Early identification of STEMI patients with emergency chest pain using lipidomics combined with machine learning.

OBJECTIVES: To analyze the differential expression of lipid spectrum between ST-segment elevated myocardial infarction (STEMI) and patients with emergency chest pain and excluded coronary artery disease (CAD), and establish the predictive model which could predict STEMI in the early stage. METHODS: We conducted a single-center, nested case-control study using the emergency chest pain cohort of Peking University Third Hospital. Untargeted lipidomics were conducted while LASSO regression as well as XGBoost combined with greedy algorithm were used to select lipid molecules. RESULTS: Fifty-two STEMI patients along with 52 controls were enrolled. A total of 1925 lipid molecules were detected. There were 93 lipid molecules in the positive ion mode which were differentially expressed between the STEMI and the control group, while in the negative ion mode, there were 73 differentially expressed lipid molecules. In the positive ion mode, the differentially expressed lipid subclasses were mainly diacylglycerol (DG), lysophophatidylcholine (LPC), acylcarnitine (CAR), lysophosphatidyl ethanolamine (LPE), and phosphatidylcholine (PC), while in the negative ion mode, significantly expressed lipid subclasses were mainly free fatty acid (FA), LPE, PC, phosphatidylethanolamine (PE), and phosphatidylinositol (PI). LASSO regression selected 22 lipids while XGBoost combined with greedy algorithm selected 10 lipids. PC (15: 0/18: 2), PI (19: 4), and LPI (20: 3) were the overlapping lipid molecules selected by the two feature screening methods. Logistic model established using the three lipids had excellent performance in discrimination and calibration both in the derivation set (AUC: 0.972) and an internal validation set (AUC: 0.967). In 19 STEMI patients with normal cardiac troponin, 18 patients were correctly diagnosed using lipid model. CONCLUSIONS: The differentially expressed lipids were mainly DG, CAR, LPC, LPE, PC, PI, PE, and FA. Using lipid molecules selected by XGBoost combined with greedy algorithm and LASSO regression to establish model could accurately predict STEMI even in the more earlier stage.

Association between serum cartilage oligomeric matrix protein and coronary artery calcification in maintenance hemodialysis patients.

BACKGROUND: Coronary artery calcification (CAC) is common in end-stage renal disease (ESRD) patients, and the extent of CAC is closely related to cardiovascular outcomes in ESRD patients. Cartilage oligomeric matrix protein (COMP), as a component of the vascular matrix, has been found to be an inhibitor of arterial calcification in basic studies. However, there is no clinical research on the correlation between COMP and CAC in maintenance hemodialysis (MHD) patients. The aim of this study was to explore the relationship between serum COMP levels and CAC and cardiovascular events in MHD patients. METHODS: Serum COMP levels were compared between 54 MHD patients and 66 healthy people. MHD patients were then divided into three groups according to the tertiles of the concentration of COMP level and were followed up for major adverse cardiac events (MACEs), which were defined as a combined end point of new onset angina pectoris, nonfatal myocardial infarction, heart failure, coronary artery revascularization, hospitalization due to angina pectoris and all-cause deaths. The CAC score was calculated based on computed tomography scans. RESULTS: The serum COMP level in MHD patients was significantly higher than that in the general population [984.23 (248.43-1902.61) ng/mL vs. 219.01 (97.26-821.92) ng/mL, P < 0.01]. Serum COMP levels were positively correlated with CAC (r = 0.313, P = 0.021) and serum parathyroid hormone in MHD patients (r = 0.359, P < 0.01). Linear regression suggested that after adjusting for age, fasting blood glucose (Glu) and glycosylated hemoglobin (HbAlc), CAC score was an independent predictor in the final model for COMP level (ß = 0.424, t = 3.130, P < 0.01). The receiver operating characteristic (ROC) curve showed that COMP ≥ 994 mg/mL had 68.0% sensitivity and 72.4% specificity for the prediction of severe CAC [area under the curve (AUC): 0.674, P = 0.030, 95% CI: 0.526-0.882]. After a median follow-up of 16 months (8-24 months), there was no difference in the incidence rate of MACEs between the upper, middle and lower serum COMP groups. CONCLUSIONS: Our study found that MHD patients have higher levels of circulating COMP than controls. The serum COMP level is positively correlated with CAC score and could be used as a biomarker of severe CAC in MHD patients. However, there is no obvious correlation between serum COMP levels and the incidence of cardiovascular events.

Excitation-Contraction Coupling Time is More Sensitive in Evaluating Cardiac Systolic Function.

