医院科研管理与创新对转化医学实施的推动作用

转化医学是近年来国际医学界推崇的一个重要医学理念,正日益成为生命科学和医学研究关注的热点。转化医学已不仅强 调临床医学与基础医学的结合,而且涉及多个学科之间的融会贯通。因此,医院科研管理的支持和重视程度转化医学实施的主要 动力,而科研项目的创新性、可行性是决定转化医学研究立项的关键。我院自2010 年成立转化医学研究中心以来,已将多项成果 成功转化并应用于临床实践,为生命科学研究领域中人类健康计划的发展提供了借鉴。本文结合我院实际,分析科研管理对转化 医学成果实施的促进作用,为医疗机构的科研管理人员提供参考。     

Some Observations upon Biochemical Causes of Ataxia and a New Disease Entity Ubiquinone, CoQ10 Deficiency

Some hereditary ataxias are treatable and the insight required for this has come from an in depth knowledge of the phenotypes and clinical biochemistry of the conditions. This has required both fundamental and translational clinical research. Prof John Blass was fortunate to begin his career at what we can now recognise as a golden era for such studies and he worked upon two important conditions; Refsum’s disease and Friedreich’s ataxia. More recently the mitochondrial encephalomyopathies have been described and similar investigative work has been undertaken upon them. Ubiquinone, CoQ₁₀, deficiency is the most recently recognised encephalomyopathy and is itself treatable. Though rare, it is becoming increasingly recognised and patients are benefiting from the same scholarly approach to its’ investigation as was afforded Refsums’ disease and Friedreich’s ataxia. A dedication to Professor John P. Blass.     

温度和光周期对水稻抽穗期调控的交互作用

光周期和温度是植物开花的2个关键的调控因素,植物成花转变决定于植物对光周期和温度变化的精确测量.作为短日照植物,水稻在长日低温条件下抽穗期推迟,为了阐明温度和光周期对水稻开花时间的调控效应,本文利用1个光周期不敏感的突变体及其野生型,系统地分析了不同温度和光周期处理条件下,调控水稻开花时间几个关键基因（Hd3a,RFT1,Ehd1,Ghd7,RID1/Ehd2/OsId1,Se5）的表达调控模式,结果表明Ehd1-Hd3a/RFT1通路在光周期和温度调控水稻开花途径中保守.Ehd1,Hd3a和RFT1的表达在低温（23℃）条件下急剧下降,表明Ehd1,Hd3a和RFT1表达阻抑是低温条件下水稻开花推迟的主要原因.另外,在长日照条件下,低温（23℃）处理促进了水稻开花抑制子Ghd7的表达,表明低温条件和长日照条件对Ghd7的表达具有协同作用.此外,本文还分析了Hd1与光周期开花调控途径中几个关键基因的调控关系,发现Hd1在长日照条件下负向调控Ehd1的表达而正向调控Ghd7的表达,表明在长日照条件下,Hd1-Ghd7-Ehd1-RFT1通路也是水稻抽穗期调控的一条重要途径.     

Managing expectational language: translational genetic professionals consider the clinical potential of next-generation sequencing technologies

Clinical genetic professionals are used to being flooded by claims about the seemingly endless potential and promise of next-generation sequencing (NGS) in medicine today. This paper is about managing expectations in translational medicine. From 2009 to 2011, we conducted focus groups with genetic and allied professionals concerned with genomics in the clinic to examine their attitudes and perspectives of genetic and genomic tools in this environment. In this paper, we examine and explore some of their discussions, specifically related to NGS and whole genome sequencing tests and their introduction as normal clinical tools. Informed by sociology of expectations (SE), we discuss expectational language in the arena of translational medicine. Through SE, illuminated are some barriers and strategies used by professionals to manage expectations. Further, our work suggests the importance of SE and more nuanced study to understand the discursive realm of translational genomic medicine.     

