Step‐up testing procedure for multiple comparisons with a control for a latent variable model with ordered categorical responses

In clinical studies, multiple comparisons of several treatments to a control with ordered categorical responses are often encountered. A popular statistical approach to analyzing the data is to use the logistic regression model with the proportional odds assumption. As discussed in several recent research papers, if the proportional odds assumption fails to hold, the undesirable consequence of an inflated familywise type I error rate may affect the validity of the clinical findings. To remedy the problem, a more flexible approach that uses the latent normal model with single‐step and stepwise testing procedures has been recently proposed. In this paper, we introduce a step‐up procedure that uses the correlation structure of test statistics under the latent normal model. A simulation study demonstrates the superiority of the proposed procedure to all existing testing procedures. Based on the proposed step‐up procedure, we derive an algorithm that enables the determination of the total sample size and the sample size allocation scheme with a pre‐determined level of test power before the onset of a clinical trial. A clinical example is presented to illustrate our proposed method. Copyright © 2014 John Wiley & Sons, Ltd.     

早期2型糖尿病肾病患者社区综合干预效果分析

目的 探讨早期2型糖尿病肾病患者社区综合干预方案的实施效果.方法 对社区2型糖尿病在册管理对象中选择符合早期糖尿病肾病期诊断标准,且自愿参加的患者80例作为研究对象,实施肾病早期综合干预方案.干预12个月后对血压、空腹血糖、糖化血红蛋白、血脂及尿微量白蛋白指标进行效果评价.结果 研究对象经综合干预后其相关检测指标均比干预前有好转,经t检验分析：尿微量白蛋白、TG、HDL和LDL四项指标前后差异有极显著性意义（P＜0.01）;收缩压、舒张压、FBG、HbAlc、TL及BMI六项指标前后差异有显著性意义（P＜0.05）.结论 本研究反映在社区卫生服务中心对糖尿病伴发早期肾病患者开展综合干预是可行有效的,对控制早期糖尿病肾病患者病情的发展具有重要的影响.     

内源性H2S参与了肝癌细胞HepG-2的耐热

目的探讨内源性硫化氢（hydrogen sulfide,H2S）是否参与了耐热肝癌细胞HepG-2/thermotolerance（HepG-2/tt）的耐热。方法通过PI染色流式细胞仪检测和比较HepG-2细胞与HepG-2/tt细胞耐热后的细胞凋亡率,用亚甲基蓝显色分光光度计法检测和比较HepG-2细胞与HepG-2/tt细胞耐热后H2S生成量和H2S合酶活性的差异。结果 43℃环境培养24 h后,耐热肝癌细胞HepG-2/tt的细胞凋亡率较普通肝癌细胞HepG-2明显下降（P〈0.01）;且HepG-2/tt细胞中H2S含量和H2S合酶活性均较普通HepG-2细胞明显增加（P〈0.01）。结论 HepG-2/tt较HepG-2细胞具有热耐受性,并且其内源性硫化氢合酶活性和硫化氢生成量均有提高。     

Synthesis of taurine–fluorescein conjugate and evaluation of its retina-targeted efficiency in vitro

In this work, retinal penetration of fluorescein was achieved in vitro by covalent attachment of taurine to fluorescein, yielding the F–Tau conjugate. Nuclear magnetic resonance (NMR) and high resolution mass spectrometry (HRMS) were used to confirm the successful synthesis of F–Tau. The cellular uptake of F–Tau in adult retinal pigment epithelial cells (ARPE-19) and human retinal microvascular endothelial cells (hRMECs) was visualized via confocal scanning microscopy. The results indicated an improvement of solubility and a reduction of logP of F–Tau compared with fluorescein. As compared with fluorescein, F–Tau showed little toxicity, and was retained longer by cells in uptake experiments. F–Tau also displayed higher transepithelial permeabilities than fluorescein in ARPE-19 and hRMECs monolayer cells (P<0.05). These results showed that taurine may be a useful ligand for targeting small-molecule hydrophobic pharmaceuticals into the retina.KEY WORDS: Taurine, Taurine–fluorescein conjugate, Retina-targeting, ARPE-19, hRMECs, Transepithelial permeability     

Biodegradation of bis(2-hydroxyethyl) terephthalate by a newly isolated Enterobacter sp. HY1 and characterization of its esterase properties

Bis(2-hydroxyethyl) terephthalate (BHET) is an important compound produced from poly(ethylene terephthalate) (PET) cleavage. It was selected as the representative substance for the study of PET degradation. A bacterial strain HY1 that could degrade BHET was isolated and identified as Enterobacter sp. The optimal temperature and pH for BHET biodegradation were determined to be 30°C and 8.0, respectively. The half-life of degradation was 70.20 h at an initial BHET concentration of 1,000 mg/L. The results of metabolites' analysis by liquid chromatograph–mass spectrometer revealed that BHET was first converted to mono-(2-hydroxyethyl) terephthalate (MHET) and then to terephthalic acid. Furthermore, an esterase-encoding gene, estB, was cloned from strain HY1, and the expressed enzyme EstB was characterized. The esterase has a molecular mass of approximately 25.13 kDa, with an isoelectric point of 4.68. Its optimal pH and temperature were pH 8.0 and 40°C, respectively. The analysis of the enzymatic products showed that EstB could hydrolyze one ester bond of BHET to MHET. To the best of authors' knowledge, this is the first report on the biodegradation characteristics of BHET by a member of the Enterobacter genus.     

组织工程学中骨修复材料的研究热点与进展

BACKGROUND: With the improvement in medical level, the clinical demand for bone repair materials is gradually increasing, and the requirements are also getting more and more.