Previous studies have demonstrated the regulatory roles of Transmembrane protein 147 (TMEM147) in various diseases, including cancer. However, systematic pan-cancer analyses investigating the role of TMEM147 in diagnosis, prognosis, and immunological prediction are lacking. An analysis of data from The Cancer Genome Atlas (TCGA) revealed differential TMEM147 expression across various types of cancer as well as within immune and molecular cancer subtypes. Moreover, high TMEM147 expression was associated with poor disease-specific survival (DSS), overall survival (OS), and progression-free interval (PFI) across cancers, suggesting its potential as a prognostic biomarker. Our study further revealed a significant correlation between TMEM147 expression and T helper cell and Tcm cell infiltration in most cancer types. In the case of liver hepatocellular carcinoma (LIHC), the effect of TMEM147 on prognosis varied among different clinical subtypes. Additionally, functional enrichment analysis revealed an association between TMEM147 and metabolic pathways. Finally, experiments on the MIHA cell line and four LIHC cell lines confirmed the role of TMEM147 in promoting liver cancer cell proliferation, further confirming the clinical value of TMEM147 in liver cancer diagnosis. Our findings suggest that TMEM147 may serve as a diagnostic and prognostic biomarker across cancers while also playing a significant role in LIHC.

The widespread of different NDM variants in clinical Enterobacterales isolates poses a serious public health concern, which requires continuous monitoring. In this study, three E. coli strains carrying two novel blaNDM variants of blaNDM-36, -37 were identified from a patient with refractory urinary tract infection (UTI) in China. We conducted antimicrobial susceptibility testing (AST), enzyme kinetics analysis, conjugation experiment, whole-genome sequencing (WGS), and bioinformatics analysis to characterize the blaNDM-36, -37 enzymes and their carrying strains. The blaNDM-36, -37 harboring E. coli isolates belonged to ST227, O9:H10 serotype and exhibited intermediate or resistance to all β-lactams tested except aztreonam and aztreonam/avibactam. The genes of blaNDM-36, -37 were located on a conjugative IncHI2-type plasmid. NDM-37 differed from NDM-5 by a single amino acid substitution (His261Tyr). NDM-36 differed from NDM-37 by an additional missense mutation (Ala233Val). NDM-36 had increased hydrolytic activity toward ampicillin and cefotaxime relative to NDM-37 and NDM-5, while NDM-37 and NDM-36 had lower catalytic activity toward imipenem but higher activity against meropenem in comparison to NDM-5. This is the first report of co-occurrence of two novel blaNDM variants in E. coli isolated from the same patient. The work provides insights into the enzymatic function and demonstrates the ongoing evolution of NDM enzymes.

目的:对引起中枢神经系统感染的一株罕见粘液型溶血葡萄球菌(S.haemolyticus)表型及基因组特征进行分析.方法:收集一株导致中枢神经系统感染粘液型溶血葡萄球菌,通过生物膜形成实验、药敏实验分析生物膜形成和耐药表型,全基因组测序分析其耐药等基因特征.结果:本例溶血葡萄球菌呈粘液型,可见拉丝现象,属于苯唑西林耐药凝固酶阴性葡萄球菌(MRCoNS),同时对红霉素、克林霉素、左氧氟沙星耐药,对万古霉素、利奈唑胺敏感,比普通非粘液型溶血葡萄球菌更易形成生物膜,MLST显示该菌为ST1型,携带mecA、aph(3')-Ⅲa、aac(6')-Ie、aph(2")-Ia等8种耐药基因,mecA基因由类似Tn6191的转座子所携带.结论:呈粘液型菌落特征的溶血葡萄球菌在临床上极为罕见,该变异体比通常的非粘液型菌落更易形成生物膜且呈现出多重耐药现象.临床上应关注此类葡萄球菌的粘液变异体,这有助于其早期识别和感染防控.

Tigecycline serves as one of the last-resort antibiotics to treat severe infections caused by carbapenem-resistant Enterobacterales. Recently, a novel plasmid-mediated resistance-nodulation-division (RND)-type efflux pump gene cluster, TmexCD1-ToprJ1, and its variants, TmexCD2-ToprJ2 and TmexCD3-ToprJ3, encoding tetracyclines and tigecycline resistance, were revealed. In this study, we reported three TmexCD2-ToprJ2-harboring Klebsiella species strains, collected from two teaching tertiary hospitals in China, including one K. quasipneumoniae, one K. variicola, and one K. michiganensis. The three strains were characterized by antimicrobial susceptibility testing (AST), conjugation assay, WGS, and bioinformatics analysis. AST showed that K. variicola and K. quasipneumoniae strains were resistant to tigecycline with MIC values of 4μg/ml, whereas the K. michiganensis was susceptible to tigecycline with an MIC value of 1μg/ml. The TmexCD2-ToprJ2 clusters were located on three similar IncHI1B plasmids, of which two co-harbored the metallo-β-lactamase gene blaNDM-1. Conjugation experiments showed that all three plasmids were capable of self-transfer via conjugation. Our results showed, for the first time, that this novel plasmid-mediated tigecycline resistance mechanism TmexCD2-ToprJ2 has spread into different Klebsiella species, and clinical susceptibility testing may fail to detect. The co-occurrence of blaNDM-1 and TmexCD2-ToprJ2 in the same plasmid is of particular public health concern as the convergence of “mosaic” plasmids can confer both tigecycline and carbapenem resistance. Its further spread into other clinical high-risk Klebsiella clones will likely exacerbate the antimicrobial resistance crisis. A close monitoring of the dissemination of TmexCD-ToprJ encoding resistance should be considered.