国内医院转化医学发展动态分析

从机构建设和科学研究两个角度分析国内医院转化医学发展现状。机构建设方面,美国转化医学中心的依托单位多为大学,组织架构较完善。但国内的依托单位多为医院或临床中心,较为分散,多为自发成立,缺乏国家层面的规划部署,难以形成比较高效的转化医学研究体系。但机构建设的迅速发展带来了转化研究成果的增多。国内转化医学研究多为从基础医学的角度探索疾病的致病机制和干预措施,如将实验室技术、细胞生物学、生物化学与分子生物学、药理学、应用生物技术等和临床问题的整合,特别是肿瘤、心血管病、内分泌与代谢病、消化系与腹部疾病等临床领域的转化研究受到了国内较多的关注。最后提出国内医院转化医学发展的策略和建议。     

Advances in purine and pyrimidine metabolism in health and diseases

ABSTRACT

In June, 2015, the Purine and Pyrimidine Society organized the 16th biennial symposium on Purine and Pyrimidine metabolism at the Faculty House of Columbia University, New York City. This exciting meeting focused on these important molecules, new developments in inborn errors of metabolism; therapeutic analogs. In addition, the biochemistry of mammalian and non-mammalian systems were discussed. Due to significant advances in molecular medicine, the boundaries between clinical and basic sciences have merged into exciting translational research, of which a small portion was highlighted in the presymposium.     

Proteomics and personalized medicine: a focus on kidney disease

ABSTRACT

Introduction: Inter-individual variability in response to drug treatment has induced an increased demand for decisions via personalize medicine. Also, the contribution of proteomics to the era of personalized medicine would seem to be vital in improving therapeutic outcomes.

Areas covered: We review validated biomarkers discovered by proteomics techniques and their use in personalized medicine with the focus on kidney diseases. We discuss this topic with a special emphasis on recent publications and relevant initiatives and depict some limitations that remain for personalized medicine.

Expert opinion: The development of highly accurate biomarkers is essential for optimizing the management of kidney diseases. Various biomarkers of kidney diseases have been identified using proteomic techniques. However, only a few of these biomarkers showed the potential to be used in clinical practice concerning personalized medicine. Therefore, it becomes evident that the combination of multiple biomarkers confers higher accuracy and the ability to depict complex pathophysiological conditions, a prerequisite for personalized treatment. CKD273, a multimarker panel for early CKD detection may serve as a first example for personalized medicine in nephrology. Based on this successful example, proteomics is expected to develop into the key technology to guide personalized intervention.     

The promise of protein glycosylation for personalised medicine

BackgroundComplex diseases such as cancer are a consequence of numerous causes. State of the art personalised medicine approaches are mostly based on evaluating patients' individual genetic background. Despite the advances of genomics it fails to take individual dynamic influences into account that contribute to the individual and unique glycomic and glycoproteomic “configurations” of every living being.Scope of reviewGlycomic and glycoproteomic-based personalised medicine diagnostics are still in their infancies, however some initial success stories indicate that these fields are highly promising to mediate novel early diagnosis and disease stratification markers, subsequently resulting in improved patient well-being and reduced treatment costs. In this review we not only summarise current protein glycosylation based examples that substantially improve or possess great potential for personalised medicine, but also describe current limitations as well as future perspectives and challenges associated with establishing protein glycosylation aspects for this purpose.Major conclusionsMany protein biomarkers currently in clinical use are glycoproteins, however, their glycosylation status is seldom evaluated in a clinical context. To date just few examples have already been successfully translated into clinical practice, making protein glycosylation a highly promising diagnostic target with humongous potential for personalised medicine.General significanceThere is an urgent need for markers that enable the establishment of an individualised and optimised patient treatment at the earliest disease stage possible. The glycosylation status of a patient and/or specific marker proteins can provide important clues that result in improved patient management. This article is part of a Special Issue entitled “Glycans in personalised medicine” Guest Editor: Professor Gordan Lauc.     

分子影像:转化医学的重要工具和主要路径

随着基础医学与临床医学脱节现象的日益凸显,作为二者之间连接纽带和桥梁的转化医学越来越受到重视.近年来,转化医学在美、欧等西方国家迅速发展,在我国也正成为"十二五"期间医学领域的重要发展方向之一.分子影像作为现代分子生物学与先进医学影像技术相结合的产物,可以利用影像方法对活体内分子的生物化学过程进行定性和定量研究,是将基...     

