妊娠期糖尿病合并甲状腺功能减退症47例临床分析

目的：观察甲状腺功能减退症（简称甲减）对妊娠期糖尿病患者各项代谢指标的影响。方法回顾性分析2010年1月至2014年1月在该院就诊的妊娠期糖尿病合并甲减孕妇47例,随机选取同期妊娠期糖尿病孕妇74例作为对照,检测两组孕妇的空腹血糖（ FBG）、口服葡萄糖耐量1 h时血糖（1hBG）、口服葡萄糖耐量2 h时血糖（2hBG）、糖化血红蛋白（ HbA1c）、甘油三酯（TG）、胆固醇（TC）、低密度脂蛋白（LDL-C）、高密度脂蛋白（HDL-C）、载脂蛋白a（Apoa）、载脂蛋白b（Apob）、血清肌酐（Cr）、胰岛素用量等。结果甲减组的TG、TC、LDL-C显著高于对照组（P＜0．05）;FBG、1hBG、2hBG、HbA1c、HDL-C、Apoa、Apob、Cr无显著差别（P＞0．05）;甲减组的胰岛素用量与对照组比较,差异无统计学意义（P＞0．05）。 TSH与TG、TC和LDL成正相关（P＜0．05）。结论临床上应重视妊娠期糖尿病孕妇甲状腺功能及各项代谢指标的筛查并早期干预治疗,减少甲减对脂代谢的影响。     

Intracellular target delivery of 10-hydroxycamptothecin with solid lipid nanoparticles against multidrug resistance

The main objective of this study was to design a suitable drug delivery system for 10-hydroxycamptothecin (HCPT). In this study, HCPT-loaded solid lipid nanoparticle (HCPT-loaded SLN) was successfully prepared. The HCPT-loaded SLN was characterized by size, entrapment efficiency and drug release manner. The cytotoxicity of HCPT-loaded SLN was assessed in vitro using HepG2/HCPT cells and in vivo utilizing human tumor xenograft nude mouse model. HCPT-loaded SLN indicated the ability to target HepG2/HCPT cells and accumulated higher drug content in HepG2/HCPT cells. HCPT-loaded SLN enhanced the cytotoxicity of HCPT in a concentration-dependent manner. Based on these results, HCPT-loaded SLN suggested being a promising vehicle for liver-targeted drug delivery. Moreover, it can be of clinical interest to overcome multidrug resistance (MDR) effectively.     

Plasma miR-200b in ovarian carcinoma patients: distinct pattern of pre/post-treatment variation compared to CA-125 and potential for prediction of progression-free survival

Ovarian carcinomas (OvCa) are highly heterogeneous malignancies. We investigated four circulating plasma microRNAs (miR-21, miR-34a, miR-200b and miR-205) as candidate biomarkers. Using qPCR, we assessed the plasma concentration of these markers in 101 women, including 51 previously untreated OvCa patients, 25 healthy women and 25 patients bearing benign pelvic lesions. For a subset of 33 OvCa patients, the assay was repeated at the end of the primary treatment. The pattern of variations (post- minus pre-treatment) of concentration was compared to that of CA-125. A Cox regression model was used to study the association between variations and the progression-free survival (PFS). Plasma miR-200b proved to have a greater average concentration in OvCa samples (median 2^−ΔΔCt = 15.18) than in samples linked to non-malignant lesions (median 2^−ΔΔCt = 1.26, p-value = 0.0004). Its concentration was highly heterogeneous among OvCa patients, without any correlations with the FIGO stage and the pre-treatment CA-125 level. The decrease in CA-125 concentration was constant and often dramatic, while the variations of miR-200b concentration were much more diverse. The variation of miR-200b was marginally associated with the PFS (hazard ratio=2.95 95%CI=[0.94; 9.28], p=0.06) while miR-200b as a continuous time-dependent variable was significantly associated (HR=1.06 [1.02; 1.10], p=0.003). This study is the first direct empirical evidence that miR-200b can provide additional information, independent of CA-125 in OvCa patients.     

