High glucose levels accelerate atherosclerosis via NLRP3-IL/ MAPK/NF-κB-related inflammation pathways.

BACKGROUND: As a chronic inflammatory disease, diabetes mellitus (DM) contributes to the development of atherosclerosis (AS). However, how the NLRP3 inflammasome participates in diabetes-related AS remains unclear. Therefore, this study aimed to elucidate the mechanism through which NLRP3 uses high glucose (HG) levels to promote AS. METHODS: Serum and coronary artery tissues were collected from coronary artery disease (CAD) patients with and without DM, respectively. The expression of NLRP3 was detected, and the effects of this inflammasome on diabetes-associated AS were evaluated using streptozotocin (STZ)-induced diabetic apoE-/- mice injected with Adenovirus-mediated NLRP3 interference (Ad-NLRP3i). To elucidate the potential mechanism involved, ox-LDL-irritated human aortic smooth muscle cells were divided into the control, high-glucose, Si-NC, and Si-NLRP3 groups to observe the changes induced by downregulating NLRP3 expression. For up-regulating NLRP3, control and plasmid contained NLRP3 were used. TNF-α, IL-1ß, IL-6, IL-18, phosphorylated and total p38, JNK, p65, and IκBα expression levels were detected following the downregulation or upregulation of NLRP3 expression. RESULTS: Patients with comorbid CAD and DM showed higher serum levels and expression of NLRP3 in the coronary artery than those with only CAD. Moreover, mice in the Ad-NLRP3i group showed markedly smaller and more stable atherosclerotic lesions compared to those in other DM groups. These mice had decreased inflammatory cytokine production and improved glucose tolerance, which demonstrated the substantial effects of NLRP3 in the progression of diabetes-associated AS. Furthermore, using the siRNA or plasmid to downregulate or upregulate NLRP3 expression in vitro altered cytokines and the MAPK/NF-κB pathway. CONCLUSIONS: NLRP3 expression was significantly increased under hyperglycemia. Additionally, it accelerated AS by promoting inflammation via the IL/MAPK/NF-κB pathway.

Chinese Herbal Cardiotonic Pill Stabilizes Vulnerable Plaques in Rabbits by Decreasing the Expression of Adhesion Molecules.

The cardiotonic pill (CP), consisting of a mixture of Radix Salviae Miltiorrhizae, Radix Notoginseng, and Borneolum Syntheticum, has been widely used in the prevention and treatment of cardiovascular disease. Adhesion molecules, including intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1, are involved in the development of vulnerable plaque. We investigated the effect of the CP in a rabbit model of vulnerable plaque established by local transfection with p53 gene. Compared with the control group, rabbits with vulnerable plaque showed a significantly lower intima-media thickness and plaque burden after CP treatment for 12 weeks. Moreover, the reduction in rate of plaque rupture and vulnerability index was similar. On enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and immunohistochemistry analysis, the expression of intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1 was inhibited with CP treatment. CP treatment could postpone atherosclerotic plaque development and stabilize vulnerable plaque by inhibiting the expression of adhesion molecules in treatment of cardiovascular disease.

Effect of AC electric field on enhancing phytoremediation of Cd-contaminated soils in different pH soils.

To increase the efficiency of phytoremediation to clean up heavy metals in soil, assisted with alternating current (AC) electric field technology is a promising choice. Our experiments utilized the hyperaccumulator Sedum alfredii Hance and the fast-growing, high-biomass willow (Salix sp.). We investigated the efficiency of AC field combined with S. alfredii-willow intercropping for removing Cd from soils with different pH values. In the AC electric field treatment with S. alfredii-willow intercropping, the available Cd content in acidic soil increased by 50.00% compared to the control, and in alkaline soil, the increase was 100.00%. Furthermore, AC electric field promoted Cd uptake by plants in both acidic and alkaline soils, with Cd accumulation in the aboveground increased by 20.52% (P < 0.05) and 11.73%, respectively. In conclusion, the integration of AC electric fields with phytoremediation demonstrates significant favorable effectiveness.

Echocardiographic Measurements in Normal Chinese Adults (EMINCA) II focusing on left ventricular and left atrial size and function by three-dimensional echocardiography.

