目的探究盆底功能障碍性疾病(pelvic floor dysfunctional disease,PFD)患者血清微小RNA(microRNA,miR)-4429和微小RNA(microRNA,miR)-19-3p水平表达及意义。方法选取2021年6月~2022年6月衡水市第二人民医院收治的PFD患者90例作为PFD组...目的探究盆底功能障碍性疾病(pelvic floor dysfunctional disease,PFD)患者血清微小RNA(microRNA,miR)-4429和微小RNA(microRNA,miR)-19-3p水平表达及意义。方法选取2021年6月~2022年6月衡水市第二人民医院收治的PFD患者90例作为PFD组,分为盆腔器官脱垂(pelvic organ prolapse,POP)组(n=50)、压力性尿失禁(stress urinary incontinence,SUI)组(n=25)和POP并发SUI组(n=15);并选取同期在衡水市第二人民医院检查的健康女性80例为对照组。比较对照组与PFD组分娩方式、既往流产史、PFD家族史等一般资料。比较各组血清miR-4429和miR-19-3p水平。受试者工作特征(receiver operating characteristic,ROC)曲线分析血清miR-4429,miR-19-3p水平对PFD的诊断价值。Logistic回归分析影响PFD的因素。配对样本t检验比较PFD治疗前后血清miR-4429,miR-19-3p水平变化。结果PFD组在分娩方式、既往流产史、PFD家族史方面与对照组相比差异均有统计学意义(t=4.415,6.444,4.707,均P<0.05)。PFD组血清miR-4429水平较对照组降低(0.71±0.19 vs 1.00±0.25),miR-19-3p水平较对照组升高(1.44±0.35 vs 1.01±0.28),差异具有统计学意义(t=8.927,8.772,均P<0.05)。POP组和SUI组血清miR-4429水平高于POP并发SUI组(0.73±0.22,0.74±0.16 vs 0.59±0.16),POP组和SUI组血清miR-19-3p水平低于POP并发SUI组(1.35±0.39,1.41±0.31 vs 1.77±0.56),差异具有统计学意义(t=3.531,3.411;5.003,3.865,均P<0.05)。ROC曲线分析显示,miR-4429,miR-19-3p可辅助评估是否发生PFD的曲线下面积(area under curve,AUC)分别为0.805,0.825,二者联合检测的AUC为0.865。多因素分析显示,miR-19-3p是影响PFD的危险因素,miR-4429是保护因素。经过治疗发现,PFD患者血清miR-4429水平升高(0.93±0.23 vs 0.71±0.19),miR-19-3p水平降低(1.12±0.29 vs 1.44±0.35),差异具有统计学意义(t=6.996,6.679,均P<0.05)。结论PFD患者血清miR-4429水平降低,miR-19-3p水平升高,血清miR-4429,miR-19-3p水平与PFD疾病的发生发展密切相关,可作为预测PFD的评估指标。展开更多
The cancer cell metastasis is a major death reason for patients with non-small cell lung cancer(NSCLC).Although researchers have disclosed that interleukin 17(IL-17)can increase matrix metalloproteinases(MMPs)inductio...The cancer cell metastasis is a major death reason for patients with non-small cell lung cancer(NSCLC).Although researchers have disclosed that interleukin 17(IL-17)can increase matrix metalloproteinases(MMPs)induction causing NSCLC cell metastasis,the underlying mechanism remains unclear.In the study,we found that IL-17 receptor A(IL-17RA),p300,p-STAT3,Ack-STAT3,and MMP19 were up-regulated both in NSCLC tissues and NSCLC cells stimulated with IL-17.p300,STAT3 and MMP19 overexpression or knockdown could raise or reduce IL-17-induced p-STAT3,Ack-STAT3 and MMP19 level as well as the cell migration and invasion.Mechanism investigation revealed that STAT3 and p300 bound to the same region(−544 to−389 nt)of MMP19 promoter,and p300 could acetylate STAT3-K631 elevating STAT3 transcriptional activity,p-STAT3 or MMP19 expression and the cell mobility exposed to IL-17.Meanwhile,p300-mediated STAT3-K631 acetylation and its Y705-phosphorylation could interact,synergistically facilitating MMP19 gene transcription and enhancing cell migration and invasion.Besides,the animal experiments exhibited that the nude mice inoculated with NSCLC cells by silencing p300,STAT3 or MMP19 gene plus IL-17 treatment,the nodule number,and MMP19,Ack-STAT3,or p-STAT3 production in the lung metastatic nodules were all alleviated.Collectively,these outcomes uncover that IL-17-triggered NSCLC metastasis involves up-regulating MMP19 expression via the interaction of STAT3-K631 acetylation by p300 and its Y705-phosphorylation,which provides a new mechanistic insight and potential strategy for NSCLC metastasis and therapy.展开更多
