Synergistic Effect of Lipoprotein-Associated Phospholipase A2 with Classical Risk Factors on Coronary Heart Disease: A Multi-Ethnic Study in China.

AIMS: We evaluated the synergistic effect of lipoprotein-associated phospholipase A2 (Lp-PLA2) in association with classical risk factors in predicting coronary heart disease (CHD) and demonstrated the diagnostic value of Lp-PLA2 for predicting coronary stenotic lesions in subjects with CHD. METHODS: Blood samples were acquired from 911 consecutive adult subjects (662 males and 249 females) from 11 ethnic groups. Lp-PLA2 plasma levels were detected using a commercially available turbidimetric immunoassay (TIA). CHD in patients was confirmed using coronary angiography, and the severity of coronary atherosclerosis was assessed using the Gensini scoring system. RESULTS: A binary logistic regression was performed to analyse the relationships between Lp-PLA2 and other risk factors. A multivariate logistic regression analysis revealed that Lp-PLA2 levels were significantly associated with CHD (OR, 1.882; 95% CI, 1.369-2.587, p=0.000).The area under the receiver operating characteristic curve for Lp-PLA2 was 0.589 (95%CI, 0.549-0.629, p=0.000).The synergism between Lp-PLA2 and other risk factors was also investigated. The proportion of CHD attributable to the interaction between Lp-PLA2 and age was as high as 64%. CONCLUSIONS: Lp-PLA2 levels in human plasma were positively associated with the severity of CHD, and there was a clear positive interaction between Lp-PLA2 and classical risk factors in predicting CHD.

Meteorological parameters and the onset of chest pain in subjects with acute ST-elevation myocardial infarction: an eight-year, single-center study in China.

OBJECTIVE: The purpose of this study was to investigate the influence of weather on the occurrence of acute ST-elevation myocardial infarction in Chinese subjects. METHODS: Weather and climate data, as well as the occurrence of STEMI, were monitored at 2 am, 8 am, 2 pm, and 8 pm between 2003 and 2010. Generalized additive Poisson models were utilized to plot the numbers of patients with STEMI within 6 hour intervals against climatological variations, after accounting for the effects of the hour and season. RESULTS: The inclusion of meteorological conditions, including observed atmospheric pressure (hPa, hectopascal) variations during the previous three hours and temperature (°C, degrees Celsius), significantly affected the occurrence of STEMI, as measured every six hours. Compared with the 50th percentile of atmospheric pressure variations, the RRs (95% CI) for the first percentile, 10th percentile, 25th percentile, 75th percentile, 90th percentile, and 99th percentile of atmospheric pressure variation over lag 0 were 1.66 (1.36∼2.03), 1.47 (1.30∼1.67), 1.22 (1.12∼1.33), 1.16 (1.07∼1.25), 1.27 (1.13∼1.43), and 1.16 (0.92∼1.46), respectively. Compared to the 50th percentile of temperature, the RRs (95% CI) for the first percentile, 10th percentile, 25th percentile, 75th percentile, 90th percentile, and 99th percentile of temperature over lag 0 were 0.58 (0.40∼0.83), 0.60 (0.46∼0.78), 0.69 (0.57∼0.83), 1.33 (1.14∼1.56), 1.39 (1.13∼1.71), and 1.17 (0.84∼1.63), respectively. CONCLUSIONS: Based on the eight-year, single-center study, significant relationships were observed among the occurrence of STEMI and atmospheric pressure variations during the previous three hours and temperature after account for long-term time trends.

Hemoglobin A1c risk score for the prediction of coronary artery disease in subjects with angiographically diagnosed coronary atherosclerosis.

OBJECTIVE: To develop a risk score by incorporating Hemoglobin A1c(HbA1c) with traditional risk factors for the prediction of coronary artery disease (CAD) in Chinese subjects. METHODS: A total of 196 consecutive subjects (131 males and 65 females) aged 38-89 years who underwent coronary angiography were enrolled in this study. HbA1c risk score sheets for the prediction of CAD were developed using age, gender and HbA1c. A receiver-operating characteristic curve analysis was used to determine the optimum cut-off levels of the HbA1c risk score for predicting CAD. RESULTS: In the ROC curve analysis, the optimal cut-off value of the HbA1c score for predicting CAD was 5.1, with a sensitivity of 72.0% and a specificity of 75.5% (area under the curve 0.781, 95% confidence interval 0.709 to 0.854, p=0.000). CONCLUSIONS: The HbA1c score system is a simple and feasible method that can be used for the prediction of CAD. Large-scale studies are needed to further substantiate these results.

