目的研究昆明地区RhD初筛阴性献血者RHD基因的多态性及其分子机制,为建立区域性献血者RHD基因数据库提供数据支持。方法选择昆明地区2023年11月-2024年8月初筛RhD阴性标本218例,采用间接抗球蛋白试验法(IAT)进行RhD阴性确认,采用盐水试...目的研究昆明地区RhD初筛阴性献血者RHD基因的多态性及其分子机制,为建立区域性献血者RHD基因数据库提供数据支持。方法选择昆明地区2023年11月-2024年8月初筛RhD阴性标本218例,采用间接抗球蛋白试验法(IAT)进行RhD阴性确认,采用盐水试管法进行RhCE表型鉴定。提取全血基因组DNA,采用PCR-SSP法/SSP荧光PCR染料法进行RHD基因分型,对无法确定基因型的标本进行RHD基因1~10外显子Sanger测序分析。结果检出RhD真阴性表型179例(82.11%),其中RHD*01N.01(RHD全缺失)型154例(86.03%),表型以ccee为主(87.01%);携带非功能性RHD等位基因25例(13.97%),包括RHD*01N.0320例、RHD*01N.163例、RHD*01N.051例、RHD*01N.591例,表型以Ccee为主(64%)。检出D变异型39例(15.89%),其中RHD*DEL1(c.1227G>A)型34例,表型均为C抗原阳性(Ccee 27例,CCee 7例);弱D/部分D型4例,包括RHD*DVI.32例、RHD*weak D type 711例、RHD*weak D type1081例;另检出1例RHD*01/RHD*01N.01,基因型与血清学表型结果不一致。RHD*01N.01女性献血者不规则抗体(主要为抗-D)阳性率9.84%。结论昆明地区RhD初筛阴性献血者RHD基因多态性显著,RhD真阴性比例高于国内部分地区,D变异型以“亚洲型”DEL为主,比例低于国内部分地区。研究结果为本地区RhD阴性和D变异型个体精准输血提供了理论和数据支持。展开更多
目的通过对比分析“亚洲型”DEL孕妇与真阴性孕妇的临床抗-D同种免疫发生率,评估“亚洲型”DEL孕妇免于抗-D监测及RhD免疫球蛋白注射的可行性。方法收集2022年12月至2024年8月期间在本院就诊的165例经盐水法初筛为RhD阴性的孕妇作为研...目的通过对比分析“亚洲型”DEL孕妇与真阴性孕妇的临床抗-D同种免疫发生率,评估“亚洲型”DEL孕妇免于抗-D监测及RhD免疫球蛋白注射的可行性。方法收集2022年12月至2024年8月期间在本院就诊的165例经盐水法初筛为RhD阴性的孕妇作为研究对象。采用吸收放散试验、DEL基因分型和基因测序等技术将孕妇分为“亚洲型”DEL组和真阴性组。在获得知情同意的前提下,本研究对“亚洲型”DEL孕妇实施以下临床管理方案:免除常规抗-D检测、免于RhD免疫球蛋白注射和孕妇输注RhD阳性红细胞,待产后送检胎儿新生儿溶血病(hemolytic disease of the fetus and newborn,HDFN)检测。对真阴性孕妇实施常规管理方案。观察对比2组的同种免疫和HDFN发生情况。结果在165例初筛RhD阴性孕妇中,经血清学检测和基因分型鉴定,最终确认42例为“亚洲型”DEL、9例为D变异型和114例为真阴性。在42例“亚洲型”DEL孕妇中,3例因接受RhD免疫球蛋白注射而导致HDFN检测阳性;其余39例在充分告知风险后免除抗-D检测,未接受RhD免疫球蛋白预防,新生儿出生后HDFN检测均阴性。真阴性组中,20例检测到抗-D,其中6例HDFN检测阳性。1例“亚洲型”DEL孕妇在输注2单位RhD阳性红细胞后,未出现RhD同种免疫反应。统计结果显示,“亚洲型”DEL孕妇发生抗-D同种免疫的风险显著低于真阴性孕妇(P<0.05)。结论“亚洲型”DEL孕妇可免于常规抗-D检测,无需常规预防性RhD免疫球蛋白注射。展开更多
del Nido停搏液过去重点用于儿科先天性心脏病手术,目前其从儿科先心病正在逐步拓展到成人心脏外科并广泛应用于各种心脏外科手术中,包括心脏瓣膜手术、大血管手术、冠状动脉手术以及左心辅助装置手术等。随着微创在心外科的蓬勃发展,...del Nido停搏液过去重点用于儿科先天性心脏病手术,目前其从儿科先心病正在逐步拓展到成人心脏外科并广泛应用于各种心脏外科手术中,包括心脏瓣膜手术、大血管手术、冠状动脉手术以及左心辅助装置手术等。随着微创在心外科的蓬勃发展,期待未来能有更完善的心肌保护监测手段和应用策略,从而更有利于选择最适合的停搏液为手术提供有力的支持。本文旨在对del Nido停搏液从过去的应用、目前的发展及今后可能在新领域的潜在应用等方面进行总结,以期为相关领域的发展提供参考。展开更多
Intervertebral disc degeneration is a major risk factor contributing to chronic low back and neck pain.While the etiological factors for disc degeneration vary,age is still one of the most important risk factors.Recen...Intervertebral disc degeneration is a major risk factor contributing to chronic low back and neck pain.While the etiological factors for disc degeneration vary,age is still one of the most important risk factors.Recent studies have shown the promising role of SIRT6 in mammalian aging and skeletal tissue health,however its role in the intervertebral disc health remains unexplored.We investigated the contribution of SIRT6 to disc health by studying the age-dependent spinal phenotype of mice with conditional deletion of Sirt6 in the disc(AcanCreERT2;Sirt6fl/fl).Histological studies showed a degenerative phenotype in knockout mice compared to Sirt6fl/fl control mice at 12 months,which became pronounced at 24 months.RNA-Seq analysis of NP and AF tissues,in vitro quantitative histone analysis,and RNA-seq with ATAC-seq multiomic studies revealed that SIRT6-loss resulted in changes in acetylation and methylation status of specific Histone 3 lysine residues and affected DNA accessibility and transcriptomic landscape.A decrease in autophagy and an increase in DNA damage were also noted in Sirt6-deficient cells.Further mechanistic insights revealed that loss of SIRT6 increased senescence and SASP burden in the disc characterized by increased p21,p19,γH2AX,IL-6,IL-1β,and TGF-βabundance.Taken together,our study highlights the contribution of SIRT6 in modulating DNA damage,autophagy,and cell senescence and its importance in maintaining disc health during aging,thereby underscoring it as a potential therapeutic target to treat intervertebral disc degeneration.展开更多
