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miR-10b介导NKG2D调节脑胶质瘤细胞免疫效应的实验研究
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作者 袁岗 巨虎 +3 位作者 肖宗宇 李文辉 曹立新 惠超杰 《中国免疫学杂志》 CAS CSCD 北大核心 2024年第3期507-512,共6页
目的:观察微小核糖核酸-10b(miR-10b)对脑胶质瘤细胞免疫效应的调节作用并探讨其作用机制。方法:取人脑胶质瘤细胞U251进行培养和传代,获得处于对数生长期的细胞。按照1.0×105个/ml浓度制备细胞悬液,并设置对照组、过表达组、低表... 目的:观察微小核糖核酸-10b(miR-10b)对脑胶质瘤细胞免疫效应的调节作用并探讨其作用机制。方法:取人脑胶质瘤细胞U251进行培养和传代,获得处于对数生长期的细胞。按照1.0×105个/ml浓度制备细胞悬液,并设置对照组、过表达组、低表达组、空白组,每组6个复孔。对照组、过表达组、低表达组分别采用脂质体转染法转染阴性对照、miR-10b模拟物、miR-10b抑制剂,空白组予以等量无菌生理盐水。分离和培养1例健康志愿者外周血自然杀伤(NK)细胞。MTT法检测不同效靶比时NK细胞的杀伤活性;流式细胞仪检测各组NK细胞表面NK细胞激活受体(NKG2D)表达,并检测各组人脑胶质瘤细胞U251表面主要组织相容性复合物Ⅰ链相关基因A(MICA)、UL16结合蛋白2(ULBP2)、UL16结合蛋白3(ULBP3)表达。结果:对照组、过表达组、低表达组转染效率分别为(93.55±2.05)%、(95.67±3.14)%、(94.18±3.26)%;与对照组和空白组相比,过表达组miR-10b表达升高,低表达组miR-10b表达降低,差异均有统计学意义(P<0.05),且对照组和空白组miR-10b表达差异无统计学意义(P>0.05);与对照组和空白组相比,过表达组NK细胞不同效靶比杀伤活性均降低、NKG2D表达降低,低表达组NK细胞不同效靶比杀伤活性均增高、NKG2D表达增高,差异均有统计学意义(P<0.05),各组NK细胞杀伤活性均随效靶比增加而增高,差异均有统计学意义(P<0.05),且对照组与空白组相比,相同效靶比NK细胞杀伤活性、NKG2D表达差异均无统计学意义(P>0.05);与对照组和空白组相比,过表达组人脑胶质瘤细胞U251表面MICA、ULBP2、ULBP3表达均降低,低表达组人脑胶质瘤细胞U251表面MICA、ULBP2、ULBP3表达均增高,差异均有统计学意义(P<0.05),且对照组与空白组人脑胶质瘤细胞U251表面MICA、ULBP2、ULBP3表达差异均无统计学意义(P>0.05)。结论:抑制miR-10b表达能够增加NK细胞表面NKG2D和人脑胶质瘤细胞U251表面MICA、ULBP2、ULBP3表达,增强NK细胞对人脑胶质瘤细胞U251的杀伤活性。 展开更多
关键词 微小核糖核酸-10b 脑胶质瘤 NK细胞激活受体 主要组织相容性复合物Ⅰ链相关基因A UL16结合蛋白2 UL16结合蛋白3
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肺腺癌组织中前列腺素内过氧化物合酶2表达水平与表皮生长因子受体基因突变的相关性分析
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作者 闫琛 徐小艳 杨金花 《临床心身疾病杂志》 CAS 2024年第4期6-10,共5页
目的 分析肺腺癌组织中前列腺素内过氧化物合酶2(PTGS2)表达水平与表皮生长因子受体(EGFR)基因突变的相关性。方法 选取57例肺腺癌患者为研究对象,收集肺腺癌组织及其相应癌旁组织。采用实时荧光定量PCR(RT-PCR)法检测癌组织及癌旁组织... 目的 分析肺腺癌组织中前列腺素内过氧化物合酶2(PTGS2)表达水平与表皮生长因子受体(EGFR)基因突变的相关性。方法 选取57例肺腺癌患者为研究对象,收集肺腺癌组织及其相应癌旁组织。采用实时荧光定量PCR(RT-PCR)法检测癌组织及癌旁组织中PTGS2 mRNA表达水平;采用免疫组织化学法分析PTGS2蛋白表达;采用RT-PCR法检测癌组织及癌旁组织EGFR基因突变情况。分析肺腺癌患者临床病理参数与PTGS2 mRNA水平、EGFR基因突变情况的关系。采用Spearman秩相关分析探讨肺腺癌患者EGFR基因突变情况与PTGS2 mRNA水平的相关性。结果 57例肺腺癌患者中,5例癌旁组织EGFR基因突变型患者,其对应癌组织也均发生突变,且为同一突变类型。26例(45.61%)癌组织EGFR基因突变型患者,未发现双重突变,其中19外显子突变17例(29.82%),均为缺失突变;21外显子突变9例(15.79%),均为L858R点突变。癌组织中PTGS2mRNA表达水平、PTGS2蛋白阳性率及EGFR基因突变型比例高于癌旁组织,EGFR基因野生型比例低于癌旁组织(P<0.01)。肺腺癌患者性别、TNM分期、吸烟与PTGS2 mRNA表达水平、EGFR基因突变情况有关(P<0.05或0.01)。EGFR基因突变型PTGS2 mRNA表达水平高于EGFR基因野生型(P<0.01)。肺腺癌患者EGFR基因突变与PTGS2 mRNA表达水平呈正相关(r=0.512,P<0.01)。结论 肺腺癌患者癌组织中PTGS2mRNA表达水平及PTGS2蛋白阳性率升高,且与EGFR基因突变关系密切,二者可能共同影响疾病进程。 展开更多
关键词 肺腺癌 前列腺素内过氧化物合酶2 表皮生长因子受体 基因突变 相关性
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TRPM7和BTG2在宫颈癌组织中的表达及临床意义
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作者 周立飞 高跃丽 +4 位作者 耿欣 张静亚 耿飞龙 康非 王亚凡 《中国性科学》 2024年第10期100-105,共6页
目的探讨瞬时受体电位M7通道(TRPM7)和B细胞迁移基因2(BTG2)在宫颈癌组织中的表达及临床意义。方法选取2018年5月至2020年5月石家庄市妇幼保健院收治的110例宫颈癌患者作为研究对象,术中取其肿瘤组织及癌旁组织,根据随访情况分为预后良... 目的探讨瞬时受体电位M7通道(TRPM7)和B细胞迁移基因2(BTG2)在宫颈癌组织中的表达及临床意义。方法选取2018年5月至2020年5月石家庄市妇幼保健院收治的110例宫颈癌患者作为研究对象,术中取其肿瘤组织及癌旁组织,根据随访情况分为预后良好组与预后不良组。采用免疫组化法检测癌旁组织和肿瘤组织中TRPM7、BTG2蛋白表达,分析TRPM7、BTG2蛋白表达水平与患者临床病理特征的关系,比较预后不良组与预后良好组肿瘤组织中TRPM7、BTG2蛋白表达,采用Cox回归分析宫颈癌患者预后的影响因素,采用Kaplan-Meier曲线分析TRPM7、BTG2水平与宫颈癌患者预后的关系。结果与癌旁组织比较,肿瘤组织中TRPM7蛋白表达水平升高,BTG2蛋白表达水平降低(P<0.05)。TRPM7、BTG2蛋白表达水平与肿瘤分化程度、淋巴结转移、恶性肿瘤国际临床病理(TNM)分期有关(P<0.05)。与预后良好组比较,预后不良组肿瘤组织中TRPM7蛋白表达水平升高,BTG2蛋白表达水平降低(P<0.05)。TRPM7、TNM分期(Ⅲ期)、肿瘤低分化程度、淋巴结转移是宫颈癌患者预后的危险因素(P<0.05),BTG2是宫颈癌患者预后的保护因素(P<0.05)。TRPM7高表达组3年生存率低于TRPM7低表达组(P<0.05);BTG2高表达组3年生存率高于BTG2低表达组(P<0.05)。结论宫颈癌患者肿瘤组织中TRPM7蛋白表达上调,BTG2蛋白表达下调,均与宫颈癌预后有关。 展开更多
关键词 瞬时受体电位M7通道 B细胞迁移基因2 宫颈癌
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急性冠脉综合征患者血清sST2及NLRP3水平与介入术后无复流-慢血流的相关性分析
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作者 雷锐 殷实 李志 《现代检验医学杂志》 CAS 2024年第4期121-125,154,共6页
