吉西他滨组成方案挽救治疗非霍奇金淋巴瘤的疗效与安全性分析

目的:探讨GDP和GemOx方案治疗复发难治性非霍奇金淋巴瘤的早期疗效及安全性。方法:选取本院2016年1月至2017年8月收治的复发难治性弥漫大B细胞淋巴瘤及复发难治性NK/T细胞淋巴瘤患者共52例,其中25例接受 GDP方案化疗,27例接受GemOx方案化疗。观察两组患者早期临床疗效和毒副反应。结果:GDP方案组患者总有效率52.00%,GemOx方案组患者总有效率59.26%。两种方案的主要毒副反应均为轻度的消化道反应、血液学毒性及转氨酶升高。结论:以吉西他滨为基础的联合化疗方案可作为复发难治性非霍奇金淋巴瘤的治疗选择。     

人均GDP1 000美元后的医院发展形势与策略

人均国民生产总值突破1000美元后,医药卫生发展在出现新增长前景的同时,一些制约因素及深层次问题也逐渐显现出来,展现出一系列重要的转折性特征,如民众对健康的需求和就医观念发生变化,社会分配公平问题在医疗中的反映更为突出,医疗资源配置不合理或管理效益不高等.医院特别是在区域内具有影响力的大型医院需要有新的发展思路和策略,加大介入构建和谐社会的比重,建立良好的医患关系,实施品牌战略和文化建院策略,谋求高效率增长方式等,以促进科学发展.     

Activity and the metabolic activation pathway of the potent and selective hepatitis C virus pronucleotide inhibitor PSI-353661

PSI-353661, a phosphoramidate prodrug of 2′-deoxy-2′-fluoro-2′-C-methylguanosine-5′-monophosphate, is a highly active inhibitor of genotype 1a, 1b, and 2a HCV RNA replication in the replicon assay and of genotype 1a and 2a infectious virus replication. PSI-353661 is active against replicons harboring the NS5B S282T or S96T/N142T amino acid alterations that confer decreased susceptibility to nucleoside/tide analogs as well as mutations that confer resistance to non-nucleoside inhibitors of NS5B. Replicon clearance studies show that PSI-353661 was able to clear cells of HCV replicon RNA and prevent a rebound in replicon RNA. PSI-353661 showed no toxicity toward bone marrow stem cells or mitochondrial toxicity. The metabolism to the active 5′-triphosphate involves hydrolysis of the carboxyl ester by cathepsin A (Cat A) and carboxylesterase 1 (CES1) followed by a putative nucleophilic attack on the phosphorus by the carboxyl group resulting in the elimination of phenol and the alaninyl phosphate metabolite, PSI-353131. Histidine triad nucleotide-binding protein 1 (Hint 1) then removes the amino acid moiety, which is followed by hydrolysis of the methoxyl group at the O⁶-position of the guanine base by adenosine deaminase-like protein 1 (ADAL1) to give 2′-deoxy-2′-fluoro-2′-C-methylguanosine-5′-monophosphate. The monophosphate is phosphorylated to the diphosphate by guanylate kinase. Nucleoside diphosphate kinase is the primary enzyme involved in phosphorylation of the diphosphate to the active triphosphate, PSI-352666. PSI-352666 is equally active against wild-type NS5B and NS5B containing the S282T amino acid alteration.     

Lysophosphatidylcholine enhances I(Ks) currents in cardiac myocytes through activation of G protein, PKC and Rho signaling pathways

Lysophosphatidylcholine (LPC) is a bioactive phospholipid that accumulates rapidly in the ischemic myocardium. In recent years, it has been shown that some of the actions of LPC are mediated through the activation of the membrane G proteins. However, the precise mechanism(s) responsible for the LPC-related intracellular signaling in the regulation of cardiac ion channels are still poorly understood. The present study was undertaken to examine whether LPC regulates the slow component of the delayed rectifier K⁺ current (I_Ks) and, if so, what intracellular signals are important for this process. Isolated guinea pig cardiac myocytes were voltage-clamped using the whole-cell configuration of the patch-clamp method. The bath application of 1-palmitoyl-lysophosphatidylcholine (LPC-16) concentration-dependently (EC₅₀ = 0.7 μM) and reversibly increased I_Ks in atrial cells, but failed to potentiate I_Ks in ventricular myocytes. In contrast, 1-oleoyl-lysophosphatidylcholine (LPC-18:1) only produced a slight I_Ks increase, and 1-caproyl-lysophosphatidylcholine (LPC-6) or the LPC-16 precursor (phosphatidylcholine) had no effect on I_Ks. Pretreatment of atrial cells with an antibody against the N-terminus of the G2A receptor significantly reduced the LPC-16-induced potentiation of I_Ks. The inhibition of heterotrimeric G protein, phospholipase C (PLC) and protein kinase C (PKC) significantly reduced LPC-16-induced enhancement of I_Ks. Moreover, the blockade of Rho and Rho-kinase by specific inhibitors also inhibited the activity of LPC-16. Immunohistochemical studies demonstrated that G2A was densely distributed in the plasma membrane of atrial myocytes. Therefore, the present study suggests that the activation of a G protein (probably Gα_q) by LPC-16 potentiates I_Ks currents through the PLC-PKC and Rho-kinase pathways.     

