差异无统计学意义(P0.05);不同年龄患者宫颈衣原体、支原体感染检出率比较,差异有显著统计学意义(P0.05)。结论女性外阴阴道假丝酵母菌病、细菌性阴道病的临床发病率相对较高,阴道炎症的发生与阴道清洁度存在明显相关性;宫颈疾病中,衣原体和支原体为主要致病菌,在今后的临床防治工作中应引起重视。     

细菌性阴道病联合检测技术在阴道感染诊断中的应用

目的探讨细菌性阴道病(BV)联合检测技术在阴道感染诊断中的应用价值。方法取2009年9月至2010年2月至苏州市木渎人民医院妇科门诊就诊的6 500例育龄期妇女阴道分泌物,分别对霉菌、滴虫、清洁度进行生理盐水涂片的检测与过氧化氢、唾液酸苷酶和白细胞酯酶三项联合测定。结果应用湿片镜检发现霉菌性阴道炎1 274例,阳性率为19.6%,滴虫性阴道炎195例,阳性率为3.0%。应用BV三项联合技术测定6 500例患者的阴道分泌物,BV阳性1 612例,阳性率为24.8%,其中BV合并霉菌性阴道炎感染465例,占BV发病的28.9%,BV合并滴虫感染79例,占BV发病的4.9%。结论三项联合检测技术操作简单、快速、准确,从功能学分别反映阴道正常菌和致病菌的指标,可与白带常规镜检互补,建议作为阴道分泌物常规检查对阴道感染进行筛查。     

1 830例女性阴道炎患者阴道微生态调查

目的调查分析本地区阴道炎患者的阴道微生态状况。方法回顾性分析我院2017年1月至2017年12月妇科门诊就诊的1 830例阴道炎患者阴道菌群分布,并探讨阴道菌群分布与年龄、季节以及复发性阴道炎之间的关系。结果 1 830例患者中菌群正常者547例(29.89%),细菌性阴道病(BV)319例(17.43%),阴道假丝酵母菌病(VVC)331例(18.09%),滴虫性阴道炎(TV)13例(0.71%),混合性阴道炎(MCVI)94例(5.14%)。共有90例(4.92%)患者在治疗后复发,混合感染者复发率最高(10.64%)。阴道菌群异常者的年龄主要集中于30～40岁(73.00%)和41～50岁(76.06%),混合性阴道炎、VVC和BV主要集中于30～40岁和41～50岁的患者。秋冬季患者菌群异常的检出率高于春夏季,春季BV检出率最高,秋季VVC和菌群抑制检出率最高。结论阴道炎患者阴道菌群分布既可表现为正常,也可表现为失调状态,其中混合性阴道炎最容易复发。不同年龄段,不同季节患者阴道菌群分布不同。     

未婚阴道炎女性阴道分泌物检查结果调查

目的了解未婚女性阴道炎患者阴道分泌物检出情况。方法自愿接受本次调查的未婚有性生活史疑似阴道炎女性293名,对其进行阴道分泌物检查,内容包括念珠菌、支原体、衣原体、细菌性阴道病(BV)、滴虫、淋病等。结果病原体检出率为75.77%,21~25岁感染率最高(90.10%);感染率序位:解脲支原体(58.36%)>念珠菌(35.15%)>BV(16.04%)>人型支原体(14.33%)>衣原体(10.92%)>滴虫(2.39%)>淋病(0.68%)。单一病原体感染占32.08%,复合感染占43.00%。结论未婚女性阴道分泌物病原体种类多、检出率高,混合感染率高,应加强对这一人群生殖健康方面的监控。     

