TCR-T细胞免疫疗法治疗肝细胞癌的研究现状及策略

肝细胞癌是原发性肝癌的主要病理类型,目前的临床治疗方法难以达到理想的效果,迫切需要探索新的、有效的治疗方法。T细胞受体基因工程改造T细胞(TCR-T)疗法因在实体瘤中的成功应用,被认为是最有前景的免疫治疗方式之一。本文主要从TCR-T治疗在肝细胞癌中的研究进展进行综述,并针对性提出一些解决策略,包括优化TCR亲和力、降低毒性反应、减少外源性和内源性TCR双链错配、改善肿瘤微环境、促进TCR-T细胞扩增。     

Catalase-Negative Staphylococcus lugdunensis Strain with a Novel Point Mutation in the Catalase Gene Isolated from a Patient with Chronic Suppurative Otitis Media

This report describes the results of the sequence analysis of a methicillin-susceptible strain of catalase-negative Staphylococcus lugdunensis. Molecular characterization of the deduced sequence revealed a novel point mutation in the catalase gene. To our knowledge, this is the first report of a catalase-negative S. lugdunensis strain, although catalase-negative isolates of Staphylococcus aureus and Staphylococcus epidermidis have been previously reported.     

Impact of Margin Status on Survival in Patients with Pancreatic Ductal Adenocarcinoma Receiving Neoadjuvant Chemotherapy

1. Download : Download high-res image (280KB)
2. Download : Download full-size image

     

Melatonin mediates protective effects on inflammatory response induced by interleukin‐1 beta in human mesenchymal stem cells

Joint diseases like osteoarthritis usually are accompanied with inflammatory processes, in which pro‐inflammatory cytokines mediate the generation of intracellular reactive oxygen species (ROS) and compromise survival of subchondral osteoblasts. Melatonin is capable of manipulating bone formation and osteogenic differentiation of mesenchymal stem cells (MSCs). The aim of this work was to investigate the anti‐inflammatory effect of melatonin on MSC proliferation and osteogenic differentiation in the absence or presence of interleukin‐1 beta (IL‐1β), which was used to induce inflammation. Our data showed that melatonin improved cell viability and reduced ROS generation in MSCs in a dose‐dependent manner. When exposed to 10 ng/mL IL‐1β, various concentrations of melatonin resulted in significant reduction of ROS by 34.9% averagely. Luzindole as a melatonin receptor antagonist reversed the anti‐oxidant effect of melatonin in MSCs with co‐exposure to IL‐1β. Real‐time RT‐PCR data suggested that melatonin treatment up‐regulated the expression of CuZnSOD and MnSOD, while down‐regulated the expression of Bax. To investigate the effect of melatonin on osteogenesis, MSCs were cultured in osteogenic differentiation medium supplemented with IL‐1β, melatonin, or luzindole. After exposed to IL‐1β for 21 days, 1 μm melatonin treatment significantly increased the levels of type I collagen, ALP, and osteocalcin, and 100 μm melatonin treatment yielded the highest level of osteopontin. Our study demonstrated that melatonin maintained MSC survival and promoted osteogenic differentiation in inflammatory environment induced by IL‐1β, suggesting melatonin treatment could be a promising method for bone regenerative engineering in future studies.     

基于德尔菲法和层次分析法的硕士研究生生源质量评价指标体系研究

目的构建准确、有效、易操作的研究生生源质量评价体系，促进研究生教育健康发展。 方法在利益相关者调查、文献研究及专家访谈的基础上，初步确定硕士研究生生源质量评价指标体系的一级、二级指标，运用德尔菲法进行两轮专家咨询最终确定硕士研究生生源质量评价指标，运用层次分析法计算评价指标权重。 结果专家熟悉程度为0.8657、0.8648，判断依据为 0.7457、0.7484，权威系数为 0.8057、0.8314，Kendall协调系数为 0.125、0.406（ P<0.001）。确定硕士研究生生源质量评价指标包括 4项一级指标、14项二级指标。一级指标为成绩指标、背景结构、专业适配、综合素质，权重分别为 0.42、0.23、0.23、0.12，判断矩阵的一致性比例（CR）为 0.004，二级指标判断矩阵的（CR）分别为0.017、0.018、0.018、0。 结论运用德尔菲法和层次分析法构建的硕士研究生生源质量评价指标体系及其权重较为科学，结果可信，可对研究生生源质量进行科学的诊断性评估，为研究生教育的培养、就业跟踪评价奠定了重要的基础作用。     

温通膏外敷联合中频电疗治疗冻结肩的疗效观察

目的:观察温通膏外敷联合中频电疗对冻结肩的临床疗效。方法:选取90例冻结肩病例,随机分为温通膏组、中频组,联合组。温通膏组使用温通膏外敷患者患处,中频组使用中频电疗,联合组则同时给予温通膏外敷及中频电疗治疗,三组均连续治疗10天。观察患者治疗前后的Constant-Murley肩关节评分中的疼痛评分、活动度评分,并于3个月后随访患者,记录复发情况。结果:治疗后,三组患者的肩关节Constant-Murley疼痛评分、活动度评分均高于治疗前(P<0.05);联合组患者的肩关节Constant-Murley疼痛评分、活动度评分明显优于温通膏组及中频组(P<0.05);治疗3个月后联合组的复发率(6.67%)明显低于其它两组。结论:温通膏联合中频电疗可以有效缓解冻结肩患者的疼痛,改善活动度,临床效果较单独使用温通膏外敷或中频电疗更优。     

