ApoE^-/-；SAP—Tg小鼠模型的构建

目的为研究SAP蛋白在动脉粥样硬化中的作用及机制,拟构建ApoE^-/-;SAP—Tg小鼠模型。方法分别选取6～8周龄的雄性ApoE^-/-小鼠与血清淀粉样蛋白P转基因（SAP—Tg）6周龄的雌性小鼠杂交,得到的杂交后代以剪尾方式提取基因组DNA,用PCR法检测小鼠的基因型。结果雄性ApoE^-/-小鼠与雌性SAP-Tg小鼠杂交得F1代后自交,在F2代获得ApoE^-/-;SAP—Tg基因型小鼠,模型构建成功。结论将ApoE^-/-小鼠与SAP—Tg小鼠杂交2代后成功建立了ApoE^-/-;SAP—Tg小鼠模型,并可通过筛选出的F2代ApoE^-/-小鼠和ApoE^-/-;SAP—Tg小鼠交配进行繁育筛选工作。     

Rip1-Tag2;PSGL-1^-/-小鼠模型的构建

目的构建Rip1-Tag2;PSGL^-1-/-小鼠模型。方法将Rip1-Tag2小鼠与P-选择素糖蛋白配体敲除（PSGL-1 KO）小鼠杂交,剪尾提DNA后用PCR法检测小鼠的基因型。结果 Rip1-Tag2小鼠与PSGL-1KO小鼠杂交3代后,Rip1-Tag2;PSGL-1-/-小鼠模型构建成功。结论将Rip1-Tag2小鼠与PSGL-1 KO小鼠杂交3代后成功建立了Rip1-Tag2;PSGL-1-/-小鼠模型,并进行繁育。     

SphK1-S1P信号通路的激活参与糖尿病大鼠肾损伤的研究

目的观察鞘氨醇激酶1-1-磷酸鞘氨醇(SphK1-S1P)信号通路在链脲佐菌素(STZ)诱导的糖尿病大鼠肾脏中的激活情况。方法观察STZ诱导的糖尿病大鼠肾脏中SphK1-S1P信号通路的激活情况。分别检测大鼠肾脏功能及病理指标。采用液质联用分析SphK1活性及S1P含量。并采用免疫组织化学、Real-time PCR和Western blot法检测了SphK1的表达。结果 STZ诱导的糖尿病大鼠血糖、肾重体质量比、24h尿蛋白显著升高,糖尿病大鼠肾脏系膜区肥大,细胞外基质扩展。同时,糖尿病大鼠肾脏中SphK1-S1P信号通路被激活,表现为SphK1表达和活性增加,以及S1P生成增加。结论糖尿病大鼠肾脏中存在SphK1-S1P信号通路的激活,可能参与了糖尿病大鼠肾损伤过程。     

血管内皮生长因子受体2单抗的靶向超声造影剂制备及体外评价

目的探讨携血管内皮生长因子受体2(KDR)单抗的靶向脂质微泡的制备方法,并对其物理特性、生物活性、靶向黏附稳定性进行体外测定。方法采用声振仪制备生物素化脂质微泡(MB-B),再应用生物素-亲和素桥连技术构建携KDR单抗的靶向微泡(MB-BAB-KDR)。荧光显微镜下观察MB-B、单纯单抗微泡(MB-B-KDR)、MB-BAB-KDR与荧光二抗孵育后荧光强度。利用平行板流动腔技术体外模拟生理血流剪切力条件,评价靶向微泡的黏附效能。结果制备的靶向微泡MB-BAB-KDR呈圆球形,粒度分布均匀。与荧光二抗孵育后,MB-BAB-KDR发出明亮的绿色荧光(Ⅱ级),而MB-B-KDR显示微弱的绿色荧光(Ⅰ级)、MB-B无荧光(0级)。体外黏附实验显示,MB-BAB-KDR结合数目随着小鼠KDR Fc包被浓度的增高而增加(P<0.05),相同浓度下,随着时间的增加,MB-BAB-KDR结合数目增加。结论成功构建生物素-亲和素桥连的靶向脂质体微泡MB-BABKDR,体外黏附实验显示MB-BAB-KDR具有黏附稳定性,且与时间、浓度呈正相关。     

SphK1突变抑制高糖培养的系膜细胞纤维连接蛋白过度表达的研究

目的研究鞘氨醇激酶-1（SphK1）突变是否抑制了高糖培养的系膜细胞中纤维连接蛋白（FN）的过度表达。方法采用Western blot检测FN的表达。结果系膜细胞转染了SphK1突变质粒后可消除高糖诱导的FN上调效应。结论本研究结果证明了SphK1在高糖诱导的系膜细胞FN表达过程中发挥着重要的调节作用。     