BV三项在阴道分泌物检测中的应用及临床结果分析

目的探讨阴道分泌物BV三项检测在妇科患者诊断细菌性阴道病中的临床价值及BV阳性患者与妇女盆腔炎症的相互关系。方法对520例阴道分泌物进行BV三项检测（唾液酸苷酶、过氧化氢酶、白细胞酯酶）和显微镜检测,并对其中正常阴道组、滴虫性阴道炎和霉菌性阴道炎与BV进行对照比较。结果根据临床表现和BV三项检测,BV的发病率高达50．96％,滴虫性阴道炎占8．65％,霉菌性阴道炎占17．10％,BV的盆腔炎症明显高于各类阴道病组。结论BV在妇科门诊的发病率为最高,并与妇科盆腔炎症呈正相关性,在妇科门诊进行BV常规筛选是必需的。     

泌尿生殖系统支原体感染及药敏分析

目的:了解我院妇科门诊患者支原体感染情况及药敏培养结果,指导临床合理使用抗生素。方法:采用梅里埃诊断产品(上海)有限公司提供的支原体培养、鉴定、计数及药敏试验试剂盒(比色法),对患者标本进行培养、鉴定、计数及药敏分析。结果:461例样本中支原体培养阳性的286例(62.04%),其中单一UU感染229例(49.67%),53(11.50%)例为混合性感染,单一Mh感染4例(0.87%)。感染患者中UU的感染率高达到80%(229/286)。药敏结果显示单一UU感染和UU+Mh混合性感染时原始霉素的敏感率最高分别为100%和90.57%。其次为强力霉素,敏感率分别为98.69%和84.91%。而单一Mh感染时强力霉素和交沙霉素的感染率最高为100%。结论:我院妇科门诊患者支原体感染以UU感染为主,其次为混合性感染,单一Mh感染较少见。药敏结果显示单一UU感染和混合性感染时原始霉素最为敏感,其次为强力霉素。而单一Mh感染时强力霉素和交沙霉素最为敏感。因此在未做药敏实验前,可先选用强力霉素进行治疗,待药敏结果出来后,根据药敏结果调整用药,以达到良好的治疗效果。     

5863例阴道分泌物检测结果分析

目的通过对5 863例妇科疾病患者阴道分泌物进行检查,分析引起妇科疾病的病原体感染分布状况。方法选择2010年11月至2011年5月来义乌妇保院就诊的妇科患者5 863例,对其阴道分泌物进行常规镜检和生化检测。结果在5 863例样本中,清洁度Ⅰ～Ⅱ2 756例,清洁度Ⅲ～Ⅳ3 107例,不同清洁度中病原体的检出率差异有统计学意义（P〈0.05）,且20～50岁年龄组病原体感染率明显高于其他年龄组（P〈0.05）。结论育龄期妇女阴道感染率较高,细菌性阴道病发病率比白色念珠菌性和滴虫性阴道炎均要高。因此,育龄期采取合理有效的措施,预防细菌性阴道病感染是关键。     

316例输卵管性不孕患者生殖道Ct、Uu及Mh的检测及耐药性分析

目的通过对316例输卵管性不孕患者生殖道沙眼衣原体、解脲支原体、人型支原体感染以及耐药情况进行检测分析,研究其与不孕症的关系,并探讨用药合理性。方法收集316例2013年2月至2016年9月至我院进行诊治的输卵管性不孕患者作为研究组,并选取同期297例来进行检查的健康人作为对照组。对两组人员生殖道分泌物进行沙眼衣原体(Chlamydia trachomatis,Ct)、解脲支原体(Ureaplasma urealyticum,Uu)、人型支原体(Mycoplasma hominis,Mh)检测,并进行药敏试验。结果研究组患者Ct、Uu、Mh、Ct+Uu、Uu+Mh感染率以及总感染率均明显高于对照组,差异均具有统计学意义(Ps0.05)。Uu对原始霉素、四环素、强力霉素、交沙霉素、阿奇霉素、克拉霉素、红霉素敏感性较高(90%以上),对氧氟沙星、环丙沙星耐药性较高。Mh对原始霉素、四环素、强力霉素、交沙霉素敏感性较高(90%以上),对氧氟沙星、环丙沙星、阿奇霉素、克拉霉素耐药性较高。Uu+Mh对原始霉素、四环素、交沙霉素敏感性较高(90%以上),对阿奇霉素、氧氟沙星、环丙沙星耐药性较高。结论对输卵管性不孕患者,应进行生殖道分泌物Ct、Uu、Mh的检测,判断是否发生感染或混合感染,并根据药敏结果选择合适的抗生素进行治疗,以提高治疗效果。     

