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低剂量CT结合SHOX2、RASSF1A甲基化在肺癌早期预警中的应用
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作者 李志娟 董红 +2 位作者 田涛 于哲 李晓敏 《中国CT和MRI杂志》 2024年第2期73-76,共4页
目的探讨低剂量CT结合Ras相关区域家族蛋白1A(RASSF1A)、矮小同源盒基因2(SHOX2)甲基化在肺癌早期预测中的应用价值。方法选取2021年1月~2023年1月我院90例拟行肺结节手术患者,根据手术病理学分为肺良性结节组和肺癌组。2组均于术前行... 目的探讨低剂量CT结合Ras相关区域家族蛋白1A(RASSF1A)、矮小同源盒基因2(SHOX2)甲基化在肺癌早期预测中的应用价值。方法选取2021年1月~2023年1月我院90例拟行肺结节手术患者,根据手术病理学分为肺良性结节组和肺癌组。2组均于术前行低剂量CT检查、SHOX2、RASSF1A甲基化检测,采用Kappa指数分析上述检查结果与手术病理学一致性,分析低剂量CT、SHOX2、RASSF1A甲基化与血清肿瘤标志物[癌胚抗原(CEA)、神经元特异性烯醇化酶(NSE)、鳞状细胞癌抗原(SCC-Ag)、细胞角蛋白19片段(CYFRA21)]对肺癌诊断效能,采用Spearman低剂量CT检查、SHOX2、RASSF1A甲基化与临床病理特征相关性。结果低剂量CT、SHOX2、RASSF1甲基化及三者联合分别确定40例、43例、46例、58例肺癌,三者联合与手术病理学诊断肺癌效能一致性Kappa值为0.951;三者联合诊断肺癌敏感度96.67%、准确度97.78%均高于三者单一诊断效能(P<0.05);肺癌患者血清CEA、SCC、NSE、CYFRA21水平均高于肺良性结节患者(P<0.05);低剂量CT联合SHOX2、RASSF1甲基化诊断肺癌效能的AUC为0.983,近似于四种血清肿瘤标志物诊断肺癌效能的AUC 0.933;不同肿瘤直径、临床分期、组织学分化肺癌患者低剂量CT检出率及SHOX2、RASSF1A甲基化阳性率比较差异有统计学意义(P<0.05);肺癌患者低剂量CT检出率、SHOX2及RASSF1A甲基化阳性率与肿瘤直径、临床分期呈正相关,与组织学分化呈负相关(P<0.05)。结论低剂量CT联合SHOX2及RASSF1A甲基化可用于肺癌早期预警中,临床可通过其进行早期诊断、评估病情进展程度,以针对性展开后续治疗,改善预后。 展开更多
关键词 低剂量CT 矮小同源盒基因2 ras相关区域家族蛋白1A 肺癌 血清肿瘤标志物
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PTHrP促进RANKL诱导巨噬细胞分化为破骨细胞参与中耳胆脂瘤骨破坏
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作者 谢淑敏 金丽 +4 位作者 符金凤 袁秋林 殷团芳 任基浩 刘伟 《中南大学学报(医学版)》 CAS CSCD 北大核心 2024年第5期655-666,共12页
目的:骨质进行性吸收破坏是中耳胆脂瘤最重要的临床特征之一,可导致一系列颅内外并发症,而目前中耳胆脂瘤骨破坏的机制尚未明确。本研究旨在探究甲状旁腺激素相关蛋白(parathyroid hormone-related protein,PTHrP)参与中耳胆脂瘤骨破坏... 目的:骨质进行性吸收破坏是中耳胆脂瘤最重要的临床特征之一,可导致一系列颅内外并发症,而目前中耳胆脂瘤骨破坏的机制尚未明确。本研究旨在探究甲状旁腺激素相关蛋白(parathyroid hormone-related protein,PTHrP)参与中耳胆脂瘤骨破坏的机制。方法:收集后天性中耳胆脂瘤患者的25例胆脂瘤标本和13例外耳道正常皮肤组织标本。采用免疫组织化学染色方法检测PTHrP、核因子κB受体活化因子配体(receptor activator for nuclear factor-kappa B ligand,RANKL)和骨保护素(osteoprotegerin,OPG)在中耳胆脂瘤和外耳道正常皮肤组织中的表达,抗酒石酸酸性磷酸酶(tartrate-resistant acid phosphatase,TRAP)染色法检测中耳胆脂瘤和外耳道正常皮肤组织中是否存在TRAP阳性多核巨噬细胞。选取小鼠单核巨噬细胞RAW264.7细胞进行干预,分为RANKL干预组和PTHrP+RANKL共同干预组,采用TRAP染色法检测2组破骨细胞的生成情况,实时聚合酶链反应(real-time polymerase chain reaction,real-time PCR)检测干预后2组破骨细胞相关基因TRAP、组织蛋白酶K(cathepsin K,CTSK)和活化T细胞核因子1(nuclear factor of activated T cell cytoplasmic 1,NFATc1)的mRNA表达水平,骨吸收陷窝实验检测2组破骨细胞的骨吸收功能。结果:免疫组织化学染色结果显示,PTHrP和RANKL在中耳胆脂瘤组织中的表达均显著增高,OPG表达降低(均P<0.05),且PTHrP的表达与RANKL、RANKL/OPG比值均呈显著正相关,与OPG表达呈显著负相关(分别r=0.385、r=0.417、r=-0.316,均P<0.05)。同时,PTHrP、RANKL的表达水平与中耳胆脂瘤的骨破坏程度均呈显著正相关(分别r=0.413、r=0.505,均P<0.05)。TRAP染色结果显示中耳胆脂瘤上皮周围基质中有大量TRAP阳性细胞,并存在细胞核数量为3个或3个以上的TRAP阳性破骨细胞。RANKL或PTHrP+RANKL联合干预5 d后,与RANKL干预组相比,PTHrP+RANKL联合干预组的破骨细胞数量显著增加(P<0.05),且破骨细胞相关基因TRAP、CTSK和NFATc1的mRNA表达水平均升高(均P<0.05)。骨吸收陷窝扫描电镜结果显示RANKL干预组、PTHrP+RANKL联合干预组的骨片表面均形成骨吸收陷窝;与RANKL干预组相比,PTHrP+RANKL联合干预组的骨片表面骨吸收陷窝数量显著增加(P<0.05),面积也更大。结论:PTHrP可能通过促进RANKL诱导胆脂瘤组织周围基质中的巨噬细胞分化为破骨细胞,参与中耳胆脂瘤骨破坏。 展开更多
关键词 甲状旁腺激素相关蛋白 中耳胆脂瘤 核因子ΚB受体活化因子配体 骨保护素 破骨细胞 巨噬细胞
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瑞马唑仑调节EPAC1/RAP1信号通路对急性心肌梗死大鼠心肌损伤的影响
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作者 肖锦亮 汪威廉 但家朋 《天津医药》 CAS 2024年第5期475-480,共6页
目的探讨瑞马唑仑调节环腺苷酸激活的交换蛋白1(EPAC1)/RAS相关蛋白1(RAP1)信号通路对急性心肌梗死(AMI)大鼠心肌损伤的影响。方法将大鼠按照随机数字表法分为假手术组、模型组、瑞马唑仑组、瑞马唑仑+8-CPT(EPAC1的激动剂)组,每组20只... 目的探讨瑞马唑仑调节环腺苷酸激活的交换蛋白1(EPAC1)/RAS相关蛋白1(RAP1)信号通路对急性心肌梗死(AMI)大鼠心肌损伤的影响。方法将大鼠按照随机数字表法分为假手术组、模型组、瑞马唑仑组、瑞马唑仑+8-CPT(EPAC1的激动剂)组,每组20只。除假手术组外,其余各组大鼠通过左前降支结扎法构建AMI大鼠模型;小动物超声仪检测心功能指标;HE染色检测心肌组织病理情况;化学比色法检测大鼠心肌组织超氧化物歧化酶(SOD)和丙二醛(MDA)水平;JC-1染色法检测大鼠心肌细胞线粒体膜电位;TUNEL染色检测心肌细胞TUNEL阳性率;Western blot检测心肌组织EPAC1、RAP1、胱天蛋白酶3(Caspase-3)蛋白表达水平。结果与假手术组相比,模型组大鼠心肌组织结构被严重破坏且浸润大量炎性细胞;心功能指标左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD),心肌组织MDA水平,心肌细胞TUNEL阳性率,心肌组织EPAC1、RAP1、Caspase-3蛋白表达水平均明显升高;左心室射血分数(LVEF)、左心室短轴缩短率(LVFS),心肌组织SOD水平,心肌细胞线粒体膜电位明显降低(P<0.05)。与模型组相比,瑞马唑仑组大鼠心肌损伤缓解,炎性细胞浸润减轻,心功能指标LVEDD、LVESD,心肌组织MDA水平,心肌细胞TUNEL阳性率,心肌组织EPAC1、RAP1、Caspase-3蛋白表达水平均明显降低;LVEF、LVFS,心肌组织SOD水平,心肌细胞线粒体膜电位明显升高(P<0.05)。EPAC1的激动剂减弱了瑞马唑仑对AMI大鼠心肌损伤的缓解作用。结论瑞马唑仑可能通过抑制EPAC1/RAP1信号通路抑制心肌细胞凋亡,减轻AMI大鼠心肌损伤。 展开更多
关键词 心肌梗死 心肌损伤 瑞马唑仑 环腺苷酸激活的交换蛋白1 raS相关蛋白1
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Ras相关C3肉毒杆菌毒素底物1在肺部疾病中作用及机制的研究进展
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作者 许文霞 方育 《中国病理生理杂志》 CAS CSCD 北大核心 2024年第7期1338-1344,共7页
