BACKGROUND & AIMS: Rupture of atheromatous plaques leading to acute coronary syndromes usually occur in lipid-reach and well-developed coronary lesions. We describe 2 unusual patients with acute coronary syndromes in whom there was angiographic and intravascular ultrasound evidence of an intraluminal thrombus overlying a small, nonocclusive plaque in an enlarged coronary artery.

背景与目标： 导致急性冠状动脉综合征的动脉粥样硬化斑块破裂通常发生在脂质到达和发达的冠状动脉病变中。我们描述了2例不寻常的急性冠状动脉综合征患者，其中有血管造影和血管内超声证据表明腔内血栓覆盖了扩大的冠状动脉中的一个小的非闭塞斑块。

BACKGROUND & AIMS: BACKGROUND:Although the benefit of thrombolytic therapy in reducing mortality in acute myocardial infarction is well established, the types of bleeding and risk factors for bleeding are less well described in large trials.

METHODS AND RESULTS:We analyzed the baseline characteristics, outcomes, and incidence of bleeding by location, severity, and treatment assignment among 41,021 patients in the GUSTO-I trial of thrombolysis for acute myocardial infarction. Of the 40,903 patients for whom there were complete data, 1.2% suffered severe bleeding and 11.4% experienced moderate hemorrhage at a variety of sites. The most common sources of bleeding were procedure related. The thrombolytic regimen was strongly related to the incidence of bleeding; comparatively more bleeding was seen with the therapies of streptokinase plus intravenous heparin and the streptokinase and tissue plasminogen activator plus intravenous heparin combination. In multivariate analysis, the four most powerful independent predictors of hemorrhage were older age, lighter body weight, female sex, and African ancestry; they remained the most important predictors of bleeding when multivariate analysis was performed on patients who did not undergo invasive procedures. The presence of serious hemorrhage was associated with other undesirable outcomes (recurrent events, left ventricular dysfunction, arrhythmia, or stroke).

CONCLUSIONS:Important predictors of bleeding in this population are increased age, lighter weight, female sex, African ancestry, and experiencing invasive procedures. Other nonhemorrhagic adverse clinical outcomes were associated with moderate and severe bleeding, which was in turn associated with increased length of hospital stay and mortality at 30 days.

背景与目标： 背景 : 尽管溶栓治疗在降低急性心肌梗死死亡率方面的益处已得到充分证实，但在大型试验中，出血类型和出血危险因素的描述较少。
方法和结果 : 在GUSTO-I急性心肌梗死溶栓试验中，我们分析了41,021名患者的基线特征，结局和出血发生率，按位置，严重程度和治疗分配。在40,903例有完整数据的患者中，1.2% 例严重出血，11.4% 例在不同部位出现中度出血。最常见的出血来源与手术有关。溶栓方案与出血发生率密切相关; 链激酶加静脉肝素以及链激酶和组织型纤溶酶原激活剂加静脉肝素联合治疗的出血相对较多。在多变量分析中，出血的四个最有效的独立预测因子是年龄较大，体重较轻，女性和非洲血统; 当对未接受侵入性操作的患者进行多变量分析时，它们仍然是出血的最重要预测因子。严重出血的存在与其他不良结果 (复发事件，左心室功能障碍，心律失常或中风) 相关。
结论 : 该人群出血的重要预测因素是年龄增加，体重减轻，女性，非洲血统，经历侵入性手术。其他非出血性不良临床结局与中度和重度出血相关，而中度和重度出血又与30天时的住院时间和死亡率增加相关。

BACKGROUND & AIMS: The expression and localization of hepatocyte growth factor/scatter factor (HGF/SF) were examined immunohistochemically in 59 human coronary artery lesions retrieved by directional coronary atherectomy and compared with the localization of transforming growth factor beta isoforms (TGF-beta 1, -beta 2, and -beta 3). In 21 of the 59 specimens (35.6%) HGF-like immunoreactivity (HGF-IR) was revealed. The HGF immunopositivity rate of 45% (14/31) in thrombotic tissue was significantly (P < 0.05) higher than the rates of 7.3% (4/55), 7.1% (3/42), and 0% (0/14) in fibrous tissue, neointimal hyperplasia and atheromatous gruel, respectively. Immunoreactivity for HGF was much weaker than that for TGF-beta isoforms in these components except in thrombotic tissue. These cells exhibiting strong HGF-IR were inflammatory cells such as monocytes/macrophages in thrombotic tissue, in tissue lesions adjacent to a thrombus, and outside the capillary walls in a portion of the neovascularized lesions. Smooth muscle cells (SMCs) hardly demonstrated HGF-IR. In contrast, in control coronary arteries obtained at autopsy, the HGF-IR was strongly expressed in SMCs. These findings suggest that HGF produced by macrophages play a part in the process of coronary plaque formation attributable to thrombus in man.