OLR1, PON1 and MTHFR gene polymorphisms, conventional risk factors and the severity of coronary atherosclerosis in a Chinese Han population.

AIMS: To explore the association between six single-nucleotide polymorphisms in OLR1, PON1, MTHFR gene and the angiographical characteristics of coronary atherosclerosis to determine if any of the conventional factors correlate with genetic polymorphisms in the advent of the disease. METHODS: We examined rs1801131, rs1801133, rs3736232, rs3736234, rs854563 and rs662 by TaqMan® SNP Genotyping Assays in 1075 subjects that underwent angiography. The angiographical characteristics of coronary atherosclerosis were defined by the Gensini Score system. RESULTS: The T allele of rs1801133 was associated with coronary atherosclerosis severity with the OR = 1.49, 95% CI = 1.04-2.14. In MTHFR gene, haplotype T-A was a susceptibility haplotype to coronary atherosclerosis (OR = 1.27, 95% CI = 1.06-1.51) whereas haplotype C-A had a protective effect (OR = 0.83, 95% CI = 0.70-0.99). In addition, several synergistic effects between rs1801133 and conventional risk factors such as diabetes and smoking were found. CONCLUSIONS: Collectively, the results demonstrate that the T allele of rs1801133 conferred an increased risk for coronary atherosclerosis. The MTHFR C-A haplotype was a protective haplotype, while T-A haplotype was a susceptibility haplotype. The presence of the T allele of rs1801133 increases the odds of coronary atherosclerosis severity when associated with conventional risk factors.

[Effect of aspirin plus clopidogrel therapy on aspirin resistance after off-pump coronary artery bypass surgery].

OBJECTIVE: To investigate the effect of the anti-platelet effect of aspirin plus clopidogrel on off-pump coronary artery bypass (OPCAB) grafting and the possible side effects of such therapy. METHODS: Sixty patients who underwent standard OPCAB were randomized immediately after surgery in two groups: the aspirin alone group of 30 patients who received aspirin (100 mg) daily; and the combination group of 30 patients who received clopidogrel (75 mg) plus aspirin (100 mg) daily. Platelet aggregation in response to arachidonic acid (PLAA) and adenosine diphosphate (PLADP) were measured at baseline (before surgery) and 1-6, 8, and 10 days after the medication. Postoperative bleeding and other perioperative parameters were compared between these two groups. RESULTS: There were no significant differences between the two groups in perioperative findings including average number of distal anastomosis, operative time, postoperative bleeding, ventilation time, and intensive care unit stay (all P>0.05). The proportion of patients with the PLAA above 20% value was significantly lower in the combination group than those in the aspirin alone group (32.1% vs 62.1%, P<0.05). PLAA of two groups one and two days after taking aspirin or plus clopidogrel were (24.2±31.9)% vs. (49.6±32.6)% and (13.8±27.2)% vs. (37.6±37.4)%, respectively (P<0.05). No obvious postoperative complication was noted in both groups. Multivariate analysis showed that clopidogrel administration was independently correlated with aspirin resistance (P=0.044, OR = 0.09;95% CI=0.07-0.48). CONCLUSION: Early combined use of aspirin plus clopidogrel after OPCAB can remarkably reduce OPCAB-related aspirin resistance and enjoy similar safety.

[Initial experience of percutaneous coronary intervention guided by computed tomography coronary angiography derived roadmap and magnetic navigation system].

OBJECTIVE: To evaluate the feasibility, efficacy and safety of the percutaneous coronary intervention (PCI)guided by computed tomography (CT) coronary angiography derived roadmap and magnetic navigation system (MNS). METHODS: During June 2011 and May 2012, thirty consecutive patients receiving elective PCI were enrolled, coronary artery disease was primarily diagnosed by dual-source CT coronary angiography (DSCT-CA) at outpatient clinic and successively proved by coronary artery angiography in the hospital. Target vessels from pre-procedure DSCT-CA were transferred to the magnetic navigation system, and consequently edited, reconstructed, and projected onto the live fluoroscopic screen as roadmap. Parameters including characters of the target lesions, time, contrast volume, radiation dosage for guidewire crossing, and complications of the procedure were recorded. RESULTS: Thirty patients with 36 lesions were recruited and intervened by PCI. Among the target lesions, sixteen were classified as type A, 11 as type B1, 8 as type B2, 1 as type C. The average length of the target lesions was (22.0 ± 9.8) mm, and the average stenosis of the target lesions was (81.3 ± 10.3)%. Under the guidance of CT roadmap and MNS, 36 target lesions were crossed by the magnetic guidewires, with a lesion crossing ratio of 100%. The time of placement of the magnetic guidewires was 92.5 (56.6 - 131.3) seconds. The contrast volume and the radiation dosage for guidewire placement were 0.0 (0.0 - 3.0) ml and 235.0 (123.5 - 395.1) µGym(2)/36.5 (21.3 - 67.8) mGy, respectively. Guidewires were successfully placed in 21 (58.3%) lesions without contrast agent. All enrolled vessels were successfully treated, and there were no MNS associated complications. CONCLUSIONS: It is feasible, effective and safe to initiate PCI under the guidance of CT derived roadmap and MNS. This method might be helpful for the guidewire placement in the treatment of total occlusions.

