Decline in Serum Cholinesterase Activities Predicts 2-Year Major Adverse Cardiac Events

Parasympathetic activity influences long-term outcome in patients with cardiovascular disease, but the underlying mechanism(s) linking parasympathetic activity and the occurrence of major adverse cardiovascular events (MACEs) are incompletely understood. The aim of this pilot study was to evaluate the association between serum cholinesterase activities as parasympathetic biomarkers and the risk for the occurrence of MACEs. Cholinergic status was determined by measuring the cumulative capacity of serum acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) to hydrolyze the AChE substrate acetylthiocholine. Cholinergic status was evaluated in randomly selected patients undergoing cardiac catheterization. The patients were divided into two groups of 100 patients in each group, with or without occurrence of MACEs during a follow-up period of 40 months. Cox regression models adjusted for potential clinical, metabolic and inflammatory confounders served to evaluate association with clinical outcome. We found that patients with MACE presented lower cholinergic status and AChE values at catheterization (1,127 ± 422 and 359 ± 153 nmol substrate hydrolyzed per minute per milliliter, respectively) than no-MACE patients (1,760 ± 546 and 508 ± 183 nmol substrate hydrolyzed per minute per milliliter, p < 0.001 and p < 0.001, respectively), whose levels were comparable to those of matched healthy controls (1,622 ± 303 and 504 ± 126 nmol substrate hydrolyzed per minute per milliliter, respectively). In a multivariate analysis, patients with AChE or total cholinergic status values below median showed conspicuously elevated risk for MACE (hazard ratio 1.85 [95% confidence interval [CI] 1.09–3.15, p = 0.02] and 2.21 [95% CI 1.22–4.00, p = 0.009]) compared with those above median, even after adjusting for potential confounders. We conclude that parasympathetic dysfunction expressed as reduced serum AChE and AChE activities in patients compared to healthy controls can together reflect impaired parasympathetic activity. This impairment predicts the risk of MACE up to 40 months in such patients. Monitoring these parasympathetic parameters might help in the risk stratification of patients with cardiovascular disease.     

Renal Function Interferes with Copeptin in Prediction of Major Adverse Cardiac Events in Patients Undergoing Vascular Surgery

Objective

Precise perioperative risk stratification is important in vascular surgery patients who are at high risk for major adverse cardiovascular events (MACE) peri- and postoperatively. In clinical practice, the patient’s perioperative risk is predicted by various indicators, e.g. revised cardiac index (RCRI) or modifications thereof. Patients suffering from chronic kidney disease (CKD) are stratified into a higher risk category. We hypothesized that Copeptin as a novel biomarker for hemodynamic stress could help to improve the prediction of perioperative cardiovascular events in patients undergoing vascular surgery including patients with chronic kidney disease.

Methods

477 consecutive patients undergoing abdominal aortic, peripheral arterial or carotid surgery from June 2007 to October 2012 were prospectively enrolled. Primary endpoint was 30-day postoperative major adverse cardiovascular events (MACE).

Results

41 patients reached the primary endpoint, including 63.4% aortic, 26.8% carotid, and 9.8% peripheral surgeries. Linear regression analysis showed that RCRI (P< .001), pre- (P< .001), postoperative Copeptin (P< .001) and Copeptin level change (P= .001) were associated with perioperative MACE, but CKD remained independently associated with MACE and Copeptin levels. Multivariate regression showed that increased Copeptin levels added risk predictive information to the RCRI (P= .003). Especially in the intermediate RCRI categories was Copeptin significantly associated with the occurrence of MACE. (P< .05 Kruskal Wallis test). Subdivision of the study cohort into CKD stages revealed that preoperative Copeptin was significantly associated with CKD stages (P< .0001) and preoperative Copeptin measurements could not predict MACE in patients with more severe CKD stages.

Conclusion

Preoperative Copeptin loses its risk predictive potential for perioperative MACE in patients with chronic kidney disease undergoing vascular surgery.     

