MALDI-TOF MS在药物基因组学检测中的应用及展望

药物基因组学是临床基因检测的新兴领域,是个体化医学模式的重要组成部分。药物基因组学检测的结果能够在安全、合理用药中发挥指导作用,这使得越来越多的研究者更加关注遗传信息多态性与个体药物反应差异之间的关系。诞生于上世纪80年代的基质辅助激光解吸飞行时间质谱(MALDI-TOF MS)已成为临床领域进行基因检测的主流技术之一。对于药物基因组学检测中常见的单核苷酸多态性(SNP)、拷贝数变异(CNV)、插入/缺失(In/Del)等分子标记,MALDI-TOF MS均能实现准确检出,同时以其检测的多重性、精准性、简便性、经济性得到越来越多的关注和应用。本文介绍了MALDI-TOF MS的技术原理并总结了MALDI-TOF MS在药物基因组学检测中的多个研究案例,旨在推广该技术在药物基因组研究中的应用,并加深研究者对该技术平台的认识,通过该技术平台的推广促进药物基因组学在临床的转化应用。     

抗过敏和精神药物加剧老年人健忘

加拿大、美国和澳大利亚研究人员联合在最新一期的美国《药物与衰老》杂志发表研究报告说,老年人服用治疗失眠、焦虑等的药物加重了对记忆力的损伤。调查显示,在日常生活中,65岁以上的老年人大约90%服用至少一种药物,近半数服用5种以上药物,其中有很多是精神类药物和抗过敏药物。研究人员对以往162份研究报告作了评估。研究报告说,有一     

口服降糖药的药物基因组学临床研究进展

2型糖尿病的流行已成为全球化的公共卫生问题,不仅造成社会经济负担的增加,也给患者带来极大痛苦。因此,能够有效地控制血糖,降低用药成本的个性化用药成为后基因组时代的研究热点,而其理论基础则是药理基因组学。该文从药物代谢酶、药物转运蛋白、药物受体或作用靶点以及下游信号通路入手,分别对目前临床应用广泛、研究较为深入的四类口服降糖药的药物基因组学研究成果进行综述,以期对2型糖尿病药物临床应用和研究提供参考和依据。     

药物基因组学(pharmacogenomics)

应用基因组科学研究药物的一门新分支学科。迄今 ,该学科主要研究任务有 4方面 :一是根据基因组结构和传统药物作用靶点 ,确定新的药物作用靶点 ,结合计算机辅助设计、组合化学及其他手段进行高通量新药筛选 ;二是根据某些基因多态性和表达谱的特异性改变与其对药物敏感性相关联的事实 ,为个体化治疗提供科学依据 ;三是根据与疾病相关的蛋白质的空间结构 ,寻找药物作用新靶点 ;四是进行药理作用机制的研究。药物基因组学(pharmacogenomics)@方福德!100005北京$中国医学科学院基础医学研究所     

疾病相关基因-药物关联抽取规程设计

目的立足于信息科学,面向疾病靶向药物研发,进行疾病相关基因-药物关联抽取,致力于发现新的基因-药物关联,为新药研发提供科学假设。方法具体从疾病相关的基因-药物关系类型界定、关联抽取方法对比筛选、优选方法在研究问题中的实现、方法评价及知识发现等4个方面展开论述。结果形成了疾病相关基因-药物关联抽取的规范化流程,促进疾病靶向药物研发。     

维生素D可增强中年男性脑力

一项新的研究显示,来自油脂丰富的鱼类和经曝晒阳光后在皮肤合成的维生素D,与中年男性脑力增强有关。发表在最近出版的《神经学、神经外科和精神病学杂志》(JNNP)上的这份研究报告称,维生素D的增加与信息处理的加速有关联,这种关联在60岁以     

过早添加辅食，奶粉喂养婴儿更易肥胖

英国研究人员日前公布的一份研究报告显示：过早给用奶粉喂养的婴儿添加辅食．将显著增加他们日后肥胖的风险，但对于母乳喂养的婴儿来说．添加辅食时间的早晚却与其日后肥胖的风险无明显关联。     

吉百利糖果公司进口原料携带有害生物

科学家发现，雷帕霉素或许能让人寿命显著延长。雷帕霉素是一种广泛用于治疗自身免疫和移植排斥疾病的免疫抑制药物。不过《自然》杂志7月刊登的研究报告指出，这种药物的致命缺陷是——会削弱免疫系统。     

