安徽地区汉族心血管疾病患者SLCO1B1与ApoE基因多态性分布及其在他汀类药物临床个体化应用中的意义

目的：探讨脂质及药物代谢相关基因SLCO1B1和ApoE的基因多态性在安徽地区汉族心血管疾病患者中的分布，以评估他汀类药物个体化用药的效益/风险比。方法：利用PCR-荧光探针法技术检测2019年1月至2020年8月合肥市第二人民医院736例心血管疾病患者外周血基因组中SLCO1B1基因的rs2306283（388A>G）和rs4149056（521T>C）位点和ApoE基因的rs429358（388T>C）和rs7412（526C>T）位点的基因多态性分布特点，并与已报道的中国其他地区汉族心血管疾病患者的数据进行比较，分析不同地区间的基因型分布差异。结果：检测到安徽地区汉族心血管疾病患者中SLCO1B1基因型有6种，分别为*1a/*1a型（6.11%）、*1a/*1b型（29.08%）、*1b/*1b型（44.57%）、*1a/*15型（4.08%）、*1b/*15型（15.49%）、*15/*15型（0.68%），未检测到*1a/*5型、*5/*5型和*5/*15型；ApoE基因有6种表型，分别为E2/E2型（0.41%）、E2/E3型（11.96%）、E2/E4型（1.09%）、E3/E3型（67.66%）、E3/E4型（17.93%）、E4/E4型（0.95%）。两种基因的基因多态性频率分布满足Hardy-Weinberg遗传平衡，具有群体代表性。本研究人群中携带SLCO1B1正常肌病风险型的比例最高，约占79.76%；SLCO1B1中度肌病风险型和高度肌病风险型的人群比例较低，分别为19.57%和0.68%。ApoE大众类基因型比例最高，约占68.75%；ApoE保护类基因型及风险类基因型的人群比例分别为12.37%和18.88%。不同性别间SLCO1B1和ApoE基因表型患者差异无统计学意义。与华南地区心血管疾病患者相比，安徽地区ApoE基因多态性分布差异有统计学意义（P<0.05）。结论：安徽地区736例心血管疾病患者SLCO1B1和ApoE基因型分别以他汀药物剂量耐受性较高的正常肌病风险型和对他汀药物敏感的大众类基因型为主，服用他汀类药物诱发肌病的风险较低，降脂疗效较好；且两种基因的多态性分布均不受性别的影响，但ApoE基因多态性分布特征可能在地域上存在差异。因此，检测SLCO1B1和APOE基因多态性对于临床评估效益/风险比有重要的指导意义。     

基于MF-DCCA 的呼吸道疾病与大气污染物相关性分析

针对呼吸道系统疾病与大气 PM2:5、 SO2 浓度序列的相关性特征, 应用多重分形消除趋势波动分析法 (MF-DCCA), 对张家界市永定区呼吸道系统疾病患病人数与大气 PM2:5、 SO2 浓度序列进行了研究。结果发现该地区 呼吸道系统疾病患病人数与大气 PM2:5、 SO2 浓度的相关性具有长期持续特征和多重分形特征。随后对它们相关性 多重分形特征的动力来源进行了分析, 通过随机重排和相位随机处理, 结果表明在不同时间尺度上的长期持续性影响 是其主要动力来源。进一步研究发现该地区呼吸道系统疾病与大气 PM2:5、 SO2 浓度序列的相关性在四个季节均具 有长期持续性的多重分形特征, 且夏季多重分形特征相对强于其他季节。     

细胞模型在临床营养研究中应用现状

传统临床营养研究多停留在人群和动物试验阶段,随着临床营养研究的深入发展,细胞模型试验也逐渐成为临床营养研究中的重要方式。本文主要综述了临床营养中的细胞模型试验常用的细胞系,详细阐述了细胞模型在临床营养中的应用现状,涉及动脉粥样硬化性心脑血管疾病、肌肉衰减综合征、肾脏疾病、肿瘤、胃肠疾病、肝损伤、过敏性炎症、烧伤等领域,就我国居民死因排名靠前的4种疾病做了重点阐述,分别指出各种疾病临床营养研究中常用细胞模型、细胞模型试验的应用优势及其科学意义,以及细胞模型发展应用趋势(三维细胞、细胞组、微流控、高通量高内涵),总结了临床营养中传统细胞模型试验的局限性,并对细胞模型试验中新技术新方法的应用前景进行展望。     

