背景转录相关酸性卷曲蛋白3(transforming acidic coiled coil protein 3,TACC3)是TACC家族的重要成员,研究表明,TACC3基因在乳腺癌,非小细胞肺癌,胃癌中高表达,并与预后较差有关.但是其在肝癌中的表达情况及与患者预后的关系鲜见报道....背景转录相关酸性卷曲蛋白3(transforming acidic coiled coil protein 3,TACC3)是TACC家族的重要成员,研究表明,TACC3基因在乳腺癌,非小细胞肺癌,胃癌中高表达,并与预后较差有关.但是其在肝癌中的表达情况及与患者预后的关系鲜见报道.目的通过生物信息学手段探讨TACC3基因在肝癌中的表达及其与患者的预后关系.方法分别检索BioGPS、Oncomine、癌症细胞系百科全书(cancer cell line encyclopedia,CCLE)数据库,挖掘分析TACC3基因在正常人体组织、肝癌组织及肝癌细胞系中的表达情况,应用Kaplan-Meier Plotter、GEPIA等数据库分析TACC3基因对肝癌患者预后的影响.结果BioGPS数据库分析结果显示TACC3基因在人体各组织中均有表达,肝脏组织中的表达值中位数略高于其他正常组织(8.95 vs 7.1).从Oncomine数据库检索出TACC3基因相关研究290项,显示肝癌组织中TACC3基因高表达4项,低表达1项,Meta分析显示与正常肝组织相比TACC3基因在肝癌组织中呈高表达状态[中位秩(Median Rank)=442.5,P<0.05].CCLE数据库分析显示,在肝癌细胞系中TACC3 mRNA高表达.Kaplan-Meier Plotter及GEPIA数据库生存分析结果显示,TACC3基因高表达组的肝癌患者总体生存时间(OS)和无进展生存时间(PFS)等生存预后指标均较低表达组差(P<0.05).结论TACC3基因在肝癌组织中呈高表达,且TACC3基因高表达与肝癌患者生存预后差有关.展开更多
A case of surgical nursing cooperation during extracorporeal membrane oxygenation(ECMO)-assisted hybrid sleeve left pneumonectomy,which included a right open carinal resection,tracheal bronchial anastomosis,and thorac...A case of surgical nursing cooperation during extracorporeal membrane oxygenation(ECMO)-assisted hybrid sleeve left pneumonectomy,which included a right open carinal resection,tracheal bronchial anastomosis,and thoracoscopic left pneumonectomy,has been documented.A thorough nursing intervention focused on patient safety and proactive measures to address potential complications was implemented throughout the surgical process.The procedure was completed without incident,and no postoperative complications were reported.展开更多
目的探讨具有青少年多形性低级别神经上皮肿瘤(polymorphous low-grade neuroepithelial tumor of the young,PLNTY)特征的弥漫性胶质瘤的临床病理学和分子遗传学特征及其预后意义。方法回顾性分析2020年6月至2024年8月福建医科大学附...目的探讨具有青少年多形性低级别神经上皮肿瘤(polymorphous low-grade neuroepithelial tumor of the young,PLNTY)特征的弥漫性胶质瘤的临床病理学和分子遗传学特征及其预后意义。方法回顾性分析2020年6月至2024年8月福建医科大学附属第一医院14例具有PLNTY特征的弥漫性胶质瘤病例,总结其临床病理特征,通过二代测序及甲基化分析检测分子遗传学及表观遗传学特征,并分析预后影响因素。结果14例患者中,男性8例,女性6例;年龄3~62岁,中位年龄29(9,50)岁。所有病例初次诊断时组织学均为低级别弥漫性胶质瘤,且均具有PLNTY的组织学及免疫组织化学特征。分子层面均存在丝裂原活化蛋白激酶通路异常,包括FGFR3::TACC3(F3T3)融合5例、FGFR2融合3例、BRAF V600E突变5例、FGFR1突变1例。其中,F3T3融合肿瘤中TERT启动子突变高频出现,非F3T3融合肿瘤则以NCOR2框内插入突变为主;5例F3T3融合病例均合并TERT启动子突变。临床随访显示3例患者复发,均为F3T3融合合并TERT启动子突变病例。预后分析显示,F3T3融合及TERT启动子突变是该类肿瘤潜在的预后负向因子。结论具有PLNTY特征的弥漫性胶质瘤在临床病理及分子遗传学上具有异质性,以FGFR3、FGFR2融合及BRAF、FGFR1突变为主要分子特征。其中,F3T3融合患者常合并TERT启动子突变,预后不良,对此类患者应考虑分子胶质母细胞瘤的可能。建议对具有PLNTY特征的弥漫性胶质瘤进行上述基因检测,以助于整合诊断并提供预后相关的分子遗传学依据。展开更多
