A framework for a distributed, hybrid, multiple-ontology clinical-guideline library, and automated guideline-support tools

Clinical guidelines are a major tool in improving the quality of medical care. However, most guidelines are in free text, not in a formal, executable format, and are not easily accessible to clinicians at the point of care. We introduce a Web-based, modular, distributed architecture, the Digital Electronic Guideline Library (DeGeL), which facilitates gradual conversion of clinical guidelines from text to a formal representation in chosen target guideline ontology. The architecture supports guideline classification, semantic markup, context-sensitive search, browsing, run-time application, and retrospective quality assessment. The DeGeL hybrid meta-ontology includes elements common to all guideline ontologies, such as semantic classification and domain knowledge; it also includes four content-representation formats: free text, semi-structured text, semi-formal representation, and a formal representation. These formats support increasingly sophisticated computational tasks. The DeGeL tools for support of guideline-based care operate, at some level, on all guideline ontologies. We have demonstrated the feasibility of the architecture and the tools for several guideline ontologies, including Asbru and GEM.     

Guideline-based development of quality indicators for subfertility care

BACKGROUND: Internationally, several organizations have developed clinicalguidelines for subfertility care to supply patients with thebest possible care. However, to improve the implementation ofsuch guidelines, we first need to gain insight into the applicationof clinical guidelines in daily practice. Valid quality indicatorsare necessary to estimate actual guideline adherence. However,none of the existing subfertility guideline programmes is accompaniedby a satisfactory set of quality indicators. In this study,we develop a set of valid guideline-based quality indicatorsfor subfertility care. METHODS: A systematic RAND-modified Delphi method was used to developa set of key recommendations based on 10 national Dutch subfertilityguidelines, international literature and existing internationalindicators. Experts’ opinions were used to appraise recommendationsregarding specific criteria such as efficacy, level of healthgain, applicability and potential for care improvement. RESULTS: A representative set of 39 key recommendations was selectedfrom 303 initial recommendations. The recommendations coveredtwo structural and 37 procedural aspects, the latter encompassing‘indications for treatment’, ‘diagnostic procedures’,‘treatment procedures’ and ‘patient information’. CONCLUSIONS: This study describes the systematic, stepwise method used todevelop 39 process and structure indicators that can be usedto monitor subfertility care.     

Sex differences in mechanisms of cardiac excitation–contraction coupling

The incidence and expression of cardiovascular diseases differs between the sexes. This is not surprising, as cardiac physiology differs between men and women. Clinical and basic science investigations have shown important sex differences in cardiac structure and function. The pervasiveness of sex differences suggests that such differences must be fundamental, likely operating at a cellular level. Indeed, studies have shown that isolated ventricular myocytes from female animals have smaller and slower contractions and underlying calcium transients compared to males. Recent evidence suggests that this arises from sex differences in components of the cardiac excitation–contraction coupling pathway, the sequence of events linking myocyte depolarization to calcium release from the sarcoplasmic reticulum and subsequent contraction. The concept that sex hormones may regulate intracellular calcium at the level of the cardiomyocyte is important, as levels of these hormones decline in both men and women as the incidence of cardiovascular disease rises. This review focuses on the impact of sex on cardiac contraction, in particular at the cellular level, and highlights specific components of the excitation–contraction coupling pathway that differ between the sexes. Understanding sex hormone regulation of calcium homeostasis in the heart may reveal new avenues for therapeutic strategies to treat cardiac dysfunction and cardiovascular diseases.     

Characteristics of effective clinical guidelines for general practice.

BACKGROUND: The use of clinical guidelines in general practice is often limited. Research on barriers to guideline adherence usually focuses on attitudinal factors. Factors linked to the guideline itself are much less studied. AIM: To identify characteristics of effective clinical guidelines for general practice, and to explore whether these differ between therapeutic and diagnostic recommendations. DESIGN OF STUDY: Analysis of performance data from an audit study of 200 general practitioners (GPs) in The Netherlands conducted in 1997. SETTING: Panel of 12 GPs in The Netherlands who were familiar with guideline methodology. METHOD: A set of 12 attributes, including six potential facilitators and six potential barriers to guideline use, was formulated. The panel assessed the presence of these attributes in 96 guideline recommendations formulated by the Dutch College of General Practitioners. The attributes of recommendations with high compliance rates (70% to 100%) were compared with those with low compliance rates (0% to 60%). RESULTS: Recommendations with high compliance rates were to a lesser extent those requiring new skills (7% compared with 22% in recommendations with low compliance rates), were less often part of a complex decision tree (12% versus 25%), were more compatible with existing norms and values in practice (87% versus 76%), and more often supported with evidence (47% versus 31%). For diagnostic recommendations, the ease of applying them and the potential (negative) reactions of patients were more relevant than for therapeutic recommendations. CONCLUSION: To bridge the gap between research and practice, the evidence as well as the applicability should be considered when formulating recommendations. If the recommendations are not compatible with existing norms and values, not easy to follow or require new knowledge and skills, appropriate implementation strategies should be designed to ensure change in daily practice.     