Current guidelines encourage large studies in a diverse population to establish normal reference ranges for three-dimensional (3D) echocardiography for different ethnic groups. This study was designed to establish the normal values of 3D-left ventricular (LV) and left atrial (LA) volume and function in a nationwide, population-based cohort of healthy Han Chinese adults. A total of 1117 healthy volunteers aged 18-89 years were enrolled from 28 collaborating laboratories in China. Two sets of 3D echocardiographic instruments were used, and full-volume echocardiographic images were recorded and transmitted to a core laboratory for image analysis with a vendor-independent off-line workstation. Finally, 866 volunteers (mean age of 48.4 years, 402 men) were qualified for final analysis. Most parameters exhibited substantial differences between different sex and age groups, even after indexation by body surface area. The normal ranges of 3D-LV and 3D-LA volume and function differed from those recommended by the American Society of Echocardiography and the European Association of Cardiovascular Imaging guidelines, presented by the World Alliance Societies of Echocardiography (WASE) study, and from the 2D values in the EMINCA study. The normal reference values of 3D echocardiography-derived LV and LA volume and function were established for the first time in healthy Han Chinese adults. Normal ranges of 3D-LV and 3D-LA echocardiographic measurements stratified with sex, age, and race should be recommended for clinical applications.

Right ventricular volume and function by three-dimensional echocardiography: results of the echocardiographic measurements in normal Chinese adults (EMINCA) II.

Three-dimensional (3D) echocardiography is an emerging technique for assessing right ventricular (RV) volume and function, but 3D-RV normal values from a large Chinese population are still lacking. The aim of the present study was to establish normal values of 3D-RV volume and function in healthy Chinese volunteers. A total of 1117 Han Chinese volunteers from 28 laboratories in 20 provinces of China were enrolled, and 3D-RV images of 747 volunteers with optimal image quality were ultimately analyzed by a core laboratory. Both vendor-dependent and vendor-independent software platforms were used to analyze the 3D-RV images. We found that men had larger RV volumes than women did in the whole population, even after indexing to body surface area, and older individuals had smaller RV volumes. The normal RV volume was significantly smaller than that recommended by the American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines in both sexes. There were significant differences in 3D-RV measurements between the two vendor ultrasound systems and the different software platforms. The echocardiographic measurements in normal Chinese adults II study revealed normal 3D-RV volume and function in a large Chinese population, and there were significant differences between the sexes, ages, races, and vendor groups. Thus, normal 3D-RV values should be stratified by sex, age, race, and vendor.

Effects of willow and Sedum alfredii Hance planting patterns on phytoremediation efficiency under AC electric field.

Heavy metal contamination to soil is tricky due to its difficult removal, long retention time, and biomagnified toxicity. The green and low-cost phytoremediation with electric field treatment and planting pattern selection is an emerging and more effective approach to remove heavy metals from soils. In this study, alternating current (AC) electric field-assisted phytoremediation was examined with different planting patterns, i.e., monoculture willow (Salix sp.), monoculture Sedum alfredii Hance, and interplanting of willow and S. alfredii. AC electric field greatly increased phytoremediation efficiency to soil cadmium (Cd) regardless of planting patterns, either single plant species of willow or S. alfredii. The Cd removal capacity of willow and S. alfredii raises apparently under 0.5 V cm-1 AC electric field. Under different planting patterns of AC electric field treatment, Cd accumulation in the whole plant by interplanting was 5.63 times higher than monoculture willow, but only 0.75 times as high as monoculture S. alfredii. The results showed that AC electric field-assisted interplanting of willow and S. alfredii is a promising remediation technique for efficiently clean-up Cd-contaminated soil.

Comparisons of Two-dimensional Echocardiographic Aortic Dimensions between Chinese, Japanese, and Europeans.

PURPOSE: We aimed to investigate the impacts of age, gender, and race on aortic dimensions in healthy adults. METHODS: We analyzed data from 3 large population-based sample studies, including Chinese Echocardiographic Measurements in Normal Chinese Adults, Japanese the Normal Values for Echocardiographic Measurements Project, and European Normal Reference Ranges for Echocardiography, to compare the two-dimensional echocardiography-derived aortic diameters at different levels and to explore the effects of age, gender, and race on aortic measurements. We also compared the values corrected by body surface area (BSA) or height. RESULTS: The results are as follows: (1) Aortic diameters showed positive correlations with age (r=0.12-0.42, P<0.05), and there were significant inter-age group differences before and after indexing to BSA (P<0.05); (2) Men had greater measurements of aortic diameters than women, with the differences being the same when indexed to height. However, indexing to BSA reversed the differences; (3) The aortic diameters at annulus (Ao-a) and sinus (Ao-s) levels were very close with minor differences between the Chinese and Japanese regardless of whether BSA was used for correction; and (4) The aortic measurements at Ao-s and proximal ascending aorta (Ao-asc) levels in the Chinese were significantly lower than in the Europeans for both genders, with the differences remaining the same even after indexing to BSA or height (P<0.05). CONCLUSION: Aortic dimensions vary with age and gender, and there are significant differences between races or ethnicities even when stratified by gender and age. The indexation by BSA or height cannot eliminate these differences. Therefore, age-specific, gender-specific, race-specific, and nationality-specific reference values may be more appropriate at present for clinical practice to avoid misdiagnosis and misclassification of aortic dilation.

