Pancreatic ductal adenocarcinoma(PDAC) is an incurable lethal disease whose incidence rate is growing. There is no effective screening for detection of early stage tumors and,in most cases,PDAC is diagnosed at advance...Pancreatic ductal adenocarcinoma(PDAC) is an incurable lethal disease whose incidence rate is growing. There is no effective screening for detection of early stage tumors and,in most cases,PDAC is diagnosed at advanced disease stages,when radical pancreatic resection is not possible. The aggressive nature of pancreatic tumor cells lies in the complex genetic mechanisms behind their uncontrolled capability to grow and metastasize,which involve essential adaptive changes in cellular metabolism,signaling,adhesion and immunoediting. In addition,PDAC cells promote a dense functional stroma that facilitates tumor resistance to chemotherapy and radiation. During the last two decades,gemcitabine has been the reference for the systemic treatment of PDAC. However,recently,a regimen combining fluorouracil,irinotecan,oxaliplatin,and leucovorin(FOLFIRINOX) and another combining albumin-bound paclitaxel with gemcitabine have shown clear therapeutic advantage in advanced PDAC,with survival outcomes of 11.3 and 8.5 mo on phase Ⅲ trials,respectively,over singleagent gemcitabine. With the pending issue of their higher toxicities,these regimens set the reference for ongoing and future clinical studies in advanced PDAC. In addition,the efficacy of oral fluoropyrimidine(S-1) has been well documented in Asiatic PDAC patients. The development of therapeutic approaches other than cytotoxic drugs has proven difficult in the past,with only one drug(erlotinib) approved to date. Besides,a number of agents targeting signaling pathways in tumor or stroma cells are being investigated. Likewise,immunotherapies that target PDAC in various ways are the subject of a number of clinical trials. The search for reliable biomarkers with diagnostic and prognostic value using genomics and mass spectrometry methods may facilitate monitoring and refinement of therapies. This review focuses on current understanding of the pathogenesis of PDAC and the latest developments in the treatment of advanced PDAC.展开更多
目的分析山东省烟台市乙型脑炎减毒活疫苗（Japanese encephalitis attenuated live vaccine，JEV-L）疑似预防接种异常反应（Adverse events following immunization，AEFI）的特征，评价JEV-L预防接种的安全性。方法通过全国AEFI信息...目的分析山东省烟台市乙型脑炎减毒活疫苗（Japanese encephalitis attenuated live vaccine，JEV-L）疑似预防接种异常反应（Adverse events following immunization，AEFI）的特征，评价JEV-L预防接种的安全性。方法通过全国AEFI信息管理系统和山东省免疫规划监测信息管理系统，收集烟台市2012-2016年报告的AEFl个案数据和疫苗接种数据，采用描述流行病学方法进行分析。结果烟台市2012-2016年报告JEV-L的AEFI651例，报告发生率为11．19／万剂。一般反应643例（98．77％，11．05／万剂），其中发热618例（96．11％，10．63／万剂）、局部红肿55例（8．55％，0．95／万剂）；异常反应7例（1．08％，0．12／万剂），均为过敏性皮疹。在不良反应中，第1剂次、接种后0-1d发生分别占70．oo％（455／650）、93．85％（610／650）。结论JEV-L具有较好的预防接种安全性，不良反应以发热和局部反应为主。展开更多
为了统一描述军事电子信息系统(command control communication computers intelligence surveil-lance and reconnaissance,C4ISR)系统功能和效能两方面的需求,提出了一种基于统一建模语言/对象约束语言(unified modeling language/obj...为了统一描述军事电子信息系统(command control communication computers intelligence surveil-lance and reconnaissance,C4ISR)系统功能和效能两方面的需求,提出了一种基于统一建模语言/对象约束语言(unified modeling language/object constraint language,UML/OCL)的C4ISR效能概念建模和形式化验证方法。首先,利用效能相关概念扩展了DoDAF 2.0能力元模型,构建一个能够同时引导C4ISR能力的功能分析和效能分析的元模型;将该元模型描述为UML Profile,形成一种基于UML的C4ISR效能概念建模语言,并支持C4ISR效能概念模型检验;最后借助一个假想案例分析说明了该建模语言对C4ISR能力的功能和效能概念建模及模型验证的能力。该方法可弥补UML建模技术在特定领域效能分析方面的不足。展开更多