他汀预处理对急性冠脉综合症患者住院期间MACCE发生率的影响

目的:探讨入院前他汀药物预处理对急性冠脉综合征患者住院期间主要心脑血管事件(MACCE)发生的影响.方法:回顾性分析2000年1月-2006年9月我院心内科急性冠脉综合症患者650例,他汀治疗组(n=350)和非他汀预处理组(n=300).采用多因素logistic回归分析他汀预处理对急性冠脉综合症患者的在住院期间的主要心脑血管事件的影响.结果:多元回归分析结果显示他汀类预处理组住院期间的死亡率和总的MACCE事件低于与非他汀预处理组,分别为0.9%(VS 1.3%)和2.9%(VS 4.8%).结论:他汀的预处理可以减低住院期间总心血管事件和住院期阃死亡率的风险,为住院期间死亡率和总MACCE事件的独立的预测因素.     

血清NT-proBNP 与hs-CRP在预测急性ST段抬高性心肌梗死主要心脏 不良事件的价值

目的:探讨血清N末端脑钠肽前体(NT-pro BNP)及超敏C反应蛋白(hs-CRP)在预测急性ST段抬高性心肌梗死(STEMI)近期主要心脏不良事件(MACE)的价值。方法:选取172例STEMI患者为研究对象,按照住院期间是否发生MACE分为MACE组(n=56例)和非MACE组(n=116例),记录两组之间的入院时血清NT-pro BNP及hs-CRP水平及一般临床资料及实验室检查指标,将NT-pro BNP及hs-CRP水平按照四分位分组(Q_1、Q_2、Q_3和Q_4组),比较各组相关指标的差异,用多因素Logistic回归模型分析NT-pro BNP及hs-CRP水平与MACE发生的关系,用ROC曲线评价血清NT-pro BNP及hs-CRP预测MACE发生的价值。结果:MACE组和非MACE组在血清NT-pro BNP及hs-CRP存在显著的统计学差异(P0.05),MACE组两指标高于非MACE组;两者四分位分组之间MACE发生率存在统计学差异(P0.05),NT-pro BNP Q_4组和hs-CRP Q_4组中的MACE发生率高于NT-pro BNP Q_1~Q_2组及hs-CRP Q_1~Q_2组;多因素Logistic回归分析显示血清NT-pro BNP及hs-CRP是STEMI患者近期MACE发生的独立危险因素,且NT-pro BNP Q_1~Q_4组及hs-CRP Q_1~Q_4组之间风险值(OR)逐渐增大。ROC曲线提示血清NT-pro BNP及hs-CRP预测MACE发生的ROCACU分别为:0.887、0.797;灵敏度分别为91.1、85.6;特异度分别为82.6、75.2。结论:血清NT-pro BNP及hs-CRP可能是STEMI患者近期MACE发生的独立危险因素,应当引起临床重视。     

早期心电图QRS 波宽度对急性ST 段抬高型心肌梗死患者心脏不良事件的影响

目的:探讨早期心电图QRS波宽度(QRSw)对急性ST段抬高型心肌梗死(STEMI)患者近期主要心脏不良事件(MACE)的影响。方法:选取我院收治的135例STEMI患者为研究对象,按照入院时的心电图QRSw将患者分为A组(QRSw为60 ms≤QRSw≤80 ms)、B组(QRSw为80 msQRSw100 ms)、C组(QRSw为QRSw≥100 ms),将是否发生MACE分为MACE组和非MACE组,比较各组相关指标的差异,分析QRSw与MACE发生的关系。结果:A、B及C组三组患者在梗死面积、肌酸激酶同工酶(CK-MB)、肌钙蛋白I(c Tn I)、B型脑钠肽(BNP)、高敏C反应蛋白(hs-CRP)、左室射血分数(LVEF)方面存在显著的统计学差异(P0.05),与A组及B组比较,C组血清hs-CRP、BNP、c Tn I、CK-MB较高,梗死面积大、LVEF偏低。三组患者在MACE发生率方面亦存在显著的统计学差异(P0.05),C组高于A组及B组。MACE组患者QRSw高于非MACE组(P0.05),其含有QRSw≥100 ms患者的比例亦高于非MACE组(P0.05);QRSw(OR=1.214,CI:1.104~1.441,P0.05)是STEMI患者近期MACE发生的独立危险因素。结论:STEMI患者随着QRSw增大,MACE的发生风险亦增加,QRSw可能是STEMI患者近期MACE发生的独立危险因素,应当引起临床重视。     

