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Long noncoding RNAs HAND2-AS1 ultrasound microbubbles suppress hepatocellular carcinoma progression by regulating the miR-873-5p/tissue inhibitor of matrix metalloproteinase-2 axis
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作者 Qiang Zou Hao-Wen Wang +2 位作者 Xi-Liang Di Yuan Li Hui Gao 《World Journal of Gastrointestinal Oncology》 SCIE 2024年第4期1547-1563,共17页
BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found t... BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found that the expression of lncRNA HAND2-AS1 was downregulated in HCC tissues,but its role in HCC progression is unclear.Ultrasound targeted microbubble destruction mediated gene transfection is a new method to overexpress genes.AIM To study the role of ultrasound microbubbles(UTMBs)mediated HAND2-AS1 in the progression of HCC,in order to provide a new reference for the treatment of HCC.METHODS In vitro,we transfected HAND2-AS1 siRNA into HepG2 cells by UTMBs,and detected cell proliferation,apoptosis,invasion and epithelial-mesenchymal transition(EMT)by cell counting kit-8 assay,flow cytometry,Transwell invasion assay and Western blotting,respectively.In addition,we transfected miR-837-5p mimic into UTMBs treated cells and observed the changes of cell behavior.Next,the UTMBs treated HepG2 cells were transfected together with miR-837-5p mimic and tissue inhibitor of matrix metalloproteinase-2(TIMP2)overexpression vector,and we detected cell proliferation,apoptosis,invasion and EMT.In vivo,we established a mouse model of subcutaneous transplantation of HepG2 cells and observed the effect of HAND2-AS1 silencing on tumor formation ability.RESULTS We found that UTMBs carrying HAND2-AS1 restricted cell proliferation,invasion,and EMT,encouraged apoptosis,and HAND2-AS1 silencing eliminated the effect of UTMBs.Additionally,miR-873-5p targets the gene HAND2-AS1,which also targets the 3’UTR of TIMP2.And miR-873-5p mimic counteracted the impact of HAND2-AS1.Further,miR-873-5p mimic solely or in combination with pcDNA-TIMP2 had been transformed into HepG2 cells exposed to UTMBs.We discovered that TIMP2 reversed the effect of miR-873-5p mimic caused by the blocked signalling cascade for matrix metalloproteinase(MMP)2/MMP9.In vivo results showed that HAND2-AS1 silencing significantly inhibited tumor formation in mice.CONCLUSION LncRNA HAND2-AS1 promotes TIMP2 expression by targeting miR-873-5p to inhibit HepG2 cell growth and delay HCC progression. 展开更多
关键词 Hepatocellular carcinoma Ultrasound microbubbles Long noncoding RNA HAND2-AS1 miR-873-5p Tissue inhibitor of matrix metalloproteinase-2
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PRMT5和CDKN2B在宫颈癌组织的表达及临床意义
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作者 胡晓菡 周强 +3 位作者 孙武 陈静 沈瀚 李强 《疑难病杂志》 CAS 2024年第4期412-417,共6页
目的研究蛋白精氨酸甲基转移酶5(PRMT5)、细胞周期蛋白依赖性激酶抑制剂2B(CDKN2B)在宫颈癌中的表达及临床意义。方法收集2019年3月—2020年3月南京大学医学院附属鼓楼医院妇产科诊治宫颈癌患者88例。免疫组织化学法检测宫颈癌和癌旁组... 目的研究蛋白精氨酸甲基转移酶5(PRMT5)、细胞周期蛋白依赖性激酶抑制剂2B(CDKN2B)在宫颈癌中的表达及临床意义。方法收集2019年3月—2020年3月南京大学医学院附属鼓楼医院妇产科诊治宫颈癌患者88例。免疫组织化学法检测宫颈癌和癌旁组织中PRMT5、CDKN2B表达;采用Spearman相关分析PRMT5与CDKN2B表达的相关性;比较不同临床特征宫颈癌癌组织中PRMT5、CDKN2B表达的差异;Kaplan-Meier曲线评估PRMT5、CDKN2B表达对宫颈癌患者无进展生存预后的影响;多因素Cox回归分析宫颈癌患者无进展生存预后的影响因素。结果癌组织中PRMT5蛋白阳性率70.45%(62/88),高于癌旁组织6.82%(6/88)(χ^(2)=75.155,P<0.001)。宫颈癌组织中CDKN2B阳性率22.73%(20/88),低于癌旁组织79.55%(71/88)(χ^(2)=75.336,P<0.001)。宫颈癌中PRMT5与CDKN2B呈负相关(r=-0.734,P<0.001)。FIGOⅠB2~ⅡA期、有淋巴结转移宫颈癌组织中PRMT5阳性率高于FIGOⅠA~ⅠB1期、无淋巴结转移者,而CDKN2B阳性率则降低(χ^(2)/P=6.359/0.012、4.606/0.032、5.205/0.023、3.893/0.048)。PRMT5阳性组3年累积无进展生存率74.19%(46/62),低于PRMT5阴性组92.31%(24/26)(Log-Rankχ^(2)=4.386,P=0.017)。CDKN2B阴性组3年累积无进展生存率75.00%(51/68),低于CDKN2B阳性组95.00%(19/20)(Log-Rankχ^(2)=4.423,P=0.012)。FIGO分期ⅠB2~ⅡA期、合并淋巴结转移、PRMT5阳性、CDKN2B阴性是影响宫颈癌患者无进展生存预后的独立危险因素[OR(95%CI)=1.407(1.159~1.696),1.464(1.201~1.784),1.614(1.189~2.192),1.595(1.191~2.136)]。结论宫颈癌组织中PRMT5表达升高,CDKN2B表达降低,两者与宫颈癌患者的不良临床病理特征有关,是评估宫颈癌预后的标志物。 展开更多