目的探讨急性冠脉综合征(acute coronary syndrome,Acs)患者血清可溶性生长刺激表达基因蛋白2(soluble growth stimulation expression gene 2 protein,sST2),核苷酸寡聚化结构域样受体热蛋白结构域相关蛋白3(nucleotide oligomerizatio... 目的探讨急性冠脉综合征(acute coronary syndrome,Acs)患者血清可溶性生长刺激表达基因蛋白2(soluble growth stimulation expression gene 2 protein,sST2),核苷酸寡聚化结构域样受体热蛋白结构域相关蛋白3(nucleotide oligomerization domain like receptor heat protein domain associated protein 3,NLRP3)水平与经皮冠状动脉介入治疗(percutaneous coronary intervention,PCI)术后无复流-慢血流的关系。方法选择2020年1月~2022年12月佳木斯市中心医院收治的97例急性冠脉综合征患者,所有患者均接受PCI治疗,根据术后无复流-慢血流发生情况分为无复流-慢血流组(n=20)和对照组(n=77)。术前检测血清sST2及NLRP3水平,分析影响急性冠脉综合征患者PCI术后无复流-慢血流的因素以及sST2,NLRP3预测急性冠脉综合征患者PCI术后无复流-慢血流的价值。结果无复流-慢血流组血清sST2(14.32±2.65 ng/ml vs 11.02±2.13 ng/ml),NLRP3(68.23±10.17 pg/ml vs 42.05±8.23 pg/ml)水平高于对照组,差异具有统计学意义(t=5.860,12.055,均P<0.05)。多因素Logistic回归分析显示高血栓负荷(OR:7.791,95%CI:2.834~21.421)、高水平sST2(OR=2.071,95%CI:1.146~3.743)、高水平NLRP3(OR=2.008,95%CI:1.228~3.284)是急性冠脉综合征患者PCI术后无复流-慢血流的危险因素(均P<0.05)。sST2,NLRP3诊断急性冠脉综合征患者PCI术后无复流-慢血流的临界值分别为12.91ng/ml,55.39 pg/ml,曲线下面积分别为0.737,0.686,联合sST2,NLRP3诊断急性冠脉综合征患者PCI术后无复流-慢血流的曲线下面积为0.907,高于单独诊断(Z=2.662,2.856,均P<0.05)。结论急性冠脉综合征患者血清sST2,NLRP3水平增高与PCI术后无复流-慢血流的发生有关,联合检测sST2和NLRP3可提高对术后无复流-慢血流的诊断效能。 展开更多
关键词 急性冠脉综合征 经皮冠状动脉介入术 无复流-慢血流 可溶性生长刺激表达基因蛋白2 核苷酸寡聚化结构域样受体热蛋白结构域相关蛋白3
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PXR基因单核苷酸多态性与2型糖尿病患病风险的关系
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作者 刘强 李素芳 +3 位作者 王楠 卢永霞 邓洁 何丽 《山东医药》 CAS 2024年第25期26-29,34,共5页
目的探讨孕烷X受体(PXR)基因单核苷酸多态性(SNP)与2型糖尿病(T2DM)患病风险的关系。方法选择T2DM患者285例(观察组)、同期体检健康的志愿者230例(对照组),采集所有研究对象空腹外周静脉血,提取基因组DNA,然后对PXR基因rs1523127、rs381... 目的探讨孕烷X受体(PXR)基因单核苷酸多态性(SNP)与2型糖尿病(T2DM)患病风险的关系。方法选择T2DM患者285例(观察组)、同期体检健康的志愿者230例(对照组),采集所有研究对象空腹外周静脉血,提取基因组DNA,然后对PXR基因rs1523127、rs3814055、rs6785049位点进行测序和基因分型;采用ELISA法检测血清PXR、葡萄糖转运体2(GLUT2)、葡萄糖激酶(GCK)。比较两组PXR基因rs1523127、rs3814055、rs6785049位点基因型及等位基因频率,以及血清PXR、GLUT2、GCK水平。分析PXR基因SNP与T2DM患病风险的关系。结果经Hardy-Weinberg遗传平衡检验,两组PXR基因不同位点基因型、等位基因频率均符合遗传平衡定律。两组PXR基因rs1523127、rs6785049位点基因型及等位基因频率比较差异均无统计学意义(P均>0.05)。观察组PXR基因rs3814055位点CT/TT基因型及T等位基因频率均高于对照组(P均<0.05),携带CT、TT基因型者罹患T2DM的优势比(OR)分别为携带CC基因型者的1.591、2.398倍,携带T等位基因者罹患T2DM的OR为携带C等位基因者的1.638倍。观察组血清PXR水平高于对照组,血清GLUT2、GCK水平低于对照组(P均<0.05)。T2DM患者PXR基因rs3814055位点CT/TT基因型者血清PXR水平高于CC基因型者,血清GLUT2、GCK水平低于CC基因型者(P均<0.05)。结论PXR基因rs3814055位点C等位基因突变为T等位基因能够增加其转录活性,抑制血清GLUT2、GCK水平,使其糖耐量受损,进而增加T2DM的患病风险。 展开更多
关键词 2型糖尿病 孕烷X受体基因 单核苷酸多态性 患病风险
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抑制SHP2和FGFR2调控RAS/ERK及PI3K/AKT通路治疗FGFR2融合胃癌
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作者 张玥 汪越 +3 位作者 魏禹焘 禹立霞 刘宝瑞 魏嘉 《中国肿瘤临床》 CAS CSCD 北大核心 2024年第14期703-709,共7页
目的:探究共抑制成纤维细胞生长因子受体2(fibroblast growth factor receptor 2,FGFR2)和Src同源2结构域的蛋白酪氨酸磷酸酶2(Src homology region 2-containing protein tyrosine phosphatase 2,SHP2)在FGFR2融合胃癌中的应用前景与... 目的:探究共抑制成纤维细胞生长因子受体2(fibroblast growth factor receptor 2,FGFR2)和Src同源2结构域的蛋白酪氨酸磷酸酶2(Src homology region 2-containing protein tyrosine phosphatase 2,SHP2)在FGFR2融合胃癌中的应用前景与作用机制。方法:构建过表达TACC2-FGFR2融合基因与对照慢病毒载体的人胃癌细胞系MKN45ACC2T-FGFR2、MKN45NC、NUGC4TACC2-FGFR2、NUGC4NC,分别用FGFR2抑制剂AZD4547、SHP2抑制剂SHP099或联药进行处理,通过细胞计数试剂盒(CCK-8)、划痕实验检测肿瘤细胞的增殖、迁移能力。以不同处理方式作用于MKN45TACC2-FGFR2、MKN45NC1 h或48 h后,采用Western blot法检测FGFR2、SHP2以及下游RAS/ERK、PI3K/AKT信号通路变化。结果:在MKN45TACC2-FGFR2与NUGC4TACC2-FGFR2中联用AZD4547与SHP099可以比单药更显著地抑制肿瘤细胞的增殖与迁移。药物处理1 h后,相较于AZD4547单药,联药在MKN45TACC2-FGFR2中进一步抑制了RAS/ERK、PI3K/AKT信号通路。药物处理48 h与1 h相比,AZD4547单药组中磷酸化FGFR与磷酸化SHP2出现了反馈性激活,且始终不能抑制RAS/ERK通路,但联药组可以持续地抑制上游的FGFR2、SHP2信号以及下游的RAS/ERK、PI3K/AKT通路。结论:共抑制FGFR2和SHP2可以通过下调RAS/ERK及PI3K/AKT通路有效抑制FGFR2融合胃癌,为FG-FR2融合突变胃癌患者带来新的治疗模式。 展开更多
关键词 胃癌 靶向治疗 融合基因 纤维细胞生长因子受体2 Src同源2结构域的蛋白酪氨酸磷酸酶2
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NDRG2调控IRE1α-XBP1介导内质网应激逆转ER+乳腺癌他莫昔芬耐药
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作者 王守莹 杜彦艳 +5 位作者 曹鹏 刘文宇 齐俊愉 石炜业 张春晓 周晓雷 《中国生物化学与分子生物学报》 CAS CSCD 北大核心 2024年第10期1409-1416,共8页
他莫昔芬(tamoxifen,TAM)作为雌激素受体阳性(estrogen receptor,ER+)乳腺癌的一线化疗药物使大多数患者受益,但原发性和继发性耐药问题严重影响临床治疗效果。深入研究ER+乳腺癌TAM耐药机制,改善治疗效果是当前亟待解决的问题。抑癌因... 他莫昔芬(tamoxifen,TAM)作为雌激素受体阳性(estrogen receptor,ER+)乳腺癌的一线化疗药物使大多数患者受益,但原发性和继发性耐药问题严重影响临床治疗效果。深入研究ER+乳腺癌TAM耐药机制,改善治疗效果是当前亟待解决的问题。抑癌因子NDRG2(N-myc downstream regulated gene 2,NDRG2)在肿瘤发生发展中发挥重要作用,但是否参与ER+乳腺癌TAM耐药尚不清楚。本研究旨在探明NDRG2在ER+乳腺癌TAM耐药中发挥的作用和机制。通过RT-PCR与免疫印迹分析对比TAM敏感型和耐药型ER+乳腺癌细胞发现,NDRG 2的mRNA转录水平和蛋白质翻译水平在TAM耐药细胞中表达显著下调,且与耐药能力负相关(P<0.001);CCK-8细胞毒性实验和软琼脂克隆形成实验证实,在耐药细胞中过表达NDRG2可显著降低TAM药物半抑制浓度IC 50和软琼脂克隆形成率(P<0.001),逆转耐药表型。分子机制上,X-box结合蛋白1(X-box binding protein 1,XBP1)mRNA剪切实验与内质网相关降解(endoplasmic-reticulum associated degradation,ERAD)报告蛋白的结果显示,过表达NDRG2可增强耐药细胞中剪切型XBP1s mRNA转录与ERAD报告蛋白CD3ε-YFP表达(P<0.001),引发耐药细胞内质网强应激反应;免疫印迹检测结果显示,过表达NDRG2可显著提高耐药细胞中内质网应激感受器肌醇需要激酶1α(inositol requiring enzyme 1,IRE1α)的磷酸化水平及其下游因子,例如内质网EIP辅助因子(endoplasmic reticulum-localized DnaJ 4,ERdj4)、PKR蛋白激酶的细胞抑制剂(cellular Inhibitor of the PKR protein kinase,P58 IPK)、α甘露糖苷酶样应激蛋白(er degradation enhancingαmannosidase likeprotein,EDEM)和蛋白质二硫键异构酶家族A成员5(protein disulfide isomerase family a member 5,PDIA5)的表达水平(P<0.001)。小鼠异种移植瘤研究进一步证实,在耐药细胞中过表达NDRG2可增强TAM治疗效果,显著抑制耐药移植瘤生长(P<0.001)。以上研究结果表明,通过提高耐药细胞中NDRG2表达,增强TAM治疗引发的内质网强烈应激,可逆转ER+乳腺癌细胞耐药性,改善TAM治疗效果。研究结果为解决ER+乳腺癌TAM耐药问题提供了新的思路和有价值的潜在药物靶点。 展开更多