背景与目标： 通过免疫组织化学检查了通过定向冠状动脉粥样斑块切除术检索的59例人冠状动脉病变中肝细胞生长因子/散射因子 (HGF/SF) 的表达和定位，并将其与转化生长因子 β 亚型 (tgf-β1，-β2和-β3) 的定位进行了比较。在59个标本中的21个 (35.6%) 中，HGF样免疫反应性 (hgf-ir) 被揭示。血栓组织中45% (14/31) 的HGF免疫阳性率显着 (P < 0.05) 高于纤维组织，新内膜增生和动脉粥样硬化稀粥中的7.3% (4/55)，7.1% (3/42) 和0% (0/14)。分别。除血栓形成组织外，这些成分中HGF的免疫反应性比TGF-β 同工型的免疫反应性弱得多。这些表现出强hgf-ir的细胞是炎性细胞，例如血栓形成组织中，与血栓相邻的组织病变以及部分新生血管病变的毛细血管壁外部的单核细胞/巨噬细胞。平滑肌细胞 (smc) 几乎不显示HGF-IR。相反，在尸检获得的对照冠状动脉中，hgf-ir在smc中强烈表达。这些发现表明，巨噬细胞产生的HGF在人类血栓形成引起的冠状动脉斑块形成过程中发挥了作用。

BACKGROUND & AIMS: :A major problem in the search for new cancer drug targets is that the drugs are often toxic to normal tissues and require high doses to kill tumor cells. Therefore cellular targets which appear to involve low dose responses to cancer therapy are especially interesting since they could selectively target normal tissues which are not targeted by the treatment and thus may be responsible for unpleasant side effects or may be amenable to exploitation in order to improve the therapeutic ratio. One such target, which is the subject of this review, is radiation-induced bystander effects [RIBE], which result in the observation of radiation like responses in cells which have not been irradiated. RIBE is a novel phenomenon which indicates that at low doses, cell signaling is more important than direct DNA damage. Historically, DNA has always been considered to be the target for radiation therapy. The growing realization that signaling is important opens up several important therapeutic strategies which will be discussed in this review. RIBE appears to be the result of a generalized stress response in tissues or cells which is expressed at the level of the tissue, organ or organism rather than at the level of the individual cell. The signals may be produced by all exposed cells, but the response may require a quorum of cells in order to be expressed. The major response involving low LET (x- or gamma-ray) radiation exposure discussed in the existing literature is a death response. This has many characteristics of apoptosis but may be detected in cell lines without p53 expression, although the death response is suppressed in many tumor cell lines. While a death response in unirradiated normal cells around a tumor might appear to be adverse, it can in fact be protective and remove damaged cells from the population. If harnessed correctly, it could lead to the development of new drugs aimed not at tissue destruction but at enabling homeostatic mechanisms to control tumor expansion. In this scenario, the level of harmful or beneficial response will be related to the background damage, carried by the cell population, and the genetic programme determining response to damage. This focus may be important when attempting to predict the consequences of mixed therapies involving radiation and other cytotoxic agents. In this review, our current knowledge of the mechanisms underlying the induction of bystander effects by ionizing radiation is reviewed, and the question of how bystander effects may be harnessed to produce a new generation of anti-cancer drugs aimed at stabilization of tissue homeostasis rather than tissue destruction is considered.

