FLT3突变急性淋巴细胞白血病的临床特征

目的：探讨急性淋巴细胞白血病（acute lymphoblastic leukemia,ALL）患者FLT3（Fms-like tyrosine kinase）基因内部串联重复（internal tandem duplication,ITD）与其ASP835（D835）突变（mutation in the tyrosine kinase domain,FLT3-TKD）的发生情况及临床意义。方法采用聚合酶链反应法（polymerase chain reaction, PCR）扩增产物,采用限制性酶切产物分析法分析初诊患者基因易突变区的突变情况。结果147例ALL患者中,11例（7.5%）存在FLT3突变。FLT3突变患者与无突变患者在年龄、性别、骨髓原始细胞计数和外周血原始细胞计数的比较均无统计学意义（均P＞0.05）。T细胞型ALL（T-ALL）患者中FLT3突变的发生率为17.2%,其他类型ALL患者中FLT3突变的发生率为5.1%,差异具有非常显著的统计学意义（P＜0.001）。结论 ALL患者存在FLT3突变,且T-ALL患者的FLT3突变率高于其他类型患者。     

Absorption,distribution, metabolism and excretion of novel phosphodiesterase type 4 inhibitor ASP3258 in rats

The potent and selective phosphodiesterase 4 inhibitor ASP3258 is a novel therapeutic agent for asthma and chronic obstructive pulmonary disease (COPD). After a single oral administration to rats, ASP3258 is rapidly absorbed with a bioavailability of 106%. In situ absorption data indicated that ASP3258 is mainly absorbed in the small intestine. Tissue distribution data after oral administration of ¹⁴C‐ASP3258 showed rapid and extensive distribution to various tissues. Excluding the gastrointestinal tract, the tissues with the highest concentrations were liver, heart and plasma. Liquid chromatography‐nuclear magnetic resonance spectroscopy data revealed that O‐glucuronidation of the carboxylic acid moiety of ASP3258 (formation of an acyl glucuronide) plays a key role in metabolism. No indication was found that the acyl glucuronide reacted with proteins in plasma or tissues. When ¹⁴C‐ASP3258 was orally administered to intact rats, urinary and fecal excretion accounted for 1.3% and 100.6% of the administered radioactivity, respectively. After a single oral administration of ¹⁴C‐ASP3258 to bile‐cannulated rats, urinary and biliary excretion accounted for 0.7% and 93.8% of the administered radioactivity, respectively. These findings suggest that fecal excretion via bile plays an important role in the elimination of ASP3258‐derived radioactivity. In vitro metabolic profiles were relatively similar among the species examined, suggesting that our findings in rats may help us to understand pharmacokinetics, efficacy and safety profiles in humans and other species. Copyright © 2014 John Wiley & Sons, Ltd.     

The ALK inhibitor ASP3026 eradicates NPM-ALK+ T-cell anaplastic large-cell lymphoma in vitro and in a systemic xenograft lymphoma model

NPM-ALK⁺ T-cell anaplastic large-cell lymphoma (ALCL) is an aggressive type of cancer. Standard treatment of NPM-ALK⁺ ALCL is CHOP polychemotherapy. Although patients initially respond favorably to CHOP, resistance, relapse, and death frequently occur. Recently, selective targeting of ALK has emerged as an alternative therapeutic strategy. ASP3026 is a second-generation ALK inhibitor that can overcome crizotinib resistance in non-small cell lung cancer, and is currently being evaluated in clinical trials of patients with ALK⁺ solid tumors. However, NPM-ALK⁺ ALCL patients are not included in these trials. We studied the effects of ASP3026 on NPM-ALK⁺ ALCL cell lines in vitro and on systemic lymphoma growth in vivo. ASP3026 decreased the viability, proliferation, and colony formation, as well as induced apoptotic cell death of NPM-ALK⁺ ALCL cells. In addition, ASP3026 significantly reduced the proliferation of 293T cells transfected with NPM-ALK mutants that are resistant to crizotinib and downregulated tyrosine phosphorylation of these mutants. Moreover, ASP3026 abrogated systemic NPM-ALK⁺ ALCL growth in mice. Importantly, the survival of ASP3026-treated mice was superior to that of control and CHOP-treated mice. Our data suggest that ASP3026 is an effective treatment for NPM-ALK⁺ ALCL, and support the enrollment of patients with this lymphoma in the ongoing clinical trials.     

