Leflunomide therapy for adult patients with steroid-dependent minimal change disease or primary focal segmental glomerulosclerosis

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Mixed invasive pulmonary Mucor and Aspergillus infection: a case report and literature review

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Natural killer cells in obstetric antiphospholipid syndrome

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Cocaine self-administration on a hold-down schedule of reinforcement in rats

Rationale and objective  Although many contingencies operating in the natural environment include continuous dimensions of responses and reinforcers, previous studies of drug self-administration have almost exclusively used discrete dimensions of responses (e.g., a lever press) and reinforcers (e.g., 1.0 mg/kg/injection cocaine). Therefore, the present study provides an initial examination under experimental conditions with both responses and reinforcers measured along continuous dimensions. Materials and methods  Cocaine-maintained responding was studied in rats under a novel, hold-down schedule of reinforcement wherein the duration of the response was directly related to the magnitude of the reinforcer. These conditions were established by activating the syringe pump when the lever was pressed down and turning the pump off when the lever was released. The concentration of cocaine available in the syringe was varied across sessions. Results  Cocaine self-administration was readily maintained under these conditions and remained stable across sessions. Responding was concentration dependent, with the number of responses and total duration of the response inversely related to concentration, and overall session intake of cocaine was stable across concentrations. In general, the duration of the responses were less than 0.5 s and did not vary as a function of concentration. Conclusions  Stability of responding under these schedule conditions was acquired quickly. This schedule of reinforcement may be useful for comparing across drug classes, can be extended for use with other types of responses and reinforcers, and may be more representative of the natural world where response-reinforcer contingencies are more likely to be experienced along continuous, rather than discrete, dimensions. Drake Morgan and Yu Liu contributed equally to this publication.     

Biochemical Modulation of Aracytidine (Ara-C) Effects by GTI-2040, a Ribonucleotide Reductase Inhibitor, in K562 Human Leukemia Cells

GTI-2040 is a potent antisense to the M2 subunit of the ribonucleotide reductase (RNR), an enzyme involved in the de novo synthesis of nucleoside triphosphates. We hypothesized that combination of GTI-2040 with the cytarabine (Ara-C) could result in an enhanced cytotoxic effect with perturbed intracellular deoxynucleotide/nucleotide (dNTP/NTP) pools including Ara-C triphosphate (Ara-CTP). This study aims to provide a direct experimental support of this hypothesis by monitoring the biochemical modulation effects, intracellular levels of Ara-CTP, dNTPs/NTPs following the combination treatment of Ara-C, and GTI-2040 in K562 human leukemia cells. GTI-2040 was introduced into cells via electroporation. A hybridization-ligation ELISA was used to quantify intracellular GTI-2040 concentrations. Real-time PCR and Western blot methods were used to measure the RNR M2 mRNA and protein levels, respectively. 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt assay was used to measure the cytotoxicity following various drug treatments. A non-radioactive HPLC-UV method was used for measuring the intracellular Ara-CTP, while a LC-MS/MS method was used to quantify intracellular dNTP/NTP pools. GTI-2040 was found to downregulate M2 mRNA and protein levels in a dose-dependent manner and showed significant decrease in dNTP but not NTP pool. When combining GTI-2040 with Ara-C, a synergistic cytotoxicity was observed with no further change in dNTP/NTP pools. Importantly, pretreatment of K562 cells with GTI-2040 was found to increase Ara-CTP level for the first time, and this effect may be due to inhibition of RNR by GTI-2040. This finding provides a laboratory justification for the current phase I/II evaluation of GTI-2040 in combination with Ara-C in patients with acute myeloid leukemia.     

60例老年乳腺癌的临床病理特点及分子分型

目的 探讨老年女性乳腺癌临床病理特点及分子分型.方法 回顾性分析郑州人民医院2011年1月至2016年8月收治的60例60岁以上(包括60岁)老年女性乳腺癌及同期随机选取的60例青年乳腺癌(年龄≤35岁)的临床及病理资料.结果 60例老年女性乳腺癌中临床分期Ⅰ期12例,Ⅱ期44例,Ⅲ期4例;浸润性导管癌49例,有腋窝淋巴结转移32例;雌激素受体阳性48例,孕激素受体阳性43例,CerbB-2受体阳性表达18例;与青年组比较,在临床分期、肿块大小及ER、PR受体阳性表达差异均有统计学意义(P值分别为0.028、0.040、0.044、0.038);而在淋巴结有无转移、病理类型及CerbB-2受体阳性表达上差异均无统计学意义(P值分别为0.199、0.178、0.404);老年组LuminalA 29例、Luminal B 19例、TNBC(三阴性乳腺癌)5例、CerbB-2过表达7例,与青年组乳腺癌分子分型比较,P值为0.035.结论 老年乳腺癌具有独特的生物学特点,临床分期以Ⅰ、Ⅱ期为主,ER、PR受体阳性较多,病理类型以浸润性导管癌为主,分子分型以Luminal A、Luminal B较多.     

诸子蜂起 百家争鸣(二)——英国中医药的现状与展望

中医药面临着"诸子蜂起,百家争鸣"的国际医药保健时代,处于有机会又有曲折的局面.故从1)中医药在国外的发展.2)中医药在英国的现状.3)英国推动中医教育的经验.4)英国偶尔发生的中医事故影响中医界整体形象.5)英国中医的立法过程与国际影响.6)建立中医药企业文化和品牌标准--英国的经验.7)中医药发展展望.8)中医药的宣传和外交等方面论述.指出在"诸子蜂起,百家争鸣"的新"全球医学"时代,中医界人士需团结一致,既往开来,为把中医真正纳入世界主流医学,并能恩泽于全人类而全心全力、努力不懈!     

不同产地金银花挥发油GC-MS的比较分析

金银花为忍冬科植物忍冬 Lonicera japonicaThunb.的干燥花蕾 ,具有清热解毒、凉散风热的功效。金银花分布广泛 ,山东和河南是我国传统的道地产区 ,而产地不同 ,其有效成分含量存在着较大差异 [1,2 ] 。有关挥发油的成分研究曾有报道[3～ 5] ,为全面了解其挥发油成分的差异及变化 ,提高金银花的质量 ,我们采用 GC- MS首次对山东、河南及江苏等地金银花的挥发油成分做了比较分析。1　实验部分1 .1　样品及挥发油的提取 :样品分别采自山东平邑、日照 ,河南封丘、新密 ,江苏南京等地 ,经鉴定为L.japonica Thunb.。称取新鲜的花蕾 1 0 0 g,…     

平调饮对原发性肝癌AFP mRNA、GPC-3 mRNA影响的研究

目的探讨平调饮对原发性肝癌患者AFP mRNA、GPC-3 mRNA表达的影响。方法抽取60例肝癌患者的抗凝血液,配对法随机分为试验组和对照组各30例。采用Tr-Izol一步法提取总RNA,用逆转录巢式聚合酶链反应(RT-nested PCR)技术检测治疗前后试验组及对照组患者AFP mRNA、GPC-3 mRNA的表达情况。结果治疗后试验组及对照组AFP mRNA、GPC-3 mRNA表达均显著下降,在降低AFP mRNA表达方面试验组与对照组无显著性差异,降低GPC-3 mRNA表达方面试验组明显优于对照组(P0.05)。结论平调饮能有效抑制人血液中AFP mRNA、GPC-3 mRNA的高表达,在降低GPC-3 mRNA表达方面效果优于华蟾素。其治疗原发性肝癌机制与临床应用价值值得进一步研究。