关键词 雌激素受体阳性乳腺癌 N-myc下游调节基因2 他莫昔芬 耐药 内质网应激
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血清L/A、NRG-1、Tie-2水平与首发精神分裂症患者临床症状严重程度的相关性
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作者 戴璐 任学娟 殷旭园 《临床误诊误治》 CAS 2024年第7期60-66,共7页
目的探讨血清瘦素与脂联素比值(L/A)、神经调节蛋白-1(NRG-1)、血管生成素受体酪氨酸激酶-2(Tie-2)水平与首发精神分裂症患者临床症状严重程度的相关性及对认知障碍的评估价值。方法选择2021年5月—2023年5月收治的首发精神分裂症103例... 目的探讨血清瘦素与脂联素比值(L/A)、神经调节蛋白-1(NRG-1)、血管生成素受体酪氨酸激酶-2(Tie-2)水平与首发精神分裂症患者临床症状严重程度的相关性及对认知障碍的评估价值。方法选择2021年5月—2023年5月收治的首发精神分裂症103例为研究组,另选取同期正常健康体检志愿者103例为对照组。比较2组血清L/A、NRG-1、Tie-2水平,对比研究组认知障碍与认知正常患者临床症状[阳性和阴性症状量表(PANSS)、简明精神病评定量表(BPRS)评分]、血清L/A、NRG-1、Tie-2水平。分析血清L/A、NRG-1、Tie-2水平与临床症状严重程度的相关性及其联合检测对认知障碍的评估价值。结果研究组血清瘦素、L/A水平高于对照组,脂联素、NRG-1、Tie-2水平低于对照组(P<0.01)。研究组认知障碍患者PANSS各分量表评分及总分、BPRS量表各维度评分及总分、血清瘦素、L/A水平高于认知正常患者,脂联素、NRG-1、Tie-2水平低于认知正常患者(P<0.01)。血清L/A水平与PANSS各分量表评分及总分、BPRS量表各维度评分及总分呈正相关,NRG-1、Tie-2水平与PANSS各分量表评分及总分、BPRS量表各维度评分及总分呈负相关(P<0.01)。血清L/A、NRG-1、Tie-2评估认知障碍的曲线下面积(AUC)分别为0.764、0.708、0.755,最佳截断值分别为6.81、8.52 pg/mL、1962.62 pg/mL;血清L/A高表达、NRG-1、Tie-2低表达分别提示认知障碍发生风险增加5.237、6.172、4.538倍;L/A、NRG-1、Tie-2两两联合及三者联合评估认知障碍的AUC分别为0.882、0.868、0.876、0.932。结论血清L/A、NRG-1、Tie-2与首发精神分裂症患者临床症状严重程度显著相关,异常表达增加认知障碍发生风险,联合评估认知障碍的价值更为可靠。 展开更多
关键词 精神分裂症 认知障碍 瘦素 脂联素 神经调节蛋白-1 血管生成素受体酪氨酸激酶-2 阳性和阴性症状量表 简明精神病评定量表
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SNP Identification in α_(2A)-Adrenergic Receptor Gene in Chinese and the Effect on Gene Expression
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作者 袁栎 沈士弼 罗超权 《Journal of Nanjing Medical University》 2003年第6期277-282,共6页
Objective: To scan single nucleotide polymorphism ( SNP ) in Chinese alpha-2Aadrenergic receptor (α_(2A)-AR) gene and study the effects of the SNP on the gene expression.Methods: The complete sequence of α_(2A)-AR g... Objective: To scan single nucleotide polymorphism ( SNP ) in Chinese alpha-2Aadrenergic receptor (α_(2A)-AR) gene and study the effects of the SNP on the gene expression.Methods: The complete sequence of α_(2A)-AR gene was analyzed with automated DNA sequencer to scanSNPs. Genomic DNA was extracted from whole blood and a 239 bp fragment containing the G/Cpolymorphism was amplified with PCR using a pair of. specific primers. PCR-RFLP was used to performthe genotyping of the SNP at the site-1 296 bp of the people in the North of China. Electrophoresismobility shift assay ( EMSA ) was used to study the binding of the 390 bp fragments (- 1 414-1 025bp) with G or C at the site-1 296 bp and nuclear extracts . Results: In our study, two SNPs werefound in α_(2A)-AR gene. Allele frequencies of the SNP at the site-1 296 bp were 0.61 and 0.39 forG and C , and the genotype frequencies were 0.34 , 0.54 and 0.13 for GG, GC and CC respectively fromthe people in the North of China. In the EMSA, a specific binding appeared in the complex ofnuclear extracts and DNA with C at-1 296 bp . Conclusion: Two SNPs exist in α_(2A)-AR gene from thepeople in the North of China , and DNA fragment with allele C of the SNP at the site-1 296 bp couldbind with a specific protein, which could influence the gene expression. 展开更多
关键词 α_(2A)-adrenergic receptor single nucleotide polymorphism gene expression
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分化型甲状腺腺癌患者血清ADPN、adipoR2和HSP70水平的临床意义 被引量:1
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作者 熊睿 殷剑光 王华 《检验医学与临床》 CAS 2023年第10期1422-1426,共5页
