An Observational Study of the Relationship Between Outcome and Platelet Reactivity in Chinese Patients Undergoing PCI Loading with 600 mg Clopidogrel

Objectives: We sought to determine whether high posttreatment platelet reactivity (HPPR) to a 600 mg loading dose of clopidogrel affects outcomes in Chinese patients with acute coronary syndrome (ACS) following percutaneous coronary intervention (PCI) and to investigate whether there is a relationship between the number of platelet reactivity units (PRUs) and the characteristics of the patients. Background: Although impaired platelet response to clopidogrel is a strong predictor of unfavorable outcome after PCI, the impact of HPPR to a 600 mg loading dose of clopidogrel in Chinese patients with ACS undergoing PCI is still unknown. Methods: We performed observational research on 134 unselected patients with ACS undergoing urgent or planned PCI with a 600 mg loading dose of clopidogrel. Platelet activation was expressed as the PRU value measured by the VerifyNow assay. Results: Among the 134 patients (mean age 60.62 years [standard deviation 9.13 years], 60.4% male), there were 46 patients with HPPR (34.3%) and 88 patients without HPPR (65.7%). At a mean follow-up of 6 months (standard deviation 1 month), the rates of cardiac death, unstable angina, and rehospitalization for target lesion revascularization were higher in the HPPR group (19.6% vs. 6.8%, P=0.029). Multivariate analysis identified hemoglobin level and sex as independent predictors of the PRU value ( y =456.355−1.736 x 1 −31.880 x 2 , P<0.05). On receiver operating characteristic curve analysis, PRU values could significantly discriminate between patients with and patients without cardiac death, unstable angina, and rehospitalization for target lesion revascularization (area under the curve 0.758, 95% confidence interval 0.62–0.85, P=0.001, P<0.05). Conclusion: In patients with ACS, HPPR to a 600 mg loading dose of clopidogrel is associated with worse outcomes after PCI. There is some relationship between the PRU value and the hemoglobin level and sex. PRU values can predict the prognosis

Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations

We conducted a joint (pooled) analysis of three genome-wide association studies (GWAS) 1-3 of esophageal squamous cell carcinoma (ESCC) in ethnic Chinese (5,337 ESCC cases and 5,787 controls) with 9,654 ESCC cases and 10,058 controls for follow-up. In a logistic regression model adjusted for age, sex, study, and two eigenvectors, two new loci achieved genome-wide significance, marked by rs7447927 at 5q31.2 (per-allele odds ratio (OR) = 0.85, 95% CI 0.82-0.88; P=7.72x10−20) and rs1642764 at 17p13.1 (per-allele OR= 0.88, 95% CI 0.85-0.91; P=3.10x10−13). rs7447927 is a synonymous single nucleotide polymorphism (SNP) in TMEM173 and rs1642764 is an intronic SNP in ATP1B2, near TP53. Furthermore, a locus in the HLA class II region at 6p21.32 (rs35597309) achieved genome-wide significance in the two populations at highest risk for ESSC (OR=1.33, 95% CI 1.22-1.46; P=1.99x10−10). Our joint analysis identified new ESCC susceptibility loci overall as well as a new locus unique to the ESCC high risk Taihang Mountain region

A role of age-dependent DNA methylation reprogramming in regulating the regeneration capacity of Boea hygrometrica leaves

Plants can regenerate new individuals under appropriate culture conditions. Although the molecular basis of shoot regeneration has steadily been unraveled, the role of age-dependent DNA methylation status in the regulation of explant regeneration remains practically unknown. Here, we established an effective auxin/cytokinin-induced shoot regeneration system for the resurrection plant Boea hygrometrica via direct organogenesis and observed that regeneration was postponed with increasing age of donor plants. Global transcriptome analysis revealed significant upregulation of genes required for hormone signaling and phenylpropanoid biosynthesis and downregulation of photosynthetic genes during regeneration. Transcriptional changes in the positive/negative regulators and cell wall-related proteins involved in plant regeneration, such as ELONGATED HYPOCOTYL5 (HY5), LATERAL ORGAN BOUNDARIES DOMAIN, SHOOT-MERISTEMLESS, and WUSCHEL, were associated with the regeneration process. Comparison of DNA methylation profiling between leaves from young seedlings (YL) and mature plants (ML) revealed increased asymmetrical methylation in ML, which was predominantly distributed in promoter regions of genes, such as HY5 and a member of ABA-responsive element (ABRE) binding protein/ABRE binding factor, as well as genes encoding glycine-rich cell wall structural protein, CENTRORADIALIS-like protein, and beta-glucosidase 40-like essential for shoot meristem and cell wall architecture. Their opposite transcription response in ML explants during regeneration compared with those from YL demonstrated the putative involvement of DNA methylation in regeneration. Moreover, a significant lower expression of DNA glycosylase-lyase required for DNA demethylation in ML was coincident with its postponed regeneration compared with those in YL. Taken together, our results suggest a role of promoter demethylation in B. hygrometrica regeneration

