The impact of COVID-19 on short-term prognosis of ST-segment elevation myocardial infarction patients receiving primary percutaneous coronary intervention in Wuhan China.

ST-segment elevation myocardial infarction (STEMI) is a common cardiovascular emergency for which timely reperfusion therapies are needed to minimize myocardial necrosis. The aim of this study was to investigate the impact of the COVID-19 pandemic and reorganization of chest pain centers (CPC) on the practice of primary percutaneous coronary intervention (PPCI) and prognosis of STEMI patients. This single-center retrospective survey included all patients with STEMI admitted to our CPC from January 22, 2020 to April 30, 2020 (during COVID-19 pandemic in Wuhan), compared with those admitted during the analogous period in 2019, in respect of important time points of PPCI and clinical outcomes of STEMI patients. In the present article, we observed a descending trend in STEMI hospitalization and a longer time from symptom onset to first medical contact during the COVID-19 pandemic as compared to the control period (4.35 h versus 2.58 h). With a median delay of 17 minutes in the door to balloon time (D2B), the proportion of in-hospital cardiogenic shock was significantly higher in the COVID-19 era group (47.6% versus 19.5%), and major adverse cardiac events (MACE) tend to increase in the 6-month follow-up period (14.3% versus 2.4%). Although the reorganization of CPC may prolong the D2B time, immediate revascularization of the infarct-related artery could be offered to most patients within 90 minutes upon arrival. PPCI remained the preferred treatment for patients with STEMI during COVID-19 pandemic in the context of timely implementation and appropriate protective measures.

Sphingosine-1-phosphate promotes the proliferation and attenuates apoptosis of Endothelial progenitor cells via S1PR1/S1PR3/PI3K/Akt pathway.

Sphingosine-1-phosphate (S1P) is a bioactive lysophospholipid that involves in numerous pathophysiological processes. Endothelial progenitor cells (EPCs) play a crucial role in endothelial repair and tumor angiogenesis. The aim of study was to determine the effects of S1P on proliferation and anti-apoptosis of EPCs and their signaling pathways. In this study, we showed that S1P, SEW2871 (a selective S1P receptor 1 (S1PR1) agonist), or CYM5541 (a selective S1P receptor 3 (S1PR3) allosteric agonist promotes the proliferation and attenuates apoptosis of bone marrow (BM)-derived EPCs. Futhermore, it was showed that S1P could promote EPCs proliferation, which could be significantly inhibited by pretreatment with CAY10444 (an S1PR3 antagonist), VPC23019 (a selective S1PR(1)/S1PR(3) antagonist), or LY294002 (a PI3K inhibitor). Moveover, we discovered that S1P could significantly attenuate H2 O2 -induced apoptosis and activation of caspase-3 in vitro, while W146 (an S1PR1 antagonist), VPC23019, or LY294002 could significantly increase the activation of caspase-3 and subsequent augmented apoptosis. Our results indicated that the protective effect of S1P is mediated by activating the PI3K/Akt pathway. In addition, S1P promotion of EPCs proliferation was observed to be mainly mediated through S1PR3 and attenuation of EPCs apoptosis induced by H2 O2 was mainly mediated through S1PR1; both of these effects are mediated by activating the PI3K/Akt pathway, which provides potentially useful therapeutic targets for coronary artery disease, diabetes mellitus, and cancer treatment.

Transplantation of EPCs overexpressing PDGFR-ß promotes vascular repair in the early phase after vascular injury.