Case report: Different clinical manifestations of the rare Loeffler endocarditis.

Background: Loeffler endocarditis is a rare and fatal disease, which is prone to be misdiagnosed, owing to its various clinical manifestations. Consequently, an early identification of Loeffler endocarditis and its effective treatment are crucial steps to be undertaken for good prognosis. Case presentation: This report describes two cases of Loeffler endocarditis with different etiologies and clinical manifestations. Case 1 was caused by idiopathic eosinophilia and presented with a thrombus involving the tricuspid valve and right ventricular inflow tract (RVIT). The patient suffered from recurrent syncope following activity. After the patient underwent tricuspid valve replacement and thrombectomy, he took oral prednisone and warfarin for 2 years, consequent to which he discontinued both drugs. However, the disease recurred 6 months later, this time manifesting as edema of both legs. Echocardiography showed that a thrombus had reappeared in the RVIT. Thus, oral prednisone and warfarin therapy was readministered. Three months later, the thrombus had dissolved. Low-dose prednisone maintenance therapy was provided long term. Case 2 involved a patient who presented with recurrent fever, tightness in the chest, and asthma, and whose condition could not be confirmed, despite multiple local hospitalizations. In our hospital, echocardiography revealed biventricular apical thrombi. After comprehensive examinations, the final diagnosis was eosinophilic granulomatosis polyangiitis (EGPA) involving multiple organs, including the heart (Loeffler endocarditis), lungs, and kidneys. After administration of corticosteroid, anticoagulant, and immunosuppressive agents along with drugs to improve cardiac function, the patient's symptoms improved significantly. Conclusion: In Loeffler endocarditis due to idiopathic eosinophilia, long-term corticosteroid use may be required. Diverse and non-specific symptoms cause Loeffler endocarditis to be easily misdiagnosed. So, when a patient shows a persistent elevation of the eosinophil count with non-specific myocardial damage, the possibility of this disease, should always be considered. Furthermore, even when an invasive clinical procedure such as endomyocardial biopsy (EMB) is not available or acceptable, corticosteroids should be administered promptly to bring the eosinophil count back to the normal range, thereby halting the progression of disease and reducing patient mortality.

Left ventricular and atrial remodelling in hypertensive patients using thresholds from international guidelines and EMINCA data.

AIMS: To investigate differences in the prevalence of left ventricular (LV) and left atrial (LA) remodelling in hypertensive patients using various thresholds defined by international guidelines and data from the Echocardiographic Measurements in Normal Chinese Adults (EMINCA) study and different indexation methods. METHODS AND RESULTS: LV mass (LVM), relative ventricular wall thickness, and LA volume (LAV) were measured using 2D echocardiography in 612 healthy volunteers selected from the EMINCA study population and 306 adult Chinese patients with hypertension who were age- and gender-matched using propensity score-matched analysis. LVM and LAV values were indexed to body surface area (BSA), height2.7, height1.7, and height2 recommended by guidelines or investigators. Using a previously reported method, LV geometry was divided into normal geometry, concentric remodelling, eccentric hypertrophy, and concentric hypertrophy. The prevalence of LV hypertrophy (LVH) and LV geometric patterns in hypertensive patients were compared using different thresholds and indexation methods. Echocardiographic thresholds from guidelines and healthy volunteers exhibited notable differences, particularly for LAV indexed to height2 and for LVM indexed to height1.7, which resulted in a significantly lower prevalence of LA dilatation and LVH in healthy volunteers. The total proportion of abnormal LV geometric patterns was significantly lower with thresholds from healthy volunteers than from guidelines when LVM was indexed to BSA, height1.7, and height2,7. CONCLUSION: Using current echocardiographic thresholds and indexing methods recommended by guidelines may lead to significant misdiagnosis of LA dilatation, and abnormal LV geometry in Chinese patients with hypertension, and thresholds based on ethnic-specific normal echocardiographic reference values and an accurate indexing algorithm are warranted.

