强心合剂治疗慢性心力衰竭40例

目的观察强心合剂对慢性心力衰竭患者的心功能改善作用。方法将慢性心力衰竭病人40例分为对照组和治疗组,各20例。对照组根据临床药物指南推荐采用西医常规治疗,治疗组在西医常规治疗的基础上加用强心合剂方,连服4周后观察疗效。结果 2组患者主要症状、体征、心脏结构功能、运动耐量均具有显著性差异,心功能疗效治疗组总有效率90%优于对照组的70%(P<0.05)。结论治疗组较对照组,能够进一步缓解临床症状、改善心功能、提高运动耐量,强心合剂方与常规西药治疗有协同作用。     

GHEP-ISFG collaborative exercise on mixture profiles of autosomal STRs (GHEP-MIX01, GHEP-MIX02 and GHEP-MIX03): Results and evaluation

One of the main objectives of the Spanish and Portuguese-Speaking Group of the International Society for Forensic Genetics (GHEP-ISFG) is to promote and contribute to the development and dissemination of scientific knowledge in the area of forensic genetics. Due to this fact, GHEP-ISFG holds different working commissions that are set up to develop activities in scientific aspects of general interest. One of them, the Mixture Commission of GHEP-ISFG, has organized annually, since 2009, a collaborative exercise on analysis and interpretation of autosomal short tandem repeat (STR) mixture profiles. Until now, three exercises have been organized (GHEP-MIX01, GHEP-MIX02 and GHEP-MIX03), with 32, 24 and 17 participant laboratories respectively. The exercise aims to give a general vision by addressing, through the proposal of mock cases, aspects related to the edition of mixture profiles and the statistical treatment.The main conclusions obtained from these exercises may be summarized as follows. Firstly, the data show an increased tendency of the laboratories toward validation of DNA mixture profiles analysis following international recommendations (ISO/IEC 17025:2005). Secondly, the majority of discrepancies are mainly encountered in stutters positions (53.4%, 96.0% and 74.9%, respectively for the three editions). On the other hand, the results submitted reveal the importance of performing duplicate analysis by using different kits in order to reduce errors as much as possible. Regarding the statistical aspect (GHEP-MIX02 and 03), all participants employed the likelihood ratio (LR) parameter to evaluate the statistical compatibility and the formulas employed were quite similar. When the hypotheses to evaluate the LR value were locked by the coordinators (GHEP-MIX02) the results revealed a minor number of discrepancies that were mainly due to clerical reasons. However, the GHEP-MIX03 exercise allowed the participants to freely come up with their own hypotheses to calculate the LR value. In this situation the laboratories reported several options to explain the mock cases proposed and therefore significant differences between the final LR values were obtained. Complete information concerning the background of the criminal case is a critical aspect in order to select the adequate hypotheses to calculate the LR value. Although this should be a task for the judicial court to decide, it is important for the expert to account for the different possibilities and scenarios, and also offer this expertise to the judge. In addition, continuing education in the analysis and interpretation of mixture DNA profiles may also be a priority for the vast majority of forensic laboratories.     

Piecewise Growth Mixture Tobit Models: Application to AIDS Studies

Piecewise growth models are very flexible methods for assessing distinct phases of development or progression in longitudinal data. As an extension of these models, this paper presents piecewise growth mixture Tobit models (PGMTMs) for describing phasic changes of individual trajectories over time where the longitudinal data has a mixture of subpopulations and where left censoring due to a lower limit of detection (LOD) is also observed. There has been relatively little work done simultaneously modeling heterogeneous growth trajectories, segmented phases of progression, and left-censoring with skewed responses. The proposed methods are illustrated using real data from an AIDS clinical study. Analysis results suggested two classes of viral load growth trajectories: Class 1 started with a decline in viral load after treatment but rebound after change-point; Class 2 had a decrease the same as the Class 1 and continued a slower decrease over time.     

