发育性和癫痫性脑病93(Developmental and epileptic encephalopathy 93,DEE93)(MIM:618012)是一种常染色体显性遗传神经系统疾病,主要特点为精神运动发育迟缓、早发难治性癫痫和智力低下等,且与ATP6V1A基因变异有关^([1])。DEE93临床...发育性和癫痫性脑病93(Developmental and epileptic encephalopathy 93,DEE93)(MIM:618012)是一种常染色体显性遗传神经系统疾病,主要特点为精神运动发育迟缓、早发难治性癫痫和智力低下等,且与ATP6V1A基因变异有关^([1])。DEE93临床表现差异大,病情轻重不一,重者可因快速进展的早期致命性脑病而死亡,轻者仅表现为轻度至中度智力障碍,伴或不伴癫痫发作^([2-3])。ATP6V1A基因(MIM#607027)染色体位置为3q13.3,包含15个外显子,编码617个氨基酸,是组成ATP酶(V-ATPase)的一个亚基,参与介导真核细胞内的质子运输过程和细胞器的酸化。本文报告了1例全外显子测序发现ATP6V1A基因杂合致病性变异c.937G>C:p.Ala313Pro的婴儿,描述了其临床表现并复习相关文献内容,扩展了ATP6V1A基因突变相关DEE93的临床特征和遗传谱,为该病的诊断、治疗和遗传咨询提供参考。展开更多
目的探讨心电图P波参数与脑白质病变(white matter lesions,WMLs)严重程度之间的关联,为WMLs的预防和治疗提供科学依据。方法选取289例符合入组标准的WMLs住院患者作为研究对象,其均接受常规12导联心电图和头颅磁共振成像检查。根据Faze...目的探讨心电图P波参数与脑白质病变(white matter lesions,WMLs)严重程度之间的关联,为WMLs的预防和治疗提供科学依据。方法选取289例符合入组标准的WMLs住院患者作为研究对象,其均接受常规12导联心电图和头颅磁共振成像检查。根据Fazekas量表评分将这些患者分为无-轻度组(158例)和中-重度组(131例)。收集两组患者的临床资料、既往病史、心电图P波参数[包括P波时限、P波电轴、V_(1)导联P波终末电势(terminal force of P-wave in lead V_(1),PTFV_(1))],以及血脂等数据,并进行比较分析。采用Logistic回归模型分析影响WMLs的独立危险因素。结果中-重度组患者的年龄、有高血压或糖尿病病史者占比及PTFV_(1)>4000μV·ms者占比均明显高于无-轻度组,且差异均有统计学意义(均P<0.01)。多变量Logistic回归分析表明,年龄增长、高血压、糖尿病以及PTFV_(1)>4000μV·ms均为WMLs的独立危险因素。结论无创心电图指标PTFV_(1)经济便捷、易于获取,可用于评估心房异常,对WMLs的防治具有一定的应用价值。展开更多
精氨酸加压素(Arginine Vasopressin, AVP),又称抗利尿激素(Antidiuretic Hormone, ADH),是一种由下丘脑合成的环状九肽神经激素,在机体水盐平衡和血压稳态调节中发挥核心调控作用。AVP通过特异性结合G蛋白偶联受体(G Protein-Coupled R...精氨酸加压素(Arginine Vasopressin, AVP),又称抗利尿激素(Antidiuretic Hormone, ADH),是一种由下丘脑合成的环状九肽神经激素,在机体水盐平衡和血压稳态调节中发挥核心调控作用。AVP通过特异性结合G蛋白偶联受体(G Protein-Coupled Receptor, GPCR)家族成员V1受体(Vasopressin type 1 receptor, V1R)和V2受体(Vasopressin type 2 receptor, V2R)介导其生理功能:V1R主要分布于血管平滑肌,参与调控血管张力及血小板活化;V2R则高表达于肾脏集合管和远端肾小管,通过调节水通道蛋白2 (Aquaporin-2, AQP2)的膜转运介导水的重吸收。近年来,随着冷冻电子显微镜(Cryogenic Electron Microscopy, Cryo-EM)等结构生物学技术的突破,研究人员成功解析了AVP受体复合物的高分辨率三维结构,为阐明其配体识别机制和信号转导途径提供了重要的结构基础。这些研究成果不仅深化了对AVP信号通路的分子机制理解,也为基于结构的精准药物设计提供了新思路。基于V1R和V2R结构特征开发的高选择性配体有望为高血压、尿崩症等疾病的治疗提供更安全有效的治疗方案。Arginine vasopressin (AVP), also known as antidiuretic hormone (ADH), is a cyclic nonapeptide neurohormone synthesized in the hypothalamus, playing a critical role in maintaining water-electrolyte balance and blood pressure homeostasis. AVP mediates its effects through specific binding to G protein-coupled receptors (GPCRs), primarily V1R and V2R. V1R is predominantly expressed in vascular smooth muscle, where it regulates vascular tone and platelet activation, V2R is highly expressed in the renal collecting ducts and