Abstract:转化医学研究是探索促进基础医学和临床医学相结合的关键环节,能打破基础研究到临床实践之间的壁垒,运用基础研究取得的成就,改善临床的预防和诊疗。心血管疾病发病和预后的早期预警和风险分层是改善疾病防治的必经之路。文章将以青年冠心病为例,阐述目前疾病精准防治的困境以及转化医学研究如何通过实现疾病发病和预后的早期预警和风险分层从而提升疾病防治水平。青年冠心病在发病危险因素、生物标志物、临床表型、治疗预后等方面都有其自身特点,是有别于老年冠心病的独特冠心病亚类。以往冠心病研究集中在常见老年冠心病,缺乏青年冠心病发病和预后相关生物标志物,因此尚无适用于青年冠心病的精准防治方案。通过转化医学研究,结合基因组和代谢组学技术,鉴定与青年冠心病发病及预后相关的遗传和代谢标志物,有助于实现青年冠心病发病和预后的早期预警和风险分层,改善中国青年冠心病的精准预防和诊疗策略,提升预防效果和诊疗水平。

Abstract:整合素家族受体是细胞表面重要的黏附分子,在细胞和微环境之间的相互作用中发挥着重要作用。整合素与多种人类疾病密切相关,如心血管疾病、血栓症、炎症、癌症等,是重要的药物靶点。本文主要论述整合素在心血管疾病中的研究进展。

Abstract:交感神经系统通过释放各种交感神经递质直接参与血管正常生理功能的调节,对维持血管稳态具有重要作用。然而病理条件下交感神经系统的改变会影响血管张力以及血管的反应性等,从而导致高血压、动脉粥样硬化和肺动脉高压等血管性疾病。本文主要综述交感神经系统在相关血管性疾病的发生发展中的作用。

Abstract:Aim To investigate the effect of coiled-coil domain containing protein 80 (CCDC80) on the expression of inflammatory factors in THP-1 macrophage-derived foam cells and related molecular mechanisms. Methods THP-1 cells were treated with phorbol ester (160 nmol/L) to induce the cells to differentiate into macrophages, and then treated with oxidized low density lipoprotein (50 mg/L) to form foam cell, performing conventional cell culture in vitro. The expression of interleukin-1β(IL-1β), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α) and monocyte chemoattractant protein-1(MCP-1) was detected by ELISA, the expression of Toll like report 4(TLR4), lipoprotein lipase(LPL) and nuclear factor-κB(NF-κB) was detected by real-time PCR and Western blot. Foam cells were treated with TLR4 siRNA and LPL siRNA, and the effects of CCDC80 on the expression of TLR4, LPL, NF-κB and p-NF-κB in foam cells were detected by fluorescence quantitative PCR and Western blot. Results CCDC80 significantly increased THP-1 macrophage-derived foam cell inflammatory factor secretion and p-NF-κB expression. After TLR4 siRNA treated foam cells, the expression of TLR4, LPL and p-NF-κB reduced significantly. After LPL siRNA treated foam cells, the expression of LPL and p-NF-κB decreased significantly. Conclusion CCDC80 promotes the activation of NF-κB signaling pathway through the TLR4/LPL pathway, thereby increasing the secretion of IL-1β, IL-6, TNF-α and MCP-1.

Abstract:Aim To explore the effect of paeonol (Pae) on the FXR-FGF15 signaling pathway by regulating the metabolism of bile acids in ApoE－/－ mice, thereby affecting lipid metabolism to play an anti-atherosclerotic effect. Methods ApoE－/－ mice were fed high-fat diet for 20 weeks to establish an atherosclerotic plaque model, and the model was created and injected with paeonol (200 mg/kg). Oil red O staining was used to observe the pathomorphological changes of the aorta and liver tissues; Enzymatic method was used to detect the lipid levels of blood and liver; LC-MS/MS was used to detect changes in mouse intestinal bile acid composition; Western blot was used to detect the expression of mouse liver CYP7A1, ileum FXR and FGF15. Results Paeonol significantly reduced the plaque area of the aorta in atherosclerotic model mice and reduced lipid deposition in the liver; significantly reduced the levels of triglyceride, total cholesterol and liver coefficient in serum and liver; increased the content of FXR antagonists TαMCA and TβMCA, reduced the content of FXR agonists CDCA and LCA, inhibited the intestinal FXR-FGF15 signaling pathway, induced the expression of CYP7A1 protein in liver tissue, and increased the efflux of total bile acid in feces. Conclusion Paeonol may affect the metabolism of bile acids and inhibit the FXR-FGF15 axis to promote the synthesis and excretion of bile acids in the liver, reduce cholesterol accumulation, and achieve its anti-atherosclerotic effect.