目的探讨血清脂联素(ADPN)、脂联素受体2(adipoR2)和热休克蛋白70(HSP70)检测在分化型甲状腺腺癌中的临床价值。方法选择2020年8月至2022年6月在上海市嘉定区江桥医院/上海市第一人民医院嘉定分院进行手术治疗的甲状腺腺癌患者75例为甲... 目的探讨血清脂联素(ADPN)、脂联素受体2(adipoR2)和热休克蛋白70(HSP70)检测在分化型甲状腺腺癌中的临床价值。方法选择2020年8月至2022年6月在上海市嘉定区江桥医院/上海市第一人民医院嘉定分院进行手术治疗的甲状腺腺癌患者75例为甲状腺腺癌组。选择同期在上海市嘉定区江桥医院/上海市第一人民医院嘉定分院诊断为甲状腺腺瘤的患者和健康体检者分别纳入甲状腺腺瘤组(65例)和对照组(45例)。比较甲状腺腺癌组(术前)与甲状腺腺瘤组、对照组,以及甲状腺腺癌组术前与术后血清ADPN、adipoR2和HSP70水平。分析3项指标之间的相关性,以及血清ADPN、adipoR2和HSP70对甲状腺腺癌的临床诊断价值及其与临床病理特征的关系。结果甲状腺腺癌组(术前)血清ADPN和adipoR2水平明显低于甲状腺腺瘤组和对照组,而甲状腺腺瘤组明显低于对照组,差异有统计学意义(P<0.05);而甲状腺腺癌组(术前)血清HSP70水平明显高于甲状腺腺瘤组和对照组,甲状腺腺瘤组明显高于对照组,差异有统计学意义(P<0.05)。血清ADPN、adipoR2和HSP70联合检测诊断甲状腺腺癌的灵敏度为85.3%,特异度为83.1%,曲线下面积(AUC)为0.906,AUC明显高于ADPN(Z=4.391,P<0.001)、adipoR2(Z=3.253,P<0.001)和HSP70(Z=3.795,P<0.001)单独检测,而3项指标单独检测的AUC比较,差异无统计学意义(P>0.05)。不同肿瘤最大径、淋巴结转移情况和TNM分期的甲状腺腺癌患者ADPN、adipoR2、HSP70水平比较,差异有统计学意义(P<0.05)。不同年龄、性别的甲状腺腺癌患者血清ADPN、adipoR2和HSP70水平比较,差异无统计学意义(P>0.05)。结论血清ADPN、adipoR2和HSP70水平参与了甲状腺腺癌的发生、发展过程,联合检测ADPN、adipoR2和HSP70有助于提高甲状腺腺癌的诊断效能。 展开更多
关键词 脂联素 脂联素受体2 热休克蛋白70 甲状腺腺癌
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Transcriptome sequencing and experiments reveal the effect of formyl peptide receptor 2 on liver homeostasis
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作者 Hui Liu Ze-Yu Sun +7 位作者 Hua Jiang Xu-Dong Li Yong-Qiang Jiang Peng Liu Wen-Hua Huang Qing-Yu Lv Xiang-Lilan Zhang Rong-Kuan Li 《World Journal of Gastroenterology》 SCIE CAS 2023年第24期3793-3806,共14页
BACKGROUND Formyl peptide receptor 2(Fpr2)is an important receptor in host resistance to bacterial infections.In previous studies,we found that the liver of Fpr2-/-mice is the most severely damaged target organ in blo... BACKGROUND Formyl peptide receptor 2(Fpr2)is an important receptor in host resistance to bacterial infections.In previous studies,we found that the liver of Fpr2-/-mice is the most severely damaged target organ in bloodstream infections,although the reason for this is unclear.AIM To investigate the role of Fpr2 in liver homeostasis and host resistance to bacterial infections.METHODS Transcriptome sequencing was performed on the livers of Fpr2-/-and wild-type(WT)mice.Differentially expressed genes(DEGs)were identified in the Fpr2-/-and WT mice,and the biological functions of DEGs were analyzed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.Quantitative real time-polymerase chain reaction(qRT-PCR)and western blot(WB)analyses were used to further validate the expression levels of differential genes.Cell counting kit-8 assay was employed to investigate cell survival.The cell cycle detection kit was used to measure the distribution of cell cycles.The Luminex assay was used to analyze cytokine levels in the liver.The serum biochemical indices and the number of neutrophils in the liver were measured,and hepatic histopathological analysis was performed.RESULTS Compared with the WT group,445 DEGs,including 325 upregulated genes and 120 downregulated genes,were identified in the liver of Fpr2-/-mice.The enrichment analysis using GO and KEGG showed that these DEGs were mainly related to cell cycle.The qRT-PCR analysis confirmed that several key genes(CycA,CycB1,Cdc20,Cdc25c,and Cdk1)involved in the cell cycle had significant changes.The WB analysis confirmed a decrease in the expression of CDK1 protein.WRW4(an antagonist of Fpr2)could inhibit the proliferation of HepG2 cells in a concentration dependent manner,with an increase in the number of cells in the G0/G1 phase,and a decrease in the number of cells in the S phase.Serum alanine aminotransferase levels increased in Fpr2-/-mice.The Luminex assay measurements showed that interleukin(IL)-10 and chemokine(C-X-C motif)ligand(CXCL)-1 levels were significantly reduced in the liver of Fpr2-/-mice.There was no difference in the number of neutrophils,serum C-reactive protein levels,and liver pathology between WT and Fpr2-/-mice.CONCLUSION Fpr2 participates in the regulation of cell cycle and cell proliferation,and affects the expression of IL-10 and CXCL-1,thus playing an important protective role in maintaining liver homeostasis. 展开更多
关键词 Cell cycle Cell proliferation CDK1 Differentially expressed genes Formyl peptide receptor 2 RNA-sequencing
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Clinical significance of NOD2/CARD15 and Toll-like receptor 4 gene single nucleotide polymorphisms in inflammatory bowel disease 被引量:8
