2020年3—4月全球主要疫情回顾

本刊对2020年3—4月全球重点传染病疫情(截至4月28日)汇总如下。1新冠肺炎疫情肆虐全球,全球确诊病例数破300万新冠肺炎疫情自2019年底发生后,截至2020年2月底,全球病例数约8.3万例,进入3月以后,病例数呈指数增长。从2019年底确诊首例新冠肺炎病例到全球病例数达10万,共花了67 d时间,达到第2个10万仅用了11 d,达到第3个10万用了4 d,达到第4个10万用了3 d。     

酵母双杂交技术筛选与克隆白细胞中与NS5ATP7蛋白结合的蛋白编码基因

目的 应用酵母双杂交体系寻找与丙型肝炎病毒(HCV)非结构蛋白5A反式激活蛋白7(human gene 5 transactivated by nonstructural protein 5A of hepatitis C virus,NS5ATP7)相互作用的白细胞蛋白,以探讨SN5ATP7的生物功能。方法 应用酵母双杂交系统3,构建NS5ATP7诱饵质粒,转化酵母AH109,与含人白细胞cDNA文库质粒的酵母Y187进行配合,于涂有X-α-gal营养缺陷型培养基(SD／-Trp-Leu-His-Ade)上筛选生长。挑选蓝色克隆,提取此酵母克隆的质粒转化大肠杆菌提取质粒。DNA后进行测序,然后进行生物信息学分析。结果 筛选出15个与NS5ATP7特异性相互作用的克隆,其中包括人类RhoGDF分裂抑制剂α、人类细胞色素b558a亚单位、人类MLL(MLL)基因外显子、人类S100钙结合蛋白A9(钙粒蛋白B)、人类移动抑制因子相关蛋白14变体E(S100A9)、人类金属硫蛋白2A、人类染色体序列及人类cDNA序列等,1个是未知功能基因。结论 初步克隆了NSSATP7与白细胞结合蛋白基因,根据所克隆到的基因,对以后研究NS5ATP7的功能有一定的提示作用;为以后研究这些能与NS5ATP7相互作用的基因在白细胞中的生理功能奠定了基础。     

新媒体环境下医学图书馆服务水平的提升

介绍新媒体的内涵和特征,阐述新媒体在信息传播中的表现形式丰富、获取信息便捷等优势,论述新媒体环境下医学资源的采集与揭示,提出完善新媒体服务形式、理念的途径和方法。     

蛇毒毒素的抗肿瘤作用及其在医药领域的应用

目的 探讨蛇毒毒素的抗肿瘤作用及其在医药领域的应用。方法 综述蛇毒毒素的抗肿瘤组分、抗肿瘤作用及其机制的研究进展。结果 蛇毒毒素对多种肿瘤均有抑制作用,具有直接杀伤肿瘤细胞、诱导肿瘤细胞凋亡、抑制血管再生等作用。结论 对蛇毒毒素抗肿瘤组分及其作用机制进行深入研究,是当前抗肿瘤药物研究的重要方向。     

A population pharmacokinetic study of tacrolimus in healthy Chinese volunteers and liver transplant patients

Aim:

To develop a population pharmacokinetic (PopPK) model of tacrolimus in healthy Chinese volunteers and liver transplant recipients for investigating the difference between the populations, and for potential individualized medication.

Methods:

A set of 1100 sparse trough concentration data points from 112 orthotopic liver transplant recipients, as well as 851 dense data points from 40 healthy volunteers receiving a single dose of tacrolimus (2 mg, po) were collected. PopPK model of tacrolimus was constructed using the program NONMEM. Related covariates such as age, hepatic and renal functions that were potentially associated with tacrolimus disposition were evaluated. The final model was validated using bootstrapping and a visual predictive check.

Results:

A two-compartment model of tacrolimus could best describe the data from the two populations. The final model including two covariates, population (liver transplant recipients or volunteers) and serum ALT (alanine aminotransferase) level, was verified and adequately described the pharmacokinetic characteristics of tacrolimus. The estimates of V2/F, Q/F and V3/F were 22.7 L, 76.3 L/h and 916 L, respectively. The estimated CL/F in the volunteers and liver transplant recipients was 32.8 and 18.4 L/h, respectively. Serum ALT level was inversely related to CL/F, whereas age did not influence CL/F. Thus, the elderly (≥65 years) and adult (<65 years) groups in the liver transplant recipients showed no significant difference in the clearance of tacrolimus.

Conclusion:

Compared with using the sparse data only, the integrating modeling technique combining sparse data from the patients and dense data from the healthy volunteers improved the PopPK analysis of tacrolimus.     

Implantable vaccine development using in vitro antigen-pulsed macrophages absorbed on laser micro-structured Si scaffolds

To overcome the limiting antigenic repertoire of protein sub-units and the side effects of adjuvants applied in second generation vaccines, the present work combined in vitro and in vivo manipulations to develop biomaterials allowing natural antigen-loading and presentation in vitro and further activation of the immune response in vivo. 3-dimensional laser micro-textured implantable Si-scaffolds supported mouse macrophage adherence, allowed natural seeding with human serum albumin (antigen) and specific antibody and inflammatory cytokine production in vitro. Implantation of Si-scaffolds loaded with antigen-activated macrophages induced an inflammatory reaction along with antigen-specific antibody production in vivo, which could be detected even 30 days post implantation. Analysis of implant histology using scanning electron microscopy showed that Si-scaffolds could be stable for a 6-month period. Such technology leads to personalized implantable vaccines, opening novel areas of research and treatment.     