文摘Pancreatic ductal adenocarcinoma(PDAC) is an incurable lethal disease whose incidence rate is growing. There is no effective screening for detection of early stage tumors and,in most cases,PDAC is diagnosed at advanced disease stages,when radical pancreatic resection is not possible. The aggressive nature of pancreatic tumor cells lies in the complex genetic mechanisms behind their uncontrolled capability to grow and metastasize,which involve essential adaptive changes in cellular metabolism,signaling,adhesion and immunoediting. In addition,PDAC cells promote a dense functional stroma that facilitates tumor resistance to chemotherapy and radiation. During the last two decades,gemcitabine has been the reference for the systemic treatment of PDAC. However,recently,a regimen combining fluorouracil,irinotecan,oxaliplatin,and leucovorin(FOLFIRINOX) and another combining albumin-bound paclitaxel with gemcitabine have shown clear therapeutic advantage in advanced PDAC,with survival outcomes of 11.3 and 8.5 mo on phase Ⅲ trials,respectively,over singleagent gemcitabine. With the pending issue of their higher toxicities,these regimens set the reference for ongoing and future clinical studies in advanced PDAC. In addition,the efficacy of oral fluoropyrimidine(S-1) has been well documented in Asiatic PDAC patients. The development of therapeutic approaches other than cytotoxic drugs has proven difficult in the past,with only one drug(erlotinib) approved to date. Besides,a number of agents targeting signaling pathways in tumor or stroma cells are being investigated. Likewise,immunotherapies that target PDAC in various ways are the subject of a number of clinical trials. The search for reliable biomarkers with diagnostic and prognostic value using genomics and mass spectrometry methods may facilitate monitoring and refinement of therapies. This review focuses on current understanding of the pathogenesis of PDAC and the latest developments in the treatment of advanced PDAC.
文摘目的分析山东省烟台市乙型脑炎减毒活疫苗（Japanese encephalitis attenuated live vaccine，JEV-L）疑似预防接种异常反应（Adverse events following immunization，AEFI）的特征，评价JEV-L预防接种的安全性。方法通过全国AEFI信息管理系统和山东省免疫规划监测信息管理系统，收集烟台市2012-2016年报告的AEFl个案数据和疫苗接种数据，采用描述流行病学方法进行分析。结果烟台市2012-2016年报告JEV-L的AEFI651例，报告发生率为11．19／万剂。一般反应643例（98．77％，11．05／万剂），其中发热618例（96．11％，10．63／万剂）、局部红肿55例（8．55％，0．95／万剂）；异常反应7例（1．08％，0．12／万剂），均为过敏性皮疹。在不良反应中，第1剂次、接种后0-1d发生分别占70．oo％（455／650）、93．85％（610／650）。结论JEV-L具有较好的预防接种安全性，不良反应以发热和局部反应为主。
文摘为了统一描述军事电子信息系统(command control communication computers intelligence surveil-lance and reconnaissance,C4ISR)系统功能和效能两方面的需求,提出了一种基于统一建模语言/对象约束语言(unified modeling language/object constraint language,UML/OCL)的C4ISR效能概念建模和形式化验证方法。首先,利用效能相关概念扩展了DoDAF 2.0能力元模型,构建一个能够同时引导C4ISR能力的功能分析和效能分析的元模型;将该元模型描述为UML Profile,形成一种基于UML的C4ISR效能概念建模语言,并支持C4ISR效能概念模型检验;最后借助一个假想案例分析说明了该建模语言对C4ISR能力的功能和效能概念建模及模型验证的能力。该方法可弥补UML建模技术在特定领域效能分析方面的不足。