Heart failure(HF)is a medical condition associated with high morbidity and mortality,despite ongoing advances in diagnosis and treatment.Among the various causes of HF,cardiomyopathies are particularly significant and...Heart failure(HF)is a medical condition associated with high morbidity and mortality,despite ongoing advances in diagnosis and treatment.Among the various causes of HF,cardiomyopathies are particularly significant and must be thoroughly diagnosed and characterized from the outset.In this review,we aim to present a brief overview of cardiomyopathies as a driver of HF,with a specific focus on the genetic causes,particularly nexilin(NEXN)cardiomyopathy,illustrated by a clinical case.The case involves a 63-year-old male who presented with HF symptoms at moderate exertion.Six months prior,he had been asymptomatic,and a routine transthoracic echocardiography had shown a preserved left ventricular ejection fraction(LVEF).However,during the current evaluation,transthoracic echocardiography revealed a dilated left ventricle with a severely reduced LVEF of 30%.Subsequent coronary angiography ruled out ischemic heart disease,while cardiac magnetic resonance imaging indicated a non-inflammatory,non-infiltrative dilated cardiomyopathy with extensive LV fibrosis.Genetic testing identified a heterozygous in-frame deletion variant in the NEXN gene[c.1949_1951del,p.(Gly650del)],classified as likely pathogenic.State-of-the-art HF treatment was initiated,including cardiac resynchronization therapy with defibrillator support.Following treatment,the patient’s symptoms resolved,and LVEF improved to 42%.Interestingly,this patient experienced the onset of symptoms and left ventricular dysfunction within just six months,a much faster progression compared to previously documented cases where the G650del NEXN variant is typically linked to a more gradual development of dilated cardiomyopathy.Current literature offers limited data on patients with NEXN mutations,and the connection between this gene and both dilated and hypertrophic cardiomyopathies remains an area of active research.展开更多
文摘目的研究昆明地区RhD初筛阴性献血者RHD基因的多态性及其分子机制,为建立区域性献血者RHD基因数据库提供数据支持。方法选择昆明地区2023年11月-2024年8月初筛RhD阴性标本218例,采用间接抗球蛋白试验法(IAT)进行RhD阴性确认,采用盐水试管法进行RhCE表型鉴定。提取全血基因组DNA,采用PCR-SSP法/SSP荧光PCR染料法进行RHD基因分型,对无法确定基因型的标本进行RHD基因1~10外显子Sanger测序分析。结果检出RhD真阴性表型179例(82.11%),其中RHD*01N.01(RHD全缺失)型154例(86.03%),表型以ccee为主(87.01%);携带非功能性RHD等位基因25例(13.97%),包括RHD*01N.0320例、RHD*01N.163例、RHD*01N.051例、RHD*01N.591例,表型以Ccee为主(64%)。检出D变异型39例(15.89%),其中RHD*DEL1(c.1227G>A)型34例,表型均为C抗原阳性(Ccee 27例,CCee 7例);弱D/部分D型4例,包括RHD*DVI.32例、RHD*weak D type 711例、RHD*weak D type1081例;另检出1例RHD*01/RHD*01N.01,基因型与血清学表型结果不一致。RHD*01N.01女性献血者不规则抗体(主要为抗-D)阳性率9.84%。结论昆明地区RhD初筛阴性献血者RHD基因多态性显著,RhD真阴性比例高于国内部分地区,D变异型以“亚洲型”DEL为主,比例低于国内部分地区。研究结果为本地区RhD阴性和D变异型个体精准输血提供了理论和数据支持。
文摘目的通过对比分析“亚洲型”DEL孕妇与真阴性孕妇的临床抗-D同种免疫发生率,评估“亚洲型”DEL孕妇免于抗-D监测及RhD免疫球蛋白注射的可行性。方法收集2022年12月至2024年8月期间在本院就诊的165例经盐水法初筛为RhD阴性的孕妇作为研究对象。采用吸收放散试验、DEL基因分型和基因测序等技术将孕妇分为“亚洲型”DEL组和真阴性组。在获得知情同意的前提下,本研究对“亚洲型”DEL孕妇实施以下临床管理方案:免除常规抗-D检测、免于RhD免疫球蛋白注射和孕妇输注RhD阳性红细胞,待产后送检胎儿新生儿溶血病(hemolytic disease of the fetus and newborn,HDFN)检测。对真阴性孕妇实施常规管理方案。观察对比2组的同种免疫和HDFN发生情况。结果在165例初筛RhD阴性孕妇中,经血清学检测和基因分型鉴定,最终确认42例为“亚洲型”DEL、9例为D变异型和114例为真阴性。在42例“亚洲型”DEL孕妇中,3例因接受RhD免疫球蛋白注射而导致HDFN检测阳性;其余39例在充分告知风险后免除抗-D检测,未接受RhD免疫球蛋白预防,新生儿出生后HDFN检测均阴性。真阴性组中,20例检测到抗-D,其中6例HDFN检测阳性。1例“亚洲型”DEL孕妇在输注2单位RhD阳性红细胞后,未出现RhD同种免疫反应。统计结果显示,“亚洲型”DEL孕妇发生抗-D同种免疫的风险显著低于真阴性孕妇(P<0.05)。结论“亚洲型”DEL孕妇可免于常规抗-D检测,无需常规预防性RhD免疫球蛋白注射。