Ras相关C3肉毒杆菌毒素底物1(Ras-related C3 botulinum toxin substrate 1,RAC1)是Ras GTPase超家族的重要成员,在细胞的运动、增殖、黏附等方面发挥核心作用,同时还参与调节血管通透性以及细胞屏障功能。近年来,RAC1在多种肺部疾病发... Ras相关C3肉毒杆菌毒素底物1(Ras-related C3 botulinum toxin substrate 1,RAC1)是Ras GTPase超家族的重要成员,在细胞的运动、增殖、黏附等方面发挥核心作用,同时还参与调节血管通透性以及细胞屏障功能。近年来,RAC1在多种肺部疾病发生、发展过程的作用逐渐受到关注,并逐渐成为肺部疾病研究的新方向。本文系统阐述了RAC1的生物学特性并总结了其在肺肿瘤、慢性阻塞性肺疾病、肺损伤和动脉型肺动脉高压中的功能及分子机制,以期为肺部疾病的治疗提供新思路。 展开更多
关键词 ras相关C3肉毒杆菌毒素底物1 肺癌 慢性阻塞性肺疾病 肺损伤 动脉型肺动脉高压
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高分辨CT三维重建联合肺泡灌洗液中SHOX2、RASSF1A基因甲基化检测诊断早期肺结节的价值
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作者 黎欣 庄仕龙 +1 位作者 刘芸 肖泽林 《淮海医药》 CAS 2024年第4期351-354,359,共5页
目的:探究高分辨CT三维重建联合肺泡灌洗液(BALF)中矮小同源盒基因2(SHOX2)、Ras相关区域家族A1(RASSF1A)基因甲基化检测诊断早期肺结节的价值。方法:选取2021年5月—2022年5月某院就诊并经纤维支气管镜(FB)检查的肺结节患者100例,FB下... 目的:探究高分辨CT三维重建联合肺泡灌洗液(BALF)中矮小同源盒基因2(SHOX2)、Ras相关区域家族A1(RASSF1A)基因甲基化检测诊断早期肺结节的价值。方法:选取2021年5月—2022年5月某院就诊并经纤维支气管镜(FB)检查的肺结节患者100例,FB下收集患者的BALF,通过实时荧光定量PCR法测定BALF中SHOX2和RASSF1A基因甲基化状态,同时收集高分辨CT三维重建检查、BALF检测结果。依据病检结果将患者分为恶性结节组(n=40)和良性结节组(n=60),分析高分辨CT三维重建检查、BALF中SHOX2、RASSF1A基因甲基化检测对早期肺结节的诊断价值,并绘制ROC曲线评价各检测方法在早期肺结节诊断中的效能。结果:SHOX2甲基化诊断恶性结节的敏感度为50.00%,AUC为0.708,RASSF1A甲基化诊断恶性结节的敏感度为52.50%,AUC为0.713,2基因甲基化联合诊断恶性结节的敏感度为75.00%,AUC为0.767。高分辨CT三维重建诊断恶性结节的敏感度为72.50%,特异度为73.33%,AUC为0.729,BALF对恶性结节的诊断敏感度为25.00%,特异度为100.00%,AUC为0.625。2基因甲基化联合+高分辨CT三维重建诊断恶性肺结节的AUC为0.890,敏感度与特异度分别为90.00%和73.33%,其诊断效能高于2基因甲基化联合+BALF细胞学分析和高分辨CT三维重建+BALF细胞学分析(Z=2.453、2.736,P均<0.05)。结论:高分辨CT三维重建联合BALF中SHOX2、RASSF1A基因甲基化检测在肺结节良恶性诊断中的鉴别效能较高,值得在临床中应用。 展开更多
关键词 肺结节 高分辨CT 三维重建 肺泡灌洗液 矮小同源盒基因2 ras相关区域家族A1
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Hp、RASAL2、CDH1及TP53对胃癌前病变与早期胃癌的鉴别诊断价值
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作者 马越 陈伟 +2 位作者 刘宝英 付丹丹 周彤 《临床误诊误治》 CAS 2024年第11期39-45,共7页
目的探讨幽门螺杆菌(Hp)、RAS蛋白激活样因子2(RASAL2)、钙黏蛋白1(CDH1)及肿瘤抑制基因P53(TP53)对胃癌前病变与早期胃癌的鉴别诊断价值。方法选取2021年6月至2023年6月收治的早期胃癌52例,根据1:1选例原则另选取同期胃癌前病变52例、... 目的探讨幽门螺杆菌(Hp)、RAS蛋白激活样因子2(RASAL2)、钙黏蛋白1(CDH1)及肿瘤抑制基因P53(TP53)对胃癌前病变与早期胃癌的鉴别诊断价值。方法选取2021年6月至2023年6月收治的早期胃癌52例,根据1:1选例原则另选取同期胃癌前病变52例、胃炎52例,分别纳入胃癌组、癌前组、胃炎组。比较3组及不同病理特征的早期胃癌患者Hp、RASAL2、CDH1、TP53阳性表达率,比较胃癌组Hp阳性、阴性患者RASAL2、CDH1、TP53阳性表达率,采用Spearman相关分析探讨各指标阳性表达与早期胃癌患者部分病理特征的相关性,采用受试者工作特征(ROC)曲线分析联合检测对早期胃癌及胃癌前病变的鉴别诊断价值。结果3组Hp、CDH1、TP53阳性表达率胃癌组>癌前组>胃炎组,RASAL2阳性表达率胃癌组<癌前组<胃炎组,差异有统计学意义(P<0.05,P<0.01)。胃癌组Hp阳性患者CDH1、TP53阳性表达率高于Hp阴性患者,RASAL2阳性表达率低于Hp阴性患者(P<0.05,P<0.01);早期胃癌患者Hp、RASAL2、CDH1、TP53阳性表达率在肿瘤浸润深度及淋巴结转移方面比较差异有统计学意义(P<0.05,P<0.01)。Hp、CDH1、TP53阳性表达与早期胃癌肿瘤浸润深度、淋巴结转移均呈正相关,RASAL2阳性表达与之呈负相关(P<0.01)。ROC曲线分析结果显示,Hp、RASAL2、CDH1、TP53联合诊断胃癌前病变的曲线下面积(AUC)为0.904(95%CI:0.846,0.945),联合诊断早期胃癌的AUC为0.894(95%CI:0.819,0.946)。结论Hp、CDH1、TP53在早期胃癌组织中阳性表达率较高,RASAL2阳性表达率较低,联合检测对胃癌前病变及早期胃癌具有一定鉴别诊断价值,可作为临床鉴别诊断胃癌前病变、早期胃癌的辅助指标。 展开更多
关键词 胃肿瘤 癌前病变 胃炎 幽门螺杆菌 raS蛋白激活样因子2 钙黏蛋白1 肿瘤抑制基因P53 诊断价值
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连翘脂素调节Ras/Raf/MEK/ERK信号通路对结直肠癌细胞恶性生物学行为的影响
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作者 郑声友 李叶若 肖嘉伍 《河北医药》 CAS 2024年第12期1771-1776,共6页
目的 探究连翘脂素(PG)对结直肠癌细胞增殖、迁移、侵袭、凋亡以及上皮间质转化的影响及机制。方法 培养HCT116结直肠癌细胞,采用10~200μmol/L的连翘脂素处理细胞,检测细胞存活率,筛选最佳实验浓度。将细胞分为对照组(Control组),连翘... 目的 探究连翘脂素(PG)对结直肠癌细胞增殖、迁移、侵袭、凋亡以及上皮间质转化的影响及机制。方法 培养HCT116结直肠癌细胞,采用10~200μmol/L的连翘脂素处理细胞,检测细胞存活率,筛选最佳实验浓度。将细胞分为对照组(Control组),连翘脂素低、中、高浓度组(PG-L组、PG-M组、PG-H组),连翘脂素高浓度+转染慢病毒阴性对照组(PG-H+NC组),连翘脂素高浓度+Ras慢病毒组(PG-H+Ras组)。平板克隆形成实验检测细胞增殖;划痕实验检测细胞迁移;Transwell小室法检测细胞侵袭;流式细胞术以及Hoechst33258染色法检测细胞凋亡;Western blot法检测上皮间质转化(EMT)标志蛋白E型钙黏蛋白(E-cadherin)、波形蛋白(Vimentin)以及信号通路相关蛋白p-Raf、p-MEK、p-ERK表达;建立荷瘤小鼠模型评价连翘脂素对结直肠癌肿瘤生长的影响。结果 10~200μmol/L的连翘脂素处理HCT116结直肠癌细胞,可以显著抑制细胞存活率,经计算IC50值为(140.4±2.147)μmol/L,选择10、50、100μmol/L连翘脂素进行后续实验;与Control组比较,PG-L组、PG-M组、PG-H组HCT116细胞克隆形成率、划痕愈合率、细胞侵袭个数以及Vimentin、p-Raf、p-MEK、p-ERK表达显著降低,细胞凋亡率以及E-cadherin表达显著升高,且呈浓度依赖性(P<0.05);与PG-H+NC组比较,PG-H+Ras组HCT116细胞克隆形成率、划痕愈合率、细胞侵袭个数以及Vimentin、p-Raf、p-MEK、p-ERK表达显著升高,细胞凋亡率以及E-cadherin表达显著降低(P<0.05);连翘脂素可以显著抑制结直肠癌移植瘤的生长。结论 连翘脂素可以抑制结直肠癌细胞增殖、迁移、侵袭、凋亡以及上皮间质转化,其作用机制可能与抑制Ras/Raf/MEK/ERK信号通路激活有关。 展开更多
关键词 连翘脂素 ras/raf/MEK/ERK信号通路 结直肠癌 上皮间质转化 增殖 凋亡
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Relative active tectonics evaluation using geomorphic and drainage indices, in Dadra and Nagar Haveli, western India 被引量:3
