Anti eotaxin-2 antibodies attenuate the initiation and progression of experimental atherosclerosis

Background: The chemokine eotaxin-2 is a potent chemoattractant for inflammatory cells, the predominants of which are eosinophils. Human and murine atherosclerotic plaques are known to exhibit inflammatory phenotypes where a complex interaction of cytokine and chemokines plays a role. We tested the hypothesis that eotaxin-2 (eo-2) plays a causative role in the initiation and progression of experimental atherosclerosis. Methods and Results: Sera collected from atherosclerotic ApoE knockout (KO) mice, exhibited significantly higher levels of eo-2 compared to sera collected from their background age matched C57BL/6 litters by ELISA. Moreover, levels of eo-2 were higher in old atherosclerotic ApoE KO mice than in young animals. Similarly, the expression level of the eo-2 receptor, CCR3, was increased in splenocytes of old ApoE compared to the young littermates. Administration of polyclonal blocking antibodies to eotaxin-2 resulted in a significant reduction of early atherosclerotic plaques in ApoE KO mice whereas prolonged treatment of mice with advanced plaques led to atheroma stabilization. A monoclonal antibody (D8) prepared against eo-2 attenuated adhesion of lymphocytes to fibronectin and potently inhibited their migration towards VEGF. Monoclonal blocking antibodies to eo-2 also significantly reduced atherosclerotic plaques in ApoE KO mice. Conclusion: Eo-2 serum levels are elevated in sera of ApoE KO mice with experimental atherosclerosis and its blockade is associated with reduced fatty streak accumulation and increased plaque stabilization.

Age-related increase of early afterdepolarization in calsequestrin-2 knock-in mouse cardiomycyte

描绘引起的早 afterdepolarizations (EAD ) 的目的在 calsequestrin-2 (CASQ2 ) 之中触发了活动(TA ) 敲门在里面(CASQ2 KI ) 有老化的老鼠和它的关系。室的 myocytes 从的方法 Electrophysiological 性质 3 月(瞬间，年轻) ， 9 瞬间(adult-1 ) 和 12 瞬间(adult-2 ) 在野类型(WT ) 并且 CASQ2 KI 老鼠与补丁夹钳被调查技术。在 CASQ2 KI cardiomyocytes 的 EAD 和 TA 的发生与增加增加了的结果变老。相反， WT 老鼠 cardiomyocytes 没在火柴年龄组显示出重要变化。与相比在 3 瞬间 CASQ2 KI 老鼠，行动潜力(APD50 ) 的 50% 极化在 9 瞬间和 12 瞬间显示出延伸(9.

Homocysteinemia and methylene tetrahydrofolate reductase gene’s relation to increased risk of coronary artery disease

Objective To review the association of methylene tetrahydrofolate reductase (MTHFR) C677T mutant with coronary artery disease, as well as to highlight the results of some of these studies and to emphasize the need to focus on the genetic architecture of CAD. Data SourcesData used in this article is mainly from relevant articles obtained through Pubmed, OVID and Google Scholar published from 1980 to 2008. Major studies and trials in this period were taken into account to draw accurate conclusion on the relation of those mutations in MTHFR with homocysteinemia and CAD. ResultOur analysis shows that hyperhomocysteinemia, a risk factor for occlusive arterial diseases, can be caused by disruptions of homocysteine metabolism catalyzed by MFTHR. A common alanine to valine mutation in MTHFR may contribute to mild heperhomocysteinemia in CAD. Individuals with the homozygous mutant genotype had higher plasma homocysteine, particularly when plasma folate was below the median value. ConclusionThis MTHFR mutant in the setting of insufficient folate may be a risk factor of CAD and can be regarded as a model of genetic-environmental interaction in the development of CAD.

