目的探讨母亲糖尿病、解偶联蛋白2基因(UCP2)多态性及两者的交互作用与子代先天性心脏病(CHD)的关系。方法采用以医院为基础的病例对照研究,选择2018年3月至2019年8月在湖南省儿童医院确诊的464例单纯CHD患儿的母亲为病例组,选择同期住...目的探讨母亲糖尿病、解偶联蛋白2基因(UCP2)多态性及两者的交互作用与子代先天性心脏病(CHD)的关系。方法采用以医院为基础的病例对照研究,选择2018年3月至2019年8月在湖南省儿童医院确诊的464例单纯CHD患儿的母亲为病例组,选择同期住院、无先天畸形的504例患儿的母亲为对照组。通过问卷调查,收集相关暴露信息,同时采集母亲静脉血5 mL,用于UCP2基因多态性检测。采用多因素logistic回归分析探讨母亲糖尿病、UCP2基因多态性及两者交互作用与子代CHD的关联性。结果多因素logistic回归分析显示,在控制混杂因素后,患有妊娠期糖尿病(OR=2.96,95%CI:1.57~5.59)、有妊娠期糖尿病史(OR=3.16,95%CI:1.59~6.28)和妊娠前患有糖尿病(OR=4.52,95%CI:2.41~8.50)均显著增加子代CHD的风险(P<0.05)。母亲UCP2基因两个位点rs659366(T/C vs C/C:OR=1.49,95%CI:1.02~2.16;T/T vs C/C:OR=2.77,95%CI:1.67~4.62)和rs660339(A/A vs G/G:OR=2.19,95%CI:1.34~3.58)的多态性与子代CHD的风险存在关联(P<0.05)。交互作用分析显示,UCP2基因两个位点(rs659366和rs660339)的多态性与母亲糖尿病在子代CHD发生中存在交互作用(P<0.05)。结论母亲糖尿病、UCP2基因多态性及其交互作用与子代CHD发病相关。展开更多
Chloride solid electrolytes(SEs)have attracted widespread attention due to their high room-temperature ionic conductivity and excellent cathode compatibility.However,the conventionally selected central metal elements(...Chloride solid electrolytes(SEs)have attracted widespread attention due to their high room-temperature ionic conductivity and excellent cathode compatibility.However,the conventionally selected central metal elements(e.g.,In,Y and Ta)are usually rare and heavy,inevitably causing the high cost and high density of the obtained chloride SEs.Here,by choosing abundant and light Mg and Al as central metal elements,we develop a cheap and low density Li_(1.2)Mg_(0.95)Al_(0.3)Cl_(4)SE for high active material ratio in all solid state cathode.Partial replacement of Mg^(2+)by Al^(3+)in the framework yields vacancies and lowers the non-lithium metal ions occupancy at Mg/Li co-occupied 16d site,effectively relieving the blocking effects by Mg^(2+)in the pristine spinel Li_(2-2x)Mg_(1+x)Cl_(4).Thus,a significantly improved room-temperature conductivity of 3.08×10^(-4)S·cm^(-1)is achieved,two orders of magnitude higher than that of Li_(1.2)Mg_(1.4)Cl_(4).More attractively,its low density of only 1.98 g·cm-3 enables low SE mass ratio in cathodes(only 16 wt.%)with still effective electrolyte/cathode contact and lithium-ion conduction inside.When charged to potential of 4.30 V,the asfabricated Li_(1.2)Mg_(0.95)Al_(0.3)Cl_(4)-based solid lithium battery with uncoated NCM523 cathode can be cycled for over 100 cycles with a capacity retention of 86.68%at room temperature.展开更多