关键词 宫颈癌 蛋白精氨酸甲基转移酶5 细胞周期蛋白依赖性激酶抑制剂2B 预后 肿瘤标志物
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磷酸二酯酶5在心力衰竭中作用的研究进展
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作者 杨洋 张雅茸 +2 位作者 杨红琴 王婧 赵红梅 《基础医学与临床》 CAS 2024年第5期724-728,共5页
磷酸二酯酶5(PDE5)是环磷酸鸟苷(cGMP)特异性水解酶,是由一氧化氮(NO)激活的可溶性鸟苷酸环化酶(sGC)靶向cGMP产生的。PDE5催化cGMP中磷酸二酯键的水解,从而将cGMP转化为无活性的5′-GMP形式,cGMP-PKG轴功能障碍将引起心脏重塑,是心力衰... 磷酸二酯酶5(PDE5)是环磷酸鸟苷(cGMP)特异性水解酶,是由一氧化氮(NO)激活的可溶性鸟苷酸环化酶(sGC)靶向cGMP产生的。PDE5催化cGMP中磷酸二酯键的水解,从而将cGMP转化为无活性的5′-GMP形式,cGMP-PKG轴功能障碍将引起心脏重塑,是心力衰竭(HF)的主要原因之一。但PDE5抑制剂治疗心力衰竭的临床疗效存在争议。本文总结了近年来PDE5在心力衰竭中的作用机制和研究进展,对未来临床应用PDE5靶向治疗心力衰竭具有重要的指导意义。 展开更多
关键词 心力衰竭 磷酸二酯酶5 磷酸二酯酶抑制剂 环磷酸鸟苷
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老年经皮冠状动脉介入治疗术后支架内再狭窄患者胱抑素C、基质金属蛋白酶抑制剂-1、分泌型卷曲相关蛋白5表达及临床意义
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作者 邸杰 李新政 张晓敬 《心脑血管病防治》 2024年第1期21-25,共5页
目的探讨老年经皮冠状动脉介入治疗(PCI)术后支架内再狭窄(ISR)患者胱抑素C(CysC)、基质金属蛋白酶抑制剂-1(TIMP-1)、分泌型卷曲相关蛋白5(SFRP-5)表达及对靶血管病变的预测价值。方法选取2020年5月至2022年5月保定市第一中心医院PCI术... 目的探讨老年经皮冠状动脉介入治疗(PCI)术后支架内再狭窄(ISR)患者胱抑素C(CysC)、基质金属蛋白酶抑制剂-1(TIMP-1)、分泌型卷曲相关蛋白5(SFRP-5)表达及对靶血管病变的预测价值。方法选取2020年5月至2022年5月保定市第一中心医院PCI术后1年内发生ISR的65例老年冠心病患者作为观察组,选取同期65例PCI术后1年内未发生ISR的老年冠心病患者作为对照组,比较两组一般资料、术后血清CysC、TIMP-1、SFRP-5水平,分析血清CysC、TIMP-1、SFRP-5水平与ISR发生的相关性,并比较观察组不同Mehran分型患者血清CysC、TIMP-1、SFRP-5水平,分析各指标水平与Mehran分型的相关性,分析血清CysC、TIMP-1、SFRP-5水平预测靶血管发生ISR的价值。结果观察组血清CysC水平高于对照组(t=6.949,P<0.05),TIMP-1、SFRP-5水平低于对照组(t=7.301、8.765,P<0.05);血清CysC水平与ISR的发生呈正相关(r=0.587,P<0.05),TIMP-1、SFRP-5水平与ISR的发生呈负相关(r=-0.609、-0.640,P<0.05)。观察组四种Mehran分型的患者CysC、TIMP-1、SFRP-5水平差异有统计学意义(F=10.759、8.326、19.764,P<0.05)。随着Mehran分型Ⅰ型到Ⅳ型的变化,CysC水平逐渐升高,TIMP-1、SFRP-5水平逐渐下降,差异有统计学意义(P<0.05)。血清CysC水平与ISR患者Mehran分型呈正相关关系(r=0.722,P<0.05),TIMP-1、SFRP-5水平与Mehran分型呈负相关关系(r=-0.799、-0.826,P<0.05)。血清CysC、TIMP-1、SFRP-5水平预测老年冠心病患者PCI术后1年内靶血管发生ISR的曲线下面积(AUC)分别为0.807(95%CI=0.729~0.871)、0.786(95%CI=0.706~0.853)、0.811(95%CI=0.733~0.874),联合预测的AUC最大,为0.943(95%CI=0.887~0.976)。结论老年冠心病PCI术后患者血清CysC水平升高,TIMP-1、SFRP-5水平降低与ISR的发生发展相关,术后早期检测各指标水平有助于预测靶血管发生ISR风险。 展开更多
关键词 冠心病 经皮冠状动脉介入治疗 支架内再狭窄 胱抑素C 基质金属蛋白酶抑制剂-1 分泌型卷曲相关蛋白5
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NDM-5-C208A突变大肠埃希菌的构建及大蒜辣素与NDM-5相互作用位点分析
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作者 叶志滨 王晓明 +5 位作者 吕茜 刘雨桐 金季赜晓 朱馨艺 黄金虎 王丽平 《南京农业大学学报》 CAS CSCD 北大核心 2024年第1期61-68,共8页
[目的]产新德里金属β-内酰胺酶5(NDM-5)的革兰阴性耐药菌对人畜健康产生巨大威胁。本文旨在初步探究大蒜辣素对NDM-5的抑制作用及其相关作用位点,为临床开发新型β-内酰胺酶抑制剂提供理论支持。[方法]通过AutoDock模拟分子对接,预测... [目的]产新德里金属β-内酰胺酶5(NDM-5)的革兰阴性耐药菌对人畜健康产生巨大威胁。本文旨在初步探究大蒜辣素对NDM-5的抑制作用及其相关作用位点,为临床开发新型β-内酰胺酶抑制剂提供理论支持。[方法]通过AutoDock模拟分子对接,预测大蒜辣素与NDM-5的结合位点;构建突变型载体pET21a-NDM-5-C208A,测序验证无误后转入感受态大肠埃希菌BL21(DE3),通过药敏试验进行突变表型确认;采用微量肉汤棋盘法和时间杀菌曲线测定大蒜辣素与美罗培南对NDM-5突变型细菌的联合抑菌效果。通过体外表达突变蛋白NDM-5-C208A,建立酶活性测定体系,比较大蒜辣素对C208突变型NDM-5和野生型NDM-5酶活性的抑制效果。[结果]经测序证实NDM-5的C208A突变株BL21(DE3)pET21a-NDM-5-C208A构建成功,C208A突变株恢复了对头孢类和碳青霉烯类抗生素的敏感性,且大蒜辣素与美罗培南联用的联合抑菌指数由0.375增加至2,联用表现为独立作用而非协同作用;体外酶活测定结果显示NDM-5-C208A突变不仅使酶活性下降约85%,而且该位点突变导致大蒜辣素对NDM-5失去抑制作用。[结论]Cys208位点是维持NDM-5水解酶活性的关键位点,且大蒜辣素可通过与该位点结合发挥抑制酶活性的作用。该结果为大蒜辣素作为新型β-内酰胺酶抑制剂的开发和应用提供试验依据。 展开更多
关键词 大蒜辣素 NDM-5 美罗培南 酶抑制剂
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Histone deacetylase inhibitor pracinostat suppresses colorectal cancer by inducing CDK5-Drp1 signaling-mediated peripheral mitofission
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作者 Xiao-Ling Liang Lan Ouyang +6 位作者 Nan-Nan Yu Zheng-Hua Sun Zi-Kang Gui Yu-Long Niu Qing-Yu He Jing Zhang Yang Wang 《Journal of Pharmaceutical Analysis》 SCIE CAS CSCD 2023年第10期1168-1182,共15页
