Outcomes After Aortic Valve Replacement for Asymptomatic Severe Aortic Regurgitation and Normal Ejection Fraction

1. Download : Download high-res image (123KB)
2. Download : Download full-size image

     

Maximizing intelligence obtained from higher-order DNA mixtures from volume crime samples

ABSTRACT

This work collates data from the analysis of complex mixtures analysed in STRmix during routine no-suspect volume crime work. It interrogates the upload rate for these types of mixtures and which component of the profile has been able to be interpreted for upload. The number of profiles giving multiple uploads and the amount of replicate PCR analysis has been collated.     

TLR9在不同胎龄新生儿脐血中的表达变化

目的 通过观察早产儿不同胎龄Toll样受体9（TLR9）的表达，探讨早产儿免疫功能低下的机制。方法 采集2010年7月至2014年6月在上海市嘉定区妇幼保健院产科出生的活产新生儿的脐血229份，按胎龄分为4组，28~31周组，31~34周组，34~37周组，≥37周组，采用流式细胞术和实时荧光定量PCR方法，分别检测其TLR9的蛋白和mRNA表达情况，了解其与胎龄之间的关系，并分析mRNA和蛋白表达间的相关性。结果 TLR9阳性细胞率在28~31周组，31~34周组，34~37周组，≥37周组分别为（15.93±6.23）%，（11.63±6.70）%，（13.66±6.88）%，（20.51±12.06）%；其在胎龄28~31周较高，至31~34周逐渐下降至最低，两组差异有统计学意义（P<0.05）；34~37周后TLR9阳性细胞率表达逐渐升高，至≥37周达最高，两胎龄组比较，差异具有统计学意义（P<0.05）。31~37周间新生儿脐血TLR9阳性细胞率与胎龄呈正相关（r=0.273，P=0.006）。TLR9 mRNA表达在28~31周组，31~34周组，34~37周组，≥37周组分别为（4.95±3.44）%，（8.89±8.49）%，（13.91±10.92）%，（7.19±7.11）%；其在28~36周逐渐升高，与胎龄呈正相关（r=0.355，P< 0.001）。≥37周TLR9 mRNA表达量下降，该值虽高于28~31周，但差异无统计学意义（P>0.05）。相关性分析表明，同胎龄时期同样本新生儿的TLR9 mRNA和TLR9阳性细胞率之间存在负相关（r=-0.227，P=0.011）。结论 TLR9阳性细胞率和TLR9 mRNA表达在不同胎龄组新生儿间有差异，TLR9阳性细胞率表达在31~37周间随着胎龄的增加而增加，TLR9 mRNA在28~36周间随着胎龄的增加而增加。     

中医药调控IL-1治疗肿瘤机制的研究进展

炎症已成为影响肿瘤细胞增殖转移的第七大因素,而白细胞介素-1(IL-1)是炎性微环境的重要因子之一。中医药在治疗肿瘤时具有多途径、多靶点的优势,同时炎性微环境致病特点与现代中医学"癌毒"的理论相吻合。查阅近年中医药调控IL-1家族分子治疗肿瘤机制的文献,对其进行梳理,并做出概括及评价,从中医药主要调控IL-1α、IL-1β和IL-18因子治疗肿瘤展开综述,为中医药更系统化治疗肿瘤提供参考。     

Recent advances in preclinical in vitro approaches towards quantitative prediction of hepatic clearance and drug-drug interactions involving organic anion transporting polypeptide (OATP) 1B transporters