提高胰岛素敏感性有新法

美国一项研究报告说，去除实验鼠体内的一种关键调控蛋白，可显著提高其对胰岛素的敏感性。这项研究为糖尿病治疗和药物研发提供了新途径。     

脑部的缺陷易导致睡眠呼吸暂停综合征发生

两项新的研究报告显示．数百万美国人被睡眠问题所困，而这样的问题有可能是因为脑部的化学物质不平衡所致。这项研究报告的主要研究人员密西根大学的Gilman博士认为，这是证实这项关系的第一项证据，这项研究同时引导一种可以治疗常见的睡眠问题如呼吸暂停的药物治疗方式。     

Strengthening the Reporting of Observational Studies in Epidemiology – nutritional epidemiology (STROBE‐nut): An extension of the STROBE statement

Concerns have been raised about the quality of reporting in nutritional epidemiology. Research reporting guidelines such as the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement can improve quality of reporting in observational studies. Herein, we propose recommendations for reporting nutritional epidemiology and dietary assessment research by extending the STROBE statement into Strengthening the Reporting of Observational Studies in Epidemiology – Nutritional Epidemiology (STROBE‐nut). Recommendations for the reporting of nutritional epidemiology and dietary assessment research were developed following a systematic and consultative process, co‐ordinated by a multidisciplinary group of 21 experts. Consensus on reporting guidelines was reached through a three‐round Delphi consultation process with 53 external experts. In total, 24 recommendations for nutritional epidemiology were added to the STROBE checklist. When used appropriately, reporting guidelines for nutritional epidemiology can contribute to improve reporting of observational studies with a focus on diet and health.     

Some guidelines on guidelines: they should come with expiration dates

The STROBE guidelines (for Strengthening the Reporting of OBservational Studies in Epidemiology) add to a lengthy catalog of attempts to keep epidemiologists on more or less straight and more or less narrow paths charted by guideline authors. STROBE has an ambitious goal, and may prove highly useful for some. It raises concern, however, about a problem generic to guidelines, namely how long they will be useful. Guidelines may be inevitable, but they can foster ossification and be counterproductive. Who today would be happy with epidemiology guidelines issued in, say, 1960, 1970, 1980, or even, 1990? One solution is to offer each set of guidelines with an expiration date, beyond which it would cease to apply. Such a policy would at least prompt revisions. We propose that the STROBE guidelines might expire on 31 December 2010 or 3 years after any revision.     

Why ethics is indispensable for good-quality operational research

This article outlines challenges encountered when ethics is taught and promoted in the Operational Research courses of the International Union Against Tuberculosis and Lung Disease, with a focus on ethical issues related to studies that involve health records reviews. Problems observed by the Ethics Advisory Group include engagement of all stakeholders, maintenance of confidentiality and authorship. The omission of ethics in the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) statement and its explanatory commentary published in 2007 is highlighted and questioned.     

Method and reporting quality in health professions education research: a systematic review

Medical Education 2011: 45 : 227–238 Context Studies evaluating reporting quality in health professions education (HPE) research have demonstrated deficiencies, but none have used comprehensive reporting standards. Additionally, the relationship between study methods and effect size (ES) in HPE research is unknown. Objectives This review aimed to evaluate, in a sample of experimental studies of Internet‐based instruction, the quality of reporting, the relationship between reporting and methodological quality, and associations between ES and study methods. Methods We conducted a systematic search of databases including MEDLINE, Scopus, CINAHL, EMBASE and ERIC, for articles published during 1990–2008. Studies (in any language) quantifying the effect of Internet‐based instruction in HPE compared with no intervention or other instruction were included. Working independently and in duplicate, we coded reporting quality using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement, and coded study methods using a modified Newcastle–Ottawa Scale (m‐NOS), the Medical Education Research Study Quality Instrument (MERSQI), and the Best Evidence in Medical Education (BEME) global scale. Results For reporting quality, articles scored a mean ± standard deviation (SD) of 51 ± 25% of STROBE elements for the Introduction, 58 ± 20% for the Methods, 50 ± 18% for the Results and 41 ± 26% for the Discussion sections. We found positive associations (all p < 0.0001) between reporting quality and MERSQI (ρ = 0.64), m‐NOS (ρ = 0.57) and BEME (ρ = 0.58) scores. We explored associations between study methods and knowledge ES by subtracting each study’s ES from the pooled ES for studies using that method and comparing these differences between subgroups. Effect sizes in single‐group pretest/post‐test studies differed from the pooled estimate more than ESs in two‐group studies (p = 0.013). No difference was found between other study methods (yes/no: representative sample, comparison group from same community, randomised, allocation concealed, participants blinded, assessor blinded, objective assessment, high follow‐up). Conclusions Information is missing from all sections of reports of HPE experiments. Single‐group pre‐/post‐test studies may overestimate ES compared with two‐group designs. Other methodological variations did not bias study results in this sample.     