Divisions at the periphery and midzone of mitochondria are two fission signatures that determine the fate of mitochondria and cells.Pharmacological induction of excessively asymmetric mitofissionassociated cell death(... Divisions at the periphery and midzone of mitochondria are two fission signatures that determine the fate of mitochondria and cells.Pharmacological induction of excessively asymmetric mitofissionassociated cell death(MFAD)by switching the scission position from the mitochondrial midzone to the periphery represents a promising strategy for anticancer therapy.By screening a series of paninhibitors,we identified pracinostat,a pan-histone deacetylase(HDAC)inhibitor,as a novel MFAD inducer,that exhibited a significant anticancer effect on colorectal cancer(CRC)in vivo and in vitro.Pracinostat increased the expression of cyclin-dependent kinase 5(CDK5)and induced its acetylation at residue lysine 33,accelerating the formation of complex CDK5/CDK5 regulatory subunit 1 and dynaminrelated protein 1(Drp1)-mediated mitochondrial peripheral fission.CRC cells with high level of CDK5(CDK5-high)displayed midzone mitochondrial division that was associated with oncogenic phenotype,but treatment with pracinostat led to a lethal increase in the already-elevated level of CDK5 in the CRC cells.Mechanistically,pracinostat switched the scission position from the mitochondrial midzone to the periphery by improving the binding of Drp1 from mitochondrial fission factor(MFF)to mitochondrial fission 1 protein(FIS1).Thus,our results revealed the anticancer mechanism of HDACi pracinostat in CRC via activating CDK5-Drp1 signaling to cause selective MFAD of those CDK5-high tumor cells,which implicates a new paradigm to develop potential therapeutic strategies for CRC treatment. 展开更多
关键词 HDAC inhibitor Pracinostat CDK5 Mitochondrial fission ACETYLATION Drp1
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慢性阻塞性肺疾病急性加重期患者血清CCR5、PAI-1水平与肺功能及病情严重程度的关系
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作者 宋文党 朱承坡 +1 位作者 张鹏 刘春 《国际检验医学杂志》 CAS 2024年第10期1257-1261,共5页
目的 探究慢性阻塞性肺疾病急性加重期(AECOPD)患者血清细胞趋化因子受体5(CCR5)、纤溶酶原激活物抑制剂-1(PAI-1)水平变化与肺功能及病情严重程度之间的关系。方法 选取该院2020年1月至2022年1月急诊收治的114例AECOPD患者为AECOPD组,... 目的 探究慢性阻塞性肺疾病急性加重期(AECOPD)患者血清细胞趋化因子受体5(CCR5)、纤溶酶原激活物抑制剂-1(PAI-1)水平变化与肺功能及病情严重程度之间的关系。方法 选取该院2020年1月至2022年1月急诊收治的114例AECOPD患者为AECOPD组,并选取同期稳定期慢性阻塞性肺疾病(COPD)患者114例为对照组。采用酶联免疫吸附试验(ELISA)测定CCR5、PAI-1水平;比较AECOPD组与对照组及不同病情程度AECOPD患者血清CCR5、PAI-1水平及肺功能指标;Pearson相关性分析AECOPD患者血清CCR5、PAI-1水平与肺功能指标之间的关系;Spearman相关性分析AECOPD患者血清CCR5、PAI-1水平与病情严重程度之间的关系。结果 与对照组相比,AECOPD组患者血清CCR5、PAI-1水平均显著升高,差异均有统计学意义(P<0.05),肺功能指标:第1秒用力呼气量(FEV_(1))、FEV_(1)与用力肺活量比值(FEV_(1)/FVC)、FEV_(1)占预计值百分比(FEV_(1)%pred)、最大呼气中期流量(MMEF)占预计值百分比(MMEF%pred)均显著降低,差异有统计学意义(P<0.05),且随着病情程度的增加,血清CCR5、PAI-1水平逐渐增加(P<0.05),FEV_(1)、FEV_(1)/FVC、FEV_(1)%pred、MMEF%pred水平逐渐降低(P<0.05);Pearson相关性分析结果显示,血清CCR5、PAI-1水平与FEV_(1)、FEV_(1)/FVC、FEV_(1)%pred、MMEF%pred均呈显著负相关(P<0.05);Spearman相关性分析结果显示,AECOPD患者血清CCR5、PAI-1水平与病情程度呈显著正相关(r_(1)=0.432,r_(2)=0.451,P<0.05)。结论 AECOPD患者血清CCR5、PAI-1水平显著升高,且血清CCR5、PAI-1水平与AECOPD患者肺功能及病情程度密切相关。 展开更多
关键词 慢阻肺急性加重期 细胞趋化因子受体5 纤溶酶原激活物抑制剂-1 肺功能 病情程度
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组蛋白去乙酰化酶HDAC5调控乳腺癌的研究进展
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作者 刘承华 梅惠卿 +2 位作者 张嘉乐 李华琴 吴文梅 《激光生物学报》 CAS 2024年第2期108-114,共7页
乳腺癌是世界范围内最常见的恶性肿瘤之一,在女性群体中发病率较高。作为IIa组蛋白去乙酰化酶(HDACs),组蛋白去乙酰化酶5(HDAC5)在乳腺癌患者和健康人群中的表达存在巨大的差异,从而成为在乳腺癌乃至其他癌症中具有潜在价值的生物标志... 乳腺癌是世界范围内最常见的恶性肿瘤之一,在女性群体中发病率较高。作为IIa组蛋白去乙酰化酶(HDACs),组蛋白去乙酰化酶5(HDAC5)在乳腺癌患者和健康人群中的表达存在巨大的差异,从而成为在乳腺癌乃至其他癌症中具有潜在价值的生物标志物之一,被认为是抗癌药物的可靠分子治疗靶点。本文将对HDAC5的结构表征和其在乳腺癌发生发展中的作用,以及HDAC5抑制剂的应用作一简要总结,并为早期乳腺癌HDACs的检测、HDACs抑制剂(HDACi)的设计以及与HDACi联用的相关药物作用靶点等方面提供可行性建议,以期为乳腺癌肿瘤治疗提供理论策略参考。 展开更多
关键词 乳腺癌 组蛋白去乙酰化酶 组蛋白去乙酰化酶5 组蛋白去乙酰化酶5抑制剂 药物作用靶点
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5-苯基-1,2,4-噁二唑衍生物的合成及其作为乙酰辅酶A羧化酶抑制剂的生物活性
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作者 王婕 袁家英 +3 位作者 杨奕 刘文雅 钱茹雨 黄统辉 《合成化学》 CAS 2024年第5期451-456,共6页
乙酰辅酶A羧化酶(Acetyl-CoA Carboxylase,ACC)是一种脂肪酸合成限速酶,是肿瘤治疗的热门靶点之一。本文以3-氯苯胺和亚甲基丁二酸为起始原料,经环化、缩合和酰胺化等反应获得了一系列5-苯基-1,2,4-噁二唑类化合物(9a~9i),其中,化合物9a... 乙酰辅酶A羧化酶(Acetyl-CoA Carboxylase,ACC)是一种脂肪酸合成限速酶,是肿瘤治疗的热门靶点之一。本文以3-氯苯胺和亚甲基丁二酸为起始原料,经环化、缩合和酰胺化等反应获得了一系列5-苯基-1,2,4-噁二唑类化合物(9a~9i),其中,化合物9a、9b、9e~9h为全新结构,经^(1)H MNR、^(13)C MNR和MS(ESI)进行了表征。通过Molsoft软件计算目标化合物9a~9i的脂水分配系数和类药性分数,使用ADP-Glo^(TM)激酶检测试剂盒检测化合物ACC抑制活性。结果表明:化合物9g在10μM浓度下对ACC抑制活性达到95.26%,与阳性对照药CP-640186相当。 展开更多