BACKGROUND: Pressure overload-induced myocardial hypertrophy is a key step leading to heart failure. Previous cellular and animal studies demonstrated that deteriorated excitation-contraction coupling occurs as early as the compensated stage of hypertrophy before the global decrease in left ventricular ejection fraction (LVEF). This study was to evaluate the cardiac electromechanical coupling time in evaluating cardiac systolic function in the early stage of heart failure. METHODS: Twenty-six patients with Stage B heart failure (SBHF) and 31 healthy controls (CONs) were enrolled in this study. M-mode echocardiography was performed to measure LVEF. Tissue Doppler imaging (TDI) combined with electrocardiography (ECG) was used to measure cardiac electromechanical coupling time. RESULTS: There was no significant difference in LVEF between SBHF patients and CONs (64.23 ± 8.91% vs. 64.52 ± 5.90%; P = 0.886). However, all four electromechanical coupling time courses (Qsb: onset of Q wave on ECG to beginning of S wave on TDI, Qst: onset of Q wave on ECG to top of S wave on TDI, Rsb: top of R wave on ECG to beginning of S wave on TDI, and Rst: top of R wave on ECG to top of S wave on TDI) of SBHF patients were significantly longer than those of CONs (Qsb: 119.19 ± 35.68 ms vs. 80.30 ± 14.81 ms, P < 0.001; Qst: 165.42 ± 60.93 ms vs. 129.04 ± 16.97 ms, P = 0.006; Rsb: 82.43 ± 33.66 ms vs. 48.30 ± 15.18 ms, P < 0.001; and Rst: 122.37 ± 36.66 ms vs. 93.25 ± 16.72 ms, P = 0.001), and the Qsb, Rsb, and Rst time showed a significantly higher sensitivity than LVEF (Rst: P =0.032; Rsb: P = 0.003; and Qsb: P = 0.004). CONCLUSIONS: The cardiac electromechanical coupling time is more sensitive than LVEF in evaluating cardiac systolic function.

Admission macrophage migration inhibitory factor predicts long-term prognosis in patients with ST-elevation myocardial infarction.

Aims: We previously showed in patients with ST-segment elevated myocardial infarction (STEMI) that admission levels of macrophage migration inhibitory factor (MIF) predict infarct size. We studied whether admission MIF alone or in combination with other biomarkers is useful for risk assessment of acute and chronic clinical outcomes in STEMI patients. Methods and results: A total of 658 STEMI patients treated with primary percutaneous coronary intervention (PCI) were consecutively recruited. MIF level was determined at admission and echocardiography performed on day-3 and then 12 months post-MI. Patients were followed for a median period of 64 months. Major endpoints included ST-segment resolution, all-cause mortality, and major adverse cardiovascular events (MACE). High MIF level was associated with larger enzymatic infarct size, incomplete resolution of ST-segment elevation post-PCI, impaired left ventricular ejection fraction (LVEF), and poorer improvement of LVEF (all P < 0.001). After adjustment for classical risk factors standard biomarkers and day-3 LVEF, admission MIF remained independently prognostic for all-cause mortality [hazard ratio (HR) 2.27, 95% confidence interval (CI) 1.43-3.22], and MACE (HR 1.39, 95% CI 1.12-1.71, both P < 0.05). MIF was a significant additive predictor of all-cause mortality with a net reclassification improvement of 0.34 (P = 0.02). Furthermore, patients in high tertile of both admission MIF and day-3 Nt-proBNP had the highest mortality risk relative to other tertile groups (HR 11.28, 95% CI 4.82-26.94; P < 0.001). Conclusion: STEMI patients with high admission MIF level experienced a poorer recovery of cardiac function and worse long-term adverse outcomes. Combination of Nt-proBNP with MIF further improves prognostic capability.

IL-18 cleavage triggers cardiac inflammation and fibrosis upon ß-adrenergic insult.