Increased Cardiac Myocyte PDE5 Levels in Human and Murine Pressure Overload Hypertrophy Contribute to Adverse LV Remodeling

Background

The intracellular second messenger cGMP protects the heart under pathological conditions. We examined expression of phosphodiesterase 5 (PDE5), an enzyme that hydrolyzes cGMP, in human and mouse hearts subjected to sustained left ventricular (LV) pressure overload. We also determined the role of cardiac myocyte-specific PDE5 expression in adverse LV remodeling in mice after transverse aortic constriction (TAC).

Methodology/Principal Findings

In patients with severe aortic stenosis (AS) undergoing valve replacement, we detected greater myocardial PDE5 expression than in control hearts. We observed robust expression in scattered cardiac myocytes of those AS patients with higher LV filling pressures and BNP serum levels. Following TAC, we detected similar, focal PDE5 expression in cardiac myocytes of C57BL/6NTac mice exhibiting the most pronounced LV remodeling. To examine the effect of cell-specific PDE5 expression, we subjected transgenic mice with cardiac myocyte-specific PDE5 overexpression (PDE5-TG) to TAC. LV hypertrophy and fibrosis were similar as in WT, but PDE5-TG had increased cardiac dimensions, and decreased dP/dt_max and dP/dt_min with prolonged tau (P<0.05 for all). Greater cardiac dysfunction in PDE5-TG was associated with reduced myocardial cGMP and SERCA2 levels, and higher passive force in cardiac myocytes in vitro.

Conclusions/Significance

Myocardial PDE5 expression is increased in the hearts of humans and mice with chronic pressure overload. Increased cardiac myocyte-specific PDE5 expression is a molecular hallmark in hypertrophic hearts with contractile failure, and represents an important therapeutic target.     

Ferritin in the Serum of Normal Subjects and Patients with Iron Deficiency and Iron Overload

The concentration of ferritin in serum gives a quantitative measure of the amount of storage iron in normal subjects and those with iron deficiency or overload. The mean level in normal men is 69 ng/ml, compared with 35 ng/ml in normal women. A concentration below 10 ng/ml is associated with a low transferrin saturation and iron-deficient erythropoiesis.     

抗阻训练联合八段锦对慢性心力衰竭患者心功能、生活质量和不良心脏事件的影响

摘要 目的：观察抗阻训练联合八段锦对慢性心力衰竭（CHF）患者心功能、生活质量和不良心脏事件的影响。方法：纳入2019年6月~2020年7月期间湖南中医药大学第一附属医院心血管内科收治的120例CHF患者,按随机数表法分为对照组、研究组各60例。两组均采取常规抗心衰治疗,在此基础上,对照组接受抗阻训练,研究组接受抗阻训练联合八段锦训练,两组均干预6个月。对比两组疗效以及干预前、干预6个月后的心功能、生活质量,记录随访期间不良心脏事件发生情况。结果：研究组的临床总有效率高于对照组（P<0.05）。干预6个月后,研究组左室收缩末期内径（LVESD）、左室舒张末期内径（LVEDD）小于对照组,左心室射血分数（LVEF）大于对照组（P<0.05）。干预6个月后,研究组SF-36各维度（躯体健康、心理健康、总体健康、情绪功能、躯体功能、社会功能、躯体疼痛、精力）评分高于对照组（P<0.05）。研究组的不良心脏事件发生率低于对照组（P<0.05）。结论：抗阻训练联合八段锦可有效改善CHF患者心功能,提高其生活质量,并降低不良心脏事件发生率。     

ESA Hyporesponsiveness Is Associated with Adverse Events in Maintenance Hemodialysis (MHD) Patients,But Not with Iron Storage

Objective

It has been reported that hyporesponsiveness to erythropoiesis-stimulating agent (ESA) is associated with adverse events in patients on maintenance hemodialysis (MHD). However, it has not been determined whether higher iron storage is associated with an improved response, including better survival, to ESA.