关键词 5-苯基-1 2 4-噁二唑衍生物 乙酰辅酶A羧化酶 抑制剂 抑制活性
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特发性矮小症患儿血清Vaspin和SFRP5水平表达及其诊断价值研究
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作者 吴迎爽 薛向东 +4 位作者 杜志辉 王利红 程渊博 牛晓庆 王大伟 《现代检验医学杂志》 CAS 2024年第1期95-99,共5页
目的探索特发性矮小症(idiopathic short stature,ISS)患儿血清中内脏脂肪特异性丝氨酸蛋白酶抑制剂(visceral adipose tissue-derived serine protease inhibitor,Vaspin)和分泌型卷曲相关蛋白5(secreted frizzled-related protein5,SF... 目的探索特发性矮小症(idiopathic short stature,ISS)患儿血清中内脏脂肪特异性丝氨酸蛋白酶抑制剂(visceral adipose tissue-derived serine protease inhibitor,Vaspin)和分泌型卷曲相关蛋白5(secreted frizzled-related protein5,SFRP5)的表达水平及其诊断价值。方法选取2021年12月~2023年2月在张家口市第一医院确诊的70例ISS患儿作为疾病组,同期选择72例体检健康的志愿儿童作为对照组。采用免疫发光法检测Vaspin的表达水平,酶联免疫吸附法(enzyme-linked immunosorbent assay,ELISA)检测SFRP5的表达水平,对两组儿童的临床资料进行分析。受试者工作特征(receiver operator characteristics curve,ROC)曲线分析血清Vaspin和SFRP5对ISS的诊断价值,多因素Logistic回归分析ISS发生的影响因素。结果与对照组比较,疾病组的血清Vaspin水平显著升高(2.89±0.92 ng/ml vs1.81±0.42 ng/ml),SFRP5水平显著降低(10.22±2.84 pg/ml vs 13.21±3.53 pg/ml),差异具有统计学意义(t=9.040,5.552,均P<0.05)。疾病组儿童的体重、身高、身体质量指数(body mass index,BMI)、性发育状态Ⅱ~Ⅴ期比例显著低于对照组儿童,差异具有统计学意义(t=7.687,6.330,5.559,7.074,均P<0.05);ROC曲线下面积(AUC)显示,Vaspin,SFRP5及二者联合检测诊断ISS患儿的AUC分别为0.768,0.849和0.925,二者联合诊断效能优于血清Vaspin,SFRP5各自单独诊断(Z=3.829,P<0.001;Z=2.141,P=0.032)。多因素Logistic回归分析显示BMI(OR=0.508,95%CI=0.260~0.991),Vaspin(OR=3.458,95%CI:1.125~10.631),SFRP5(OR=0.378,95%CI:0.153~0.935)是ISS的影响因素(均P<0.05)。结论ISS患儿血清中Vaspin表达水平显著升高,SFRP5表达水平显著降低,二者是ISS发生的影响因素,二者联合检测对ISS的诊断具有一定的价值。 展开更多
关键词 特发性矮小症 内脏脂肪特异性丝氨酸蛋白酶抑制剂 分泌型卷曲相关蛋白5
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5-Aza-CdR联合EBNA1-DC疫苗诱导的淋巴细胞对鼻咽癌C666-1细胞的杀伤作用
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作者 谢云青 黄丽洁 +2 位作者 林晓为 陈莉 陈珊珊 《中国肿瘤生物治疗杂志》 CAS CSCD 北大核心 2023年第8期701-706,共6页
目的:探讨EB病毒核抗原1(EBNA1)mRNA修饰的DC(EBNA1-DC)诱导的淋巴细胞联合甲基化抑制剂5-Aza-CdR对鼻咽癌C666-1细胞的杀伤作用。方法:以构建的EBNA1-pCDNA3.1质粒为模板,体外转录获得EBNA1 mRNA,通过脂质体转染至健康人外周血来源DC,... 目的:探讨EB病毒核抗原1(EBNA1)mRNA修饰的DC(EBNA1-DC)诱导的淋巴细胞联合甲基化抑制剂5-Aza-CdR对鼻咽癌C666-1细胞的杀伤作用。方法:以构建的EBNA1-pCDNA3.1质粒为模板,体外转录获得EBNA1 mRNA,通过脂质体转染至健康人外周血来源DC,构建EBNA1-DC疫苗。流式细胞术检测转染后DC表型及5-Aza-CdR处理后的C666-1细胞凋亡情况。实时无标记动态细胞分析技术检测EBNA1-DC疫苗诱导的淋巴细胞联合5-Aza-CdR的特异性抗肿瘤活性。结果:转染EBNA1 mRNA后EBNA1-DC表面EBNA1阳性率为(59.3±5.85)%,HLA-DR的表达与未转染DC相比显著升高[(84.9±5.5)%vs(68.0±5.8)%,P=0.026],CD80的表达也显著升高([88.2±3.9)%vs(61.1±4.4)%,P=0.015]。低剂量5-Aza-CdR处理后的C666-1细胞凋亡情况与未处理的细胞相比无显著差异。经低浓度5-Aza-CdR预处理的C666-1细胞中IRF7基因表达与未处理的细胞相比显著升高(P=0.0001)。与空载的DC相比,EBNA1-DC诱导的淋巴细胞对EBV阳性表达的C666-1细胞具有更强的特异性杀伤活性(P=0.049);经低浓度5-Aza-CdR预处理的C666-1细胞对EBNA1-DC诱导的特异性免疫杀伤更敏感(P=0.019)。结论:5-Aza-CdR与EBNA1-DC疫苗联合可显著增强对C666-1细胞的特异性免疫杀伤,本研究为开拓以mRNA为基础的DC疫苗及其在临床综合治疗中的应用转化提供前期研究基础。 展开更多
关键词 EB病毒核抗原1 甲基化抑制剂 5-AZA-CDR Epstein Barr病毒 DC疫苗 鼻咽癌
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左炔诺孕酮联合miRNA-21-5p抑制剂对子宫内膜癌细胞增殖、转移的作用及机制
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作者 马鸿云 田春花 +2 位作者 马钊 吴阳 桂甜甜 《中国老年学杂志》 CAS 北大核心 2023年第18期4483-4488,共6页
目的利用左炔诺孕酮(LNG)和miRNA-21-5p抑制剂(inhibitor)联合靶向多发性肿瘤抑制基因磷酸酶基因(PTEN)评估对子宫内膜癌细胞增殖、转移的作用。方法将实验用人子宫内膜癌细胞分为Control组、LNG处理组、LNG处理+miR-21 NC组和LNG处理+m... 目的利用左炔诺孕酮(LNG)和miRNA-21-5p抑制剂(inhibitor)联合靶向多发性肿瘤抑制基因磷酸酶基因(PTEN)评估对子宫内膜癌细胞增殖、转移的作用。方法将实验用人子宫内膜癌细胞分为Control组、LNG处理组、LNG处理+miR-21 NC组和LNG处理+miR-21 inhibitor组;免疫组化检测LNG治疗前后子宫内膜癌患者内膜组织中PTEN表达;CCK8和流式细胞仪筛选LNG最佳作用浓度和时间;实时荧光定量(qRT)-聚合酶链反应(PCR)法检测miR-21-5p inhibitor处理后miR-21-5p mRNA表达水平;LNG联合miR-21-5p inhibitor处理后CCK8检测增殖,流式检测凋亡,Transwell检测侵袭,划线检测迁移,Western印迹检测细胞中PTEN、磷脂酰肌醇3-激酶(PI3K)、p-PI3K、丝氨酸/苏氨酸激酶(AKT)和p-AKT蛋白表达水平。结果与治疗前比,LNG治疗后子宫内膜组织中PTEN表达水平显著升高(P=0.000)。筛选出LNG最佳浓度为100μmol/L,时间为24 h。miR-21-5p inhibitor处理后miR-21-5p表达显著降低(P<0.05)。与Control组相比,LNG组处理后细胞凋亡及PTEN表达显著升高,细胞迁移、侵袭能力及细胞活力显著下降(P<0.05),miR-21-5p、p-AKT/AKT、p-PI3K/PI3K表达也明显下降(P<0.05);与LNG组相比,LNG+miR-21-5p inhibitor组细胞活力、细胞凋亡、迁移、侵袭能力、miR-21-5p表达、p-AKT/AKT、p-PI3K/PI3K明显下降,PTEN表达则明显升高(P<0.05)。结论LNG联合miR-21-5p inhibitor具有协同抑制子宫内膜癌细胞增殖、转移的作用,此过程与靶向上调PTEN并抑制PI3K/AKT通路活化相关。 展开更多