Improvement of heart function in postinfarct heart failure swine models after hepatocyte growth factor gene transfer: comparison of low-, medium- and high-dose groups.

Despite advances in surgical and reperfusion therapy, there is no effective therapy currently exists to prevent the progressive decline in cardiac function following myocardial infarction. Hepatocyte growth factor has potent angiogenic and anti-apoptotic activities. The aim of this study was to investigate the therapeutic effect and dose-effect relationship on postinfarction heart failure with different doses of adenovirus-mediated human hepatocyte growth factor (Ad(5)-HGF) transference in swine models. Totally twenty swine were randomly divided into four groups: (a) control group (null- Ad(5), 1 ml); (b) low-dose group (1 x 10(9) Pfu/ml Ad(5)-HGF, 1 ml); (c) medium-dose group (5 x 10(9) Pfu/ml Ad(5)-HGF, 1 ml); (d) high-dose group (1 x 10(10) Pfu/ml Ad(5)-HGF, 1 ml). Four weeks after left anterior descending coronary artery (LAD) ligation, different doses of Ad(5)-HGF were transferred in three therapeutic groups via right coronary artery. Four and seven weeks after LAD ligation, gate cardiac perfusion imaging was performed to evaluate cardiac perfusion and left ventricular ejection fraction (LVEF). Seven weeks after surgery, the apoptotic index of cardiocyte was observed by TUNEL, the expression of Bcl-2, Bax, alpha-SMA and Factor VIII in the border zones were evaluated by immunohistochemistry, respectively. Four weeks after myocardial infarction, no significant difference was observed among four groups. Three weeks after Ad(5)-HGF transfer, the improvement of cardiac perfusion and LVEF was obviously observed, especially after 1 x 10(10) Pfu Ad(5)-HGF transfer. TUNEL assay showed that 5 x 10(9) Pfu and 1 x 10(10) Pfu Ad(5)-HGF treatment had a obvious reduction in the apoptotic index compared with the null-Ad(5) group, especially after 1 x 10(10) Pfu Ad(5)-HGF treatment. The expression of Bcl-2 protein was increased and the expression of Bax protein was inhibited in the 5 x 10(9) Pfu and 1 x 10(10) Pfu Ad(5)-HGF groups compared with the null-Ad(5) group. The vessel density of Factor VIII(+) and alpha-SMA(+) was increased in Ad(5)-HGF groups compared with the null-Ad(5) group. There were no significant differences in angiogenesis, reducing apoptosis and ameliorating heart function between the 1 x 10(9) Pfu Ad(5)-HGF group and the null-Ad(5) group. Although no statistical difference was observed between 1 x 10(10) Pfu and 5 x 10(9) Pfu Ad(5)-HGF groups, the cardiac protective effects of 1 x 10(10) Pfu Ad(5)-HGF treatment were greater than 5 x 10(9) Pfu Ad(5)-HGF treatment. Different doses of Ad5-HGF injected via noninfarct-related artery could induce angiogenesis, reduce apoptosis and ameliorate heart function, and the cardiac protective effects of 1 x 10(10) Pfu Ad5-HGF is of most significance.

Point-of-care test of heart-type fatty acid-binding protein for the diagnosis of early acute myocardial infarction.