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作者 Naveen Kumar Rakesh K.Dumka +1 位作者 Kapil Mohan Sumer Chopra 《Geodesy and Geodynamics》 CSCD 2022年第3期219-229,共11页
The present study area,Dadra and Nagar Haveli,contains several lineaments and traces of active faults.The various aspect of the geomo rphic analysis,i.e.,stream length(SL) gradient,hypsometric integral(HI),basin shape... The present study area,Dadra and Nagar Haveli,contains several lineaments and traces of active faults.The various aspect of the geomo rphic analysis,i.e.,stream length(SL) gradient,hypsometric integral(HI),basin shape(BS),valley floor(VF),have been applied to evaluate the relative index of active tectonics(RIAT) of the Damanganga watershed.The high and low zones of tectonic activity have been identified based on the geomorphic analysis of the watershed.After evaluation of all indices,three classes,class IIhigh(1.3 ≤RIAT <1.5),class Ⅲ-moderate(1.5 ≤RIAT <1.8),and class Ⅳ-low(1.8 ≤RIAT),have been obtained to outline the degree/gradation of comparative tectonic activities in the study area.The appraised outcome of the RIAT dispersal is also well reinforced by the geomorphic evidence in the field.The collective outcomes of geomorphic evidence,such as stream deflection and analysis of lineament,deflection of streams,and geomorphic indices,conceal that the Damanganga watershed is affected by tectonic activity. 展开更多
关键词 Active tectonics Geomorphic indices relative index of active tectonics(RIAT) Drainage indices
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Relationships of growth and mortality to enzymatic activity,and the relative mRNA expression of cultured scallops Patinopecten yessoensis in the Yellow Sea, China 被引量:2
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作者 LIU Chao WU Fucun +1 位作者 QUE Huayong ZHANG Guofan 《Journal of Oceanology and Limnology》 SCIE CAS CSCD 2019年第4期1409-1422,共14页
The bottom aquaculture of yesso scallop (Patinopecten yessoensis) has developed rapidly in the north of Yellow Sea, China, but not without accompanying productivity problems. We, therefore, conducted field surveys to ... The bottom aquaculture of yesso scallop (Patinopecten yessoensis) has developed rapidly in the north of Yellow Sea, China, but not without accompanying productivity problems. We, therefore, conducted field surveys to investigate factors related to growth and mortality rates of bottom-cultured scallops after release. Specifically, we focused on the effects of total antioxidant capacity (TAOC) and three key enzymes involved in antioxidant and metabolic function:glutamic pyruvic transaminase (GPT), lactic dehydrogenase (LDH), and superoxide dismutase (SOD). Across summer and winter, we also measured the relative mRNA expression of GPT and SOD to understand their seasonal variation in the scallops, along with how such variation correlated to growth and mortality. Results show that bottom cultured scallops experienced mass mortality during the first six months post-release. During winter (December), scallops grew more rapidly and suffered less mortality than in summer (August). The observed lower performance probably resulted from less advantageous environmental factors during the summer seasons, such as high temperature and low dissolved oxygen. These environmental stressors enhance protein consumption while decreasing energetic resources in scallops. Furthermore, scallops in summer exhibited high antioxidant levels that probably competed for energy with process integral to growth and survival. These negative factors combined to elevate mortality rates. In conclusion, we provided evidence suggesting correlations between metabolic/antioxidant activity and growth and mortality of bottom-cultured yesso scallops. These correlations implied us an accurate method to estimate the performance of bottom culture system. Suggestions about innovative aquaculture techniques were also discussed in the study. Our results might provide a possible guideline to the improvement of bottom culture techniques for this commercially valuable seafood species. 展开更多
关键词 yesso SCALLOP (Patinopecten yessoensis) bottom culture GROWTH and MORTALITY rate antioxidant and metabolic activity relative mRNA expression