关键词 miR-21-5p抑制剂(inhibitor) 左炔诺孕酮(LNG) 人子宫内膜癌
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卵巢癌组织中长链非编码RNA生长阻滞特异性抑制物5、微小RNA-205的表达及意义
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作者 陈姣 刘帅 +2 位作者 帅旭 熊浩然 杨旭 《河北医药》 CAS 2023年第12期1780-1784,共5页
目的分析长链非编码RNA(lncRNA)生长阻滞特异性抑制物5(GAS5)、微小RNA-205(miR-205)在卵巢癌组织中的表达及其临床意义。方法前瞻性收集2019年1月至2020年6月收治的初诊卵巢癌患者于术中取其癌组织和癌旁组织(距肿瘤边缘>2cm);采用... 目的分析长链非编码RNA(lncRNA)生长阻滞特异性抑制物5(GAS5)、微小RNA-205(miR-205)在卵巢癌组织中的表达及其临床意义。方法前瞻性收集2019年1月至2020年6月收治的初诊卵巢癌患者于术中取其癌组织和癌旁组织(距肿瘤边缘>2cm);采用实时荧光定量PCR法检测lncRNA GAS5、miR-205表达情况;问卷调查法统计患者临床病理资料;术后随访2年(截止时间至2022年6月),统计患者生存时间。比较癌组织和癌旁组织lncRNA GAS5、miR-205表达,并采用Pearson相关分析lncRNA GAS5与miR-205的关系;以癌组织lncRNA GAS5、miR-205表达的中位数将卵巢癌患者分为lncRNA GAS5与miR-205高表达组和低表达组,比较不同病理特征卵巢癌患者lncRNA GAS5、miR-205高表达、低表达情况;比较不同lncRNA GAS5、miR-205表达情况的卵巢癌患者生存时间。结果共82例卵巢癌患者纳入本次研究,其中2例失访,最终80例患者进入本次研究。卵巢癌组织lncRNA GAS5相对表达量小于癌旁正常组织,miR-205相对表达量大于癌旁正常组织(P<0.05);Pearson相关分析显示,卵巢癌组织中lncRNA GAS5相对表达量与miR-205相对表达量呈负相关(r=-0.606,P<0.001)。lncRNA GAS5高表达45例,低表达35例;miR-205高表达40例,低表达40例。Ⅲ~Ⅳ期、伴淋巴结转移的卵巢癌患者的卵巢组织中lncRNA GAS5低表达率高于Ⅰ~Ⅱ期、无淋巴结转移患者(P<0.05);Ⅲ~Ⅳ期、伴淋巴结转移的卵巢癌患者的卵巢组织中miR-205高表达率高于Ⅰ~Ⅱ期、无淋巴结转移患者(P<0.05)。lncRNA GAS5低表达量卵巢癌患者2年生存时间(21.50±0.89)个月,低于高表达患者(23.89±0.09)个月(χ2=5.150,P=0.023)。miR-205高表达量卵巢癌患者2年生存时间(21.71±0.79)个月,低于低表达患者(23.98±0.03)个月(χ2=6.337,P=0.012)。结论lncRNA GAS5、miR-205在卵巢癌组织表达存在一定的差异,其中lncRNA GAS5低表达,miR-205高表达,并影响卵巢癌患者的临床病理特征和预后。 展开更多
关键词 卵巢癌 长链非编码RNA生长阻滞特异性抑制物5 微小RNA-205 临床病理特征 生存时间
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Effects of phosphodiesterase 5 inhibitors on sperm parameters and fertilizing capacity 被引量:11
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作者 F. Dimitriadis D. Giannakis +11 位作者 N. Pardalidis K. Zikopoulos E. Paraskevaidis N. Giotitsas V. Kalaboki P.Tsounapi D. Baltogiannis Georgiou M.Saito T.Watanabe I. Miyagawa N.Sofildtis 《Asian Journal of Andrology》 SCIE CAS CSCD 2008年第1期115-133,共19页
The aim of this review study is to elucidate the effects that phosphodiesterase 5 (PDE5) inhibitors exert on spermatozoa motility, capacitation process and on their ability to fertilize the oocyte. Second messenger ... The aim of this review study is to elucidate the effects that phosphodiesterase 5 (PDE5) inhibitors exert on spermatozoa motility, capacitation process and on their ability to fertilize the oocyte. Second messenger systems such as the cAMP/adenylate cyclase (AC) system and the cGMP/guanylate cyclase (GC) system appear to regulate sperm functions. Increased levels of intracytosolic cAMP result in an enhancement of sperm motility and viability. The stimulation of GC by low doses of nitric oxide (NO) leads to an improvement or maintenance of sperm motility, whereas higher concentrations have an adverse effect on sperm parameters. Several in vivo and in vitro studies have been carried out in order to examine whether PDE5 inhibitors affect positively or negatively sperm parameters and sperm fertilizing capacity. The results of these studies are controversial. Some of these studies demonstrate no significant effects of PDE5 inhibitors on the motility, viability, and morphology of spermatozoa collected from men that have been treated with PDE5 inhibitors. On the other hand, several studies demonstrate a positive effect of PDE5 inhibitors on sperm motility both in vivo and in vitro. In vitro studies of sildenafil citrate demonstrate a stimulatory effect on sperm motility with an increase in intracellular cAMP suggesting an inhibitory action of sildenafil citrate on a PDE isoform other than the PDE5. On the other hand, tadalafil's actions appear to be associated with the inhibitory effect of this compound on PDE11. In vivo studies in men treated with vardenafil in a daily basis demonstrated a significantly larger total number of spermatozoa per ejaculate, quantitative sperm motility, and qualitative sperm motility; it has been suggested that vardenafil administration enhances the secretory function of the prostate and subsequently increases the qualitative and quantitative motility of spermatozoa. The effect that PDE5 inhibitors exert on sperm parameters may lead to the improvement of the outcome of assisted reproductive technology (ART) programs. In the future PDE5 inhibitors might serve as adjunct therapeutical agents for the alleviation of male infertility. 展开更多