目的利用美国FDA不良事件报告系统(FAERS)对钠-葡萄糖共转运蛋白2(SGLT2)抑制剂的生殖系统药物毒性进行全面分析,挖掘潜在的生殖系统不良事件信号,以期为临床合理用药提供参考。方法采用压缩估计的不相称测定分析,选取报告比值比法(ROR...目的利用美国FDA不良事件报告系统(FAERS)对钠-葡萄糖共转运蛋白2(SGLT2)抑制剂的生殖系统药物毒性进行全面分析,挖掘潜在的生殖系统不良事件信号,以期为临床合理用药提供参考。方法采用压缩估计的不相称测定分析,选取报告比值比法(ROR)和成分信息法(IC)对FAERS中2013年第1季度至2021年第2季度有关SGLT2抑制剂的数据进行挖掘,借助重要医疗事件(IME)列表筛选出生殖系统IME。所有的不良事件及IME均由《国际医学用语词典》(MedDRA)24.0版编码。分析患者的临床特征、预后、信号检测结果及指定不良事件的事件发生时间(TTO)。结果将SGLT2抑制剂作为“首要怀疑”和“次要怀疑”的生殖系统不良事件报告纳入分析,共获得2700条记录。男性生殖系统不良事件发生频率(57.59%,1555/2700)高于女性(35.70%,964/2700),单药治疗与生殖不良事件的关联强度高于联合用药(IC的95%CI下限:1.40 vs 1.21;ROR的95%CI下限:2.65 vs 2.37)。在单药治疗中共检测出56个信号,出现8个强信号和13个IME。常见的生殖系统不良事件是Fournier坏疽、生殖器真菌感染、龟头包皮炎等。说明书中未提及的IME共10个,包括男性外生殖器蜂窝织炎、乳腺癌、阴茎癌等。结论除了已知的生殖系统不良事件,SGLT2抑制剂还存在其他重要的生殖系统不良事件信号。不同SGLT2抑制剂的生殖毒性存在差异性,临床医师应充分考量用药的风险与收益,对严重不良事件进行重点监测。展开更多
Background Aims:To summarize the epidemiologic evidence on the association between single nucleotide polymorphisms(SNPs)of folate metabolism genes from parents and children and risk of congenital heart diseases(CHDs)b...Background Aims:To summarize the epidemiologic evidence on the association between single nucleotide polymorphisms(SNPs)of folate metabolism genes from parents and children and risk of congenital heart diseases(CHDs)by a comprehensive systematic review and meta-analysis.Methods and results:Pub Med,Embase,Google Scholar,Cochrane Libraries,and Chinese databases were searched to identify potential studies through July2021 For mothers,the polymorphisms of Methylenetetrahydrofolate Reductase(MTHFR)at rs1801133 and rs1801131 were significantly associated with risk of CHDs in the homozygote comparisons(T/T vs C/C at rs1801133:OR:1.50,95%CI:1.31-1.71;C/C vs A/A at rs1801131:OR:1.39,95%CI:1.04-1.86).For fathers,the polymorphisms of MTHFR at rs1801133 were significantly associated with risk of CHDs in the heterozygote comparisons(C/T vs C/C:OR:1.26,95%CI:1.04-1.53).For children,the polymorphisms of MTHFR at rs1801133(T/T vs C/C:OR:2.05,95%CI:1.57-2.66),rs1801131(A/C vs A/A:OR:1.32,95%CI:1.06-1.63),and rs2274976(G/A vs G/G:OR:0.75,95%CI:0.61-0.92),and methionine synthase reductase(MSR)at rs1801394(G/G vs A/A:OR:1.85,95%CI:1.21-2.85)and rs1532268(T/T vs C/C:OR:2.44,95%CI:1.15-5.21;C/T vs C/C:OR:1.53,95%CI:1.11-2.10).This review also assessed the risk of specific CHD subtypes associated with folate metabolism gene SNPs of children.Relevant heterogeneity moderators have been identified by subgroup analysis.Sensitivity analysis yielded consistent results.No evidence of publication bias was observed.Conclusions:The present study indicates that polymorphisms of maternal MTHFR at rs1801133 and rs1801131,parental MTHFR at rs1801133,as well as children’s MTHFR at rs1801133,rs1801131 and rs2274976,and MSR at rs1801394 and rs1532268 are significantly associated with risk of CHDs.展开更多
