Background:Hepatocellular carcinoma(HCC)is a highly lethal malignancy driven by both intrinsic oncogenic pathways and immune microenvironmental regulation.Emerging evidence suggests that DNASE1L3 may influence tumor b...Background:Hepatocellular carcinoma(HCC)is a highly lethal malignancy driven by both intrinsic oncogenic pathways and immune microenvironmental regulation.Emerging evidence suggests that DNASE1L3 may influence tumor biology and immune responses;however,its specific roles in HCC progression and macrophage-mediated regulation remain unclear.This study aimed to elucidate the biological functions of DNASE1L3 in HCC and to determine how it modulates tumor behavior and immune interactions.Methods:Bioinformatics analyses of the GSE41804 and Cancer Genome Atlas-Liver Hepatocellular Carcinoma(TCGA-LIHC)datasets were used to identify hub genes.Functional assays assessed the impact of DNASE1L3 on HCC cell proliferation,migration,invasion,and cell cycle progression.The effects of DNASE1L3 on macrophage polarization and the Wnt/β-catenin signaling pathway were examined using a co-culture system.An HCC organoid model was established to further validate its regulatory function.Results:Eight prognostic signature genes were identified,with deoxyribonuclease I-like 3(DNase I-like 3)selected as the hub gene.DNASE1L3 overexpression suppressed HCC cell growth,inhibited migration and invasion,induced G1 arrest,and modulated epithelial-mesenchymal transition(EMT)markers.DNASE1L3 knockdown promoted M2-like macrophage polarization.Mechanistically,DNASE1L3 interacted withβ-catenin to enhance its ubiquitination and degradation,thereby inhibiting Wnt/β-catenin signaling and reducing PD-L1 expression.DNASE1L3 overexpression similarly restricted organoid growth and suppressed pathway activity.Conclusion:DNASE1L3 acts as a negative regulator of HCC progression by targeting the Wnt/β-catenin pathway and reducing PD-L1 expression,thereby influencing both tumor cell behavior and macrophage-mediated immune responses.展开更多
Objectives:The current treatment options and therapeutic targets for triple-negative breast cancer(TNBC),an aggressive subtype of breast cancer(BrCA),are limited.This study aimed to identify novel biomarkers and trans...Objectives:The current treatment options and therapeutic targets for triple-negative breast cancer(TNBC),an aggressive subtype of breast cancer(BrCA),are limited.This study aimed to identify novel biomarkers and transcriptional regulatory networks(TRN)inherent in TNBC samples.Methods:We analyzed pan-cancer BrCA datasets from The Cancer Genome Atlas(TCGA)to compare triple-positive breast cancer(TPBC)with TNBC.TRN algorithms and virtual inference of protein-enriched regulon(VIPER)were used to identify master regulators and their target genes.Utilizing TNBC cells(MDA-MB-231 and MDA-MB-468),we validated the relationship of nuclear