Metabolomics analysis of multidrug-resistant breast cancer cells in vitro using methyl-tert-butyl ether method

The comprehensive characterization of metabolome and lipidome to reveal unknown pathological conditions, are being used to investigate the molecular mechanisms of cancer, especially in the field of early diagnosis, treatment, and prognosis. The multidrug resistance (MDR) of tumor cells limits the therapeutic effect of anti-cancer drugs and is the main obstacle for chemotherapy. Here, we adopted a methyl-tert-butyl ether (MTBE)-based extraction method to simultaneously extract small polar molecules and lipophilic metabolites for nontargeted metabolomics of multidrug-resistant breast cancer cell line MCF-7/ADR and its parental cell line MCF-7/S by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Distinctly different metabolic features were shown between MCF-7/ADR cells and MCF-7/S on the basis of multivariate analyses. 17 potential biomarkers were identified. And these potential biomarkers were mainly correlated with cell membrane lipids composition, cell signaling regulated by lipids, and anti-oxidation ability. The studies of cellular ultrastructure and morphology by in situ atomic force microscopy (AFM) also demonstrated the cellular membrane changed along with the MDR. We expect that this study could provide a new method for monitoring drug resistance during clinical chemotherapy and be useful for the development of drugs to overcome the MDR.

MTBE-based cellular lipidomics to investigate the mechanisms of multidrug resistance of breast cancer.     

The frequency of early-activated hapten-specific B cell subsets predicts the efficacy of vaccines for nicotine dependence

Therapeutic vaccines for nicotine addiction show pre-clinical efficacy. Yet, clinical evaluation of the first-generation nicotine vaccines did not meet expectations because only a subset of immunized subjects achieved effective serum antibody levels. Recent studies suggest that vaccine design affects B cell activation, and that the frequency of the hapten-specific B cell subsets contributes to vaccine efficacy against drugs of abuse. To extend this hypothesis to nicotine immunogens, we synthesized a novel hapten containing a carboxymethylureido group at the 2-position of the nicotine structure (2CMUNic) and compared its efficacy to the previously characterized 6CMUNic hapten. Haptens were conjugated to the keyhole limpet hemocyanin (KLH) carrier protein, and evaluated for efficacy against nicotine in mice using the clinically approved alum adjuvant. Using a novel fluorescent antigen-based magnetic enrichment strategy paired with multicolor flow cytometry analysis, polyclonal hapten-specific B cell subsets were measured in mice immunized with either 6CMUNic-KLH or 2CMUNic-KLH. The 6CMUNic-KLH showed significantly greater efficacy than 2CMUNic-KLH on nicotine distribution to serum and to the brain. The 6CMUNic-KLH elicited higher anti-nicotine serum antibody titers, and greater expansion of hapten-specific B cells than 2CMUNic-KLH. Within the splenic polyclonal B cell population, a higher number of hapten-specific IgM^high and germinal centre B cells predicted greater vaccine efficacy against nicotine distribution. These early pre-clinical findings suggest that hapten structure affects activation of B cells, and that variations in the frequency of early-activated hapten-specific B cell subsets underlie individual differences in vaccine efficacy.     

黄连解毒汤对小鼠酒精性脂肪肝的预防作用

目的 研究黄连解毒汤(HLJDT)对小鼠酒精性肝损伤的预防作用,为黄连解毒汤临床防治酒精性肝病提供实验依据。方法 选取60只C57小鼠随机分为空白对照组、模型对照组和HLJDT低、中、高剂量(0.61、1.22、2.44 g/kg/d)模型组,每组各12只。模型组用50%乙醇灌胃,同时采用HLJDT进行实验干预,6周后,对各组小鼠的体质量、肝指数、血清生化指标以及肝脏和结肠的病理学改变进行综合对比分析。结果 HLJDT各剂量模型组小鼠的体重增长量均显著增加(P<0.05),肝指数明显降低(P<0.05),同时HLJDT各剂量模型组能显著降低血清ALT、AST和TG的含量(P<0.05)。病理结果显示HLJDT各剂量均对酒精性肝损伤有显著的改善作用,且从低剂量到高剂量组对肠粘膜通透性具有递增的改善作用。结论 黄连解毒汤可显著降低肠粘膜的通透性,对小鼠酒精性肝损伤具有一定的预防保护作用。     

“文献”定义的几个问题

阐述了文献定义的重要性和界定文献的主要依据,包括文献自身存在的主要特征——知识信息,文献中的知识信息显示的信号——文字、符号、图像、音频、视频,文献中知识信息的外在形态——物质载体,知识信息固化在载体上的过程——记录,评析了已有文献的多种定义并进行了归纳,总结出文献的四要素主要包括知识信息,载体,记录,以及文字、符号、图像等。