Jiafu Wei

A meta-analysis of impact of proton pump inhibitors on antiplatelet effect of clopidogrel

Previous mechanistic studies have suggested a possible interaction between proton pump inhibitor (PPIs) and clopidogrel. However, the results of clinical trials about the effects of PPIs on safety and efficacy of clopidogrel are controversial. The study sought to estimate the impact of PPIs on antiplatelet effect of clopidogrel. The study performed a meta-analysis of comparative concomitant use of clopidogrel with PPIs versus clopidogrel without PPIs studies published or presented to October 2010. Cardiovascular death, readmission for myocardial infarction/readmission for acute coronary syndrome, and nonfatal stroke were set as clinical endpoints. In randomized control trials (RCTs), the clinical endpoints risk ratio for clopidogrel with PPIs versus clopidogrel without PPIs was 1.20 (P= 0.34) in the random-effects model and 1.03 (P= 0.63) in the fixed-effects model. In observational studies, the risk ratio for the clinical endpoints for clopidogrel with PPI versus clopidogrel without PPI was 1.40 (P < 0.001) in the random-effects model and 1.49 (P < 0.001) in the fixed-effects model. Different assay methods showed that coadministration of clopidogrel with PPIs was associated with attenuation of clopidogrels antiplatelet effect in vitro. This meta-analysis indicated an obvious discrepancy between RCTs and observational studies with respect to the interaction between PPIs and clopidogrel.

Nitrates for stable angina: A systematic review and meta-analysis of randomized clinical trials

OBJECTIVE To assess the effect (harms and benefits) of nitrates for stable angina. METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE. Randomized controlled trials with both parallel and crossover design were included. The following outcome measures were evaluated: number of angina attacks weekly and nitroglycerin consumption, quality of life, total exercise duration, time to onset of angina and time to 1 mm ST depression. RESULTS Fifty-one trials with 3595 patients meeting inclusion criteria were analyzed. Both intermittent and continuous regimens of nitrates lengthened exercise duration significantly by 31 and 53 s respectively. The number of angina attacks was significantly reduced by 2.89 episodes weekly for continuous administration and 1.5 episodes weekly for intermittent administration. With intermittent administration, increased dose provided with 21 s more length of exercise duration. With continuous administration, exercise duration was pronged more in low-dose group. Quality of life was not improved by continuous application of GTN patches and was similar between continuous and intermittent groups. In addition, 51.6% patients receiving nitrates complained with headache. CONCLUSION Long-term administration of nitrates was beneficial for angina prophylaxis and improved exercise performance but might be ineffective for improving quality of life. With continuous regimen, low-dose nitrates were more effective than high-dose ones for improving exercise performance. By contrast, with intermittent regimen, high-dose nitrates were more effective. In addition, intermittent administration could bring zero-hour effect.

Association between cytochrome P450 2C19 polymorphism and clinical outcomes in Chinese patients with coronary artery disease

BACKGROUND Cytochrome P450 (CYP)2C19 is expressed in vascular endothelium and metabolizes arachidonic acid to biologically active epoxyeicosatrienoic acids, which play a key role in regulating vascular tone. The aim of this study was to investigate whether the genetic functional variant 681G>A (*2) of cytochrome CYP2C19 is associated with adverse cardiovascular outcomes in Chinese patients with coronary artery disease (CAD). METHODS Between July 2008 and September 2009, 654 consecutive patients with CAD were enrolled in this study. All participants underwent CYP2C19 genotyping. The primary study endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. Secondary endpoints included the components of the primary endpoint, death from any cause, and recurrent revascularization. RESULTS The baseline characteristics were well-balanced between carriers (heterozygous *1/*2, n=291; homozygous *2/*2, n=57) and non-carriers (n=306) of the CYP2C19*2 variant. During the follow-up period (11.42±4.23 months), the primary endpoint occurred more frequently in homozygous *2/*2 than in non-carriers (n=306) of CYP2C19*2 variant (12.28% versus 3.27%; adjusted hazard ratio [HR]=5.191; 95% confidence interval [CI]=1.936-13.917; P=0.001); however, no such increase was evident in heterozygous *1/*2 patients (4.12% versus 3.27%; adjusted HR=1.208; 95% CI 0.517-2.822; P=0.662). CONCLUSIONS The homozygous CYP2C19*2/*2 genotype is an independent determinant of adverse vascular events in Chinese patients with CAD.

COMPARISON OF THE SORTING EFFICIENCY AND INFLUENCE ON CELL FUNCTION BETWEEN THE STERILE FLOW CYTOMETRY AND IMMUNOMAGNETIC BEAD PURIFICATION METHODS

Currently, flow cytometry and immunomagnetic bead purification are the most commonly used cell sorting methods. We performed this study because there are few reports that directly compare the sorting efficiency and influence on cell functions of these two methods. The in vitro cultured third-generation bone marrow mesenchymal cells from newborn Sprague-Dawley rats were sorted and purified using sterile flow cytometry and immunomagnetic beads to obtain CXCR4-positive bone marrow mesenchymal stem cells (CXCR4+-MSCs). The yield and purity (detected by flow cytometry), in vitro viability (detected by the MTT method), and in vitro chemotactic capacity (detected by stromal cell-derived factor-1α [SDF-1α] induction) of sorted target cells using these two methods were compared. The purity of CXCR4+-MSCs obtained using sterile flow cytometry was higher than that using immunomagnetic bead purification. The MTT method and growth curves showed that the viability of cells was lower and that the amplification rate of cells decreased using sterile flow cytometry, whereas the cell viability was higher after cells were sorted using immunomagnetic beads (p < 0.01). The number of CXCR4+-MSCs cells that underwent chemotactic migration induced by SDF-1α after sorting using sterile flow cytometry was smaller than that using immunomagnetic bead purification (15.60 ± 1.14 vs. 26.40 ± 1.67, p < 0.01). Although the purity of CXCR4+-MSCs sorted by the immunomagnetic bead purification method was lower than that by sterile flow cytometry, the influence on cell activity of the former was smaller, including improved cell viability and improved SDF-1α -induced chemotactic migration in vitro.