distal nephron, where V2R orchestrates water reabsorption by modulating the membrane trafficking of aquaporin-2 (AQP2). In recent years, with the breakthroughs in structural biology techniques such as Cryogenic Electron Microscopy (Cryo-EM), researchers have successfully determined the high-resolution three-dimensional structure of the arginine vasopressin (AVP) receptor complex. This achievement provides a crucial structural foundation for elucidating the ligand recognition mechanism and signal transduction pathway of the AVP receptor. These research findings not only deepen our understanding of the molecular mechanisms underlying the AVP signaling pathway but also offer novel insights into structure-based precision drug design. Highly selective ligands developed based on the structural characteristics of V1R (vasopressin receptor 1) and V2R (vasopressin receptor 2) hold great promise for providing safer and more effective therapeutic strategies for diseases such as hypertension and diabetes insipidus.展开更多
Bet v 1基因家族编码植物病程相关蛋白PR10,参与植物的非生物和生物胁迫应答。本研究对新疆沙冬青Bet v 1基因家族进行筛选和进化分析,并通过实时荧光定量PCR分析了Bet v 1基因在低温和渗透胁迫下的表达模式。结果表明筛选到27个新疆沙...Bet v 1基因家族编码植物病程相关蛋白PR10,参与植物的非生物和生物胁迫应答。本研究对新疆沙冬青Bet v 1基因家族进行筛选和进化分析,并通过实时荧光定量PCR分析了Bet v 1基因在低温和渗透胁迫下的表达模式。结果表明筛选到27个新疆沙冬青Bet v 1基因家族成员,均包含内含子,分布于6条染色体上。在新疆沙冬青中有11个Bet v 1基因在大豆、拟南芥基因组中具有直系同源基因。该基因家族成员的启动子中含有大量与逆境胁迫和激素响应相关的元件。基因表达分析显示EVM0015604.1、EVM0020624.1、EVM000-0761.1、EVM0033568.1和EVM0004485.1的表达量在低温和渗透胁迫下升高,推测Bet v 1基因参与了新疆沙冬青响应低温和干旱胁迫。本研究为理解植物Bet v 1基因的功能提供了一定的理论依据。展开更多
文摘发育性和癫痫性脑病93(Developmental and epileptic encephalopathy 93,DEE93)(MIM:618012)是一种常染色体显性遗传神经系统疾病,主要特点为精神运动发育迟缓、早发难治性癫痫和智力低下等,且与ATP6V1A基因变异有关^([1])。DEE93临床表现差异大,病情轻重不一,重者可因快速进展的早期致命性脑病而死亡,轻者仅表现为轻度至中度智力障碍,伴或不伴癫痫发作^([2-3])。ATP6V1A基因(MIM#607027)染色体位置为3q13.3,包含15个外显子,编码617个氨基酸,是组成ATP酶(V-ATPase)的一个亚基,参与介导真核细胞内的质子运输过程和细胞器的酸化。本文报告了1例全外显子测序发现ATP6V1A基因杂合致病性变异c.937G>C:p.Ala313Pro的婴儿,描述了其临床表现并复习相关文献内容,扩展了ATP6V1A基因突变相关DEE93的临床特征和遗传谱,为该病的诊断、治疗和遗传咨询提供参考。
文摘目的探讨心电图P波参数与脑白质病变(white matter lesions,WMLs)严重程度之间的关联,为WMLs的预防和治疗提供科学依据。方法选取289例符合入组标准的WMLs住院患者作为研究对象,其均接受常规12导联心电图和头颅磁共振成像检查。根据Fazekas量表评分将这些患者分为无-轻度组(158例)和中-重度组(131例)。收集两组患者的临床资料、既往病史、心电图P波参数[包括P波时限、P波电轴、V_(1)导联P波终末电势(terminal force of P-wave in lead V_(1),PTFV_(1))],以及血脂等数据,并进行比较分析。采用Logistic回归模型分析影响WMLs的独立危险因素。结果中-重度组患者的年龄、有高血压或糖尿病病史者占比及PTFV_(1)>4000μV·ms者占比均明显高于无-轻度组,且差异均有统计学意义(均P<0.01)。多变量Logistic回归分析表明,年龄增长、高血压、糖尿病以及PTFV_(1)>4000μV·ms均为WMLs的独立危险因素。结论无创心电图指标PTFV_(1)经济便捷、易于获取,可用于评估心房异常,对WMLs的防治具有一定的应用价值。
