金地鼠颊囊癌前病变的细胞增殖动力学研究

目的研究口腔上皮组织癌和癌前病变的细胞动力学变化特征。方法采用Ｓａｌｅｙ的ＤＭＢＡ涂布诱导法，建立金地鼠颊囊癌前病变模型，并用溴脱氧尿苷流式细胞动力学检测方法，对３０只叙利亚种金地鼠进行分组对照研究。结果涂药组光镜下的细胞病变程度随涂药时间延长而逐渐加重，而空白对照组无变化；ＦＣＭ检测显示涂药组与对照组在Ｓ期阳性细胞检出率存在显著差异。即使在光镜下表现为轻度不典型增生时，ＦＣＭ检测结果也有显著差别。结论金地鼠颊囊癌前病变具有细胞异常增殖的细胞动力学特征     

Skeletal unloading induces resistance to insulin-like growth factor-I (IGF-I) by inhibiting activation of the IGF-I signaling pathways.

We showed that unloading markedly diminished the effects of IGF-I to activate its signaling pathways, and the disintegrin echistatin showed a similar block in osteoprogenitor cells. Furthermore, unloading decreased alphaVbeta3 integrin expression. These results show that skeletal unloading induces resistance to IGF-I by inhibiting activation of the IGF-I signaling pathways at least in part through downregulation of integrin signaling. INTRODUCTION: We have previously reported that skeletal unloading induces resistance to insulin-like growth factor-I (IGF-I) with respect to bone formation. However, the underlying mechanism remains unclear. The aim of this study was to clarify how skeletal unloading induces resistance to the effects of IGF-I administration in vivo and in vitro with respect to bone formation. MATERIALS AND METHODS: We first determined the response of bone to IGF-I administration in vivo during skeletal unloading. We then evaluated the response of osteoprogenitor cells isolated from unloaded bones to IGF-I treatment in vitro with respect to activation of the IGF-I signaling pathways. Finally we examined the potential role of integrins in mediating the responsiveness of osteoprogenitor cells to IGF-I. RESULTS: IGF-I administration in vivo significantly increased proliferation of osteoblasts. Unloading markedly decreased proliferation and blocked the ability of IGF-I to increase proliferation. On a cellular level, IGF-I treatment in vitro stimulated the activation of its receptor, Ras, ERK1/2 (p44/42 MAPK), and Akt in cultured osteoprogenitor cells from normally loaded bones, but these effects were markedly diminished in cells from unloaded bones. These results were not caused by altered phosphatase activity or changes in receptor binding to IGF-I. Inhibition of the Ras/MAPK pathway was more impacted by unloading than that of Akt. The disintegrin echistatin (an antagonist of the alphaVbeta3 integrin) blocked the ability of IGF-I to stimulate its receptor phosphorylation and osteoblast proliferation, similar to that seen in cells from unloaded bone. Furthermore, unloading significantly decreased the mRNA levels both of alphaV and beta3 integrin subunits in osteoprogenitor cells. CONCLUSION: These results indicate that skeletal unloading induces resistance to IGF-I by inhibiting the activation of IGF-I signaling pathways, at least in part, through downregulation of integrin signaling, resulting in decreased proliferation of osteoblasts and their precursors.     

褪黑素对结肠黏膜上皮细胞氧化应激的影响

目的 探讨褪黑素对大鼠结肠黏膜上皮细胞氧化应激的影响。方法 在分离培养正常大鼠结肠黏膜上皮细胞基础上，利用FeSO4 H2O2产生*OH攻击制备结肠黏膜细胞氧化损伤模型，同时预先加入褪黑素并观察损伤减轻程度。实验设正常对照组、模型对照组、5-氨基水杨酸给药组(0.1mmol／L)，褪黑素给药组(0．01、0．1、l.0mmol／L)。培养一定时间后，取上清测乳酸脱氢酶(LDH)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSHPx)、过氧化氢酶(CAT)、超氧化物歧化酶(SOD)、一氧化氮(NO)和黏液含量。结果 模型组大鼠结肠黏膜上皮细胞：MDA、LDH和NO水平增高，CAT、GSHPX、SOD和黏液含量减少。不同剂量褪黑素呈剂量依赖性的减少LDH释放，抑制MDA和NO的形成，恢复黏液、CAT、GSHPX及SOD水平。结论 褪黑素对大鼠结肠黏膜氧化损伤具有保护作用。     