BACKGROUND Gastric cancer(GC)is a common malignant tumor,long non-coding RNA and microRNA(miRNA)are important regulators that affect tumor proliferation,metastasis and chemotherapy resistance,and thus participate in t...BACKGROUND Gastric cancer(GC)is a common malignant tumor,long non-coding RNA and microRNA(miRNA)are important regulators that affect tumor proliferation,metastasis and chemotherapy resistance,and thus participate in tumor progression.CASC19 is a new bio-marker which can promote tumor invasion and metastasis.However,the mechanism by which CASC19 affects the progression of GC through miRNA is not clear.AIM To explore the role of the CASC19/miR-491-5p/HMGA2 regulatory axis in GC.METHODS To explore the expression and prognosis of CASC19 in GC through clinical samples,and investigate the effects of inhibiting CASC19 on the proliferation,migration,invasion and other functions of GC cells through cell counting Kit-8(CCK-8),ethynyldeoxyuridine,Wound healing assay,Transwell,Western blot and flow cytometry experiments.The effect of miR-491-5p and HMGA2 in GC were also proved.The regulatory relationship between CASC19 and miR-491-5p,miR-491-5p and HMGA2 were validated through Dual-luciferase reporter gene assay and reverse transcription PCR.Then CCK-8,Transwell,Wound healing assay,flow cytometry and animal experiments verify the role of CASC19/miR-491-5p/HMGA2 regulatory axis.RESULTS The expression level of CASC19 is related to the T stage,N stage,and tumor size of patients.Knockdown of the expression of CASC19 can inhibit the ability of proliferation,migration,invasion and EMT conversion of GC cells,and knocking down the expression of CASC19 can promote the apoptosis of GC cells.Increasing the expression of miR-491-5p can inhibit the proliferation of GC cells,miR-491-5p mimics can inhibit EMT conversion,and promote the apoptosis of GC cells,while decreasing the expression of miR-491-5p can promote the proliferation and EMT conversion and inhibit the apoptosis of GC cells.The expression of HMGA2 in GC tissues is higher than that in adjacent tissues.At the same time,the expression level of HMGA2 is related to the N and T stages of the patients.Reducing the level of HMGA2 can promote cell apoptosis and inhibit the proliferation of GC cells.Cell experiments and animal experiments have proved that CASC19 can regulates the expression of HMGA2 through miR-491-5p,thereby affecting the biological functions of GC.CONCLUSION CASC19 regulates the expression of HMGA2 through miR-491-5p to affect the development of GC.This axis may serve as a potential biomarker and therapeutic target of GC.展开更多
