血清酸溶性蛋白定量在日本血吸虫病研究中的应用

本文研究动物感染日本血吸虫及毗喹酮治疗过程中血清酸溶性蛋白(ASP)浓度的动态变化。结果显示:家兔感染早期,血清ASP浓度明显升高,中期降至正常水平,末期再次明显升高,感染小鼠经吡喹酮治疗,血清ASP降低程腰与疗效、减虫率、病变消退等相符合。本文提示:血清ASP浓度测定可作为监护病情、判定药物疗效的指标,有一定的临床实用价值。     

血清酸溶性蛋白定量测定在疟疾研究中实用价值的探讨

本文采用Bradford法的改良法,对感染伯氏鼠疟(P.b,ANKA株)及用酮替芬、青蒿素、放线菌酮、氯喹、威灵仙5种抗疟药治疗后小鼠血清ASP进行定量测定。结果显示:感染疟疾小鼠血清ASP含量显著高于正常小鼠,其浓度与疟原虫感染率成正比关系;用以上5种抗疟药治疗后,小鼠血清ASP含量显著降低,但有差异,其浓度与抗疟药对疟原虫的抑制率成反比关系。以上结果提示,血清ASP定量测定,可作为疟疾病情监护和判定抗疟药疗效的一项指标,亦是抗疟药筛选的一种较好方法。     

Human mass balance,metabolite profile and identification of metabolic enzymes of [14C]ASP015K,a novel oral janus kinase inhibitor

Abstract

1.?The human mass balance of ¹⁴C-labelled ASP015K ([¹⁴C]ASP015K), an orally bioavailable Janus kinase (JAK) inhibitor, was characterized in six healthy male subjects after a single oral dose of [¹⁴C]ASP015K (100?mg, 3.7?MBq) in solution. [¹⁴C]ASP015K was rapidly absorbed with t_max of 1.6 and 1.8?h for ASP015K and total radioactivity in plasma, respectively. Mean recovery in urine and feces amounted to 36.8% and 56.6% of the administered dose, respectively. The main components of radioactivity in plasma and urine were ASP015K and M2 (5′-O-sulfo ASP015K). In feces, ASP015K and M4 (7-N-methyl ASP015K) were the main components.

2.?In vitro study of ASP015K metabolism showed that the major isozyme contributing to the formation of M2 was human sulfotransferase (SULT) 2A1 and of M4 was nicotinamide N-methyltransferase (NNMT).

3.?The in vitro intrinsic clearance (CL_{int_in?vitro}) of M4 formation from ASP015K in human liver cytosol (HLC) was 11-fold higher than that of M2. The competitive inhibitory effect of nicotinamide on M4 formation in the human liver was considered the reason for high CL_{int_in vitro} of M4 formation, while each metabolic pathway made a near equal contribution to the in vivo elimination of ASP015K. ASP015K was cleared by multiple mechanisms.     

Hepatoprotective effects of Rubus aleaefolius Poir. and identification of its active constituents

The purpose of this study was to study the hepatoprotective effects of the most promising extract of the root from Rubus aleaefolius Poir. and to isolate and identify the active components. Various crude forms of Rubus aleaefolius have been evaluated for their effects on CCl₄-induced acute liver injury in mice vivo experimental model. Treatment groups contained 5 sub-groups that were ethanol crude extract; the high/low dosage ethyl acetate or n-butanol fraction; extracted with ethyl acetate or n-butanol after the residues and major constituent; intragastrically administrated with 35 mg/kg; 35, 4.6 mg/kg; 35, 5.8 mg/kg; 35 mg/kg and 3.5 mg/kg for 7 days. The serum samples were collected for biological analysis and also carried out histopathological studies.     

早期营养支持对急性重症胰腺炎病人机体组成的影响

目的:探讨早期肠内营养(EN)联合肠外营养(PN)对急性重症胰腺炎(ASP)病人机体组成的影响. 方法:将30例病人随机分成治疗组和对照组.治疗组病人采取早期EN加PN,并逐渐减少PN的用量,直至停止PN.对照组病人采取完全胃肠外营养(TPN).两组病人平均治疗15 d.用皮皱测量法测定两组病人机体密度,用MRI方法测量全身各部位脂肪变化情况,核素稀释法测定全身水量(TBW)、总脂肪量(TBF)、无脂肪体重(LBM)、细胞内液(ICM)、细胞外液(ECM)的变化.同时常规测定血清清蛋白、血红蛋白、转铁蛋白和淋巴细胞数量等. 结果:治疗组在TBW、TBF、LBM、ICM、ECM、血清清蛋白、血红蛋白、转铁蛋白与对照组差异无显著性意义(P＞0.05),治疗组的淋巴细胞数高于对照组(P＜0.05). 结论:早期EN联合PN可以改善ASP病人的机体免疫功能,对机体组成的影响,与TPN无差异.     

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.     

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.     

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.     

基于ASP.NET的医疗器械标准信息检索系统的设计与实现

该文在分析了医疗器械标准信息检索系统的设计目标后,并以ASP.NETC#为编程语言,IIS为Web服务器,SQL Server2000作数据库,在.NET环境中构建一个基于B/S结构的医疗器械标准检索系统。文中还介绍其系统构成、检索系统功能模块、系统开发环境及系统详细设计。