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作者 Luciana Rigoli Claudio Romano +12 位作者 Rosario Alberto Caruso Maria A Lo Presti Chiara Di Bella Vincenzo Procopio Giuseppina Lo Giudice Maria Amorini Giuseppe Costantino Maria D Sergi Caterina Cuppari Giovanna Elisa Calabrò Romina Gallizzi Carmelo Damiano Salpietro Walter Fries 《World Journal of Gastroenterology》 SCIE CAS CSCD 2008年第28期4454-4461,共8页
AIM: To evaluate the role of genetic factors in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC), we investigated the single nucleotide polymorphisms (SNPs) of NOD2/CARD15 (R702W, Gg08R an... AIM: To evaluate the role of genetic factors in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC), we investigated the single nucleotide polymorphisms (SNPs) of NOD2/CARD15 (R702W, Gg08R and L1007finsC), and Toll-like receptor 4 (TLR4) genes (D299G and T399I) in a selected inflammatory bowel disease (IBD) population coming from Southern Italy. METHODS: Allele and genotype frequencies of NOD2/ CARD15 (R702W, Gg08R and L1007finsC) and TLR4 (D299G and T399I) SNPs were examined in 133 CD patients, in 45 UC patients, and in 103 healthy controls. A genotype-phenotype correlation was performed. RESULTS: NOD2/CARD15 R702W mutation was significantly more frequent in CD (9.8%) than in controls (2.4%, P = 0.001) and in UC (2.3%, P = 0.03). No significant difference was found between UC patients and control group (P 〉 0.05). In CD and UC patients, no significant association with G908R variant was found. L1007finsC SNP showed an association with CD (9.8%) compared with controls (2.9%, P = 0.002) and UC patients (2.3%, P = 0.01). Moreover, in CD patients, G908R and L1007finsC mutations were significantly associated with different phenotypes compared to CD wild-type patients. No association of IBD with the TLR4 SNPs was found in either cohort (allele frequencies: D299G-controls 3.9%, CD 3.7%, UC 3.4%, P 〉 0.05; T399I-controls 2.9%, CD 3.0%, UC 3.4%, P 〉 0.05). CONCLUSION: These findings confirm that, in our IBD patients selected from Southern Italy, the NOD2/ CARD15, but not TLR4 SNPs, are associated with increased risk of CD. 展开更多
关键词 Crohn's disease Ulcerative colitis NOD2/ CARD15 gene Toll-like receptor 4 gene Single nucleotide polymorphisms
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The 5-HT2c receptor gene Cys23Ser polymorphism influences the intravaginal ejaculation latency time in Dutch Caucasian men with lifelong premature ejaculation 被引量:3
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作者 Paddy KC Janssen Ron van Schaik +1 位作者 Berend Olivier Marcel D Waldinger 《Asian Journal of Andrology》 SCIE CAS CSCD 2014年第4期607-610,共4页
It has been postulated that the persistent short intravaginal ejaculation latency time (IELT) of men with lifelong premature ejaculation (LPE) is related to 5-hydroxytryptamine (HT)2c receptor functioning. The a... It has been postulated that the persistent short intravaginal ejaculation latency time (IELT) of men with lifelong premature ejaculation (LPE) is related to 5-hydroxytryptamine (HT)2c receptor functioning. The aim of this study was to investigate the relationship of Cys23Ser 5-HT2c receptor gene polymorphism and the duration of IELT in men with LPE. Therefore, a prospective study was conducted in 64 Dutch Caucasian men with LPE. Baseline IELT during coitus was assessed by stopwatch over a 1-month period. All men were genotyped for Cys23Ser 5-HT2c receptor gene polymorphism. Allele frequencies and genotypes of Cys and Ser variants of 5-HT2c receptor gene polymorphism were determined. Association between Cys/Cys and Ser/Ser genotypes and the natural logarithm of the IELT in men with LPE were.investigated. As a result, the geometric mean, median and natural mean IELT were 25.2, 27.0, 33.9s, respectively. Of all men, 20.0%, 10.8%, 23.1% and 41.5% ejaculated within 10, 10-20, 20-30 and 30-60s after vaginal penetration. Of the 64 men, the Cys/Cys and Ser/Ser genotype frequency for the Cys23Ser polymorphism of the 5-HT2c receptor gene was 81% and 19%, respectively. The geometric mean IELT of the wildtypes (Cys/Cys) is significantly lower (22.6s; 95% CI 18.3-27.8s) than in male homozygous mutants (Ser/Ser) (40.4s; 95% CI 20.3-80.4s) (P = 0.03). It is concluded that Cys23Ser 5-HT2c receptor gene polymorphism is associated with the IELT in men with LPE. Men with Cys/Cys genotype have shorter IELTs than men with Ser/Ser genotypes. 展开更多