整骨疗法治疗非特异性下腰痛：解读2016年美国骨科协会的指南

文题释义：整骨疗法：文章中提及的整骨疗法是指美式整骨手法,指南中明确为由整骨医师或其他在整骨手法治疗方面受过培训和精通的医师(如欧洲接受过整骨培训项目的医师)提供的手法治疗。该方法强调徒手操作技巧,通过调整脊柱的结构紊乱,改善肌肉骨骼系统功能,能对其他神经肌肉骨骼组织与器官的功能障碍、组织病理条件或是复杂的症状产生积极影响。 非特异性下腰痛：美国骨科协会指南适用的范围为非特异性下腰痛患者,所有非特异性肌肉及骨骼源性下腰痛患者均符合指南建议。而有内脏疾病引起腰痛的患者应被排除在指南之外。其他应排除发生以下确定的下腰痛来源的情况：脊椎骨折;椎关节脱位;肌肉撕裂;脊柱或脊椎关节韧带断裂;椎间盘、脊柱关节突关节、肌肉或筋膜的炎症;皮肤撕裂伤;骶髂关节炎;强直性脊柱炎;肿块在或从背部下部引起疼痛的患者。但是指南特别指出,排除在指南之外并不意味着整骨手法在这些情况下是禁忌的。 背景：下腰痛是骨科常见疾病之一,非特异性下腰痛在临床中占到了非常大的比重。为更好的治疗该疾病,2016年美国骨科协会制定了整骨疗法治疗非特异性下腰痛患者的临床指南。 目的：通过解读指南让骨科医生以及其他医生、其他卫生专业人员和第三方付费者了解关于适当使用整骨手法治疗非特异性下腰痛患者的潜在建议的证据,帮助临床骨科医生在遇到非特异性下腰痛患者选择治疗方法时提供参考。同时科研工作者可借鉴、学习指南中科学严谨的设计思路与评价方法。 方法：指南是建立在先前指南和最新高质量荟萃分析的基础上进行的修订,确定了采用整骨手法治疗非特异性下腰痛为确实有效的治疗手段,明确其推荐等级。文章通过详细解读指南中的相关定义、循证医学的评价方法、具体内容和结果,并结合中国临床实际进行分析与讨论。 结果与结论：指南共纳入17项研究,系统评价了整骨手法在治疗急慢性非特异性下腰痛以及妊娠期及产后妇女非特异性下腰痛的治疗效果,结果证实患者在疼痛及功能状态等方面都有极大的改善,美国骨科协会的最终建议是建议骨科医生使用整骨手法治疗下腰痛患者。该治疗方法安全性及科学性较高,适合在国内进行推广。 ORCID: 0000-0001-6897-1581(谢瑞) 中国组织工程研究杂志出版内容重点：人工关节;骨植入物;脊柱;骨折;内固定;数字化骨科;组织工程     

Clinical guidelines: their implementation in general practice.

In recent years the development of clinical guidelines has received increasing attention from medical educators and those involved in standard setting, and has been initiated at both central and local levels. This review article outlines the current state of knowledge with regard to clinical guideline implementation in medical practice. It deals with the main aspects of the current guideline debate, such as, clinical freedom and doctor autonomy, the importance of ownership in guideline implementation, the effectiveness of guidelines in changing practice and, in particular, the strategies needed to implement clinical guidelines in general practice. Mechanisms of behavioural change that have been recognized as being important for implementation are also discussed. If implementation strategies are not treated as an integral part of the development process then clinical guidelines may fail to achieve their potential in changing clinical practice.     