Recent evidence has highlighted immune checkpoint inhibitors as among the most promising immunotherapies for various malignancies.However,a significant proportion of HCC patients exhibit poor responses.Lipid metabolic...Recent evidence has highlighted immune checkpoint inhibitors as among the most promising immunotherapies for various malignancies.However,a significant proportion of HCC patients exhibit poor responses.Lipid metabolic heterogeneity is considered a key driver of cancer progression.However,the role of lipid metabolic reprogramming in HCC immunotherapy resistance remains poorly understood.Herein,we aimed to illuminate the potential relationship between lipid metabolic reprogramming and ICI resistance and provide novel strategies to increase the HCC immunotherapy response.Patients who received PD-1/PD-L1 inhibitors were enrolled.The effect of TACC3 on the tumor microenvironment was validated via single-cell RNA sequencing in HCC-bearing mouse models.Targeted metabolomics was performed to analyze the regulatory role of TACC3 in HCC metabolism.To address HCC immunotherapy resistance,we developed a targeted nucleic acid therapeutic utilizing N-acetylgalactosamine(GalNAc)to conjugate siTACC3.Through clinical cohort analysis,we found that TACC3 was overexpressed in HCC patients with poor response to immunotherapy.Furthermore,we demonstrated that silencing tumor-derived TACC3 optimizes the cytotoxicity of infiltrating CD8^(+)T lymphocytes.Both in vitro and in vivo assays suggested that TACC3 maintains ACSL4-mediated polyunsaturated fatty acid(PUFA)metabolism in HCC cells.Additionally,TACC3 accelerates ACSL4 expression by interacting with LARP1 and PABPC1,which stabilize ACSL4 mRNA.The results of preclinical models demonstrated the satisfactory efficacy of GalNAc-conjugated siTACC3 combined with PD-1 inhibitor therapy for HCC.In summary,tumor-derived TACC3 impairs the tumor-killing activity of CD8^(+)T lymphocytes through PUFA metabolism-associated crosstalk.Targeting TACC3 represents a novel and practicable strategy to augment ICI efficacy against HCC.展开更多
基金supported by the National Natural Science Foundation of China(Nos.30871295)the National Ministry of Personnel Scientific Research Foundation of student(No.[2001]33)+1 种基金the Science Research of the Science Committee of Chongqing(No.CSTC 2009BB5065)
文摘背景转录相关酸性卷曲蛋白3(transforming acidic coiled coil protein 3,TACC3)是TACC家族的重要成员,研究表明,TACC3基因在乳腺癌,非小细胞肺癌,胃癌中高表达,并与预后较差有关.但是其在肝癌中的表达情况及与患者预后的关系鲜见报道.目的通过生物信息学手段探讨TACC3基因在肝癌中的表达及其与患者的预后关系.方法分别检索BioGPS、Oncomine、癌症细胞系百科全书(cancer cell line encyclopedia,CCLE)数据库,挖掘分析TACC3基因在正常人体组织、肝癌组织及肝癌细胞系中的表达情况,应用Kaplan-Meier Plotter、GEPIA等数据库分析TACC3基因对肝癌患者预后的影响.结果BioGPS数据库分析结果显示TACC3基因在人体各组织中均有表达,肝脏组织中的表达值中位数略高于其他正常组织(8.95 vs 7.1).从Oncomine数据库检索出TACC3基因相关研究290项,显示肝癌组织中TACC3基因高表达4项,低表达1项,Meta分析显示与正常肝组织相比TACC3基因在肝癌组织中呈高表达状态[中位秩(Median Rank)=442.5,P<0.05].CCLE数据库分析显示,在肝癌细胞系中TACC3 mRNA高表达.Kaplan-Meier Plotter及GEPIA数据库生存分析结果显示,TACC3基因高表达组的肝癌患者总体生存时间(OS)和无进展生存时间(PFS)等生存预后指标均较低表达组差(P<0.05).结论TACC3基因在肝癌组织中呈高表达,且TACC3基因高表达与肝癌患者生存预后差有关.