Establishment of animal models for chronic pulmonary embolism

Objective:To establish the animal model for the chronic pulmonary embolism and do some research on it.Methods:Pulmonary arteriography by DSA were performed in 6 goats and the stent was released in the infer-pulmonary arterary.Arterial blood gas analysis and right heart catheterization were done.After 3 days of embolism,pulmonary arteriography were performed again.After the animal was sacrificed,the right and left infer-pulmonary tissues were prepared and pathologically studied.Results:Stents were smoothly released in 6 animals.Compared with that before embolism,the arterial blood gas showed no difference 10 minutes later and 3 days later of the stent released.The pulmonary angiography showed that the right infra pulmonary artery was partly blocked and the blood could still pass by.3 d of the embolism later,the stent was placed well and the right pulmonary artery was completely blocked.Compared with that before embolism,the right atrial pressure,ventricular pressure and the pulmonary pressure in 10 min after embolism did not change much(P>0.05),while 3 d after embolism,the pressures were obviously changed(P<0.05).There was no atelectasis,pleural effusion in the right infra lobe in the experimental group.The wall of blood capillary among the alveolar wall were significantly dilated.Hyperemia and edema were also observed.Lots of monocyte infiltrated.Localized exudates appeared in alveolar.Conclusion:By releasing stent in the pulmonary,the chronic pulmonary embolism model could be established in the animal experiment,and it should have great potential value in the following study.

血清组织蛋白酶S、胱抑素C水平与冠状动脉粥样硬化病变严重程度相关性的研究——附107例报告

目的:探讨冠状动脉粥样硬化性心脏病(冠心病)患者血清组织蛋白酶S(cathepsinS,CatS)及胱抑素C水平与冠状动脉病变程度的关系。方法:对155例疑诊心绞痛患者进行冠状动脉造影(coronary angiography,CAG),根据CAG结果分为冠心病组(107例)及对照组(48例),测定所有入选者的空腹血清CatS、胱抑素C水平,采用Gensini积分对冠状动脉病变程度进行评价并分析它们之间的关系。结果:冠心病组血清CatS、胱抑素C水平较对照组高(P(0.01),前者上升幅度更大,血清CatS水平与Gensini积分呈正相关(r=0.69,P(0.01),Logistic回归分析剔除年龄、性别、收缩压、血清总胆固醇等因素后,此相关性仍存在(r=0.71,P(0.01)。结论:冠心病患者的血清CatS、胱抑素C的水平增高,且CatS与冠状动脉粥样硬化病变程度密切相关,说明CatS及胱抑素C可能参与细胞外基质重塑的过程。

Treatment and Clinical Management of Chronic Thromboembolic Pulmonary Hypertension:An Update of Literature Review

Chronic thromboembolic pulmonary hypertension(CTEPH)is a chronic,progressive,debilitating,and life-threa-tening complication of pulmonary embolism(PE).Recent technological advances have permitted various treat-ment options for the treatment of CTEPH,including surgery,angioplasty,and medical treatment,depending on the location and characteristics of lesions.Pulmonary endarterectomy(PEA)is the treatment of choice for CTEPH,as it offers excellent long-term outcomes and a high probability of recovery.Moreover,various medical and interventional therapies are currently being developed for patients with inoperable CTEPH.This review mainly summarizes the current treatment approaches of CTEPH,offering more options for specialist physicians to,thus,better manage chronic thromboembolic syndromes.

Angiotensin-converting enzyme and bradykinin gene polymorphisms and cough:A meta-analysis

AIM:To evaluate the association between genetic polymorphisms and angiotensin converting enzyme in-hibitor (ACEI)-related cough,and the race-or ethnicity-related difference in the prevalence of cough attributed to ACEI therapy.METHODS:We conducted a search in PubMed,EM-BASE,Cinahl,and the Cochrane Database without language limitation.A database of 11 studies on ACEI-related cough,with detailed information regarding ACE I/D or bradykinin B 2 receptor polymorphisms,was created.Eligible studies were synthesized using meta-analysis methods,including cumulative meta-analysis.A subgroup analysis was also performed using ethnicity.RESULTS:Six studies were included on ACE I/D poly-morphism (398 Caucasians,723 East Asians),and three studies were included on bradykinin B 2 receptor poly-morphism (300 East Asians).The distribution of ACE genotypes showed significant differences in the entire population (P=0.004) and in East Asians (P=0.005)but not in Caucasians (P=0.23).Allelic frequencies of ACE showed significant differences in East Asians [odds ratio (OR)=1.49 (1.11-2.02)].The meta-analysis with a random effects model showed a significant associa-tion between ACE allele I/D and ACEI-related cough [random effects (RE) OR=1.49 (1.11-2.02),P=0.009] in East Asians,but not in Caucasians [RE OR=0.90 (0.60-1.35)].The allelic frequencies of the bradykinin B 2 receptor gene were significantly different [OR=2.25 (1.42-3.57)].The distributions of the T/C genotypes of the bradykinin B 2 receptor gene were significantly dif-ferent (χ 2=8.366,P=0.015).The meta-analyses re-vealed that there was a significant association between the bradykinin B 2 receptor allele and ACEI-related cough in East Asians [RE OR=2.29 (1.42-3.69),P=0.001].CONCLUSION:ACE I/D and Bradykinin B 2 receptor polymorphisms contributed to the risk of ACEI-related cough in East Asians,but a negative association be-tween ACE I/D polymorphism and ACEI-related cough was observed in Caucasians.

