Incidence of T790M in Patients With NSCLC Progressed to Gefitinib,Erlotinib, and Afatinib: A Study on Circulating Cell-free DNA

BackgroundInsights into the mechanism of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) could provide important information for further patient management, including the choice of second-line treatment. The EGFR T790M mutation is the most common mechanism of resistance to first- and second-generation EGFR TKIs. Owing to its biologic relevance in the response of non–small-cell lung cancer (NSCLC) to the selective pressure of treatment, the present study investigated whether the occurrence of T790M at progression differed among patients receiving gefitinib, erlotinib, or afatinib.Patients and MethodsThe present retrospective study included patients with NSCLC with an EGFR activating mutation, who had received gefitinib, erlotinib, or afatinib as first-line treatment. Plasma samples for the analysis of cell-free DNA were taken at disease progression and analyzed using a digital droplet polymerase chain reaction EGFR mutation assay.ResultsA total of 83 patients were enrolled; 42 had received gefitinib or erlotinib and 41afatinib. The patient characteristics were comparable across the 2 groups. The median time to progression (TTP) was 14.4 months for the gefitinib and erlotinib group and 10.2 months for the afatinib group (P = .09). Of the 83 patients, 47 (56.6%) were positive for the T790M in plasma. A greater incidence of T790M was observed in patients with progression during gefitinib or erlotinib therapy compared with patients treated with afatinib (33 [79%] vs. 14 [34%], respectively; odds ratio, 7.1; 95% confidence interval, 2.7-18.5; P = .0001).ConclusionsAlthough gefitinib, erlotinib, and afatinib showed a comparable TTP in patients receiving first-line therapy, the incidence of T790M differed among them, as demonstrated by the present study, which could have implications for the choice of second-line treatment.     

刍议医院纪检监察在医院建设中的作用和实施

随着社会经济的快速发展,国内医疗事业的竞争日益激烈,医疗机构需要积极提高自身的业务水平和管理水平,才能强化医疗技术水平,获得更多的社会经济效益。在国内医疗体制深化变革的趋势下,纪检监察在医院建设中发挥着越来越重要的作用,主要职责是管理和监督医院各项制度的落实、健康环境的建设等,旨在规范机构医疗服务,提高机构服务质量,促使医院树立良好的社会形象,保障医院的社会经济效益。该文针对医院纪检监察在医院建设中的作用和实施展开分析。     

Recent advances in construction of small molecule-based fluorophore-drug conjugates

As a powerful tool to advance drug discovery, molecular imaging may provide new insights into the process of drug effect and therapy at cellular and molecular levels. When compared with other detection methods, fluorescence-based strategies are highly attractive and can be used to illuminate pathways of drugs’ transport, with multi-color capacity, high specificity and good sensitivity. The conjugates of fluorescent molecules and therapeutic agents create exciting avenues for real-time monitoring of drug delivery and distribution, both in vitro and in vivo. In this short review, we discuss recent developments of small molecule-based fluorophore-drug conjugates, including non-cleavable and cleavable ones, that are capable of visualizing drug delivery.     

青黛作用于急性幼粒细胞白血病的可视化“药靶蛋白模型”分析

目的:目前青黛已是治疗急性幼粒细胞白血病(APL)的临床有效药物,但其分子机制与物质基础仍不明确。基于此本研究构建青黛与APL可视化药靶蛋白模型,以探究青黛作用于APL的分子机制。方法:通过GEO数据库检索APL微阵列芯片分析APL差异表达基因,使用TCMSP数据库筛选青黛活性成分,结合PubChem和SwissTargetPrediction匹配活性成分的靶基因并进行富集分析。String用于挖掘并构建APL可视化蛋白互作数据,将其读入Cytoscape,通过Centiscape实现网络拓扑分析。综合APL差异表达基因,通过Sybyl与青黛活性成分构建药靶蛋白模型。结果:筛选出3张APL微阵列芯片,164个差异表达基因,9种青黛活性成分,541个靶基因,这些靶点较多地参与细胞凋亡、药物结合、癌症途径、慢性粒细胞白血病等,这些都在APL中起重要作用。拓扑分析显示ELANE,CTSS为核心基因,将其与青黛9种活性成分进行药靶蛋白模型预测,显示靛玉红和靛蓝与核心基因结合度最佳。结论:APL是受多基因调控的复杂疾病,而青黛成分中靛玉红和靛蓝可通过结合ELANE,CTSS作用于APL的发生发展。     