Aims: Rapid over-activation of ß-adrenergic receptor (ß-AR) upon stress leads to cardiac inflammation, a prevailing factor that underlies heart injury. However, mechanisms by which acute ß-AR stimulation induce cardiac inflammation still remain unknown. Here, we set out to identify the crucial role of inflammasome/interleukin (IL)-18 in initiating and maintaining cardiac inflammatory cascades upon ß-AR insult. Methods and results: Male C57BL/6 mice were injected with a single dose of ß-AR agonist, isoproterenol (ISO, 5 mg/kg body weight) or saline subcutaneously. Cytokine array profiling demonstrated that chemokines dominated the initial cytokines upregulation specifically within the heart upon ß-AR insult, which promoted early macrophage infiltration. Further investigation revealed that the rapid inflammasome-dependent activation of IL-18, but not IL-1ß, was the critical up-stream regulator for elevated chemokine expression in the myocardium upon ISO induced ß1-AR-ROS signalling. Indeed, a positive correlation was observed between the serum levels of norepinephrine and IL-18 in patients with chest pain. Genetic deletion of IL-18 or the up-stream inflammasome component NLRP3 significantly attenuated ISO-induced chemokine expression and macrophage infiltration. In addition, IL-18 neutralizing antibodies selectively abated ISO-induced chemokines, proinflammatory cytokines and adhesion molecules but not growth factors. Moreover, blocking IL-18 early after ISO treatment effectively attenuated cardiac inflammation and fibrosis. Conclusion: Inflammasome-dependent activation of IL-18 within the myocardium upon acute ß-AR over-activation triggers cytokine cascades, macrophage infiltration and pathological cardiac remodelling. Blocking IL-18 at the early stage of ß-AR insult can successfully prevent inflammatory responses and cardiac injuries.

Altered serum level of cartilage oligomeric matrix protein and its association with coronary calcification in patients with coronary heart disease.

BACKGROUND: Cartilage oligomeric matrix protein (COMP) is mainly found in the skeletal system and vascular smooth muscle cells. Recent researches showed that it had a protective function on blood vessels and could also inhibit vascular calcification. We investigated the serum COMPs in coronary heart disease (CHD) patients, and the relationship between serum COMP and the calcification of coronary artery. METHODS: A total of 233 consecutive chest pain patients who first underwent coronary angiography followed by multi-slice computed tomography (MSCT) within six months were recruited and divided into two groups according to the coronary angiography luminal diameter narrowing percentages: CHD group (diameter narrowing ≥ 50%, n = 194) and control group (diameter narrowing < 50%, n = 39). The Gensini score, Syntax score and coronary artery calcium score (CACs) were calculated. The serum COMP level was determined using ELISA. RESULTS: The levels of COMP were significantly higher in the CHD group than in the control group 155.7 (124.5-194.5) ng/mL vs. 128.4 (113.0-159.9) ng/mL, P = 0.019. There were no correlation between COMP, Gensini score, Syntax score, severity of coronary stenosis and the number of coronary artery with stenosis > 50%. The serum COMP was correlated with age (r = 0.294, P < 0.001), fasting glucose (r = 0.163, P = 0.015), HbA1c (r = 0.194, P = 0.015) and CACs (r = 0.137, P = 0.037). Stepwise linear regression analysis showed that COMP level and age were independent predictors of CACs in the CHD patients (ß = 0.402, t = 2.612, P = 0.015; ß = 0.472, t = 3.077, P = 0.005). Performance of COMP for predicting CHD was shown as area under curve (AUC): 0.632, 95% CI: 0.549-0.715 and upper tertile CACs was AUC: 0.602, 95% CI: 0.526-0.678 in receiver operating characteristic (ROC) curve analysis. CONCLUSION: Calcification of coronary artery was an independent predictor of serum COMPs.

Effect of high temperature on immune response of grass carp (Ctenopharyngodon idellus) by transcriptome analysis.

Exposure to high temperature is an inherent feature of grass carp culture in southern China and juvenile grass carps are predisposed to infectious disease in this condition. To understand how high temperature impacts the immune response to pathogens in grass carp, the transcriptomic profiles of the spleens from immune injected grass carp groups undergoing heat stress and normal temperature were investigated. An average of 72 million clean reads per library was obtained, and approximate 80% of these genes were successfully mapped to the reference genome. A total of 2287 up-regulated and 1068 down-regulated genes were identified. 10 immune-related categories involving 90 differently expressed genes were scrutinized. Expression patterns of 18 differentially expressed genes involving in immune response were validated by quantitative real-time RT-PCR. These results provide further significant insights into the influence mechanism of high temperature to immune response in grass carp.

Correlation between growth differentiation factor-15 and collagen metabolism indicators in patients with myocardial infarction and heart failure.