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Binding activity of H-Ras is necessary for in vivo inhibition of ASK1 activity 被引量:4
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作者 JunDU ShaoHuiCAI +1 位作者 ZheSHI FumihikoNAGASE 《Cell Research》 SCIE CAS CSCD 2004年第2期148-154,共7页
H-Ras is well known as one of the essential components of Ras/Raf/MEK/ERK cascade, which is a critical prosurvival signaling mechanism in most eukaryotic cells. Ras targets Raf/MEK/ERK cascade by integrating and trans... H-Ras is well known as one of the essential components of Ras/Raf/MEK/ERK cascade, which is a critical prosurvival signaling mechanism in most eukaryotic cells. Ras targets Raf/MEK/ERK cascade by integrating and transmitting extracellular signals from growth factor receptors to Raf, leading to the propagation of signals to modulate a serious of cellular survival events. Apoptosis signal-regulating kinasel (ASK1) serves as a general mediator of cell death because it is responsive to a variety of death signals. In this study, we found that H-Ras interacted with ASK1 to cause the inhibition of both ASK1 activity and ASK1-induced apoptosis in vivo, which was reversed only partially by addition of RafS621A, an antagonist of Raf, whereas MEK inhibitor, PD98059, and PI3K inhibitor, LY294002, did not disturb the inhibitory effect of H-Ras on ASK-1-induced apoptosis. Furthermore, by means of immunoprecipitate and kinase assays, we demonstrated that the interaction between H-Ras and ASK1 as well as the inhibition of ASK1 activity were dependent on the binding activity of H-Ras. These results suggest that a novel mechanism may be involved in H-Rasmediated cell survival in addition to the well established MEK/ERK and PI3K/Akt kinase-dependent enhancement of cell survival. 展开更多
关键词 H-raS ASKl 细胞凋亡 结合活性 抑制 真核细胞
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经皮冠状动脉介入治疗术后支架内再狭窄患者血浆Rap1A水平变化及其机制 被引量:1
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作者 高浩东 匡圆圆 +3 位作者 刘昱博 张银妆 王萍 马琦琳 《中南大学学报(医学版)》 CAS CSCD 北大核心 2023年第11期1650-1658,共9页
目的:经皮冠状动脉介入治疗(percutaneous coronary intervention,PCI)是冠状动脉疾病(coronary artery disease,CAD)的主要治疗方法之一,PCI术后支架内再狭窄(in-stent restenosis,ISR)是其一种严重的并发症,然而目前缺乏有效的防治手... 目的:经皮冠状动脉介入治疗(percutaneous coronary intervention,PCI)是冠状动脉疾病(coronary artery disease,CAD)的主要治疗方法之一,PCI术后支架内再狭窄(in-stent restenosis,ISR)是其一种严重的并发症,然而目前缺乏有效的防治手段。本研究拟检测Ras相关蛋白1A(Ras-related protein 1A,Rap1A)在ISR患者血浆中的表达水平及肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)诱导人脐静脉内皮细胞(human umbilical vein endothelial cells,HUVECs)炎症损伤模型中的表达差异,并探讨Rap1A在调控TNF-α诱导的HUVECs炎症中的作用,为ISR的防治提供一个新的潜在靶点。方法:纳入2020年12月至2022年7月于中南大学湘雅医院心血管内科接受PCI支架植入术,且术后1年复查经皮冠状动脉造影(coronary arteriography,CAG)的冠心病住院患者共60例。患者入院后根据CAG诊断27例为PCI术后ISR,33例为无支架内再狭窄(non-in-stent restenosis,non-ISR)。收集2组患者的临床资料,并通过酶联免疫吸附法(enzyme linked immunosorbent assay,ELISA)测定患者血浆Rap1A水平,比较2组患者血浆Rap1A水平。在细胞实验中,通过TNF-α(10 ng/mL,24 h)构建HUVECs炎症损伤模型,采用实时反转录聚合酶链反应(realtime reverse transcription PCR,real-time RT-PCR)和蛋白质印迹法检测Rap1A、白细胞介素-6(interleukin-6,IL-6)和血管细胞黏附分子-1(vascular cell adhesion molecule-1,VCAM-1)的mRNA及蛋白质表达水平。以TNF-α处理HUVECs诱导内皮细胞炎症,并运用小干扰RNA(small interfering RNA,siRNA)敲减Rap1A,以探究Rap1A在调控TNF-α诱导的HUVECs炎症中的作用。结果:与non-ISR患者相比,ISR患者中有吸烟史(P=0.005)及合并糖尿病者比例更高(P=0.028),糖化血红蛋白(glycosylated hemoglobin,HbA1c)(P=0.012)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-c)(P=0.014)及高敏C反应蛋白(hypersensitive C-reactive protein,hs-CRP)(P=0.027)水平升高,余指标在2组间差异均无统计学意义(均P>0.05)。而ISR组的血浆Rap1A水平显著高于non-ISR组[942.14(873.28~1133.81)μg/mL vs 886.93(812.61~930.98)μg/mL;P=0.004]。单因素logistic回归分析结果显示糖尿病、LDL-c、Rap1A是ISR的危险因素(均P<0.05)。在细胞实验中,与对照组相比,以10 ng/mL TNF-α诱导24 h后,HUVECs中炎症因子IL-6、VCAM-1的mRNA及蛋白质表达水平均升高(均P<0.05),同时Rap1A的mRNA及蛋白质水平升高(均P<0.05)。进一步通过敲减HUVECs中Rap1A基因的表达,TNF-α诱导的IL-6、VCAM-1的mRNA及蛋白质表达水平均显著降低(均P<0.05)。结论:在冠心病PCI术后ISR患者血浆及TNF-α诱导的内皮细胞炎症损伤模型中,Rap1A蛋白质水平显著升高,提示Rap1A可能是预测ISR的潜在生物标志物。而在敲减Rap1A基因表达后,TNF-α诱导的内皮细胞炎症反应水平下降,提示Rap1A可能是治疗ISR内皮细胞炎症的潜在靶点。 展开更多
关键词 支架内再狭窄 ras相关蛋白1A 内皮细胞 炎症损伤
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高表达RAB7A通过促进肿瘤侵袭影响胃癌患者的预后 被引量:1
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作者 张敏 刘生宝 +7 位作者 张诺 张文静 夏勇生 宋雪 张小凤 左芦根 李静 胡建国 《南方医科大学学报》 CAS CSCD 北大核心 2023年第10期1734-1743,共10页