关键词 sperm fertilizing capacity phosphodiesterase 5 inhibitors SPERMATOZOA TESTIS male infertility
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Changes in aortic endothelium ultrastructure in male rats following castration, replacement with testosterone and administration of 50α-reductase inhibitor 被引量:14
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作者 Ying-Li Lu Lin Kuang +5 位作者 Hui Zhu Hui Wu Xue-Fang Wang Yu-Ping Pang Ning-Jian Wang Dan-Lu Yu 《Asian Journal of Andrology》 SCIE CAS CSCD 2007年第6期843-847,共5页
Aim: To investigate the relationship between low androgen level and ultrastructure of vascular endothelium. Methods: Forty-eight male Sprague-Dawley rats were randomly divided into four groups: group A, normal rats... Aim: To investigate the relationship between low androgen level and ultrastructure of vascular endothelium. Methods: Forty-eight male Sprague-Dawley rats were randomly divided into four groups: group A, normal rats with sham castration; group B, castrated rats; group C, castrated rats given testosterone (T) undecanoate; and group D, intact rats treated with 5α-reductase inhibitor. After 10 weeks of treatment or castration, rats in different groups were killed and serum T, free T (FT) and dihydrotestosterone (DHT) were measured. The aortic endothelia were scanned under electron microcopy and the Vascular Endothelium Structure Score (VESS) was computed. Results: Serum T and FT concentrations of rats in group B were significantly lower than those of the other three groups (P 〈 0.01); DHT concentrations of group D rats were significantly decreased (P 〈 0.01 ) when compared with those of groups A and C. Rats in groups B and D rats (with low androgen levels) had obvious damage to their endothelial surfaces, which appeared crimpled, rough, adhesive and ruptured, and had high destruction of VESS. Conclusion: These results suggest that low concentrations of T and DHT are associated with ultrastructural damage of the aortic endothelia in male rats. 展开更多
关键词 ENDOTHELIUM ULTRASTRUCTURE TESTOSTERONE 5α-reductase inhibitor CASTRATION
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GDM患者miRNA-125b、SFRP5、SerpinB1变化及益生菌联合胰岛素治疗效果
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作者 刘敏 缪华珍 《中国计划生育学杂志》 2023年第10期2354-2358,共5页
目的:探究微小RNA-125b(miRNA-125b)、分泌型卷曲相关蛋白-5(SFRP5)和丝氨酸蛋白酶抑制剂B1(SerpinB1)对妊娠期糖尿病(GDM)诊断价值及益生菌联合胰岛素治疗效果。方法:选取2020年1月-2022年12月入院接受治疗的GDM孕妇90例纳入病例组,同... 目的:探究微小RNA-125b(miRNA-125b)、分泌型卷曲相关蛋白-5(SFRP5)和丝氨酸蛋白酶抑制剂B1(SerpinB1)对妊娠期糖尿病(GDM)诊断价值及益生菌联合胰岛素治疗效果。方法:选取2020年1月-2022年12月入院接受治疗的GDM孕妇90例纳入病例组,同期待产的90例健康孕妇纳入健康组;病例组给予益生菌冻干粉联合门冬胰岛素治疗,PCR分析miRNA-125b相对表达水平,酶联免疫吸附试验法测定SFRP5和SerpinB1水平;检测病例组空腹血糖(FBG)、糖化血红蛋白(HbA1c)水平、餐后2 h血糖(2 h PG)水平。对比病例组和健康组miRNA-125b、SFRP5和SerpinB1水平,分析miRNA-125b、SFRP5和SerpinB1对GDM诊断价值;对比干预前后病例组miRNA-125b、SFRP5、SerpinB1和血糖水平。结果:病例组miRNA-125b(0.62±0.11)和SFRP5(9.16±1.37 ng/ml)均低于健康组(1.55±0.29、14.96±3.18 ng/ml),SerpinB1(2.89±0.95 ng/ml)高于健康组(2.34±0.58 ng/ml)(均P<0.05);miRNA-125b、SFRP5、SerpinB1联合诊断GDM的ROC曲线下面积为0.941,特异性(93.2%)敏感度(96.5%)高于单独指标检测(P<0.05);病例组治疗3个月后,miRNA-125b和SFRP5水平均高于治疗前,SerpinB1、FBG、2hPG和HbAlc水平均低于治疗前(均P<0.05),发生低血糖2例、皮疹1例、恶心呕吐2例,但症状均较轻,减少用药剂量或停药后症状均消失。结论:相较于健康孕妇,GDM患者miRNA-125b和SFRP5水平降低,SerpinB1水平升高,3项联合检测对GDM有较高诊断价值;应用益生菌联合门冬胰岛素治疗,可明显改善GDM患者miRNA-125b、SFRP5、SerpinB1和血糖水平。 展开更多
关键词 妊娠期糖尿病 微小RNA-125b 分泌型卷曲相关蛋白-5 丝氨酸蛋白酶抑制剂B1 益生菌 门冬胰岛素 诊断价值
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Peptide Inhibitors of HIV-1 Virus Infection Based on Cullin-5 被引量:2