女性不孕症患者支原体的检测及耐药性分析

目的了解女性不孕症患者支原体感染及耐药性状况。方法用解脲脲原体(Uu)和人型支原体(Mh)培养、鉴定、药敏一体化试剂盒,对宫颈拭子标本进行检测。结果 2008年1月至2010年6月检测的2 325份患者标本,共检出阳性1 028份,总检出率44.2%,检出支原体共1117株,包括Uu 998株(89.3%),Mh 119株(10.7%),其中单一Uu感染率为87.5%(900/1028),单一Mh感染率为2.0%(21/1028),Uu和Mh同时感染率为9.5%(98/1028);强力霉素、交沙霉素、四环素、克拉霉素、原始霉素对Uu和Mh的敏感率为77.3%~93.3%,阿奇霉素敏感率为58.8%~78.0%;喹诺酮类药物的敏感率仅为21.0%~42.0%。结论 Uu是主要感染菌种,有生殖泌尿道症状或不洁性行为史的女性不孕患者,都有必要检测支原体;混合感染Uu和Mh患者的治疗用药应兼顾2种支原体的效果;四环素类、大环内酯类可作为支原体治疗的首选药物之一,阿奇霉素治疗Mh疗效不佳,喹诺酮类药物因其较高的耐药率而应慎用。     

Small Molecule Screening in Human Induced Pluripotent Stem Cell-derived Terminal Cell Types

A need for better clinical outcomes has heightened interest in the use of physiologically relevant human cells in the drug discovery process. Patient-specific human induced pluripotent stem cells may offer a relevant, robust, scalable, and cost-effective model of human disease physiology. Small molecule high throughput screening in human induced pluripotent stem cell-derived cells with the intent of identifying novel therapeutic compounds is starting to influence the drug discovery process; however, the use of these cells presents many high throughput screening development challenges. This technology has the potential to transform the way drug discovery is performed.     

The challenges of developing novel antiparasitic drugs

Only a few novel classes of antiparasitic drugs have emerged over the last few decades, reflecting the difficulties associated with bringing a safe, effective molecule to market. In recent years, the screening paradigm has shifted from empirical whole parasite screening towards mechanism-based high throughput screening. This approach requires investment in molecular parasitology and in understanding the basic biology of parasites, as well as requiring considerable investment in an infrastructure for screening. Add to this the fact that the drug discovery process is iterative with high attrition, the Animal Health industry by necessity must focus on discovering medicines for diseases, which will deliver a return on investment. In recent years the rapid progression of genomics has unlocked a plethora of tools for target identification, validation and screening, revolutionising mechanism-based screening for antiparasitic drug discovery. The challenge still remains; however, to identify novel chemical entities with the properties required to deliver a safe, effective antiparasitic drug.     

Identification and Functional Characterization of a Novel Bacterial Type Asparagine Synthetase A: A tRNA SYNTHETASE PARALOG FROM LEISHMANIA DONOVANI*