BACKGROUND: Endothelial progenitor cells (EPCs) play important roles in the regeneration of the vascular endothelial cells (ECs). Platelet-derived growth factor receptor (PDGFR)-ß is known to contribute to proliferation, migration, and angiogenesis of EPCs, this study aims to investigate effects of transplantation of EPCs overexpressing PDGFR-ß on vascular regeneration. METHODS: We transplanted genetically modified EPCs overexpressing PDGFR-ß into a mouse model with carotid artery injury. After 3 days of EPCs transplantation, the enhanced green fluorescent protein (EGFP)-expressing cells were found at the injury site and the lining of the lumen by laser scanning confocal microscope (LSCM). At 4, 7, and 14 days of the carotid artery injury, reendothelialization was evaluated by Evans Blue staining. Neointima formation was evaluated at day 14 with hematoxylin and eosin (HE) staining by calculating the neointimal area, medial area, and neointimal/media (NI/M) ratio. Intimal cell apoptosis was evaluated using TUNEL assay. Then we tested whether PDGF-BB-induced VSMC migration and PDGF-BB's function in reducing VSMC apoptosis can be attenuated by EPCs overexpressing PDGFR-ß in a transwell co-culture system. RESULTS: Our results showed that EPCs overexpressing PDGFR-ß accelerates reendothelialization and mitigates neointimal formation at 14 days after injury. Moreover, we found that there is great possibility that EPCs overexpressing PDGFR-ß enhanc VSMC apoptosis and suppress VSMC migration by competitive consumption of PDGF-BB in the early phase after carotid artery injury in mice. CONCLUSIONS: We report the first in vivo and in vitro evidence that transplantation of genetically modified EPC can have a combined effect of both amplifying the reendothelialization capacity of EPCs and inhibiting neointima formation so as to facilitate better inhibition of adverse remodeling after vascular injury.

The thrombodynamic ratio as a predictor of 28-day mortality in sepsis patients.

BACKGROUND: The thrombodynamic ratio (TDR) as a composite thromboelastography (TEG) parameter, has been proven to be valuable in multiple diseases. However, the association between TDR and mortality in sepsis has not been studied. METHODS: One hundred forty-one patients were enrolled in this retrospectively study. TEG was performed immediately at admission. Two cox proportional hazards models were developed for the prediction of 28-day mortality. The C statistic, continuous net reclassification index (cNRI) and integrated discriminatory index (IDI) were calculated to compare the discrimination performance of clinical models with and without the TDR value. The integrated calibration index (ICI) and E50 were calculated to compare the calibration. RESULTS: Patients with lower TDR were more likely to have organ impairments and increased 28-day mortality. The TDR value improved discrimination performance in both Model 1 (C statistic, 0.745 vs 0.735; cNRI 19.4%, p = 0.044; IDI 5.6%, p = 0.012) and Model 2 (C statistic, 0.761 vs 0.751; IDI, 5.1%, p = 0.012). Compared to the calibration curve of Model 1 without TDR, addition of TDR displayed better calibration (ICI, 0.023; E50, 0.021). CONCLUSION: TDR value significantly predicts 28-day mortality in patients with sepsis and could improve the discrimination and calibration performance of clinical prediction models.

Combinatorial interference of toll-like receptor 2 and 4 synergistically stabilizes atherosclerotic plaque in apolipoprotein E-knockout mice.

To test the hypothesis that combinatorial interference of toll-like receptor 2 (TLR2) and TLR4 is superior to isolated interference of TLR2 or TLR4 in stabilizing atherosclerotic plaques, lentiviruses carrying small interfering RNA of TLR2 or TLR4 were constructed and proved efficacious for knocking down mRNA and protein expression of TLR2 or TLR4 significantly in vitro. One hundred and fifty apolipoprotein E(-/-) mice fed a high-fat diet were divided into the control, mock, TLR2i, TLR4i and TLR2 + 4i subgroups and a constrictive collar was placed around carotid artery of these mice to induce plaque formation. TLR2i and TLR4i viral suspension was transfected into carotid plaques, respectively, in TLR2i and TLR4i subgroups, or in combination in TLR2 + 4i subgroup. Four weeks after lentivirus transfection, mRNA and protein expression of TLR2 or TLR4 was attenuated markedly in carotid plaques, leading to reduced local inflammatory cytokine expression and plaque content of lipid and macrophages, increased plaque content of collagen and lowered plaque vulnerability index. Factorial ANOVA analysis revealed that there was a synergistic effect between TLR4i and TLR2i in stabilizing plaques. In conclusion, combinatorial interference of TLR2 and TLR4 reduces local inflammation and stabilizes plaques more effectively than interference of TLR2 or TLR4 alone.

Atorvastatin suppresses LPS-induced rapid upregulation of Toll-like receptor 4 and its signaling pathway in endothelial cells.

