耐碳青霉烯革兰阴性杆菌耐药性及耐药基因blaKPC的分子特征

目的 探讨耐碳青霉烯类革兰阴性杆菌的临床耐药性及耐药基因blaKPC的分子特征。方法 分析2017年1月-2018年12月某院临床检出的耐碳青霉烯类革兰阴性杆菌。通过WHONET 5.6软件对药物敏感试验数据进行统计分析,采用PCR检测碳青霉烯耐药基因blaKPC、blaNDM、blaIMP、blaVIM、blaOXA-48,对PCR阳性产物进行DNA测序,分析耐药基因的分子结构特点。结果 共收集510株耐碳青霉烯类革兰阴性杆菌,其中耐碳青霉烯类肠杆菌科细菌（CRE）420株,耐碳青霉烯非肠杆菌科细菌90株。菌株主要来自重症监护病房（ICU）、神经外科和呼吸科,分别占60.8%、11.8%、5.3%;标本来自痰、脓性分泌物、静脉血、无菌中段尿,分别占66.9%、8.8%、8.2%、6.5%。耐碳青霉烯类革兰阴性杆菌对常用抗菌药物具有较高的耐药性。PCR结果显示,420株CRE中blaKPC、blaNDM、blaIMP的阳性率分别为54.3%（228/420）、1.2%（5/420）、1.4%（6/420）,未检测出blaVIM和blaOXA-48基因,其中肺炎克雷伯菌、产气肠杆菌、大肠埃希菌分别占携带blaKPC CRE的83.8%、11.8%、2.6%;其他少见菌种中也检出blaKPC基因。非肠杆菌科细菌中仅有2株鲍曼不动杆菌检测出blaKPC。DNA测序结果显示,174株携带blaKPC的菌株中173株检测为blaKPC-2、1株检测为blaKPC-1。结论 该地区耐碳青霉烯类革兰阴性菌以CRE为主,其中以携带blaKPC-2的肺炎克雷伯菌占绝对优势,其他菌株中也均有发现。提示临床需重点加强耐碳青霉烯类肺炎克雷伯菌的监测及预防,防控blaKPC的传播流行。     

阴沟肠杆菌对碳青霉烯类药物的耐药机制

 目的 研究耐碳青霉烯类阴沟肠杆菌分子流行病学特征和碳青霉烯耐药机制,为临床经验性用药及医院感染防控提供依据。方法 对某院2019年4—9月分离的耐碳青霉烯类阴沟肠杆菌进行菌种鉴定及药敏分析,mCIM联合eCIM试验筛选碳青霉烯酶,聚合酶链反应（PCR）方法检测碳青霉烯酶耐药基因,多位点序列分型（MLST）和脉冲场凝胶电泳（PFGE）进行分子流行病学特征分析。结果 8株耐碳青霉烯类阴沟肠杆菌中5株来自于重症监护病房（ICU）,对临床常用头孢类及加酶抑制剂药物均表现出高水平耐药的特性。所有菌株均携带金属β-内酰胺酶,7株为bla_NDM-1,1株为bla_IPM-4。MLST分子分型及PFGE同源性分析有6个ST序列类型,6个克隆群。ST596（3株）均为A群、ST121（1株）为C群、ST993（1株）为F群、ST91（1株）为E群、ST794（1株）为B群、ST88（1株）为D群。结论 该院耐碳青霉烯类阴沟肠杆菌主要来源于ICU,产金属酶bla_NDM-1β-内酰胺酶是其主要耐药机制。ST596 A群阴沟肠杆菌短时间内在ICU存在局部流行,应加强医院感染防控措施,遏制暴发流行。     