关键词 5-HT2c receptor gene Cys23Ser polymorphism intravaginal ejaculation latency time lifelong premature ejaculation
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Effect of Dai-Saiko-To (Da-Chai-Hu-Tang) on LDL-Receptor Gene Expression in Human Hepatoma Cell Line (HepG2) 被引量:1
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作者 Akira Iizuka Fumihiko Yoshie +5 位作者 Sakae Amagaya Takaaki Yasuda Maki Iizuka Haruyo Yamaguchi Seiji Nagumo Kazuo Kondo 《American Journal of Plant Sciences》 2013年第2期454-459,共6页
We previously reported that Dai-saiko-to (Da-Chai-Hu-Tang), a traditional Japanese kampo medicine, increased LDL receptor mRNA expression in the liver of the hypercholesterolemic rabbits. In this study, we focused on ... We previously reported that Dai-saiko-to (Da-Chai-Hu-Tang), a traditional Japanese kampo medicine, increased LDL receptor mRNA expression in the liver of the hypercholesterolemic rabbits. In this study, we focused on LDL receptor gene expression in a human hepatoma cell line (HepG2) treated with Dai-saiko-to extract and the extracts of eight herbs presented in Dai-saiko-to. Dai-saiko-to extract significantly increased LDL receptor gene and SREBP2 gene expression compared with the control. The extracts of four herbs, Bupleurum root, Pinellia tuber, Scutellaria root and Peony root significantly increased the LDL receptor gene expression. Whereas, Jujube, Immature orange, Ginger and Rhubarb extracts did not change the gene expression. These results suggest that Dai-saiko-to increased the expression of the cholesterol transport gene (LDL receptor) regulated by SREBP2 gene in the human hepatoma cell line. The pharmacological activity of Dai-saiko-to against hypercholesterolemia and atheromatous lesions related for these four herbal components. 展开更多
关键词 KAMPO Dai-Saiko-To LDL receptor gene Expression HEPG2
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The human δ2 glutamate receptor gene is not mutated in patients with spinocerebellar ataxia
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作者 Jinxiang Huang Aiyu Lin +1 位作者 Haiyan Dong Chaodong Wang 《Neural Regeneration Research》 SCIE CAS CSCD 2014年第10期1068-1074,共7页
The human glutamate receptor delta 2 gene (GRID2) shares 90%homology with the orthologous mouse gene. The mouse Grid2 gene is involved with functions of the cerebellum and sponta-neous mutation of Grid2 leads to a s... The human glutamate receptor delta 2 gene (GRID2) shares 90%homology with the orthologous mouse gene. The mouse Grid2 gene is involved with functions of the cerebellum and sponta-neous mutation of Grid2 leads to a spinocerebellar ataxia-like phenotype. To investigate whether such mutations occur in humans, we screened for mutations in the coding sequence of GRID2 in 24 patients with familial or sporadic spinocerebellar ataxia and in 52 normal controls. We de-tected no point mutations or insertion/deletion mutations in the 16 exons of GRID2. However, a polymorphic 4 nucleotide deletion (IVS5-121_-118 GAGT) and two single nucleotide polymor-phisms (c.1251G〉T and IVS14-63C〉G) were identiifed. The frequency of these polymorphisms was similar between spinocerebellar ataxia patients and normal controls. These data indicate that spontaneous mutations do not occur in GRID2 and that the incidence of spinocerebellar ataxia in humans is not associated with GRID2 mutation or polymorphisms. 展开更多
关键词 nerve regeneration spinocerebellar ataxia δ2 glutamate receptor MUTATION gene polymorphism single nucleotide polymorphism NSFC grant neural regeneration
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Genetic variations of beta 2-adrenergic receptor gene are associated with essential hypertension in Xinjiang Kazakans
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作者 Zhi-Tao Yan Nan-Fang Li Jin Yang Ling Zhou Hui Liu Qin Luo 《Journal of Geriatric Cardiology》 SCIE CAS CSCD 2010年第1期52-57,共6页