基金supported by the Michael Michelson Gift FundNIA grants R01AG073349 (M.V.R.), R01AG044034 (R.F.L.), and R01AG078609 (J.C.)
文摘Intervertebral disc degeneration is a major risk factor contributing to chronic low back and neck pain.While the etiological factors for disc degeneration vary,age is still one of the most important risk factors.Recent studies have shown the promising role of SIRT6 in mammalian aging and skeletal tissue health,however its role in the intervertebral disc health remains unexplored.We investigated the contribution of SIRT6 to disc health by studying the age-dependent spinal phenotype of mice with conditional deletion of Sirt6 in the disc(AcanCreERT2;Sirt6fl/fl).Histological studies showed a degenerative phenotype in knockout mice compared to Sirt6fl/fl control mice at 12 months,which became pronounced at 24 months.RNA-Seq analysis of NP and AF tissues,in vitro quantitative histone analysis,and RNA-seq with ATAC-seq multiomic studies revealed that SIRT6-loss resulted in changes in acetylation and methylation status of specific Histone 3 lysine residues and affected DNA accessibility and transcriptomic landscape.A decrease in autophagy and an increase in DNA damage were also noted in Sirt6-deficient cells.Further mechanistic insights revealed that loss of SIRT6 increased senescence and SASP burden in the disc characterized by increased p21,p19,γH2AX,IL-6,IL-1β,and TGF-βabundance.Taken together,our study highlights the contribution of SIRT6 in modulating DNA damage,autophagy,and cell senescence and its importance in maintaining disc health during aging,thereby underscoring it as a potential therapeutic target to treat intervertebral disc degeneration.
文摘Heart failure(HF)is a medical condition associated with high morbidity and mortality,despite ongoing advances in diagnosis and treatment.Among the various causes of HF,cardiomyopathies are particularly significant and must be thoroughly diagnosed and characterized from the outset.In this review,we aim to present a brief overview of cardiomyopathies as a driver of HF,with a specific focus on the genetic causes,particularly nexilin(NEXN)cardiomyopathy,illustrated by a clinical case.The case involves a 63-year-old male who presented with HF symptoms at moderate exertion.Six months prior,he had been asymptomatic,and a routine transthoracic echocardiography had shown a preserved left ventricular ejection fraction(LVEF).However,during the current evaluation,transthoracic echocardiography revealed a dilated left ventricle with a severely reduced LVEF of 30%.Subsequent coronary angiography ruled out ischemic heart disease,while cardiac magnetic resonance imaging indicated a non-inflammatory,non-infiltrative dilated cardiomyopathy with extensive LV fibrosis.Genetic testing identified a heterozygous in-frame deletion variant in the NEXN gene[c.1949_1951del,p.(Gly650del)],classified as likely pathogenic.State-of-the-art HF treatment was initiated,including cardiac resynchronization therapy with defibrillator support.Following treatment,the patient’s symptoms resolved,and LVEF improved to 42%.Interestingly,this patient experienced the onset of symptoms and left ventricular dysfunction within just six months,a much faster progression compared to previously documented cases where the G650del NEXN variant is typically linked to a more gradual development of dilated cardiomyopathy.Current literature offers limited data on patients with NEXN mutations,and the connection between this gene and both dilated and hypertrophic cardiomyopathies remains an area of active research.