Guideline-based careflow systems

This paper describes a methodology for achieving an efficient implementation of clinical practice guidelines. Three main steps are illustrated: knowledge representation, model simulation and implementation within a health care organisation. The resulting system can be classified as a 'guideline-based careflow management system'. It is based on computational formalisms representing both medical and health care organisational knowledge. This aggregation allows the implementation of a guideline, not only as a simple reminder, but also as an 'organiser' that facilitates health care processes. As a matter of fact, the system not only suggests the tasks to be performed, but also the resource allocation. The methodology initially comprehends a graphical editor, that allows an unambiguous representation of the guideline. Then the guideline is translated into a high-level Petri net. The resources, both human and technological necessary for performing guideline-based activities, are also represented by means of an organisational model. This allows the running of the Petri net for simulating the implementation of the guideline in the clinical setting. The purpose of the simulation is to validate the careflow model and to suggest the optimal resource allocation before the careflow system is installed. The final step is the careflow implementation. In this phase, we show that the 'workflow management' technology, widely used in business process automation, may be transferred to the health care setting. This requires augmenting the typical workflow management systems with the flexibility and the uncertainty management, typical of the health care processes. For illustrating the proposed methodology, we consider a guideline for the management of patients with acute ischemic stroke.     

The quantity and quality of clinical practice guidelines for the management of depression in primary care in the UK.

BACKGROUND: Despite research evidence that guidelines can improve patient care, concerns remain over their cost-effectiveness. This is particularly so when there is a proliferation of guidelines for the same condition. Faced with differing recommendations, users will wish to make informed decisions on which guideline to follow. In creating a guideline appraisal instrument we have assessed guidelines developed in the United Kingdom (UK) for the management of a range of disorders including depression in primary care. AIM: To identify the number of UK clinical guidelines for the management of depression in primary care and to describe their quality and clinical content. METHOD: A survey was undertaken to identify all depression guidelines developed in the UK between January 1991 and January 1996. All guidelines produced by national organizations and a random sample of local guidelines were appraised using a validated instrument by six assessors: a national expert in the disease area, a general practitioner, a public health physician, a hospital consultant, a nurse specializing in the disease area, and a researcher on guideline methodology. The clinical content of each guideline was then assessed by one of the researchers (RB) according to a defined framework. RESULTS: Forty-five depression guidelines were identified. While there was a considerable range in the quality of the six national and three local guidelines appraised, at a group level their performance was similar to guidelines for other diseases. Clinical recommendations tended to reflect the joint consensus statement produced by the Royal College of General Practitioners and Royal College of Psychiatrists in 1992. The most obvious difference was in the style in which the guidelines were written and presented. CONCLUSION: A 'national template' was the starting place for most guidelines. Steps need to be taken to ensure that these templates are based on the best possible research evidence and professional opinion. Local clinicians should concentrate on effective dissemination and implementation strategies, rather than creating new guidelines.     

Epidemiological stratification of malaria in the Comoro archipelago]

In the Comoros Islands, the level of malarial endemicity varies greatly from one island to the other, even though the total area (4 islands) covers less than 2,300 km2 and has a population of some 600,000 people only. The epidemiological stratification is based on the diversity of human and physical characterisation. They both determine the presence and the behaviour as well as the size of the vector's populations. Vectorial dynamics can explain varying levels of endemicity given parasitological indicators and specific morbidity. Analyzing these criteria shows up different epidemiological features and serves as a basic guideline for malaria control. The efficiency of this control depends on the relationships between the intensity and the length of the transmission, in the framework of protection mechanisms; it is of crucial importance for clinical treatment. Further elements are the age of the patient, the season and the geographic situation of the area. Stratification provides explanations for these relationships and helps to define antimalarial programmes adapting to each situation a range of therapeutic and antivectorial methods. The availability and accessibility of anti-malarial medicine is the minimum requirement for reducing mortality: domestic spray insecticides for reducing transmission are effective for several years and should be followed by the use of mosquito nets or curtains impregnated with pyrethrinoids, and in the particular case of Grande Comore, the use of larvivorous fish. As anywhere else, the economic development, which is dependent on political stability, is the essential basis for malaria control.     