GDP和DICE方案治疗老年晚期复发难治性弥漫大B细胞淋巴瘤的临床研究

目的：比较GDP与DICE两种二线方案治疗老年晚期复发难治性弥漫大B细胞淋巴瘤的疗效和不良反应。方法：将42例老年晚期复发难治性弥漫大B细胞淋巴瘤患者随机分为GDP组（20例）和DICE组（22例）。观察近期疗效、毒副反应和生存情况。结果：GDP组和DICE组1年无事件生存率分别为85％和63．6％,无进展生存分别为35％和22．7％;CR分别为35％和18．2％,PR分别为40％和22．7％,SD分别为15％和27．3％,PD分别为10％和36．4％,疾病缓解率分别为75％和40．9％,差异显著。两组末梢神经炎发生率分别为2．5％和8．4％;脱发发生率分别为2．5％和7．5％;胃炎发生率分别为2．5％和10．9％,差别显著（P〈0．05）,血液学毒性发生率分别为20．7％和18．5％（P〉0．05）,无显著差别,但GDP组血栓形成明显大于DICE组,差别显著。结论：在治疗老年晚期复发难治性弥漫大B细胞淋巴瘤中GDP方案优于DICE方案,毒副反应较轻,但血液学毒性中血栓形成明显高于DICE组。     

VAR模型在我国人口出生率预测中的应用

摘要:目的　基于我国人均GDP,使用向量自回归模型预测我国人口出生率,探讨其在我国卫生领域应用的可行性。方法　收集1952-2013年我国人均GDP及人口出生率资料,用Excel2007和Eviews8.0建立VAR模型,并用2012-2013年的数据评价模型的预测效果。结果　VAR（2）模型拟合及预测的平均相对误差和希尔不等系数分别为8.78%,0.146和3.903%,0.087。结论　VAR（2）模型对我国人口出生率的拟合精度较高,短期预测效果较好。     

缺氧缺血I生脑损伤新生大鼠脑神经细胞凋亡及脑组织中Rho GDP解离抑制因子和Bcl-2表达的变化

目的研究RhoGDP解离抑制因子（Rho GDP dissociation inhibitor 2,RhoGDI2）mRNA及Bcl-2mRNA的表达在缺氧缺血性脑损伤（hypoxic-ischemic brain damage,HIBD）中的作用和机制。方法30只新生7日龄SD大鼠按照完全随机化方法分为假手术组及HIBD6h和48h组,每组10只。采用流式细胞仪检测脑细胞凋亡情况,并用Real—timeRT—PCR方法测定脑组织中RhoGDI2和Bcl-2mRNA表达水平。结果（1）新生大鼠HIBD后48h结扎侧大脑半球脑水肿明显。（2）HIBD6h出现典型的凋亡细胞峰,细胞凋亡率为（1．40±0．12）％。HIBD48h凋亡峰更为明显,细胞凋亡率达到（15．86±0．98）％。缺氧缺血后与假手术组相比,差异有统计学意义（P〈0．01）。（3）假手术组大鼠RhoGDI2和Bcl-2mRNA表达水平较高（4．12±0．74、2．55±0．65）,在HIBD6h后二者表达开始下降（3．19±0．77、1．96±0．36）,48h降低更加明显（1．04±0．18、1．06±0．17）,与假手术组比较,HIBD各时间点RhoGDI2和Bcl-2mRNA的表达均明显降低,差异有统计学意义（P〈0．01）。（4）缺氧缺血后各时间点RhoGDI2mRNA的表达和Bcl-2mRNA的表达呈正相关（r=0．831,P〈0．05）。结论脑缺氧缺血后,随着凋亡的出现,RhoGDI2和Bcl-2mRNA表达水平降低,提示RhoGDI2表达失衡可能通过Bcl-2参与新生大鼠HIBD中凋亡的发生。     

国际注册中的运输验证探讨

随着中国2010版GMP的实施推进,以及国际药品贸易的广泛开展,如何保障药品在运输环节的质量稳定,成为国际注册和国际贸易的重要话题和关注热点。笔者长期跟踪研究药品国际认证和注册,以及药品运输过程中的稳定性,搜集并分析了关于运输环节药品质量保证的相关法规和指南,进行系统研究,提供药品企业借鉴。