AIM: To investigate the efficacies of point-of-care test of heart-type fatty-acid binding protein (H-FABP) and its combinations with the conventional biomarkers in the diagnosis of early acute myocardial infarction (AMI). METHODS: 227 patients suspected of AMI were consecutively recruited in two centers. Biomarkers including H-FABP, myoglobin (MYO), creatine kinase-myocardial band (CK-MB) and cardiac troponin T (cTnT) were determined simultaneously at admission. AMI was defined according to the universal definition of myocardial infarction. Chi-Square test was adopted for the analysis. RESULTS: In patients presenting within 12 h of symptom onset, the sensitivity of H-FABP[93.0% (95% CI: 86.6%-96.9%)] was significantly higher than that of initial CK-MB [67.5% (95% CI: 58.1%-76.0%), P<0.0001], cTnT [69.3% (95%CI: 60.0%-77.6%), P<0.0001] and MYO [68.6% (95% CI: 54.1%-80.9%), P<0.05]. The negative predictive value of H-FABP [92.8% (95%CI: 86.3%-96.8%)] was significantly higher than that of initial CK-MB [74.7% (95% CI: 66.8%-81.5%), P<0.001] and cTnT [75.9% (95% CI: 68.1%-82.6%), P<0.001]. The sensitivity of H-FABP+cTnT combination [94.7% (95% CI: 88.9%-98.0%)] was significantly higher than that of admission cTnT [69.3% (95% CI: 60.0%-77.6%), P<0.0001], CK-MB+cTnT [75.4% (95% CI: 66.5%-83.0%), P<0.0001] and MYO+CK-MB+cTnT [74.5% (95% CI: 60.4%-85.7%), P<0.05]. The negative predictive value of H-FABP+cTnT [94.5% (95% CI: 88.4%-98.0%] was significantly higher than that of initial cTnT [75.9% (95% CI: 68.1%-82.6%), P<0.001] and CK-MB+cTnT [79.1% (95% CI: 71.2%-85.6%), P<0.001]. Subgroup analysis showed that the superiorities of both the sensitivities and the negative predictive values of H-FABP and H-FABP+cTnT combination occurred only in patients who presented within 6 h of the symptom onset. CONCLUSION: Point-of-care test of H-FABP can be used as a valuable biomarker to detect or exclude an early-stage AMI. Combining H-FABP and cTnT provides the best performance for early AMI diagnosis.

[Comparative studies on identification of maize secreted proteome by different analyzing techniques].

Maize roots release a battery of proteins into the rhizosphere during growth and development. In the present study, mucilage secreted by primary roots of 3-4 d old maize seedlings was collected under axenic conditions, and the constitutively secreted proteins were analyzed by different methods, including two-dimensional electrophoresis--MADLI-TOF, LC-MS, and Shotgun techniques. The results showed that 200 protein spots could be observed on two-dimensional electrophoresis gel stained by silver nitrate. However, due to the low protein content for each protein spot, there was not reliable result after identification by MADLI-TOF. On the other hand, 152 and 2848 proteins were identified by LC/MS and Shotgun technique, respectively. All 152 proteins identified by LC/MS method could be found in the proteins identified by Shotgun method, and thus the results obtained by LC/MS and Shotgun method could be authenticated mutually. The results demonstrated that the Shotgun method is more sensitive than the other methods for protein identification, especially for the proteins with lower contents and complex interfering substances, such as the plant root released proteins.

[Clinical study on the coronary artery interventions guided by the magnetic navigation system].

OBJECTIVE: To investigate the efficacy and safety of the magnetic navigation system used in the real world percutaneous coronary artery intervention. METHODS: All lesions detected by the coronary artery angiography in the magnetic-navigation catheter lab indicated for percutaneous coronary artery intervention (PCI) were included and treated under the guidance of the magnetic navigation system. The characteristics of the target lesion, process of the procedure, time and dosage of the X-ray exposure, and procedure-related complication were recorded and analyzed. RESULTS: One hundred and twenty one patients with 138 lesions were recruited and intervened by PCI during the period from April 2006 to June 2008. Thirty lesions were classified as type A, 50 as type B1, 36 as type B2, 22 as type C (including seven total occlusions). The average stenosis of the target lesions was (85.3 +/- 10.0)%, mean length was (21.1 +/- 10.0) mm. Under the guidance of the magnetic navigation system, 134 target lesions were passed by the magnetic guide-wires, the lesion passing ratio was 97.1%. The X-ray exposure time, X-ray dosage and the contrast volume used during the period of the wire placement were (55.9 +/- 35.4) seconds, (98.0 +/- 86.1) mGy/(490.0 +/- 422.2) microGym(2) and (8.0 +/- 5.4) ml, respectively. A total of 164 stents were implanted in the vessels where the target lesions were passed by the magnetic wires. There was no magnetic navigation system associated complication. Magnetic guide-wires failed to pass four target lesions, two of which were chronic total occlusions (CTOs), and the other two were calcified subtotal occlusions. CONCLUSIONS: It is feasible and safe to adopt the magnetic navigation system for the real-world coronary artery intervention. The magnetic guide-wire possesses a high lesion-passing ratio. The CTOs and calcified subtotal occlusions are not ideal lesions for use of the magnetic navigation system.