ESCMID-ECMM guideline: diagnosis and management of invasive aspergillosis in neonates and children

ScopePresenting symptoms, distributions and patterns of diseases and vulnerability to invasive aspergillosis (IA) are similar between children and adults. However, differences exist in the epidemiology and underlying conditions, the usefulness of newer diagnostic tools, the pharmacology of antifungal agents and in the evidence from interventional phase 3 clinical trials. Therefore, the European Society for Clinical Microbiology and Infectious Diseases (ESCMID) and the European Confederation of Medical Mycology (ECMM) have developed a paediatric-specific guideline for the diagnosis and management of IA in neonates and children.MethodsReview and discussion of the scientific literature and grading of the available quality of evidence was performed by the paediatric subgroup of the ESCMID-ECMM-European Respiratory Society (ERS) Aspergillus disease guideline working group, which was assigned the mandate for the development of neonatal- and paediatric-specific recommendations.QuestionsQuestions addressed by the guideline included the epidemiology of IA in neonates and children; which paediatric patients may benefit from antifungal prophylaxis; how to diagnose IA in neonates and children; which antifungal agents are available for use in neonates and children; which antifungal agents are suitable for prophylaxis and treatment of IA in neonates and children; what is the role of therapeutic drug monitoring of azole antifungals; and which management strategies are suitable to be used in paediatric patients. This guideline provides recommendations for the diagnosis, prevention and treatment of IA in the paediatric population, including neonates. The aim of this guideline is to facilitate optimal management of neonates and children at risk for or diagnosed with IA.     

Diagnosis and treatment of asthma in childhood: a PRACTALL consensus report

Asthma is the leading chronic disease among children in most industrialized countries. However, the evidence base on specific aspects of pediatric asthma, including therapeutic strategies, is limited and no recent international guidelines have focused exclusively on pediatric asthma. As a result, the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology nominated expert teams to find a consensus to serve as a guideline for clinical practice in Europe as well as in North America. This consensus report recommends strategies that include pharmacological treatment, allergen and trigger avoidance and asthma education. The report is part of the PRACTALL initiative ** , which is endorsed by both academies.     

Guidelines for the diagnosis,treatment, prevention and control of infections caused by carbapenem-resistant gram-negative bacilli

The dissemination of carbapenem-resistant Gram-negative bacilli (CRGNB) is a global public health issue. CRGNB isolates are usually extensively drug-resistant or pandrug-resistant, resulting in limited antimicrobial treatment options and high mortality. A multidisciplinary guideline development group covering clinical infectious diseases, clinical microbiology, clinical pharmacology, infection control, and guideline methodology experts jointly developed the present clinical practice guidelines based on best available scientific evidence to address the clinical issues regarding laboratory testing, antimicrobial therapy, and prevention of CRGNB infections. This guideline focuses on carbapenem-resistant Enterobacteriales (CRE), carbapenem-resistant Acinetobacter baumannii (CRAB), and carbapenem-resistant Pseudomonas aeruginosa (CRPA). Sixteen clinical questions were proposed from the perspective of current clinical practice and translated into research questions using PICO (population, intervention, comparator, and outcomes) format to collect and synthesize relevant evidence to inform corresponding recommendations. The grading of recommendations, assessment, development and evaluation (GRADE) approach was used to evaluate the quality of evidence, benefit and risk profile of corresponding interventions and formulate recommendations or suggestions. Evidence extracted from systematic reviews and randomized controlled trials (RCTs) was considered preferentially for treatment-related clinical questions. Observational studies, non-controlled studies, and expert opinions were considered as supplementary evidence in the absence of RCTs. The strength of recommendations was classified as strong or conditional (weak). The evidence informing recommendations derives from studies worldwide, while the implementation suggestions combined the Chinese experience. The target audience of this guideline is clinician and related professionals involved in management of infectious diseases.     

Regulatory aspects of allergen products for immunotherapy--considerations from the viewpoint of manufacturers

The present publication describes the actual situation anno 2005 with respect to registration of allergen products for specific immunotherapy (SIT) in Europe. It is concluded that the lack of the implementation of regulations and directives in force, is due to underestimation of the specific demands and aspects of the pathogenicity of allergic diseases at the one hand and of allergen products as a unique set of biological medicinal products at the other. The issues of regulatory nature that need careful attention and consideration in the opinion of the manufacturers are given in a number of statements. The main conclusion is that an EU-guideline for allergen products is urgently needed. A dialogue between regulatory authorities and representatives of the manufacturers, prior to the formulation of a new guideline seems of the utmost importance, as to prevent a similar stalemate as after the introduction of the foreseen regulatory measures of the past. The new guideline should include: An allergen product monograph. Recommendations for clinical development of allergen products like: Number of patients for efficacy and safety Acceptability of different efficacy parameters. Recommendations for toxicology.     

