84例颈椎结核患者影像学分析

目的 总结颈椎结核的影像学表现,为其诊断和治疗提供参考。 方法 回顾性分析2002年1月至2012年12月收治的84例颈椎结核患者的X线片、CT及MRI检查。对结核病变部位累及椎体数量及分布情况、椎体的改变情况（骨质破坏的方式、骨质缺损高度）、病变椎体的椎间隙改变情况等进行分析,同时对于椎管的改变和椎旁软组织的改变情况进行分析。对于颈椎生理弧度的变化,如存在后凸成角畸形,则测量其Cobb角的度数,通过Pearson相关分析（软件SPSS 19.0）研究Cobb角与病变椎体前缘骨质缺损高度、病程时间的相关性,并计算相关系数,以P〈0.05为差异有统计学意义。 结果 颈椎结核累及单个椎体者1例,占1.2%（1/84）;累及相邻2个椎体者63例,占75.0%（63/84）;累及3个及以上椎体者20例,占23.8%（20/84）;伴附件受累者13例,占15.5%（13/84）,未见附件单独受累。84例患者颈椎的生理弧度均有改变。其中64例颈椎生理前曲表现不同程度的减小,占76.2%（64/84）;20例颈椎或颈胸椎表现不同程度的后凸畸形,占23.8%（20/84）;后凸畸形患者Cobb角范围12°～82°,平均（29.0±19.6）°。Cobb角与病变椎体前缘骨质缺损高度、病程时间显著相关（r＝0.752～0.962,P〈0.01,差异具有统计学意义）。76例椎体有不同程度的骨质破坏,占90.5%（76/84）;8例椎体未见明显骨质破坏,仅MRI上有信号改变,占9.5%（8/84）。72例椎间隙有不同程度的狭窄,占85.7%（72/84）;12例椎间隙未见狭窄,占14.3%（12/84）。39例患者椎管变形,硬膜囊、神经根受压,占57.4%（39/68）;临床上伴有瘫痪症状者23例,占27.4%（23/84）,其中有12例病变累及颈胸段椎体（C7～T1）,占52.2%（12/23）。76例表现为椎旁软组织肿胀,占90.5%（76/84）,其中28例表现为单纯椎旁软组织肿胀,占36.8%（28/76）;48例脓肿形成,占63.2%（48/76）。 结论 影像学检查对于颈椎结核的诊断具有极为重要的意义,有助于明确病变侵及范围和程度,了解病变所致的颈椎形态变化,指导临床制订治疗规划。     

成年血行播散性肺结核并发颅内结核的临床及头颅MRI表现特征

目的 探讨成年血行播散性肺结核并发颅内结核的临床及头颅MRI表现特征,以减少漏诊与误诊。方法 收集2015年2月至2019年7月首都医科大学附属北京胸科医院临床确诊的53例成年血行播散性肺结核并发颅内结核患者的临床资料,纳入资料完整的48例患者作为研究对象,所有患者均进行了结核病相关实验室检查(包括脑脊液检测)、头颅MR平扫及增强扫描检查,分析评价患者的临床及头颅MRI表现特征。结果 48例患者中,24例(50.0%)存在结核中毒症状和呼吸系统症状,36例(75.0%)出现发热、头痛,29例(60.4%)具有神经系统症状和体征;胸部CT平扫均可见两肺弥漫性粟粒状影;脑脊液常规和生化检查异常者45例(93.8%),其中蛋白升高43例(89.6%),葡萄糖含量降低38例(79.2%),氯化物降低37例(77.1%);所有患者均行腰椎穿刺术检查,颅内压增高[>180mm H₂O (1mm H₂O=0.0098kPa)]者31例(64.6%)。48例患者行头颅MR增强扫描,8例(16.7%)未发现明确结核病灶,40例有脑实质和(或)脑膜结核病变,分别为单纯脑膜结核9例(18.8%)、单纯脑实质结核19例(39.6%)、混合型颅内结核12例(25.0%);而48例行头颅MR平扫的患者仅35例显示颅内结核病灶,除8例增强MR未显示的患者外,仍有5例未发现结核病灶。25例患者抗结核药物治疗3个月后进行了头颅MR复查,其中11例较前好转,7例较前加重,5例出现部分病灶好转和部分病灶加重,2例未见变化。结论 血行播散性肺结核并发颅内结核患者临床多见发热、头痛、神经系统症状和体征、脑脊液常规和生化检查指标异常、颅内压增高。MR头颅扫描对该病的发现率较高,尤以MR增强扫描更为明显,是发现和诊断颅内结核的重要技术。     