背景与目标： : 寻找新的癌症药物靶标的一个主要问题是，这些药物通常对正常组织有毒，需要高剂量才能杀死肿瘤细胞。因此，似乎涉及对癌症治疗的低剂量反应的细胞靶标是特别令人感兴趣的，因为它们可以选择性地靶向不被治疗靶向的正常组织，并且因此可能导致令人不快的副作用或可能易于利用以提高治疗比率。作为本综述主题的一个这样的目标是辐射诱导的旁观者效应 [RIBE]，该效应导致在未辐照的细胞中观察到类似辐射的反应。RIBE是一种新现象，表明在低剂量下，细胞信号传导比直接DNA损伤更重要。从历史上看，DNA一直被认为是放射治疗的目标。越来越多的意识到信号很重要，这开辟了一些重要的治疗策略，这些策略将在本文中进行讨论。RIBE似乎是组织或细胞中普遍应激反应的结果，该应激反应在组织，器官或生物体的水平而不是单个细胞的水平上表达。信号可能由所有暴露的细胞产生，但是响应可能需要一定数量的细胞才能表达。现有文献中讨论的涉及低LET (x射线或伽马射线) 辐射暴露的主要反应是死亡反应。这具有许多凋亡特征，但可以在没有p53表达的细胞系中检测到，尽管在许多肿瘤细胞系中死亡反应受到抑制。虽然肿瘤周围未照射的正常细胞的死亡反应似乎是不利的，但实际上它可以起到保护作用并从人群中清除受损的细胞。如果正确使用，它可能会导致新药的开发，其目的不是组织破坏，而是使稳态机制能够控制肿瘤的扩张。在这种情况下，有害或有益反应的水平将与细胞群体携带的背景损害以及确定对损害反应的遗传程序有关。在尝试预测涉及辐射和其他细胞毒性药物的混合疗法的后果时，此重点可能很重要。在这篇综述中，我们对电离辐射诱导旁观者效应的潜在机制的当前知识进行了综述，并讨论了如何利用旁观者效应来生产旨在稳定组织稳态而不是组织破坏的新一代抗癌药物的问题。

BACKGROUND & AIMS: OBJECTIVE:To investigate clinically relevant intra-individual and mean changes in health-related quality of life (HRQoL) with the Short Form-36 Health Survey (SF-36) need to acknowledge that SF-36 is trademarked ie: SF-36(R) following cardiac intervention for Australian and Danish patients. DESIGN:Prospective observational study in tertiary cardiac centres in Townsville, Queensland, Australia and Copenhagen, Denmark. Two hundred coronary artery bypass graft surgery (CABG) patients of two Townsville hospitals, and 47 CABG or percutaneous coronary intervention (PCI) patients of a Copenhagen hospital. The main outcome measures are eight SF-36 health subscales at baseline and six months post-intervention. RESULTS:Australian and Danish patients experienced similar HRQoL pre-intervention. By six months post-intervention, patients experienced a significant mean improvement in all subscales of the SF-36 survey (p < or = 0.05), although up to 27% of patients had a clinically significant decline in HRQoL from baseline. CONCLUSIONS:These results demonstrate that it is necessary to investigate intra-individual changes in HRQoL as well as group mean changes as they produce different conclusions. In addition, establishing clinically significant intra-individual change standards may assist researchers and clinicians in determining whether an individual may benefit from therapy or intervention.

背景与目标：

BACKGROUND & AIMS: Epoxyeicosatrienoic acids (EETs) are endothelium-derived arachidonic acid metabolites of cytochrome P450. They dilate coronary arteries, open K+ channels, and hyperpolarize vascular smooth muscles. However, the mechanisms of these smooth muscle actions remain unknown. This study examined the effects of EETs on the large-conductance Ca(2+)-activated K+ channel (KCa) in smooth muscle cells of small bovine coronary arteries. In cell-attached patch-clamp experiments, 11,12-EET produced a 0.5- to 10-fold increase in the activity of the KCa channels when added in concentrations of 1, 10, and 100 nmol/L. In the inside-out excised membrane patch mode, 11,12-EET was without effect on the activity of the KCa channel unless GTP (0.5 mmol/L) or GTP and ATP (1 mmol/L) were added to the bath solution. In the presence of GTP and ATP, the increase in the KCa channel activity with 11,12-EET in inside-out patches was comparable to that in cell-attached patches. This effect of 11,12-EET in inside-out patches was blocked by the addition of GDP-beta-S (100 mumol/L). In outside-out patches, 11,12-EET also increased the KCa channel activity when GTP and ATP were added to the pipette solution. The addition of a specific anti-Gs alpha antibody (100 nmol/L) in the pipette solution completely blocked the activation of the KCa channels induced by 11,12-EET. An anti-G beta gamma or anti-Gi alpha antibody was without effect. We conclude that 11,12-EET activates the KCa channels by a Gs alpha-mediated mechanism. This mechanism contributes to the effects of EETs as endothelium-derived hyperpolarizing factors to hyperpolarize and relax arterial smooth muscle.