霍乱弧菌(Vibrio cholerae)是一种致病性革兰阴性杆菌,是导致急性腹泻的病原体.根据其菌体脂多糖O抗原的不同,可将霍乱弧菌分为200多种血清型,其中O1群和O139群霍乱弧菌曾多次在世界范围内引起霍乱暴发性流行[1].非O1/非O139群霍乱弧菌(non-O1 non-O139 Vibrio cholerae,NOVC)菌株不产生霍乱毒素,因此不会引起霍乱.这些微生物的临床意义在很长一段时间内都被忽视.然而,在过去的几十年中,越来越多的报道显示NOVC与人类多种感染性疾病有关[2-3].最常见的NOVC感染是胃肠炎,中耳炎和软组织感染.目前估计发展中国家和发达国家急性腹泻发病率的1％～3.4％是由于NOVC引起的[3].NOVC菌血症是NOVC感染中病死率最高的一种,近年来报告数呈上升趋势.然而,一些临床医生对这种疾病知之甚少.本文描述了1例酒精性肝硬化肝性脑病并发NOVC菌血症的患者,血清凝集试验显示该NOVC血液分离株具有自凝性.这种现象在NOVC感染病例中非常罕见,现予以报道.同时本研究首次对国内NOVC菌血症相关的病例进行回顾性分析,以期对NOVC菌血症的临床特征和流行病学有更好的认识.

In mainland China, the clinical, epidemiological and genetic features of non-O1/non-O139Vibrio cholerae(NOVC) bacteraemia have been scarcely investigated. Herein, we describe a patient with NOVC bacteraemia diagnosed in our hospital and present a retrospective analysis of literature reports of 32 other cases in China, detailing the clinical epidemiology, antibiotic resistance and molecular characteristics of isolates. Most patients were male (84.8%; median age, 53 years) and had predisposing factors, such as cirrhosis, malignant tumours, blood diseases and diabetes. In addition to fever, gastroenteritis was the most frequent presenting symptom. The mortality rate during hospitalisation was 12.1%. NOVC bacteraemia cases were more common in June-August, with the majority in coastal provinces and the Yangtze River basin. Only 42.4% of cases were attributed to consumption of marine (aquatic) products. Tetracycline, third-generation cephalosporins, and fluoroquinolones were the most effective antimicrobial agents, and the highest frequencies of resistance were recorded for ampicillin/sulbactam (37.5%), amoxicillin/clavulanic acid (33.3%), ampicillin (29.2%) and sulfamethoxazole (20%). Multi-drug resistant isolates were not detected. Limited data indicate thatctxABandtcpAgenes were absent in all NOVC isolates but other putative virulence genes (hlyA,toxR,hapandrtxA) were common. Ten multilocus sequence types were identified with marked genetic heterogeneity between different isolates. As clinical manifestations of NOVC bacteraemia may vary widely, and isolates exhibit genetic diversity, clinicians and public health experts should be alerted to the possibility of infection with this pathogen because of the high prevalence of liver disease in China.

In mainland China, the clinical, epidemiological and genetic features of non-O1/non-O139Vibrio cholerae(NOVC) bacteraemia have been scarcely investigated. Herein, we describe a patient with NOVC bacteraemia diagnosed in our hospital and present a retrospective analysis of literature reports of 32 other cases in China, detailing the clinical epidemiology, antibiotic resistance and molecular characteristics of isolates. Most patients were male (84.8%; median age, 53 years) and had predisposing factors, such as cirrhosis, malignant tumours, blood diseases and diabetes. In addition to fever, gastroenteritis was the most frequent presenting symptom. The mortality rate during hospitalisation was 12.1%. NOVC bacteraemia cases were more common in June-August, with the majority in coastal provinces and the Yangtze River basin. Only 42.4% of cases were attributed to consumption of marine (aquatic) products. Tetracycline, third-generation cephalosporins, and fluoroquinolones were the most effective antimicrobial agents, and the highest frequencies of resistance were recorded for ampicillin/sulbactam (37.5%), amoxicillin/clavulanic acid (33.3%), ampicillin (29.2%) and sulfamethoxazole (20%). Multi-drug resistant isolates were not detected. Limited data indicate thatctxABandtcpAgenes were absent in all NOVC isolates but other putative virulence genes (hlyA,toxR,hapandrtxA) were common. Ten multilocus sequence types were identified with marked genetic heterogeneity between different isolates. As clinical manifestations of NOVC bacteraemia may vary widely, and isolates exhibit genetic diversity, clinicians and public health experts should be alerted to the possibility of infection with this pathogen because of the high prevalence of liver disease in China.

