Chromatographic fingerprint analysis of Cephalotaxus sinensis from various sources by high-performance liquid chromatography-diodearray detection-electrospray ionization-tandem mass spectrometry

Selective and efficient analytical methods are required not only for quality assurance but also for authentication of Chinese herbal medicine. A simple, rapid and valid fingerprint method has been first carried out for the quality control of Cephalotaxus sinensis by using high-performance liquid chromatography (HPLC) coupled with photodiode array detection (DAD) and electrospray ionisation-tandem mass spectrometry (ESI-MS). The characteristic analytical fingerprints of this plant extract showed 18 common peaks, and out of these, 10 compounds involving 2 new compounds were identified by comparing the retention time, UV and ESI-MS/MS spectrum of each standard with those of each peak separated by on-line HPLC-DAD-MS/MS. Moreover, the effects of collecting locations, harvesting time, storage time, drying methods, and medicinal portions on herbal chromatographic fingerprints were examined by similarity analysis and principal component analysis (PCA) along with markers. Using the reference fingerprint along with markers, the best harvesting time, cultivation location and medicinal part were determined. The results obtained suggest that the chromatographic fingerprint combining similarity evaluation and PCA along with markers or pharmacologically active constituents can efficiently identify raw herb of Cephalotaxus sinensis from different sources, which provide helpful clues to the study of plant's secondary metabolites and benefit quality control.     

斑蝥药材气相色谱特征图谱研究

目的:建立斑蝥药材气相色谱(GC)特征图谱。方法:以广西产斑蝥为研究对象,采用GC法,选择Agilent 6890N气相色谱仪,ChemStations工作站;INNOWAX(30m×0.32mm×0.5μm)色谱柱;气化温度230℃,柱温210℃;FID检测:230℃。采用中国药典委员会出版的中药色谱特征图谱相似度评价系统软件(版本:2004A)进行相似度计算。结果:运用此方法能很好的分离斑蝥的各种成分,通过软件的比较,斑蝥药材的特征图谱相似度均大于0.90。结论:所建立的方法可作为斑蝥药材的特征图谱。     

Did We Interpret the Same Thing?

PURPOSE: Motivated by the potential application of "similarity theory" in nursing communication, the primary objectives of this paper are (a) to seek an in‐depth understanding of how nurses identify like concepts when comparing two similar but different images, and (b) to pinpoint the thinking process nurses use to determine "similarity" as a pretest of a framework that is meant to improve nursing communication for better patients' care. METHODS: A think‐aloud approach is used to elicit both written and verbal responses from six participants, who are medical‐surgical registered nurses with an associate degree, by comparing two specifically designed images for similarity determination. Data collected from participants include responses about four levels of similarities, a similarity rating using a 1–10 Likert‐type scale, and a most meaningful concept shared by the image pair. FINDINGS: Collected data indicate noticeable variability in the level and quality of details, which in turn demonstrates inconsistencies. The findings from analyzing the collected think‐aloud responses indicate that the proposed framework of thinking process was undertaken by at least three participants (i.e., 50%) before they reached the similarity rating and a meaningful concept. This study shows how misunderstandings in interpretation can occur simply because nurses used different similarity approaches. Anomalies are also found in the collected data (i.e., think‐aloud responses). Possible causes and explanations are given, along with suggestions for further investigation and validation of the proposed framework. CONCLUSIONS: In this study, a communication framework based on similarity theory was proposed to highlight the thinking process of nursing concept development. A think‐aloud pilot study was conducted. Results suggest that similarity theory and the proposed framework can be used to explain how nurses classify and determine similarities, though an in‐depth validation is needed. This framework may guide nurse educators to promote higher levels of thinking when educating students and nurses in the process of extracting quality information during patient care. The limitations of current research have been addressed. Additional research issues and extensions to this study are also provided in order to further improve nursing communication education.     

A Group Sequential Approach to Evaluation of Bridging Studies

Abstract

The International Conference on Harmonization (ICH) E5 guideline defines a bridging study as a supplementary study conducted in the new region to provide pharmacodynamic or clinical data on efficacy, safety, dosage, and dose regimen to allow extrapolation of the foreign clinical data to the population of the new region. Therefore, a bridging study is usually conducted in the new region only after the test product has been approved for commercial marketing in the original region due to its proven efficacy and safety. The issue of analysis of clinical data generated by the bridging study conducted in the new region to evaluate the similarity for extrapolation of the foreign clinical data to the population of the new region is the information on efficacy, safety, dosage, and dose regimen of the original region that cannot be concurrently obtained from the local bridging studies but is available in the trials conducted in the original region. A group sequential approach is therefore proposed to overcome the issue of internal validity. In particular, we use the region as a group sequence to enroll the patients from the original region first and then to enroll patients from the new region subsequently. Methods for sample size determination for the bridging study in the new region are also proposed.     

BRIDGING STUDIES IN CLINICAL DEVELOPMENT

Global development of pharmaceutical products has become the key to the success of any pharmaceutical sponsors. It is therefore crucial to address the efficacy and safety variations of a new test pharmaceutical product among different geographic regions due to ethnic factors. Recently, geotherapeutics has attracted much attention from sponsors as well as regulatory authorities from different geographic regions. To address this issue, the International Conference on Harmonization (ICH) has published a guideline entitled “Ethnic Factors in the Acceptability of Foreign Clinical Data,” which is known as ICH E5 guideline. The ICH E5 guideline provides a general framework for evaluation of the impact of ethnic factors on the efficacy, safety, dosage, and dose regimen. We provide an overview of ICH E5 guideline including ethnic sensitivity, necessity of bridging studies, types of bridging studies, and assessment of similarity between regions based on bridging evidence. In addition, challenges on the establishment of regulatory requirements, the assessment of bridging evidence, and design and analysis of bridging studies are addressed.     