背景与目标： 环氧二十碳三烯酸 (EETs) 是细胞色素p450的内皮衍生的花生四烯酸代谢产物。它们扩张冠状动脉，打开K通道，并使血管平滑肌超极化。然而，这些平滑肌作用的机制仍然未知。这项研究检查了EETs对小冠状动脉平滑肌细胞中大电导Ca(2) 激活的K通道 (KCa) 的影响。在细胞附着的膜片钳实验中，当以1、10和100 nmol/L的浓度添加时，11,12-eet使KCa通道的活性增加了0.5至10倍。在由内向外切除的膜贴片模式中，11,12-eet对KCa通道的活性没有影响，除非将GTP (0.5 mmol/L) 或GTP和ATP (1 mmol/L) 添加到浴液中。在存在GTP和ATP的情况下，由内而外的贴片中11,12-eet的KCa通道活性增加与细胞附着的贴片相当。由内而外的贴片中11,12-eet的这种作用被添加GDP-β-S (100 mumol/L) 所阻断。在向外贴剂中，当将GTP和ATP添加到移液器溶液中时，11,12-eet也会增加KCa通道活性。在移液器溶液中添加特异性抗Gs α 抗体 (100 nmol/L) 完全阻断了由11,12-eet诱导的KCa通道的激活。抗G β γ 或抗Gi α 抗体无效。我们得出的结论是，11,12-eet通过Gs α 介导的机制激活了KCa通道。该机制有助于EETs作为内皮衍生的超极化因子，使动脉平滑肌超极化和松弛。

BACKGROUND & AIMS: :We investigated the ability of systolic and diastolic carotid artery longitudinal wall motion (CALM) to delineate expected differences in arterial health in individuals representing a range of both age and health status. We recruited 161 younger healthy adults (aged 24 ± 5 y), 51 older healthy adults (aged 70 ± 5 y) and 14 adults with coronary artery disease (aged 67 ± 8 y) for resting assessment of CALM and arterial stiffness. All CALM parameters were reduced in the old healthy adults and adults with coronary artery disease compared with the young healthy adults (p < 0.01), with diastolic velocity and maximum diastolic acceleration being further reduced in the adults with coronary artery disease than in the older healthy adults (p < 0.01). Diastolic CALM parameters were more strongly related to age (β range: -0.46 to -0.53) than systolic CALM parameters (β range: -0.24 to -0.44). In contrast to previous examinations of a variety of CALM parameters, diastolic CALM may provide superior promise in terms of characterizing arterial wall properties, with additional sensitivity to cardiovascular disease status.

背景与目标： : 我们研究了收缩期和舒张期颈动脉纵向壁运动 (CALM) 描绘代表年龄和健康状况范围的个体的动脉健康预期差异的能力。我们招募了161名年轻的健康成年人 (24 ± 5岁)，51名老年健康成年人 (70 ± 5岁) 和14名患有冠状动脉疾病的成年人 (67 ± 8岁) 进行静息评估平静和动脉僵硬度。与年轻健康成年人相比，老年健康成年人和患有冠状动脉疾病的成年人的所有CALM参数均降低 (p <0.01)，与老年健康成年人相比，患有冠状动脉疾病的成年人的舒张速度和最大舒张加速度进一步降低 (p <0.01)。舒张期平静参数与年龄 (β 范围: -0.46至-0.53) 的相关性高于收缩期平静参数 (β 范围: -0.24至-0.44)。与以前对各种平静参数的检查相比，舒张期平静在表征动脉壁特性方面可能具有出色的前景，并且对心血管疾病状态具有额外的敏感性。

BACKGROUND & AIMS: BACKGROUND:The complement system is an important mediator of inflammation, which plays a pivotal role in atherosclerosis and acute myocardial infarction (AMI). Animal studies suggest that activation of the complement cascade resulting in the formation of soluble membrane attack complex (sMAC), contributes to both atherosclerosis and plaque rupture and may be the direct cause of tissue damage related to ischemia/reperfusion injury. However clinical data of sMAC during an AMI is sparse. Accordingly the aim was to investigate the prognostic role of sMAC in patients with ST-segment elevation myocardial infarction (STEMI). METHODS:We included 725 STEMI-patients admitted to a single, high-volume invasive heart centre, treated with primary percutaneous coronary intervention (PCI), from September 2006 to December 2008. Blood samples were drawn immediately before PCI. Plasma sMAC was measured using an in-house immunoassay. Endpoints were all-cause mortality (n = 62) and the combined endpoint (n = 122) of major cardiovascular events (MACE) defined as cardiovascular mortality and admission due recurrent AMI or heart failure. Follow-up time was 12 months. RESULTS:During 12 months of follow-up 62 patients died from all causes and 122 patients reached the combined end-point of MACE. Patients with high sMAC (>75th percentile) had increased risk of both all-cause mortality and MACE. Even after adjustment for confounding risk factors by Cox-regression analyses, high levels of sMAC remained an independent predictor of all-cause mortality (hazard ratio 1.81 [95% CI 1.06-3.06; P = .029]) and MACE (hazard ratio 1.70 [95% CI 1.16-2.48; P = .006]). CONCLUSIONS:High plasma sMAC independently predicts all-cause mortality and MACE in STEMI-patients treated with PCI.

