初诊2型糖尿病患者血清胱抑素C的变化及影响因素的研究

目的研究初次诊断为2型糖尿病患者的血清胱抑素C变化规律,并探讨其影响因素。方法以2008年10月—2011年6月在我院内分泌科就诊的108例初诊2型糖尿病患者为观察组,按入选时的尿微量清蛋白水平分为尿微量清蛋白升高亚组48例,尿微量清蛋白正常亚组60例。以同期门诊体检健康者30名作为对照组。用免疫比浊法测定血清胱抑素C和尿微量清蛋白水平。同时测定受试者的血糖、血脂、血压、体质指数、血清肌酐、血尿酸、肾小球滤过率(GFR)等生化指标,并在3组间进行比较。结果 (1)观察组中两个亚组的血清胱抑素C水平均高于对照组,差异均有统计学意义(P<0.05)。尿微量清蛋白升高亚组的胱抑素C水平高于尿微量清蛋白正常亚组,差异有统计学意义(P<0.05)。(2)在观察组中进行单因素分析显示,胱抑素C与收缩压(SBP)、低密度脂蛋白胆固醇(LDL-C)、体质指数(BMI)、糖化血红蛋白(HbA1c)、吸烟、尿微量清蛋白(MALB)呈正相关,与GFR呈负相关。(3)多元逐步回归显示:SBP、HbA1C、GFR为影响胱抑素C显著因素。结论胱抑素C患者自罹患2型糖尿病就开始升高,除反映肾小球滤过率外,与尿微量清蛋白以及部分糖尿病肾病的危险因子呈正相关,是检测初诊2型糖尿病患者肾功能变化的新的内源性指标。     

微小RNA和衰老

微小RNA（miRNA）是一类非编码的单链小分子RNA,不仅是机体有目的编码RNA的重要调控分子,并且参与生长、发育、衰老的调控。本文主要描述了miRNA参与的有关衰老调控的一些可能通路和相关机制,如调控端粒酶的表达、p53信号通路、Rb通路;另外,本文还综述了通过调控miRNA合成的酶而影响衰老的一些特殊途径,以阐明当前miRNA与衰老关系的研究成果。     

左氧氟沙星对金黄葡萄球菌小RNA表达的影响

目的研究左氧氟沙星对金黄葡萄球菌小RNA表达的影响及对细菌生长的作用。方法分别在不同抑菌浓度左氧氟沙星干扰情况下,培养金黄葡萄球菌实验株RN6390和RN1HG001,提取RNA,用实时定量逆转录聚合酶链反应(qRT-PCR)检测不同菌株中RNAⅢ、RsaA、RsaE、RsaG、RsaH的含量,比较不同抑菌浓度左氧氟沙星作用下小RNA的表达差异。结果在MH培养液和BH培养液中左氧氟沙星对RN6390和RN1HG001的MIC均为0.25μg/ml。5种小RNA中,RNAⅢ的表达量最多,RsaG最少;当左氧氟沙星浓度≥1/4MIC时,开始对金黄葡萄球菌的生长产生明显抑制作用,5种小RNA的表达均开始下降;在RN6390菌株,1/16 MIC和1/8 MIC的左氧氟沙星能促进RsaH表达。结论不同浓度左氧氟沙星对金黄葡萄球菌小RNA表达具有抑制或者促进作用,提示除了其本身具有的阻碍细菌DNA合成的功能外还可能影响细菌基因的转录。     

Assessment of contrast‐enhanced computed tomography for imaging of cartilage during fracture healing

Assessment of the early stages of fracture healing via X‐rays and computed tomography is limited by the low radio‐opacity of cartilage. We validated a method of contrast‐enhanced computed tomography (CECT) for non‐destructive identification of cartilage within a healing fracture callus. Closed, stabilized fractures in femora of C57BL/6 mice were harvested on post‐operative day 9.5 and imaged ex vivo with micro‐computed tomography (µCT) before and after incubation in a cationic contrast agent that preferentially accumulates in cartilage due to the high concentration of sulfated glycosaminoglycans in the tissue. Co‐registration of the pre‐ and post‐incubation images, followed by image subtraction, enabled two‐ and three‐dimensional delineation of mineralized tissue, soft callus, and cartilage. The areas of cartilage and callus identified with CECT were compared to those identified with the gold‐standard method of histomorphometry. No difference was found between the areas of cartilage measured by the two methods (p = 0.999). Callus area measured by CECT was smaller than, but strongly predictive of (R² = 0.80, p < 0.001), the corresponding histomorphometric measurements. CECT also enabled qualitative identification of mineralized cartilage. These findings indicate that the CECT method provides accurate, quantitative, and non‐destructive visualization of the shape and composition of the fracture callus, even during the early stages of repair when little mineralized tissue is present. The non‐destructive nature of this method would allow subsequent analyses, such as mechanical testing, to be performed on the callus, thus enabling higher‐throughput, comprehensive investigations of bone healing. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 567–573, 2013     

Phase zero trials: a novel approach in drug development process

Abstract

Objective: The objective of this review is to explore the concept of phase 0, its contribution and also its practical guidance in drug development process. The process of drug development is protracted, complicated and requires lot of money. Phase 0 focuses on the aspect of microdosing, which determines the relation between PK & PD profile of drug; also selection of lead compound. Concept of phase 0 balances the planning of study scale between animal and human being, and creates a new way of defining phase I. Time is not too far when advance techniques and methods will be developed for the phase 0 studies to make it convenient and widely applicable in the design and development of majority of drugs. Conclusion: Although studies are yet to be done for phase 0 trial, it can be recognized that phase 0 trials would provide an opportunity to generate essential human PK and PD data much earlier in a drug development process, which could be a major advantage in design and decision making for further clinical development of an agent.     