Allometric model improves scaling of left atrial size in obese population: the use of body weight containing variables is challenged.

BACKGROUND: Scaling left atrial (LA) size remains a challenge. An allometric model using body weight (BW) as scaling variable was recently proposed. We sought to examine the performance of this model in an obese population. METHODS: A total of 266 consecutive overweight (110) and obese subjects (class I, II, and III obese 81, 47, and 28, respectively) were studied; 46 normal subjects with normal body mass index (BMI) served as controls. LA dimension (LAD) was scaled to BW, body surface area (BSA), BMI and height, respectively, using both isometric and allometric models. RESULTS: There were no significant differences in age, gender, or height among the five groups. The prevalence of comorbid conditions, wall thickness, E/E' and LAD measures increased significantly with increasing weight group (P < 0.01-0.001). With the isometric model, LAD corrected by BW, BSA, and BMI significantly but paradoxically decreased across the groups (P < 0.05-0.001). With the allometric model, LAD overcorrection by BM, BSA, and BMI was improved, but remained in the class III obese group. In contrast, scaling LAD to height showed significant and graded increase across the five groups in accordance with the increases of BMI, E/E' and the prevalence of comorbid conditions. CONCLUSION: All isometric models that correct LAD by BW or BW containing variables underestimate LA size in overweight and obese groups. The allometric model using height provides more consistent results and should be preferred to models using BW or BW containing variables in scaling LAD in obese population.

Wavelet Scattering Transform for ECG Beat Classification.

An electrocardiogram (ECG) records the electrical activity of the heart; it contains rich pathological information on cardiovascular diseases, such as arrhythmia. However, it is difficult to visually analyze ECG signals due to their complexity and nonlinearity. The wavelet scattering transform can generate translation-invariant and deformation-stable representations of ECG signals through cascades of wavelet convolutions with nonlinear modulus and averaging operators. We proposed a novel approach using wavelet scattering transform to automatically classify four categories of arrhythmia ECG heartbeats, namely, nonectopic (N), supraventricular ectopic (S), ventricular ectopic (V), and fusion (F) beats. In this study, the wavelet scattering transform extracted 8 time windows from each ECG heartbeat. Two dimensionality reduction methods, principal component analysis (PCA) and time window selection, were applied on the 8 time windows. These processed features were fed to the neural network (NN), probabilistic neural network (PNN), and k-nearest neighbour (KNN) classifiers for classification. The 4th time window in combination with KNN (k = 4) has achieved the optimal performance with an averaged accuracy, positive predictive value, sensitivity, and specificity of 99.3%, 99.6%, 99.5%, and 98.8%, respectively, using tenfold cross-validation. Thus, our proposed model is capable of highly accurate arrhythmia classification and will provide assistance to physicians in ECG interpretation.

Transmural peak systolic strain and strain rate predict transmural myocardial blood flow in a pig myocardial infarction model.

OBJECTIVE: To test the hypothesis that the transmural variation of the longitudinal myocardial peak systolic strain (Sp) and strain rate (SRp) can predict the transmural distribution of myocardial blood flow (MBF) in a pig model of acute myocardial infarction. METHODS: The longitudinal Sp and SRp were measured by echocardiography in both subendocardium (Sp-endo, SRp-endo) and subepicardium (Sp-epi, SRp-epi) in the normal, ischemic and infarct segments, respectively. The MBF in corresponding sites was measured by colored microspheres technique. The subendocardial to subepicardial ratio of Sp (Sp-EER), SRp (SRp-EER) and MBF (MBF-EER) were calculated. RESULTS: In the normal segments, Sp-endo and SRp-endo were significantly higher than Sp-epi and SRp-ep, respectively. In the ischemic segments, Sp-endo and SRp-endo decreased to a greater extent than Sp-epi and SRp-epi, respectively. In the infarct segments, Sp-endo, SRp-endo Sp-epi and SRp-epi were all remarkably reduced. High correlations were found between Sp and SRp measurements and MBF in both subendocardium and subepicardium (r = -0.75 to -0.84, p < 0.001). CONCLUSION: Strain and strain rate imaging provides a reliable approach to the noninvasive estimation of the transmural blood distribution across the normal, ischemic and infarct segments.

[The correlation of human serum Lp-PLA2 and hs-CRP and stability of coronary atherosclerotic plaques].