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作者 ZHU Ke-tong ZHANG Xi-zhen LOU Chao-ping GUO Bo DU Juan WANG Xiao-dan WU Yong-ge KONG Wei YU Xiang-hui 《Chemical Research in Chinese Universities》 SCIE CAS CSCD 2008年第3期338-343,共6页
Virion infectivity factor(Vif) is one of the six accessory proteins of HIV-1 and is necessary for viral infectivity. Human Apolipoprotein B editing complex protein 3G(h-APOBEC3G) is a cytidine deaminase only expre... Virion infectivity factor(Vif) is one of the six accessory proteins of HIV-1 and is necessary for viral infectivity. Human Apolipoprotein B editing complex protein 3G(h-APOBEC3G) is a cytidine deaminase only expressed in "nonpermissive" cells and exhibits virus suppressive activity. With the aid of a Cullin-5 E3 ligase, Vif induces h-APOBEC3G degradation and with the destruction of this ligase, Vif is functionally inactive. Therefore, it is expected that blocking this E3 pathway would be a new therapeutic strategy against HIV-1 infection. In this article, the authors' took sequence alignment of the N-termini of Cullin-5 and three other members of the Cullin protein family, respectively. A set of small peptides has been synthesized based on the sequence comparison results and possible Vif-Cullin-5 interaction domains. Moreover, it has been demonstrated that several peptides can reduce virus infectivity in "nonpermissive" cells with a dose-responsive manner, but not in "permissive" cells. The results also indicate that the loss of viral infectivity may be because of the increase of APOBEC3G amount in the peptide-treated cells. It is concluded that peptides derived from Cullin-5 can block the APOBEC3G degradation induced by Vif and suppress HIV-1 infectivity. Therefore this study starts a novel strategy for the development of a new HIV-1 inhibitor. 展开更多
关键词 HIV-1 inhibitor PEPTIDE VIF Cullin-5 APOBEC3G
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Erectile potentials of a new phosphodiesterase type 5 inhibitor, DA-8159, in diet-induced obese rats 被引量:2
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作者 Jae-Young Yu Kyung-Koo Kang Moohi Yoo 《Asian Journal of Andrology》 SCIE CAS CSCD 2006年第3期325-329,共5页
Aim: To examine the changes in the erectile function in diet-induced obese rats and investigate the oral efficacy of DA-8159, a new phosphodiesterase type 5 (PDE5) inhibitor, on penile erection in obese rats. Meth... Aim: To examine the changes in the erectile function in diet-induced obese rats and investigate the oral efficacy of DA-8159, a new phosphodiesterase type 5 (PDE5) inhibitor, on penile erection in obese rats. Methods: The rats were fed a high-energy diet for 12 weeks and divided into three groups: an obesity-resistant (OR) control group, an obesity-prone (OP) control group, and an OP-DA-8159 treatment (DA-8159) group. The electrostimulation-induced erectile responses were measured in all groups. The body weight, plasma cholesterol, triglyceride and glucose levels were also measured. Results: In the OP control group, the maximum intracavernous pressure (ICP) and ICP/blood pressure (ICP/BP) ratio after electric stimulation were significantly lower than those in OR control group. The corresponding area under the curve (AUC) of the ICP/BP ratio, the detumescence time and the baseline cavernous pressure were also lower than those in the OR control group, but this difference was not significant. The body weight gain, plasma cholesterol and triglyceride level in the OP group were significantly higher than those in the OR group. After administering the DA-8159, a significant increase in the maximum ICP and the ICP/BP ratio were observed. The corresponding AUCs in the DA-8159 group were also higher than those in the two control groups. Furthermore, the detumescence time was significantly prolonged after treatment with DA-8159. Conclusion: These results demon- strate that diet-induced obesity affects the erectile function in rats and these erectile dysfunction (ED) can be improved by the treatment with DA-8159, indicating DA-8159 might be a treatment option for ED associated with obesity. 展开更多