[Psychological status in 1083 hospitalized patients with coronary artery disease].

OBJECTIVE: To explore the prevalence and associated factors of anxiety and depression symptoms in hospitalized Chinese patients with coronary artery disease (CAD). METHODS: From June 2007 to May 2009, 1083 hospitalized patients with confirmed coronary artery disease were recruited in this study. The ZUNG Self-rating Anxiety Scale (SAS) and the ZUNG Self-rating Depression Scale (SDS) were used for the psychological assessment. Economic status, living condition and the environment of both living and working places were evaluated by epidemiological questionnaires. RESULTS: The prevalence of pure anxiety, pure depression symptoms and the combination of anxiety and depression symptoms were 7.9%, 28.3% and 14.3% respectively. Incidence of anxiety and depression symptoms was significantly higher in female patients compared with in male patients (P = 0.003, 0.012 respectively) and in aged patients than in middle-aged patients (P = 0.001). The elderly, less than 9 years of education and poor sleep quality increased the risk of anxiety symptom with ORs of 1.63 (95%CI: 1.21 - 2.21), 1.54 (95%CI: 1.15 - 2.07) and 1.62 (95%CI: 1.34 - 1.96), respectively, while workplace noise, history of chronic disease and poor sleep quality increased the risk of depression symptom with ORs of 1.52 (95%CI: 1.18 - 1.98), 1.36 (95%CI: 1.06 - 1.75) and 1.27 (95%CI: 1.08 - 1.50), respectively. Female (OR = 1.91, 95%CI: 1.22-2.98), aged patient (OR = 1.84, 95%CI: 1.23 - 2.76), workplace noise (OR = 1.61, 95%CI: 1.07 - 2.42), history of chronic disease (OR = 1.84, 95%CI: 1.24 - 2.71) and poor sleep quality (OR = 1.73, 95%CI: 1.35 - 2.21) were significantly correlated with the combined incidence of anxiety and depression symptoms. CONCLUSION: Around half of the Chinese hospitalized CAD patients were complicated with various degrees of anxiety and/or depression symptoms. Female and aged patients were at higher risk for anxiety and depression symptoms. Sleep quality, workplace noise, years of education and history of chronic disease were independent risk factors for anxiety or depression symptoms.

Cyclic RGD functionalized liposomes targeted to activated platelets for thrombosis dual-mode magnetic resonance imaging.

Thrombotic disease is a serious threat to human health. The rapid and accurate detection of thrombosis is still a clinical challenge. To achieve the accurate diagnosis of thrombosis with magnetic resonance imaging (MRI), nanomaterials-based contrast agents have been developed in recent years. In this study, cyclic RGD functionalized liposomes targeted to the activated platelets are developed for thrombosis dual-mode MRI. The cyclic RGD functionalized liposomes (cRGD@MLP-Gd) encapsulated with gadolinium diethylenetriamine penta-acetic acid (Gd-DTPA) and superparamagnetic iron oxide (SPIO) are prepared, and their thrombus-targeted T1 and T2 MRI potential is evaluated in vitro and in vivo. Results show that cRGD@MLP-Gd could actively bind to the activated platelets and gradually accumulate at the thrombus site with a T1 - T2 contrast enhancement imaging effect in vitro. In in vivo MRI experiments, cRGD@MLP-Gd exhibits a T2 contrast enhancement at 1 h after intravenous administration, followed by a visibly larger T1 contrast enhancement at the thrombus site. This dynamic property showed that cRGD@MLP-Gd could actively bind to thrombus and possessed an enhanced T1 and T2 dual-mode MRI effect in vivo. Our results establish the characterization, feasibility and superiority of cRGD@MLP-Gd for the rapid identification of thrombosis, showing great potential to improve diagnostic accuracy and sensitivity to thrombosis of the MRI technique.

Association of the mutation for the human carboxypeptidase E gene exon 4 with the severity of coronary artery atherosclerosis.