目的分析不同民族缺血性卒中患者对基于快速细胞色素P450酶家族2亚家族C成员19(cytochrome P450 family 2 subfamily C member 19,CYP2C19)基因检测指导抗血小板治疗方案的反应差异。方法前瞻性连续纳入2023年1—7月在南宁市第三人民医...目的分析不同民族缺血性卒中患者对基于快速细胞色素P450酶家族2亚家族C成员19(cytochrome P450 family 2 subfamily C member 19,CYP2C19)基因检测指导抗血小板治疗方案的反应差异。方法前瞻性连续纳入2023年1—7月在南宁市第三人民医院住院治疗的汉族(对照组)和壮族(试验组)非心源性轻型缺血性卒中患者。所有患者在CYP2C19基因检测结果指导下进行抗血小板治疗:对于基因表型为氯吡格雷快代谢的患者,抗血小板药物选择硫酸氢氯吡格雷;对于中间代谢或慢代谢的患者,抗血小板药物选择阿司匹林肠溶片或替格瑞洛片。随访90 d,记录mRS评分、日常生活能力量表(activity of daily living scale,ADL)评分、NIHSS评分以及90 d缺血性卒中累积复发率。结果共纳入1036例缺血性卒中患者,对照组743例,CYP2C19基因检测结果显示,氯吡格雷快代谢、中间代谢、慢代谢型患者分别为299例(40.24%)、345例(46.43%)和99例(13.32%)。试验组293例,氯吡格雷快代谢、中间代谢、慢代谢型患者分别为107例(36.52%)、161例(54.95%)和25例(8.53%)。两组不同CYP2C19基因表型的比例差异无统计学意义。随访90 d,两组间的mRS评分、ADL评分、NI HSS评分差异无统计学意义。对照组和试验组的90 d缺血性卒中累积复发率分别为5.52%(41/743)和5.12%(15/293),差异无统计学意义。结论基于CYP2C19基因检测指导的抗血小板治疗在汉族和壮族的缺血性卒中患者人群中,预防缺血性卒中复发的效果相似。展开更多
本文报道了一例老年女性院内卒中患者的临床诊疗过程。该患者于肛肠外科手术后2 d突发急性缺血性卒中,经影像学检查确诊为右侧颈内动脉起始部重度狭窄。在接受了1个月的卒中二级预防药物治疗后,择期行血管内治疗。术前该患者进行了快速...本文报道了一例老年女性院内卒中患者的临床诊疗过程。该患者于肛肠外科手术后2 d突发急性缺血性卒中,经影像学检查确诊为右侧颈内动脉起始部重度狭窄。在接受了1个月的卒中二级预防药物治疗后,择期行血管内治疗。术前该患者进行了快速细胞色素P450酶家族2亚家族C成员19(cytochrome P450 family 2 subfamily C member 19,CYP2C19)基因检测,结果为中间代谢型,提示应用氯吡格雷的效果可能不佳。基于这一检测结果调整抗血小板治疗方案,选择替格瑞洛联合阿司匹林作为替代治疗。治疗后,患者病情稳定,预后较好。本病例报道提示,在非轻型卒中患者中,快速CYP2C19基因检测可帮助选择抗血小板治疗策略,改善患者预后。展开更多
文摘目的探究盆底功能障碍性疾病(pelvic floor dysfunctional disease,PFD)患者血清微小RNA(microRNA,miR)-4429和微小RNA(microRNA,miR)-19-3p水平表达及意义。方法选取2021年6月~2022年6月衡水市第二人民医院收治的PFD患者90例作为PFD组,分为盆腔器官脱垂(pelvic organ prolapse,POP)组(n=50)、压力性尿失禁(stress urinary incontinence,SUI)组(n=25)和POP并发SUI组(n=15);并选取同期在衡水市第二人民医院检查的健康女性80例为对照组。比较对照组与PFD组分娩方式、既往流产史、PFD家族史等一般资料。比较各组血清miR-4429和miR-19-3p水平。受试者工作特征(receiver operating characteristic,ROC)曲线分析血清miR-4429,miR-19-3p水平对PFD的诊断价值。Logistic回归分析影响PFD的因素。配对样本t检验比较PFD治疗前后血清miR-4429,miR-19-3p水平变化。结果PFD组在分娩方式、既往流产史、PFD家族史方面与对照组相比差异均有统计学意义(t=4.415,6.444,4.707,均P<0.05)。PFD组血清miR-4429水平较对照组降低(0.71±0.19 vs 1.00±0.25),miR-19-3p水平较对照组升高(1.44±0.35 vs 1.01±0.28),差异具有统计学意义(t=8.927,8.772,均P<0.05)。POP组和SUI组血清miR-4429水平高于POP并发SUI组(0.73±0.22,0.74±0.16 vs 0.59±0.16),POP组和SUI组血清miR-19-3p水平低于POP并发SUI组(1.35±0.39,1.41±0.31 vs 1.77±0.56),差异具有统计学意义(t=3.531,3.411;5.003,3.865,均P<0.05)。ROC曲线分析显示,miR-4429,miR-19-3p可辅助评估是否发生PFD的曲线下面积(area under curve,AUC)分别为0.805,0.825,二者联合检测的AUC为0.865。多因素分析显示,miR-19-3p是影响PFD的危险因素,miR-4429是保护因素。经过治疗发现,PFD患者血清miR-4429水平升高(0.93±0.23 vs 0.71±0.19),miR-19-3p水平降低(1.12±0.29 vs 1.44±0.35),差异具有统计学意义(t=6.996,6.679,均P<0.05)。结论PFD患者血清miR-4429水平降低,miR-19-3p水平升高,血清miR-4429,miR-19-3p水平与PFD疾病的发生发展密切相关,可作为预测PFD的评估指标。
基金National Natural Science Foundation of China(Grants Numbers 81902878 and 81971468).