中国精神分裂症的全基因组关联分析及其转化医学进展

我国在精神分裂症的遗传学和生命组学研究方面取得了很大进展,如在全基因组关联分析(genome-wide association study,GWAS)方面工作获得了一系列成果.随着我国对重大疾病转化医学的逐步关注和重视,利用在精神分裂症上已经获得的广泛和深入的研究结果,寻找精神分裂症各种临床应用的生物标记物研究,系统性地建立适合于类似精神分裂症这类复杂疾病的早期诊断、干预和预防的临床咨询和应用体系等将是该疾病转化医学方面可实施的方法和案例.精神分裂症的转化医学方面还涉及精神分裂症患者的个体化用药方案建立.药物疗效和药物不良反应的个体差异具有较复杂的环境和遗传背景,结合精神分裂症的遗传学病因和药物作用的遗传学差异,将有效发挥治疗药物的功效,并降低重大不良反应在敏感个体上的发生.对精神分裂症这类给国家和社会带来极其重大负担的重大疾病,积极推动我国在此类疾病上的基础研究成果转化和转化医学的实施具有重要的社会效应和积极的带动作用.     

Proteomic analysis of red blood cells and the potential for the clinic: what have we learned so far?

Introduction: Red blood cells (RBC) are the most abundant host cells in the human body. Mature erythrocytes are devoid of nuclei and organelles and have always been regarded as circulating ‘bags of hemoglobin’. The advent of proteomics has challenged this assumption, revealing unanticipated complexity and novel roles for RBCs not just in gas transport, but also in systemic metabolic homeostasis in health and disease.

Areas covered: In this review we will summarize the main advancements in the field of discovery mode and redox/quantitative proteomics with respect to RBC biology. We thus focus on translational/clinical applications, such as transfusion medicine, hematology (e.g. hemoglobinopathies) and personalized medicine. Synergy of omics technologies – especially proteomics and metabolomics – are highlighted as a hallmark of clinical metabolomics applications for the foreseeable future.

Expert commentary: The introduction of advanced proteomics technologies, especially quantitative and redox proteomics, and the integration of proteomics data with omics information gathered through orthogonal technologies (especially metabolomics) promise to revolutionize many biomedical areas, from hematology and transfusion medicine to personalized medicine and clinical biochemistry.     

Prospects for translational regenerative medicine

Translational medicine is an evolutional concept that encompasses the rapid translation of basic research for use in clinical disease diagnosis, prevention and treatment. It follows the idea "from bench to bedside and back", and hence relies on cooperation between laboratory research and clinical care. In the past decade, translational medicine has received unprecedented attention from scientists and clinicians and its fundamental principles have penetrated throughout biomedicine, offering a sign post that guides modern medical research toward a patient-centered focus. Translational regenerative medicine is still in its infancy, and significant basic research investment has not yet achieved satisfactory clinical outcomes for patients. In particular, there are many challenges associated with the use of cell- and tissue-based products for clinical therapies. This review summarizes the transformation and global progress in translational medicine over the past decade. The current obstacles and opportunities in translational regenerative medicine are outlined in the context of stem cell therapy and tissue engineering for the safe and effective regeneration of functional tissue. This review highlights the requirement for multi-disciplinary and inter-disciplinary cooperation to ensure the development of the best possible regenerative therapies within the shortest timeframe possible for the greatest patient benefit.     