背景与目标：

BACKGROUND & AIMS: OBJECTIVE:To investigate: (1) the course of coronary heart disease risk factors (lipid profiles and body mass index (BMI)) in the first five years after discharge from inpatient spinal cord injury (SCI) rehabilitation and (2) the association between lifestyle (physical activity, self-care related to fitness, smoking, alcohol, body mass and low-fat diet) and coronary heart disease risk factors during that period. DESIGN:Prospective cohort study. PARTICIPANTS/METHODS:Individuals with SCI (N=130). Total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG) and BMI were determined at discharge from inpatient rehabilitation and 1 and 5 years after discharge. Using multilevel regression models, the effects of lifestyle (drinking alcohol, smoking, active lifestyle and self-care) on the lipid profiles and BMI were determined. RESULTS:After correction for lesion and personal characteristics, no changes in lipid profiles in the five years after discharge were seen, whereas the BMI increased significantly with 1.8 kg m(-2). A high percentage was at risk of cardiovascular disease due to high BMI (63-75%) or HDL (66-95%). The individuals who indicated to maintain their fitness level as good as possible and the individuals with a low BMI showed better lipid profiles. Individuals with a more active lifestyle showed higher HDL levels. Individuals who avoid smoking showed a 1.5 kg m(-2) higher BMI. CONCLUSION:Lipid profiles seem to stabilize in the years after discharge from inpatient SCI rehabilitation, whereas the BMI increased. Lifestyle factors associated with a favorable lipid profile and BMI could be identified.

背景与目标：

BACKGROUND & AIMS: :This article sets out the findings from research on the impact of a, UK based, chefs in schools teaching programme on food, health, nutrition and cookery. Professional chefs link with local schools, where they deliver up to three sessions to one class over a year. The research measured the impact of a standardised intervention package and changes in food preparation and consumption as well as measuring cooking confidence. The target group was 9-11year olds in four schools. The main data collection method was a questionnaire delivered 2weeks before the intervention and 2weeks afterwards. There was a group of four matched control schools. Those taking part in the intervention were enthused and engaged by the sessions and the impact measures indicated an intention to change. There were gains in skills and confidence to prepare and ask for the ingredients to be purchased for use in the home. Following the session with the chef, the average reported cooking confidence score increased from 3.09 to 3.35 (by 0.26 points) in the intervention group - a statistically significant improvement. In the control group this change was not statistically significant. Children's average reported vegetable consumption increased after the session with the chef, with the consumption score increasing from 2.24 to 2.46 points (0.22 points) again, a statistically significant increase with no significant changes in the control group. The research highlights the need to incorporate evaluation into school cooking initiatives as the findings can provide valuable information necessary to fine-tune interventions and to ensure consistency of the healthy eating messages.

背景与目标： : 本文阐述了基于英国a的学校厨师对食品，健康，营养和烹饪教学计划的影响研究结果。专业厨师与当地学校建立联系，在那里他们一年为一堂课提供多达三节课。该研究测量了标准化干预包的影响以及食物制备和消费的变化，并测量了烹饪信心。目标群体是四所学校的9-11岁儿童。主要数据收集方法为干预前2周及干预后2周发放问卷。有一组由四所匹配的控制学校组成。参加干预的人受到会议的热情和参与，影响措施表明有改变的意图。准备和要求购买用于家庭的食材的技能和信心得到了提高。与厨师会谈后，干预组的平均烹饪信心得分从3.09增加到3.35 (0.26分)，这是统计学上的显着改善。在对照组中，这种变化没有统计学意义。与厨师见面后，儿童平均报告的蔬菜消费量增加，消费得分从2.24分增加到2.46分 (0.22分)，在统计学上显着增加，而对照组没有显着变化。该研究强调了将评估纳入学校烹饪计划的必要性，因为研究结果可以提供必要的宝贵信息，以微调干预措施并确保健康饮食信息的一致性。