Hypertension,fluid overload and micro inflammation are associated with left ventricular hypertrophy in maintenance hemodialysis patients

Abstract

This cross-sectional study aims to identify the potential risk factors of left ventricular hypertrophy (LVH) in hemodialysis (HD) patients. Echocardiography, anthropometric measurements and biochemical analyses were performed for 112 HD patients. In univariate analysis, body mass index, systolic blood pressure, diastolic blood pressure, glycosylated hemoglobin, glycated albumin, high sensitivity C-reactive protein (hs-CRP), cardiac troponin T (cTnT), amino-terminal pro-B-natriuretic peptide (NT-proBNP) and carotid artery intima-media thickness were positively correlated with left ventricular mass index (LVMI); pre-albumin, serum creatinine, left ventricular ejection fraction (LVEF) and fractional shortening were negatively correlated with LVMI. Linear regression analysis showed systolic blood pressure, NT-proBNP and LVEF were independently associated with LVMI. According to a binary logistic regression model, higher systolic blood pressure, NT-proBNP and hs-CRP levels showed independent correlation with LVH. Receiver operator characteristic curves analysis showed the associations between NT-proBNP and LVH more closely than hs-CRP and cTnT. The area under the curve for NT-proBNP, hs-CRP and cTnT was 0.762 (95% CI: 0.660–0.864, p?<?0.001), 0.734 (95% CI: 0.624–0.844, p?<?0.001) and 0.677 (95% CI: 0.563–0.790, p?=?0.004), respectively. These data support the main conclusions: hypertension, fluid overload and micro inflammation are associated with LVH in maintenance HD patients. It demonstrates traditional and nontraditional risk factors all play important roles in the development of LVH.     

The long-non-coding RNA NEAT1 is a novel target for Alzheimer’s disease progression via miR-124/BACE1 axis

ABSTRACT

Objectives: Long-non-coding RNAs (lncRNAs) have been involved in central nervous system recently. A number of studies have reported that lncRNA NEAT1 exerts critical roles in neurodegenerative disorder. Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) has been reported to exert function in the accumulation of amyloid-β (Aβ). Moreover, BACE1 acts as a target of miR-124 in the progression of AD. So far, the biological role and underlying mechanisms of NEAT1 and miR-124 in AD remains elusive.

Methods: The relative NEAT1 and miR-124 expression was examined by qRT-PCR in the tissues and cells line of AD. Cell apoptosis was examined by FACS. Luciferase reporter assay was performed to verify that miR-124 is a direct target of NEAT1, and BACE1 is a downstream target of miR-124. qRT-PCR and western blot analysis were also performed to determinate the BACE1 and the phosphorylation of tau protein.

Results: NEAT1 was notably up-regulated and miR-124 was remarkably down-regulated in AD mouse model. Knockdown of NEAT1 or overexpression of miR-124 showed the protective effects on cellular AD model induced by Aβ. Moreover, miR-124 expression could be up- and down-regulated by suppression or overexpression of NEAT1, respectively. In addition, the expression of BACE1 was the potential functional target of miR-124. These findings suggested that NEAT1 might play a vital role in the development of AD by regulating miR-124/BACE1 axis.

Discussion: The present study showed that NEAT1 worked as a regulating factor to promote the development of AD via modulating miR-124/BACE1 axis, which might be considered as a novel target in AD treatment.     

Validation of micro-CT against the section method regarding the assessment of marginal leakage of sealants

Background: The aim of this study was to validate the micro‐CT and related software against the section method using the stereomicroscope for marginal leakage assessment along the sealant‐enamel interface. Methods: Pits and fissures of the occlusal surface of 10 teeth were sealed with a resin‐fissure sealant material without acid etching, thermocycled for 5000 cycles, immersed in 50% silver nitrate for three hours and scanned using micro‐CT. Teeth were embedded in epoxy resin and cut in three sections. The middle section was subjected to micro‐CT and stereomicroscopy. Images were taken from the left and right sides of the sealant‐enamel interface at both the left and the right site of the section. Two experienced evaluators assessed marginal leakage. Results: Both assessment instruments observed no leakage in 37 out of the 40 images evaluated. Leakage at the sealant‐enamel interface was observed in three stereomicroscopy images only. A fracture line in the sealant was seen on eight stereomicroscopy images and observed in only two micro‐CT images. Conclusions: The quality of the micro‐CT and related software used in the present study does not qualify it to replace the section method as the gold standard for marginal leakage assessment at the sealant‐enamel interface of permanent teeth.