In the present study, we tested our hypothesis that atorvastatin exerts its anti-inflammation effect via suppressing LPS-induced rapid upregulation of Toll-like receptor 4 (TLR4) mRNA and its downstream p38, ERK, and NF-κB signaling pathways in human umbilical-vein endothelial cells (HUVECs) and human aortic endothelial cells (HAECs). TLR4 mRNA expression and its downstream kinase activities induced by LPS alone or atorvastatin + LPS in endothelial cells were quantified using quantitative real-time PCR and enzyme-linked immunosorbent assay. Preincubation of LPS-stimulated endothelial cells with TLR4 siRNA was conducted to identify the target of the anti-inflammatory effects of atorvastatin. Atorvastatin incubation resulted in the reduction of LPS-induced TLR4 mRNA expression, ERK1/2 and P38 MAPK phosphorylation, and NF-κB binding activity. Pretreatment with MEK/ERK1/2 inhibitor PD98059 attenuated atorvastatin + LPS-induced NF-κB activity but had no effect on P38 MAPK phosphorylation. In contrast, pretreatment with P38 MAPK inhibitor SB203580 resulted in upregulation of atorvastatin + LPS-induced ERK1/2 phosphorylation but had no significant effects on NF-κB activity. On the other hand, blocking NF-κB with SN50 produced no effects on atorvastatin + LPS-induced ERK1/2 and P38 MAPK phosphorylation. Moreover, TLR4 gene silencing produced the same effects as the atorvastatin treatment. In conclusion, atorvastatin downregulated TLR4 mRNA expression by two distinct signaling pathways. First, atorvastatin stabilized Iκ-Bα, which directly inhibited NF-κB activation. Second, atorvastatin inactivated ERK phosphorylation, which indirectly inhibited NF-κB activation. Suppression of p38 MAPK by atorvastatin upregulates ERK but exerts no effect on NF-κB.

[Use of the AKIN criteria to assess the incidence of acute renal injury, outcome and prognostic factors of ICU mortality in critically ill patients].

OBJECTIVE: To evaluate the value of the AKIN criteria of acute kidney injury (AKI) in the incidence and prognoses in critically ill patients, and to further identify risk factors associated with the prognoses of the critically ill patients. METHODS: We retrospectively studied 544 adult patients hospitalized for ≥24 h to a comprehensive ICU with 16 beds in teaching hospital from January 2008 to December 2009. Based on AKIN criteria, these patients were classified into four groups: NAKI (no AKI), AKII, AKIII, and AKIIII respectively. RESULTS: (1) Of the patients, 191 (35.5%) fulfilled the criteria for AKI (14.8% had AKI I 8.2% had AKI II and 11.9% had AKIIII). (2) Mortality in the ICU was much higher in patients with AKI than in patients with no AKI (48% vs 11%, OR 7.48, 95%CI 4.831-11.587, P<0.001). The mortality rate was 37% for AKII group, 51% for AKIII group and 60% for AKIIII group. (3) In multivariate analysis, each AKIN category was independently associated with ICU mortality. The other independent risk factors for ICU mortality included internal medical diseases, septic shock, pre-existing chronic illness, APACHEII score, the number of failed organs, mechanical ventilation and CRRT. CONCLUSIONS: The AKIN category closely relates to the prognoses in critically ill patients, even the mild degree of AKI with a much higher mortality rate than the patients without AKI. The AKIN criteria has some direction significance to the early detection and classification of AKI and to the prediction of clinical outcomes in critically ill patients.

A causal relationship between shear stress and atherosclerotic lesions in apolipoprotein E knockout mice assessed by ultrasound biomicroscopy.

The present study was undertaken to examine the hemodynamic state using the latest ultrasound biomicroscopy (UBM) technique and to investigate the effect of local shear stress on the development of atherosclerosis in the constrictive collar-treated carotid arteries of apolipoprotein E-deficient (apoE(-/-)) mice. Fifty-six male apoE(-/-) mice fed a high-lipid diet were divided into an interventional group (n = 48) and the control group (n = 8). Constrictive and nonconstrictive collars were placed around the carotid artery of the mice in the interventional group and the control group, respectively. The carotid lumen diameters and flow velocities were measured by UBM, and shear stress in the lesion region was calculated. Histopathology and electron microscopy were performed to observe the morphological changes in the carotid artery. In the region proximal to the constrictive collar, shear stress was significantly reduced 2 days after collar placement and remained low over time compared with the baseline level. In contrast, within the constrictive collar region, shear stress was increased significantly. Although endothelial permeability was enhanced in both regions, monocyte chemotaxis protein-1 (MCP-1) expression, macrophage infiltration, and atherosclerotic lesions were more prominent in the region proximal to the constrictive collar. Moreover, increased MCP-1 expression was observed as early as 2 days after constrictive collar placement, which preceded the morphological changes of the vessel wall. In conclusion, UBM offers a noninvasive and reliable technique for measuring shear stress in apoE(-/-) mice. Persistent low shear stress promotes endothelial permeability and enhances MCP-1 expression and macrophage recruitment, which were essential in the pathogenesis of atherosclerosis in apoE(-/-) mice.