BACKGROUND & AIMS: BACKGROUND:International guidelines do not provide uniform recommendations regarding the use of antiplatelet treatment in the perioperative period in patients undergoing coronary artery bypass grafting (CABG). METHODS:A questionnaire was sent to all 16 cardiothoracic centres in the Netherlands to determine which antiplatelet treatment is used in the perioperative setting. Furthermore, a single-centre prospective observational cohort study was performed which included all patients undergoing isolated CABG in July 2014. RESULTS:Eleven centres responded to the survey. Acetylsalicylic acid monotherapy was discontinued before surgery in 6 centres. In patients with an acute coronary syndrome receiving dual antiplatelet therapy (DAPT), most centres discontinued the P2Y12 inhibitor preoperatively. DAPT was restarted after surgery in 4 centres. However, 6 centres continued DAPT in patients who had undergone coronary stenting within one month of surgery. In patients with coronary stents, variation in the management of antiplatelet therapy increased in proportion to the interval between stenting and surgery. A total of 70 patients were included in the registry. Acetylsalicylic acid monotherapy was discontinued in 51% of patients and restarted in all patients. P2Y12 inhibitor treatment was discontinued before surgery in 70% of patients and re-initiated after CABG in 29%. CONCLUSIONS:Major differences were observed in the preoperative and postoperative management of antiplatelet treatment between different Dutch cardiothoracic centres and within a single centre. Part of this variation is probably due to lack of evidence and differences between the current guidelines; however, many of the strategies were not in accordance with any of these guidelines.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Clinicians are encouraged to use guidelines to assist in providing evidence-based secondary prevention to patients with coronary heart disease. However, the expanding number of publications providing guidance about exercise training may confuse cardiac rehabilitation clinicians. We therefore sought to explore the number, scope, publication characteristics, methodological quality, and clinical usefulness of published exercise-based cardiac rehabilitation guidance. METHODS:We included publications recommending physical activity, exercise or cardiac rehabilitation for patients with coronary heart disease. These included systematically developed clinical practice guidelines, as well as other publications intended to support clinician decision making, such as position papers or consensus statements. Publications were obtained via electronic searches of preventive cardiology societies, guideline databases and PubMed, to November 2016. Publication characteristics were extracted, and two independent assessors evaluated quality using the 23-item Appraisal of Guidelines Research and Evaluation II (AGREE) tool. RESULTS:Fifty-four international publications from 1994 to 2016 were identified. Most were found on preventive cardiology association websites (n = 35; 65%) and were freely accessible (n = 50; 93%). Thirty (56%) publications contained only broad recommendations for physical activity and cardiac rehabilitation referral, while 24 (44%) contained the necessary detailed exercise training recommendations. Many were labelled as "guidelines", however publications with other titles (e.g. scientific statements) were common (n = 24; 44%). This latter group of publications contained a significantly greater proportion of detailed exercise training recommendations than clinical guidelines (p = 0.017). Wide variation in quality also existed, with 'applicability' the worst scoring AGREE II domain for clinical guidelines (mean score 53%) and 'rigour of development' rated lowest for other guidance types (mean score 33%). CONCLUSIONS:While a large number of guidance documents provide recommendations for exercise-based cardiac rehabilitation, most have limitations in either methodological quality or clinical usefulness. The lack of rigorously developed guidelines which also contain necessary detail about exercise training remains a substantial problem for clinicians.