BACKGROUND: Growth differentiation factor (GDF)-15, a divergent member of the transforming growth factor beta super-family does appear to be up-regulated in response to experimental pressure overload and progression of heart failure (HF). HF frequently develops after myocardial infarction (MI), contributing to worse outcome. The aim of this study is to assess the correlation between GDF-15 levels and markers related to collagen turnover in different stages of HF. METHODS: The study consists of a cohort of 179 patients, including stable angina pectoris patients (AP group, n = 50), old MI patients without HF (OMI group, n = 56), old MI patients with HF (OMI-HF group, n = 38) and normal Control group (n = 35). Both indicators reflecting the synthesis and degradation rates of collagen including precollagen I N-terminal peptide (PINP), type I collagen carboxy-terminal peptide (ICTP), precollagen III N-terminal peptide (PIIINP) and GDF-15 were measured using an enzyme-linked inmunosorbent assay. RESULTS: The plasma GDF-15 level was higher in OMI-HF group (1373.4 ± 275.4 ng/L) than OMI group (1036.1 ± 248.6 ng/L), AP group (784.6 ± 222.4 ng/L) and Control group (483.8 ± 186.4 ng/L) (P < 0.001). The indicators of collagen turnover (ICTP, PINP, PIIINP) all increased in the OMI-HF group compared with Control group (3.03 ± 1.02 µg/L vs. 2.08 ± 0.95 µg/L, 22.2 ± 6.6 µg/L vs. 16.7 ± 5.1 µg/L and 13.2 ± 7.9 µg/L vs. 6.4 ± 2.1 µg/L, respectively; P < 0.01). GDF-15 positively correlated with ICTP and PIIINP (r = 0.302, P < 0.001 and r = 0.206, P = 0.006, respectively). GDF-15 positively correlated to the echocardiographic diastolic indicators E/Em and left atrial pressure (r = 0.349 and r = 0.358, respectively; P < 0.01), and inversely correlated to the systolic indicators left ventricular ejection fraction and the average of peak systolic myocardial velocities (Sm) (r = -0.623 and r = -0.365, respectively; P < 0.01). CONCLUSION: Plasma GDF-15 is associated with the indicators of type I and III collagen turnover.

Serial changes of mean platelet volume in relation to Killip Class in patients with acute myocardial infarction and primary percutaneous coronary intervention.

INTRODUCTION: Mean platelet volume (MPV) is related to the reactivity of platelets. Among survivors of acute myocardial infarction (MI), greater MPV is known to be associated with impaired reperfusion and higher mortality. The aims of the study is to investigate the dynamic changes of MPV and the relation between MPV and cardiac function in patients with acute MI and received primary percutaneous coronary intervention (PCI). MATERIALS AND METHODS: This retrospective cohort study included patients presented during January 2008 to March 2011 to Peking University Third Hospital with ST-segment elevation MI. All patients received successful PCI. MPV was measured serially, using a Sysmex XE2100 haematology analyser, from admission to day-7 after MI. RESULTS: In 375 patients, MPV was at its highest value (10.2±1.0 fL) and correlated well with platelet distribution width (PDW, r=0.833, p<0.0001) at the admission, and then reduced by 16% within the 24 hours, together with marked weakening of its correlation with PDW. Patients with poorer ventricular function, estimated by high Killip Class (≥2, n=96), had higher MPV values at all-time points. By logistic regression model and after adjusting for related confounders, high MPV remained as an independent predictor of Killip Class ≥2 (OR 1.873, CI 95% 1.373-2.673, p=0.001). Clopidogrel pre-usage resulted in significant MPV reduction on admission. CONCLUSIONS: MPV undergoes rapid and dynamic changes during the acute phase of MI, and was higher in patients with high Killip Class, suggesting a predictive value of MPV in ventricular dysfunction and clinical outcome of acute phase of MI.

Macrophage migration inhibitory factor for the early prediction of infarct size.

BACKGROUND: Early diagnosis and knowledge of infarct size is critical for the management of acute myocardial infarction (MI). We evaluated whether early elevated plasma level of macrophage migration inhibitory factor (MIF) is useful for these purposes in patients with ST-elevation MI (STEMI). METHODS AND RESULTS: We first studied MIF level in plasma and the myocardium in mice and determined infarct size. MI for 15 or 60 minutes resulted in 2.5-fold increase over control values in plasma MIF levels while MIF content in the ischemic myocardium reduced by 50% and plasma MIF levels correlated with myocardium-at-risk and infarct size at both time-points (P < 0.01). In patients with STEMI, we obtained admission plasma samples and measured MIF, conventional troponins (TnI, TnT), high sensitive TnI (hsTnI), creatine kinase (CK), CK-MB, and myoglobin. Infarct size was assessed by cardiac magnetic resonance (CMR) imaging. Patients with chronic stable angina and healthy volunteers were studied as controls. Of 374 STEMI patients, 68% had elevated admission MIF levels above the highest value in healthy controls (> 41.6 ng/mL), a proportion similar to hsTnI (75%) and TnI (50%), but greater than other biomarkers studied (20% to 31%, all P < 0.05 versus MIF). Only admission MIF levels correlated with CMR-derived infarct size, ventricular volumes and ejection fraction (n = 42, r = 0.46 to 0.77, all P < 0.01) at 3 day and 3 months post-MI. CONCLUSION: Plasma MIF levels are elevated in a high proportion of STEMI patients at the first obtainable sample and these levels are predictive of final infarct size and the extent of cardiac remodeling.