Severe pneumonia and acute myocardial infarction complicated with pericarditis after percutaneous coronary intervention:A case report

BACKGROUND Cases of severe pneumonia complicated with acute myocardial infarction(AMI)with good prognosis after percutaneous coronary intervention(PCI)are rare,especially those with postoperative pericarditis and intestinal obstruction.CASE SUMMARY A 53-year-old male patient was admitted to the emergency department of our hospital because of paroxysmal chest tightness for 4 d,aggravated with chest pain for 12 h.The symptoms,electrocardiography,biochemical parameters,echocardiography and chest computed tomography confirmed the diagnosis of severe pneumonia complicated with AMI.The patient was treated with antiplatelet aggregation,anticoagulation,lipid regulation,vasodilation,anti-infective agents and direct PCI.The patient was discharged after 3 wk of treatment.Follow-up showed that the patient was asymptomatic without recurrence.CONCLUSION For patients with severe pneumonia complicated with AMI,PCI and antibiotic therapy is a life-saving strategy.

Hypoxia response element-directed expression of bFGF in dental pulp stem cells improve the hypoxic environment by targeting pericytes in SCI rats

Cell-based transplantation strategies possess great potential for spinal cord injury(SCI)repair.Basic fibroblast growth factor(bFGF)has been reported to have multiple neuro-promoting effects on developing and adult nervous system of mammals and considered a promising therapy for nerve injury following SCI.Human dental pulp stem cells(DPSCs)are abundant stem cells with low immune rejection,which can be considered for cell replacement therapy.The purpose of this study was to investigate the roles of DPSCs which express bFGF under the regulation of five hypoxia-responsive elements(5HRE)using an adeno-associated virus(AAV-5HRE-bFGF-DPSCs)in SCI repairing model.In this study,DPSCs were revealed to differentiate into CD13^(+)pericytes and up-regulate N-cadherin expression to promote the re-attachment of CD13^(+)pericytes to vascular endothelial cells.The re-attachment of CD13^(+)pericytes to vascular endothelial cells subsequently increased the flow rate of blood in microvessels via the contraction of protuberance.As a result,increased numbers of red blood cells carried more oxygen to the damaged area and the local hypoxia microenvironment in SCI was improved.Thus,this study represents a step forward towards the potential use of AAV-5HRE-bFGF-DPSCs in SCI treatment in clinic.

Long-term amelioration of an early-onset familial atrial fibrillation model with AAV-mediated in vivo gene therapy

Atrial fibrillation(AF)is a common cardiac disease with high prevalence in the general population.Despite a mild manifestation at the onset stage,it causes serious consequences,including sudden death,when the disease progresses to the late stage.Most available treatments of AF focus on symptom management or alleviation,due to a lack of fundamental knowledge and the fact that considerable variations of AF exist.With the popularisation of the next-generation sequencing technology,several causal genetic factors,including MYL4,have been discovered to contribute to AF,giving hope to developing its gene therapies.In this study,we attempted to treat a previously established rat AF model,which carried Myl4E11K/E11K loss of function mutation,via overexpression of exogenous wild-type Myl4 by AAV9 vectors.Our results showed that delivery of Myl4 expressing AAV9 to postnatal rat models rescued the symptoms of AF,indicating the therapeutic potential that early gene therapy intervention can achieve long-term effects in treating cardiac arrhythmias caused by gene mutations.