Identification of Differentially Expressed Genes with Multivariate Outlier Analysis

Abstract

DNA microarray offers a powerful and effective technology to monitor the changes in the gene expression levels for thousands of genes simultaneously. It is being widely applied to explore the quantitative alternation in gene regulation in response to a variety of aspects including diseases and exposure of toxicant. A common task in analyzing microarray data is to identify the differentially expressed genes under two different experimental conditions. Because of the large number of genes and small number of arrays, and higher signal-noise ratio in microarray data, many traditional approaches seem improper. In this paper, a multivariate mixture model is applied to model the expression level of replicated arrays, considering the differentially expressed genes as the outliers of the expression data. In order to detect the outliers of the multivariate mixture model, an effective and robust statistical method is first applied to microarray analysis. This method is based on the analysis of kurtosis coefficient (KC) of the projected multivariate data arising from a mixture model so as to identify the outliers. We utilize the multivariate KC algorithm to our microarray experiment with the control and toxic treatment. After the processing of data, the differential genes are successfully identified from 1824 genes on the UCLA M07 microarray chip. We also use the RT-PCR method and two robust statistical methods, minimum covariance determinant (MCD) and minimum volume ellipsoid (MVE), to verify the expression level of outlier genes identified by KC algorithm. We conclude that the robust multivariate tool is practical and effective for the detection of differentially expressed genes.     

Mixture experiment methods in the development and optimization of microemulsion formulations

Microemulsion formulations represent an interesting delivery vehicle for lipophilic drugs, allowing for improving their solubility and dissolution properties. This work developed effective microemulsion formulations using glyburide (a very poorly-water-soluble hypoglycaemic agent) as a model drug. First, the area of stable microemulsion (ME) formations was identified using a new approach based on mixture experiment methods. A 13-run mixture design was carried out in an experimental region defined by constraints on three components: aqueous, oil and surfactant/cosurfactant. The transmittance percentage (at 550 nm) of ME formulations (indicative of their transparency and thus of their stability) was chosen as the response variable. The results obtained using the mixture experiment approach corresponded well with those obtained using the traditional approach based on pseudo-ternary phase diagrams. However, the mixture experiment approach required far less experimental effort than the traditional approach. A subsequent 13-run mixture experiment, in the region of stable MEs, was then performed to identify the optimal formulation (i.e., having the best glyburide dissolution properties). Percent drug dissolved and dissolution efficiency were selected as the responses to be maximized. The ME formulation optimized via the mixture experiment approach consisted of 78% surfactant/cosurfacant (a mixture of Tween 20 and Transcutol, 1:1, v/v), 5% oil (Labrafac Hydro) and 17% aqueous phase (water). The stable region of MEs was identified using mixture experiment methods for the first time.     

Assessment of toxic interactions of heavy metals in multi-component mixtures using sea urchin embryo-larval bioassay

The toxicities of copper, lead, zinc and cadmium ions and various concentrations of mixtures of them were studied using sea urchin (Strongylocentyotus intermedius) embryo-larval bioassay. Toxic unit analysis was used to determine type of joint action for each mixture combination (binary, ternary and quaternary). For the majority of the binary combinations, the interactions were of synergistic nature, but in ternary or quaternary mixtures, the joint action was mainly concentration additive, while antagonism was only observed for two mixtures (Cu + Pb and Zn + Cd) among all the 11 combinations. Two prevailing theoretical models: the concentration addition (CA) model and the independent action (IA) model were used to predict the mixture toxicities. The weak correlation obtained (R ? 0.55) indicated that the hypotheses of mode of action involved in the two models to some extent failed to describe the behavior of the mixture system. Then a novel bio-concentration factor-based model was developed and was successful to predict the toxicities of mixtures, with an obtained R of 0.92. This model indicated that in a mixture system of heavy metals, the joint toxicity was mainly determined by the combined action of bio-concentrations of metals other than the simply similar (CA) or dissimilar (IA) modes of action of the mixture components.     

