Xiao-jing Liu

Effects of autologous stem cell transplantation on ventricular electrophysiology in doxorubicin-induced heart failure

To investigate whether stem cell transplantation affects ventricular electrophysiology in vivo, either autologous bone marrow mesenchymal stem cells or skeletal myoblast cells were transplanted via a catheter into a doxorubicin‐treated failing heart. Four weeks after transplantation, electrophysiological investigation showed that transplantation of either cell type prolonged the local activation time and increased the activation time dispersion. In the stem cell transplantation groups, a positive correlation was demonstrated between activation time dispersion and the number of stem cell‐derived cells in the pacing site. It is concluded that transplantation of either mesenchymal stem cells or skeletal myoblast cells might exacerbate abnormalities of local ventricular conduction in the doxorubicin‐treated failing heart.

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.

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.

Cell transplantation with a catheter-based approach: an efficient method for the treatment of heart failure with multiple lesions.

Abstract.  Cell transplantation is emerging as a potential therapeutic approach for the treatment of heart failure. At present, popular methods of cell delivery may not be efficient in perfusing cells through the whole myocardium. We have developed a novel catheter‐based method for global transplantation of cells. Heart failure was induced in rabbit by intravenous administration of doxorubicin. Autologous bone marrow mononuclear cells were transplanted into failing hearts via the root of the aorta. Bilateral sinus aortae and coronary arteries were visualized by angiography during the cell transplantation procedure; there was no intraprocedural death. Four weeks after cell transplantation, there was an improvement in the mean left ventricular ejection fraction from baseline 72.13% to 81.54% (P = 0.034). Transplanted cells were observed throughout the cardiac layers of left and right ventricles. In conclusion, cell transplantation through the root of the aorta is a useful approach to globally supply cells into the heart.

Admission Serum Calcium Levels Improve the GRACE Risk Score Prediction of Hospital Mortality in Patients With Acute Coronary Syndrome.

The Global Registry of Acute Coronary Events (GRACE) risk score has been extensively validated to predict risk during hospitalization in patients with acute coronary syndrome (ACS). Recently, serum calcium has been suggested as an independent predictor for in‐hospital mortality in patients with ST‐segment elevation myocardial infarction; however, the relationship between the 2 has not been evaluated.

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.

Gene polymorphisms in dual antiplatelet therapy and the presence of hypo-attenuated leaflet thickening after transcatheter aortic valve replacement

The imaging finding of hypo-attenuated leaflet thickening (HALT) on bioprosthesis after transcatheter aortic valve replacement (TAVR) has been reported. The underlying mechanism is not clear, but leaflet thrombosis is speculated to be the cause. Heterogeneous antiplatelet responses may play a role in the process. This is a prospective, single-center pilot study in patients who received successful TAVR from June 2012 to November 2016. HALT on post-procedural multi-detector computed tomography. We thoroughly genotyped 34 SNPs and 8 SNPs that have been reported for clopidogrel and aspirin resistance. A total of 148 patients were enrolled. There were 15 patients demonstrating signs of HALT. Patients with HALT had a higher rate of atrial fibrillation (AF) pre-TAVR (33.3 vs. 7.5%, P = 0.01). We found that rs4244285 G>A polymorphism of the CYP2C19 gene was associated with the risk of HALT in the overdominant model (OR 4.00 [1.15–13.97], P = 0.02 for GA vs. GG+AA) adjusted by sex and the presence of pre-TAVR AF. Antiplatelet drug resistance is a reasonable possibility involved in HALT. Potential directions were suggested in polymorphisms of the CYP2C19 gene.

Age-related changes in cortical and subcortical structures of healthy adult brains: A surface-based morphometry study: Age-Related Study in Healthy Adult Brain Structure

Cerebral structures in both cortical and subcortical regions change with aging. More specific and comprehensive studies are needed to better elucidate these changes.

Age-related changes in fiber tracts in healthy adult brains: A generalized q-sampling and connectometry study: Aging Study in Healthy Adults Brain Tracts

Generalized q‐sampling (GQI) and connectometry analysis provide new indices, i.e., quantitative anisotropy (QA) and spin distribution function (SDF) in comparison with diffusion tensor imaging (DTI). They may provide more age‐related changes in white matter (WM) in aging.

The Volume of Hippocampal Subfields in Relation to Decline of Memory Recall Across the Adult Lifespan

Background: The hippocampus is an important limbic structure closely related to memory function. However, few studies have focused on the association between hippocampal subfields and age-related memory decline. We investigated the volume alterations of hippocampal subfields at different ages and assessed the correlations with Immediate and Delayed recall abilities. Materials and Methods: A total of 275 participants aged 20–89 years were classified into 4 groups: Young, 20–35 years; Middle-early, 36–50 years; Middle-late, 51–65 years; Old, 66–89 years. All data were acquired from the Dallas Lifespan Brain Study (DLBS). The volumes of hippocampal subfields were obtained using Freesurfer software. Analysis of covariance (ANCOVA) was performed to analyze alterations of subfield volumes among the 4 groups, and multiple comparisons between groups were performed using the Bonferroni method. Spearman correlation with false discovery rate correction was used to investigate the relationship between memory recall scores and hippocampal subfield volumes. Results: Apart from no significant difference in the left parasubiculum (P = 0.269) and a slight difference in the right parasubiculum (P = 0.022), the volumes of other hippocampal subfields were significantly different across the adult lifespan (P < 0.001). The hippocampal fissure volume was increased in the Old group, while volumes for other subfields decreased. In addition, Immediate recall scores were associated with volumes of the bilateral molecular layer, granule cell layer of the dentate gyrus (GC-DG), cornus ammonis (CA) 1, CA2/3, CA4, left fimbria and hippocampal amygdala transition area (HATA), and right fissure (P < 0.05). Delayed recall scores were associated with the bilateral molecular layer, GC-DG, CA2/3 and CA4; left tail, presubiculum, CA1, subiculum, fimbria and HATA (P < 0.05). Conclusion: The parasubiculum volume was not significantly different across the adult lifespan, while atrophy in dementia patients in some studies. Based on these findings, we speculate that volume changes in this region might be considered as a biomarker for dementia disorders. Additionally, several hippocampal subfield volumes were significantly associated with memory scores, further highlighting the key role of the hippocampus in age-related memory decline. These regions could be used to assess the risk of memory decline across the adult lifespan.