目的采用高通量测序技术,对一个综合征型耳聋家系的致病变异进行鉴定。方法详细询问一综合征型耳聋家系的病史及家族史,绘制家系图。对该家系进行听力学检查,采用全外显子组测序及生物信息学分析,筛选疑似致病变异,使用Sanger测序进行...目的采用高通量测序技术,对一个综合征型耳聋家系的致病变异进行鉴定。方法详细询问一综合征型耳聋家系的病史及家族史,绘制家系图。对该家系进行听力学检查,采用全外显子组测序及生物信息学分析,筛选疑似致病变异,使用Sanger测序进行变异共分离验证,并通过转录组测序探究内含子对剪切的影响。结果该家系中先证者(男性,2岁2个月)患有听神经病,伴有发育缓慢、肌无力、癫痫发作等症状。患者携带NARS2(NM_024678.6)c.[779A>C];[372+3A>G]复合杂合变异,其中c.779A>C p.(Glu260Ala)遗传自父亲,c.372+3A>G遗传自母亲,两变异均未见文献报道或数据库收录。转录组测序结果表明c.372+3A>G变异会导致转录跳过第三个外显子。依据美国医学遗传学与基因组学学会(American College of Medical Genetics and Genomics,ACMG)相关指南将c.779A>C变异及c.372+3A>G变异评级为可能致病。基于患者表型及基因检测结果,该患者诊断为联合氧化磷酸化缺乏症24型。结论NARS2基因致病变异可能是该患者的致病原因,新变异的检出丰富了NARS2基因的变异谱,为进一步明确NARS2与联合氧化磷酸化缺乏症24型的关系提供了参考依据。展开更多
Chemotherapy is the cornerstone of cancer treatment,and paclitaxel(PTX),as a first-line broad-spectrum chemotherapy drug,is widely used in the treatment of multiple tumors in the clinic.However,unsatisfactory efficacy...Chemotherapy is the cornerstone of cancer treatment,and paclitaxel(PTX),as a first-line broad-spectrum chemotherapy drug,is widely used in the treatment of multiple tumors in the clinic.However,unsatisfactory efficacy and drug resistance of single chemotherapy have severely hampered the clinical progress of PTX.Herein,three-in-one naringenin(NAR)-loaded PTX polymer prodrug micelles were constructed for efficient and synergistic antitumor therapy.Firstly,the polymer prodrug micelles could simultaneously act as nanoreservoirs for two hydrophobic drugs,PTX and NAR.Secondly,the polymer prodrug micelles enabled dual-responsive intelligent release of PTX and NAR triggered by reduction and acid.Finally,released PTX and NAR exerted synergistic antitumor effects for reversing tumor resistance,while NAR enhanced the immune and anti-inflammatory functions of polymer prodrug micelles.Due to the cascade-enhanced chemotherapeutic augmentation,the intelligent-responsive nanoreservoir proved to be an excellent antitumor therapeutic platform.This work was of great interest for designing superior chemotherapeutic augmentation regimens.展开更多
文摘目的采用高通量测序技术,对一个综合征型耳聋家系的致病变异进行鉴定。方法详细询问一综合征型耳聋家系的病史及家族史,绘制家系图。对该家系进行听力学检查,采用全外显子组测序及生物信息学分析,筛选疑似致病变异,使用Sanger测序进行变异共分离验证,并通过转录组测序探究内含子对剪切的影响。结果该家系中先证者(男性,2岁2个月)患有听神经病,伴有发育缓慢、肌无力、癫痫发作等症状。患者携带NARS2(NM_024678.6)c.[779A>C];[372+3A>G]复合杂合变异,其中c.779A>C p.(Glu260Ala)遗传自父亲,c.372+3A>G遗传自母亲,两变异均未见文献报道或数据库收录。转录组测序结果表明c.372+3A>G变异会导致转录跳过第三个外显子。依据美国医学遗传学与基因组学学会(American College of Medical Genetics and Genomics,ACMG)相关指南将c.779A>C变异及c.372+3A>G变异评级为可能致病。基于患者表型及基因检测结果,该患者诊断为联合氧化磷酸化缺乏症24型。结论NARS2基因致病变异可能是该患者的致病原因,新变异的检出丰富了NARS2基因的变异谱,为进一步明确NARS2与联合氧化磷酸化缺乏症24型的关系提供了参考依据。
基金supported by the National Natural Science Foundation of China(No.U1904155)the Henan Provincial Key Research Development and Special Project for Promotion(Nos.242102310455,242102310473)+4 种基金the Key Project of Science and Technology Research funded by the Henan Provincial Department of Education(No.24A350002)Postdoctoral Fellowship Program of CPSF(No.GZC20231732)China Postdoctoral Science Foundation(Nos.2023TQ0222,2023MD744229)General Program of Department of Education of Liaoning Province(No.JYTMS20231372)Doctoral Scientific Research Staring Foundation of Liaoning Province(No.2024-BS-073)。
文摘Chemotherapy is the cornerstone of cancer treatment,and paclitaxel(PTX),as a first-line broad-spectrum chemotherapy drug,is widely used in the treatment of multiple tumors in the clinic.However,unsatisfactory efficacy and drug resistance of single chemotherapy have severely hampered the clinical progress of PTX.Herein,three-in-one naringenin(NAR)-loaded PTX polymer prodrug micelles were constructed for efficient and synergistic antitumor therapy.Firstly,the polymer prodrug micelles could simultaneously act as nanoreservoirs for two hydrophobic drugs,PTX and NAR.Secondly,the polymer prodrug micelles enabled dual-responsive intelligent release of PTX and NAR triggered by reduction and acid.Finally,released PTX and NAR exerted synergistic antitumor effects for reversing tumor resistance,while NAR enhanced the immune and anti-inflammatory functions of polymer prodrug micelles.Due to the cascade-enhanced chemotherapeutic augmentation,the intelligent-responsive nanoreservoir proved to be an excellent antitumor therapeutic platform.This work was of great interest for designing superior chemotherapeutic augmentation regimens.