[Clopidogrel resistance of patients with coronary artery disease and its correlation with platelet count and mean platelet volume].

OBJECTIVE: To explore the association between clopidogrel resistance (CR) as assessed by whole blood electrical impedance aggregometry (EIA) and platelet parameters. METHODS: The prospective study comprised 152 patients with coronary artery disease (CAD) on the therapy of clopidogrel. EIA employed adenosine diphosphate (ADP) as an inductor to measure platelet aggregation. CR was defined by spontaneous aggregation (electrical impedance ≥ 10 Ω). The subjects were divided into 2 groups of CR and clopidogrel sensitive (CS). Platelet parameters were measured by routine blood test. And their clinical data and outcomes were analyzed. RESULTS: The prevalence of CR was 10.5% (n = 16). The ratio of patients with diabetes in CR group was higher than that in CS group (7/16 vs 29/136, P = 0.046). Platelet counts and mean platelet volume (MPV) were also higher in CR group than those in CS group ((241 ± 58) ×10(9)/L vs (185 ± 56)×10(9)/L, (8.0 ± 0.8) fl vs (7.4 ± 0.9) fl, both P < 0.05). Logistic regression indicated each 10×10(9)/L increase in platelet and each 1 fl increase in MVP were associated with 0.376 and 1.015 folds increase in CR onset respectively (OR = 1.376, 95%CI 1.097 - 1.725, P = 0.006;OR = 2.015, 95%CI 1.148 - 3.537, P = 0.015). The patients with CR had more cardiovascular events during an average follow-up of 53 months (6/16 vs 23/136, P = 0.047). CONCLUSIONS: CAD patients with CR had higher incidence of cardiovascular events. Increased platelet counts and MPV levels are independent predictors for CR in CAD patients.

Predictive value of antiplatelet resistance on early stent thrombosis in patients with acute coronary syndrome.

BACKGROUND: Despite outstanding antiplatelet properties of aspirin and clopidogrel, some patients taking these drugs continue to suffer complications. Antiplatelet resistance appears to be a new prognostic factor in acute coronary syndrome patients for clinical events associated with stent thrombosis (ST). However, there is no optimal method to identify it and assess its correlation to clinical outcomes. This study sought to evaluate the predictive value of antiplatelet resistance assessed by whole blood impedance aggregometry for the risk of early ST in patients with acute coronary syndrome who underwent coronary stenting. METHODS: Platelet responses to aspirin and clopidogrel in 86 patients with acute coronary syndrome were measured by whole blood impedance aggregometry. Spontaneous platelet aggregation was defined as antiplatelet resistance identified by the increased electrical impedance. The clinical endpoint was early stent thrombosis during 30-day follow-up after coronary stenting. RESULTS: The prevalence of aspirin resistance, clopidogrel resistance and dual resistance of combined clopidogrel and aspirin resistance were 19.8%, 12.8% and 5.8% respectively. Diabetes, female and higher platelet counts were more frequently detected in clopidogrel-resistant and dual-resistant patients. During 30-day follow-up, the patients with clopidogrel resistance and dual resistance had higher incidence of early stent thrombosis (18.2% vs. 1.3%, 40.0% vs. 1.2%, P < 0.05). Binary Logistic Regression analysis indicated that dual resistance remained an independent predicator for early stent thrombosis (odds ratio 34.064, 95%CI 1.919 - 604.656, P = 0.016). CONCLUSIONS: Antiplatelet resistance assessed by whole blood impedance aggregometry is paralleled to clinical events, and dual antiplatelet resistance is an independent predicator for early stent thrombosis in patients with acute coronary syndrome. As a physiological assessment of platelet reactivity, whole blood impedance aggregometry is a convenient and accurate option for measuring antiplatelet resistance and hence predicting early stent thrombosis.

Up-regulating relaxin expression by G-quadruplex interactive ligand to achieve antifibrotic action.