OBJECTIVE: To explore the relationship of serum lipoprotein-associated phospholipase A2 and high sensitive C-reactive protein in vulnerable coronary atherosclerotic plaques. METHODS: Patients undergoing coronary angiography (CAG) were examined for CAD with intravascular ultrasound (IVUS). According to the findings of CAG and IVUS, all the patients were divided into three groups: a control group without plaque, stable plaque group and vulnerable plaque group. The total serum Lp-PLA2 and hs-CRP were measured before angiography and they were valued with T test and Pearson's correlation analysis. RESULTS: (1) Lp-PLA2 level in stable plaque group and vulnerable plaque group was higher than that in control group (P < 0.05). (2) Lp-PLA2 level in the vulnerable plaque group was higher than that in stable plaque group (P < 0.05). (3) hs-CRP level in the vulnerable plaque group is higher than that in the stable plaque group and control group (P < 0.05) and there was significant difference between them. (4) To discriminate vulnerable plaque, the specificity of serum Lp-PLA2 was stronger than that of hs-CRP. CONCLUSIONS: Serum Lp-PLA2 level has higher sensitivity in predicting the vulnerability of the coronary atherosclerotic plaque than hs-CRP. In combination with hs-CRP, we can use Lp-PLA2 as a new biomarker to predict the presence of vulnerable plaque.

A Novel Mathematical Model for Correcting the Physiologic Variance of Two-Dimensional Echocardiographic Measurements in Healthy Chinese Adults.

BACKGROUND: To facilitate differentiation between normal and abnormal values, it is necessary to correct echocardiographic measurements for physiologic variance induced by age, gender, and body size variables. METHODS: A total of 34 two-dimensional echocardiographic parameters were measured in 1,224 healthy Chinese adults with body mass index < 25.0 kg/m2. An optimized multivariate allometric model and scaling equations were first developed in 858 subjects (group A), and their reliability was then verified in the remaining 366 subjects (group B). The traditional single-variable isometric model in which parameters are linearly corrected by a single body size variable (height, weight, body mass index, or body surface area) was used for comparison. The success of correction was defined as the absence of significant correlations (r > 0.20, P < .05) between the corrected values and age or any body size variables, while maintaining high correlations (r > 0.80) between the corrected and uncorrected values. RESULTS: Before correction, all 34 parameters correlated significantly with one or more of the physiologic variables of age and body size and differed significantly between men and women on 29 parameters (85.3%) in both groups. The success rate of correction with the single-variable isometric model was only 11.0% (15 of 136 corrections due to four variable corrections used for each parameter), while use of the optimized multivariate allometric model successfully corrected all 34 parameters (100%) for physiologic variance induced by age and body size variables and eliminated the gender differences in 32 parameters (94.1%). A new set of reference values for corrected echocardiographic measurements independent of age, gender, and body size variables were established. CONCLUSIONS: The novel optimized multivariate allometric model developed in this study is superior to traditional the single-variable isometric model in the correction of echocardiographic parameters for physiologic effects of age, gender, and body size variables and thus should be encouraged in both scientific research and clinical practice.

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.

Quantification of regional volume and systolic function of the left ventricle by real-time three-dimensional echocardiography.

Real-time three-dimensional (3D) echocardiography (RT-3DE) provides a unique technique to evaluate left ventricular regional function in a 3D format. We aimed to explore whether the left ventricular segmental volume and systolic function is uniform and to establish normal values of volume and systolic function parameters of 16 regions in healthy subjects. RT-3DE was performed in 41 normal subjects and four-dimensional (4D)-left ventricle (LV) analysis software and a TomTec workstation were used to analyze data for regional end-diastolic volume (EDV(R)), regional end-systolic volume (ESV(R)), regional stroke volume (SV(R)), regional ejection fraction (EF(R)), ratio of SV(R) to global SV (SV(R/G)) and ratio of SV(R) to global EDV (EF(R/G)). All regional volume and systolic function parameters were not uniform among the left ventricular walls. They all increased in the order of inferior, posterior, lateral, septal, anterior and antero-septal walls with an increasing trend from the apical, middle to basal segments. The systolic function (EF(R), SV(R/G) and EF(R/G)) of the anterior and antero-septal walls was significantly higher than that of the lateral, inferior and posterior walls. And the intra- and interobserver variability for EDV(R), ESV(R), SV(R/G) and EF(R/G) ranged from 2.9% to 5.8%. In conclusion, the regional volume and systolic function of the left ventricle is not uniform and, therefore, a normal left ventricle cannot be regarded as a symmetric model for assessing the regional systolic function. This information may improve the accuracy of RT-3DE techniques in the assessment of the left ventricular regional function. (E-mail: zhangyun@sdu.edu.cn and yaogh@yahoo.com).