Non-O1/non-O139 Vibrio cholerae (NOVC) are increasingly being recognized as causes of sporadic cases of gastroenteritis and extra-intestinal invasive infections, such as bacteremia as well as skin and wound infections in immunosuppressed hosts. However, oral infections caused by these microorganisms have rarely been reported. We present a case of oral infection caused by NOVC in a patient undergoing chemoradiotherapy after esophagectomy for esophageal cancer. The patient recovered well after antibiotic treatment. The isolate from the patient was screened for phenotypic and genetic characteristics with reference to their major virulence genes. Our report provides supporting evidence for oral infection due to NOVC in a patient with esophageal cancer and suggests that some putative accessory virulence factors may be crucial in the pathogenicity of this strain. To the best of our knowledge, this is the first documented case of oral infection due to NOVC.

目的:了解2019年山东千佛山医院临床细菌分离株的分布及耐药性,为临床合理使用抗生素提供依据.方法:通过Bruker MALDI-TOF、Walkaway 96 plus或VITEK-2 Compact自动化细菌鉴定仪进行细菌鉴定,纸片扩散法 、Walkaway 96 plus或VITEK-2 Compact自动化药敏系统进行药物敏感性测定.药敏按照2019年CLSI M100中规定的折点.使用WHONET 5.6软件分析数据.结果:2019年1月～12月共检出7634株临床分离株,其中革兰氏阴性菌和革兰阳性菌分别占70.5％和27.4％.前五种病原体分别是大肠杆菌、肺炎克雷伯菌、铜绿假单胞菌、金黄色葡萄球菌以及鲍曼不动杆菌.甲氧西林耐药金黄色葡萄球菌(MRSA)和凝固酶阴性葡萄球菌(MRCNS)占比分别为22.1％和31％.没有检测到对万古霉素,替考拉宁或利奈唑胺耐药的葡萄球菌.0.7％的屎肠球菌菌株对万古霉素耐药.分离出239株耐碳青霉烯的肠杆菌科细菌,占所有肠杆菌科分离株的7.6％.不动杆菌属对亚胺培南和美罗培南耐药率分别为72.2％和71.9％.铜绿假单胞菌对亚胺培南和美罗培南的耐药率分别为17.3％和14.3％.结论:我院的多重耐药细菌较前两年呈下降趋势,但形势仍较严峻,医院应做好抗菌药物临床使用管理,加强感染控制措施的落实,同时保持良好的细菌耐药性监测.

目的 对1例食管癌术后放化疗患者口腔感染的霍乱弧菌进行菌株鉴定和病原特征分析.方法 取患者口腔分泌物进行分离培养并观察细菌形态特征,用基质辅助激光解吸电离飞行时间质谱(MALDI-TOF MS)进行蛋白质水平鉴定,并进行血清群检测;用K-B纸片扩散法进行药敏试验;提取细菌基因组DNA构建文库并进行细菌基因组重测序,通过核糖体多位点序列分型(rMLST)、平均核苷酸相似度(ANI)分析和非冗余蛋白质库(NR)比对,对菌株进行分子生物学鉴定,并进一步对其MLST分子分型和毒力基因进行分析.结果 MALDI-TOF MS鉴定分值为2.151,rMLST分析显示该菌株与霍乱弧菌吻合度为100％,ANI分析显示ANIb值为96.05％,ANIm值为96.56％,NR数据库基因注释得到霍乱弧菌相关的基因2981个,血清群检测为非O1/O139群霍乱弧菌.药敏试验结果显示该菌对哌拉西林/他唑巴坦、氨曲南、头孢哌酮/舒巴坦、头孢他啶、头孢吡肟、庆大霉素、阿米卡星、左氧氟沙星、环丙沙星、亚胺培南、美罗培南均敏感.MLST显示该菌株为新的ST型(ST-986),且携带toxR、hlyA、nanH、hapA、mshA、ompU、rtxC以及T6SS等毒力基因,而未检出ctxAB、tcpA、zot、ace及st等5种毒力基因.结论 检出ST-986新型非O1/O139群霍乱弧菌.临床医生应警惕免疫力低下人群中口腔感染这种病原体的可能性.