OBJECTIVE: To test the hypothesis that the identification of mutation in the carboxypeptidase E (CPE) gene which leads to marked hyperproinsulinaemia is consistent with a possible role for mutations in CPE in the development of coronary atherosclerosis. METHODS: The study subjects consisted of 1084 consecutive patients (812 males and 272 females) who will undergo coronary angiography. The severity of coronary atherosclerosis was defined by the Gensini's score system. The proinsulin level was measured using highly sensitive two-site sandwich ELISA methods. Screening for mutations of the 4th exon and exon-intron junctional region of the CPE gene was performed by polymerase chain reaction followed by bidirectional sequencing. RESULTS: Sequencing of the CPE gene exon 4 in 1084 consecutive patients revealed 2 genetic variants, the G-to-A substitution at nucleotide 2855 in exon 4 (synonymous mutation) and A-to-G substitution at nucleotide 2925 in intron 4. Although the proinsulin level was not influenced by the presence of the two point mutation, the Gensini score was significantly influenced by the presence of the A2925G mutant (P = 0.023). Furthermore, we found a higher prevalence of subjects with the A2925G heterozygous mutant among higher Gensini score subjects than it among lower Gensini score subjects, and this difference reached statistical significance (P = 0.006, OR 1.465, 95%CI 1.116-1.924). In addition, the frequency distribution of the G2855A mutant was differed in the higher Gensini score subjects than it in the lower Gensini score subjects belonging to high-risk category as smokers, and the statistical significance was reached (P = 0.043, OR 2.075, 95%CI 1.024-4.207). CONCLUSIONS: In the present study, the severity of the coronary atherosclerosis estimated by Gensini score was significantly influenced by the presence of the A2925G mutant and G2855A mutant of the CPE gene, and the exactly mechanism underlying the association needs further study.

Phase I clinical trial on intracoronary administration of Ad-hHGF treating severe coronary artery disease.

OBJECTIVE: Therapeutic angiogenesis is a new strategy for treatment of vascular insufficiency. Hepatocyte growth factor (HGF)-induced angiogenesis has been applied to induce the neovascularization of ischemic adult tissues in preclinical studies. This report summarizes a phase I clinical trial on the safety of adenovirus-mediated human HGF (Ad-HGF) gene transfer to treat clinically significant coronary artery disease. METHODS: The 18 patients with severe and diffused triple vessel disease determined by coronary angiography, 1-3 of the main coronary arteries not amenable to bypassing grafting and to catheter-based revascularization were assigned to 3 study groups according to the dose of Ad-HGF (from low to high), and the total dose as follows: 5 x 10(9) pfu (group A, n = 6); 1 x 10(10) pfu (group B, n = 6); 2 x 10(10) pfu (group C, n = 6). Arterial gene transfer was performed by over-the wire balloon to the distal of the accessible artery or otherwise the ostium of the target vessels by diagnostic coronary catheter. General safety parameters and cardiac-specific parameters were measured through the preoperative period and on day 7, 21, and 35 postoperatively. The safety and tolerance of Ad-HGF for patients were evaluated according to functional and cytological assessments. RESULTS: During the acute phase up to day 35 and at 11-14 months of follow-up there were no serious adverse events. A mild fever during the first 3 days was not present at day 4, and no long term or paroxysmal fever was found. There were no acute alterations in hemodynamic parameters and the electrocardiogram remained normal. No serious pericardial effusion was reported and there were no arrhythmia on Holter registrations. Moreover, the serum levels of HGF were not changed and the serum anti-adenovirus in the patients was not detected up to day 35. CONCLUSIONS: The present study demonstrates that it is feasible to safely use an adenovirus gene-transfer vector to deliver the human hepatocyte growth factor gene to individuals with clinically significant coronary artery disease by direct intracoronary injection. However, a great deal of additional work must be done before administration of Ad-HGF can be recommended for clinical practice.

Hepatocyte growth factor plays a critical role in the regulation of cytokine production and induction of endothelial progenitor cell mobilization: a pilot gene therapy study in patients with coronary heart disease.