Asparagine is formed by two structurally distinct asparagine synthetases in prokaryotes. One is the ammonia-utilizing asparagine synthetase A (AsnA), and the other is asparagine synthetase B (AsnB) that uses glutamine or ammonia as a nitrogen source. In a previous investigation using sequence-based analysis, we had shown that Leishmania spp. possess asparagine-tRNA synthetase paralog asparagine synthetase A (LdASNA) that is ammonia-dependent. Here, we report the cloning, expression, and kinetic analysis of ASNA from Leishmania donovani. Interestingly, LdASNA was both ammonia- and glutamine-dependent. To study the physiological role of ASNA in Leishmania, gene deletion mutations were attempted via targeted gene replacement. Gene deletion of LdASNA showed a growth delay in mutants. However, chromosomal null mutants of LdASNA could not be obtained as the double transfectant mutants showed aneuploidy. These data suggest that LdASNA is essential for survival of the Leishmania parasite. LdASNA enzyme was recalcitrant toward crystallization so we instead crystallized and solved the atomic structure of its close homolog from Trypanosoma brucei (TbASNA) at 2.2 Å. A very significant conservation in active site residues is observed between TbASNA and Escherichia coli AsnA. It is evident that the absence of an LdASNA homolog from humans and its essentiality for the parasites make LdASNA a novel drug target.     

多粘菌素耐药性的研究进展

多粘菌素因在多重耐药革兰氏阴性菌上的治疗效果良好,再度被应用于临床,其耐药水平在多种抗菌药中曾一度较低,但目前有研究表明多粘菌素的耐药率有增加趋势。作为抗击多重耐药革兰氏阴性菌的最后一道防线,如何抑制其耐药的发生就显得尤为重要。本文就多粘菌素的耐药性现状、产生机制及防控措施三个方面进行了综述,为指导临床科学合理使用多粘菌素及革兰氏阴性菌耐药菌株传播和蔓延的防控措施提供理论依据。     

A comprehensive approach for drug safety assessment

A comprehensive, multidisciplinary approach is proposed here for the development of a drug with an acceptable safety profile. Key parameters to be considered for drug safety evaluation based on this comprehensive approach include the following: (1) Pharmacology: Possible toxicity due to drug-target interactions, including interactions with unintended molecular targets, or with molecular targets in unintended organs. (2) Chemistry: Chemical scaffolding and side-chains with safety concerns. (3) Toxicology: Toxicity in animals in vivo, and in relevant animal and human cells in culture. (4) Drug metabolism and pharmacokinetics: Safety concerns due to toxification or detoxification, organ distribution, clearance and pharmacokinetic drug-drug interactions. (5) Risk factors: Physiological, environmental and genetic factors that may enhance a patient's susceptibility. It is proposed that this integrated, multidisciplinary approach to safety evaluation may enhance the accuracy of the prediction of drug safety and thereby the efficiency of drug development.     

脑膜炎败血伊丽莎白菌耐药性的研究进展

脑膜炎败血伊丽莎白菌(Elizabethkingia meningoseptica, EM)可引起肺部感染、新生儿脑膜炎、菌血症等疾病,医院重症监护病房检出率较高,是院内感染的重要病原体之一。随着抗菌药物的广泛使用,EM对β-内酰胺类、氨基糖苷类、氟喹诺酮类等临床常用抗菌药物呈多重耐药,给临床治疗带来极大困难。目前EM的耐药机制研究主要集中于产生药物灭活酶、药物作用靶位改变、外排泵、形成生物膜等方面。EM可同时携带多个耐药基因,如GOB、BlaB、CME等,从而介导多重耐药。本文就国内外EM耐药现状、耐药机制进行综述,旨在为预防和控制EM的医院内感染提供参考。     

Chemotoxicity and survival of tumor-bearing mice under exposure to randomized photoperiodic regimen