Epigenetic Regulations in Autoimmunity and Cancer: from Basic Science to Translational Medicine

Epigenetics, as a discipline that aims to explain the differential expression of phenotypes arising from the same gene sequence and the heritability of epigenetic expression, has received much attention in medicine. Epigenetic mechanisms are constantly being discovered, including DNA methylation, histone modifications, noncoding RNAs and m6A. The immune system mainly achieves an immune response through the differentiation and functional expression of immune cells, in which epigenetic modification will have an important impact. Because of immune infiltration in the tumor microenvironment, immunotherapy has become a research hotspot in tumor therapy. Epigenetics plays an important role in autoimmune diseases and cancers through immunology. An increasing number of drugs targeting epigenetic mechanisms, such as DNA methyltransferase inhibitors, histone deacetylase inhibitors, and drug combinations, are being evaluated in clinical trials for the treatment of various cancers (including leukemia and osteosarcoma) and autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis). This review summarizes the progress of epigenetic regulation for cancers and autoimmune diseases to date, shedding light on potential therapeutic strategies.     

The Emerging Role of Leptin Antagonist as Potential Therapeutic Option for Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is a chronic relapsing immune-mediated inflammatory disorder that affects millions of people around the world. Leptin is a satiety hormone produced primarily by adipose tissue and acts both centrally and peripherally. Leptin has been shown to play a major role in regulating metabolism, which increases during IBD progression. Leptin mediates several physiological functions including elevated blood pressure, tumorogenesis, cardiovascular pathologies and enhanced immune response in many autoimmune diseases. Recent development of a leptin mutant antagonist that blocks leptin activity raises great hope and opens up new possibilities for therapy in many autoimmune diseases including IBD. To this end, preliminary data from an ongoing study in our laboratory on pegylated leptin antagonist mutant L39A/D40A/F41A (PEG-MLA) treatment shows an inhibition of chronic colitis in IL-10^?/? mice. PEG-MLA effectively attenuates the overall clinical scores, reverses colitis-associated pathogenesis including a decrease in body weight, and decreases systemic leptin level. PEG-MLA induces both central and peripheral leptin deficiency by mediating the cellular immune response. In summary, after blocking leptin activity, the correlative outcome between leptin-mediated cellular immune response, systemic leptin levels, and amount of adipose tissue together may provide new strategies for therapeutic intervention in autoimmune diseases, especially for intestinal inflammation.     

Angiostatic proteins and peptides

Angiogenesis, or the formation of new vasculature out of preexisting capillaries, is a sequence of events that is essential in the normal physiological processes of tissue growth and in a broad spectrum of pathologies. The diseases in which angiogenesis plays a key role are divided into diseases that are characterized by hypoxia/ ischemia and diseases that are dependent on neovascularization. The formerpathologies may benefit from therapeutic angiogenesis stimulation. This review concentrates on the different strategies to inhibit angiogenesis in diseases that are characterized by excessive angiogenesis, for example, cancer, arthritis, diabetic retinopathy, and inflammatory diseases. These diseases are dependent on the development of newvasculature, and hence, a large variety of different strategies to inhibit angiogenesis are underwayin laboratories throughout the world. At present, over250 angiogenesis inhibitors are described, and approximately half of them display activity in in vivo models. A large percentage of these molecules are natural, nonnatural, or synthetic so-called small molecules. Others are of protein origin, either endogenous or exogenous by nature. The authors highlight the current knowledge on the development of angiostatic proteins and peptides and their potential in the treatment of disease.     