目的探讨Ras相关蛋白7A(RAB7A)在胃癌组织中的表达对预后的影响及其作用机制。方法基于癌症公共数据库和本院接受胃癌根治术的104例患者,分析RAB7A在胃癌及癌旁组织中表达的差异以及其与患者临床病理学参数和预后的关系;采用生物信息学... 目的探讨Ras相关蛋白7A(RAB7A)在胃癌组织中的表达对预后的影响及其作用机制。方法基于癌症公共数据库和本院接受胃癌根治术的104例患者,分析RAB7A在胃癌及癌旁组织中表达的差异以及其与患者临床病理学参数和预后的关系;采用生物信息学富集分析预测RAB7A影响胃癌侵袭途径的作用和机制;通过慢病毒转染获得过表达和低表达RAB7A的胃癌细胞系(MGC803),采用免疫印迹、划痕及Transwell实验探究RAB7A对ECM降解的影响以及RAB7A对胃癌细胞迁移、侵袭的作用和机制。结果癌症公共数据库分析显示胃癌组织中RAB7A的表达高于正常对照组,且负面影响患者生存期(P<0.01)。本院患者数据显示,胃癌组织中RAB7A的表达高于癌旁组织(P<0.01),且与外周血胚抗原、糖类抗原19-9水平正相关(P<0.001)。单因素结合Cox多因素分析显示,RAB7A高表达是影响胃癌5年生存率的独立危险因素(HR:2.882;95%CI:1.459~5.693);ROC曲线分析显示,以RAB7A相对表达量2.625为截断值,其预测患者术后5年死亡的敏感性为84.62%,特异性为71.15%。生物信息学富集分析显示,RAB7A参与了胃癌组织ECM降解和PI3K/AKT信号激活;体外实验证实,过表达RAB7A可激活胃癌细胞PI3K/AKT信号(P<0.01),增强基质金属蛋白酶(MMP-2和MMP-9)表达(P<0.01),以及胃癌细胞迁移和侵袭能力(P<0.01)。结论RAB7A在胃癌组织中高表达并影响患者预后,其作用和激活胃癌PI3K/AKT信号并促进ECM降解和肿瘤侵袭有关。 展开更多
关键词 胃癌 raB7A 预后 侵袭 PI3K/AKT
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Regional homogeneity of intrinsic brain activity related to the main alexithymia dimensions 被引量:1
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作者 Han Dai Li Mei +1 位作者 Mei Minjun Sun Xiaofei 《General Psychiatry》 CSCD 2018年第4期17-23,共7页
Background Alexithymia is a multidimensional personality construct.Objective This study aims to investigate the neuronal correlates of each alexithymia dimension by examining the regional homogeneity(ReHo) of intrinsi... Background Alexithymia is a multidimensional personality construct.Objective This study aims to investigate the neuronal correlates of each alexithymia dimension by examining the regional homogeneity(ReHo) of intrinsic brain activity in a resting situation.Methods From university freshmen, students with alexithymia and non-alexlthymia were recruited. Their alexithymic traits were assessed using the Toronto Alexithymia Scale-20. The ReHo was examined using a resting-state functional MRI approach.Results This study suggests significant gro叩 differences in ReHo in multiple brain regions distributed in the frontal lobe, parietal lobe, temporal lobe, occipital lobe and insular cortex. However, only the ReHo in the insula was positively associated with difficulty identifying feelings, a main dimension of alexithymia. The ReHo in the lingual gyrus,precentral gyrus and postcentral gyrus was positively associated with difficulty describing feelings in participants with alexithymia. Lastly, the ReHo in the right dorsomedial prefrontal cortex(DMPFC_R) was negatively related to the externally oriented thinking style of participants with alexithymia.Conclusion In conclusion, these results suggest that the main dimensions of alexithymia are correlated with specific brain regions' function, and the role of the insula,lingual gyrus, precentral gyrus, postcentral gyrus and DMPFC_R in the neuropathology of alexithymia should be further investigated. 展开更多
关键词 Regional homogeneity of intrinsic brain activity related to the main alexithymia dimensions MFG
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电针对佐剂性关节炎大鼠膝关节滑膜VEGF/Vav2/Rac1信号通路的影响 被引量:1
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作者 孙晓莹 龙轶映 +6 位作者 赵凌云 吴庆泽 瞿启睿 祁芳 刘梨 艾坤 张亮 《湖南中医药大学学报》 CAS 2023年第10期1830-1837,共8页
目的观察电针对佐剂性关节炎(adjuvant arthritis,AA)大鼠膝关节滑膜组织内血管内皮生长因子(vascular endothelial growth factor,VEGF)、鸟嘌呤核苷酸交换因子2(vav guanine nucleotide exchange factor 2,Vav2)和Ras相关C3肉毒素底物... 目的观察电针对佐剂性关节炎(adjuvant arthritis,AA)大鼠膝关节滑膜组织内血管内皮生长因子(vascular endothelial growth factor,VEGF)、鸟嘌呤核苷酸交换因子2(vav guanine nucleotide exchange factor 2,Vav2)和Ras相关C3肉毒素底物1(Ras-related C3 botulinum toxin substrate 1,Rac1)表达的影响,探究电针干预类风湿关节炎(rheumatoid arthritis,RA)血管新生的可能机制。方法将40只SPF级SD雄性大鼠随机分成4组(空白组、模型组、西药组和电针组),每组10只。除空白组,其他3组采用尾根部皮下注射完全弗氏佐剂制成AA大鼠模型。造模后第2天开始干预,电针组进行电针干预,以左侧足三里与关元穴配穴,右侧足三里与同侧阿是穴配穴,每次20 min,每天干预1次,共干预21次;西药组给予甲氨蝶呤灌胃给药,每周1次,共干预3次。观察各组体质量、关节红肿等一般情况,每3天测量1次大鼠后双侧足跖容积。干预结束后,通过大鼠一般情况、体质量、足跖容积分析各组大鼠足跖肿胀程度,HE染色观察AA大鼠膝关节滑膜组织的病理形态学,免疫组织化学法检测膝关节滑膜组织内CD31表达变化,Western blot法检测大鼠膝关节滑膜组织VEGF、Vav2和Rac1蛋白表达量。结果与空白组相比,模型组大鼠第21天足跖容积均明显增大(P<0.01),膝关节滑膜组织出现显著性病理改变,CD31表达量明显升高(P<0.05),VEGF、Vav2、Rac1蛋白表达量显著升高(P<0.01)。与模型组相比,西药组足跖容积在第21天显著减小(P<0.01),膝关节滑膜组织病理改变明显改善,VEGF、Vav2表达量明显下降(P<0.05),Rac1蛋白表达量显著下降(P<0.01);电针组足跖容积在第21天显著减小(P<0.01),膝关节滑膜组织病理改变明显改善,VEGF、Rac1表达量明显下降(P<0.05),Vav2蛋白表达量显著下降(P<0.01)。结论电针改善RA的作用机制可能与抑制VEGF/Vav2/Rac1信号通路,进而抑制血管新生有关。 展开更多