Design and Method

We measured serum ferritin, hemoglobin (Hb), and transferrin saturation (TSAT) levels every three months for two years in 1,095 MHD patients. The weekly dose of ESA to Hb ratio was also calculated as an index of ESA responsiveness (ERI).

Results

A significant correlation (p<0.001, R = 0.89) between ferritin and Hb was only observed in the patients with ferritin levels <50 ng/mL. High-dose (≥50 mg/week) intravenous iron administration, female sex, low serum albumin, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use were significant predictors of a high ERI value (>280); however, serum ferritin and TSAT levels did not predict a higher ERI. In the time-dependent Cox hazard model, the risk for a composite event in the patients with a high ERI (≥280) and a high ferritin level (≥100 ng/mL) was significantly greater (hazard ratio [HR], 2.09, P = 0.033) than that for patients with a high ERI and a low ferritin (<100 ng/mL) level.

Conclusion

Hb was dependent upon ferritin levels in patients with ferritin levels <50 ng/mL but not in patients with ferritin levels ≥50 ng/mL. Patients with hyporesponsiveness to ESA had a greater risk of composite events, but ERI was unrelated to iron storage.     

Interplay between Genetic and Clinical Variables Affecting Platelet Reactivity and Cardiac Adverse Events in Patients Undergoing Percutaneous Coronary Intervention

Several clinical and genetic variables are associated with influencing high on treatment platelet reactivity (HTPR). The aim of the study was to propose a path model explaining a concurrent impact among variables influencing HTPR and ischemic events. In this prospective cohort study polymorphisms of CYP2C19*2, CYP2C19*17, ABCB1, PON1 alleles and platelet function assessed by Multiple Electrode Aggregometry were assessed in 416 patients undergoing percutaneous coronary intervention treated with clopidogrel and aspirin. The rates of major adverse cardiac events (MACE) were recorded during a 12-month follow up. The path model was calculated by a structural equation modelling. Paths from two clinical characteristics (diabetes mellitus and acute coronary syndrome (ACS)) and two genetic variants (CYP2C19*2 and CYP2C19*17) independently predicted HTPR (path coefficients: 0.11 0.10, 0.17, and -0.10, respectively; p<0.05 for all). By use of those four variables a novel score for prediction of HTPR was built: in a factor-weighted model the risk for HTPR was calculated with an OR of 3.8 (95%CI: 3.1–6.8, p<0.001) for a score level of ≥1 compared with a score of <1. While MACE was independently predicted by HTPR and age in the multivariate model (path coefficient: 0.14 and 0.13, respectively; p<0.05), the coexistence of HTPR and age ≥75 years emerged as the strongest predictor of MACE. Our study suggests a pathway, which might explain indirect and direct impact of variables on clinical outcome: ACS, diabetes mellitus, CYP2C19*2 and CYP2C19*17 genetic variants independently predicted HTPR. In turn, age ≥75 years and HTPR were the strongest predictors of MACE.     

Angiopoietin-2 as a Prognostic Biomarker of Major Adverse Cardiovascular Events and All-Cause Mortality in Chronic Kidney Disease

Background

Chronic kidney disease (CKD) patients have higher prevalence of major adverse cardiovascular events (MACE) and all-cause mortality. Endothelial damage and dysfunction have been regarded as early portents of MACE in CKD patients. Angiopoietin-2 (Ang-2) impairs endothelial function and promotes aberrant neovascularization. The aim of the study was to assess the relationship between circulating Ang-2 and MACE or all-cause mortality in a CKD cohort.

