鼻咽癌患者血清中miR-141-3p和miR-155-3p的表达水平及其临床意义北大核心

目的:探讨鼻咽癌患者血清中miR-141-3p及miR-155-3p的表达水平及临床意义。方法:选取2017年01月至2020年09月我院收治的95例鼻咽癌患者和45例健康对照组作为研究对象,采用实时荧光定量PCR法检测miR-141-3p及miR-155-3p表达水平。应用受试者工作特征(receiver operating characteristic, ROC)曲线分析血清中miR-141-3p及miR-155-3p表达水平对鼻咽癌的诊断价值。Pearson相关分析分析鼻咽癌患者血清中miR-141-3p与miR-155-3p表达水平的相关性。结果:鼻咽癌组血清中miR-141-3p(3.25±1.28 vs 0.64±0.17)及miR-155-3p(1.47±0.83 vs 0.35±0.08)表达水平均明显高于对照组(P均<0.001)。鼻咽癌患者血清中miR-141-3p及miR-155-3p表达水平升高与临床分期高、分化程度低、淋巴结转移及远处转移相关(P均<0.001)。ROC曲线显示,血清中miR-141-3p及miR-155-3p表达水平诊断鼻咽癌的最佳截断值分别为2.18、0.97,两项联合诊断鼻咽癌的曲线下面积(0.940,95%CI:0.877~0.998)最大,其敏感度和特异度为97.0%和86.2%。相关分析显示,鼻咽癌患者血清中miR-141-3p与miR-155-3p表达水平呈正相关(r=0.853,P<0.001)。结论:鼻咽癌患者血清中miR-141-3p及miR-155-3p表达水平明显升高,有望作为鼻咽癌诊断的潜在标志物。     

miRNA141表达的调控对人前列腺癌DU145细胞恶性生物行为的影响

目的：研究microRNA-141（miR-141）表达的调控对人前列腺癌细胞系DU145细胞增殖、周期、凋亡、侵袭和迁移等恶性生物学行为的影响及其作用机制。方法：利用脂质体Lipofectamine2000将miR-141 mimics（miR-141 up组）和miR-141 inhibi‐tiors（miR-141 down 组）分别转染至人前列腺癌DU145细胞中，同时设置未转染组（Control组）和miRNA无义序列转染组（NC组）。qPCR检测转染前后各组DU145细胞中miR-141表达变化，MTT方法检测各组DU145细胞的增殖活力和对顺铂（DDP）作用敏感性变化，流式细胞术检测各组DU145细胞周期和顺铂作用下凋亡率变化，Transwell方法检测各组细胞侵袭和迁移能力的变化，Western blotting检测各组细胞中VEGF、EGFR蛋白表达量变化。结果：与Control组和NC组相比，miR-141 down组DU145细胞中miRNA-141表达水平下降为（0.18±0.08），其细胞增殖活力显著下降而对DDP敏感性显著上升、细胞周期被阻滞于G0+G1期而细胞凋亡率显著上升至（46.67±5.86）%、细胞侵袭率和迁移率分别显著下降至（44.34±8.32）%和（57.73±6.19）%、VEGF和EGFR相对表达量分别下降至（0.47±0.06）和（0.36±0.06）（上述各指标分别P<0.05或P<0.01）。miR-141 up组DU145细胞中miR‐NA-141表达水平上升为（4.23±0.53），其细胞增殖活力显著上升而对DDP敏感性显著下降、细胞周期提前进入S和G2期而细胞凋亡率显著下降至（18.77±4.24）%、细胞侵袭率和迁移率分别显著上升至（89.94±6.34）%和（94.44±5.84）%、VEGF和EGFR相对表达量分别上升至（0.89±0.07）和（0.73±0.06）（上述各指标分别P<0.05或P<0.01）。结论：miR-141在前列腺癌DU145细胞中发挥促癌因子作用，其下调表达能够显著抑制DU145细胞增殖活力、周期、侵袭与迁移，而促进对DDP的敏感性和细胞凋亡，其机制可能与其抑制VEGF和EGFR蛋白表达有关。     