关键词 佐剂性关节炎 电针 血管内皮生长因子 鸟嘌呤核苷酸交换因子2 ras相关C3肉毒素底物1 血管新生
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Quantitative distinction of the relative actions of climate change and human activities on vegetation evolution in the Yellow River Basin of China during 1981-2019 被引量:4
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作者 LIU Yifeng GUO Bing +3 位作者 LU Miao ZANG Wenqian YU Tao CHEN Donghua 《Journal of Arid Land》 SCIE CSCD 2023年第1期91-108,共18页
Under the combined influence of climate change and human activities,vegetation ecosystem has undergone profound changes.It can be seen that there are obvious differences in the evolution patterns and driving mechanism... Under the combined influence of climate change and human activities,vegetation ecosystem has undergone profound changes.It can be seen that there are obvious differences in the evolution patterns and driving mechanisms of vegetation ecosystem in different historical periods.Therefore,it is urgent to identify and reveal the dominant factors and their contribution rates in the vegetation change cycle.Based on the data of climate elements(sunshine hours,precipitation and temperature),human activities(population intensity and GDP intensity)and other natural factors(altitude,slope and aspect),this study explored the spatial and temporal evolution patterns of vegetation NDVI in the Yellow River Basin of China from 1989 to 2019 through a residual method,a trend analysis,and a gravity center model,and quantitatively distinguished the relative actions of climate change and human activities on vegetation evolution based on Geodetector model.The results showed that the spatial distribution of vegetation NDVI in the Yellow River Basin showed a decreasing trend from southeast to northwest.During 1981-2019,the temporal variation of vegetation NDVI showed an overall increasing trend.The gravity centers of average vegetation NDVI during the study period was distributed in Zhenyuan County,Gansu Province,and the center moved northeastwards from 1981 to 2019.During 1981-2000 and 2001-2019,the proportion of vegetation restoration areas promoted by the combined action of climate change and human activities was the largest.During the study period(1981-2019),the dominant factors influencing vegetation NDVI shifted from natural factors to human activities.These results could provide decision support for the protection and restoration of vegetation ecosystem in the Yellow River Basin. 展开更多
关键词 vegetation evolution driving mechanisms climate change human activities relative actions Geodetector Yellow River Basin
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The Relation of Department Components and Activity in Spatial Information Infrastructure
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作者 Yi Shan zhen 1, Zhou Li zhu 1,Cheng Ji cheng 2, Li Qi 2 1.Department of Computer Science and Technology,Tsinghua University, Beijing 100084, China 2.Institute of Remote Sensing and Geographical Information System,Peking University,Beijing 1008 《Wuhan University Journal of Natural Sciences》 CAS 2001年第Z1期460-466,共7页
Spatial Information Infrastructure (SII) facilitates the sharing, interoperability and integration of geographical information among department components of a region or a country. The SII is developed and shared by d... Spatial Information Infrastructure (SII) facilitates the sharing, interoperability and integration of geographical information among department components of a region or a country. The SII is developed and shared by different department components. The relation of department components is a fundament for collaborating tasks and information exchange in SII. There are two kinds of department components, one is the provider which produces geospatial data of SII, other is the consumer which uses geospatial data of SII. The consumer includes two kinds of user, one is the user which only uses and does not produce geospatial data in SII, other is the special user which not only uses but also produces geospatial data in SII. The provider includes different hierarchies corresponding