Abstract:Aim To investigate the effect of high wall shear stress (WSS) caused by arterio-venous fistula (AVF) on neointimal hyperplasia (NIH) after stent implantation. Methods 36 male New Zealand white rabbits were randomly divided into three groups with 12 rabbits in each group:stent group:right common carotid artery (CCA) stent implantation; stent＋arterio-venous fistula (AVF) group:right CCA stent implantation and right carotid AVF; control group:no treatment. After 21 days, CCA specimen of stent segment was taken for histological staining and protein expression analysis. Results In stent segment CCA, WSS was maintained at 43.2%-48.9% of baseline in stent group, and WSS gradually increased to 86% above baseline level in stent＋AVF group. NIH in stent＋AVF group was less than that in stent group (neointimal area:0.19 mm² vs. 0.87 mm²; neointima-to-media area ratio:0.18 vs. 1.13). Western blot results showed that the level of endothelial nitric oxide synthase (eNOS) in the stent＋AVF group was significantly higher than that in the stent group, while the levels of proliferating cell nuclear antigen (PCNA), vascular cell adhesion molecule-1 (VCAM-1), phosphorylated p38 mitogen-activated protein kinase (p-p38) and phosphorylated c-Jun NH₂-terminal protein kinase (p-JNK) in the stent＋AVF group were significantly lower than those in the stent group. Conclusion High WSS induced by AVF can reduce NIH after stent implantation, and its potential mechanism may be related to the regulation of eNOS, VCAM-1, p38 and JNK expression and activation.

Abstract:Aim To evaluate the incidence of intramyocardial hemorrhage (IMH) after percutaneous coronary intervention surgery for acute ST-segment elevation myocardial infarction (STEMI) in the Chinese population, and to explore the relevant predictive factors for the IMH formation and provide individualized diagnosis and treatment measures for patients with STEMI . Methods The observation cohort study of our center was conducted in patients with STEMI undergoing successful myocardial reperfusion. The cardiac magnetic resonance (CMR) examination was (5.71±2.46) days after emergency percutaneous coronary intervention (PCI). T2 weighting was used to observe IMH in cardiac tissue, and the basic data, laboratory examination, echocardiography (UCG) and CMR parameters of IMH and non-intramyocardial hemorrhage (non-IMH) patients were compared. Logistic regression analysis was used to screen out risk factors related to intramyocardial hemorrhage. Results 44 (48.9%) of the 90 patients enrolled had IMH. Compared with the non-IMH group, IMH patients had a higher incidence of obsolete cerebral infarction and pre-hospital oral diuretics. Faster heart rate, higher C-reactive protein (CRP), relatively lower myocardial staining score (all P＜0.05) were also observed in IMH group. Compared with non-IMH group, UCG showed that left ventricular end diastolic diameter (LVEDd) increased in IMH group, CMR showed that left ventricular end-diastolic volume (LVEDV), total myocardial infarction size (IS)/the volume of left ventricular (LV), microvascular occlusion (MVO) area/the volume of LV were all increased (all P＜0.05). Compared with non-IMH group, the incidence of IMH was significantly related to the decrease of left ventricular ejection fraction (LVEF), global radial strain (GRS),global circumferential strain (GCS) and global longitudinal strain (GLS) (all P＜0.05). In IMH group, the left anterior descending artery (LAD) lesions were more frequent, and the myocardial infarction sites were more frequent in the anterior wall, interventricular septum and apex of the heart, meanwhile pericardial effusion and aneurysm were more likely to occur (both P＜0.05). Multivariate Logistic regression analysis suggested that IMH was independently associated with anterior myocardial infarction (OR:5.9,5%CI:1.28～27.95, P＜0.05), decreased percentage of peak GLS measured by CMR (OR:1.7,5%CI:1.21～2.03, P＜0.05) and high low density lipoprotein cholesterol (LDLC) (OR:4.2,5% CI:1.45～15.38, P＜0.05). Conclusion Among STEMI patients treated with myocardial reperfusion, the IMH has a strong correlation with anterior wall myocardial infarction, GLS reduction, and LDLC increase, which can be used to identify the potential risk factors for IMH in STEMI patients. IMH is associated with more severe infarction and worse left ventricular function, and is more likely to be associated with ventricular aneurysm and pericardial effusion.