Methods

A total of 621 pre-dialysis stage 3–5 CKD patients were enrolled from January 2006 to December 2011 and were followed up till October 2014. Plasma Ang-2 was measured in duplicate using commercial enzyme-linked immunosorbent assays (ELISA). Clinical outcomes included MACE or all-cause mortality

Results

Of all patients, 122 (19.8%) reached MACE or all-cause mortality. Seventy-two had MACE, 79 died, and 29 had both MACE and all-cause mortality during the follow-up period of 41.5±28.3 months. Ang-2 quintile was divided at 1405.0, 1730.0, 2160.9, and 2829.9 pg/ml. The adjusted HR of MACE or all-cause mortality for every single higher log Ang-2 was 5.69 (95% CI: 2.00–16.20, P = 0.001). The adjusted HR of MACE or all-cause mortality was 2.48 (95% CI: 1.25–4.90) for patients of quintile 5 compared with those of quintile 1. A longitudinal association between MACE or all-cause mortality and stepwise increases in Ang-2 levels was found (P-trend = 0.008).

Conclusions

Ang-2 is an independent predictor of MACE or all-cause mortality in CKD patients. Additional study is necessary in order to explore the mechanism of the association of Ang-2 with adverse outcomes in patients with CKD.     

Short- and Long-Term Major Cardiovascular Adverse Events in Carotid Artery Interventions: A Nationwide Population-Based Cohort Study in Taiwan

Introduction

Carotid artery stenosis is one of the leading causes of ischemic stroke. Carotid artery stenting has become well-established as an effective treatment option for carotid artery stenosis. For this study, we aimed to determine the efficacy and safety of carotid stenting in a population-based large cohort of patients by analyzing the Taiwan National Healthcare Insurance (NHI) database.

Methods

2,849 patients who received carotid artery stents in the NHI database from 2004 to 2010 were identified. We analyzed the risk factors of outcomes including major adverse cardiovascular events including death, acute myocardial infarction, and cerebral vascular accidents at 30 days, 1 year, and overall period and further evaluated cause of death after carotid artery stenting.

Results

The periprocedural stroke rate was 2.7% and the recurrent stroke rate for the overall follow-up period was 20.3%. Male, diabetes mellitus, and heart failure were significant risk factors for overall recurrent stroke (Hazard Ratio (HR) = 1.35, p = 0.006; HR = 1.23, p = 0.014; HR = 1.61, p < 0.001, respectively). The periprocedural acute myocardial infarction rate was 0.3%. Age and Diabetes mellitus were the significant factors to predict periprocedural myocardial infarction (HR = 3.06, p = 0.019; HR = 1.68, p < 0.001, respectively). Periprocedural and overall mortality rates were 1.9% and 17.3%, respectively. The most significant periprocedural mortality risk factor was acute renal failure. Age, diabetes mellitus, acute or chronic renal failure, heart failure, liver disease, and malignancy were factors correlated to the overall period mortality.

Conclusion

Periprocedural acute renal failure significantly increased the mortality rate and the number of major adverse cardiovascular events, and the predict power persisted more than one year after the procedure. Age and diabetes mellitus were significant risk factors to predict acute myocardial infarction after carotid artery stenting.     