海口市儿童肺炎患者呼吸道标本流感嗜血杆菌的耐药性与分子流行病学特征

 目的 调查海口市肺炎患儿分离的流感嗜血杆菌临床分布、耐药状况及克隆传播情况,为预防和治疗儿童流感嗜血杆菌性肺炎提供理论依据。方法 收集2021年海口市妇幼保健院5 342例住院肺炎患儿临床资料,分析患儿呼吸道标本流感嗜血杆菌阳性情况,检测菌株耐药性,并采用多位点序列分型（MLST）分析其同源性。结果 5 342例肺炎患儿共分离352株流感嗜血杆菌,检出率为6.59%;男患儿检出率为7.10%,女患儿检出率为5.82%;年龄<30 d检出率为0.30%,30 d~为8.45%,2岁~为11.62%,4岁~为12.88%,≥ 6岁为2.56%,各年龄段检出率比较差异有统计学意义（P<0.05）;春季检出率为14.04%,夏季为4.48%,秋季为4.62%,冬季为4.40%,各季节检出率比较差异有统计学意义（P<0.001）。流感嗜血杆菌β-内酰胺酶阳性率为42.60%（141/331）,对复方磺胺甲口恶唑、氨苄西林、头孢呋辛的耐药率分别为76.43%、69.19%、51.36%,对阿奇霉素、阿莫西林/克拉维酸、头孢他啶和头孢曲松的耐药率<30%,对美罗培南和左氧氟沙星的耐药率<1%。51株流感嗜血杆菌经MLST测序分成15个ST型;其中ST107包含11株（21.57%）,主要分布在4个月~1岁患儿（9株）和3岁患儿（2株）。结论 海口市肺炎患儿分离的流感嗜血杆菌具有遗传多样性,且发生社区克隆传播,以2~3岁幼儿感染多见。春季是感染高发季节,ST107是春季流行优势克隆型。经验治疗时须谨慎使用复方磺胺甲口恶唑、氨苄西林和头孢呋辛,阿莫西林/克拉维酸耐药率和β-内酰胺酶阴性菌株对氨苄西林耐药率升高,临床应引起重视。     

Risks and Complications After Arthroplasty for Pathological or Impending Pathological Fracture of the Hip

BackgroundTreatment options for metastatic osseous lesions of the proximal femur include hemiarthroplasty (HA) or total hip arthroplasty (THA) depending on lesion characteristics and patient demographics. Studies assessing short-term outcomes after HA/THA in this patient population are limited. Therefore, the purpose of this present study was to identify short-term rates of morbidity and mortality after HA/THA for pathological proximal femur fractures, as well as readmission and reoperation rates and reasons.MethodsThis study utilized a large, prospectively collected registry to identify patients who underwent HA/THA between 2011 and 2018. Patients were stratified by indication for surgery, including pathological fracture, nonpathological fracture, and osteoarthritis. Baseline patient characteristics and postoperative complications were compared using bivariate and/or multivariate analysis.ResultsIn total, 883 patients undergoing HA/THA for a pathological fracture were identified. Relative to an osteoarthritis cohort, these patients tended to be older, had a lower body mass index, and had significantly more preoperative comorbidities. These patients had high rates of total complications (13.93%), including thirty-day mortality (3.29%), unplanned return to the operating room (4.98%), and pulmonary complications (3.85%). Patients with pathological fracture had a longer operative duration relative to osteoarthritis and nonpathological cohorts (+27 and +25 minutes, respectively), despite having high rates of HAs performed.ConclusionPatients undergoing hip arthroplasty for pathologic proximal femur fracture have increased morbidity and mortality relative to an osteoarthritis cohort. However, patients with a pathological fracture have similar rates of morbidity and mortality when compared with a nonpathological fracture cohort, but did experience higher rates of perioperative blood transfusion and unplanned readmissions.Level of EvidenceIII.     