Hepatic uptake mediated by organic anion transporting polypeptide (OATP) 1B1 and 1B3 can serve as a major elimination pathway for various anionic drugs and as a site of drug-drug interactions (DDIs). This article provides an overview of the in vitro approaches used to predict human hepatic clearance (CL_h) and the risk of DDIs involving OATP1Bs. On the basis of the so-called extended clearance concept, in vitro–in vivo extrapolation methods using human hepatocytes as in vitro systems have been used to predict the CL_h involving OATP1B-mediated hepatic uptake. CL_h can be quantitatively predicted using human donor lots possessing adequate OATP1B activities. The contribution of OATP1Bs to hepatic uptake can be estimated by the relative activity factor, the relative expression factor, or selective inhibitor approaches, which offer generally consistent outcomes. In OATP1B1 inhibition assays, substantial substrate dependency was observed. The time-dependent inhibition of OATP1B1 was also noted and may be a mechanism underlying the in vitro–in vivo differences in the inhibition constant of cyclosporine A. Although it is still challenging to quantitatively predict CL_h and DDIs involving OATP1Bs from only preclinical data, understanding the utility and limitation of the current in vitro methods will pave the way for better prediction.     

维生素D与多囊卵巢患者胰岛素抵抗相关性及其机制研究

目的:探讨维生素D对多囊卵巢综合征(PCOS)患者胰岛素抵抗(IR)的影响及其机制研究.方法:选取自2013年2月～2014年2月在该院就诊的48例PCOS患者作为PCOS组,另选30例健康育龄期妇女作为对照组,测量研究者身高、体质量参数,计算体质指数(BMI),采用全自动生化分析仪葡萄糖氧化酶检测空腹血糖浓度(FBG)、化学发光法检测血清空腹胰岛素(FI)及胰岛素样生长因子-1(IGF-1)水平、ELISA方法测定血清25-(OH)D3浓度,计算稳态胰岛素评价指数(HOMA-IR)用于评价胰岛素抵抗性,量化胰岛素敏感指数(QUICKI)用于评价胰岛素敏感度,并分析FI、HOMA-IR、QUICKI及IGF-1与血清25-(OH)D3浓度的相关性.结果:PCOS组BMI及FBG与对照组相比,差异无统计学差异(P＞0.05),而FI、HOMA-IR、QUICKI、25-(OH) D3及IGF-1与对照组比较,差异均有统计学差异(P＜0.05);并且PCOS组FI和HOMA-IR与血清25-(OH)D3浓度呈显著负相关,差异有统计学意义(P＜0.05),QUICKI和IGF-1水平与血清25-(OH)D3浓度呈显著正相关,差异有统计学意义(P＜0.05).结论:PCOS患者IR可能与血清中维生素D缺乏有关,而IGF-1分泌减少又可能是导致PCOS患者维生素D缺乏的重要原因.     

Genome wide identification of new genes and pathways in patients with both autoimmune thyroiditis and type 1 diabetes

Autoimmune thyroid diseases (AITD) and Type 1 diabetes (T1D) frequently occur in the same individual pointing to a strong shared genetic susceptibility. Indeed, the co-occurrence of T1D and AITD in the same individual is classified as a variant of the autoimmune polyglandular syndrome type 3 (designated APS3v). Our aim was to identify new genes and mechanisms causing the co-occurrence of T1D + AITD (APS3v) in the same individual using a genome-wide approach. For our discovery set we analyzed 346 Caucasian APS3v patients and 727 gender and ethnicity matched healthy controls. Genotyping was performed using the Illumina Human660W-Quad.v1. The replication set included 185 APS3v patients and 340 controls. Association analyses were performed using the PLINK program, and pathway analyses were performed using the MAGENTA software. We identified multiple signals within the HLA region and conditioning studies suggested that a few of them contributed independently to the strong association of the HLA locus with APS3v. Outside the HLA region, variants in GPR103, a gene not suggested by previous studies of APS3v, T1D, or AITD, showed genome-wide significance (p < 5 × 10⁻⁸). In addition, a locus on 1p13 containing the PTPN22 gene showed genome-wide significant associations. Pathway analysis demonstrated that cell cycle, B-cell development, CD40, and CTLA-4 signaling were the major pathways contributing to the pathogenesis of APS3v. These findings suggest that complex mechanisms involving T-cell and B-cell pathways are involved in the strong genetic association between AITD and T1D.