ABSTRACT
@#[Abstract] Objective: To explore the mechanism of TRIM21 regulating the proliferation of ovarian cancer cells and the resistance of PARP inhibitors by activating Wnt/β-catenin signaling pathway. Methods: Eight pairs of ovarian cancer tissues and cervical epithelial tissues that surgically removed at Yan'an People's Hospital from January 2018 to January 2019 were collected for this study. And the tissues were classified into resistant group and non-resistant group (4 case/group) according to whether the patients were resistant to PARP inhibitor (nilapanib). Ovarian cancer cell lines CAOV3, SKOV3, OVCAR3, ES-2, HO8910, A2780 and OV2008 were also collected for this study. qPCR and Western blotting (WB) were used to detect the expression levels of TRIM21 and β-catenin in the above mentioned tissues and cell lines. Cell lines with TRIM21 overexpression and knockdown were constructed. CCK-8 method was used to detect the proliferation activity of ovarian cancer cells in each group, TOP/FOP dual luciferase assay was used to detect the effect of TRIM21 on Wnt signaling pathway activation, qPCR and WB were used to detect the effect of TRIM21 on mRNA and protein levels of β-catenin, which was further verified by Wnt pathway inhibitor XAV-939. Results: The expression level of TRIM21 in ovarian cancer tissues was significantly higher than that in cervical epithelial tissues (P<0.01), and its expression was more higher in the drug-resistant tissues (P<0.01). TRIM21 expression was the highest in ES-2 cells but comparatively low in CAOV3 and A270 cells (all P<0.01). After TRIM21 knockdown, the expression of TRIM21 in ES-2 cells was significantly decreased, and the cell proliferation was significantly reduced (all P<0.01). After overexpressing TRIM21, the proliferative capacity of ovarian cancer CAOV3 cells was significantly increased (P<0.01), and the antitumor effect of nilaparib was inhibited; TRIM21 overexpression could regulate Wnt/β -catenin pathway activation, while β -catenin knockdown or Wnt/β -catenin inhibitor XAV-939 could significantly reverse the effect of TRIM21 in ovarian cancer. Conclusion: TRIM21 can enhance the proliferation of ovarian cancer cells via regulating Wnt/β-catenin pathway, it plays a certain role in the process of drug resistance of PARP inhibitor nilapani.
ABSTRACT
Objective To investigate the effect of prehospital transport mode on delay care in patients withacutestroke.Methods From March 2016 to August 2016,a total of 255 consecutive patients with acute stroke who met the inclusion criteria in Xuanwu Hospital,Capital Medical University were analyzed prospectively. Seven patients were excluded because of incomplete data. A total of 248 valid cases were enrolled. They were divided into either an ambulance transport group (n=88)or a non-ambulance transport group (n=160)according to whether they were transported by ambulance or not. The differences of the baseline data,prehospital status,onset-to-door time,door-to-examination time,door-to-CT scan time,door-to-intravenous thrombolysis time of the 2 groups were compared,and the related factors of ambulance use were analyzed in patients with acute stroke. Results (1)The ambulance utilization rate of 248 patients was 35. 5%. The age,the coronary heart disease rate,National Institutes of Health Stroke Scale (NIHSS)score of the patients in the ambulance transport group were higher than those of the non-ambulance transport group. There were significant differences between the two groups (65 ± 11 vs. 61 ± 11 years,15. 9%[14/88]vs. 5. 6%[9/160],9 [3,17]vs. 2 [1,5];all P <0. 05). The stroke rate of the patients in the ambulance transport group was lower than that of the non-ambulance transport group(23. 9%[21/88]vs. 37. 5%[60/160],P<0. 05). (2)There were significant differences in self-identified acute disease and self-health care consciousness between the ambulance transport group and the non-ambulance transport group (all P<0. 01). (3)Compared with the non-ambulance transport group,the onset-to-door time,door-to-examination time,door-to-CT scan time,door-to-intravenous thrombolysis time were shorter in patients of the ambulance transport group (102[64,150]min vs. 136[86,230]min,3[1,8]min vs. 7[4,11]min, 15[18,23]min vs. 16[22,27]min,and 41 ± 9 min vs. 50 ± 10 min;all P <0. 05). (4)The result of Logistic regression analysis showed that the acute stroke patients with advanced age (OR,1. 04,95%CI 1. 01-1. 08,P =0. 01),higher NIHSS score (OR,1. 13,95%CI 1. 08-1. 19,P <0. 01),they or the insiders thought that the disease was emergent (OR,17. 08,95%CI 5. 78-50. 41,P<0. 01),they would seek medical advice in time when they felt sick (OR,38. 13,95%CI 10. 13-143. 61,P<0. 01),and they would take medicine by themselves when they felt sick (OR,6. 82,95%CI 2. 33-19. 99,P<0. 01)were more likely to be transported to hospital by ambulance.Conclusion Using ambulance can reduce the treatment de-lay for patients with acute stroke. The patients with self-health care consciousness are more likely to choose am-bulance transport. The importance of using ambulance should be strengthened for patients with stroke.
ABSTRACT
Objective To investigate the baseline factors that influenced prognosis after intravenous thrombolytic therapy. Methods All 82 patients received intravenous urokinase (UK) for acute ischemic stroke. The modified Rankin scale score at 90 days was dichotomized into good outcome (mRS 0-1) and poor outcome (mRS 2-6) as the primary outcome measure. Multivariable logistic regression method was used to analyze independent predictors of good outcome. Results The mRS was good in 36.6% and poor in 63.4%. Univariate analysis indicated that age, time from stroke onset to treatment, atrial fibrillation, pretreatment ESS score, baseline serum glucose, early ischemic changes on baseline CT scans and dose of UK were shown correlated significantly with mRS. However, the multivariate logistic regression did select the ESS score, time to treatment, dose of UK and serum glucose as the independent predictors of good outcome. Conclusion Pretreatment ESS score, time to treatment, dose of UK and baseline serum glucose should be independently predictive of outcome in patients with acute cerebral infarction treated by intravenous UK.