背景与目标：

BACKGROUND & AIMS: :Human coronary artery endothelial cells (HCAECs) have the potential to undergo fibrogenic endothelial-mesenchymal transition (EndMT), which results in matrix-producing fibroblasts and thereby contributes to the pathogenesis of cardiac fibrosis. Recently, the profibrotic cytokine transforming growth factor-β (TGF-β) is shown to be the crucial pathogenic driver which has been verified to induce EndMT. C-Ski is an important regulator of TGF-β signaling. However, the detailed role of c-Ski and the molecular mechanisms by which c-Ski affects TGF-β-induced EndMT in HCAECs are not largely elucidated. In the present study, we treated HCAECs with TGF-β of different concentrations to induce EndMT. We found that overexpression of c-Ski in HCAECs either blocked EndMT via hindering Vimentin, Snail, Slug, and Twist expression while enhancing CD31 expression, with or without TGF-β treatment. In contrast, suppression of c-Ski further enhanced EndMT. Currently, miRNA expression disorder has been frequently reported associating with cardiac fibrosis. By using online tools, we regarded miR-155 as a candidate miRNA that could target c-Ski, which was verified using luciferase assays. C-Ski expression was negatively regulated by miR-155. TGF-β-induced EndMT was inhibited by miR-155 silence; the effect of TGF-β on Vimentin, CD31, Snail, Slug, and Twist could be partially restored by miR-155. Altogether, these findings will shed light on the role and mechanism by which miR-155 regulates TGF-β-induced HCAECs EndMT via c-Ski to affect cardiac fibrosis, and miR-155/c-Ski may represent novel biomarkers and therapeutic targets in the treatment of cardiac fibrosis.

背景与目标： : 人冠状动脉内皮细胞 (HCAECs) 具有发生纤维化的内皮-间质转化 (EndMT) 的潜力，这导致产生基质的成纤维细胞，从而有助于心脏纤维化的发病机理。最近，纤维化细胞因子转化生长因子-β (TGF-β) 被证明是关键的致病驱动因素，已被证实可诱导EndMT。C-ski是TGF-β 信号的重要调节因子。然而，c-Ski的详细作用以及c-Ski影响HCAECs中TGF-β 诱导的EndMT的分子机制尚未得到很大的阐明。在本研究中，我们用不同浓度的TGF-β 处理HCAECs以诱导EndMT。我们发现，有或没有TGF-β 处理，HCAECs中c-Ski的过表达通过阻碍波形蛋白，蜗牛，Slug和Twist的表达来阻断EndMT，同时增强CD31的表达。相比之下，抑制c-ski进一步增强了EndMT。目前，miRNA表达紊乱经常被报道与心脏纤维化有关。通过使用在线工具，我们将miR-155视为可以靶向c-Ski的候选miRNA，使用荧光素酶分析验证了这一点。C-Ski表达受miR-155负调节。TGF-β 诱导的EndMT被miR-155沉默抑制; TGF-β 对波形蛋白，CD31，蜗牛，Slug和Twist的作用可以通过miR-155部分恢复。总之，这些发现将阐明miR-155通过c-Ski调节TGF-β 诱导的HCAECs EndMT以影响心脏纤维化的作用和机制，并且miR-155/c-Ski可能代表治疗心脏纤维化的新型生物标志物和治疗靶标。

BACKGROUND & AIMS: :Thallium tomographic imaging and exercise electrocardiography were performed on 136 diabetic patients without symptoms of heart disease. Thirty three patients had post-exercise thallium defects and 19 had ST 1 mm greater than or equal to segment depression during exercise electrocardiography. Both tests were positive in 13 patients. Coronary angiography was subsequently performed on 33 patients with either scintigraphic and/or electrocardiographic evidence of myocardial ischaemia. Angiographically significant coronary artery disease (greater than or equal to 50% narrowing of the coronary artery lumen) was detected in 13 patients. Six patients had minimal coronary artery stenosis (less than 50%), and 14 had normal coronary arteries. Six patients refused cardiac catheterisation. In 14 out of 27 patients with post-exercise thallium defects coronary angiography did not show any coronary artery stenoses (positive predictive accuracy 48%). Exercise electrocardiography showed only one false positive result (positive predictive accuracy 94%) but failed to detect coronary artery disease in three patients with a positive scintigraphic result. The accuracy of a positive exercise electrocardiographic test seems to be better than that of a positive thallium tomographic scan for detecting asymptomatic coronary artery disease in diabetic patients. The high number of false positive thallium defects may be the result of technical features inherent in thallium tomography and/or the possible disease of the small intramyocardial arteries in diabetic patients.