Objective The aims of the present study were to investigate the associations of 46 A〉G, 79 C〉G, 491 C〉T and 659 C〉G genetic variants of the human beta 2-adrenergic receptor (β2-AR), ADRB2, gene with essential h... Objective The aims of the present study were to investigate the associations of 46 A〉G, 79 C〉G, 491 C〉T and 659 C〉G genetic variants of the human beta 2-adrenergic receptor (β2-AR), ADRB2, gene with essential hypertension (EH) in Xinjiang Kazakans population.Methods A gender-matched case-control (271 hypertensive cases and 267 normotensive controls) study was used to investigate the associations of the four variations in the coding region of ADRB2 with EH. The genotypes of the variants were identified by the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) methods. Results 46 A〉G, 79 C〉G and 659 C〉G polymorphisms were common in the Kazakan population, but 491 C〉T was a mutation (frequency ofT allele was only 0.003) and only found in EH group. The fxequency distributions of genotypes and alleles for 659 C〉G between the EH and control groups was significantly different (P〈0.05), while those for 46 A〉G and 79 C〉G polymorphisms were not statistically different. Logistic regression analysis suggested that the G allele of 659 C〉G polymorphism was a risk factor for hypertension (minor allele vs common homo; odds ratio, 13.240, 95% CI, 4.052-43.274; P〈0.05). Covariance analysis showed that systolic and diastolic blood pressure levels in GG+CG group of 659 C〉G were significantly higher than those in the CC group, but no significant difference of blood pressure were found between common homo and minor allele for 46 A〉G and 79C〉G polymorphisms. Haplotype analysis showed that two hyplotypes, HI: 46A-79C-491C-523C(48%)and H5:46A-79C-491C-659G, were associated with EH.Conelusion ADRB2 genetic variants may play independent roles in the molecular genetic mechanism of EH in Xinjiang Kazakans population (d Geriatr Cardio12010; 7:52-57). 展开更多
关键词 β2-adrenergic receptor gene variant essential hypertension HAPLOTYPE Xinjiang Kazakan
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人乳头瘤病毒感染对乳腺癌患者p53、bcl-2和c-erbB-2表达及预后的影响 被引量:5
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作者 李娟 王建成 陈小红 《中国肿瘤外科杂志》 CAS 2023年第1期76-79,共4页
目的探讨人乳头瘤病毒(HPV)感染对乳腺癌患者p53、B淋巴细胞瘤2基因(bcl-2)和人类表皮生长因子受体2(c-erbB-2)的表达及预后的影响。方法选取2017年2月至2020年1月在首都医科大学附属北京友谊医院行乳腺癌根治术的乳腺癌患150例,原位杂... 目的探讨人乳头瘤病毒(HPV)感染对乳腺癌患者p53、B淋巴细胞瘤2基因(bcl-2)和人类表皮生长因子受体2(c-erbB-2)的表达及预后的影响。方法选取2017年2月至2020年1月在首都医科大学附属北京友谊医院行乳腺癌根治术的乳腺癌患150例,原位杂交法检测乳腺癌患者HPV感染情况,按照是否有HPV感染将150例患者分成HPV感染组86例和未感染组64例。采用免疫组化法检测乳腺癌组织中p53、bcl-2和c-erbB-2蛋白表达情况。收集患者的临床特征并分析HPV感染及p53、bcl-2、c-erbB-2蛋白阳性表达与临床特征的关系;随访患者术后2年的生存情况。结果150例乳腺癌患者中HPV感染86例,感染率57.33%。HPV感染组p53、c-erbB-2阳性表达率高于未感染组,bcl-2阳性表达率低于未感染组(P<0.05);HPV感染与国际妇产科协会(FIGO)肿瘤分期有关,p53阳性表达淋巴转移有关,bcl-2阳性表达与FIGO分期有关,c-erbB-2阳性表达与组织学分级、淋巴转移有关(P<0.05)。HPV感染组2年生存率低于未感染组[82.55%(71/86)vs.93.75%(60/64),χ2=4.155,P=0.042]。结论乳腺癌患者HPV感染率较高,HPV感染可能通过促进c-erbB-2和p53表达以及抑制bcl-2表达,促进乳腺癌进展并导致患者预后不良。 展开更多
关键词 人乳头瘤病毒 乳腺癌 B淋巴细胞瘤2基因 人类表皮生长因子受体2 p53
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Congenital nephrogenic diabetes insipidus arginine vasopressin receptor 2 gene mutation at new site:A case report
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作者 Lu-Lu Yang Yan Xu +3 位作者 Jian-Li Qiu Qian-Yi Zhao Man-Man Li Hui Shi 《World Journal of Clinical Cases》 SCIE 2022年第36期13443-13450,共8页
BACKGROUND Congenital nephrogenic diabetes insipidus(CNDI)is a rare hereditary disorder.It is associated with mutations in the arginine vasopressin receptor 2(AVPR2)gene and aquaporin 2(AQP2)gene,and approximately 270... BACKGROUND Congenital nephrogenic diabetes insipidus(CNDI)is a rare hereditary disorder.It is associated with mutations in the arginine vasopressin receptor 2(AVPR2)gene and aquaporin 2(AQP2)gene,and approximately 270 different mutation sites have been reported for AVPR2.Therefore,new mutations and new manifestations are crucial to complement the clinical deficiencies in the diagnosis of this disease.We report a case of a novel AVPR2 gene mutation locus and a new clinical manifestation.CASE SUMMARY We describe