文摘目的探讨母亲糖尿病、解偶联蛋白2基因(UCP2)多态性及两者的交互作用与子代先天性心脏病(CHD)的关系。方法采用以医院为基础的病例对照研究,选择2018年3月至2019年8月在湖南省儿童医院确诊的464例单纯CHD患儿的母亲为病例组,选择同期住院、无先天畸形的504例患儿的母亲为对照组。通过问卷调查,收集相关暴露信息,同时采集母亲静脉血5 mL,用于UCP2基因多态性检测。采用多因素logistic回归分析探讨母亲糖尿病、UCP2基因多态性及两者交互作用与子代CHD的关联性。结果多因素logistic回归分析显示,在控制混杂因素后,患有妊娠期糖尿病(OR=2.96,95%CI:1.57~5.59)、有妊娠期糖尿病史(OR=3.16,95%CI:1.59~6.28)和妊娠前患有糖尿病(OR=4.52,95%CI:2.41~8.50)均显著增加子代CHD的风险(P<0.05)。母亲UCP2基因两个位点rs659366(T/C vs C/C:OR=1.49,95%CI:1.02~2.16;T/T vs C/C:OR=2.77,95%CI:1.67~4.62)和rs660339(A/A vs G/G:OR=2.19,95%CI:1.34~3.58)的多态性与子代CHD的风险存在关联(P<0.05)。交互作用分析显示,UCP2基因两个位点(rs659366和rs660339)的多态性与母亲糖尿病在子代CHD发生中存在交互作用(P<0.05)。结论母亲糖尿病、UCP2基因多态性及其交互作用与子代CHD发病相关。
基金the National Natural Science Foundation of China(Nos.22325505,52073271,and 22305236)the USTC Research Funds of the Double First-Class Initiative(No.YD2060002034)+1 种基金the Collaborative Innovation Program of Hefei Science Center,CAS(No.2022HSC-CIP018)the China Postdoctoral Science Foundation(Nos.2023M733375 and 2023T160619).
文摘Chloride solid electrolytes(SEs)have attracted widespread attention due to their high room-temperature ionic conductivity and excellent cathode compatibility.However,the conventionally selected central metal elements(e.g.,In,Y and Ta)are usually rare and heavy,inevitably causing the high cost and high density of the obtained chloride SEs.Here,by choosing abundant and light Mg and Al as central metal elements,we develop a cheap and low density Li_(1.2)Mg_(0.95)Al_(0.3)Cl_(4)SE for high active material ratio in all solid state cathode.Partial replacement of Mg^(2+)by Al^(3+)in the framework yields vacancies and lowers the non-lithium metal ions occupancy at Mg/Li co-occupied 16d site,effectively relieving the blocking effects by Mg^(2+)in the pristine spinel Li_(2-2x)Mg_(1+x)Cl_(4).Thus,a significantly improved room-temperature conductivity of 3.08×10^(-4)S·cm^(-1)is achieved,two orders of magnitude higher than that of Li_(1.2)Mg_(1.4)Cl_(4).More attractively,its low density of only 1.98 g·cm-3 enables low SE mass ratio in cathodes(only 16 wt.%)with still effective electrolyte/cathode contact and lithium-ion conduction inside.When charged to potential of 4.30 V,the asfabricated Li_(1.2)Mg_(0.95)Al_(0.3)Cl_(4)-based solid lithium battery with uncoated NCM523 cathode can be cycled for over 100 cycles with a capacity retention of 86.68%at room temperature.