Evaluating ecosystem health

In the past decade, metaphors drawn from human health are finding increasing application in environmental assessment at ecosystem levels. If ecosystem medicine is to come of age, it must cope with three fundamental dilemmas. The first stems from the recognition that there are no strictly objective criteria for judging health. Assessments of health, as in humans, inevitably are based on some combination of established norms and desirable attributes. The second stems from the irregular pulse of nature which either precludes the early recognition of substantive changes or gives rise to false alarms. The third is posed by the quest for indicators that have the attributes of being holistic, early warning, and diagnostic. Indicators that excel in one of these aspects, often fail in another.Advances in ecosystem medicine are likely to come from closer collaboration with medical colleagues in both clinical and epidemiological areas. In particular the time appears ripe for a more systematic effort to characterize ecosystem maladies, to validate treatments and to develop more sophisticated diagnostic protocols. These aspects are illustrated with comparisons drawn from studies of environmental transformation in the Laurentian Great Lakes, the Baltic Sea and Canadian terrestrial ecosystems.Dedicated to Prof. J. Stan Rowe whose pioneering work in formulating a holistic perspective on ecosystem health has substantially contributed to the development of these ideas.     

Pathology,proteomics and the pathway to personalised medicine

Introduction: As we move from a discovery to a translational phase in proteomics, with a focus on developing validated clinical assays to assist personalized medicine, there is a growing need for strong bidirectional interactions with the clinical pathology community. Thus, while on one hand the proteomics community will provide candidate biomarkers to assist in diagnosis, prognosis, surveillance, identification of individualized patient medication, and development and validation of new assays for diagnostic use, on the other the pathology community will assist with specific tissue identification and selection (e.g. laser capture microdissection, tissue sections for MS imaging), biobanking, validation of emerging automated histopathology techniques, preparation and classification of relevant patient medical reports, and assisting with the optimization of experimental design for clinical trials.

Areas covered: Here we discuss these topics with a particular emphasis on recent publications and relevant initiatives and outline some of the hurdles that still remain for personalized medicine.

Expert commentary: It is clear that effective crosstalk between the proteomics and pathology communities will greatly accelerate crossover of candidate biomarkers to personalized medicine, which will have significant benefits not only for patient wellbeing, but also the global healthcare budget. However, analysis of the big data generated may become rate-limiting.     

军校预防医学专业本科学员临床课程教学现状及建议

随着医学模式的转变,预防医学已经成为现代医疗体系的重要组成部分,在提高公共卫生健康水平方面发挥着越来越重要的作用。为了更好地开展预防医学工作,预防医学专业学员不仅要掌握牢固的预防医学专业知识,更要具备丰富的临床医学知识。针对预防医学专业本科学员的临床课程教学,我校经过多年的探索与改革,已经积累了丰富经验,教学质量较高;但现阶段仍然存在着一些问题。本文分析我校预防医学专业本科学员临床课程的教学现状及存在的主要问题,并提出建议;从而为进一步提高预防医学专业本科学员的临床课程教学质量提供依据。     

Advances in cell-free protein array methods

Introduction: Cell-free protein microarrays represent a special form of protein microarray which display proteins made fresh at the time of the experiment, avoiding storage and denaturation. They have been used increasingly in basic and translational research over the past decade to study protein-protein interactions, the pathogen-host relationship, post-translational modifications, and antibody biomarkers of different human diseases. Their role in the first blood-based diagnostic test for early stage breast cancer highlights their value in managing human health. Cell-free protein microarrays will continue to evolve to become widespread tools for research and clinical management.

Areas covered: We review the advantages and disadvantages of different cell-free protein arrays, with an emphasis on the methods that have been studied in the last five years. We also discuss the applications of each microarray method.

Expert commentary: Given the growing roles and impact of cell-free protein microarrays in research and medicine, we discuss: 1) the current technical and practical limitations of cell-free protein microarrays; 2) the biomarker discovery and verification pipeline using protein microarrays; and 3) how cell-free protein microarrays will advance over the next five years, both in their technology and applications.     