A cardioembolic stroke

A 76-year-old woman with unspecified congenital heart disease was admitted on April 25th for TIA. She had a possible history of atrial fibrillation. A slight fever was noted on admission. Her ECG was abnormal, as well as her transthoracic echocardiography (TTE). Troponin I was slightly increased. On May 11th, a stroke occurred, in relation with an occlusion of the basilar artery. The patient was transferred to our institution for an emergency desobstruction. A dramatic improvement allowed her to be discharged to a rehabilitation center on May 18th. However, she was re-hospitalized on June 5th, due to sepsis and neurological worsening. MRI showed new ischemic brain lesions. Several episodes of paroxysmal atrial fibrillation were documented, as well as pulmonary hypertension. Effective heparin therapy was initiated and transesophageal echocardiography (TEE) was requested this time. It revealed a congenital valvular heart disease (a subaortic membrane), complicated by infective endocarditis. Despite a monitoring of aPTT, a fatal hemorrhagic shock occurred. We report this unfortunately remarkable case to address the following important points: 1) In the setting of a neurological event, abnormal ECG and/or abnormal TTE and/or Troponin I elevation may indicate a cardioembolic mechanism and therefore seek a cardiac source of embolism. 2) When TTE fails to identify a cardiac source of embolism, TEE should be performed, especially when a preexisting heart disease is suspected or known. 3) The multiplicity in space (infarcts in both the anterior and posterior circulation, or bilateral) and/or the multiplicity in time (infarcts of different age) may indicate a cardioembolic stroke. 4) Congenital subaortic membrane predisposes to infective endocarditis. 5) When anticoagulant therapy is initiated on strong arguments in a septic patient (much discussed in infective endocarditis), aPTT monitoring alone may not be enough. An anti-Xa monitoring may be more appropriate.

稳定型和不稳定型心绞痛患者血清白介素-18水平的比较

Recent evidence suggests that atherosclerosis is an inflammatory disorder in which cytokines appear to play an important role. Special attention centered over the possible contribution of cytokines to the destabilization of the plaque. IL-18 is a proinflammatory cytokine of the IL-1 family, recognized for its ability to promote IFN-γsecretion. It has recently been detected in human plaques and its administration was associated with increased atheros-clerosis in apolipoprotein E(apoE) mice concomitant with an increase in plaque infiltrating inflammatory cells. In our study, we investigated whether patients with established atherosclerosis, with either stable or unstable angina, possessed high levels of IL-18. Patients with stable angina(n=48) were from the outpatient clinic whereas patients with unstable angina(n=73) were recruited upon admission and prior to performance of coronary angiography. Control patients(n=19) were healthy subjects with no evidence of coronary artery disease. Serum levels of IL-18 were assayed by ELISA. Patients with stable and unstable angina exhibited higher serum levels of IL-18(77.1±7.2 and 61.5±5.1 pg/ml, respectively) in comparison to control subjects(p=0.002 and p=0.02, respectively). However, levels of IL-18 did not differ significantly between patients with stable and unstable angina. No differences were evident in the serum concentrations of IL-18 in patients with unstable angina(n=17) upon admission and 1-3 months later when the angina was already controlled. Although IL-18 serum levels appear elevated in the presence of coronary atherosclerosis, there is no evidence to associate this progression towards plaque instability.

奈比洛尔对高血压患者血小板激活的影响:与美托洛尔的比较研究

目的：通过测定平均血小板体积（MPV）和血浆可溶性P-选择素（SP-sel）水平来评价奈比洛尔对高血压患者血小板激活的影响，并与服用美托洛尔的患者进行了比较。方法：共有80例新近诊断为高血压1级的患者被纳入此项随机化、盲法、前瞻性研究。72例患者完成了研究。经过基线评估后，随机分配患者接受5mg／d奈比洛尔（n=37，男性20例）或100mg／d美托洛尔（n=35，男性18例），共治疗6个月。分别在治疗前后，测定患者的血压、心率、血脂、血糖、SP-sel水平、血小板计数和MPV。

Modified Double-Fenestrated Stent Graft for Branched Thoracic Endovascular Aortic Repair of an Irregular Aortic Arch Aneurysm:A Case Report

A 43-year-old male was admitted to General Hospital of Northern Theater Command with exacerbation of chest pain for 10 d.Computed tomographic angiography(CTA)showed an irregular aortic arch aneurysm involving the left subclavian artery(LSA),with penetrating aortic ulcer and intramural hematoma.A modified fenestrated thoracic endovascular aortic repair(TEVAR)technique was performed successfully.Follow-up CTA showed that stent grafts were well-apposed,without endoleaks,migration,or branch artery occlusion,and the hematoma was almost completely absorbed.In this case,precise fenestrations were created by measurements based on three-dimensional CT reconstruction and angiography.Furthermore,the physician chose an LSA approach to catch the guide wire and deployed branched stent grafts,considering the oblique direction of this branch and the small size of the fenestration.This case shows that pre-fenestrated and inner bare stent enhancing TEVAR is a safe and feasible technique for repair of complicated aortic arch aneurysm.