心悦胶囊联合替罗非班对急性心肌梗死PCI术患者心功能及心血管不良事件的影响

摘要 目的：观察心悦胶囊联合替罗非班对急性心肌梗死（AMI）经皮冠状动脉介入治疗（PCI）术患者心功能及心血管不良事件的影响。方法：选取120例行PCI术治疗的AMI患者,将其按随机信封抽签法分为对照组60例（替罗非班治疗）和研究组60例（心悦胶囊联合替罗非班治疗）,对比两组疗效、临床症状改善情况、心肌肌钙蛋白I（cTnI）、左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)、左室射血分数（LVEF）、肌酸激酶同工酶（CK-MB）、脑钠肽(BNP)、不良反应、心血管不良事件发生率及预后情况。结果：对照组、研究组临床总有效率分别为75.00%（45/60）、90.00%（54/60）,研究组的临床总有效率高于对照组（P<0.05）。研究组胸痛、胸闷,恶心呕吐,大汗缓解率高于对照组（P<0.05）,两组心悸、气短,乏力,晕厥,大小便失禁对比无差异（P>0.05）。研究组治疗后LVEDD为（49.38±6.73）mm,LVESD为（38.14±4.35）mm,低于对照组的（55.27±5.24）mm、（43.73±5.24）mm,LVEF为（57.09±4.34）%,高于对照组的（52.63±5.33）%（P<0.05）。研究组治疗后CK-MB为（13.46±2.34）ng/mL、cTnI为（0.29±0.08）μg/L、BNP为（363.44±29.66）pg/mL,低于对照组的（24.75±2.63）ng/mL、（0.41±0.12）μg/L、（548.12±57.61）pg/mL（P<0.05）。对照组、研究组的不良反应发生率分别为8.33%（5/60）、11.67%（7/60）,两组不良反应发生率对比无差异（P>0.05）。对照组、研究组的心血管不良事件发生率分别为5.00%（3/60）、16.67%（10/60）,研究组的心血管不良事件发生率低于对照组（P<0.05）。结论：心悦胶囊联合替罗非班可保护行PCI术的AMI患者的心功能,减少心血管不良事件发生率,用药安全可靠,疗效明确。     

CXCL17 Expression Predicts Poor Prognosis and Correlates with Adverse Immune Infiltration in Hepatocellular Carcinoma

CXC ligand 17 (CXCL17) is a novel CXC chemokine whose clinical significance remains largely unknown. In the present study, we characterized the prognostic value of CXCL17 in patients with hepatocellular carcinoma (HCC) and evaluated the association of CXCL17 with immune infiltration. We examined CXCL17 expression in 227 HCC tissue specimens by immunohistochemical staining, and correlated CXCL17 expression patterns with clinicopathological features, prognosis, and immune infiltrate density (CD4 T cells, CD8 T cells, B cells, natural killer cells, neutrophils, macrophages). Kaplan-Meier survival analysis showed that both increased intratumoral CXCL17 (P = 0.015 for overall survival [OS], P = 0.003 for recurrence-free survival [RFS]) and peritumoral CXCL17 (P = 0.002 for OS, P<0.001 for RFS) were associated with shorter OS and RFS. Patients in the CXCL17^low group had significantly lower 5-year recurrence rate compared with patients in the CXCL17^high group (peritumoral: 53.1% vs. 77.7%, P<0.001, intratumoral: 58.6% vs. 73.0%, P = 0.001, respectively). Multivariate Cox proportional hazards analysis identified peritumoral CXCL17 as an independent prognostic factor for both OS (hazard ratio [HR] = 2.066, 95% confidence interval [CI] = 1.296–3.292, P = 0.002) and RFS (HR = 1.844, 95% CI = 1.218–2.793, P = 0.004). Moreover, CXCL17 expression was associated with more CD68 and less CD4 cell infiltration (both P<0.05). The combination of CXCL17 density and immune infiltration could be used to further classify patients into subsets with different prognosis for RFS. Our results provide the first evidence that tumor-infiltrating CXCL17⁺ cell density is an independent prognostic factor that predicts both OS and RFS in HCC. CXCL17 production correlated with adverse immune infiltration and might be an important target for anti-HCC therapies.     