MicroRNA-141靶向Keap1调控Nrf2/ARE信号通路对乳腺癌T47D细胞活力的影响

目的:探讨微小RNA-141(miRNA-141)靶向Keap1调控Nrf2/ARE信号通路对乳腺癌T47D细胞活力的影响。方法:乳腺癌T47D细胞分别转染miRNA-141模拟物(mimic)和阴性对照序列(NC),作为miRNA-141组和NC组,并设立未转染空白对照组,采用real-time PCR法检测细胞中miRNA-141的含量;MTT法与荧光探针2’,7’-二氢二氯荧光素二乙酸酯(DCFH-DA)法分别检测细胞活力和活性氧簇(ROS)水平;Western blot法检测胞质接头蛋白Keap1、核因子E2相关因子2(Nrf2)、超氧化物歧化酶2(SOD2)和谷胱甘肽过氧化酶1(GPx1)的表达;双萤光素酶实验检测miRNA-141与Keap1的关系。结果:转染miRNA-141 mimic后,miRNA-141组的miRNA-141表达量明显增高,细胞活力、ROS水平和Keap1蛋白表达均下降,而细胞核Nrf2蛋白SOD2和GPx1表达升高(P0.05);双萤光素酶实验结果显示Keap1为miRNA-141的靶基因。结论:miRNA-141可能通过靶向负调控Keap1激活Nrf2/ARE信号通路,诱导抗氧化酶的表达,以降低细胞氧化应激水平,从而抑制乳腺癌细胞的活力。     

A meta-analysis of the associations between the Q141K and Q126X ABCG2 gene variants and gout risk

Background: Gout is an inflammatory disease in which genetic factors play a role. ABCG2 is a urate transporter, and the Q141K and Q126X variants of ABCG2 have been associated with a risk of developing gout, though previous studies of these associations have been inconsistent. Therefore, we conducted a meta-analysis to explore the relationship between these genetic variants and gout. Methods: We examined 8 electronic literature databases. In total, 9 eligible articles on the associations between the Q141K (rs2231142) and Q126X (rs72552713) variants and gout risk, including 11 case-control studies were selected. We used odds ratios (OR) and 95% confidence intervals (CI) to assess the strength of these relationships in dominant, recessive, and co-dominant models. Results: This study included 6652 participants (2499 gout patients and 4153 controls). The Q141K variant was found to significantly increase the risk of gout in Asians (dominant model: OR=2.64, 95% CI=2.04-3.43, P=0.02 for heterogeneity; recessive model: OR=3.19, 95% CI=2.56-3.97, P=0.28 for heterogeneity; co-dominant model: OR=1.37, 95% CI=1.18-1.59, P=0.09 for heterogeneity) and other populations (dominant model: OR=1.85, 95% CI=1.20-2.85, P<0.0001 for heterogeneity; recessive model: OR=3.78, 95% CI=2.28-6.27, P=0.19 for heterogeneity; co-dominant model: OR=1.48, 95% CI=1.26-1.74, P=0.19 for heterogeneity). The Q126X variant also significantly increased the risk of gout in Asians (dominant model: OR=3.87, 95% CI=2.07-7.24, P=0.06 for heterogeneity). Conclusions: These results suggest associations between the rs2231142 and rs72552713 ABCG2 gene polymorphisms and gout risk, which led to unfavorable outcomes. However, studies with larger sample sizes and homogeneous populations should be performed to confirm these results.     

非小细胞肺癌中miRNA-141的表达及临床意义

目的:探讨miRNA-141在非小细胞肺癌中的表达及其与临床病理特征的关系。方法:采用real time-PCR法对54例非小细胞患者,肺癌组织及正常肺组织的miRNA-141表达水平进行定量分析,结果由2-△△CT处理,并分析与临床病理资料的关系。结果:在NSCLC患者肿瘤组织中miRNA-141表达水平明显升高,其表达与临床分期、病理类型显著相关(P<0.05)。而在不同年龄、性别、肿瘤大小、吸烟史患者间差异无统计学意义(P>0.05)。结论:MiRNA-141高表达与非小细胞肺癌的临床分期、病理分型密切相关,miRNA-141有可能作为非小细胞肺癌的重要肿瘤标志物之一。     

Safety and Efficacy of Repeated Thrombolysis with Alteplase in Early Recurrent Ischemic Stroke: A Systematic Review