Abstract:目的 对比颈动脉斑块易损性评分和斑块积分与脑白质病变(WML)及认知损害的相关性,明确易损性评分是否能更敏感地评估WML及认知损害。方法 以2016年4月至2019年5月苏州大学附属第一医院老年医学科住院患者为研究对象,收集经颈动脉超声证实的201例颈动脉斑块患者的基本资料、实验室资料、颈动脉超声及头颅磁共振等影像学数据。将所有研究对象根据斑块易损性分为稳定组和易损组,计算两组对象的颈动脉斑块易损性评分及Crouse积分,所有对象均采用Fazekas量表和蒙特利尔认知评价量表(MoCA)分别进行WML视觉评分及认知功能评价,以上数据进行组间统计学分析。结果 稳定组与易损组之间高血压、Fazekas评分、脑室旁白质病变(PVWML)、深部白质病变(DWML)、MoCA总分、斑块总数、斑块形态、回声特征、均质性及血管狭窄程度有统计学差异(P＜0.05),易损组高血压比例、斑块总数及斑块各特征评分均高于稳定组,而认知功能评分低于稳定组,且全脑WML、PVWML及DWML均更严重。易损性评分和Crouse积分与Fazekas评分正相关(r＝0.23和r＝0.26,P＜0.05),与MoCA总分显著负相关(r＝－0.39和r＝－0.34,P＜0.001)。Logistic回归分析结果显示,易损性评分分别是PVWML、Fazekas评分及MoCA总分的独立危险因子(P＜0.05)。结论 对比颈动脉斑块积分,易损性评分可作为评价WML及认知损害严重程度的敏感指标。

Abstract:目的 探讨脂质代谢水平与冠状动脉粥样硬化病变的关系。方法 回顾性分析182例疑似冠状动脉粥样硬化病变患者的资料,均实施冠状动脉数字减影血管造影(DSA)检查,将有冠状动脉粥样硬化病变者列为研究组,否则列为对照组。检测受试者血浆甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDLC)、低密度脂蛋白胆固醇(LDLC)、载脂蛋白AⅠ(ApoAⅠ)、载脂蛋白B(ApoB)水平,采用Logistic逐步回归分析探讨这些指标与冠状动脉粥样硬化病变的关系；根据研究组Gensini积分分组,对比Gensini积分＜20分、20~40分、＞40分患者脂质代谢水平差异；采用Pearson相关性分析法评价研究组脂质代谢指标水平与Gensini积分的相关性。结果 受试者中冠状动脉粥样硬化病变检出率为59.34%,且研究组血浆HDLC、ApoAⅠ水平均低于对照组(P＜0.05),TG、TC、LDLC、ApoB水平均高于对照组(P＜0.05)；研究组年龄≥80岁、合并高血压、合并2型糖尿病、合并高脂血症、肥胖、吸烟史、饮酒史、TG＞2.3 mmol/L、TC＞5.98 mmol/L、HDLC＜1.2 mmol/L、LDLC＞3.1 mmol/L、ApoAⅠ＜1.02 g/L、ApoB＞1.14 g/L占比均高于对照组(P＜0.05),且均是冠状动脉粥样硬化病变的危险因素。研究组中不同Gensini积分患者血浆ApoAⅠ、ApoB水平对比差异均有统计学意义(P＜0.05),血浆HDLC、ApoAⅠ水平在Gensini积分＜20分组最高,20~40分组稍低,＞40分组最低,而血浆TG、TC、LDLC、ApoB水平在Gensini积分＞40分组最高,20~40分组次之,＜20分组最低；研究组中血浆HDLC、ApoAⅠ与Gensini积分呈负相关(r＝－0.842,P＝0.023；r＝－0.789,P＝0.007),TG、TC、LDLC、ApoB水平与Gensini积分呈正相关(r＝0.798,P＝0.004；r＝0.812,P＝0.015；r＝0.803,P＝0.008；r＝0.808,P＝0.013)。结论 在冠状动脉粥样硬化病变患者中血浆HDLC和ApoAⅠ水平偏低,TG、TC、LDLC、ApoB水平偏高,均可增加冠状动脉粥样硬化病变发生风险,且前者与Gensini积分呈负相关,后者与Gensini积分呈正相关。