中国胆囊癌外科治疗现状与病理学特征多中心回顾性研究（附4345例报告）

目的 探讨中国胆囊癌病人的外科治疗模式、病理学特征和预后。方法 收集中国13个省市的26家医院自2010年1月至2017年12月收治的4345例胆囊癌病人临床资料,分析中国胆囊癌病人的地区、性别、年龄分布;基于病人的诊疗记录与检查结果对手术病人肿瘤的可切除性进行评估,分析可切除性肿瘤病人的外科治疗模式,参照术前检查、手术记录和术后病理学检查结果评估可切除性肿瘤手术治疗是否达到根治标准,分析行根治性手术胆囊癌病人的病理学特征。结果 4345例胆囊癌病人中,男性1664例（38.23%）,女性2681例（61.77%）。行外科手术治疗的病人3129例（71.01%）,其中可切除性肿瘤2074例（66.28%）。在可切除性肿瘤2074例病人中,仅1133例（54.63%）在术前即诊断为胆囊恶性肿瘤,1002例（48.31%）行根治性切除,1072例（51.69%）未达根治标准。胆囊癌根治性切除病人的病理学检查结果中,736例（73.45%）为腺癌,348例（34.73%）为低分化癌,376例（37.52%）伴肝侵犯,152例（15.17%）伴神经浸润,96例（9.58%）伴血管内癌栓,78例（7.78%）伴周围脂肪组织浸润,89例（8.88%）伴周围器官受累,328例（32.73%）活体组织病理学检查淋巴结阳性。获得生存随访资料的2357例手术治疗病人术后中位生存期为16.17个月,多因素Cox回归生存分析结果显示肿瘤TNM分期（P<0.001）、肿瘤分化程度（P<0.001）、肝脏侵犯（P<0.001）、R0切除（P=0.003）均为术后生存期的独立预后因素。结论 中国胆囊癌术前诊断率有待提高;胆囊癌外科治疗模式亟待规范;病理学检查报告中反映的多个因素与胆囊癌病人预后密切相关,其描述的规范化对指导胆囊癌病人的精准治疗有重要意义。     

生信分析肾阴虚型绝经后骨质疏松症分子机制及熟地黄靶向治疗

目的基于生信数据挖掘探究肾阴虚型绝经后骨质疏松症的病理机制及熟地黄的治疗靶点。方法通过GEO数据库挖掘阴虚型绝经后骨质疏松症患者差异表达基因,运用GeneCards及OMIM数据库预测骨质疏松症相关基因,采用R软件对阴虚靶点与骨质疏松靶点映射匹配。借助String数据库在线平台进行蛋白互作网络构建。分子对接预测熟地黄治疗阴虚型骨质疏松症的靶点。采用DAVID数据库进行生物过程及通路注释。结果通过分析得到差异表达基因1 272个,骨质疏松症靶点662个,阴虚型骨质疏松症相关靶点45个,主要涉及细胞凋亡调节、雌激素应答、骨骼肌系统发育等生物过程,并由PI3K-Akt、Wnt信号通路、MAPK信号通路、卵巢类固醇生成等信号通路调节。熟地2种有效成分能够作用于核心蛋白IGF1、VEGFA等。结论熟地黄可能靶向IGF1、VEGFA等核心蛋白,通过PI3K-Akt、MAPK等信号通路调节细胞凋亡及雌激素应答过程,从而实现防治阴虚型骨质疏松症的疗效。     

结直肠锯齿状腺瘤的临床特征及恶变影响因素分析

目的锯齿状腺瘤被公认为结直肠癌的癌前病变,锯齿状通路被认为是可以独立发展成结直肠癌的重要通路,但目前对于锯齿状腺瘤恶变的相关危险因素还知之甚少。本文旨在分析锯齿状腺瘤在结直肠中的分布特点及潜在恶变因素。方法采用病例对照研究方法,回顾性收集2017年4月至2019年7月期间在中国医学科学院肿瘤医院行肠镜检查并经病理诊断为锯齿状腺瘤患者的临床资料,排除同时具有两种及以上病理类型病变的患者。总结锯齿状腺瘤的临床特征,并进行单因素和Logistic多因素回归分析,探讨锯齿状腺瘤发生恶变的影响因素。结果共在28730例行肠镜检查患者中,发现311例(1.08%)锯齿状腺瘤患者,共发现锯齿状腺瘤372枚。按WHO分类,无蒂锯齿状腺瘤/息肉22枚(5.9%),传统锯齿状腺瘤84枚(22.6%),未分类锯齿状腺瘤266枚(71.5%)。病理结果显示:无异型增生病变106枚(28.5%),低级别上皮内瘤变病变228枚(61.3%),高级别上皮内瘤变或癌变38枚(10.2%)。病变长径<10 mm有204枚(54.8%),≥10 mm有168枚(45.2%);病变位于左半结直肠238枚(64.0%),右半结肠134枚(36.0%)。内镜下大体分型:扁平型16枚(4.3%),无蒂型174枚(46.8%),亚蒂型117枚(31.5%),带蒂型59枚(15.9%)。窄带成像国际结直肠内镜(NICE)分型:Ⅰ型85枚(22.8%),Ⅱ型280枚(75.3%),Ⅲ型4枚(1.1%)。单因素分析显示,病变大小、病变位置、病变部位及不同WHO分类与结直肠锯齿状腺瘤发生恶变有关(均P<0.05);不同NICE分型的锯齿状腺瘤,其恶变率的差异亦有统计学差异(P=0.001)。多因素分析结果显示,病变长径≥10 mm(OR=6.699,95%CI:2.843~15.786)以及病变位于左半结直肠(OR=2.657,95%CI:1.042~6.775)是结直肠锯齿状腺瘤发生恶变的独立危险因素。结论锯齿状腺瘤主要位于左半结直肠,当病变长径≥10 mm或病变位于左半结直肠时,易发生恶变。     