Plaque volume compression ratio, a novel biomechanical index, is independently associated with ischemic cerebrovascular events.

OBJECTIVE: The purpose of this study was to develop a new biomechanical index for assessing the elastic characteristics of carotid plaques and to test the association between carotid plaque elasticity and ischemic cerebrovascular events (ICEs). METHODS: One hundred and eighteen carotid plaques were detected with real-time three-dimensional ultrasonography in 104 patients. All patients received MRI and were divided into two groups according to the history of ICEs: patients with ICEs (n=58, including 20 patients with transient ischemic attack and 38 with ischemic stroke) and patients without ICEs (n=46). The carotid plaque volume at end diastole (Vd) and end systole (Vs) was measured by use of a TomTec (Munich, Germany) workstation. Plaque volume compression ratio (VCR) was calculated as (Vd-Vs)/Vd x 100 and the reproducibility of VCR measurement was analyzed. The carotid intima-media thickness, plaque area and plaque acoustic density were also measured. Multivariate logistic regression was used to test the association between ICEs and plaque ultrasonic parameters or traditional risk factors including age, sex, smoking, blood pressure, history of coronary heart disease, levels of serum low-density lipoprotein, triglyceride and glucose. RESULTS: Satisfactory images of carotid plaques were obtained in all patients by real-time three-dimensional ultrasonography. Patients with ICEs and patients without ICEs differed significantly in VCR (22.19+/-8.42 vs. 13.95+/-7.86, P<0.01). Regression analysis revealed that systolic blood pressure, [odds ratio (OR)=1.054, 95% confidence interval (CI)=1.028-1.081, P<0.001] and VCR (OR=1.074, 95% CI=1.022-1.128, P<0.001) were associated with ICEs independently. Plaque volume had only a marginal association with ICEs (OR=1.007, 95% CI=1.000-1.013, P=0.05). CONCLUSION: Measurement of VCR provides a noninvasive approach to the evaluation of the elasticity of carotid plaques, which is associated independently with ICEs. Thus, real-time three-dimensional ultrasonography-derived VCR holds a great potential in identifying patients with high risk of ICEs.

[Relationship between blood lactic level, lactic clearance, duration of lacticemia and prognosis of critically ill patients in intensive care unit].

OBJECTIVE: To study and quantify the relationship between dynamic lactic acid monitoring indexes and prognosis of critically ill patients in intensive care unit (ICU). METHODS: One hundred and one critically ill patients with elevated blood lactic acid level were included in this study and divided into death group (n=50) and survival group (n=51). Differences in their lactic acid indexes (including: lactic acid level, duration of lacticemia, lactic clearance), acute physiology and chronic health evaluation II (APACHEII) score, and other clinical indicators which reflected organ/system status were compared, and prognostic significant lacticemia indexes were formulated by multi-variable logistic analysis. Subsequently, patients were grouped by significant lactic indexes separately and compared with incidence of shock/multiple organ dysfunction syndrome (MODS), APACHE II score and mortality. RESULTS: Differences in lactic acid level, peak lactic acid level, 12-hour and 24-hour lactic acid clearance between death group and survival group showed statistically significant difference (P<0.05 or P<0.01). Peak lactic acid level, 12-hour lactic clearance, APACHE II score and blood pH had significant correlation with prognosis, odds ratios (OR) were 1.466, 0.922, 1.208, 0.032, respectively. Patients with peak lactic acid value> or =10 mmol/L or 12-hour lactic clearance< or =10% had significantly higher mortality: 77.8% and 70.6%, respectively (P<0.05 and P<0.01). Although patients with lacticemia>24 hours had higher mortality, there was no statistically significant difference. CONCLUSION: Peak lactic acid level, 12-hour lactic clearance, APACHE II score and blood pH are good indicators to evaluate patients' prognosis. Peak lactic acid value> or =10 mmol/L or 12-hour lactic clearance< or =10% is an alert of extremely bad prognosis. Prognosis value of duration of lacticemia is limited.

