Identification of Potential Biological Factors Affecting the Treatment of Ticagrelor After Percutaneous Coronary Intervention in the Chinese Population.

BACKGROUND: Generally, many individual factors can affect the clinical application of drugs, of which genetic factors contribute more than 20%. Ticagrelor is a new class of receptor inhibitors receptor antagonist of P2Y12 and is used as an antiplatelet agents. But it is not affected by the influence of CYP2C19 polymorphism. With lack of predicted biomarkers, especially the research data of Chinese, it has the important significance in studying individual differences of ticagrelor in the antiplatelet efficacy and safety, through pharmacogenomics research. METHODS: Whole-exome sequencing (WES) was performed in 100 patients after PCI with ticagrelor treatment. Clinical characteristics and WES of patients were used to performed genome-wide association analysis (GWAS), region-based tests of rare DNA variant to find the influencing factors of antiplatelet effect to ticagrelor and bleeding events. Co-expression, protein-protein interaction (PPI) network and pathway enrichment analysis were then used to find possible genetic mechanisms. Atlas of GWAS (https://atlas.ctglab.nl/) were used for external data validation. RESULTS: DNAH17, PGS1 and ABCA1 as the potential variant genes are associated with the expected antiplatelet effect to ticagrelor. The affected pathways may include the synthesis and metabolism of lipoprotein cholesterol and the catabolic process of pyrimidine-containing compound (GO:0072529). Age, sex and PLT were found may be potential factors for ticagrelor bleeding events. CONCLUSION: We systematically identified new genetic variants and some risk factors for reduced efficacy of ticagrelor and highlighted related genes that may be involved in antiplatelet effects and bleeding event of ticagrelor. Our results enhance the understanding of the absorption and metabolic mechanisms that influence antiplatelet response to ticagrelor treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03161002. First Posted: May 19, 2017. https://clinicaltrials.gov/ct2/show/study/NCT03161002.

Altered Microstructure of Cerebral Gray Matter in Neuromyelitis Optica Spectrum Disorder-Optic Neuritis: A DKI Study.

The purpose of this study was to analyze microstructural alterations in cerebral gray matter using non-Gaussian diffusion kurtosis imaging (DKI) in neuromyelitis optica spectrum disorder (NMOSD) patients with optic neuritis (NMOSD-ON). DKI was performed in 14 NMOSD-ON patients and 22 normal controls (NCs). DKI-derived metrics, including mean kurtosis (MK), radial kurtosis (RK), axial kurtosis (AK), fractional anisotropy (FA), and mean diffusivity (MD), were voxel-wisely compared by two-sample t-tests with gaussian random field (GRF) correction between the two groups. The correlations between altered DKI metrics and clinical features were analyzed. Compared with NCs, NMOSD-ON patients showed significantly decreased MK and RK both in the left inferior temporal gyrus (ITG), and decreased AK in the bilateral calcarine (CAL). While increased MD in the left fusiform gyrus (FFG), right CAL, and right hippocampus (HIP)/parahippocampal gyrus (PHG) were found. Furthermore, correlation analysis showed that mean deviation was negatively correlated with AK values of bilateral CAL and positively correlated with MD values of right CAL (q < 0.05, false discovery rate (FDR) corrected). For NMOSD-ON patients, microstructural abnormalities in the occipital visual cortex are correlated with clinical disability. These findings may provide complementary information to understand the neuropathological mechanisms underlying the impairments of cerebral gray matter in NMOSD-ON.

Lower Platelet Aggregation Is a Risk Factor for Dual Antiplatelet Therapy-Associated Bleeding: A Preliminary Retrospective Study with Genotype Analysis.

BACKGROUND The purpose of this study was to investigate factors influencing bleeding in patients with acute coronary syndrome (ACS) who are on aspirin and ticagrelor as dual antiplatelet therapy. MATERIAL AND METHODS This retrospective case-control study included 50 patients with ACS (25 with reported bleeding events and 25 without) on aspirin and ticagrelor. Adenosine diphosphate (ADP)- and arachidonic acid (ACA)-induced platelet aggregation rates were measured using light transmission aggregometry. Single-nucleotide polymorphisms (SNPs) in PEAR1, GP1BA, and GSTP1 were genotyped. RESULTS ACA-induced platelet aggregation rates were obviously lower in patients with bleeding events than in those without (13.28±8.46% vs. 24.93±9.89%, P<0.001). No significant differences in ADP-induced platelet aggregation rates were observed between the 2 groups (16.17±9.74% vs. 16.88±12.69%, P>0.05). Among those with bleeding events and among controls, 70% and 80% had an ACA-induced platelet aggregation rate of 0-18% and 18-50%, respectively. Mutation rates of rs6065 in GP1BA and rs1695, rs4891, and rs8191439 in GSTP1 also differed significantly between the 2 groups. CONCLUSIONS Lower ACA-induced platelet aggregation rates are associated with increased risk of bleeding in patients with ACS who are on aspirin and ticagrelor. An ACA-induced platelet aggregation rate of 18% may be considered the cutoff point for identifying high risk of aspirin-associated bleeding events in patients with ACS. SNP genotyping may also help predict the risk of bleeding in patients with ACS.

Aberrant sylvian vein: A newly described cause of pulsatile tinnitus.

We herein report a newly described cause of venous pulsatile tinnitus: protrusion of an aberrant sylvian vein into the tympanum. A 60-year-old woman presented with a 4-month history of objective persistent pulsatile tinnitus in the right ear with no other complaints. The pulsatile tinnitus diminished with rotation of the head to the right side or by compression of the right cervical vascular structures. The frequency and intensity of the tinnitus were 125 Hz and 20 dB HL, respectively. Audiometry and otoscopic examination findings were normal. Radiologic examination showed that the right sylvian vein protruded into the tympanum through the dehiscent anterior cortical plate of the tympanum.

[Studies on the chemical constituents of Epimedium brevicornum].

OBJECTIVE: To study the chemical constituents of Epimedium breviconum. METHODS: Compounds were purificated with various chromatographic techniques such as silica vacuum liquid chromatography and Sephadex LH-20 column chromatography. Their structures were elucidated by physico-chemical methods and spectral analysis. RESULTS: Ten compounds were obtained and indentified as (7R, 8S) 4,9-dihydroxyl-3,3'-dimethyoxyl-7, 8-dihydrobenzofunan-1'-propanolneolignan-9'-O-alpha-L-rhamnopyranoside (1), (7R, 8S, 8' R) 4, 4', 8', 9-tetrahydroxyl-3, 3'-dimethyoxyl-7, 9'-monoepoxylignan (2), (+)-cycloolivil (3), (3, 5, 7, 4')-tetrahydroxyl-8-isopentene group flavonoids-3-O-alpha-L-rhamnopyranoside (4), beta-sitosterol (5), p-hydroxybenzaldehyde (6), succinic acid (7) and p-hydroxyphenethyl (8). CONCLUSIONS: Compound 1 is isolated from this genus for the first time. Compounds 2,3,5 -8 are isolated from the plant for the first time.