Myocardial fibrosis is a key pathological change in a variety of heart diseases contributing to the development of heart failure, arrhythmias, and sudden death. Recent studies have shown that relaxin prevents and reverses cardiac fibrosis. Endogenous expression of relaxin was elevated in the setting of heart disease; the extent of such up-regulation, however, is insufficient to exert compensatory actions, and the mechanism regulating relaxin expression is poorly defined. In the rat relaxin-1 (RLN1, Chr1) gene promoter region we found presence of repeated guanine (G)-rich sequences, which allowed formation and stabilization of G-quadruplexes with the addition of a G-quadruplex interactive ligand berberine. The G-rich sequences and the G-quadruplexes were localized adjacent to the binding motif of signal transducer and activator of transcription (STAT)3, which negatively regulates relaxin expression. Thus, we hypothesized that the formation and stabilization of G-quadruplexes by berberine could influence relaxin expression. We found that berberine-induced formation of G-quadruplexes did increase relaxin gene expression measured at mRNA and protein levels. Formation of G-quadruplexes significantly reduced STAT3 binding to the promoter of relaxin gene. This was associated with consequent increase in the binding of RNA polymerase II and STAT5a to relaxin gene promoter. In cardiac fibroblasts and rats treated with angiotensin II, berberine was found to suppress fibroblast activation, collagen synthesis, and extent of cardiac fibrosis through up-regulating relaxin. The antifibrotic action of berberine in vitro and in vivo was similar to that by exogenous relaxin. Our findings document a novel therapeutic strategy for fibrosis through up-regulating expression of endogenous relaxin.

[Correlation between antiplatelet resistance and recurrent cardiac ischemic events of patients with acute myocardial infarction].

OBJECTIVE: To evaluate the predictive value of antiplatelet resistance assessed by whole blood electronic impedance aggregometry (EIA) for the risk of recurrent cardiac ischemic events in patients with acute myocardial infarction (AMI) who underwent coronary stenting. METHODS: We enrolled 109 patients with AMI, 72 (66.1%) men and 37 (33.9%) women with mean age (63 ± 12) years, who were treated with aspirin and clopidogrel daily after coronary stenting. EIA used arachidonic acid (AA) and adenosine diphosphate (ADP) as inductors to measure platelet aggregation inhibited by aspirin and clopidogrel respectively. The subjects were divided into four groups: pure aspirin resistant group (AR, electrical impedance > 0 Ω), pure clopidogrel resistant group (CR, electrical impedance ≥ 10 Ω), dual resistant group (DR) and dual sensitive group (DS). The primary outcomes were recurrent cardiac ischemic events during the 12-month follow-up. RESULTS: Antiplatelet resistance occurred more often in patients with type 2 diabetes (P = 0.027). The platelet counts (PLT) were higher in antiplatelet resistant groups than DS group (P = 0.013). During the 12-month follow-up, the antiplatelet resistant patients had a higher incidence of recurrent cardiac ischemic events and stent thrombosis (ST) than the patients without (12.5%, 10.0%, 50.0% vs 3.8%, P = 0.036; 6.3%, 10.0%, 50.0% vs 1.3%, P = 0.000; respectively). Binary Logistic regression indicated that dual resistance remained an independent predicator of recurrence cardiac ischemic events and ST (OR 5.99, 95%CI 1.05 - 34.34, P = 0.045; OR 6.36, 95%CI 1.13 - 35.78, P = 0.036; respectively). CONCLUSIONS: As a physiological assessment of platelet reactivity, EIA is a convenient and accurate option for measuring aspirin resistance. Antiplatelet resistance assessed by EIA is paralleled to clinical events. Dual resistance is an independent predicator for ST and recurrence cardiac ischemic events in patients with AMI.

[Correlation between levels of serum growth differentiation factor-15 and acute coronary syndrome].