文摘The cancer cell metastasis is a major death reason for patients with non-small cell lung cancer(NSCLC).Although researchers have disclosed that interleukin 17(IL-17)can increase matrix metalloproteinases(MMPs)induction causing NSCLC cell metastasis,the underlying mechanism remains unclear.In the study,we found that IL-17 receptor A(IL-17RA),p300,p-STAT3,Ack-STAT3,and MMP19 were up-regulated both in NSCLC tissues and NSCLC cells stimulated with IL-17.p300,STAT3 and MMP19 overexpression or knockdown could raise or reduce IL-17-induced p-STAT3,Ack-STAT3 and MMP19 level as well as the cell migration and invasion.Mechanism investigation revealed that STAT3 and p300 bound to the same region(−544 to−389 nt)of MMP19 promoter,and p300 could acetylate STAT3-K631 elevating STAT3 transcriptional activity,p-STAT3 or MMP19 expression and the cell mobility exposed to IL-17.Meanwhile,p300-mediated STAT3-K631 acetylation and its Y705-phosphorylation could interact,synergistically facilitating MMP19 gene transcription and enhancing cell migration and invasion.Besides,the animal experiments exhibited that the nude mice inoculated with NSCLC cells by silencing p300,STAT3 or MMP19 gene plus IL-17 treatment,the nodule number,and MMP19,Ack-STAT3,or p-STAT3 production in the lung metastatic nodules were all alleviated.Collectively,these outcomes uncover that IL-17-triggered NSCLC metastasis involves up-regulating MMP19 expression via the interaction of STAT3-K631 acetylation by p300 and its Y705-phosphorylation,which provides a new mechanistic insight and potential strategy for NSCLC metastasis and therapy.
基金Supported by Natural Science Foundation of Anhui Province,No.2108085QH337Research Fund of Anhui Medical University,No.2022xkj156+1 种基金Key Projects of Anhui Provincial Department of Education,No.2023AH053330Anhui Institute of Translational Medicine Research Fund,No.2022zhyx-C88.