Although disruption of the circadian rhythm had been traditionally considered as a pathological sign, there is an increasing recognition that an existence of internal disorder (or chaos) in the organism's homeostasis is, to some degree, essential to the organism's well being. In this study we explored the effects of rhythm scrambling by exposure to random light/dark (RLD) alternation or by hydrocortisone administration. The variables measured were the toxicity of Adriamycin, Vincristin, Cisplatinum and Cyclophosphamide in C57Bl/6J mice and the survival of EL4 lymphoma-bearing mice, before and after chemotherapy. Rhythm alterations were determined by WBC counts and plasma Alkaline Phosphatase activity. Injections of Adriamycin, Cisplatinum and Vincristin in RLD conditions resulted in a better survival than in control groups of mice kept in LD illumination regimen, although the differences between the groups were significant only for injection of Adriamycin. RLD conditions imposed a "protective" effect on survival of tumor-bearing mice. On the 94th day, 20% of the injected mice in RLD conditions still survived while, there were no survivors beyond 38 days in control group. Chemotherapy had a more prominent beneficial effect on survival in RLD group, as compared to LD group. The injections of hydrocortisone had detrimental effect on survival in both illumination schedules. However, the survival in the RLD group was still better than in the LD group. These experiments indicate that temporal disorganization has beneficial effects on lymphoma-bearing mice and could be used for development of new therapeutic modalities.     

假病毒技术用于抗HIV-1药物筛选及抗药性分析

HIV抗药性的产生严重阻碍了HIV疾病的治疗进程,因此开发新的抗HIV药物以及对病毒进行抗药性分析对于提高HIV疾病的治疗效果非常重要。将利用HIV假病毒构建的抗HIV药物评价系统及病毒抗药性分析系统应用于药物筛选及耐药性分析具有常规方法无法替代的优点。介绍了目前常用的几种类型HIV假病毒的特点和构建方法,同时介绍了假病毒感染细胞的系统及其在细胞水平筛选抗HIV药物和对HIV临床分离株进行耐药性分析这两方面的应用,并通过与常规方法进行比较来分析利用假病毒技术进行研究的优势及局限性, 还通过总结大量学者的研究成果证明了利用假病毒技术进行药物筛选和抗药性分析具有准确、安全和高效的特点。     

SynergyFinder Plus: Toward Better Interpretation and Annotation of Drug Combination Screening Datasets

Combinatorial therapies have been recently proposed to improve the efficacy of anticancer treatment. The SynergyFinder R package is a software used to analyze pre-clinical drug combination datasets. Here, we report the major updates to the SynergyFinder R package for improved interpretation and annotation of drug combination screening results. Unlike the existing implementations, the updated SynergyFinder R package includes five main innovations. 1) We extend the mathematical models to higher-order drug combination data analysis and implement dimension reduction techniques for visualizing the synergy landscape. 2) We provide a statistical analysis of drug combination synergy and sensitivity with confidence intervals and P values. 3) We incorporate a synergy barometer to harmonize multiple synergy scoring methods to provide a consensus metric for synergy. 4) We evaluate drug combination synergy and sensitivity to provide an unbiased interpretation of the clinical potential. 5) We enable fast annotation of drugs and cell lines, including their chemical and target information. These annotations will improve the interpretation of the mechanisms of action of drug combinations. To facilitate the use of the R package within the drug discovery community, we also provide a web server at www.synergyfinderplus.org as a user-friendly interface to enable a more flexible and versatile analysis of drug combination data.     

细菌药物耐受

细菌药物耐受(Drug tolerance)是指在没有发生耐药突变的情况下细菌耐受抗生素杀菌的能力,表现为细菌群体难以或不能被杀菌型药物清除。细菌药物耐受的调控机制包括群体异质性和压力应答两种途径。药物耐受性的本质是细菌通过调控或遗传突变的方式改变生理代谢状态,从而抵制药物引起的细胞死亡途径。比如,处于缓慢生长或生长停滞生理状态的细菌往往能够抵抗药物的杀菌作用。临床研究发现细菌药物耐受是导致持续性感染疾病迁延难愈、复发率高的病原学机制之一。同时,研究证明耐受性的形成是细菌耐药性(Drug resistance)产生的进化途径之一。因此,揭示细菌药物耐受的机制将有助于人们深入了解抗生素的杀菌机理,以及细菌耐药性形成的适应性进化机制,并为新型杀菌药物以及药物增效剂靶标的发现和抗生素合理使用策略的开发奠定理论基础。