OBJECTIVE: To explore the association between the levels of serum growth differentiation factor-15(GDF-15) and acute coronary syndrome(ACS) in patients undergoing coronary angiography(CAG). METHODS: In this prospective study, 120 candidates (30 healthy controls and 90 patients with ACS) admitted to our hospital from March 2006 to April 2008 were included. The patients with ACS were divided into 3 groups: (1)Group AMI-emergency (AMI-E), including 30 patients with acute myocardial infarction (AMI) who underwent CAG within 12 hours of the onset of symptoms. (2) Group AMI 7-14 d, including 30 patients with AMI who underwent CAG within 7-14 days of the onset of symptoms. (3)Group UAP including 30 patients with unstable angina pectoris. The serum level of GDF-15 was determined by ELISA. RESULTS: The level of GDF-15 for group ACS was (649.0 ± 224.21) ng/L, which was significantly higher than that of control group [(537.2 ± 262.9)ng/L,P<0.01]. The level of serum GDF-15 significantly increased in group AMI-E [(801.6 ± 218.4)ng/L] compared with group AMI 7-14 d [(656.2 ± 252.4)ng/L,P=0.042, 95% CI 1.001-1.061], group UAP [(586.9 ± 225.6)ng/L, P=0.001, 95% CI 0.809-0.950] and control group(P<0.05, 95% CI 1.000-1.012) after being adjusted for relevant covariates. The elevated level of GDF-15 was related to biomarkers, such as white blood cells count (WBC, r(2)=0.276, P=0.002), lactate dehyerogenase(LDH, r(2)=0.288, P=0.004), creatine kinase 2(CK-MB, r(2)=0.350, P<0.001) and troponin T(TnT, r(2) =0.344, P=0.001). CONCLUSION: GDF-15 protein expression increases in ACS, and the level of GDF-15 rapidly increases and remains elevated in the early period of acute myocardial infarction. The elevated level of GDF-15 is related to biomarkers, such as WBC, LDH, CK-MB, and TnT. GDF-15 could be a new and independent biomarker in evaluating the patients with cardiovascular disease.

[Mitochondrial fusion protein Mfn2 and cardiovascular diseases].

Mitofusin 2 (Mfn2) is a mitochondrial dynamin-related protein involved in the mitochondrial fusion reaction and is also connected to an altered mitochondrial energy supply. Mfn2 is a signaling molecule, plays an important role in cell proliferation, differentiation and apoptosis, which participates in the pathophysiology of several cardiovascular diseases, such as hypertension, restenosis after angioplasty, atherosclerosis, cardiac hypertrophy, and cardiac oxidative stress injury. Regulating the mitochondria-related metabolism, Mfn2 affects diabetes and insulin resistance pathogenesis. In addition, Mfn2 could be an important biomarker and therapeutic target molecule for cardiovascular diseases.

Preliminary study on a single balloon cross-midline expansion via unipedicular approach in kyphoplasty / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Recently, bilateral transpedicular kyphoplasty with a single balloon was performed for osteoporotic vertebral body compression fractures (OVCFs) to reduce the fees of the operation, but the time of operation and radiation exposure are longer. The aim of this study was to determine the safety and effectiveness of a single balloon cross-midline expansion via unipedicular approach in kyphoplasty for OVCFs.</p><p><b>METHODS</b>Thirty-six patients with painful OVCFs (61 vertebrae) were enrolled in this research. Unilateral transpedicular puncture was performed under the fluoroscopy monitoring of an oblique angle down the pedicle. A single balloon was introduced through unipedicular approach. The final balloon position was in the midline of the vertebral body with the balloon cross-midline expansion and bone cement filled. Clinical outcomes were determined by comparison of the preoperative and postoperative visual analogue scale (VAS) and Oswestry disability index (ODI). Radiographic assessment included restoration of vertebral height and correction of kyphosis. Follow-up was conducted for 6 - 12 months (mean 9.2 months).</p><p><b>RESULTS</b>Thirty-six consecutive patients with 61 vertebrae were successfully operated on with a mean operation time of 37.4 minutes per vertebra. All patients had dramatic pain relief and functional recovery within 96 hours after the procedure with no surgery or device-related complications. VAS score improved from 7.27 +/- 1.02 preoperatively to 2.71 +/- 0.75 postoperatively (P < 0.01). ODI score was decreased from (71.14 +/- 10.94)% preoperatively to (26.56 +/- 6.35)% postoperatively. The average loss of anterior body height was (14.33 +/- 2.76) mm before procedure and (10.03 +/- 1.83) mm after procedure (P < 0.01), while the average loss of middle body height was (10.15 +/- 2.70) mm before procedure and (5.89 +/- 1.83) mm after procedure (P < 0.01). The kyphotic deformity was corrected from (23.43 +/- 5.00) degree to (16.16 +/- 2.77) degree (P < 0.01). The pain relief and functional recovery were substantial and maintained to the last follow-up without any re-collapse or adjacent level fracture.</p><p><b>CONCLUSIONS</b>A single-balloon cross-midline expansion via unipedicular approach in kyphoplasty for OVCFs is an effective and safe procedure with less cost, less operation time and less radiation exposure when compared with the conventional kyphoplasty technique.</p>

[Hyperplasia suppressor gene induces vascular smooth muscle cell apoptosis].