Cognitive Inflexibility in Obsessive-Compulsive Disorder and Major Depression Is Associated with Distinct Neural Correlates

Obsessive-compulsive disorder (OCD) and major depressive disorder (MDD) are frequently co-morbid, and dysfunctional frontal-striatal circuits have been implicated in both disorders. Neurobiological distinctions between OCD and MDD are insufficiently clear, and comparative neuroimaging studies are extremely scarce. OCD and MDD may be characterized by cognitive rigidity at the phenotype level, and frontal-striatal brain circuits constitute the neural substrate of intact cognitive flexibility. In the present study, 18 non-medicated MDD-free patients with OCD, 19 non-medicated OCD-free patients with MDD, and 29 matched healthy controls underwent functional magnetic resonance imaging during performance of a self-paced letter/digit task switching paradigm. Results showed that both patient groups responded slower relative to controls during repeat events, but only in OCD patients slowing was associated with decreased error rates. During switching, patients with OCD showed increased activation of the putamen, anterior cingulate and insula, whereas MDD patients recruited inferior parietal cortex and precuneus to a lesser extent. Patients with OCD and MDD commonly failed to reveal anterior prefrontal cortex activation during switching. This study shows subtle behavioral abnormalities on a measure of cognitive flexibility in MDD and OCD, associated with differential frontal-striatal brain dysfunction in both disorders. These findings may add to the development of biological markers that more precisely characterize frequently co-morbid neuropsychiatric disorders such as OCD and MDD.     

Hippocampal Synaptic Expansion Induced by Spatial Experience in Rats Correlates with Improved Information Processing in the Hippocampus

Spatial water maze (WM) overtraining induces hippocampal mossy fiber (MF) expansion, and it has been suggested that spatial pattern separation depends on the MF pathway. We hypothesized that WM experience inducing MF expansion in rats would improve spatial pattern separation in the hippocampal network. We first tested this by using the the delayed non-matching to place task (DNMP), in animals that had been previously trained on the water maze (WM) and found that these animals, as well as animals treated as swim controls (SC), performed better than home cage control animals the DNMP task. The “catFISH” imaging method provided neurophysiological evidence that hippocampal pattern separation improved in animals treated as SC, and this improvement was even clearer in animals that experienced the WM training. Moreover, these behavioral treatments also enhance network reliability and improve partial pattern separation in CA1 and pattern completion in CA3. By measuring the area occupied by synaptophysin staining in both the stratum oriens and the stratun lucidum of the distal CA3, we found evidence of structural synaptic plasticity that likely includes MF expansion. Finally, the measures of hippocampal network coding obtained with catFISH correlate significantly with the increased density of synaptophysin staining, strongly suggesting that structural synaptic plasticity in the hippocampus induced by the WM and SC experience is related to the improvement of spatial information processing in the hippocampus.     

Matrix Metalloproteinase 7 Is Associated with Symptomatic Lesions and Adverse Events in Patients with Carotid Atherosclerosis

Background

Atherosclerosis is a major cause of cerebrovascular disease. Matrix metalloproteinases (MMPs) play an important role in matrix degradation within the atherosclerotic lesion leading to plaque destabilization and ischemic stroke. We hypothesized that MMP-7 could be involved in this process.

Methods

Plasma levels of MMP-7 were measured in 182 consecutive patients with moderate (50–69%) or severe (≥70%) internal carotid artery stenosis, and in 23 healthy controls. The mRNA levels of MMP-7 were measured in atherosclerotic carotid plaques with different symptomatology, and based on its localization to macrophages, the in vitro regulation of MMP-7 in primary monocytes was examined.

Results

Our major findings were (i) Patients with carotid atherosclerosis had markedly increased plasma levels of MMP-7 compared to healthy controls, with particularly high levels in patients with recent symptoms (i.e., within the last 2 months). (ii) A similar pattern was found within carotid plaques with markedly higher mRNA levels of MMP-7 than in non-atherosclerotic vessels. Particularly high protein levels of MMP-7 levels were found in those with the most recent symptoms. (iii) Immunhistochemistry showed that MMP-7 was localized to macrophages, and in vitro studies in primary monocytes showed that the inflammatory cytokine tumor necrosis factor-α in combination with hypoxia and oxidized LDL markedly increased MMP-7 expression. (iv) During the follow-up of patients with carotid atherosclerosis, high plasma levels of MMP-7 were independently associated with total mortality.

Conclusion

Our findings suggest that MMP-7 could contribute to plaque instability in carotid atherosclerosis, potentially involving macrophage-related mechanisms.     