A Note on Ethnic Sensitivity Studies

In this article, we propose a similarity criterion for ethnic sensitivity studies in pharmacokinetic variables. We present how this criterion can be used in the context of different dose-exposure models and how sample size and power calculations can be done. Examples for the planning and analysis of ethnic sensitivity studies are provided.     

Use of Prior Information for Bayesian Evaluation of Bridging Studies

The proportion ratio (PR) of a positive response between an experimental treatment and a standard treatment (or placebo) is often used to measure the relative treatment efficacy in a randomized clinical trial (RCT). For ethical reasons, it is almost inevitable to encounter some patients not complying with their assigned treatment. Furthermore, when there are confounders in a RCT or meta-analysis, we commonly employ stratified analysis to control the confounding effects on interval estimation of the PR. On the basis of a general risk multiplicative model, we focus our discussion on interval estimation of the PR in repeated binary data under a stratified RCT with noncompliance. We develop seven asymptotic closed-form interval estimators for the PR. We apply Monte Carlo simulation to study the finite-sample performance of these interval estimators in a variety of situations. We note that the two interval estimators with the logarithmic transformation based on the commonly used weighted least squares (WLS) approach can be liberal, while the three interval estimators with the Mantel–Haenszel (MH) weight derived from various methods can consistently perform well. We also note that the two estimators with the estimated optimal weight defined in the context using Fieller's Theorem and a randomization-based approach may not necessarily produce a confidence interval preferable to the MH-type interval estimators for the PR with respect to accuracy and precision.     

Cross-reactivity studies and predictive modeling of “Bath Salts” and other amphetamine-type stimulants with amphetamine screening immunoassays

Introduction. The increasing abuse of amphetamine-like compounds presents a challenge for clinicians and clinical laboratories. Although these compounds may be identified by mass spectrometry-based assays, most clinical laboratories use amphetamine immunoassays that have unknown cross-reactivity with novel amphetamine-like drugs. To date, there has been a little systematic study of amphetamine immunoassay cross-reactivity with structurally diverse amphetamine-like drugs or of computational tools to predict cross-reactivity. Methods. Cross-reactivities of 42 amphetamines and amphetamine-like drugs with three amphetamines screening immunoassays (AxSYM^® Amphetamine/Methamphetamine II, CEDIA^® amphetamine/Ecstasy, and EMIT^® II Plus Amphetamines) were determined. Two- and three-dimensional molecular similarity and modeling approaches were evaluated for the ability to predict cross-reactivity using receiver–operator characteristic curve analysis. Results: Overall, 34%–46% of the drugs tested positive on the immunoassay screens using a concentration of 20,000 ng/mL. The three immunoassays showed differential detection of the various classes of amphetamine-like drugs. Only the CEDIA assay detected piperazines well, while only the EMIT assay cross-reacted with the 2C class. All three immunoassays detected 4-substituted amphetamines. For the AxSYM and EMIT assays, two-dimensional molecular similarity methods that combined similarity to amphetamine/methamphetamine and 3,4-methylenedioxymethampetamine most accurately predicted cross-reactivity. For the CEDIA assay, three-dimensional pharmacophore methods performed best in predicting cross-reactivity. Using the best performing models, cross-reactivities of an additional 261 amphetamine-like compounds were predicted. Conclusions. Existing amphetamines immunoassays unevenly detect amphetamine-like drugs, particularly in the 2C, piperazine, and β-keto classes. Computational similarity methods perform well in predicting cross-reactivity and can help prioritize testing of additional compounds in the future.     

自然疗养因子的作用机制研究进展

自然疗养因子所涵盖的内容丰富,其生物学效应及形成复杂。现代疗养学在形成过程中相继提出自然疗养因子对机体作用的理论或假说。随着医学模式的转变和现代医学的发展,自然疗养因子作用机制研究从分子、细胞到组织器官,涉及机体物质代谢、神经系统、内分泌和免疫等功能的相互作用,形成整体的各个水平产生适应的作用机制;研究证实自然疗养因子的作用最根本的表现为改善机体内环境稳态和机体与外环境间的平衡,是靠机体的适应性反应机制实现的;其次与祖国医学“天人合一”整体观一脉相承。近年来,研究证实环境因素通过基因的重返表达对表观遗传产生影响,同时疗养因子参与机体的生物节律调控不断深入,机体对自然疗养因子的应答反应是受到多种因素的影响,包括机体状态、疗养因子的种类、性质、作用剂量、应用时间、季节及个体差异等。本文主要对自然疗养因子的作用机制及对机体的作用等方面进行总结。     

基于改进SLNC的2D-3D医学图像配准

介绍了一种基于改进SLNC(sum of local normalized correlation,SLNC)的2D-3D医学图像配准方法。首先对CT体积数据进行三线性插值,得到各向分辨率相同的体积数据,采用光线跟踪算法对其进行数字图像重建。针对不同位置和方向的重建图像,在灰度级压缩的基础上,用改进SLNC函数评价其与X线透视图像的相似性,利用与Brent相结合的Powell优化方法,搜索出相似性最大时的投影变换参数。将此方法用于移动数字X线投影设备——Biplanar 500采集的X线透视图像与相应CT体积数据的配准实验,得到较好的2D-3D图像配准效果。