2015—2018年上海市浦东新区食源性疾病主动监测病原学及流行病学特征分析

目的 了解上海市浦东新区特定病原体食源性疾病的流行趋势和特征,为制定食源性疾病防控策略提供参考。方法 采集2015—2018年于上海市浦东新区开展食源性疾病主动监测的数据,2家哨点医院采集以腹泻症状为主诉感染病例的粪便或肛拭子标本,进行副溶血性弧菌、沙门菌、志贺菌、致泻大肠埃希菌、空肠弯曲菌和诺如病毒检验,同时对患者进行相关信息采集、分析。结果 共监测和采集2 871例腹泻病例的粪便或肛拭子标本,病原体总体检出率为23.55%(676/2 871),其中,诺如病毒为20.04%(97/484)、致泻大肠埃希菌为11.84%(340/2 871)、空肠弯曲菌为7.21%(68/943)、副溶血性弧菌为4.01%(115/2 871)、沙门菌为3.27%(94/2 871)、志贺菌为0.28%(8/2 871)；第三季度的病原体检出率较高,呈现较明显的夏秋季高峰；可疑食物主要是混合/多种食品(41.12%,278/676),其次为水产动物及其制品(22.19%,150/676)和肉与肉制品(10.95%,74/676)。结论 诺如病毒和致泻大肠埃希菌是上海市浦东新区腹泻病例的主要病原体,应进一步完善食源性疾病主动监测,对特定病原体阳性病例开展流行病学个案调查,为开展有效防控提供技术支持。     

Flow Cytometry: From Experimental Design to Its Application in the Diagnosis and Monitoring of Respiratory Diseases

Recent advances in the field of flow cytometry (FCM) have highlighted the importance of incorporating it as a basic analysis tool in laboratories. FCM not only allows the identification of cell subpopulations by detecting the expression of molecules in the cell membrane or cytoplasm, but it can also quantify and identify soluble molecules. The proper functioning of the FCM requires six fundamental systems, from those related to the transport of events to the systems dedicated to the analysis of information. In this review, we have identified the main considerations that every FCM user must know for an optimal antibody panel design, the quality systems that must govern the FCM protocols to guarantee reproducible results in research or clinical laboratories. Finally, we have introduced the current evidence that highlights the relevance of FCM in the investigation and clinical diagnosis of respiratory diseases, establishing important advances in the basic and clinical study of diseases as old as Tuberculosis along with the recent proposals for the monitoring and classification of patients infected with the new SARS-CoV2 virus.     

High Levels of the Cleaved Form of Galectin-9 and Osteopontin in the Plasma Are Associated with Inflammatory Markers That Reflect the Severity of COVID-19 Pneumonia

Numbers of patients with coronavirus disease 2019 (COVID-19) have increased rapidly worldwide. Plasma levels of full-length galectin-9 (FL-Gal9) and osteopontin (FL-OPN) as well as their truncated forms (Tr-Gal9, Ud-OPN, respectively), are representative inflammatory biomarkers. Here, we measured FL-Gal9, FL-OPN, Tr-Gal9, and Ud-OPN in 94 plasma samples obtained from 23 COVID-19-infected patients with mild clinical symptoms (CV), 25 COVID-19 patients associated with pneumonia (CP), and 14 patients with bacterial infection (ID). The four proteins were significantly elevated in the CP group when compared with healthy individuals. ROC analysis between the CV and CP groups showed that C-reactive protein had the highest ability to differentiate, followed by Tr-Gal9 and ferritin. Spearman’s correlation analysis showed that Tr-Gal9 and Ud-OPN but not FL-Gal9 and FL-OPN, had a significant association with laboratory markers for lung function, inflammation, coagulopathy, and kidney function in CP patients. CP patients treated with tocilizumab had reduced levels of FL-Gal9, Tr-Gal9, and Ud-OPN. It was suggested that OPN is cleaved by interleukin-6-dependent proteases. These findings suggest that the cleaved forms of OPN and galectin-9 can be used to monitor the severity of pathological inflammation and the therapeutic effects of tocilizumab in CP patients.     

Phenotypic Discovery of SB1501, an Anti-obesity Agent,through Modulating Mitochondrial Activity

Obesity has become a pandemic that threatens the quality of life and discovering novel therapeutic agents that can reverse obesity and obesity-related metabolic disorders are necessary. Here, we aimed to identify new anti-obesity agents using a phenotype-based approach. We performed image-based high-content screening with a fluorogenic bioprobe (SF44), which visualizes cellular lipid droplets (LDs), to identify initial hit compounds. A structure-activity relationship study led us to yield a bioactive compound SB1501, which reduces cellular LDs in 3T3-L1 adipocytes without cytotoxicity. SB1501 induced the expression of gene products that regulate mitochondrial biogenesis and fatty acid oxidation in 3T3-L1 adipocytes. Daily treatment with SB1501 improved the metabolic states of db/db mice by reducing body fat mass, adipose tissue mass, food intake, and increasing glucose tolerance. The anti-obesity effect of SB1501 may result from perturbation of the PGC-1α–UCP1 regulatory axis in inguinal white adipose tissue and brown adipose tissue. These data suggest the therapeutic potential of SB1501 as an anti-obesity agent via modulating mitochondrial activities.