Quantification of transmural gradient of blood flow in myocardial ischemia with real-time myocardial contrast echocardiography and dipyridamole stress test.

Transmural redistribution of myocardial blood flow (MBF) is the earliest sign of myocardial ischemia. We aimed to evaluate the ability of real-time myocardial contrast echocardiography (MCE) combined with dipyridamole stress to quantify the transmural gradient of MBF during graded coronary stenosis. Real-time MCE was performed in 14 open-chest dogs at seven experimental stages: baseline; hyperemia induced by 6-min infusion of dipyridamole; 50%, 75% and 90% reduction of hyperemic flow after constriction in each stage for 10 min; reperfusion for 10 min; and subtotal occlusion of the left anterior descending coronary artery (LAD) for 90 min. We obtained MCE perfusion parameters from subendocardial (A-endo, beta-endo and A x beta-endo) and subepicardial (A-epi, beta-epi and A x beta-epi) layers of the ventricular septum and calculated their transmural gradients (A-EER, beta-EER and A x beta-EER) and systolic wall thickening (SWT). The sensitivity and specificity of each parameter for predicting 75% reduction of hyperemic flow, which was defined as mild myocardial ischemia, were derived by receiver operating characteristic (ROC) curve analysis. No transmural gradients were found at baseline; during maximal hyperemia and 50% reduction of hyperemic flow. beta-endo, A x beta-endo, beta-EER and A x beta-EER decreased significantly when the hyperemic flow was reduced by 75% or more. In contrast, SWT remained unchanged until the hyperemic flow was reduced by 90%. Among all parameters measured, beta-EER and A x beta-EER had the highest and SWT the lowest sensitivity and specificity in predicting mild myocardial ischemia. In conclusion, real-time MCE combined with dipyridamole stress allows for quantification of the transmural gradient of MBF. beta-EER and A x beta-EER are more sensitive than SWT and other MCE parameters in detecting mild myocardial ischemia.

Usefulness of high-frequency vascular ultrasound imaging and serum inflammatory markers to predict plaque rupture in patients with stable and unstable angina pectoris.

It remains unclear what kind of morphologic and biochemical features best predict plaque rupture in patients with angina pectoris (AP). This study aimed to investigate whether combined high-frequency vascular ultrasound imaging and measurements of serum inflammatory biomarkers can predict coronary plaque ruptures in patients with AP. The study population consisted of 20 patients with stable AP and 40 patients with unstable AP. High-frequency vascular ultrasound imaging was performed in the 2 groups to measure intima-media thickness, the plaque acoustic density of the common carotid arteries, and the flow-mediated dilation of the brachial arteries. Serum lipid profile and inflammatory biomarkers were measured in all patients. Using intravascular ultrasound, a list of coronary imaging parameters was obtained. A multivariate logistic regression model was applied to calculate the odds ratio of each parameter to predict coronary plaque ruptures detected by intravascular ultrasound. Of 139 coronary artery plaques identified by intravascular ultrasound, 48 plaques (9 in stable AP and 39 in unstable AP) developed ruptures. Among measured parameters, the values of carotid intima-media thickness, coronary external elastic membrane area, plaque area, plaque burden, plaque eccentric index and remodeling index, serum high-sensitivity C-reactive protein, soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule-1 were significantly higher in unstable AP than in stable AP (p <0.05 to 0.01). Of these parameters, carotid intima-media thickness, serum high-sensitivity C-reactive protein, and the coronary remodeling index were found to be significant predictors of coronary plaque rupture, with odds ratios of 9.51 (95% confidence interval 1.29 to 21.81), 3.02 (95% confidence interval 1.01 to 7.65), and 0.01 (95% confidence interval 0.00 to 0.34), respectively. In conclusion, combined high-frequency ultrasound imaging of coronary and carotid arteries and measurements of serum inflammatory markers are able to predict coronary plaque ruptures in patients with AP.

How many planes are required to get an accurate and timesaving measurement of left ventricular volume and function by real-time three-dimensional echocardiography in acute myocardial infarction?

