Radiosynthesis of the iodine‐124 labeled Hsp90 inhibitor PU‐H71

Heat shock protein 90 (Hsp90) is an ATP dependent molecular chaperone protein whose function is critical for maintaining several key proteins involved in survival and proliferation of cancer cells. PU‐H71 (1), is a potent purine‐scaffold based ATP pocket binding Hsp90 inhibitor which has been shown to have potent activity in a broad range of in vivo cancer models and is currently in Phase I clinical trials in patients with advanced solid malignancies, lymphomas, and myeloproliferative neoplasms. In this report, we describe the radiosynthesis of [¹²⁴I]‐PU‐H71(5); this was synthesized from the corresponding Boc‐protected stannane precursor 3 by iododestannylation with [¹²⁴I]‐NaI using chloramine‐T as an oxidant for 2 min, followed by Boc deprotection with 6 N HCl at 50 °C for 30 min to yield the final compound. The final product 5 was purified using HPLC and was isolated with an overall yield of 55 ± 6% (n = 6, isolated) from 3, and >98% purity and an average specific activity of 980 mCi/µmol. Our report sets the stage for the introduction of [¹²⁴I]‐PU‐H71 as a potential non‐invasive probe for understanding biodistribution and pharmacokinetics of PU‐H71 in living subjects using positron emission tomography imaging.     

基于机素-机元解析周仲瑛病机辨证规律研究

辨证论治体系的逻辑结构可分为辨证与论治两大部分,或曰两大层次。而辨证,是由疾病部位、病理因素、病因分类、疾病性质、疾病势态和确定疾病证名六大步骤或曰部分所组成。研究首先应用形式逻辑,将中医病机构成元素还原或抽象为机素及机元两个基本病理元素及单元,然后采用辩证逻辑,将相应机素和机元又复归于相应的疾病部位、病理因素、病因分类、疾病性质、疾病动态类别之中,从而既解析了病机的构成规律,体现了中医辨证的执简驭繁的简约性原则,又将拆开的基本病理单元按照辨证论治整体的、动态的规律,再行复杂的非线性组合,以使其复归于辨证论治的整体思维过程,从而使前面的抽象与后面的复归,具备了完整的方法论指导意义。     

补肾益髓生血法再障大鼠含药血清对大鼠造血祖细胞增殖分化及其机制的影响

目的：探讨补肾益髓生血法再障大鼠含药血清对大鼠骨髓造血祖细胞增殖分化及其机制的影响。方法：60Co-γ射线联合环磷酰胺建立再障大鼠模型,以正常对照组、模型组、康力龙组、益髓生血组、温肾生血组和滋肾生血组复方中药灌胃大鼠,制备其含药血清培养正常大鼠骨髓细胞,培养体系中含药血清比例为20豫,进行骨髓造血祖细胞集落形成单位（CFU）计数;收集集落细胞,RT-PCR 检测红系GATA-1 mRNA及粒系PU.1 mRNA表达。结果：与正常对照组相比,模型组骨髓有核细胞显著减少（P<0.01）,造血祖细胞红系集落形成单位（CFU-E）、红系爆式集落形成单位（BFU-E）和粒单核系造血祖细胞集落（CFU-GM）数目均明显降低（P<0.01）,GATA-1、PU.1 mRNA表达显著降低（P<0.01）;与模型组相比,各个治疗组大鼠骨髓有核细胞升高,造血祖细胞CFU-E、BFU-E 和CFU-GM 数目显著增加（P<0.01）;滋肾生血组CFU-E、BFU-E明显优于益髓生血组（P<0.01）;滋肾生血组CFU-GM优于益髓生血组、温肾生血组。各治疗组GATA-1、PU.1 mRNA表达明显高于模型组（P<0.01）;滋肾生血组GATA-1 mRNA表达明显高于益髓生血组、温肾生血组（P<0.05）;滋肾生血组PU.1 mRNA表达高于益髓生血组、温肾生血组。结论：补肾益髓生血法可能通过增加GATA-1、PU.1 mRNA表达而促进骨髓造血祖细胞增殖分化,其中滋肾生血法优于益髓生血法和温肾生血法。     

消化性溃疡与事件相关电位的关系研究

目的探讨消化性溃疡与事件相关电位P300的关系。方法对符合消化性溃疡诊断标准的38例患者(PU)以及38例健康对照者进行事件相关电位P300检测。结果病例组与对照组比较N2、P3潜伏期与反应时间明显延长,波幅明显降低(P<0.05)。结论消化性溃疡患者存在一定的认知功能损害,事件相关电位P300可试作为消化性溃疡辅助诊断标志之一。