文摘A case of surgical nursing cooperation during extracorporeal membrane oxygenation(ECMO)-assisted hybrid sleeve left pneumonectomy,which included a right open carinal resection,tracheal bronchial anastomosis,and thoracoscopic left pneumonectomy,has been documented.A thorough nursing intervention focused on patient safety and proactive measures to address potential complications was implemented throughout the surgical process.The procedure was completed without incident,and no postoperative complications were reported.
文摘目的探讨具有青少年多形性低级别神经上皮肿瘤(polymorphous low-grade neuroepithelial tumor of the young,PLNTY)特征的弥漫性胶质瘤的临床病理学和分子遗传学特征及其预后意义。方法回顾性分析2020年6月至2024年8月福建医科大学附属第一医院14例具有PLNTY特征的弥漫性胶质瘤病例,总结其临床病理特征,通过二代测序及甲基化分析检测分子遗传学及表观遗传学特征,并分析预后影响因素。结果14例患者中,男性8例,女性6例;年龄3~62岁,中位年龄29(9,50)岁。所有病例初次诊断时组织学均为低级别弥漫性胶质瘤,且均具有PLNTY的组织学及免疫组织化学特征。分子层面均存在丝裂原活化蛋白激酶通路异常,包括FGFR3::TACC3(F3T3)融合5例、FGFR2融合3例、BRAF V600E突变5例、FGFR1突变1例。其中,F3T3融合肿瘤中TERT启动子突变高频出现,非F3T3融合肿瘤则以NCOR2框内插入突变为主;5例F3T3融合病例均合并TERT启动子突变。临床随访显示3例患者复发,均为F3T3融合合并TERT启动子突变病例。预后分析显示,F3T3融合及TERT启动子突变是该类肿瘤潜在的预后负向因子。结论具有PLNTY特征的弥漫性胶质瘤在临床病理及分子遗传学上具有异质性,以FGFR3、FGFR2融合及BRAF、FGFR1突变为主要分子特征。其中,F3T3融合患者常合并TERT启动子突变,预后不良,对此类患者应考虑分子胶质母细胞瘤的可能。建议对具有PLNTY特征的弥漫性胶质瘤进行上述基因检测,以助于整合诊断并提供预后相关的分子遗传学依据。
基金supported by the National Natural Science Foundation of China(82430089,82202974)the China Postdoctoral Science Foundation(2024M750533)the Shanghai Anti-Cancer Association(SACA-CY22C10).
文摘Recent evidence has highlighted immune checkpoint inhibitors as among the most promising immunotherapies for various malignancies.However,a significant proportion of HCC patients exhibit poor responses.Lipid metabolic heterogeneity is considered a key driver of cancer progression.However,the role of lipid metabolic reprogramming in HCC immunotherapy resistance remains poorly understood.Herein,we aimed to illuminate the potential relationship between lipid metabolic reprogramming and ICI resistance and provide novel strategies to increase the HCC immunotherapy response.Patients who received PD-1/PD-L1 inhibitors were enrolled.The effect of TACC3 on the tumor microenvironment was validated via single-cell RNA sequencing in HCC-bearing mouse models.Targeted metabolomics was performed to analyze the regulatory role of TACC3 in HCC metabolism.To address HCC immunotherapy resistance,we developed a targeted nucleic acid therapeutic utilizing N-acetylgalactosamine(GalNAc)to conjugate siTACC3.Through clinical cohort analysis,we found that TACC3 was overexpressed in HCC patients with poor response to immunotherapy.Furthermore,we demonstrated that silencing tumor-derived TACC3 optimizes the cytotoxicity of infiltrating CD8^(+)T lymphocytes.Both in vitro and in vivo assays suggested that TACC3 maintains ACSL4-mediated polyunsaturated fatty acid(PUFA)metabolism in HCC cells.Additionally,TACC3 accelerates ACSL4 expression by interacting with LARP1 and PABPC1,which stabilize ACSL4 mRNA.The results of preclinical models demonstrated the satisfactory efficacy of GalNAc-conjugated siTACC3 combined with PD-1 inhibitor therapy for HCC.In summary,tumor-derived TACC3 impairs the tumor-killing activity of CD8^(+)T lymphocytes through PUFA metabolism-associated crosstalk.Targeting TACC3 represents a novel and practicable strategy to augment ICI efficacy against HCC.