A recent update on the use of Chinese medicine in the treatment of inflammatory bowel disease

BackgroundInflammatory bowel disease (IBD) is a chronic idiopathic disease that is characterized by inflammation of the gastrointestinal tract. Proper management of IBD requires both early diagnosis and novel therapies and management programs. Many reports have suggested that Chinese medicine has unique properties favorable to the treatment of IBD. However, there are no systematic analyses on this topic.PurposeThis review summarizes recent studies that assessed the effects and mechanisms of Chinese medicine in the treatment of IBD in order to fully understand the advantages of Chinese medicine in the management of IBD.MethodsA literature search was conducted using peer-reviewed and clinical databases, including PubMed, Web of Science, ClinicalTrials.gov, MEDLINE, EMBASE, Springer LINK, Wan-fang database, the Chinese Biomedicine Database, and the China National Knowledge Infrastructure (CNKI). Keywords used were inflammatory bowel disease (including Ulcerative colitis or Crohn's disease) and Chinese medicine. All selected articles were from 1997 to 2021, and each were assessed critically for our exclusion criteria. Studies describing the pathogenesis of IBD, the effects and mechanisms of Chinese medicine in the treatment of IBD, in particular their roles in immune regulation, intestinal flora regulation, and improvement of intestinal barrier function, were included.ConclusionThis review highlights recent progress in the use of Chinese medicine in the treatment of IBD. It also provides a reference for further evaluation and exploration of the potential of classical multi-herbal Chinese medicine in the treatment of IBD.     

The hidden potential of glycomarkers: Glycosylation studies in the service of cancer diagnosis and treatment

Changes in the glycosylation process appear early in carcinogenesis and evolve with the growth and spread of cancer. The correlation of the characteristic glycosylation signature with the tumor stage and the appropriate therapy choice is an important issue in translational medicine. Oncologists also pay attention to extracellular vesicles as reservoirs of new cancer glycomarkers that can be potent for cancer diagnosis/prognosis. In this review, we recall glycomarkers used in oncology and show their new glycoforms of improved clinical relevance. We summarize current knowledge on the biological functions of glycoepitopes in cancer-derived extracellular vesicles and their potential use in clinical practice. Is glycomics a future of cancer diagnosis? It may be, but in combination with other omics analyses than alone.     

Methods for the absolute quantification of N-glycan biomarkers

BackgroundMany treatment options especially for cancer show a low efficacy for the majority of patients demanding improved biomarker panels for patient stratification. Changes in glycosylation are a hallmark of many cancers and inflammatory diseases and show great potential as clinical disease markers. The large inter-subject variability in glycosylation due to hereditary and environmental factors can complicate rapid transfer of glycan markers into the clinical practice but also presents an opportunity for personalized medicine.Scope of reviewThis review discusses opportunities of glycan biomarkers in personalized medicine and reviews the methodology for N-glycan analysis with a specific focus on methods for absolute quantification.Major conclusionsThe entry into the clinical practice of glycan markers is delayed in large part due to a lack of adequate methodology for the precise and robust quantification of protein glycosylation. Only absolute glycan quantification can provide a complete picture of the disease related changes and will provide the method robustness required by clinical applications.General significanceGlycan biomarkers have a huge potential as disease markers for personalized medicine. The use of stable isotope labeled glycans as internal standards and heavy-isotope labeling methods will provide the necessary method precision and robustness acceptable for clinical use. This article is part of a Special Issue entitled “Glycans in personalized medicine” Guest Editor: Professor Gordan Lauc.     

An interview with Olivia Gude about connecting school and community arts practice

ABSTRACT

Olivia Gude has a long and distinguished career as both a public artist and an art educator. She is currently the Angela Gregory Paterakis Professor and Chair of Art Education at the School of the Art Institute of Chicago (SAIC), where she works with graduate and undergraduate students to prepare for working as artist educators in school and community settings. Her scholarly work includes a number of articles and book chapters about art education and community art. Prof. Gude has worked as a community public artist for many years and has created over 30 large-scale mural and mosaic projects, working with intergenerational groups, teens, elders, and children. I interviewed Prof. Gude at the SAIC building in downtown Chicago to discuss how her school, university, and community art engagement as well as her work with the National Coalition for Core Arts Standards, might offer suggestions for transforming arts education for the twenty-first century and provide authentic connections between school and community. Prof. Gude discusses important enduring understandings and big ideas from the new Visual Arts National Core Arts Standards, the Spiral Workshop youth art and research project she created while at University of Illinois at Chicago, and how her experience as a community artist informs her work with students in classroom settings.