factor erythroid 2-like 3(NFE2L3)and basic helix-loop-helix family member E 40(BHLHE40)by performing a luciferase assay.The expression levels of these targets were measured after transfections with plasmid and siRNA via qRT-PCR and western blots.The effect of these genes on cell proliferation and migration was studied using phenotypic assays.Results:Using computational approaches,we identified NFE2L3 as a master regulator with BHLHE40 as its target gene.NFE2L3 protein binds to the promoter region of BHLHE40 and regulates its transcriptional activity.Additionally,silencing and overexpressing NFE2L3 and BHLHE40 in TNBC cell lines MDA-MB-231 and MDA-MB-468 showed that NFE2L3 directly regulates BHLHE40 at both transcriptional and translational levels.We found that BHLHE40 requires NFE2L3 for cell proliferation and migration in TNBC.Conclusion:These findings underscore the significance of NFE2L3 and BHLHE40 in TNBC,highlighting NFE2L3’s role in regulating the oncogenic activity of BHLHE40 in TNBC cells.展开更多
目的探究膈肌浅快呼吸指数(diaphragm rapid shallow breathing index,D-RSBI)与L3骨骼肌指数(skeletal muscle index at the third lumber vertebra,L3 SMI)对老年重症肺炎患者撤机结局的预测价值。方法收集2023年1月至2023年12月南京...目的探究膈肌浅快呼吸指数(diaphragm rapid shallow breathing index,D-RSBI)与L3骨骼肌指数(skeletal muscle index at the third lumber vertebra,L3 SMI)对老年重症肺炎患者撤机结局的预测价值。方法收集2023年1月至2023年12月南京医科大学附属淮安第一医院收治的96例老年重症肺炎患者的临床资料,根据撤机结局分为撤机成功组和和失败组。两组患者均进行D-RSBI评估并检测L3 SMI水平。比较两组患者的临床资料、D-RSBI和L3 SMI水平。Logistic回归分析用于明确老年重症肺炎患者撤机失败的影响因素并基于回归分析结果构建列线图模型。通过受试者工作特征曲线(Receiver Operating Characteristic,ROC)分析L3 SMI联合D-RSBI对老年重症肺炎患者撤机失败的预测价值。结果96例老年重症肺炎机械通气患者中60例患者撤机成功,36例撤机失败,撤机失败率为37.5%。相较于撤机成功组,撤机失败组的机械通气时间和D-RSBI水平均增高,L3 SMI水平降低(P<0.05)。Logistic结果显示机械通气时间、D-RSBI是老年重症肺炎患者撤机失败的危险因素,而L3 SMI水平是老年重症肺炎患者撤机失败的保护因素(P<0.05)。预测老年重症肺炎患者撤机失败的列线图模型一致性指数(C-index)为0.794,校准曲线拟合良好。ROC分析显示L3 SMI水平评估老年重症肺炎患者撤机失败的AUC为0.788,95%CI为0.697~0.879,D-RSBI的AUC为0.748,95%CI为0.637~0.859,二者联合预测的AUC为0.819,95%CI为0.738~0.901。结论D-RSBI与L3 SMI联合使用对老年重症肺炎患者撤机失败的预测价值更高。展开更多
目的:探究L3-L4椎间隙穿刺硬膜外镇痛对大龄初产妇顺产结局的影响。方法:选取2022年6月至2024年4月郑州大学第三附属医院收治的64例大龄初产妇作为研究对象,按随机数字表法分为对照组和试验组,各32例。为对照组产妇实施L2-L3椎间隙穿刺...目的:探究L3-L4椎间隙穿刺硬膜外镇痛对大龄初产妇顺产结局的影响。方法:选取2022年6月至2024年4月郑州大学第三附属医院收治的64例大龄初产妇作为研究对象,按随机数字表法分为对照组和试验组,各32例。为对照组产妇实施L2-L3椎间隙穿刺硬膜外镇痛,为试验组产妇实施L3-L4椎间隙穿刺硬膜外镇痛。比较两组产妇分娩镇痛情况、妊娠结局、新生儿情况及不良反应发生情况。结果:试验组产妇镇痛起效时间短于对照组,差异具有统计学意义(P<0.05),但两组产妇爆发痛次数、镇痛药物使用剂量、硬膜外自控镇痛次数比较,差异均无统计学意义(P>0.05);试验组产妇顺产率高于对照组,阴道助产率低于对照组,差异均具有统计学意义(P<0.05);试验组新生儿1 min Apgar评分(9.81±0.12)高于对照组(9.09±0.31),差异具有统计学意义(P<0.05),而两组新生儿胎心变异率、胎儿窘迫发生率比较,差异无统计学意义(P>0.05);试验组产妇不良反应总发生率低于对照组,差异具有统计学意义(P<0.05)。结论:L3-L4椎间隙穿刺硬膜外镇痛在大龄初产妇中的应用有利于缩短镇痛起效时间,提高产妇顺产率及新生儿1 min Apgar评分,并有利于减少不良反应。展开更多
基金funded by Shanghai Science and Technology Innovation Action Plan Project(22140901100)Shanghai Key Laboratory of Molecular Imaging(18DZ2260400)Shanghai University of Medicine and Health Science Seed Fund(SSF-24-21-01).