传染病分子生物学实验教学实践与体会

随着生命科学的快速发展,分子生物学在传染病诊断和治疗研究中的作用日益重要。本文针对传染病专科医院分子生物学实验教学特点,以问题为导向的教学方法（PBL）为核心,从更新教学内容、改进教学方法、丰富教学手段及培养科学思维等方面阐述了研究生细胞生物学实验教学改革的实践及体会。     

结核病临床研究生科研能力的培养现状和教学体会

随着人们生存环境和生活方式的改变,人类的传染性疾病谱也发生了日新月异的变化。交通事业的飞速发展,人员流动的范围不断扩大,出行频度逐年增多,加快了传染性疾病的传播速度和蔓延范围。作为以收治结核病为主的传染病医院,本院不仅要履行常规的传染病的预防和诊治工作,而且要加强临床研究生科研能力的培养来应对传染性疾病谱的改变。但是,在当前医学的教育模式下,结核病临床研究生的科研能力的培养仍然存在着一些弊端和不足,因此,教育模式的转型,优秀教育方法的引进以及不断地完善自身的科研激励措施,依旧是本院教育改革的重要方面。     

EGFR和PD-L1双靶向嵌合抗原受体构建及表达

目的:构建肿瘤相关抗原表皮生长因子受体特异性嵌合抗原受体(EGFR-CAR)和程序性死亡受体-配体1(PD-L1)抗体双修饰慢病毒载体表达系统。方法:人PD-L1-Fc蛋白免疫BALB/c小鼠,经细胞融合、亚克隆筛选高分泌PD-L1特异性抗体的稳定杂交瘤,酶联免疫吸附试验(ELISA)和Western blot检测抗体特异性,流式细胞术(FACS)鉴定对PD-1配受体封阻性能,Fortebio测定抗体亲和力,抗体全长测序,经保留鼠源CRD1、CRD2和CRD3人源化改造后构建单链抗体(single-chain variable fragment,scFv);人EGFR单克隆抗体杂交瘤系,经5′RACE技术扩增其轻链和重链可变区(VL和VH)基因,构建scFv,克隆至真核载体pcDNA3.1表达鉴定。基因合成EGFR-CAR(引入CD137协同信号胞内功能域)与PD-L1-scFv借助2A序列连接,克隆入慢病毒pLVX-EF1a-IRES-ZsGreen1表达载体,使用Lenti-X Packaging Single Shots (VSV-G)共同转染293T细胞,获得包装病毒,感染293V细胞,FACS测定CAR膜表达,ELISA检测CAR感染293V细胞培养上清中PD-L1-scFv表达情况,转染激活人外周血T细胞,验证CAR膜表达。结果:获得PD-L1抗体11E3,具备高度配受体封阻性能,经人源化改造后,亲和力稳定(2.67×10 -10 mol/L),EGFR-scFv获得有效表达。进一步构建了EGFR-CAR和PD-L1双修饰慢病毒分泌型CAR(CTC0537-1)及膜表达型CAR(CTC0537-2),其病毒感染293V细胞阳性率为10%。CTZ0431-1感染293V细胞后,细胞膜表面表达EGFR-scFv,检测培养上清存在PD-L1-ScFv;CTZ0431-2感染293V细胞后,细胞膜表面EGFR-scFv和PD-L1-scFv有效表达,双表达病毒感染活化T细胞的CAR表达率为39.3%。 结论:成功构建了EGFR-CAR和PD-L1-scFv双表达慢病毒载体,EGFR-CAR中度结合亲和力,此为EGFR靶向和PD-L1抗体双修饰CAR-T细胞的实体瘤治疗研究提供了关键工具。     

Liquid Formulation of Gemcitabine Increases Venous Pain in Patients With Cancer: A Retrospective Study