背景与目标： 对136例无心脏病症状的糖尿病患者进行了th断层显像和运动心电图检查。运动心电图期间，有33例患者存在运动后th缺陷，19例ST 1毫米大于或等于节段压低。13例患者的两项测试均为阳性。随后对33例具有心肌缺血的闪烁显像和/或心电图证据的患者进行了冠状动脉造影。在13例患者中检测到血管造影显著的冠状动脉疾病 (大于或等于冠状动脉腔的50% 变窄)。6例冠状动脉狭窄 (小于50%)，14例冠状动脉正常。六名患者拒绝心脏导管插入术。在运动后th缺陷的27例患者中，有14例冠状动脉造影未显示任何冠状动脉狭窄 (阳性预测准确性48%)。运动心电图仅显示一个假阳性结果 (阳性预测准确性94%)，但未能在三个闪烁显像结果阳性的患者中检测到冠状动脉疾病。在糖尿病患者中，积极的运动心电图测试的准确性似乎比阳性的th断层扫描的准确性更好。大量假阳性th缺陷可能是th断层扫描固有的技术特征和/或糖尿病患者心肌小动脉的可能疾病的结果。

BACKGROUND & AIMS: :Menopausal hormone treatment (MHT) may limit progression of cardiovascular disease (CVD) but poses a thrombosis risk. To test targeted candidate gene variation for association with subclinical CVD defined by carotid artery intima-media thickness (CIMT) and coronary artery calcification (CAC), 610 women participating in the Kronos Early Estrogen Prevention Study (KEEPS), a clinical trial of MHT to prevent progression of CVD, were genotyped for 13,229 single nucleotide polymorphisms (SNPs) within 764 genes from anticoagulant, procoagulant, fibrinolytic, or innate immunity pathways. According to linear regression, proportion of European ancestry correlated negatively, but age at enrollment and pulse pressure correlated positively with CIMT. Adjusting for these variables, two SNPs, one on chromosome 2 for MAP4K4 gene (rs2236935, β = 0.037, P value = 2.36 × 10(-06)) and one on chromosome 5 for IL5 gene (rs739318, β = 0.051, P value = 5.02 × 10(-05)), associated positively with CIMT; two SNPs on chromosome 17 for CCL5 (rs4796119, β = -0.043, P value = 3.59 × 10(-05); rs2291299, β = -0.032, P value = 5.59 × 10(-05)) correlated negatively with CIMT; only rs2236935 remained significant after correcting for multiple testing. Using logistic regression, when we adjusted for waist circumference, two SNPs (rs11465886, IRAK2, chromosome 3, OR = 3.91, P value = 1.10 × 10(-04); and rs17751769, SERPINA1, chromosome 14, OR = 1.96, P value = 2.42 × 10(-04)) associated positively with a CAC score of >0 Agatston unit; one SNP (rs630014, ABO, OR = 0.51, P value = 2.51 × 10(-04)) associated negatively; none remained significant after correcting for multiple testing. Whether these SNPs associate with CIMT and CAC in women randomized to MHT remains to be determined.

背景与目标： : 更年期激素治疗 (MHT) 可能会限制心血管疾病 (CVD) 的进展，但会带来血栓形成的风险。为了测试与颈动脉内膜中层厚度 (CIMT) 和冠状动脉钙化 (CAC) 定义的亚临床CVD相关的靶向候选基因变异，610参加Kronos早期雌激素预防研究 (KEEPS) 的妇女，MHT预防CVD进展的临床试验，在抗凝剂，促凝剂，纤溶或先天免疫途径的764基因内对13,229单核苷酸多态性 (snp) 进行基因分型。根据线性回归，欧洲血统的比例呈负相关，但入学年龄和脉压与CIMT呈正相关。调整这些变量，两个snp，一个在2号染色体上的MAP4K4基因 (rs2236935，β = 0.037，p值 = 2.36 × 10(-06))，一个在5号染色体上的IL5基因 (rs739318，β = 0.051，p值 = 5.02 × 10(-05))，与CIMT呈正相关; CCL5 17号染色体上的两个snp (rs4796119，β = -0.043，p值 = 3.59 × 10(-05); rs2291299，β = -0.032，p值 = 5.59 × 10(-05)) 与CIMT呈负相关; 校正多重测试后，只有rs2236935仍然显著。使用逻辑回归，当我们调整腰围时，两个snp (rs11465886，IRAK2，3号染色体，OR = 3.91，p值 = 1.10 × 10(-04); 和rs17751769，SERPINA1，14号染色体，OR = 1.96，p值 = 2.42 × 10(-04)) 与> 0 Agatston单位的CAC评分呈正相关; 1个SNP (rs630014，ABO，OR = 0.51，p值 = 2.51 × 10(-04)) 呈负相关; 校正多重测试后无显著。这些snp是否与CIMT和CAC相关，在随机分配到MHT的女性中仍有待确定。