Abstract:Aim To evaluate the efficacy and safety of prourokinase administration in coronary artery of patients with acute myocardial infarction before PCI. Methods Pubmed, Wanfang Data, CBM, CNKI and VIP databases were searched for randomized controlled trial (RCT) of prourokinase administration in coronary artery of patients with acute myocardial infarction before PCI. The retrieval time limit was from the establishment of database to 2020. The quality of literature was evaluated by the improved Jadad scoring method. RevMan 5.2.0 was used for statistical analysis. Results A total of 10 RCT were included, 1 252 patients with acute myocardial infarction, including 628 patients in the control group (routine treatment before PCI) and 624 patients in the experimental group (prourokinase plus the control group). The results of Meta analysis showed that TIMI blood flow grade was greater in the experimental group than that in the control group(RR=1.26,95%CI(1.16,1.36),P＜0.000 01), and the incidence rate of corrected TIMI frame count (cTFC) was greater in the experimental group than that in the control group(MD=－7.23,95%CI(－10.19,－4.27), P＜0.000 01); left ventricular ejection fraction (LVEF) was higher in the experimental group than that in the control group during hospitalization and 1 week after PCI(MD=3.47,95%CI(2.01,4.93),P＜0.000 01); LVEF was higher in the experimental group than that in the control group within one month after PCI (MD=2.92,95%CI(0.33,5.50),P=0.03); LVEF was higher in the experimental group than that in the control group within six months after PCI (MD=3.0,5%CI (2.4,5.07), P＜0.000 01); The incidence rate of major adverse cardiovascular events (MACE) was lower in the experimental group than in the control group within 1 month after PCI(RR=0.32,95%CI(0.22,0.48),P＜0.000 01); the incidence rate of MACE was lower in the experimental group than that in the control group within 1 year after PCI (RR=0.32,95%CI(0.19,0.53),P＜0.000 1). There was no significant difference between the experimental group and the control group in the incidence rate of bleeding events within one month after PCI(RR=0.93,95%CI(0.62,1.40) ,P=0.73); there was no significant difference between the experimental group and the control group in the incidence rate of bleeding events more than half a year after PCI(RR=1.49,95%CI(0.44,5.12),P=0.52). Conclusion The application of prourokinase thrombolysis in the coronary artery before PCI can further improve the myocardial perfusion level of patients with acute myocardial infarction, improve the left ventricular function of patients after PCI, reduce the incidence of MACE, and do not increase the incidence of bleeding events, which has a better clinical effect.

Abstract:In clinical practice, more and more attention has been paid to chemotherapy-related cardiotoxicity, which often hinders the optimal treatment of cancer. Anthracyclines (AC) are the most commonly used anticancer drug, which are very effective for hematological malignancies. Although modern imaging techniques can identify patients at risk of AC induced cardiotoxicity (AIC), the therapeutic effect is not good, part of the reason is that the molecular mechanism of AIC is still unclear. Although AIC is initially attributed to cellular oxidative stress, antioxidants do not prevent AIC, suggesting that AIC involves other mechanisms. A series of studies have shown that autophagy may play an important role. This review will summarize the relevant evidence of autophagy in AIC to explore the role of targeted cardiac autophagy in the prevention of AIC.

Abstract:缺血性心脏病(IHD)的发生是从多种潜在危险因素到临床显性疾病的多步骤链式进程。利用外泌体作为IHD的治疗靶点,已成为基础和临床研究的热点。大量证据表明外泌体在很大程度上参与IHD的演变,包括内皮功能障碍、脂质沉积、动脉粥样硬化斑块的形成和破裂、心肌缺血再灌注损伤和心力衰竭。本篇综述将系统地描述在IHD发展的各个阶段中多种外泌体及其活性分子miRNA的相关作用及机制,同时也揭示了外泌体miRNA作为治疗靶点的潜力和挑战,希望为后续研究提供支持背景。

Abstract:冠状动脉介入技术的日益成熟和新型药物洗脱支架(DES)的广泛使用极大降低了支架内再狭窄(ISR)的风险。然而,ISR仍然是冠状动脉介入治疗失败的重要原因。炎症和血小板活化是ISR病理生理学的重要过程。与之相关的血细胞参数,包括细胞计数和形态参数,是临床实践中炎症反应和血小板活化的有用标志物。近年来大量临床研究强调了血细胞参数独立预测DES术后ISR发生风险的价值。比如中性粒细胞/淋巴细胞比值作为一种炎症指标,被认为是ISR及动脉粥样硬化斑块不稳定性发生的风险预测因子。平均血小板体积作为被广泛应用的血小板活化参数,已被证明是ISR发生风险和抗血小板药物疗效的预测因子。血小板/淋巴细胞比率、红细胞分布宽度和血小板分布宽度等指标也与ISR的发生存在一定的相关性。因此文章对这些参数进行综述,以期对冠状动脉ISR的风险提供新的预测指标。