目的总结分析性发育异常(disorders of sex developmemt,DSD)患儿性腺的病理学特点及其临床意义。方法收集2010年8月至2018年1月间于浙江大学医学院附属儿童医院就诊并获取性腺病理学检查结果的DSD患儿临床资料,同时根据染色体结果分成...目的总结分析性发育异常(disorders of sex developmemt,DSD)患儿性腺的病理学特点及其临床意义。方法收集2010年8月至2018年1月间于浙江大学医学院附属儿童医院就诊并获取性腺病理学检查结果的DSD患儿临床资料,同时根据染色体结果分成性染色体DSD组、46 XX DSD组、46,XY DSD组共3组进行对比分析。结果共有106例DSD患儿获得性腺病理检查结果,肿瘤发生率为1.8%。3组间EMS评分无统计学差异。性染色体DSD组21例,其中卵睾型DSD 10例(47.6%)、原始性腺7例(33.3%)、发育不良卵巢1例(4.8%)、发育不良睾丸3例(14.3%)。46 XX DSD组25例,其中卵睾型DSD 11例(44%)、原始性腺3例(12%)、发育不良卵巢9例(36%)、发育不良睾丸2例(8%)。46,XY DSD组60例,其中卵睾DSD 2例(3.3%)、原始性腺7例(11.7%)、发育不良卵巢5例(8.3%)、发育不良睾丸44例(73.3%)、性腺母细胞瘤2例(3.3%)。不同DSD染色体分型中各种病理类型的构成比存在统计学差异(P<0.05)。结论对于诊断结果尚不明确、需要接受性腺病理检查的DSD患儿,EMS得分及性腺病理结果与染色体核型不存在较为明显的对应关系。性腺病理检查仍是DSD诊断及治疗的重要评估手段,这对DSD患儿的个体化处理具有重要意义。此外,性腺发生恶变的机率较小。展开更多
Objective To explore the characteristics and mechanism of sirtuin 1(SIRT1)in lipopolysaccharide(LPS)-activated pyroptosis in the renal tissue of children with congenital hydronephrosis(CHn).Methods We detected the exp...Objective To explore the characteristics and mechanism of sirtuin 1(SIRT1)in lipopolysaccharide(LPS)-activated pyroptosis in the renal tissue of children with congenital hydronephrosis(CHn).Methods We detected the expression characteristics and clinical significance of SIRT1 and pyroptosis pathway proteins in CHn renal tissues by immunohistochemistry.The degree of renal fibrosis was detected by Masson staining.The human renal tubular epithelial cell line(HK-2)was cultured in vitro and treated with LPS(1µg/mL),the SIRT1-specific agonist SRT1720(2.5µmol/L)and small interfering RNA(siRNA)-SIRT1 for 48 hours.After 48 hours,Cell Counting Kit-8 was used to detect the changes in cell proliferation ability,and ELISA was used to detect the changes in the expression of interleukin(IL)-1β and IL-18 in the cell supernatant.Real-time PCR(quantitative RT-PCR)and western blot analysis were used to detect the expression of SIRT1,caspase-1,caspase-4,NOD-like receptor thermal protein domain associated protein 3(NLRP3),and cleaved gasdermin D(GSDMD)in each group.Results Serum inflammatory cytokines were significantly elevated in 13 children with CHn with urinary tract infection,mainly caused by Gram-negative bacteria.Severe renal fibrosis occurred in children with CHn.Compared with the control group,the expression of SIRT1 in CHn kidney tissues was decreased,and the expression of caspase-4 and GSDMD was increased.LPS inhibited the expression of SIRT1 in HK-2 cells,promoted the expression of caspase-1,caspase-4,NLRP3,cleaved GSDMD,promoted the expression of IL-1β and IL-18 in the supernatant,and promoted pyroptosis in HK-2 cells.SRT1720 can inhibit LPS-activated pyroptosis by promoting SIRT1 expression,while siRNA-SIRT1 can further aggravate LPS-activated pyroptosis after inhibiting SIRT1 expression.Conclusions LPS can promote the inflammatory response in children with CHn by activating non-canonical pyroptosis and inhibiting SIRT1 expression.Promoting SIRT1 expression can inhibit pyroptosis of renal tubular epithelial cells,reduce the release of IL-18 and IL-1β,and alleviate the progression of renal fibrosis in children with CHn.展开更多