Timing and mode of intervention for patients with left sided valvular heart disease:an individualized approach

Left sided valvular heart disease poses major impact on life and lifestyle.Medical therapy merely palliates chronic severe valve disease and once symptoms or haemodynamic sequelae appear,life expectancy is markedly truncated.In this article,we review the mechanisms of valve pathology,latest evidence in the quest for pharmacological options,means by which to predict deterioration,and standard and novel treatment options.

健康志愿者心脏指数的无创性评估：胸阻抗心动图与多普勒超声心动图的对比研究

背景胸阻抗心动图（ICG），一直被认为是一种无创性、连续性、可独立操作且经济有效的方法，用于监测心输出量。本研究比较了在静息状态下改变健康志愿者血流动力学参数时，胸阻抗心动图（Niccomo装置）与经胸超声多普勒心动图对心脏指数（CI）的测量情况。方法本研究共纳入了25例健康志愿者（7例男性，18例女性；平均年龄36±6岁；体表面积1．75±0．17m^2），分别在3种实验条件进行测定：基础水平、呼气末正压通气（＋10cm H2O）、下半身加压（用医疗抗休克裤对腹部施加30cm H2O的压力）。结果在所有测量中，胸阻抗心动图的信号质量〉89％。胸阻抗心动图与多普勒心动图测定的心脏指数（CITTE和CIICG）间存在着较弱但有统计学意义的相关性（r=0．36；P=0．002）。2种技术测得的心脏指数的一致性数值为0．94L·min^-1·m^-2（95％可信区间0．77—1．11）；一致性可变范围为-0．47—2．35L·min^-1·m^-2，误差百分率为53％。施加呼气末正压＋10cm H2O（r=0．21；P=0．31）或医疗抗休克裤（r=0．22；P=0．30）后，CITTE和CIICG的变化率之间的相关性没有统计学意义。结论采用胸阻抗心动图与多普勒心动图测量健康志愿者静息状态下的CI，两者测量所得CI的绝对值相关性较差，缺乏一致性。在血流动力学变化时，使用Niccomo装置测量心脏指数的变化也缺乏可靠性.

六维生物样本银行的概念及其推动罕见病新药研发的作用

In 2001, Dr. Zhi-Cheng Jing encountered a pulmonary arterial hypertension (PAH) patient from a large pedigree. Dr. Jing collected the clinical information and blood samples from this pedigree and was the first to report the pedigree of familial PAH in China [1]. In2004, this pedigree was confirmed to carry a mutation in BMPR2(Arg491Trp), which was the first evidence of pathogenicity of BMPR2 mutation in the Chinese population [2].

Early diagnostic value for contrast-induced nephropathy in patients undergoing coronary angiography:Serum cystatin C might not be superior to serum creatinine

Background Contrast induced nephropathy(CIN) is associated with increased mortality. serum creatinine(sCr) and serum cystatin C(sCys C) have diagnostic value for CIN in patients taking coronary angiography(CAG). However, whether sCys C is superior to sCr is still controversial. Methods All 280 patients undergoing PCI from July 2015 to July 2017 in Shunde Hospital, Southern Medical University were enrolled in this prospective study. The plasma levels of sCr and sCys C were measured in fasting blood samples in the morning before angiography and at 48 hours and 72 hours after the procedure. Receiver operating characteristic curve(ROC)analysis was performed for sCr and sCys C 48 hours after procedure. Results According to sCys C criteria, CIN occurred in 85 patients(30.4%) after contrast exposure, while, CIN occurred in 22 patients(7.9%). ROC curve analysis found that AUC for sCr and sCys C was 0.741(P<0.05, 95% CI = 0.613-0.869) and 0.720(P<0.05, 95%CI = 0.590-0.851), respectively without significantly different(P=0.412). Conclusion The sCys C is not superior to s Cr for predicting CIN in angiography patients.