Evidence-Based,Non-Pharmacological Treatment Guideline for Depression in Korea

Although pharmacological treatment constitutes the main therapeutic approach for depression, non-pharmacological treatments (self-care or psychotherapeutic approach) are usually regarded as more essential therapeutic approaches in clinical practice. However, there have been few clinical practice guidelines concerning self-care or psychotherapy in the management of depression. This study introduces the ''Evidence-Based, Non-Pharmacological Treatment Guideline for Depression in Korea.'' For the first time, a guideline was developed for non-pharmacological treatments for Korean adults with mild-to-moderate depression. The guideline development process consisted of establishing several key questions related to non-pharmacologic treatments of depression, searching the literature for studies which answer these questions, assessing the evidence level of each selected study, drawing up draft recommendation, and peer review. The Scottish Intercollegiate Guidelines Network grading system was used to evaluate the quality of evidence. As a result of this process, the guideline recommends exercise therapy, bibliotherapy, cognitive behavior therapy, short-term psychodynamic supportive psychotherapy, and interpersonal psychotherapy as the non-pharmacological treatments for adult patients with mild-to-moderate depression in Korea. Hence, it is necessary to develop specific methodologies for several non-pharmacological treatment for Korean adults with depression.     

2016 guideline strategies for the use of antifungal agents in patients with hematological malignancies or hematopoietic stem cell transplantation recipients in Taiwan

The Infectious Diseases Society of Taiwan (IDST), the Hematology Society of Taiwan, the Taiwan Society of Blood and Marrow Transplantation, Medical Foundation in Memory of Dr. Deh-Lin Cheng, Foundation of Professor Wei-Chuan Hsieh for Infectious Diseases Research and Education, and CY Lee's Research Foundation for Pediatric Infectious Diseases and Vaccines cooperatively published this guideline for the use of antifungal agents in hematological patients with invasive fungal diseases (IFDs) in Taiwan. The guideline is the first one endorsed by IDST focusing on selection of antifungal strategies, including prophylaxis, empirical (or symptom-driven) and pre-emptive (or diagnostic-driven) strategy. We suggest a risk-adapted dynamic strategy and provide an algorithm to facilitate decision making in population level as well as for individual patient. Risk assessment and management accordingly is explicitly emphasized. In addition, we highlight the importance of diagnosis in each antifungal strategy among five elements of the antimicrobial stewardship (diagnosis, drug, dose, de-escalation and duration). The rationale, purpose, and key recommendations for the choice of antifungal strategy are summarized, with concise review of international guidelines or recommendation, key original articles and local epidemiology reports. We point out the interaction and influence between elements of recommendations and limitation of and gap between evidences and daily practice. The guideline balances the quality of evidence and feasibility of recommendation in clinical practice. Finally, this version introduces the concept of health economics and provides data translated from local disease burdens. All these contents hopefully facilitate transparency and accountability in medical decision-making, improvements in clinical care and health outcomes, and appropriateness of medical resource allocation.     

Psychosocial predictors of immune response following bone marrow transplantation

This study analyzed the relationship between some psychosocial variables (depression, anxiety, stress, coping strategies, social support, optimism, rationality, and need for harmony) and clinical parameters indicative of immunological response after bone marrow transplantation (BMT; day of engraftment, number of infections and hemoglobin level) while controlling for demographic variables (age, educative level, civil state, and time from cancer diagnosis). Thirty-one post BMT hematological cancer patients were evaluated. Results show that higher educative levels are associated to lower number of infections, while age is associated with a delay in the time of engraftment; coping strategies, specially redefinition of the situation, relaxation, stoicism and passivity, are positively associated with the three clinical indices; depression is positively associated to number of infections during the hospitalization period; and rationality is associated with lower hemoglobin levels. These results suggest that psychosocial variables, especially coping strategies, play an important role in determining the immunological response after BMT.     

血清同型半胱氨酸检测的临床意义回顾分析

为探讨血清同型半胱氨酸(THCY)检测的临床意义,回顾性分析173例心脑血管疾病或糖尿病患者和31名正常人血清THCY水平与其Folate,VB12,Glu,CH,Tg,ApoA,ApoB,HDL-CH,LDL-CH水平及所患疾病的关系。结果表明,血清THCY与Folate,VB12浓度呈负相关,与Glu,CH,Tg,ApoA,ApoB,HDL-CH,LDL-CH无明显的相关性。动脉硬化性心血管疾病患者及糖尿病患者的血清THCY浓度明显高于对照组。血清THCY是动脉硬化性心血管疾病及糖尿病的危险因子。Folate,VB12补充疗法可降低血清THCY,可能成为动脉硬化性心血管疾病及糖尿病患者高血THCY血症的治疗方案。