文摘目的总结分析性发育异常(disorders of sex developmemt,DSD)患儿性腺的病理学特点及其临床意义。方法收集2010年8月至2018年1月间于浙江大学医学院附属儿童医院就诊并获取性腺病理学检查结果的DSD患儿临床资料,同时根据染色体结果分成性染色体DSD组、46 XX DSD组、46,XY DSD组共3组进行对比分析。结果共有106例DSD患儿获得性腺病理检查结果,肿瘤发生率为1.8%。3组间EMS评分无统计学差异。性染色体DSD组21例,其中卵睾型DSD 10例(47.6%)、原始性腺7例(33.3%)、发育不良卵巢1例(4.8%)、发育不良睾丸3例(14.3%)。46 XX DSD组25例,其中卵睾型DSD 11例(44%)、原始性腺3例(12%)、发育不良卵巢9例(36%)、发育不良睾丸2例(8%)。46,XY DSD组60例,其中卵睾DSD 2例(3.3%)、原始性腺7例(11.7%)、发育不良卵巢5例(8.3%)、发育不良睾丸44例(73.3%)、性腺母细胞瘤2例(3.3%)。不同DSD染色体分型中各种病理类型的构成比存在统计学差异(P<0.05)。结论对于诊断结果尚不明确、需要接受性腺病理检查的DSD患儿,EMS得分及性腺病理结果与染色体核型不存在较为明显的对应关系。性腺病理检查仍是DSD诊断及治疗的重要评估手段,这对DSD患儿的个体化处理具有重要意义。此外,性腺发生恶变的机率较小。
基金supported by the National Key R&D Program of China(2018YFC100272)。
文摘Objective To explore the characteristics and mechanism of sirtuin 1(SIRT1)in lipopolysaccharide(LPS)-activated pyroptosis in the renal tissue of children with congenital hydronephrosis(CHn).Methods We detected the expression characteristics and clinical significance of SIRT1 and pyroptosis pathway proteins in CHn renal tissues by immunohistochemistry.The degree of renal fibrosis was detected by Masson staining.The human renal tubular epithelial cell line(HK-2)was cultured in vitro and treated with LPS(1µg/mL),the SIRT1-specific agonist SRT1720(2.5µmol/L)and small interfering RNA(siRNA)-SIRT1 for 48 hours.After 48 hours,Cell Counting Kit-8 was used to detect the changes in cell proliferation ability,and ELISA was used to detect the changes in the expression of interleukin(IL)-1β and IL-18 in the cell supernatant.Real-time PCR(quantitative RT-PCR)and western blot analysis were used to detect the expression of SIRT1,caspase-1,caspase-4,NOD-like receptor thermal protein domain associated protein 3(NLRP3),and cleaved gasdermin D(GSDMD)in each group.Results Serum inflammatory cytokines were significantly elevated in 13 children with CHn with urinary tract infection,mainly caused by Gram-negative bacteria.Severe renal fibrosis occurred in children with CHn.Compared with the control group,the expression of SIRT1 in CHn kidney tissues was decreased,and the expression of caspase-4 and GSDMD was increased.LPS inhibited the expression of SIRT1 in HK-2 cells,promoted the expression of caspase-1,caspase-4,NLRP3,cleaved GSDMD,promoted the expression of IL-1β and IL-18 in the supernatant,and promoted pyroptosis in HK-2 cells.SRT1720 can inhibit LPS-activated pyroptosis by promoting SIRT1 expression,while siRNA-SIRT1 can further aggravate LPS-activated pyroptosis after inhibiting SIRT1 expression.Conclusions LPS can promote the inflammatory response in children with CHn by activating non-canonical pyroptosis and inhibiting SIRT1 expression.Promoting SIRT1 expression can inhibit pyroptosis of renal tubular epithelial cells,reduce the release of IL-18 and IL-1β,and alleviate the progression of renal fibrosis in children with CHn.