The role of carotid plaque vulnerability and inflammation in the pathogenesis of acute ischemic stroke.

BACKGROUND: Increasing evidences show that disruption of carotid plaque followed by arterio-arterial thromboembolism is an important mechanism in the generation of ischemic stroke. Inflammatory mechanisms play a key role in transforming structurally vulnerable plaques into functionally unstable ones. The purpose of the present study is to evaluate the roles of carotid plaque vulnerability and inflammation in the pathogenesis of acute ischemic stroke. METHODS: Fifty-two patients with acute ischemic stroke affecting the anterior circulation (stroke group) and 44 with asymptomatic carotid stenosis (asymptomatic group) were investigated. Duplex ultrasonography was used to evaluate the characteristics of carotid plaque and grading the degree of carotid stenosis. Plaque echogenicity was assessed as echolucent, predominantly echolucent, predominantly echogenic, or echogenic. Plaque surface was classified as smooth, irregular, or ulcerated. All subjects had duplex-determined 50% to 99% carotid stenosis. Serum levels of matrix metalloproteinase-9 (MMP-9), tissue inhibitors of metalloproteinases (TIMP-1), soluble CD40 ligand (sCD40L) and high-sensitivity C-reactive protein (hsCRP) were measured. RESULTS: Plaques in the stroke group were echolucent or predominantly echolucent, whereas those of the asymptomatic group were predominantly echogenic or echogenic plaques (P<0.05). Irregular and ulcerated plaques were frequently found in stroke patients, while smooth plaques were frequently detected in asymptomatic patients (P<0.05). Serum levels of MMP-9, sCD40L, hsCRP were higher in stroke than in asymptomatic patients. By contrast, serum TIMP-1 levels were significantly higher in the asymptomatic than in the stroke group. CONCLUSIONS: The results suggest that inflammation plays a crucial role in carotid plaque vulnerability and, together with carotid plaque morphology, in the pathogenesis of acute ischemic stroke.

[Development of a new MCE-based quantitative analysis system for myocardial microcirculation].

In this paper is presented the research and development of a new myocardial contrast echocardiography (MCE)-based quantitative analysis system for myocardial microcirculation. The system can measure the values of A, beta, A x beta, A-EER (endo-epi ratio of A), beta-EER and A x beta-EER from the signal intensity of real-time 2-D grayscale images and power Doppler images; it can draw the time-intensity curves to indicate the variation of the intensity of microbubbles scattering in subendocardial layer and subepicardial layer with the varying of myocardial segments; and it can estimate the hemodynamic parameters by nonlinear regression analysis. So the MCE software system has brought the quantitative analysis of real-time MCE to success.

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.

MiR-139-5p protect against myocardial ischemia and reperfusion (I/R) injury by targeting autophagy-related 4D and inhibiting AMPK/mTOR/ULK1 pathway.

This study aimed at investigating the effect and underlying mechanism of miR-139-5p in myocardial ischemia and reperfusion (I/R) injury. A hypoxia/ reoxygenation (H/R) model was established in H9c2 cardiomyocytes. The level of miR-139-5p was detected in H/R-treated cardiomyocytes, and subsequently, the level of miR-139-5p or its target gene autophagy-related 4D (ATG4D) was up- or downregulated. Furthermore, the cell viability, apoptosis, and autophagy, as well as the expression levels of the proteins related to adenosine 5'-monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)/uncoordinated 51-like kinase 1 (ULK1) signaling pathway were determined. The MiR-139-5p was downregulated in H/R-treated cardiomyocytes in comparison to the untreated cells (P < 0.05). H/R treatment significantly decreased the cell viability but increased the cell apoptosis ratio, and autophagy-related proteins levels (P < 0.05). The overexpression of MiR-139-5p significantly promoted cell apoptosis and inhibited cell autophagy induced by H/R (P < 0.05); however, the effects of miR-139-5p on cell apoptosis and cell autophagy were inhibited by its target gene ATG4D (P < 0.05). Furthermore, the upregulated miR-139-5p remarkably inhibited the expression of p-AMPK, p-Raptor, and ULK1, but increased that of p-mTOR (P < 0.05) in H/R-treated cardiomyocytes. The MiR-139-5p has the potential of regulating cell apoptosis and cell autophagy by inhibiting AMPK/mTOR/ULK1 signaling pathway and thereby protecting against myocardial I/R injury.