1. There is growing evidence of the beneficial effects of hepatocyte growth factor (HGF) in myocardial infarction, heart failure and occlusive peripheral arterial disease. The aim of the present study was to evaluate the effects of intracoronary administration of an adenovirus vector encoding the human HGF gene (Ad-HGF) on serum levels of cytokines and mobilization of CD34(+) and CD117(+) cells in patients with coronary heart disease. 2. Twenty-one patients with severe coronary artery disease were recruited to the study: 11 patients received both a stent and administration of Ad-HGF; the remaining 10 patients received a stent alone and served as the control group. Blood samples were obtained from the femoral vein before and then 6 and 24 h, 3 and 6 days and 2 weeks after treatment for the isolation of serum and peripheral blood mononuclear cells. Intracoronary administration of Ad-HGF in patients with coronary heart disease resulted in high levels of HGF gene expression, as well as its receptor c-met, compared with the control group, as demonstrated by real-time reverse transcription-polymerase chain reaction. In addition, serum levels of HGF, vascular endothelial growth factor, monocyte chemoattractant protein-1 and interleukin (IL)-10 were increased and serum levels of IL-8 were decreased in patients administered Ad-HGF compared with the control group. The percentage of CD34(+) and CD117(+) cells in the peripheral blood increased in patients administered Ad-HGF. 3. In conclusion, HGF gene therapy may play an important role in the regulation of cytokines and the induction of endothelial progenitor cell mobilization in patients with coronary heart disease.

Nicotine concentration in leaves of flue-cured tobacco plants as affected by removal of the shoot apex and lateral buds.

It is believed that the nicotine concentration in tobacco is closely correlated with the amount of nitrogen (N) supplied. On the other hand, N uptake mainly occurs at the early growth stage, whereas nicotine concentration increases at the late growth stage, especially after removing the shoot apex. To identify the causes of the increased nicotine concentration in tobacco plants, and to compare the effects of different ways of mechanical wounding on nicotine concentration, field experiments were carried out in Fuzhou, Fujian Province in 2003 and 2004. Excision of the shoot apex had almost no influence on N content in the plant; however, it caused dramatic increases in nicotine concentration in leaves, especially in the middle and upper leaves. An additional increase of the nicotine concentration was obtained by removal of axillary buds. The wounding caused by routine leaf harvests, however, did not change the leaf nicotine concentration, and neither did reducing leaf harvest times. The present results revealed no direct relationship between N supply and nicotine concentration in tobacco leaves, and indicate that not all kinds of mechanical wounding were capable of stimulating nicotine synthesis in tobacco plants. Since nicotine production is highly dependent on the removal of apical meristems and hence on the major sources of auxin in the plant, and application of 1-naphthylacetic acid onto the cut surface of the stem after removing the shoot apex markedly decreased the nicotine concentration in different leaves and the total nicotine content in the plant, the results suggest that decreased auxin supply caused by removal of the shoot apex as a kind of mechanical wounding might regulate nicotine synthesis in the roots of tobacco plants.

Cholecystokinin octapeptide inhibits the inflammatory response and improves neurological outcome in a porcine model of cardiopulmonary resuscitation.

Previous studies have demonstrated that cholecystokinin octapeptide (CCK8) induces hypothermia and inhibits the systemic inflammatory response in septic shock in rat and murine models. The present study aimed to ascertain whether CCK8 induced hypothermia and improved the neurological outcomes in a porcine model of cardiopulmonary resuscitation (CPR). Ventricular fibrillation was induced and left untreated for 10 min in 12 male Bama miniature pigs. Defibrillation was attempted after 5 min of CPR. At 5 min following resuscitation, the pigs were randomized and equally assigned into the CCK8 or the control group. CCK8 was continuously infused for 1 h at a dose of 44.4 µg/kg/h and a rate of 20 ml/h in the CCK8 group. Body temperature, hemodynamic measurements and post-resuscitation myocardial function were monitored in the first 4 h following CPR. Neuron specific enzyme (NSE), S100B protein, tumor necrosis factor (TNF)-α and interleukin (IL)-6 were measured at baseline and 4, 12 and 24 h following resuscitation. The neurological deficient score (NDS) was recorded and cerebral samples were collected for terminal deoxynucleotidyl-transferase-mediated dUTP nick end labelling assay and integrated optical density (IOD) analysis at 24 h following CPR. The results revealed that hypothermia was not induced by CCK8; however, post-resuscitation NSE, S100B, IL-6 and TNF-α were significantly decreased, and NDS and IOD were significantly improved in the CCK8 group compared with the control group (P<0.05). The present study revealed that in a porcine model of CPR, CCK8 does not induce hypothermia, but inhibits the inflammatory response and significantly improves neurological outcomes.

Age-sex distribution of patients with high-sensitivity troponin T levels below the 99th percentile.