To derive the optimal cutting planes of real-time 3-D echocardiography (RT-3DE) for measuring left ventricular volume and ejection fraction (EF) in the presence of left ventricular regional wall motion abnormalities, 14 open-chest dogs were studied with RT-3DE full volume imaging and 2-D echocardiography (2DE) after left anterior descending coronary arteries were occluded for 90 min. Left ventricular end diastolic volume (EDV), end systolic volume (ESV), stroke volume (SV) and EF were measured off-line with 2DE and RT-3DE (2-, 4- and 8-plane) methods. The autopsy EDV was estimated by the volume of saline solution injected into the excised heart and served as the reference volume (RefV) for comparison with EDV measured by 2DE and RT-3DE. Agreement analysis was performed according to the method of Bland and Altman. There were excellent correlations between 2DE, RT-3DE (2-plane) and RT-3DE (4-plane) methods on one hand, and RT-3DE (8-plane) method on the other in the measurements of EDV, ESV and SV (r = 0.84-0.99). However, 2DE and RT-3DE (2-plane) measurements significantly underestimated RT-3DE (8-plane) (p < 0.01), whereas no significant differences between RT-3DE (4-plane) and RT-3DE (8-plane) were found in terms of EDV, ESV and SV measurements. The values of EF determined by 2DE, RT-3DE (2-plane) and RT-3DE (4-plane) methods correlated highly with that by RT-3DE (8-plane) (r = 0.82-0.98) and there was no significant difference between the two measurements. EDV values determined by 2DE, RT-3DE (2-plane), RT-3DE (4-plane) and RT-3DE (8-plane) correlated highly with RefV (r = 0.84, r = 0.92, r = 0.94 and r = 0.97, respectively) and there was no significant difference between RefV and EDV by RT-3DE (4-plane) and RT-3DE (8-plane). In contrast, EDV measured by 2DE and RT-3DE (2-plane) methods underestimated RefV significantly (p < 0.01). In conclusion, RT-3DE allows reliable and reproducible measurement of left ventricular volume and EF, even in the presence of left ventricular regional wall motion abnormalities. RT-3DE (4-plane) is the method of choice for an accurate and timesaving quantification of left ventricular volume and function.

[The role of atherosclerotic plaque stability and inflammation in the pathogenesis of acute coronary syndrome].

OBJECTIVE: To elucidate the effect of inflammation and coronary atherosclerotic plaque destabilization in the pathogenesis of acute coronary syndromes (ACS). METHODS: Twenty-eight patients with ACS and 13 patients with stable angina pectoris (SA) were examined by intravascular ultrasound (IVUS). Coronary plaque morphology and areas in culprit lesions were analyzed. The serum levels of hs-CRP, MMP-9, TIMP-1, sCD40L were also measured. RESULTS: Soft plaques were dominant in culprit lesions of ACS patients (71.4%, 20/28), and hard plaques were dominant in culprit lesions of SA patients [76.9% (10/13), P = 0.004]. At the culprit site, plaque area, plaque burden and remodeling index were all significantly larger in culprit lesions of ACS patients than those of SA patients (all P < 0.05). Positive remodeling was more frequent in ACS patients than in SA patients, whereas negative remodeling was more frequent in SA patients (P < 0.05). The serum levels of hs-CRP, MMP-9, sCD40L were higher in ACS group compared with SA group (P < 0.05, respectively). Moreover, hs-CRP level was positively correlated with MMP-9 (r = 0.671, P = 0.000) and sCD40L (r = 0.494, P = 0.008), respectively, in ACS patients. There was no difference in TIMP-1 between two groups (P = 0.234). CONCLUSIONS: These results suggest that structurally vulnerable plaques are essential element in the pathogenesis of ACS and inflammation might play an important role in plaque vulnerability.

Correlating blood levels of 8-hydroxydeoxyguanosine to hOGG1 genotypes and the incidence of ischemic cardiomyopathy.