美国医疗机构抗菌药物临床应用管理策略及对我国的启示

抗菌药物管理计划的制定与实施是国外医疗机构提高抗菌药物合理使用水平的重要措施。在Pubmed等数据库文件检索的基础上,以美国疾病控制与预防中心开发的抗菌药物应用管理机制为主要研究对象,对国外医院抗菌药物管理项目及其相关评价研究从两方面进行归纳阐述,包括宏观层面管理和抗菌药物临床使用的细节管理。旨在通过借鉴国外经验,对我国医疗机构抗菌药物管理实践与研究的发展提出建议。     

基于ASP的医疗设备管理系统的设计与开发

医疗设备管理是医院管理的重要组成部分,但医疗设备技术复杂,数量繁多,一套先进的设备管理系统已成为迫切需求。通过分析当前医疗设备管理中存在的问题,本文提出了有效的解决方案。     

Application of allele-specific RNAi in hepatitis B virus lamivudine resistance

Understanding the consequences of mutation in the tyrosine-methionine-aspartate-aspartate (YMDD) motif of hepatitis B virus (HBV) genome on replication is critical for treating chronic hepatitis B with lamivudine. Allele-specific gene silencing by RNAi (allele-specific RNAi: ASP-RNAi) is an advanced application of RNAi techniques. Use of this strategy as a means for specifically inhibiting an allele expression of interest suggested that it can specifically suppress the expression of alleles causing disease without inhibiting the expression of corresponding wild-type alleles. However, no studies have used ASP-RNAi to address the issue of HBV lamivudine resistance. In this study, we applied ASP-RNAi into two long-term eukaryotic cell lines of full-length HBV containing either lamivudine-resistant mutants (HBV-YIDD) or wild type (HBV-WT) which we generated in previously. The designed siRNAs were also used in this eukaryotic expression system together with lamivudine. ELISA and real-time PCR were performed to monitor virus-specific protein synthesis and viral DNA replication. The results showed that the base substitutions conferring marked ASP-RNAi appeared to be largely present in positions 1, 3, 6, 11, 12, 15 and 19 of the sense strand of siRNAs which were different from the most sensitive positions of this application in eukaryotes. In addition, siRNA-lamivudine combinations did not possess the prominent anti-HBV activity we expected because of some unknown mechanisms. These findings recapitulated many of the features of ASP-RNAi in hepadnaviruses which provided a new insight into the development of a potent strategy against HBV drug resistance.     

大型仪器设备共享平台的设计与实现

目的:设计并实现一个基于Web的大型仪器设备共享服务平台,提高大型仪器设备的使用和管理效率.方法:以SQL Server为后台数据库,使用ASP.NET和Ajax技术进行系统平台的构建和实现.结果:该平台已成功应用到大型仪器设备的管理和使用当中,取得了良好的实践效果.结论:大型仪器设备共享平台的投入使用,既提高了仪器设备的管理效率和使用效率,同时也为广大科研人员提供了一个高效的仪器预约使用平台.     

基于HIS的眼科诊疗质量信息系统设计

目的传统的眼科诊疗质量管理与控制体系已不能很好满足眼科医院业务不断发展的需要.为了充分发挥新管理模式的优势,提高眼科诊疗质量管理的效率,利用计算机技术模拟眼科诊疗质量的控制流程,从而提高眼科的诊疗质量.方法本文设计了一种基于医院信息系统(hospital information system,HIS)的眼科网络办公自动化信息系统,系统建立在Browser/Server/Database三层构架之上,采用ASP.NET技术开发、模块化设计.结果实现眼科诊疗信息资源共享、查询等功能和眼科科室管理功能,并且支持大型数据库,实现眼科诊疗质量控制管理功能.结论通过投入试用发现,本系统能有效地改进眼科质量管理模式,提高眼科的诊疗服务质量.     

基于.NET的标准化卫生机构信息管理系统的设计与实现

利用电子政务可以有效地提高政府的工作效率,减少政府办公支出,降低行政运营成本。其中,功能齐全、安全可靠的信息管理系统是实施政务信息化的有力保证。系统开发应用于标准化基层卫生机构信息管理工作中,发挥了较好的作用。