to different kinds of geospatial data in SII. All providers in the hierarchies form provider actor set PA. All consumers also form consumer actor set CA. The sender recipient relation SR and SRI are defined on Cartesian product of PA and CA. Five tasks and information flow in SII demonstrate the geospatial data acquisition, information production, management, and application among department components. The tasks and their sub tasks are subdivided activities. Each activity corresponds to the relation SR or RSI. The activity along with the relation of provider and consumer forms a scheme of geographical information exchange between department components. 展开更多
关键词 geographical information EXCHANGE RELATION activity information infrastructure
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Granger因果关系时空图推理的群体行为分析 被引量:1
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作者 谢昭 李骏 +1 位作者 吴克伟 焦畅 《计算机学报》 EI CAS CSCD 北大核心 2023年第4期856-876,共21页
因果关系普遍存在于群体交互行为中,体现出主动体行为对被动体行为的有向影响.因果关系检测的难点在于交互双方的行为具有复杂的时间动态性.现有方法使用循环神经网络,来描述交互关系的时间变化特性,并使用时间注意力机制,来描述时间依... 因果关系普遍存在于群体交互行为中,体现出主动体行为对被动体行为的有向影响.因果关系检测的难点在于交互双方的行为具有复杂的时间动态性.现有方法使用循环神经网络,来描述交互关系的时间变化特性,并使用时间注意力机制,来描述时间依赖关系.上述方法忽视了对多人依赖关系的分析,难以区分交互双方中的主动行为者和被动行为者.本文设计了一种基于Granger因果关系的时空图推理模型,来学习交互双方的主动和被动关系.为了实现Granger因果关系检测,该模型对单个个体时序特征进行自回归建模,来描述行为对个体自己的依赖.该模型对两个个体时序特征进行相关回归建模,来描述行为对两个个体的依赖.该模型通过比较自回归误差和相关回归误差,当自回归误差明显大于相关回归误差,则说明相关个体改变了另一方个体的行为特征,从而检测出相关个体为主动个体,另一方为被动个体.相关回归模型考虑了多种时间延迟量的两个个体的时序特征序列,用于学习两个个体之间行为的时间延迟量.该时间延迟量用于将主动个体时间特征与被动个体时间特征进行对齐.时间对齐后的主动个体特征提供了被动个体的时间和空间上下文特征,并与被动个体特征进行通道级的融合.为了充分描述个体之间的外观模式,位置约束,因果关系的交互关系,该模型构建多尺度外观的因果图,并使用图推理学习融合上下文的个体特征和群体特征.本文对Granger因果关系检测进行消融分析,并说明时间延迟量,交互融合通道比例,多尺度图推理,能够有效改善个体特征、群体特征的描述能力.本文方法在Volleyball和Collective Activity数据集上优于现有群体行为识别方法.本文的可视化结果说明Granger因果关系可以捕获群体中关键的交互关系. 展开更多
关键词 群体行为识别 GraNGER因果关系 时间延迟依赖 时空上下文 图卷积推理
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Role of the Dorsal Anterior Cingulate Cortex in Relational Memory Formation: A Deep Brain Activity Index Study
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作者 Ariko Araki Emiko Imai Yoshitada Katagiri 《Journal of Behavioral and Brain Science》 2018年第5期269-293,共25页
The dorsal area of the anterior cingulate cortex (ACC) constructs the salience network associated with the anterior insular cortex. Conventional brain imaging studies, such as functional magnetic resonance imaging (fM... The dorsal area of the anterior cingulate cortex (ACC) constructs the salience network associated with the anterior insular cortex. Conventional brain imaging studies, such as functional magnetic resonance imaging (fMRI), have demonstrated that relational memory formation occurs in the ACC. However, how such memory is encoded and retrieved remains unknown due to limited time resolution of conventional fMRI. This study aimed to investigate temporal dynamics of the dorsal ACC (dACC) during word-pair tasks based on a newly developed event-related deep brain activity (ER-DBA) method using occipital electroencephalogram (EEG) signal powers. The method assesses dACC activity at a temporal resolution of approximately 0.3 s beyond the conventional resolution limit. We found that transient deactivation of dACC during the presentation of the second word of each pair was essential for encoding success regardless of whether the words were related or unrelated. We also found that memory accuracy was not affected by the intervention of inter-trials until the recall trial. Taken together, these findings suggest that dACC deactivation for encoding success is accompanied with short-term potentiation essential for durability of memory. We further found that false memory formation associated with the presentation of word pairs was occasionally committed. In such cases, dACC exhibited a similar transient deactivation although false memory commission was independent of related or unrelated conditions. Our findings suggest that encoding and retrieval of associates are paralleled and that simultaneous production of associates seems to be an essential strategy for successful relational memory formation. The study was limited to the assessment of dACC activity and did not account for other regional brain activities or receptor regulation related to short-term potentiation. We detected fast behavior of dACC during relational memory formation using the novel ER-DBA method. Such temporal dynamics will be important for eliciting underlying mechanisms of memory dysfunctions. 展开更多
