基于全基因组测序的耐碳青霉烯类抗生素鲍曼不动杆菌耐药基因、毒力因子及同源性分析

摘要：目的 通过应用全基因组测序(whole genome sequencing, WGS)技术分析某三级医疗机构耐碳青霉烯类抗生素鲍曼不 动杆菌(carbapenem-resistant Acinetobacter baumannii, CRAB)的耐药基因、毒力因子及同源性。方法 收集该院2020年1月至3月 重症监护病房(Intensive care unit, ICU)、神经外科分离的11株医院感染CRAB菌株，通过二代测序平台进行全基因组测序, 应用 基因组流行病学中心(Center for genomic epidemiology, CGE)ResFinder 4. 0软件分析其耐药基因型，并应用MORPHEUS在线制作 热图，应用毒力因子数据库(virulence factors of pathogenic bacteria, VFDB)VFanalyzer软件筛选毒力因子，应用MLST软件检测菌 株的ST型，应用Kaptive软件检测荚膜型，应用CSI Phylogeny 1. 4软件及FigTree v1. 4. 4软件构建最大似然树(maximum likelihood tree, MLT)以分析其同源性。结果 11株CRAB对亚胺培南、美罗培南、头孢菌素、环丙沙星均呈现耐药，而对阿米卡星、左氧 氟沙星耐药的菌株株数较少。11株CRAB共检测出18种耐药基因，11株同时携带碳青霉烯酶耐药基因blaOXA-23和blaOXA-66，β-内酰 胺酶耐药基因以blaTEM-1D和blaADC-25为主，大部分菌株携带多种外排泵相关耐药基因及抗菌药物修饰酶耐药基因。11株CRAB均携 带多种毒力因子，包括外膜孔蛋白、脂多糖、生物膜、外排泵、磷脂酶和效应蛋白等，如OmpA、Lps、Csu、Pga、Ade、Plc、 Bas、Bau、Ent、Hem、Aba、Bfm、Pbp和Kat等。11株CRAB均为ST2-K22型，同源性分析结果显示C组内同源性关系相近，存 在院内传播的可能。结论 该院CRAB的耐药性、毒力特征复杂多样，同源性分析显示该院存在1种优势克隆株，该克隆株有医 院内传播的风险。     

Synthesis and automated fluorine-18 radiolabeling of new PSMA-617 derivatives with a CuAAC radiosynthetic approach

In the last decade, the development of new radiopharmaceuticals for the imaging and therapy of prostate cancer has been a highly active and important area of research, especially focusing on the prostate-specific membrane antigen (PSMA), an antigen which is upregulated in prostate, as well as in other tumor cells. A large variety of PSMA ligands have been radiolabeled, to date. Among the various derivatives, PSMA-617 resulted to be one of the most interesting in terms of interaction with the antigen and clinical properties, and its lutetium-177 labeled version has recently been approved by regulatory agencies for therapeutic purposes. For this reasons, the radiolabeling with fluorine-18 of a PSMA-617 derivative might be of interest. Beside other methodologies to radiolabel macromolecules with fluorine-18, the “click-chemistry” approach resulted to be very useful, and the copper-catalyzed azide-alkyne cycloaddition (CuAAC) is considered one of most efficient and reliable. This paper proposes the synthesis of a suitable precursor for the radiolabeling with fluorine-18 of a new PSMA-617 derivative. The whole radiosynthetic procedure has been fully automated, and the final product, which proved to be stable in plasma, has been obtained with radiochemical yield and purity suitable for subsequent preclinical studies.     

多功能套针浮刺疗法治疗神经根型颈椎病——一项随机对照观察研究＊

目的 评价多功能套针浮刺疗法对神经根型颈椎病的临床疗效。方法 选取256例神经根型颈椎病患者，按随机数字表法分为观察组与对照组各128例。观察组应用多功能套针浮刺疗法进行干预，对照组为常规针刺治疗。两组患者均治疗7天。分别于治疗前后观察两组患者的简化McGill疼痛问卷（SF-MPQ）、国际标准颈椎功能障碍指数（NDI）和田中靖久颈椎病症状20分法量表评分，并于治疗结束后3个月观察复发率。结果 两组患者治疗后的SF-MPQ量表评分、NDI量表评分及田中靖久颈椎病症状20分法评分与治疗前相比均有改善（P<0.05），且观察组优于对照组（P<0.05）；两组患者于治疗后3个月随访，SF-MPQ量表评分与治疗后相比均有改善，且观察组优于对照组（P<0.05）；观察组临床疗效总有效率为96.88%，愈显率为81.25%；对照组总有效率为78.13%，愈显率为46.88%，观察组优于对照组（P<0.05）。结论 应用多功能套针浮刺疗法治疗神经根型颈椎病临床疗效显著，见效较快，可有效降低其复发率，且作用稳定，效果持久，值得临床推广应用。