OBJECTIVE: To study the effect of hyperplasia suppressor gene (HSG) in inducing vascular smooth muscle cell apoptosis and the underlying mechanisms. METHODS: The cultured VSMCs were transfected with an adenoviral vector containing rat HSG gene. Effects of HSG on VSMC apoptosis were investigated by fluorescent dye staining to detect the tact of nuclei, and by flow cytometry to define the content of DNA and to detect the levels of caspase-3. The expressions of Bcl-2 and Bax were also performed by Western blot analysis. RESULTS: The increased expression of HSG in VSMCs infected with AdHSG induced apoptotic cell death detected by flow cytometry assay and nucleic staining. Compared with control groups, HSG induced vascular smooth muscle cell apoptosis 72 h after infected with adenoviral vector (39.6%+/-3.2% vs. 2.6%+/-0.9%, P< 0.01). Overexpression of HSG also increased the activity of caspase-3 (0.354+/-0.104 vs. 0.064+/-0.022,P<0.01)and the release of cytochrome c. The Bcl-2 protein level was decreased ( 0.26+/-0.03 vs. 1.06+/-0.07,P<0.01)in AdHSG infected cells. CONCLUSION: Hyperplasia induced vascular smooth muscle cell apoptosis. HSG downregulated the expression of Bcl-2/Bax and activated caspase-3, and therefore promoted the release of cytochrome c and induced cell apoptosis.

[Adhesion between monocytes and vascular smooth muscle cells induced by integrin beta1-mediated platelet-derived growth factor].

OBJECTIVE: To investigate the effects of platelet-derived growth factor (PDGF)-BB on the vascular smooth muscle cell (VSMC)-monocyte interaction and the mechanism thereof. METHODS: Rat aortic VSMC were pretreated with PDGF-BB of the concentrations of 0, 2.5, 5, 10, and 20 ng/ml for 8 hours and then co-incubated with human monocytes of the line THP-1 labeled with PKH26, a cellular membrane fluorescent marker, i.e., to be subjected to binding assay to observe the dose-effect relationship. Other VSMC were co-cultured with PDGF of the concentration of 10 ng/ml for 1, 2, 4, 12, and 24 hours respectively and then interacted with PKH26-abeled THP-1 cells so as to observe the time-response relationship. Monoclonal antibody against integrin beta1 was co-cultured with VSMC for 30 min, and then PKH26-labeled THP-1 cells were added to block the effect of PDGF. After the incubation of THP-1 cells and VSMC, the amount of bound cells was counted using fluorescent phase-contrast microscopy. The effect of PDGF on the expression of integrin beta1 was detected by Western blotting. RESULTS: The amounts of THP-1 cells bound to VSMC pretreated with PDGF of the concentrations of 2.5, 5, 10, and 20 ng/ml respectively were 1.1, 2.1, 3.1, and 4.4 times that of the untreated cells. Incubated with 10 ng/ml PDGF for 0-18 h, the adhesion rate between the VSMC and THP-1 cells increased time-1dependently. After the blocking by the antibody against integrin beta1, the adhesion rate between the VSMC and THP-1 cells decreased from (25.4+/-11.4)% to (9.2+/-4.1)% (P<0.01). Western blotting showed that the level of integrin beta1 of the VSMC treated by 10 ng/ml PDGF increased since 4 h after the treatment, peaked 8 h later, and then decreased gradually. CONCLUSION: PDGF-BB can induce the binding of monocytes to VSMC via the integrin-beta1 signaling pathway. The effect may therefore facilitate the progression of atherosclerosis by augmenting the VSMC-monocyte adhesive interaction.

[Prevalence and related factors of prostatitis-like symptoms in young men].

OBJECTIVE: To investigate the prevalence and related factors of prostatitis-like symptoms among young men. METHODS: The study was a cross-sectional survey of 2500 young men aged 18-30 years in the city of Weifang, and all of them completed a questionnaire on prostatitis. The univariate and multivariate logistic regression procedures were used to investigate the risk factors among the young men with chronic prostatitis-like symptoms. RESULTS: The valid response rate was 85% (n = 2125). Of the 128 subjects (6.02%) identified as having chronic prostatitis-like symptoms, the mean age was 21.8 years, the average pain score was 6.98 +/- 0.29, and the average voiding score was 3.77 +/- 0.25. Of the sampled population, 39 men had prostatitis-like symptoms with an index pain score of 8 or more. Significant risk factors include frequent masturbation, prolonged sitting, long-time fixed posture, cold environment, stress at home and work. CONCLUSION: The study suggested that chronic prostatitis-like symptoms are common among young men, and the urethritis history, frequent masturbation, prolonged sitting, long-time urine holding, cold environment, and stress at home and work might be significant risk factors.