GB virus type C E2 protein inhibits human immunodeficiency virus type 1 Gag assembly by downregulating human ADP-ribosylation factor 1

GB virus type C (GBV-C) glycoprotein E2 protein disrupts HIV-1 assembly and release by inhibiting Gag plasma membrane targeting, however the mechanism by which the GBV-C E2 inhibits Gag trafficking remains unclear. In the present study, we identified ADP-ribosylation factor 1 (ARF1) contributed to the inhibitory effect of GBV-C E2 on HIV-1 Gag membrane targeting. Expression of GBV-C E2 decreased ARF1 expression in a proteasomal degradation-dependent manner. The restoration of ARF1 expression rescued the HIV-1 Gag processing and membrane targeting defect imposed by GBV-C E2. In addition, GBV-C E2 expression also altered Golgi morphology and suppressed protein traffic through the secretory pathway, which are all consistent with a phenotype of disrupting the function of ARF1 protein. Thus, our results indicate that GBV-C E2 inhibits HIV-1 assembly and release by decreasing ARF1, and may provide insights regarding GBV-C E2''s potential for a new therapeutic approach for treating HIV-1.     

A novel modification of the Thrombelastograph assay, isolating platelet function, correlates with optical platelet aggregation

Flow cytometry, singlet platelet counting, and optical aggregation have been used to monitor clopidogrel and glycoprotein IIb/IIIa (GPIIb/IIIa) platelet antagonists. Optical aggregation is considered the gold standard, but neither it nor flow cytometry is convenient in larger-scale clinical studies or point-of-care systems. Singlet platelet counting, a point-of-care assay correlated with optical platelet aggregation, only provides a measurement of platelet function at a single point in time. The Thrombelastograph is used to assay whole blood for thrombin-generated maximal clot-shear elasticity, referred to as the maximal amplitude (MA). Although platelet dysfunction, thrombocytopenia, and the in vitro effect of strong inhibitors such as IIb/IIIa antagonists can be observed, with thrombin generation milder platelet inhibitors cannot be assessed. We modified the Thromboelastograph assay, using reptilase and factor XIIIa, to form a clot, without thrombin generation, in heparinized whole blood. The resulting clot MA is dependent on added platelet agonists such as ADP or arachidonic acid, is sensitive to platelet antagonists, and provides a continuous measure of platelet function more analogous and better correlated with optical aggregation. This novel modification of the Thromboelastograph assay should prove to be a useful point-of-care whole-blood assay with which to monitor the effects of GPIIb/IIIa, ADP, and thromboxane A(2)-receptor-inhibiting drugs in patients.     

Presurgical plasma exchange for severe factor V deficiency

We report two patients with severe congenital factor V deficiency, one of whom also had a factor V inhibitor, who required correction of their coagulopathy prior to surgical procedures. They underwent plasma exchange (PE) with fresh frozen plasma or solvent/detergent treated plasma (S/DP), with achievement of factor V levels satisfactory for hemostasis for their procedures. PE makes it possible to raise factor levels quickly and sufficiently without volume overload. In addition, transient reduction of inhibitor titers by PE may improve the level of correction achievable during the perioperative period. The advent of S/DP promises to provide an added increment of safety in patients exposed to significant volumes of plasma during PE.     

血管紧张素原基因T704C多态性及血脂水平与动脉硬化性脑梗死的相关性研究

目的探讨血管紧张素原∽G7）基因T704C多态性与血脂水平及动脉硬化性脑梗死（ACI）的关系。方法2206为离退休职工为研究对象,进行体格检查和问卷调查,资料完整者l990名入选,其中男性1289名、女性701名。1990名中共检出ACl患者170例（男性132例,女性38例）为ACI组;余1820名无ACT者（男性1155例,女性665例）为对照组。采用PCR-RFLP方法检测AGT基因T704C基因型,采用全自动生化分析仪测定血脂等生化项目。结果ACI组性别、年龄、平均收缩压、平均舒张压、体重指数、血糖与对照组比较,两组问差异有统计学意义（P〈O．05）;调查人群中,携带AGT基因CC基因型的人群中,ACI患病率高干携带TT、TC基因型者（P〈0．05）;且携带C等位基因的人群ACI患病率高于携带T等位基因的人群（P〈0．05）;两组间血脂水平比较,对照组携带TC、CC基因型者高密度脂蛋白水平高于ACI组（P〈0．05）;携带CC基因型者三酰甘油水平明显低于ACI组（P〈0．05）。结论AGT基因T704C多态性及血脂水平与ACI相关。