关键词 RELATIONAL Memory Word-Pair Task EVENT-RELATED DEEP Brain activity DORSAL ANTERIOR CINGULATE Cortex Temporal Dynamics
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Challenges in the Detection and Attribution of Northern Hemisphere Surface Temperature Trends Since 1850 被引量:1
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作者 Ronan Connolly Willie Soon +17 位作者 Michael Connolly Sallie Baliunas Johan Berglund C.J.Butler Rodolfo Gustavo Cionco Ana G.Elias Valery M.Fedorov Hermann Harde Gregory W.Henry Douglas V.Hoyt Ole Humlum David R.Legates Nicola Scafetta Jan-Erik Solheim LászlóSzarka Víctor M.Velasco Herrera Hong Yan Weijia Zhang 《Research in Astronomy and Astrophysics》 SCIE CAS CSCD 2023年第10期367-386,共20页
Since 2007,the Intergovernmental Panel on Climate Change(IPCC)has heavily relied on the comparison between global climate model hindcasts and global surface temperature(ST)estimates for concluding that post-1950s glob... Since 2007,the Intergovernmental Panel on Climate Change(IPCC)has heavily relied on the comparison between global climate model hindcasts and global surface temperature(ST)estimates for concluding that post-1950s global warming is mostly human-caused.In Connolly et al.,we cautioned that this approach to the detection and attribution of climate change was highly dependent on the choice of Total Solar Irradiance(TSI)and ST data sets.We compiled 16 TSI and five ST data sets and found by altering the choice of TSI or ST,one could(prematurely)conclude anything from the warming being“mostly human-caused”to“mostly natural.”Richardson and Benestad suggested our analysis was“erroneous”and“flawed”because we did not use a multilinear regression.They argued that applying a multilinear regression to one of the five ST series re-affirmed the IPCC's attribution statement.They also objected that many of the published TSI data sets were out-of-date.However,here we show that when applying multilinear regression analysis to an expanded and updated data set of 27 TSI series,the original conclusions of Connolly et al.are confirmed for all five ST data sets.Therefore,it is still unclear whether the observed warming is mostly human-caused,mostly natural or some combination of both. 展开更多
关键词 Sun:activity (Sun:)solar-terrestrial relations EARTH
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Comparative Molecular Field Analysis(CoMFA) of Curcumin-related Compounds for Anticancer Activity 被引量:1
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作者 周代营 杜志云 +5 位作者 汤志恺 郑希 丁宁 郑俊霞 王辉 张焜 《Chinese Journal of Structural Chemistry》 SCIE CAS CSCD 2014年第2期179-188,共10页
Three-dimensional (3D) quantitative structure-activity relationship (QSAR) studies of 44 curcumin-related compounds have been carried out based on our previously reported result for their anticancer activity again... Three-dimensional (3D) quantitative structure-activity relationship (QSAR) studies of 44 curcumin-related compounds have been carried out based on our previously reported result for their anticancer activity against pancreas cancer Panc-I cells and colon cancer HT-29 cells. The established 3D-QSAR models from the comparative molecular field analysis (CoMFA) in training set showed not only significant statistical quality, but also satisfying predictive ability, with high correlation coefficient values (R12= 0.911, R22= 0.985) and cross-validation coefficient values (q2= 0.580, q22= 0.722). Based on the CoMFA contour maps, some key structural factors responsible for anticancer activity of these series of compounds were revealed. The results provide some useful theoretical references for understanding the mechanism of action, designing new curcumin-related compounds with anticancer activity and predicting their activities prior to synthesis. 展开更多
关键词 curcumin-related compounds QSAR COMFA anticancer activity PANC-1 HT-29
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