文摘BACKGROUND Gastric cancer(GC)is a common malignant tumor,long non-coding RNA and microRNA(miRNA)are important regulators that affect tumor proliferation,metastasis and chemotherapy resistance,and thus participate in tumor progression.CASC19 is a new bio-marker which can promote tumor invasion and metastasis.However,the mechanism by which CASC19 affects the progression of GC through miRNA is not clear.AIM To explore the role of the CASC19/miR-491-5p/HMGA2 regulatory axis in GC.METHODS To explore the expression and prognosis of CASC19 in GC through clinical samples,and investigate the effects of inhibiting CASC19 on the proliferation,migration,invasion and other functions of GC cells through cell counting Kit-8(CCK-8),ethynyldeoxyuridine,Wound healing assay,Transwell,Western blot and flow cytometry experiments.The effect of miR-491-5p and HMGA2 in GC were also proved.The regulatory relationship between CASC19 and miR-491-5p,miR-491-5p and HMGA2 were validated through Dual-luciferase reporter gene assay and reverse transcription PCR.Then CCK-8,Transwell,Wound healing assay,flow cytometry and animal experiments verify the role of CASC19/miR-491-5p/HMGA2 regulatory axis.RESULTS The expression level of CASC19 is related to the T stage,N stage,and tumor size of patients.Knockdown of the expression of CASC19 can inhibit the ability of proliferation,migration,invasion and EMT conversion of GC cells,and knocking down the expression of CASC19 can promote the apoptosis of GC cells.Increasing the expression of miR-491-5p can inhibit the proliferation of GC cells,miR-491-5p mimics can inhibit EMT conversion,and promote the apoptosis of GC cells,while decreasing the expression of miR-491-5p can promote the proliferation and EMT conversion and inhibit the apoptosis of GC cells.The expression of HMGA2 in GC tissues is higher than that in adjacent tissues.At the same time,the expression level of HMGA2 is related to the N and T stages of the patients.Reducing the level of HMGA2 can promote cell apoptosis and inhibit the proliferation of GC cells.Cell experiments and animal experiments have proved that CASC19 can regulates the expression of HMGA2 through miR-491-5p,thereby affecting the biological functions of GC.CONCLUSION CASC19 regulates the expression of HMGA2 through miR-491-5p to affect the development of GC.This axis may serve as a potential biomarker and therapeutic target of GC.
文摘目的分析不同民族缺血性卒中患者对基于快速细胞色素P450酶家族2亚家族C成员19(cytochrome P450 family 2 subfamily C member 19,CYP2C19)基因检测指导抗血小板治疗方案的反应差异。方法前瞻性连续纳入2023年1—7月在南宁市第三人民医院住院治疗的汉族(对照组)和壮族(试验组)非心源性轻型缺血性卒中患者。所有患者在CYP2C19基因检测结果指导下进行抗血小板治疗:对于基因表型为氯吡格雷快代谢的患者,抗血小板药物选择硫酸氢氯吡格雷;对于中间代谢或慢代谢的患者,抗血小板药物选择阿司匹林肠溶片或替格瑞洛片。随访90 d,记录mRS评分、日常生活能力量表(activity of daily living scale,ADL)评分、NIHSS评分以及90 d缺血性卒中累积复发率。结果共纳入1036例缺血性卒中患者,对照组743例,CYP2C19基因检测结果显示,氯吡格雷快代谢、中间代谢、慢代谢型患者分别为299例(40.24%)、345例(46.43%)和99例(13.32%)。试验组293例,氯吡格雷快代谢、中间代谢、慢代谢型患者分别为107例(36.52%)、161例(54.95%)和25例(8.53%)。两组不同CYP2C19基因表型的比例差异无统计学意义。随访90 d,两组间的mRS评分、ADL评分、NI HSS评分差异无统计学意义。对照组和试验组的90 d缺血性卒中累积复发率分别为5.52%(41/743)和5.12%(15/293),差异无统计学意义。结论基于CYP2C19基因检测指导的抗血小板治疗在汉族和壮族的缺血性卒中患者人群中,预防缺血性卒中复发的效果相似。
文摘本文报道了一例老年女性院内卒中患者的临床诊疗过程。该患者于肛肠外科手术后2 d突发急性缺血性卒中,经影像学检查确诊为右侧颈内动脉起始部重度狭窄。在接受了1个月的卒中二级预防药物治疗后,择期行血管内治疗。术前该患者进行了快速细胞色素P450酶家族2亚家族C成员19(cytochrome P450 family 2 subfamily C member 19,CYP2C19)基因检测,结果为中间代谢型,提示应用氯吡格雷的效果可能不佳。基于这一检测结果调整抗血小板治疗方案,选择替格瑞洛联合阿司匹林作为替代治疗。治疗后,患者病情稳定,预后较好。本病例报道提示,在非轻型卒中患者中,快速CYP2C19基因检测可帮助选择抗血小板治疗策略,改善患者预后。