Substance use and substance use disorders in Africa: An epidemiological approach to the review of existing literature

The relationship between man and substances that have abuse potentials, and whose use has been associated with the development or progression of substance use disorders has continued to evolve in terms of geography, economic implications, and time. History shows that local plants with psychoactive constituents can get exported worldwide through global travel, commerce, or even conquest. Time and globalization also change people’s relationship with substances of abuse; hence, an area that was initially alien to certain substances might evolve to becoming a trafficking hub, and then a destination. A case in point is Africa where a rapidly increasing prevalence of substance use/abuse and substance use disorder among adolescents and young adults is putting enormous strain on the economy, healthcare system, and society at large. However, there appears to be a paucity of scientific literature and data on the epidemiology, risk assessment, and contributing factors to substance use and the development of substance use disorders across Africa. In this narrative review, we examine extant literature (PubMed, Google scholar, Medline) for information on the prevalence, trends, and influencers of substance use and the development of substance use disorders. This is with a view of understanding the determinants of substance use and factors that influence the development of substance use disorders in the region, and how this information can be channeled towards developing a comprehensive intervention and treatment program.     

Diallyl disulfide and diallyl trisulfide in garlic as novel therapeutic agents to overcome drug resistance in breast cancer

Breast cancer is one of the leading causes of cancer-related deaths in women worldwide. It is a cancer that originates from the mammary ducts and involves mutations in multiple genes. Recently, the treatment of breast cancer has become increasingly challenging owing to the increase in tumor heterogeneity and aggressiveness, which gives rise to therapeutic resistance. Epidemiological, population-based, and hospital-based case-control studies have demonstrated an association between high intake of certain Allium vegetables and a reduced risk in the development of breast cancer. Diallyl disulfide (DADS) and diallyl trisulfide (DATS) are the main allyl sulfur compounds present in garlic, and are known to exhibit anticancer activity as they interfere with breast cancer cell proliferation, tumor metastasis, and angiogenesis. The present review highlights multidrug resistance mechanisms and their signaling pathways in breast cancer. This review discusses the potential anticancer activities of DADS and DATS, with emphasis on drug resistance in triple-negative breast cancer (TNBC). Understanding the anticancer activities of DADS and DATS provides insights into their potential in targeting drug resistance mechanisms of TNBC, especially in clinical studies.     

社区获得性肺炎的中西医治疗研究进展

社区获得性肺炎(Community Acquired Pneumonia,CAP)是比较常见的院外肺部炎性疾病之一,随着细菌、支原体、衣原体等多种病原体的耐药率的上升,以及病患梯度的范围增加,CAP的发病率呈逐年上升的趋势,死亡率日益增高,导致医疗资源消耗巨大。目前临床上CAP的患者主要依靠经验性治疗。正确选择抗生素、减少病原体的耐药率,优化肺部炎症疾病的医疗方案,提高CAP临床治愈率已经成为临床医生当前面临的一项重大挑战。中药制剂具有广谱抗菌、调节免疫、不易耐药、简便价廉等特点,是解决上述难题的一个很好途径。     

药品化妆品抽样及检验的有关问题探讨

目的:对药品、药包材、化妆品抽样及检验工作中发现的问题进行分析研究,旨在为监管部门和检验机构提供参考,规范抽样和检验,提高监管效能和服务水平。方法:通过抽样、样品寄送、收样、检验等环节,对药品、药包材、化妆品抽样及检验工作中发现的有关问题进行分析研究,提出相应的解决措施和意见建议。结果与结论:部分药品/药包材/化妆品的抽查检验存在抽样不规范、抽样信息不完整、抽样与检查未能兼顾、样品寄送不规范、检验登记单和检验报告信息不完整或填写不规范、检验不规范、部分产品的批号效期标识不规范,以及部分品种因抽样量大导致抽样难以覆盖基层等问题,影响了监管效能。应根据药品、药包材、化妆品的产品特性和监管要求,分类设置并完善抽样及检验检测信息,并从强化人员培训、监督和检验有机结合、针对基层用药特点完善抽检工作机制、加强学习交流提高检验报告质量等方面加以解决。