Guidance for preparing evaluation reports in telemedicine and health informatics generally

The European Federation for Medical Informatics is developing a detailed guideline for preparing evaluation reports. By doing this, it is hoped that the quality of evaluation studies in health informatics will improve and thus the evidence base. While much of the necessary information for preparing good quality evaluation publications is available in other documents, the Statement on Reporting of Evaluation Studies in Health Informatics (STARE-HI) is valuable in bringing together many points into a single document. The current version is comprehensive and includes valuable information on a number of areas. A list of recommended items for inclusion in an evaluation report is given. There is perhaps a danger that some authors might be intimidated by the suggested detail to be provided. Nonetheless, the Federation is to be congratulated for putting together a comprehensive guideline which promises to be a useful contribution to improving the quality of evaluation studies in information technology, including telemedicine.     

Prevalence of metabolic syndrome and its components in the menopausal transition: a systematic review

Metabolic syndrome is a complex disorder involving a combination of cardiovascular risk factors. Menopausal transition can be a key factor in the increased prevalence of metabolic syndrome. The current study aims to evaluate the prevalence of metabolic syndrome and its components in the menopausal transition, using a systematic review. Three reviewers conducted an article search in PubMed. The articles' quality was evaluated according to Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). Based on the selected studies, prevalence of metabolic syndrome increases in the post-menopausal (as compared to pre-menopausal) period, regardless of the population and study design. The change was more significant for waist circumference and blood pressure, suggesting that these components have the greatest influence on prevalence of metabolic syndrome.     

Dietary Assessment Methods to Estimate (Poly)phenol Intake in Epidemiological Studies: A Systematic Review

Nutritional epidemiological studies have frequently reported associations between higher (poly)phenol intake and a decrease in the risk or incidence of noncommunicable diseases. However, the assessment methods that have been used to quantify the intakes of these compounds in large-population samples are highly variable. This systematic review aims to characterize the methods used to assess dietary (poly)phenol intake in observational studies, report the validation status of the methods, and give recommendations on method selection and data reporting. Three databases were searched for publications that have used dietary assessment methods to measure (poly)phenol intake and 549 eligible full texts were identified. Food-frequency questionnaires were found to be the most commonly used tool to assess dietary (poly)phenol intake (73%). Published data from peer-reviewed journals were the major source of (poly)phenol content data (25%). An increasing number of studies used open-access databases such as Phenol-Explorer and USDA databases on flavonoid content since their inception, which accounted for 11% and 23% of the data sources, respectively. Only 16% of the studies reported a method that had been validated for measuring the target (poly)phenols. For future research we recommend: 1) selecting a validated dietary assessment tool according to the target compounds and target period of measurement; 2) applying and combining comprehensive (poly)phenol content databases such as USDA and Phenol-Explorer; 3) detailing the methods used to assess (poly)phenol intake, including dietary assessment method, (poly)phenol content data source; 4) follow the Strengthening the Reporting of Observational Studies in Epidemiology—Nutritional Epidemiology (STROBE-nut) framework; and 5) complementing dietary intake assessment based on questionnaires with measurement of (poly)phenols in biofluids using appropriate and validated analytical methods.     

Bones of Contention: Bone Mineral Density Recovery in Celiac Disease—A Systematic Review

Metabolic bone disease is a frequent co-morbidity in newly diagnosed adults with celiac disease (CD), an autoimmune disorder triggered by the ingestion of dietary gluten. This systematic review of studies looked at the efficacy of the gluten-free diet, physical activity, nutrient supplementation, and bisphosphonates for low bone density treatment. Case control and cohort designs were identified from PubMed and other academic databases (from 1996 to 2015) that observed newly diagnosed adults with CD for at least one year after diet treatment using the dual-energy x-ray absorptiometry (DXA) scan. Only 20 out of 207 studies met the inclusion criteria. Methodological quality was assessed using the Strengthening of the Reporting of Observational Studies in Epidemiology (STROBE) statement checklist. Gluten-free diet adherence resulted in partial recovery of bone density by one year in all studies, and full recovery by the fifth year. No treatment differences were observed between the gluten-free diet alone and diet plus bisphosphonates in one study. For malnourished patients, supplementation with vitamin D and calcium resulted in significant improvement. Evidence for the impact of physical activity on bone density was limited. Therapeutic strategies aimed at modifying lifestyle factors throughout the lifespan should be studied.