阿托伐他汀联合替格瑞洛对冠心病不稳定型心绞痛患者炎性因子、血脂及不良心脏事件的影响

目的:探讨阿托伐他汀联合替格瑞洛对冠心病不稳定型心绞痛(UAP)患者炎性因子、血脂及不良心脏事件的影响。方法:选取2016年2月～2019年2月期间我院收治的103例冠心病伴UAP患者,采用乱数表法将其分为研究组(n=52)和对照组(n=51),对照组给予阿托伐他汀联合氯吡格雷治疗,研究组给予阿托伐他汀联合替格瑞洛治疗,比较两组临床疗效、炎性因子、血脂、心绞痛发作情况及不良心脏事件。结果:研究组治疗1个月后的临床疗效为88.46%(46/52),高于对照组的66.67%(34/51)(P0.05)。两组治疗1个月后总胆固醇(TC)、超敏-C反应蛋白(hs-CRP)、三酰甘油(TG)、白介素-6(IL-6)、低密度脂蛋白胆固醇(LDL-C)、心绞痛发作次数、肿瘤坏死因子-α(TNF-α)、心绞痛持续时间均降低,而高密度脂蛋白胆固醇(HDL-C)升高(P0.05),研究组治疗1个月后TC、TG、LDL-C、IL-6、hs-CRP、TNF-α、心绞痛发作次数、心绞痛持续时间低于对照组,而HDL-C则高于对照组(P0.05)。两组不良心脏事件发生率比较差异无统计学意义(P0.05)。结论:阿托伐他汀联合替格瑞洛治疗冠心病伴UAP患者,疗效确切,可有效改善其炎性因子、血脂水平,且不增加不良心脏事件发生率,临床应用价值较高。     

Urinary Vitamin D Binding Protein and KIM-1 Are Potent New Biomarkers of Major Adverse Renal Events in Patients Undergoing Coronary Angiography

Background

Vitamin-D-binding protein (VDBP) is a low molecular weight protein that is filtered through the glomerulus as a 25-(OH) vitamin D 3/VDBP complex. In the normal kidney VDBP is reabsorbed and catabolized by proximal tubule epithelial cells reducing the urinary excretion to trace amounts. Acute tubular injury is expected to result in urinary VDBP loss. The purpose of our study was to explore the potential role of urinary VDBP as a biomarker of an acute renal damage.

Method

We included 314 patients with diabetes mellitus or mild renal impairment undergoing coronary angiography and collected blood and urine before and 24 hours after the CM application. Patients were followed for 90 days for the composite endpoint major adverse renal events (MARE: need for dialysis, doubling of serum creatinine after 90 days, unplanned emergency rehospitalization or death).

Results

Increased urine VDBP concentration 24 hours after contrast media exposure was predictive for dialysis need (no dialysis: 113.06 ± 299.61ng/ml, n = 303; need for dialysis: 613.07 ± 700.45 ng/ml, n = 11, Mean ± SD, p<0.001), death (no death during follow-up: 121.41 ± 324.45 ng/ml, n = 306; death during follow-up: 522.01 ± 521.86 ng/ml, n = 8; Mean ± SD, p<0.003) and MARE (no MARE: 112.08 ± 302.00ng/ml, n = 298; MARE: 506.16 ± 624.61 ng/ml, n = 16, Mean ± SD, p<0.001) during the follow-up of 90 days after contrast media exposure. Correction of urine VDBP concentrations for creatinine excretion confirmed its predictive value and was consistent with increased levels of urinary Kidney Injury Molecule-1 (KIM-1) and baseline plasma creatinine in patients with above mentioned complications. The impact of urinary VDBP and KIM-1 on MARE was independent of known CIN risk factors such as anemia, preexisting renal failure, preexisting heart failure, and diabetes.

Conclusions

Urinary VDBP is a promising novel biomarker of major contrast induced nephropathy-associated events 90 days after contrast media exposure.