A Predictive Study of the Dynamic Development of the P‐Wave Terminal Force in Lead V1 in the Electrocardiogram in Relation to Long‐Term Prognosis in Non–ST‐Segment Elevation Acute Coronary Syndrome Patients during Hospitalization

Changes in the ECG indicator PtfV1 reflect left atrial pressure and left ventricular diastolic function in NSTE‐ACS patients during hospitalization. The value of PtfV1 in the evaluation of long‐term prognosis in NSTE‐ACS is still not clear. The purpose of this study was to investigate the relationship between the dynamic changes in P‐wave terminal force in lead V1(PtfV1) in the ECG of non–ST‐segment elevation acute coronary syndrome (NSTE‐ACS) patients during hospitalization and the long‐term major adverse cardiovascular events (MACEs) of patients.

The Value of Combining CYP2C19*2 Polymorphism with Classic Risk Factors in Prediction of Clinical Prognosis in Acute Coronary Syndrome Patients

Objectives: To assess the impact of different CYP2C19*2 polymorphisms on clinical outcomes and the effects of CYP2C19*2 polymorphism on predicting clinical outcomes in association with classic risk factors in patients with acute coronary syndromes (ACS). Methods: Between July 2008 and September 2009, 497 consecutive patients with ACS who were admitted to the West China Hospital of Sichuan University were enrolled and underwent CYP2C19*2 determination. The clinical outcomes were the composite of cardiovascular death, nonfatal myocardial infarction and nonfatal stroke. Results: Baseline characteristics were balanced between noncarrier, heterozygous and homozygous groups of the CYP2C19*2 variant. The clinical endpoint occurred more frequently in the homozygous group (HR 4.86, CI 1.62–14.56, p = 0.005). After multivariable analysis, the CYP2C19*2 genetic variant was an independent predictor of cardiovascular events (HR 5.96, CI 1.77–20.03, p = 0.0039) as well as GRACE score and Killip class. The combination of CYP2C19*2 with GRACE score and Killip class increases the potential to predict adverse outcomes. Conclusions: Homozygosity (A/A) for CYP2C19*2 mutant is an independent determinant of prognosis in patients with ACS. The combination of CYP2C19*2 polymorphism with classic risk factors may be a useful tool to predict the risk of cardiovascular events.

Investigation on the microstructure of as-deformed NiCr microwires using TEM

Ultra-fine NiCr (80/20 wt%) wires with a nanocrystalline (nc) grain and diameters that range from 21 μm to 25 μm were fabricated using a cold-drawing method. The engineering strains were 8.8%, 17.3%, 26.4%, 36.1%, and 46.6%. The microstructures of the drawn direction and wire cross-section were characterized using transmission electron microscopy (TEM). Two thinning preparation techniques were used in preparing the TEM specimens. The grain size was approximately 3 nm to 20 nm. The deformed microstructures include amorphous GBs, crystal GBs, edge dislocations and twins. Amorphous boundaries may be produced by phase transition or dislocation pile-up. Several edge dislocations existed at the grain boundaries (GBs) and grain interior. Twinning deformation microstructures were found in cross-sections with an asymmetrical relationship. The possible deformation mechanism for the formation of the microstructure is discussed.

Biotin-streptavidin cross-bridging: a novel and feasible approach for targeting transplanted cells to damaged tissue.

Background: Accumulating evidence indicates the positive impact of endothelium-derived cell therapy in vascular repair. However, low cell transplantation efficiency inevitably and greatly reduces the treatment efficacy of cell transplants. Purpose: To modify the surfaces of cells with polypeptides or small-molecule proteins that specifically recognize and bind to damaged tissue. Methods: We used a biotin-streptavidin binding approach to attach annexin V, which recognizes apoptotic cells, onto bEnd.3 cells that express vascular endothelial growth factor receptor 2 (VEGFR2) and verified that the modified cells could efficiently bind to dead cells in vitro. Results: We analyzed biotinylated VEGFR2-bEnd.3 cells, streptavidin-biotinylated VEGFR2-bEnd.3 cells, and biotinylated annexin V-streptavidin-biotinylated VEGFR2-bEnd.3 cells. Our results from flow cytometry analysis and immunofluorescent examination demonstrated that we successfully labeled the cells in a three-step process. Furthermore, we determined that the positive binding rate correlated with reagent concentration. Immunofluorescent examination illustrated that adding the biotinylated annexin V-streptavidin-biotinylated VEGFR2-bEnd.3 cells to dead cells led to the clustering and aggregation of the modified cells and the dead cells. Conclusions: Annexin V can be attached to bEnd.3 cells using a biotin-streptavidin binding approach, and the modified cells can specifically recognize and bind to dead cells.