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81.
Daniel W. Lin E. David Crawford Thomas Keane Brent Evans Julia Reid Saradha Rajamani Krystal Brown Alexander Gutin Jonathan Tward Peter Scardino Michael Brawer Steven Stone Jack Cuzick 《Urologic oncology》2018,36(6):310.e7-310.e13
Background
A combined clinical cell-cycle risk (CCR) score that incorporates prognostic molecular and clinical information has been recently developed and validated to improve prostate cancer mortality (PCM) risk stratification over clinical features alone. As clinical features are currently used to select men for active surveillance (AS), we developed and validated a CCR score threshold to improve the identification of men with low-risk disease who are appropriate for AS.Methods
The score threshold was selected based on the 90th percentile of CCR scores among men who might typically be considered for AS based on NCCN low/favorable-intermediate risk criteria (CCR = 0.8). The threshold was validated using 10-year PCM in an unselected, conservatively managed cohort and in the subset of the same cohort after excluding men with high-risk features. The clinical effect was evaluated in a contemporary clinical cohort.Results
In the unselected validation cohort, men with CCR scores below the threshold had a predicted mean 10-year PCM of 2.7%, and the threshold significantly dichotomized low- and high-risk disease (P = 1.2 × 10–5). After excluding high-risk men from the validation cohort, men with CCR scores below the threshold had a predicted mean 10-year PCM of 2.3%, and the threshold significantly dichotomized low- and high-risk disease (P = 0.020). There were no prostate cancer-specific deaths in men with CCR scores below the threshold in either analysis. The proportion of men in the clinical testing cohort identified as candidates for AS was substantially higher using the threshold (68.8%) compared to clinicopathologic features alone (42.6%), while mean 10-year predicted PCM risks remained essentially identical (1.9% vs. 2.0%, respectively).Conclusions
The CCR score threshold appropriately dichotomized patients into low- and high-risk groups for 10-year PCM, and may enable more appropriate selection of patients for AS. 相似文献82.
83.
BackgroundThe accessibility of public facilities for all is an issue increasingly gaining focus in policy debates, especially regarding the ageing population.ObjectiveThis paper describes a psychometric approach to the development of a new instrument for assessing the accessibility of public entrances.MethodsItems to include were selected by means of literature review and classified according to a typology of person-environment fit that uses the International Classification of Functioning, Disability and Health (ICF) as theoretical framework. Content validity was assessed by a scientific panel approach and construct validity by using simulation techniques and correlation analysis with a related construct. Reliability was evaluated by inter-rater agreement analysis, where 15 strategically selected public entrances were assessed by five rater pairs.ResultsContent validity was assessed as high (3.6 on a scale from 1 to 4) and correlation indicating convergent validity between instrument scores and a related construct was moderate (rs = 0.60, p < 0.001). Inter-rater reliability was acceptable to good (kappa 0.42, overall agreement 81%). After an iterative process including review of validity and reliability results, the resulting assessment instrument consisted of 56 items in 7 sections.ConclusionsThis study demonstrated good content validity and acceptable to good inter-rater reliability. Though initial results were promising, user involvement and further testing of construct validity is needed. The goal of the new instrument is a feasible tool for planning, evaluation and accomplishment of policies intended to make public entrances accessible for all. The extent to which the instrument succeeds remains to be tested by practical use. 相似文献
84.
目的构建携带人miR302和增强型绿色荧光蛋白(EGFP)基因的慢病毒表达载体pFUM3GW。方法NheⅠ和NotⅠ双酶切pmiR302ApE以释放miR302,接着补平酶切位点而获连接用miR302;BamHⅠ酶切携带EGFP的慢病毒载体pFUGW,接着补平酶切产物,并去磷酸化而获连接用载体片段,最后使用DNA连接试剂盒(TaKaRa)中的SolutionI将其与连接用miR302连接,连接产物转化,次日挑选单菌落,PCR筛选正向阳性克隆,随后将选定的含有阳性克隆的单菌落摇菌,提取质粒并行酶切鉴定及对插入的miR302测序。所构建载体命名为pFUM3GW。获pFUM3GW后,按Invitrogen公司推荐的标准程序进行慢病毒包装和确认慢病毒是否成功生产;携带miR302和EGFP基因的慢病毒感染鼻咽癌细胞株C666-1、CNE1和5-8F以建立相应病毒感染体系。结果PCR、酶切和测序证实成功构建了pFUM3GW,按标准程序生产的携带miR302和EGFP基因的慢病毒上清高效率感染小鼠胚胎成纤维细胞(MEFs)及鼻咽癌细胞株C666-1、CNE1和5-8F。结论成功构建携带人miR302和EGFP基因的慢病毒表达载体pFUM3GW,为相关后续研究打下了良好基础。 相似文献
85.
反义miRNA-221/222上调p27kip1抑制胶质瘤细胞生长的体外研究 总被引:4,自引:3,他引:1
目的 探讨敲低miRNA-221/222表达上调p27kip1抑制U251人脑胶质瘤细胞株生长的效果及机制.方法 脂质体共转染反义miRNA-221/222下调U251人脑胶质瘤细胞株miRNA-221、miRNA-222的表达.使用Northern blot方法 鉴定转染后U251细胞miRNA-221、miRNA-222表达水平下调;MTT法评价反义miRNA-221/222抑制U251细胞生长效果;流式细胞术检测转染后U251细胞周期分布;Western blot分析p27kip1蛋白的表达变化.结果 Northern blot显示反义miRNA-221/222共转染组使miRNA-221、miRNA-222的表达水平明显下降.反义miRNA-221转染组仅使miRNA-221的表达水平明显下降,反义miRNA-222转染组仅使miRNA-222的表达水平明显下降.转染无意序列组及对照组的miRNA-221、miRNA-222表达水平没有改变.MTT结果 显示反义miRNA-221/222共转染组肿瘤细胞生长速度小于对照组、转染无意序列组、转染反义miRNA-221组、转染反义miRNA-222组.流式细胞术检测可见反义miRNA-221/222共转染组细胞周期存在G0/G1期阻滞且明显高于其他各组.Western blot显示反义miRNA-221/222共转染组的p27kip1蛋白表达明显上调.结论 反义miRNA-221/222通过上调p27kip1蛋白表达来抑制胶质瘤细胞U251的生长. 相似文献
86.