Mutation profile and its correlation with clinicopathology in Chinese hepatocellular carcinoma patients

BackgroundHepatocellular carcinoma (HCC) is one of the most common causes of cancer worldwide. Although many studies have focused on oncogene characteristics, the genomic landscape of Chinese HCC patients has not been fully clarified.MethodsA total of 165 HCC patients, including 146 males and 19 females, were enrolled. The median age was 55 years (range, 27–78 years). Corresponding clinical and pathological information was collected for further analysis. A total of 168 tumor tissues from these patients were selected for next-generation sequencing (NGS)-based 450 panel gene sequencing. Genomic alterations including single nucleotide variations (SNV), short and long insertions and deletions (InDels), copy number variations, and gene rearrangements were analyzed. Tumor mutational burden (TMB) was measured by an algorithm developed in-house. The top quartile of HCC was classified as TMB high.ResultsA total of 1,004 genomic alterations were detected from 258 genes in 168 HCC tissues. TMB values were identified in 160 HCC specimens, with a median TMB of 5.4 Muts/Mb (range, 0–28.4 Muts/Mb) and a 75% TMB of 7.7 Muts/Mb. The most commonly mutated genes were TP53, TERT, CTNNB1, AXIN1, RB1, TSC2, CCND1, ARID1A, and FGF19. SNV was the most common mutation type and C:G>T:A and guanine transformation were the most common SNVs. Compared to wild-type patients, the proportion of Edmondson grade III–IV and microvascular invasion was significantly higher in TP53 mutated patients (P<0.05). The proportion of tumors invading the hepatic capsule was significantly higher in TERT mutated patients (P<0.05). The proportion of Edmondson grade I-II, alpha fetoprotein (AFP) <25 µmg/L, and those without a history of hepatitis B was significantly higher in CTNNB1 mutated patients (P<0.05). CTNNB1 mutations were associated with TMB high in HCC patients (P<0.05). Based on correlation analysis, the mutation of TP53 was independently correlated with microvascular invasion (P=0.002, OR =3.096) and Edmondson grade III–IV (P=0.008, OR =2.613). The mutation of TERT was independently correlated with tumor invasion of the liver capsule (P=0.001, OR =3.030), and the mutation of CTNNB1 was independently correlated with AFP (<25 µmg/L) (P=0.009, OR =3.414).ConclusionsThe most frequently mutated genes of HCC patients in China were TP53, TERT, and CTNNB1, which mainly lead to the occurrence and development of HCC by regulating the P53 pathway, Wnt pathway, and telomere repair pathway. There were more patients with microvascular invasion and Edmondson III–IV grade in TP53 mutated patients and more patients with hepatic capsule invasion in TERT mutated patients, while in CTNNB1 mutated patients, there were more patients with Edmondson I–II grade, AFP <25 µmg/L, and a non-hepatitis B background. Also, the TMB values were significantly higher in CTNNB1 mutated patients than in wild type patients.