Objective To investigate the association of single nucleotide polymorphisms (SNPs) in COX-2 with aspirin resistance in Chinese cerebral infarction patients. Methods A total of 150 Chinese cerebral infarction patients were recruited. Platelet aggregation response was measured by light transmission aggregometry method and four SNPs located in COX2 gene were genotyped by sequencing method. Results Sixty patients of the total were classified as aspirin non-responders. For clinical variables , concentrations of high homocysteine and the frequency of recurrence cerebral infarction were significantly higher in aspirin non-responders when compared with aspirin responders. Univariate analysis of SNPs showed that rs20417 , rs689465 and rs689466 were significantly associated with aspirin resistance. Multivariate analysis indicated that after adjusting other SNPs and clinical risk factors, rs20417 and rs689466 were still significantly associated with aspirin resistance. Conclusions Rs689466 is significantly associated with aspirin resistance in Chinese cerebral infarction patients even after the adjustment of rs20417. By combining rs689466 , rs20417 and other clinical risk factors , we may better classify the aspirin non-responders from aspirin responders.

Objective To investigate the relation of angiopoietin-1 (Ang-1) with prognoses of patients with acute ischemic stroke.Methods Eighty-nine patients with acute ischemic stroke,admitted to our hospitals fiom October 2015 to December 2017,were chosen.The patients were diagnosed as having acute ischemic stroke by digital subtraction angiography (DSA),and assessed with National Institute of Health Stroke Scale (NIHSS) on the time of admission and 21st d of admission;modified Rankin Scale (mRS) was performed on 90th d of admission.According to NIHSS and mRS scores,these patients were divided into a good prognosis group (difference value of NIHSS scores＞0,mRS scores≤ 2) and a poor prognosis group (difference value ofNIHSS scores≤ 0,mRS scores＞2).In addition,31 patients without acute ischemic stroke who were randomly selected as a control group at the same time.The clinical data of all study subjects were collected.Morning fasting blood of the patients was collected on 2nd,7th,14th,and 21st d of admission.The serum Ang-1 expression was detected by ELISA.Results (1) Fifty-seven patients were into the good prognosis group and 32 were into the poor prognosis group;there were no significant differences in age,gender,hypertension history,diabetes history,smoking history,and drinking history among the control group,good prognosis group and poor prognosis group (P＞0.05).(2) There was no statistically significant difference in Ang-1 expression level in control group among different time points (P＞0.05);however,Ang-1 level in the good prognosis group and the poor prognosis group was the highest on 2n d of admission,and then,gradually decreased,and it still had high expression on the 21st d;significant differences were noted among the 3 groups on 2nd,7th,14th,and 21st d of admission (P＜0.05),and Ang-1 level in the good prognosis group was significantly higher than that in the poor prognosis group and control group (P＜0.05).Conclusion Ang-1 level increases in patients with acute ischemic stroke;Ang-1 level in good prognosis patients is higher than that in poor prognosis patients,suggesting that Ang-1 may be related to their prognoses.

Objective: To analysis teratogenic effect of GDC-0449 to fetus and set up the animal model of GDC-0449 induced oromandibular limb hypogenesis in mouse for further research of its pathogenesis. Methods: Twenty-seven pregnant Institute of Cancer Research (ICR) mice were randomly divided into: control group, embryonic day 8.5 (E8.5) exposed groups, E9.5 exposed groups, E10.5 exposed groups, E11.5 exposed groups, E12.5 exposed groups, E13.5 exposed groups, E14.5 exposed groups and E15.5 exposed groups. Each group had 3 mice. Exposed groups were treated with the Hedgehog pathway antagonist GDC-0449 at a single dose 150 mg/kg by oral gavage from E8.5 to E15.5. At E16.5, embryonic phenotypes were analyzed in detail by stereo microscope and histology. After establish an optimal dysmorphogenic concentration, 6 pregnant ICR mice were randomly divided into control group and the optimal group, embryonic phenotypes were analyzed by whole-mount skeletal staining and micro-computed tomography at E18.5. Results: The mice were exposed to GDC-0449 on E11.5 and E12.5 had a high incidence of cleft palate. GDC-0449 exposed between E9.5 and E10.5 caused craniofacial and limb dysmorphology, including micrognathia, microglossia, ectrodactylia, partial anodontia and cleft palate. Most interestingly, these are extremely similar to oromandibular limb hypogenesis syndrome. Conclusions The results of this study indicate that GDC-0449 can be used to induce micrognathia, microglossia, ectrodactylia, partial anodontia and cleft palate. This work established a novel mouse model for oromandibular limb hypogenesis.

The Hedgehog (Hh) signalling pathway is essential for cellular proliferation and differentiation during embryonic development. Gain and loss of function of Hh signalling are known to result in an array of craniofacial malformations. To determine the critical period for Hh pathway antagonist-induced frontal bone hypoplasia, we examined patterns of dysmorphology caused by Hh signalling inhibition. Pregnant mice received a single oral administration of Hh signalling inhibitor GDC-0449 at 100 mg•kg or 150 mg•kg body weight at preselected time points between embryonic days (E)8.5 and 12.5. The optimal teratogenic concentration of GDC-0449 was determined to be 150 mg•kg. Exposure between E9.5 and E10.5 induced frontal bone dysplasia, micrognathia and limb defects, with administration at E10.5 producing the most pronounced effects. This model showed decreased ossification of the frontal bone with downregulation of Hh signalling. The osteoid thickness of the frontal bone was significantly reduced. The amount of neural crest-derived frontal bone primordium was reduced after GDC-0449 exposure owing to a decreased rate of cell proliferation and increased cell death.
Administration, Oral ; Anilides ; pharmacology ; Animals ; Bone Diseases, Developmental ; chemically induced ; Cell Proliferation ; drug effects ; physiology ; Female ; Frontal Bone ; abnormalities ; Hedgehog Proteins ; antagonists & inhibitors ; Limb Deformities, Congenital ; chemically induced ; Mice ; Micrognathism ; chemically induced ; Osteogenesis ; drug effects ; Pregnancy ; Pyridines ; pharmacology ; Signal Transduction ; drug effects