87.
《Environmental toxicology》2018,33(7):743-751
Exposure to particulate matter (PM) leads to kinds of cardiopulmonary diseases, such as asthma, COPD, arrhythmias, lung cancer, etc., which are related to PM‐induced inflammation. We have found that PM2.5 (aerodynamics diameter <2.5 µm) exposure induces inflammatory response both in vivo and in vitro. Since the toxicity of PM is tightly associated with its size and components, PM1 (aerodynamics diameter <1.0 µm) is supposed to be more toxic than PM2.5. However, the mechanism of PM1‐induced inflammation is not clear. Recently, emerging evidences prove that microRNAs play a vital role in regulating inflammation. Therefore, we studied the regulation of miR‐146a in PM1‐induced inflammation in human lung bronchial epithelial BEAS‐2B cells. The results show that PM1 induces the increase of IL‐6 and IL‐8 in BEAS‐2B cells and up‐regulates the miR‐146a expression by activating NF‐κB signaling pathway. Overexpressed miR‐146a prevents the nuclear translocation of p65 through inhibiting the IRAK1/TRAF6 expression, and downregulates the expression of IL‐6 and IL‐8. Taken together, these results demonstrate that miR‐146a can negatively feedback regulate PM1‐induced inflammation via NF‐κB signaling pathway in BEAS‐2B cells. 相似文献
88.
89.
探讨强直性脊柱炎患者辅助性T细胞17(Th17)/调节性T细胞(Treg)相关细胞因子、微小核糖核酸-155(miR-155)与脊柱活动度的关系。方法 回顾性分析2018年1月~2021年3月 我院收治的强直性脊柱炎患者116例为观察组,根据强直性脊柱炎疾病活动指数(BASDAI)分为活动期(BASDAI≥4,n=52)、稳定期(BASDAI<4,n=64);另选取同期于我院进行健康体检的健康志愿者97例为对照组。对比各组Th17/Treg相关细胞因子、miR-155表达水平;对比活动期和稳定期的脊柱活动度Bath AS测量指数(BASMI),分析强直性脊柱炎患者Th17/Treg相关细胞因子、miR-155与脊柱活动度的相关性。结果 观察组IL-17、IL-23、miR-155表达水平明显高于对照组(P<0.05)。活动期IL-17、IL-23、miR-155表达水平明显高于稳定期(P<0.05)。活动期强直性脊柱炎患者BASMI评分明显高于稳定期(P<0.05)。经 Pearson相关系数分析显示,强直性脊柱炎患者IL-17、IL-23、miR-155表达水平与BASMI评分呈正相关,IL-10、TGF-β表达水平与BASMI评分呈负相关(P<0.05)。结论 强直性脊柱炎患者高表达miR-155、Th17相关细胞因子、低表达Treg相关细胞因子,Th17/Treg呈失衡状态,且Th17/Treg相关细胞因子、miR-155与强直性脊柱炎患者脊柱活动度具有一定的相关性,可作为临床评估病情的辅助检查。 相似文献
90.
BackgroundSmoking is likely to facilitate airway inflammation and finally contributes to chronic obstructive pulmonary disease (COPD). This investigation was intended to elucidate miRNAs that were involved in smoking‐induced COPD.MethodsAltogether 155 COPD patients and 77 healthy volunteers were recruited, and their serum levels of miR‐221‐3p and miR‐92a‐3p were determined. Besides, human bronchial epithelial cells (16HBECs) were purchased, and they were treated by varying concentrations of cigarette smoke extract (CSE). The 16HBECs were, additionally, transfected by miR‐221‐3p mimic, miR‐92a‐3p mimic, miR‐221‐3p inhibitor or miR‐92a‐3p inhibitor, and cytokines released by them, including TNF‐α, IL‐8, IL‐1β, and TGF‐β1, were monitored using enzyme linked immunosorbent assay (ELISA) kits.ResultsChronic obstructive pulmonary disease patients possessed higher serum levels of miR‐221‐3p and miR‐92a‐3p than healthy volunteers (p < 0.05), and both miR‐221‐3p and miR‐92a‐3p were effective biomarkers in diagnosing stable COPD from acute exacerbation COPD. Moreover, viability of 16HBECs was undermined by CSE treatment (p < 0.05), and exposure to CSE facilitated 16HBECs’ release of TNF‐α, IL‐8, IL‐1β, and TGF‐β1 (p < 0.05). Furthermore, miR‐221‐3p/miR‐92a‐3p expression in 16HBECs was significantly suppressed after transfection of miR‐221‐3p/miR‐92a‐3p inhibitor (p < 0.05), which abated CSE‐triggered increase in cytokine production and decline in viability of 16HBECs (p < 0.05).ConclusionMiR‐221‐3p and miR‐92a‐3p were involved in CSE‐induced hyperinflammation of COPD, suggesting that they were favorable alternatives in diagnosing COPD patients with smoking history. 相似文献