SAHA and S116836, a novel tyrosine kinase inhibitor,synergistically induce apoptosis in imatinib-resistant chronic myelogenous leukemia cells

Limited treatment options are available for chronic myelogenous leukemia (CML) patients who develop imatinib mesylate (IM) resistance. Here we proposed a novel combination regimen, a co-administration of S116836, a novel small molecule multi-targeted tyrosine kinase inhibitor that was synthesized by rational design, and histone deacetylases inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA), to overcome IM resistance in CML. S116836 at low concentrations used in the present study mildly downregulates auto-tyrosine phosphorylation of Bcr-Abl. SAHA, an FDA-approved HDACi drug, at 1 μM has modest anti-tumor activity in treating CML. However, we found a synergistic interaction between SAHA and S116836 in Bcr-Abl-positive CML cells that were sensitive or resistant to IM. Exposure of KBM5 and KBM5-T315I cells to minimal or non-toxic concentrations of SAHA and S116836 synergistically reduced cell viability and induced cell death. Co-treatment with SAHA and S116838 repressed the expressions of anti-apoptosis proteins, such as Mcl-1 and XIAP, but promoted Bim expression and mitochondrial damage. Of importance, treatment with both drugs significantly reduced cell viability of primary human CML cells, as compared with either agent alone. Taken together, our findings suggest that SAHA exerts synergistically with S116836 at a non-toxic concentration to promote apoptosis in the CML, including those resistant to imatinib or dasatinib.     

大脑中动脉狭窄的临床特点分析

目的：探讨症状性大脑中动脉狭窄的预后和影响因素。方法：回顾性分析我院2005年1月～2009年6月收治的症状性大脑中动脉狭窄患者60例的临床资料。随机选择我院同期确诊的无症状性大脑中动脉狭窄的脑梗死患者60例作为对照组,并对两组患者进行分析。结果：符合入选条件的患者共37例,主要临床表现为头昏、头痛、头沉、反应迟钝、记忆力下降等。其中,左侧MCA狭窄者17例,右侧MCA狭窄者12例,双侧MCA狭窄者8例。卒中家族史、高血压、糖尿病是常见的危险因素,头颅CT异常者5例（13.5%）,主要为腔隙性脑梗死或交界区脑梗死。结论：大脑中动脉狭窄患者常存在脑血管病家族史、高血压、糖尿病等危险因素,可无典型的临床症状,但可存在无症状性脑梗死。     

Identifying optimal risk windows for self-controlled case series studies of vaccine safety

In vaccine safety studies, subjects are considered at increased risk for adverse events for a period of time after vaccination known as risk window. To our knowledge, risk windows for vaccine safety studies have tended to be pre-defined and not to use information from the current study. Inaccurate specification of the risk window can result in either including the true control period in the risk window or including some of the risk window in the control period, which can introduce bias. We propose a data-based approach for identifying the optimal risk windows for self-controlled case series studies of vaccine safety. The approach involves fitting conditional Poisson regression models to obtain incidence rate ratio estimates for different risk window lengths. For a specified risk window length (L), the average time at risk, T(L), is calculated. When the specified risk window is shorter than the true, the incidence rate ratio decreases with 1/T(L) increasing but there is no explicit relationship. When the specified risk window is longer than the true, the incidence rate ratio increases linearly with 1/T(L) increasing. Theoretically, the risk window with the maximum incidence ratio is the optimal risk window. Because of sparse data problem, we recommend using both the maximum incidence rate ratio and the linear relationship when the specified risk window is longer than the true to identify the optimal risk windows. Both simulation studies and vaccine safety data applications show that our proposed approach is effective in identifying medium and long-risk windows.     

CRISPR-Cas系统在动物及植物中不同的递送方式研究进展*

CRISPR-Cas 系统的发现彻底改变了基因编辑技术领域，在多方面都有着广阔的前景。该系统主要有Cas 蛋白和单链向导RNA 组成，其功能的发挥高度依赖于各组分的有效递送。本篇综述对目前动植物中该系统组分 的常用递送方式进行详细总结，并分析其目前仍存在的问题。     

个体主观健康抱怨的研究进展及启示

对个体主观健康抱怨的概念、特点、作用机制、测评工具、研究进展及干预方法进行综述,分析其对我国的启示,为降低个体主观健康抱怨水平,提高卫生保健人员对主观健康抱怨的认知,以及为促进保健护理工作开展提供依据。