Background and Aim: The current American Heart Association guidelines for the management of acute ischemic stroke advise against the use of intravenous (IV) alteplase in patients with recurrent stroke occurring within 90 days of their index event. Following these guidelines strictly, patients having early recurrent ischemic stroke would be unable to avail of this reperfusion strategy that has been proven to confer superior clinical outcomes. While some registry-based studies have demonstrated the safety of IV alteplase in this subgroup of patients, data on the repeated use of the drug are lacking. Thus, we aim to determine the safety and efficacy of repeated thrombolysis in patients with early recurrent ischemic strokes. Methods: The following electronic databases were searched for relevant studies: the Cochrane Central Register for Controlled Trials by The Cochrane Library, MEDLINE by PubMed, Health Research and Development Information Network, Scopus, and ClinicalTrials.gov. Data on symptomatic intracranial hemorrhage, 90-day clinical outcomes, systemic hemorrhage and allergic reactionswere synthesized. Results: Ten articles with 33 patients in total were included in our review. One patient developed symptomatic intracranial hemorrhage after the second reperfusion attempt and subsequently died from pneumonia. Another died from spontaneous rupture of previously unidentified infrarenal aortic aneurysm. Six of the 13 patients with available follow-up data had good clinical outcomes (Modified Rankin Score 0-2). There were no allergic reactions and other drug-related adverse events noted. Conclusions: Repeated IV alteplase can be safe and efficacious in patients who have early recurrent ischemic stroke. Larger studies, trials, or registry-based data are needed to ascertain the encouraging findings of our review.     

胃癌组织TGF-β对miR-200c/141表达影响的研究

目的 TGF-β能够诱导肿瘤细胞发生上皮间质转化,促进肿瘤发生侵袭转移.miR-200c/141能够抑制上皮间质转化的发生.但TGF-β在胃癌中的表达情况及其对miR-200c/141表达影响尚不清楚.本研究旨在探讨胃癌组织中TGF-β表达水平与胃癌患者临床病理特征的关系,及对miR-200c和miR-141表达影响.方法 收集河北医科大学第四医院普外科2012-05-01-2013-01-01胃癌根治性手术切除标本64例,采用qRT-PCR技术检测TGF-β、miR-200c及miR-141在胃癌组织和配对癌旁非癌组织中的表达.分析TGF-β表达水平与胃癌患者临床病理特征的关系及与miR-200c和miR-141水平的相关性.TGF-β处理胃癌细胞株SGC-7901,观察其对miR-200c和miR-141表达的影响.结果 TGF-β在胃癌组织中的表达上调率为66.67%,其在胃癌组织中的表达显著高于癌旁非癌组织[Median,Interquartile Range(2.50,2.43:0.84,0.42);P=0.005].miR-200a、miR-200b、miR-429、miR-200c和miR-141在胃癌组织中的表达下调率分别为53.13%、48.44%、50.00%、78.13%和76.19.miR-200c和miR-141在胃癌组织中的表达显著低于癌旁非癌组织,均P<0.001.miR-200c和miR-141的表达存在正相关关系,r=0.840,P<0.001.TGF-β表达水平与miR-200c和miR-141的表达水平呈显著负相关关系,均P<0.001.TGF-β能够诱导胃癌细胞株SGC-7901中miR-200c和miR-141表达显著降低.TGF-β的表达水平与淋巴结转移情况及脉管瘤栓情况存在显著相关性,与患者性别、年龄、组织学分级、TNM分期、肿瘤侵袭深度和肿瘤远处转移情况无相关性,均P>0.05.     

Disposition of tiludronate (Skelid) in animals

1. The disposition of tiludronate in mouse, rat, rabbit, dog and monkey has been studied after oral and intravenous doses. Like other bisphosphonates, tiludronate was characterized by poor absorption from the gastrointestinal tract. Peak plasma concentrations appeared shortly (0.5-1 h) after dosing, except for the baboon (4.5 h). Food intake highly impaired intestinal absorption 2. The affinity of tiludronate for bone and the slow release from this deep compartment could account for the large volume of distribution and the low plasma clearance found in all species. 3. Tiludronate has low affinity for red blood cells and binds moderately to serum proteins, mainly to serum albumin. 4. Calcified tissues appeared to be the main target for deposition. Distribution into bone was not homogenous, with higher levels in the trabecular bone than in the corticol part of the long bones. The uptake of tiludronate into bone was unequivocally less in the older animal. 5. No metabolism occurred in the tested animal species. 6. The major route of elimination of the absorbed drug is urine. 7. Preclinical observations made with tiludronate, like with other bisphosphonates, were predictive of results obtained in clinical investigation.