Comparison of thiazide‐like diuretics versus thiazide‐type diuretics: a meta‐analysis

Thiazide diuretics are widely used for the management of hypertension. In recent years, it has been actively debated that there is interchangeability of thiazide‐type diuretics hydrochlorothiazide and thiazide‐like diuretics including indapamide and chlorthalidone for the treatment of hypertension. With the purpose of seeking out the best thiazide diuretic for clinicians, we summarized the existing evidence on the two types of drugs and conducted a meta‐analysis on their efficacy in lowering blood pressure and effects on blood electrolyte, glucose and total cholesterol. Twelve trials were identified: five based on the comparison of indapamide versus hydrochlorothiazide and seven based on the chlorthalidone versus hydrochlorothiazide. In the meta‐analysis of blood pressure reduction, thiazide‐like diuretics seemed to further reduce systolic BP ([95% CI]; ?5.59 [?5.69, ?5.49]; P < 0.001) and diastolic BP ([95% CI]; ?1.98 [?3.29, ?0.66]; P = 0.003). Meanwhile, in the analysis of side effects, the incidence of hypokalemia ([95% CI]; 1.58 [0.80, 3.12]; P = 0.19), hyponatremia ([95% CI]; ?0.14 [?0.57, 0.30], P = 0.54), change of blood glucose ([95% CI];0.13 [?0.16, 0.41], P = 0.39) and total cholesterol ([95% CI]; 0.13 [?0.16, 0.41], P = 0.39) showed that there is no statistical significant differences between the two groups of drugs. In conclusion, using thiazide‐like diuretics is superior to thiazide‐type diuretics in reducing blood pressure without increasing the incidence of hypokalemia, hyponatraemia and any change of blood glucose and serum total cholesterol.     

Penalized estimating equations

Penalty models--such as the ridge estimator, the Stein estimator, the bridge estimator, and the Lasso-have been proposed to deal with collinearity in regressions. The Lasso, for instance, has been applied to linear models, logistic regressions, Cox proportional hazard models, and neural networks. This article considers the bridge penalty model with penalty sigma(j)/beta(j)/gamma for estimating equations in general and applies this penalty model to the generalized estimating equations (GEE) in longitudinal studies. The lack of joint likelihood in the GEE is overcome by the penalized estimating equations, in which no joint likelihood is required. The asymptotic results for the penalty estimator are provided. It is demonstrated, with a simulation and an application, that the penalized GEE potentially improves the performance of the GEE estimator, and enjoys the same properties as linear penalty models.     

基于复杂性度量的心率变异信号非线性分析

假设心率变异信号是累积－发放模型（Ｉｎｔｅｇｒａｔｅ－ｆｉｒｅ）与非线性动力学系统耦合产生的峰电位链（ＳｐｉｋｅＴｒａｉｎ）。以符号动力学为基础,提出利用峰电位间隔（ｉｎｔｅｒｓｐｉｋｅｉｎｔｅｒｖａｌ,ＩＳＩ）及其随机替代数据的Ｃ１、Ｃ２复杂度来定量刻划非线性动力学系统特性。结果表明：确定性驱动产生的峰电位间隔序列可以与随机性驱动产生的峰电位间隔序列区分开。因此,在噪声干扰较强的生理信号中,尤其是在不清楚非线性动力系统变量和峰电位间隔序列之间是否存在微分同胚的情况下,以复杂性度量来代替以Ｔａｋｅｎｓ嵌入定理为基础的关联维数、Ｌｙａｐｎｏｖ指数等描述动力系统特征的方法是合适的。最后通过２类共３７个个体,每个个体的心电数据为１０００个Ｒ－Ｒ间期的微分序列检验心率变异信号的非线性结构。     

Ligation of the fibrin-binding domain by β-strand addition is sufficient for expansion of soluble fibronectin

How fibronectin (FN) converts from a compact plasma protein to a fibrillar component of extracellular matrix is not understood. "Functional upstream domain" (FUD), a polypeptide based on F1 adhesin of Streptococcus pyogenes, binds by anti-parallel β-strand addition to discontinuous sets of N-terminal FN type I modules, (2-5)FNI of the fibrin-binding domain and (8-9)FNI of the gelatin-binding domain. Such binding blocks assembly of FN. To learn whether ligation of (2-5)FNI, (8-9)FNI, or the two sets in combination is important for inhibition, we tested "high affinity downstream domain" (HADD), which binds by β-strand addition to the continuous set of FNI modules, (1-5)FNI, comprising the fibrin-binding domain. HADD and FUD were similarly active in blocking fibronectin assembly. Binding of HADD or FUD to soluble plasma FN exposed the epitope to monoclonal antibody mAbIII-10 in the tenth FN type III module ((10)FNIII) and caused expansion of FN as assessed by dynamic light scattering. Soluble N-terminal constructs truncated after (9)FNI or (3)FNIII competed better than soluble FN for binding of FUD or HADD to adsorbed FN, indicating that interactions involving type III modules more C-terminal than (3)FNIII limit β-strand addition to (1-5)FNI within intact soluble FN. Preincubation of FN with mAbIII-10 or heparin modestly increased binding to HADD or FUD. Thus, ligation of FNIII modules involved in binding of integrins and glycosaminoglycans, (10)FNIII and (12-14)FNIII, increases accessibility of (1-5)FNI. Allosteric loss of constraining interactions among (1-5)FNI, (10)FNIII, and (12-14)FNIII likely enables assembly of FN into extracellular fibrils.     