PurposeVenous pain induced by peripheral intravenous infusion of gemcitabine has remained an unresolved issue in clinical practice. This study aimed to identify differences between gemcitabine formulations as well as risk factors associated with gemcitabine-induced venous pain in patients with cancer.MethodsWe retrospectively analyzed data from consecutive patients with cancer who had received chemotherapy including a lyophilized or liquid formulation of gemcitabine diluted with 5% glucose solution via a peripheral vein. The study was conducted at Ehime University Hospital using electronic medical records dated between January 2015 and July 2017. The primary end point was the prevalence of venous pain at the administration site during gemcitabine infusion, classified as injection site reaction of grade ≥2 according to the Common Terminology Criteria for Adverse Events, version 4.0. A multivariate logistic regression analysis with generalized estimating equations for longitudinal data was used to identify risk factors for venous pain during all courses of gemcitabine treatment.FindingsA total of 1150 treatment courses in 141 Japanese patients were evaluated in this study. Venous pain occurred in 115 courses (10.0%) and in 49 patients (34.8%). The multivariate logistic regression analysis with generalized estimating equations revealed that a dose increase of gemcitabine and use of the liquid formulation of gemcitabine were significantly associated with an increased risk for venous pain (dose increase, adjusted odds ratio [OR] = 1.25; 95% CI, 1.11–1.40 [P < 0.001]; and liquid formulation, adjusted OR = 12.43, 95% CI, 5.61–27.51 [P < 0.001]), whereas age, course number of gemcitabine, and use of the soft-back product of 5% glucose solution were significantly associated with a reduced risk for venous pain (age, adjusted OR = 0.75; 95% CI, 0.57–0.98 [P = 0.037]; course number, adjusted OR = 0.96; 95% CI, 0.92–0.99 [P = 0.023]; and soft back, adjusted OR = 0.39; 95% CI, 0.21–0.74 [P = 0.004]).ImplicationsThe use of the liquid formulation of gemcitabine was associated with a significant increase in the frequency of gemcitabine-induced venous pain despite dilution with 5% glucose solution compared to that with the lyophilized formulation. The lyophilized formulation of gemcitabine should hence be used in peripheral intravenous infusion for the treatment of patients with cancer.     

BioAge: Toward a multi-determined,mechanistic account of cognitive aging

The search for reliable early indicators of age-related cognitive decline represents a critical avenue for progress in aging research. Chronological age is a commonly used developmental index; however, it offers little insight into the mechanisms underlying cognitive decline. In contrast, biological age (BioAge), reflecting the vitality of essential biological systems, represents a promising operationalization of developmental time. Current BioAge models have successfully predicted age-related cognitive deficits. Research on aging-related cognitive function indicates that the interaction of multiple risk and protective factors across the human lifespan confers individual risk for late-life cognitive decline, implicating a multi-causal explanation. In this review, we explore current BioAge models, describe three broad yet pathologically relevant biological processes linked to cognitive decline, and propose a novel operationalization of BioAge accounting for both moderating and causal mechanisms of cognitive decline and dementia. We argue that a multivariate and mechanistic BioAge approach will lead to a greater understanding of disease pathology as well as more accurate prediction and early identification of late-life cognitive decline.     

Molecular typing and drug susceptibility of Mycobacterium tuberculosis isolates from Chongqing Municipality,China

China’s tuberculosis (TB) burden is second only to that of India worldwide. In Chongqing, the largest municipality in southwestern China, although the prevalence of both TB and drug-resistant TB is higher than in other municipalities, the molecular characteristics and drug susceptibility phenotypes are poorly known. In this study, 297 Mycobacterium tuberculosis isolates from Chongqing were genotyped with spacer oligonucleotide typing (spoligotyping) and 28-locus MIRU-VNTR (24-locus MIRU-VNTR scheme and 4 other loci). Spoligotyping results were compared with drug-resistant profiles. Patients who showed clustering by both spoligotyping and 28-locus MIRU-VNTR were interviewed to investigate their detailed contact history. Our data demonstrated that the Beijing genotype was the most prevalent genotype, and ST1 was the most predominant lineage in Chongqing. The Beijing genotype was significantly associated with ethambutol resistance and multidrug-resistant phenotypes. A combination of the 10 most polymorphic loci permitted to achieve higher discriminatory power than 24-VNTR. In addition, a presumed transmission pathway was observed in a cluster of patients with the same MIRU-VNTR profile. The 10-VNTR locus set is suitable for genotyping of Mycobacterium tuberculosis in Chongqing.