文摘Background:Hepatocellular carcinoma(HCC)is a highly lethal malignancy driven by both intrinsic oncogenic pathways and immune microenvironmental regulation.Emerging evidence suggests that DNASE1L3 may influence tumor biology and immune responses;however,its specific roles in HCC progression and macrophage-mediated regulation remain unclear.This study aimed to elucidate the biological functions of DNASE1L3 in HCC and to determine how it modulates tumor behavior and immune interactions.Methods:Bioinformatics analyses of the GSE41804 and Cancer Genome Atlas-Liver Hepatocellular Carcinoma(TCGA-LIHC)datasets were used to identify hub genes.Functional assays assessed the impact of DNASE1L3 on HCC cell proliferation,migration,invasion,and cell cycle progression.The effects of DNASE1L3 on macrophage polarization and the Wnt/β-catenin signaling pathway were examined using a co-culture system.An HCC organoid model was established to further validate its regulatory function.Results:Eight prognostic signature genes were identified,with deoxyribonuclease I-like 3(DNase I-like 3)selected as the hub gene.DNASE1L3 overexpression suppressed HCC cell growth,inhibited migration and invasion,induced G1 arrest,and modulated epithelial-mesenchymal transition(EMT)markers.DNASE1L3 knockdown promoted M2-like macrophage polarization.Mechanistically,DNASE1L3 interacted withβ-catenin to enhance its ubiquitination and degradation,thereby inhibiting Wnt/β-catenin signaling and reducing PD-L1 expression.DNASE1L3 overexpression similarly restricted organoid growth and suppressed pathway activity.Conclusion:DNASE1L3 acts as a negative regulator of HCC progression by targeting the Wnt/β-catenin pathway and reducing PD-L1 expression,thereby influencing both tumor cell behavior and macrophage-mediated immune responses.
文摘Objectives:The current treatment options and therapeutic targets for triple-negative breast cancer(TNBC),an aggressive subtype of breast cancer(BrCA),are limited.This study aimed to identify novel biomarkers and transcriptional regulatory networks(TRN)inherent in TNBC samples.Methods:We analyzed pan-cancer BrCA datasets from The Cancer Genome Atlas(TCGA)to compare triple-positive breast cancer(TPBC)with TNBC.TRN algorithms and virtual inference of protein-enriched regulon(VIPER)were used to identify master regulators and their target genes.Utilizing TNBC cells(MDA-MB-231 and MDA-MB-468),we validated the relationship of nuclear factor erythroid 2-like 3(NFE2L3)and basic helix-loop-helix family member E 40(BHLHE40)by performing a luciferase assay.The expression levels of these targets were measured after transfections with plasmid and siRNA via qRT-PCR and western blots.The effect of these genes on cell proliferation and migration was studied using phenotypic assays.Results:Using computational approaches,we identified NFE2L3 as a master regulator with BHLHE40 as its target gene.NFE2L3 protein binds to the promoter region of BHLHE40 and regulates its transcriptional activity.Additionally,silencing and overexpressing NFE2L3 and BHLHE40 in TNBC cell lines MDA-MB-231 and MDA-MB-468 showed that NFE2L3 directly regulates BHLHE40 at both transcriptional and translational levels.We found that BHLHE40 requires NFE2L3 for cell proliferation and migration in TNBC.Conclusion:These findings underscore the significance of NFE2L3 and BHLHE40 in TNBC,highlighting NFE2L3’s role in regulating the oncogenic activity of BHLHE40 in TNBC cells.
文摘目的:探究L3-L4椎间隙穿刺硬膜外镇痛对大龄初产妇顺产结局的影响。方法:选取2022年6月至2024年4月郑州大学第三附属医院收治的64例大龄初产妇作为研究对象,按随机数字表法分为对照组和试验组,各32例。为对照组产妇实施L2-L3椎间隙穿刺硬膜外镇痛,为试验组产妇实施L3-L4椎间隙穿刺硬膜外镇痛。比较两组产妇分娩镇痛情况、妊娠结局、新生儿情况及不良反应发生情况。结果:试验组产妇镇痛起效时间短于对照组,差异具有统计学意义(P<0.05),但两组产妇爆发痛次数、镇痛药物使用剂量、硬膜外自控镇痛次数比较,差异均无统计学意义(P>0.05);试验组产妇顺产率高于对照组,阴道助产率低于对照组,差异均具有统计学意义(P<0.05);试验组新生儿1 min Apgar评分(9.81±0.12)高于对照组(9.09±0.31),差异具有统计学意义(P<0.05),而两组新生儿胎心变异率、胎儿窘迫发生率比较,差异无统计学意义(P>0.05);试验组产妇不良反应总发生率低于对照组,差异具有统计学意义(P<0.05)。结论:L3-L4椎间隙穿刺硬膜外镇痛在大龄初产妇中的应用有利于缩短镇痛起效时间,提高产妇顺产率及新生儿1 min Apgar评分,并有利于减少不良反应。