自制新荧光剂EPQS的性能测试

作者对自制新荧光剂EPQS进行了性能测试。结果:量子产率为0.21;最大激发波长和荧光波长分别为375nm和484nm,stokes位移109nm;检测生物化合物常用的缓冲溶液对荧光峰位无影响,对荧光强度影响很小;温度的影响也小(18～43℃,FRI61.5～58.1),PH的影响也不大。说明EPQS不仅荧光参数好,而且稳定性也好。适合在较广泛的环境条件下使用。     

先天性心脏病患儿术后多脏器功能障碍的预后分析

目的 探讨小儿先天性心脏病(先心病)术后多脏器功能障碍(MODS)预后情况及其影响因素,为对此类患儿进行针对性护理提供依据.方法 收集先心病术后并发MODS 77例患儿的临床资料.结果 11例放弃治疗出院,66例中44例救治存活,22例死亡.出现时间最早、累及最多的脏器为心脏;病死率最高的为累及中枢神经系统的患儿(57.69%),其次是累及血液系统的患儿(55.56%);患儿的病死率与累及脏器的数量呈显著正相关(P＜0.01).死亡患儿手术体外循环时间和主动脉阻断时间显著长于存活患儿(均P＜0.05),术中意外及术后心肺复苏发生率显著高于存活患儿(均P＜0.05).结论 先心病术后患儿应加强心功能监护,特别是体外循环时间＞120 min,主动脉阻断时间＞60 min及术中发生过意外情况、术后采取过心肺复苏术的患儿;尽早采取有利措施避免其他脏器功能受损是提高患儿存活率的关键.     

Heritability and Expression of C-Reactive Protein in Type 2 Diabetes in the Diabetes Heart Study

Elevated C-reactive protein (CRP) levels are associated with both prevalent and incident cardiovascular disease. In this study, familial aggregation was estimated, and we tested for association between serum CRP levels and polymorphisms within the CRP and APOE genes in sib-ships with type 2 diabetes mellitus, a population at increased risk for cardiovascular disease. CRP levels were determined in 461 diabetes-affected subjects from 224 sibships from the Diabetes Heart Study (DHS). Heritability estimates of CRP levels were obtained using variance component models. Genetic influence on serum CRP levels by single nucleotide polymorphisms (SNPs) in the CRP and APOE genes was evaluated by association analysis using mixed models. Subjects were Caucasian American (84%) and African-American (16%), 53% female, and had an average age of 62.2 ± 9.2 years. The median CRP level was 3.3 mg/L (range 0 to 59.3 mg/L), and estimated heritability for CRP was approximately 40%. Estimates of heritability were significantly greater than zero (P < 0.0001) and relatively constant, despite adjustments for important modifiers (age, sex, ethnicity, diabetes duration, statin-use and anti-inflammatory use) of CRP. There was no significant evidence for association of CRP levels with CRP gene SNPs; however, consistent with previous reports, there was significant evidence of association of CRP levels with polymorphisms within the APOE gene. These data indicate CRP levels are significantly influenced by genetic (and/or environmental) factors that are shared within DHS families. While the APOE locus shows evidence of contributing to CRP levels, no evidence of CRP gene polymorphism association with CRP levels was observed.     