BACKGROUND: Recently, very low concentrations of high-sensitivity cardiac troponin T (hs-cTnT), below the 99th percentile, have been used to immediately exclude acute myocardial infarction in certain patients without taking their age and sex into consideration. RESULTS: The hs-cTnT values below the 99th percentile (≤ 14 ng/L) were higher in men (p = 0.000) and significantly increased with age (p = 0.000) among both men and women. In addition, hs-cTnT was positively associated with age (r = 0.459, p = 0.000), myoglobin (r = 0.392, p = 0.000), and creatine kinase-MB (r = 0.133, p = 0.000). Moreover, males were younger (p = 0.001) and had higher myoglobin (p = 0.000) and creatine kinase-MB (p = 0.000) concentrations than females. MATERIALS AND METHODS: A total of 5585 consecutive subjects who presented with non-traumatic chest pain/discomfort to the inpatient, outpatient, or emergency department and who underwent high-sensitivity troponin T, myoglobin and creatine kinase-MB testing at presentation, with hs-cTnT below the 99thpercentile (≤ 14 ng/L), were eligible for enrollment. CONCLUSIONS: We suggest that patients' age, sex and levels of myocardial injury biomarkers should be taken into consideration when ruling out acute myocardial infarction and/or adverse prognostic implications in patients who have very low hs-cTnT concentrations.

Intensified Antiplatelet Treatment Reduces Major Cardiac Events in Patients with Clopidogrel Low Response: A Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Clopidogrel low response (CLR) is an independent risk factor of adverse outcomes in patients undergoing percutaneous coronary intervention (PCI), and intensified antiplatelet treatments (IAT) guided by platelet function assays might overcome laboratory CLR. However, whether IAT improves clinical outcomes is controversial. METHODS: Relevant trials were identified in PubMed, the Cochrane Library, and the Chinese Medical Journal Network databases from their establishment to September 9, 2014. Trials were screened using predefined inclusion criteria. Conventional meta-analysis and cumulative meta-analysis were performed using the Review Manager 5.0 and STATA 12.0 software programs. RESULTS: Thirteen randomized controlled trials involving 5111 patients with CLR were recruited. During a follow-up period of 1-12 months, the incidences of cardiovascular (CV) death, nonfatal myocardial infarction (MI), and stent thrombosis were significantly lower in the IAT arm than in the conventional antiplatelet treatment arm (relative risk [RR] = 0.45, 95% confidence interval [CI]: 0.36-0.57, P < 0.000,01), whereas bleeding was similar between the two arms (RR = 1.05, 95% CI: 0.86-1.27, P = 0.65). CONCLUSIONS: IAT guided by platelet function assays reduces the risk of CV death, nonfatal MI, and stent thrombosis (ST) without an increased risk of bleeding in patients undergoing PCI and with CLR.

Relationship between diagonal earlobe creases and coronary artery disease as determined via angiography.

OBJECTIVE: This study was designed to examine the prevalence of unilateral and bilateral diagonal earlobe creases (DELCs) with respect to the diagnosis of coronary heart disease (CHD). METHODS: A total of 558 consecutive participants (402 males and 156 females) aged 36-91 years who underwent coronary angiography were enrolled in this study. The participants were classified as being without a DELC, having a unilateral DELC and having bilateral DELCs; participants with either a unilateral DELC or bilateral DELCs were defined as participants with DELCs. Significant CHD was defined as at least one major vessel with >50% stenosis, and coronary atherosclerosis severity was defined using the Gensini scoring system. RESULTS: In the present study, bilateral DELCs were more frequently among male (p=0.001), CHD (p=0.000), older people (p=0.000) and those with more severe coronary artery atherosclerosis (p=0.000). The results of the multiple regression analyses indicated that DELCs (OR, 4.861; 95% CI 3.093 to 7.642, p=0.000) remained independently associated with a risk of CHD. It was assumed that participants without a DELC have a certain background risk for CHD (OR is assumed to be 1); the results of the multivariate logistic regression indicated that the relative risk of CHD among participants with bilateral DELCs was 5.690 among all participants (OR, 5.690; 95% CI 3.450 to 9.384, p=0.000), 5.436 among male participants (OR, 5.436; 95% CI 2.808 to 10.523, p=0.000) and 7.148 among female participants (OR, 7.148; 95% CI 3.184 to 16.049, p=0.000). Moreover, a positive association between DELC and age (SI=1.21, SIM=1.65, AP =0.132), gender (SI=2.09, SIM=0.81, AP=0.49) and smoking status (SI=1.49, SIM=0.73, AP=0.29) was found, respectively. CONCLUSIONS: The results of the present study indicated that DELCs are a simple and a feasible means of identifying CHD. However, the exact mechanism underlying the relationship between DELCs and CHD warrants further study.