文摘目的利用美国FDA不良事件报告系统(FAERS)对钠-葡萄糖共转运蛋白2(SGLT2)抑制剂的生殖系统药物毒性进行全面分析,挖掘潜在的生殖系统不良事件信号,以期为临床合理用药提供参考。方法采用压缩估计的不相称测定分析,选取报告比值比法(ROR)和成分信息法(IC)对FAERS中2013年第1季度至2021年第2季度有关SGLT2抑制剂的数据进行挖掘,借助重要医疗事件(IME)列表筛选出生殖系统IME。所有的不良事件及IME均由《国际医学用语词典》(MedDRA)24.0版编码。分析患者的临床特征、预后、信号检测结果及指定不良事件的事件发生时间(TTO)。结果将SGLT2抑制剂作为“首要怀疑”和“次要怀疑”的生殖系统不良事件报告纳入分析,共获得2700条记录。男性生殖系统不良事件发生频率(57.59%,1555/2700)高于女性(35.70%,964/2700),单药治疗与生殖不良事件的关联强度高于联合用药(IC的95%CI下限:1.40 vs 1.21;ROR的95%CI下限:2.65 vs 2.37)。在单药治疗中共检测出56个信号,出现8个强信号和13个IME。常见的生殖系统不良事件是Fournier坏疽、生殖器真菌感染、龟头包皮炎等。说明书中未提及的IME共10个,包括男性外生殖器蜂窝织炎、乳腺癌、阴茎癌等。结论除了已知的生殖系统不良事件,SGLT2抑制剂还存在其他重要的生殖系统不良事件信号。不同SGLT2抑制剂的生殖毒性存在差异性,临床医师应充分考量用药的风险与收益,对严重不良事件进行重点监测。
基金supported by the Project Funded by National Key Research and Development Project(No.2018YFE0114500)National Natural Science Foundation Program of China(No.82073653 and 81803313)+5 种基金China Postdoctoral Science Foundation(No.2020M682644)Hunan Provincial Science and Technology Talent Support Project(No.2020TJ-N07)Hunan Provincial Key Research and Development Program(No.2018SK2063,No.2018SK2064)Natural Science Foundation of Hunan Province(No.2018JJ2551)Open Project from NHC Key Laboratory of Birth Defect for Research and Prevention(No.KF2020006)Science and Technology Planning Project of Guangdong Province(No.2020A1414010152)。
文摘Background Aims:To summarize the epidemiologic evidence on the association between single nucleotide polymorphisms(SNPs)of folate metabolism genes from parents and children and risk of congenital heart diseases(CHDs)by a comprehensive systematic review and meta-analysis.Methods and results:Pub Med,Embase,Google Scholar,Cochrane Libraries,and Chinese databases were searched to identify potential studies through July2021 For mothers,the polymorphisms of Methylenetetrahydrofolate Reductase(MTHFR)at rs1801133 and rs1801131 were significantly associated with risk of CHDs in the homozygote comparisons(T/T vs C/C at rs1801133:OR:1.50,95%CI:1.31-1.71;C/C vs A/A at rs1801131:OR:1.39,95%CI:1.04-1.86).For fathers,the polymorphisms of MTHFR at rs1801133 were significantly associated with risk of CHDs in the heterozygote comparisons(C/T vs C/C:OR:1.26,95%CI:1.04-1.53).For children,the polymorphisms of MTHFR at rs1801133(T/T vs C/C:OR:2.05,95%CI:1.57-2.66),rs1801131(A/C vs A/A:OR:1.32,95%CI:1.06-1.63),and rs2274976(G/A vs G/G:OR:0.75,95%CI:0.61-0.92),and methionine synthase reductase(MSR)at rs1801394(G/G vs A/A:OR:1.85,95%CI:1.21-2.85)and rs1532268(T/T vs C/C:OR:2.44,95%CI:1.15-5.21;C/T vs C/C:OR:1.53,95%CI:1.11-2.10).This review also assessed the risk of specific CHD subtypes associated with folate metabolism gene SNPs of children.Relevant heterogeneity moderators have been identified by subgroup analysis.Sensitivity analysis yielded consistent results.No evidence of publication bias was observed.Conclusions:The present study indicates that polymorphisms of maternal MTHFR at rs1801133 and rs1801131,parental MTHFR at rs1801133,as well as children’s MTHFR at rs1801133,rs1801131 and rs2274976,and MSR at rs1801394 and rs1532268 are significantly associated with risk of CHDs.