Synthesis and characterization of folic acid modified water-soluble chitosan derivatives for folate-receptor-mediated targeting

Three chemical modification methods of carboxymethylation, quaternization and hydroxypropylation were used to synthesize water-soluble chitosan derivatives. In order to study the feasibility of these chitosan derivatives as backbones of nuclear imaging agents, folic acid (FA) and Technetium-99m were introduced onto the water-soluble chitosan chains. The bifunctional chelating agent 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was conjugated to the folate grafted chitosan derivatives for chelating with radionuclides such as (64)Cu and (68)Ga. The structures of these new ligands were characterized with multiple methods. The solubility and stability of the (99m)Tc-complexes were both favorable. Further study of their radiochemical and biological properties will be performed to evaluate the usefulness of these water-soluble chitosan derivatives for nuclear imaging agent design.     

An Imputation Approach for Oligonucleotide Microarrays

Oligonucleotide microarrays are commonly adopted for detecting and qualifying the abundance of molecules in biological samples. Analysis of microarray data starts with recording and interpreting hybridization signals from CEL images. However, many CEL images may be blemished by noises from various sources, observed as “bright spots”, “dark clouds”, and “shadowy circles”, etc. It is crucial that these image defects are correctly identified and properly processed. Existing approaches mainly focus on detecting defect areas and removing affected intensities. In this article, we propose to use a mixed effect model for imputing the affected intensities. The proposed imputation procedure is a single-array-based approach which does not require any biological replicate or between-array normalization. We further examine its performance by using Affymetrix high-density SNP arrays. The results show that this imputation procedure significantly reduces genotyping error rates. We also discuss the necessary adjustments for its potential extension to other oligonucleotide microarrays, such as gene expression profiling. The R source code for the implementation of approach is freely available upon request.     

多源多角度遥感数据反演森林叶面积指数方法

利用北京1号和Landsat多源数据组合成4个角度多波段数据集, 在考虑森林三维垂直分布特点的基础上, 结合INFORM几何光学与辐射传输混合模型, 通过聚类+神经元网络方式, 建立相应的多源多角度LAI反演模型。最后利用实地LAI测量数据和MODIS LAI产品, 对不同角度组合和噪声水平下的LAI反演结果进行验证。结果表明: 在保证数据质量的条件下, 通过增加角度可以提高森林的LAI反演精度, 最终R²=0.713, RMSE=0.957, 比单个角度的反演精度平均提高约20%。     

Cadmium Is More Toxic on Volume Bone Mineral Density than Tissue Bone Mineral Density

It has been showed that Cd induces low areal bone mineral density, but we do not know the effect of Cd on cubic bone density. This study was aimed to investigate the effects of Cd on volumetric bone mineral density (VBMD) and tissue bone mineral density (TBMD) in male rats. Twenty-four Sprague-Dawley male rats were randomly divided into four groups that were given cadmium chloride by subcutaneous injection at doses of 0, 0.1, 0.5, and 1.5?mg/kg body weight for 8?weeks, respectively. Then, microcomputed tomography scanning was performed on the proximal tibia, and region of interest was reconstructed using microview software. The VBMD, bone volume fraction of rats treated with 1.5?mg Cd/kg, were significantly decreased compared to control (p?相似文献   

No Observable Relationship Between the 12 Genes of Nervous System and Reasoning Skill in a Young Chinese Han Population

Reasoning skill is an advanced cognitive ability which is needed for drawing inferences from given information. It is well known that the ability depends on the neural network of the frontal and parietal brain regions. In this study, we hypothesized that some genes involved in neurotransmitter systems were related to reasoning skill. To confirm this hypothesis, we examined the effects of 13 genes (BDNF, NRSF, COMT, DBH, DRD ₂ , DRD ₃ , DAT ₁ , MAOA, GRM ₁, GRIN2B, TPH ₂ , 5-HT _2A , and 5-HT ₆ ) in neurotransmitter systems on the non-verbal reasoning and verbal reasoning skills. The results indicated there were on significant effects of the 17 functional variants of these genes on the performance of non-verbal reasoning and verbal analogical reasoning skills (χ² > 3.84, df = 1, P > 0.05). This study suggests that some of the functional variations in BDNF, COMT, DBH, DRD ₂ , DRD ₃ , MAOA, 5-HT _2A , 5-HT ₆ , GRM ₁ , and GRIN2B have no observable effects on the certain reasoning skills in a young healthy Chinese Han population.