We measured the serum levels of 8-hydroxydeoxyguanosine (8-OHdG) and investigated whether these levels correlate with incidence of ischemic cardiomyopathy (ICM), and whether these levels correlate with underlying oxidative stress in patients with ICM. Polymerase chain reaction-restriction fragment length polymorphism analysis was performed to assess the prevalence of the Ser/Cys polymorphism in the human 8-oxoguanine glycosylase (hOGG1) gene. We analyzed the samples from 246 ICM cases (the ICM group) and another 246 age- and sex-matched volunteers with normal coronary artery function (the control group). Levels of 8-OHdG in participants' blood samples were 6.7 ± 1.7 and 3.0 ± 0.8 in the ICM and control groups, respectively (p < 0.05). Although there were no differences in allele frequency (p = 0.140), significant differences were present in the genotype distributions (p = 0.002). The Cys/Cys genotype correlated strongly with the risk of developing ICM (odds ratio, 2.2; 95% confidence interval, 1.4-3.3). Treating the Ser/Ser and Ser/Cys genotypes as members of the same group increased the predicted ICM risk for patients carrying the Cys/Cys genotype (odds ratio, 1.9; 95% confidence interval, 1.2-2.9). The serum level of 8-OHdG in the ICM group was higher than that in the control group (p < 0.05) and significantly increased in those carrying the Cys/Cys genotype (8.7 ± 1.7 for the Cys/Cys group, and 4.5 ± 0.8 for the Ser/Ser+Ser/Cys group; p < 0.05). Patients carrying the Cys/Cys genotype had a significantly increased risk of developing ICM. Serum levels of 8-OHdG were significantly increased in patients with ICM.

Combination of Acute Physiology and Chronic Health Evaluation II score, early lactate area, and N-terminal prohormone of brain natriuretic peptide levels as a predictor of mortality in geriatric patients with septic shock.

BACKGROUND: Given the high mortality rates in elderly patients with septic shock, the early recognition of patients at greatest risk of death is crucial for the implementation of early intervention strategies. Serum lactate and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels are often elevated in elderly patients with septic shock and are therefore important biomarkers of metabolic and cardiac dysfunction. We hypothesized that a risk stratification system that incorporates the Acute Physiology and Chronic Health Evaluation (APACHE) II score and lactate and NT-proBNP biomarkers would better predict mortality in geriatric patients with septic shock than the APACHE II score alone. METHODS: A single-center prospective study was conducted from January 2012 to December 2013 in a 30-bed intensive care unit of a triservice hospital. The lactate area score was defined as the sum of the area under the curve of serial lactate levels measured during the 24 hours following admission divided by 24. The NT-proBNP score was assigned based on NT-proBNP levels measured at admission. The combined score was calculated by adding the lactate area and NT-proBNP scores to the APACHE II score. Multivariate logistic regression analyses and receiver operating characteristic curves were used to evaluate which variables and scoring systems served as the best predictors of mortality in elderly septic patients. RESULTS: A total of 115 patients with septic shock were included in the study. The overall 28-day mortality rate was 67.0%. When compared to survivors, nonsurvivors had significantly higher lactate area scores, NT-proBNP scores, APACHE II scores, and combined scores. In the multivariate regression model, the combined score, lactate area score, and mechanical ventilation were independent risk factors associated with death. Receiver operating characteristic curves indicated that the combined score had significantly greater predictive power when compared to the APACHE II score or the NT-proBNP score (P < .05). CONCLUSIONS: A combined score that incorporates the APACHE II score with early lactate area and NT-proBNP levels is a useful method for risk stratification in geriatric patients with septic shock.

[A correlation study of serum inflammatory factors and intravascular ultrasound features of atherosclerotic plaques in patients with angina pectoris].

OBJECTIVE: To elucidate the relationship between serum inflammatory factors and intravascular ultrasound (IVUS) findings of atherosclerotic plaques in patients with stable and unstable angina. METHODS: Thirteen patients with stable angina (SA) in group A and nineteen patients with unstable angina (UA) in group B underwent study. Concentrations of hsCRP, sVCAM-1 and sICAM-1 were measured by means of Enzyme-Linked-Immunosorbent Assay (ELISA) and IVUS was used to analysis the coronary lesions. Their results were analyzed by correlate analysis. RESULTS: Concentration of hsCRP, sVCAM-1 and sICAM-1 were significantly higher in group B (4.7 mg/L +/- 2.6 mg/L, 789 micro g/L +/- 65 micro g/L and 365 micro g/L +/- 63 micro g/L) than in group A (2.4 mg/L +/- 1.8 mg/L, 544 micro g/L +/- 70 micro g/L and 264 micro g/L +/- 53 micro g/L, P < 0.01, respectively). IVUS found that 69.2% (18/26) patients in group B had soft lipid plaques, while patients in group A mainly had fibrous and mixed plaques, only 13.3% (2/15) had soft plaques. There were more eccentric plaques and EEMA in group B than in group A (P < 0.05, respectively), and PA and lumen area stenosis ratio (LAS) in group B were larger than those of group A (P < 0.01, respectively). Positive remodeling pattern was observed in 65.4% (17/26) lesions in group B while 66.6% (10/15) lesions in group A showed negative remodeling. sICAM-1 correlated well with RI (r = 0.475, P < 0.05) and C-RP with EEMA (r = 0.448, P < 0.05). CONCLUSION: High levels of hsCRP, sVCAM-1 and sICAM-1 are sensitive predictors of unstable angina. The features of unstable atherosclerotic plaques are eccentric, soft plaques, with large plaque areas. The vessel at the lesion shows positive remodeling. Inflammatory reaction correlated well with vascular enlargement and remodeling.