关键词 phosphodiesterase type 5 inhibitor penile erection OBESITY DA-8159 intracavemous pressure
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A systematic review of the effects and mechanisms of preoperative 5α-reductase inhibitors on intraoperative haemorrhage during surgery for benign prostatic hyperplasia 被引量:5
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作者 Huan-Tao Zong Xiao-Xia Peng +1 位作者 Chen-Chen Yang Yong Zhang 《Asian Journal of Andrology》 SCIE CAS CSCD 2011年第6期812-818,共7页
5α-reductase inhibitors (5α-RIs), including finasteride and dutasteride, are commonly used medical therapies for benign prostatic hyperplasia (BPH). Many studies reported that preoperative 5α-RI had impact on i... 5α-reductase inhibitors (5α-RIs), including finasteride and dutasteride, are commonly used medical therapies for benign prostatic hyperplasia (BPH). Many studies reported that preoperative 5α-RI had impact on intraoperative haemorrhage during surgery for BPH, but it was still in controversial. So, we conducted a systematic review of the effects and mechanisms of 5α-RIs on intraoperative bleeding for BPH. MEDLINE, EMBASE, the Cochrane Controlled Trail Register of Controlled Trials and the reference lists of retrieved studies were searched in the analysis. Sixteen publications involving 15 different randomized controlled trials (RCTs) and a total of 1156 patients were used in the analysis, including 10 RCTs for finasteride and five RCTs for dutasteride. We found that preoperative finasteride treatment decreases microvessel density (MVD) in resected prostate specimens. Total blood loss, blood loss per gram of resected prostate tissue and decreases in haemoglobin were all greatly reduced in the finasteride group as compared to controls. Dutasteride appeared to have no effect on bleeding. This meta-analysis shows that preoperative finasteride treatment could decrease intraoperative haemorrhage during surgery for BPH. Preoperative dutasteride had no effect on intraoperative haemorrhage, but further high-qualitv prospective studies are still needed to confirm this observation. 展开更多
关键词 5α-reductase inhibitor benign prostate hyperplasia HAEMORRHAGE META-ANALYSIS microvessel density
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The use of 5-alpha reductase inhibitors in the treatment of benign prostatic hyperplasia 被引量:12
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作者 Eric H.Kim John A.Brockman Gerald L.Andriole 《Asian Journal of Urology》 2018年第1期28-32,共5页
Benign prostatic hyperplasia(BPH)is characterized by an enlarged prostate,lower urinary tract symptoms(LUTS),and a decreased urinary flow rate.Common in older men,BPH is a progressive disease that can eventually lead ... Benign prostatic hyperplasia(BPH)is characterized by an enlarged prostate,lower urinary tract symptoms(LUTS),and a decreased urinary flow rate.Common in older men,BPH is a progressive disease that can eventually lead to complications including acute urinary retention(AUR)and the need for BPH-related surgery.Both normal and abnormal prostate growth is driven by the androgen dihydrotestosterone(DHT),which is formed from testosterone under the influence of 5-alpha reductase.Thus,5-alpha reductase inhibitors(5-ARIs)effectively reduce the serum and intraprostatic concentration of DHT,causing an involution of prostate tissue.Two 5-ARIs are currently available for the treatment of BPHdfinasteride and dutasteride.Both have been demonstrated to decrease prostate volume,improve LUTS and urinary flow rates,which ultimately reduces the risk of AUR and BPH-related surgery.Therefore,either alone or in combination with other BPH medications,5-ARIs are a mainstay of BPH management. 展开更多
关键词 Benign prostatic hyperplasia 5-alpha reductase inhibitors Lower urinary tract symptoms
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