the case of a 48-d-old boy who presented with recurrent fever and diarrhea 5 d after birth.Laboratory tests showed electrolyte disturbances and low urine specific gravity,and imaging tests showed no abnormalities.Genetic testing revealed a novel X-linked recessive missense mutation,c.283(exon 2)C>T(p.P95S).This mutation results in the substitution of a proline residue with a serine residue in the AVPR2 protein sequence.The diagnosis of CNDI was confirmed based on the AVPR2 gene mutation.The treatment strategy for this patient was divided into two stages,including physical cooling supplemented with appropriate amounts of water in the early stage and oral hydrochlorothiazide(1-2 mg/kg)after a clear diagnosis.After follow-up of one and a half years,the patient gradually improved.CONCLUSION AVPR2 gene mutations in new loci and new clinical symptoms help clinicians understand this disease and shorten the diagnosis cycle. 展开更多
关键词 Congenital nephrogenic diabetes insipidus Arginine vasopressin receptor 2 gene mutation New site DIARRHEA Case report
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肾上腺素β受体基因、G蛋白基因和CYP2D6基因多态性对美托洛尔导致脂代谢异常的影响 被引量:2
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作者 刘泽 郝言 +1 位作者 张薇 徐辉 《中国医院用药评价与分析》 2023年第6期693-695,700,共4页
目的:研究肾上腺素β受体基因、G蛋白基因和CYP2D6基因多态性对美托洛尔导致脂代谢异常的影响。方法:选取2019年10月至2022年10月该院收治的初治高血压患者120例,检测β_(1)受体基因Ser49Gly、Gly389Arg多态;β_(2)受体基因Arg16Gly、Gl... 目的:研究肾上腺素β受体基因、G蛋白基因和CYP2D6基因多态性对美托洛尔导致脂代谢异常的影响。方法:选取2019年10月至2022年10月该院收治的初治高血压患者120例,检测β_(1)受体基因Ser49Gly、Gly389Arg多态;β_(2)受体基因Arg16Gly、Gln27Glu多态;β3受体基因Trp64Arg多态;代谢酶基因CYP2D6*10的P34S多态;G蛋白基因GNB3 C825T多态。比较美托洛尔单药治疗3个月后不同表型总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白(LDL)和高密度脂蛋白(HDL)水平变化。结果:各基因位点不同基因型患者的年龄、性别、体重指数、基线TC和基线TG等指标比较,差异均无统计学意义(P>0.05)。治疗3个月后,β_(2)肾上腺素受体基因Arg16Gly患者的TG水平升高,其中Gly/Gly型患者升高幅度最高,Arg/Gly型次之,二者均高于Arg/Arg型,差异有统计学意义(P<0.05)。结论:β_(2)肾上腺素受体Arg16Gly多态与美托洛尔引起的血浆TG水平升高相关,携带2个G等位基因会导致服药后血脂水平明显升高。 展开更多
关键词 基因多态性 美托洛尔 血脂 三酰甘油 Β2肾上腺素受体
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Relationship Research of PPAR-γ Gene Polymorphisms with Adiponectin and Leptin in Type 2 Diabetes Mellitus
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作者 Jia Feng Shujin Wang +3 位作者 Hong Zuo Xufeng Liu Guohong Li Niou Yu 《Journal of Clinical and Nursing Research》 2020年第4期118-122,共5页
Objective:To investigate the peroxisome proliferator-activated receptor-γ (peroxisome)in patients with type 2 diabetes mellitus.Proliferators-activated receptors-γ ,PPARs-γ (γ )gene.polymorphisms about serum lipof... Objective:To investigate the peroxisome proliferator-activated receptor-γ (peroxisome)in patients with type 2 diabetes mellitus.Proliferators-activated receptors-γ ,PPARs-γ (γ )gene.polymorphisms about serum lipofuscin and leptin.Methods:One humdred and twenty patients with type 2 diabetes admitted to our hospital from June 2015 to June 2018 were selected.The patients were divided into an obese group and a non-obese group of 60 patients each according to their waist circumference.A polymerase chain reaction-length polymorphism protocol was implemented in all patients to explore the PPAR-γ gene polymorphism and blood glucose,lipid,adiponectin and leptin levels were measured in both groups.Results:PPAR-γ gene polymorphisms in type 2 diabetic patients were dominated by wild-type homozygous;The levels of total cholesterol,triglyceride and LDL cholesterol in the obese group were significantly higher than those in the non-obese group,while the levels of HDL cholesterol were lower than those in the non-obese group.There is significant difference in comparison between groups(P<0.05)Those canrying the A alele had a significant lipid disorder profile and decreased adiponectin levels.Conclusions:PPAR-γ gene polymorphisms in type 2 diabetes are not significantly associated with adiponectin and leptin,and only in the obese group,the patients with the Allele A showed significant dyslipidemia and a declining trend of adiponectin levels. 展开更多
关键词 Type 2 diabetes Peroxisome proliferator-activated receptor gene polymophism adiponectin LEPTIN
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