文摘精氨酸加压素(Arginine Vasopressin, AVP),又称抗利尿激素(Antidiuretic Hormone, ADH),是一种由下丘脑合成的环状九肽神经激素,在机体水盐平衡和血压稳态调节中发挥核心调控作用。AVP通过特异性结合G蛋白偶联受体(G Protein-Coupled Receptor, GPCR)家族成员V1受体(Vasopressin type 1 receptor, V1R)和V2受体(Vasopressin type 2 receptor, V2R)介导其生理功能:V1R主要分布于血管平滑肌,参与调控血管张力及血小板活化;V2R则高表达于肾脏集合管和远端肾小管,通过调节水通道蛋白2 (Aquaporin-2, AQP2)的膜转运介导水的重吸收。近年来,随着冷冻电子显微镜(Cryogenic Electron Microscopy, Cryo-EM)等结构生物学技术的突破,研究人员成功解析了AVP受体复合物的高分辨率三维结构,为阐明其配体识别机制和信号转导途径提供了重要的结构基础。这些研究成果不仅深化了对AVP信号通路的分子机制理解,也为基于结构的精准药物设计提供了新思路。基于V1R和V2R结构特征开发的高选择性配体有望为高血压、尿崩症等疾病的治疗提供更安全有效的治疗方案。Arginine vasopressin (AVP), also known as antidiuretic hormone (ADH), is a cyclic nonapeptide neurohormone synthesized in the hypothalamus, playing a critical role in maintaining water-electrolyte balance and blood pressure homeostasis. AVP mediates its effects through specific binding to G protein-coupled receptors (GPCRs), primarily V1R and V2R. V1R is predominantly expressed in vascular smooth muscle, where it regulates vascular tone and platelet activation, V2R is highly expressed in the renal collecting ducts and distal nephron, where V2R orchestrates water reabsorption by modulating the membrane trafficking of aquaporin-2 (AQP2). In recent years, with the breakthroughs in structural biology techniques such as Cryogenic Electron Microscopy (Cryo-EM), researchers have successfully determined the high-resolution three-dimensional structure of the arginine vasopressin (AVP) receptor complex. This achievement provides a crucial structural foundation for elucidating the ligand recognition mechanism and signal transduction pathway of the AVP receptor. These research findings not only deepen our understanding of the molecular mechanisms underlying the AVP signaling pathway but also offer novel insights into structure-based precision drug design. Highly selective ligands developed based on the structural characteristics of V1R (vasopressin receptor 1) and V2R (vasopressin receptor 2) hold great promise for providing safer and more effective therapeutic strategies for diseases such as hypertension and diabetes insipidus.
文摘Bet v 1基因家族编码植物病程相关蛋白PR10,参与植物的非生物和生物胁迫应答。本研究对新疆沙冬青Bet v 1基因家族进行筛选和进化分析,并通过实时荧光定量PCR分析了Bet v 1基因在低温和渗透胁迫下的表达模式。结果表明筛选到27个新疆沙冬青Bet v 1基因家族成员,均包含内含子,分布于6条染色体上。在新疆沙冬青中有11个Bet v 1基因在大豆、拟南芥基因组中具有直系同源基因。该基因家族成员的启动子中含有大量与逆境胁迫和激素响应相关的元件。基因表达分析显示EVM0015604.1、EVM0020624.1、EVM000-0761.1、EVM0033568.1和EVM0004485.1的表达量在低温和渗透胁迫下升高,推测Bet v 1基因参与了新疆沙冬青响应低温和干旱胁迫。本研究为理解植物Bet v 1基因的功能提供了一定的理论依据。