ERK1/2信号转导途径在低切应力上调人脐静脉内皮细胞IL-8基因表达中的作用

血管内皮细胞位于血流和血管壁之间,除受化学因素的调节外还受力学因素的影响。切应力可通过刺激相应的力学感受系统来调节内皮细胞某些基因的表达,其中包括诱导内皮细胞表达IL- 8。为了阐明MAPK信号途径中的ERK1/ 2信号通路是否参与调控低切应力上调人脐静脉内皮细胞IL- 8基因表达,采用Western blot分析了低切应力(4.2 0 dyne/ cm2 )处理不同时间内皮细胞ERK1/ 2的磷酸化水平及TPK抑制剂Genistein,MEK抑制剂PD980 5 9对其磷酸化的影响;采用定量RT- PCR检测内皮细胞经低切应力刺激或给予阻断剂后再行切应力刺激等处理后IL- 8基因的表达。结果显示:(1)低切应力处理可引起内皮细胞ERK1/ 2蛋白磷酸化水平上调,其磷酸化水平与切应力作用时间有关,具有快速、双向性的特点(在刺激10 min时达到高峰,2 h左右降至未刺激水平) ,阻断剂Genistein和PD980 5 9处理后,ERK1/ 2磷酸化水平与低切应力刺激10 min比较明显降低;(2 )阻断剂Genistein,PD980 5 9可显著抑制低切应力所致的内皮细胞IL- 8m RNA上调。结果表明低切应力可通过ERK1/ 2信号途径上调人脐静脉内皮细胞IL- 8基因的表达。     

基于中医诊疗指南的冠心病知识图谱构建

目的：运用知识图谱技术将诊疗指南中的辨证论治过程构建为可视化的知识图谱,通过程序将输入临床表现到输出相应的中医诊断和处方用药的过程进行可视化,为中医医师直观地显示诊疗过程和数据关系,为中医药诊治冠心病的标准化和规范化提供助力,为中医药诊疗的传承和推广提供技术依托。方法：采用Neo4j联合py2neo知识图谱技术,以中华中医药学会心血管病分会发布的《冠心病稳定型心绞痛中医诊疗指南》为模式构建知识图谱,通过编程实现以临床表现的输入调用知识图谱,可视化展示冠心病稳定型心绞痛的中医规范化诊疗过程。结果：使用py2neo库调用Neo4j,从诊疗指南中提取整理好的结构化数据导入Neo4j,构建基于冠心病稳定型心绞痛中医诊疗指南的知识图谱,且该知识图谱支持图数据库查询功能。结论：该研究结合目前中医诊疗经验传承中存在的问题,针对冠心病稳定型心绞痛这个单一病种,笔者提出了一种基于凝结了中医行业专家经验和循证证据所形成的诊疗指南,实现基于中医诊疗指南和专家经验的知识图谱可视化展示过程,为直观地展现从症状输入到遣方用药的整个中医诊疗过程和辅助中医经验传承提供助力,为中医的标准化和规范化诊疗提供了一种可参考的...     

APP17肽对卵巢去势大鼠海马神经元凋亡相关因子表达的影响

为研究卵巢去势大鼠海马神经元内凋亡相关因子Fas、Fas L、NFκB、c fos、c Jun的表达及APP1 7肽对这些因子表达的影响 ,将健康雌性Wistar大鼠行双侧卵巢切除手术造模 ,并用APP1 7肽治疗 ,分别用免疫组化方法观察Fas、Fas L、NFκB、c fos、c Jun的表达 ,用TUNEL方法检测神经元的凋亡。结果发现 :卵巢去势大鼠海马神经元Fas、Fas L、c fos、c Jun的表达增高 ,而NFκB的表达则减少 ;使用APP1 7肽治疗后 ,上述蛋白质的表达恢复到正常水平 ,TUNEL检测未发现凋亡神经元。提示卵巢去势大鼠发生了海马神经元的凋亡相关蛋白的改变 ,可能是神经元处于凋亡前状态 ;APP1 7肽可改善卵巢去势大鼠海马神经元内凋亡相关蛋白的表达 ,维持神经元的正常功能