Local gene silencing of monocyte chemoattractant protein-1 prevents vulnerable plaque disruption in apolipoprotein E-knockout mice.

Monocyte chemoattractant protein-1 (MCP-1), a CC chemokine (CCL2), has been demonstrated to play important roles in atherosclerosis and becoming an important therapeutic target for atherosclerosis. The present study was undertaken to test the hypothesis that local RNAi of MCP-1 by site-specific delivery of adenovirus-mediated small hairpin RNA (shRNA) may enhance plaque stability and prevent plaque disruption in ApoE-/- mice. We designed an adenovirus-mediated shRNA against mouse MCP-1 (rAd5-MCP-1-shRNA). Male apolipoprotein E-knockout (ApoE-/-) mice (n = 120) were fed a high-fat diet and vulnerable plaques were induced by perivascular placement of constrictive collars around the carotid artery, intraperitoneal injection of lipopolysaccharide and stress stimulation. Mice were randomly divided into RNA interference (Ad-MCP-1i) group receiving local treatment of rAd5-MCP-1-shRNA suspension, Ad-EGFP group receiving treatment of rAd5-mediated negative shRNA and mock group receiving treatment of saline. Two weeks after treatment, plaque disruption rates were significantly lower in the Ad-MCP-1i group than in the Ad-EGFP group (13.3% vs. 60.0%, P = 0.01), and local MCP-1 expression was significantly inhibited in the Ad-MCP-1i group confirmed by immunostaining, qRT-PCR and western blot (P<0.001). Compared with the Ad-EGFP group, carotid plaques in the Ad-MCP-1i group showed increased levels of collagen and smooth muscle cells, and decreased levels of lipid and macrophages. The expression of inflammatory cytokines and activities of matrix metalloproteinases (MMPs) were lower in the Ad-MCP-1i group than in the Ad-EGFP group. In conclusion, site-specific delivery of adenoviral-mediated shRNA targeting mouse MCP-1 downregulated MCP-1 expression, turned a vulnerable plaque into a more stable plaque phenotype and prevented plaque disruption. A marked suppression of the local inflammatory cytokine expression may be the central mechanism involved.

Atherosclerotic plaque components characterization and macrophage infiltration identification by intravascular ultrasound elastography based on b-mode analysis: validation in vivo.

Intravascular ultrasound elastography (IVUSE) is a promising imaging technique for early investigation of vulnerable plaques. Compared to radiofrequency signal processing, digital B-mode analysis is simple and of higher portability. However, rare studies have been reported validating the latter technique in vivo. In this study, we developed an IVUSE computer software system involving semi-automatic border delineation and block-matching algorithm and validated the system in vivo. Seven minipigs were fed with atherogenic diet for 40 weeks. For each pig, the endothelium of one side of the renal arteries was denuded at the fifth week. With cross-correlation analysis, Lagrangian strain was calculated from two intravascular ultrasound images acquired in situ. Sixty regions of interests were selected from 35 elastograms matched well with the corresponding histological slices. Plaque types within these regions were classified as fibrous, fibro-fatty or fatty on Masson's trichrome and Oil-red O staining. Macrophage infiltration was also evaluated with immunohistology. Comparison between the mean strain value of the region of interest and the histological results revealed significant differences in strain values among different plaque types and non-diseased artery walls. The extent of macrophage infiltration was found to be correlated positively with strain values. For identification of fibro-fatty and fibrous plaques and macrophage infiltration, the system showed high sensitivity (93, 96 and 92%, respectively) and specificity (89, 76 and 66%, respectively), as revealed by receiver operating characteristic analysis. Our IVUSE system based on B-mode analysis is capable of characterizing fibrous and fibro-fatty plaques and macrophage intensity, thus holds potential for identifying vulnerable plaque.