Mechanical Properties and Failure Behavior of 3D-SiCf/SiC Composites with Different Interphases

Continuous silicon carbide fiber-reinforced silicon carbide ceramic matrix composites (SiCf/SiC) are promising as thermal structural materials. In this work, the microstructure and static mechanical properties of 3D-SiCf/SiC with PyC, SiC, and PyC/SiC and without an interface prepared via polymer infiltration and pyrolysis (PIP) were investigated systematically in this paper. The results show that the microstructure and static mechanical properties of SiCf/SiC with an interphase layer were superior to the composites without an interlayer, and the interface debondings are existing in the composite without an interphase, resulting in a weak interface bonding. When the interphase is introduced, the interfacial shear strength is improved, the crack can be deflected, and the fracture energy can be absorbed. Meanwhile, the shear strength of the composites with PyC and PyC/SiC interfaces was 118 MPa and 124 MPa, respectively, and showing little difference in bending properties. This indicates that the sublayer SiC of the PyC/SiC multilayer interface limits the binding state and the plastic deformation of PyC interphase, and it is helpful to improve the mechanical properties of SiCf/SiC

The sequence analysis of origin of replication in Saccharomyces cerevisiae genomes

DNA replication is a highly precise process that is initiated from origins of replication (ORI) and is regulated by a set of regulatory proteins. The mining of DNA sequence information will be not only beneficial for understanding the regulatory mechanism of replication initiation, but also for accurately identifying ORI. In this study, the GC profile and GC skew were calculated for the analysis of compositional bias in the Saccharomyces cerevisiae (S. cerevisiae) genome. We found that the GC content in the region of replication origins is significantly lower than that in the flanking regions. By calculating the information redundancy, an estimation of the correlation of nucleotides, we found that the intensity of adjoining correlation in replication origins is dramatically higher than that in flanking regions. Furthermore, the relation between ORIs and nucleosome as well as transcription start sites were investigated. Results show that ORIs are usually not occupied by nucleosomes. Finally, we calculated the distribution of ORIs in yeast chromosomes and found that most ORIs prefer to transcription terminal regions. We hope that these results will contribute to the identification of ORIs and to the mechanisms of DNA replication

Differences in Optimal Platelet Reactivity after Potent P2Y12 Inhibitor Treatment in Acute Coronary Syndrome Patients Undergoing Percutaneous Coronary Intervention

Background: East Asian patients receiving treatment with the potent P2Y12 inhibitors prasugrel or ticagrelor experience more potent platelet inhibition than with clopidogrel. Methods: This study investigated differences in OPR rates with reduced doses of prasugrel (n = 38) or ticagrelor (n = 40) for maintenance therapy in 118 Korean ACS patients who had undergone PCI, in comparison to conventional-dose clopidogrel (n = 40). We assessed drug responses at one- and three-months post-PCI with VerifyNow and multiple electrode aggregometry assays. Results: At the one-month period, patients receiving standard-dose prasugrel or ticagrelor had lower platelet reactivity as determined by the three assays than those receiving the conventional dose of clopidogrel (VN: p = 0.000; MEA: p = 0.000; LTA: p = 0.000). At the 3-month point, platelet reactivity was lower in those receiving reduced-dose prasugrel or ticagrelor than the clopidogrel-treated patients (VN: p = 0.000; MEA: p = 0.012; LTA: p = 0.002). Prasugrel resulted in significantly lower platelet inhibition than ticagrelor as determined by VN and LTA (VN: p = 0.000; LTA: p = 0.003). At three months, there was a significant overall difference in OPR among the three groups when measured by VN (p &lt; 0.001), but not when measured by MEA (p = 0.596). OPR in the reduced-dose prasugrel group was not significantly different to the clopidogrel group at three months (VN: p = 0.180; MEA: p = 0.711). OPR in the reduced-dose ticagrelor group was similar to clopidogrel as determined by MEA at three months, but was different when assessed by VN (VN: p = 0.000; MEA: p = 0.540). Compared to standard-dose, the reduced-dose prasugrel OPR rate was significantly increased (VN: p = 0.008; MEA: p = 0.020). Conclusions: OPR values for reduced-dose prasugrel and conventional-dose clopidogrel at three months were similar but higher than for reduced-dose ticagrelor as determined by VN, but no differences were noted by MEA. The MEA assay might have less sensitivity and consistency than the VN assay. Further studies are needed to explore this discrepancy