硝普钠、多巴胺、多巴酚丁胺、钾镁合剂联合磷酸肌酸在重症心衰治疗中的疗效分析

目的观察硝普钠、多巴胺、多巴酚丁胺、钾镁合剂联合磷酸肌酸治疗重症充血性心力衰竭（CHF）的疗效。方法随机对照比较40例充血性心力衰竭（CHF）患者（治疗组、对照组各20例）,治疗组在常规治疗基础上加硝普钠、多巴胺、多巴酚丁胺、钾镁合剂、磷酸肌酸（CP）。结果治疗组治疗后心功能分级改善总有效率为95%,LVEF明显增加,LVESD、LVEDD减小,与对照组比较有统计学意义（P〈0.01）。结论 CHF患者应用硝普钠、多巴胺、多巴酚丁胺、钾镁合剂联合磷酸肌酸具有显著改善心功能的作用。     

A novel model integrated concentration addition with independent action for the prediction of toxicity of multi-component mixture

Concentration addition (CA) and independent action (IA) have been used to describe the mixture of components having similar and dissimilar mode of action (MOA), respectively. Environmentally relevant mixture does, however, not follow the strictly similar or dissimilar MOA. A novel model, which integrated CA with IA based on the multiple linear regression (ICIM), was proposed for predicting the toxicity of noninteractive mixture. The predictive power of the ICIM model was validated by data set 1 including 13 mixtures of nine components and data set 2 including six mixtures of six components. For data set 1, ten uniform design with fixed concentration ratio ray (UDCR) mixtures was used as a training set to build an ICIM model, and the model was used to predict the toxicity of the test set consisting of three equivalent-effect concentration ratio (EECR) mixtures. For data set 2, the ICIM model based on four UDCR mixtures was used to predict the remaining two EECR mixtures. It is concluded that the ICIM model shows a strong predictive power for the mixture toxicities in the two data sets, and its prediction is better than CA and IA where the two models deviate from the concentration-response data of the mixtures. Thus, ICIM model is a powerful tool to evaluate and predict mixture toxicity, and maybe offer an important approach in risk assessment of mixture toxicity.     

Non-additive hepatic gene expression elicited by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153) co-treatment in C57BL/6 mice

Interactions between environmental contaminants can lead to non-additive effects that may affect the toxicity and risk assessment of a mixture. Comprehensive time course and dose-response studies with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), non-dioxin-like 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB153) and their mixture were performed in immature, ovariectomized C57BL/6 mice. Mice were gavaged once with 30 μg/kg TCDD, 300 mg/kg PCB153, a mixture of 30 μg/kg TCDD with 300 mg/kg PCB153 (MIX) or sesame oil vehicle for 4,12, 24,72 or 168 h. In the 24 h dose-response study, animals were gavaged with TCDD (0.3,1, 3, 6, 10, 15, 30, 45 μg/kg), PCB153 (3,10, 30, 60, 100, 150, 300, 450 mg/kg), MIX (0.3 + 3, 1 + 10, 3 + 30, 6 + 60, 10 + 100, 15 + 150, 30 + 300, 45 μg/kg TCDD + 450 mg/kg PCB153, respectively) or vehicle. All three treatments significantly increased relative liver weights (RLW), with MIX eliciting significantly greater increases compared to TCDD and PCB153 alone. Histologically, MIX induced hepatocellular hypertrophy, vacuolization, inflammation, hyperplasia and necrosis, a combination of TCDD and PCB153 responses. Complementary lipid analyses identified significant increases in hepatic triglycerides in MIX and TCDD samples, while PCB153 had no effect on lipids. Hepatic PCB153 levels were also significantly increased with TCDD co-treatment. Microarray analysis identified 167 TCDD, 185 PCB153 and 388 MIX unique differentially expressed genes. Statistical modeling of quantitative real-time PCR analysis of Pla2g12a, Serpinb6a, Nqo1, Srxn1, and Dysf verified non-additive expression following MIX treatment compared to TCDD and PCB153 alone. In summary, TCDD and PCB153 co-treatment elicited specific non-additive gene expression effects that are consistent with RLW increases, histopathology, and hepatic lipid accumulation.