Survey on hospital‐acquired urinary tract infection in neurological intensive care unit

This study aimed to explore the causes, incidence, and risk factors of urinary tract infection patients in neurological intensive care unit (ICU). Patients (n = 916) admitted to the neurological ICU from January 2005 to December 2010 were retrospectively surveyed for urinary tract infections. There were 246 patients in neurological ICU who were diagnosed with hospital‐acquired urinary tract infection during that period of time (26.9%). Forty‐three cases were upper urinary tract infection, and 203 cases were lower urinary tract infection. The top three strains were Escherichia coli, Enterococcus faecalis, and Klebsiella pneumoniae. Older age (UTI rate, 22.6%), female patients (21.7%), hospital stay for more than 7 days (16.7%), diabetes (11.7%), and catheterization (21.1%) were the risk factors for hospital‐acquired urinary tract infection. There is a high incidence of nosocomial urinary tract infection in the neurological intensive care unit. Active prevention program and surveillance need to be carried out in neurological ICU, especially in those with risk factors.     

运用血清药理学初步探讨毛蕊异黄酮苷的血管新生作用＊

目的 首次运用血清药理学方法，并借助体外细胞实验，初步探讨毛蕊异黄酮苷在血管新生方面的作用，为后期深入研究该物质诱导内皮祖细胞（EPCs）参与脑缺血后血管再生修复机制提供重要帮助。方法 健康雄性Sprague-Dawley（SD）大鼠随机分为两组：一组大鼠预先实施假手术并作为空白血清供体，采用生理盐水灌胃；另一组大鼠预先实施右侧大脑中动脉阻塞再灌注手术以复制缺血性脑卒中疾病模型，并将造模成功动物作为含药血清供体，术后按照50mg/kg?bw的剂量灌胃毛蕊异黄酮苷溶液。各组动物每天早晚各给药1次，连续3天，末次给药1 h后腹主动脉采血。配置不同血清含量（5%、10%、15%）的培养基并对大鼠骨髓来源的内皮祖细胞进行培养，观察不同含药血清对EPCs形态数量的影响，进而选择适宜的含药血清，借助Transwell小室和Matrigel分别考察内皮祖细胞的迁移能力和形成管腔的能力的变化，并采用聚合酶联免疫反应（ELISA）对血清中血管内皮生长因子（VEGF）、基质细胞衍生因子1（SDF-1）、粒细胞集落刺激因子（G-CSF）、粒细胞巨噬细胞集落刺激因子（GM-CSF）以及促红细胞生成素（EPO）含量进行检测。结果 5%和10%含药血清均能促进内皮祖细胞增值且对细胞形态无影响；15%含药血清使细胞形态改变，生长受到显著抑制。10%含药血清能够显著促进内皮祖细胞的迁移作用和形成管腔的能力（P < 0.01）。ELISA结果显示，含药血清中内皮祖细胞动员因子（VEGF、SDF-1、G-CSF、GM-CSF、EPO）含量与空白血清中的各参数相比均显著升高（P < 0.01）。结论 体外实验初步表明，毛蕊异黄酮苷吸收入血后，能够调动多种内皮祖细胞动员因子进入血循环，这些物质对激活内皮祖细胞参与机体脑缺血后的血管再生修复过程起到非常关键的作用。     

基于网络药理学和生物信息学研究苍附导痰丸治疗多囊卵巢综合征的分子机制＊

目的 探讨苍附导痰丸治疗多囊卵巢综合征（Polycystic ovary syndrome，PCOS）的潜在机制。方法 通过检索中药系统药理学数据库和分析平台（Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform，TCMSP）中苍附导痰丸组成药物的成分数据，筛选其有效成分和作用靶点；检索Drug Bank、GeneCards、OMIM、PharmGKB及Uniprot疾病数据库中PCOS相关靶点；检索GEO数据库，选择多囊卵巢综合征的差异表达基因。构建苍附导痰丸和PCOS成分、靶点间的相互关系网络，利用筛选出的关键靶点，构建蛋白互作（Protein-protein interaction，PPI）网络；在GO功能和KEGG信号通路富集的基础上，得出苍附导痰丸治疗PCOS的作用机制，进一步用分子对接技术验证靶点之间结合的可靠性。结果 共筛选出活性成分单体46个，159个苍附导痰丸治疗PCOS的共同靶点。结论 苍附导痰丸治疗PCOS具有多成分、多靶点、多通路的特点，推测苍附导痰丸可能通过调节炎症微环境从而改善肥胖型PCOS患者胰岛素抵抗，通过调节雌激素信号通路改善卵巢功能，因而可以改善肥胖及卵巢排卵的临床症状，为后期研究苍附导痰丸治疗PCOS的作用机制提供了新的理论支撑。