Hypertonia is a neurological dysfunction associated with a number of central nervous system disorders, including cerebral palsy, Parkinson's disease, dystonia, and epilepsy. Genetic studies have identified a homozygo...Hypertonia is a neurological dysfunction associated with a number of central nervous system disorders, including cerebral palsy, Parkinson's disease, dystonia, and epilepsy. Genetic studies have identified a homozygous truncation mutation in Trakl that causes hypertonia in mice. Moreover, elevated Trakl protein expression is associated with several types of cancers and variants in Trakl are linked to childhood absence epilepsy in humans. Despite the importance of Trakl in health and disease, the mechanisms of Trakl action remain unclear and the pathogenic effects of Trakl mutation are unknown. Here we report that Trakl has a crucial function in regulation of mitochondrial fusion. Depletion of Trakl inhibits mitochondrial fusion, result- ing in mitochondrial fragmentation, whereas overex- pression of Trakl elongates and enlarges mitochondria. Our analyses revealed that Trakl interacts and colocal- izes with mitofusins on the outer mitochondrial mem- brane and functions with mitofusins to promote mitochondrial tethering and fusion. Furthermore, Trakl is required for stress-induced mitochondrial hyperfu- sion and pro-survival response. We found that hyper- tonia-associated mutation impairs Trakl mitochondrial localization and its ability to facilitate mitochondrial tethering and fusion. Our findings uncover a novel function of Trakl as a regulator of mitochondrial fusion and provide evidence linking dysregulated mitochon- drial dynamics to hypertonia pathogenesis.展开更多
目的:观察盆底磁刺激联合内脏松弛术在剖宫产术后盆底肌高张中的疗效。方法:本次临床研究拟选取2023年1月—2025年1月就诊于上饶市人民医院的剖宫产术后盆底肌高张患者80例作为研究对象,按随机数字表法将其分为对照组(n=40)和观察组(n=4...目的:观察盆底磁刺激联合内脏松弛术在剖宫产术后盆底肌高张中的疗效。方法:本次临床研究拟选取2023年1月—2025年1月就诊于上饶市人民医院的剖宫产术后盆底肌高张患者80例作为研究对象,按随机数字表法将其分为对照组(n=40)和观察组(n=40),其中对照组给予盆底磁刺激治疗,观察组在对照组的基础上联合应用内脏松弛术治疗。对比两组盆底肌及盆骨带VAS评分、Ⅰ和Ⅱ类肌纤维肌力、盆底功能情况(前后静息电位、快慢肌收缩肌电位)、女性性功能指数量表(female sexual function index,FSFI)评分及最大尿流率(maximum urinary flow rate,Qmax)和排尿后残余尿量(post-void residual urine volume,PVR)水平。结果:治疗3个月后,相较于对照组,观察组的盆底肌及骨盆带VAS评分均较低(P<0.05);相较于对照组,观察组Ⅰ、Ⅱ类肌纤维肌力水平均较高(P<0.05);在盆底表面肌电方面,治疗3个月后两组均有明显改善(P<0.05),相较于对照组,观察组治疗3个月后的前、后静息电位均较低(P<0.05);两组快、慢肌收缩电位差异无统计学意义(P>0.05);治疗3个月后,相较于对照组,观察组FSFI中性欲、性唤起、阴道湿润度、性高潮、性生活满意度、性交疼痛评分水平均较高(P<0.05);相较于对照组,治疗3个月后,观察组Qmax水平较高,PVR较低(P<0.05);两组患者均未发现并发症。结论:盆底磁刺激联合内脏松弛术治疗剖宫产术后盆底肌高张能够有效缓解盆底肌及盆骨带疼痛程度、提升肌纤维肌力及改善盆底肌电静息电位及排尿情况,并且在性功能改善方面也更具优势,安全性良好。展开更多
文摘Hypertonia is a neurological dysfunction associated with a number of central nervous system disorders, including cerebral palsy, Parkinson's disease, dystonia, and epilepsy. Genetic studies have identified a homozygous truncation mutation in Trakl that causes hypertonia in mice. Moreover, elevated Trakl protein expression is associated with several types of cancers and variants in Trakl are linked to childhood absence epilepsy in humans. Despite the importance of Trakl in health and disease, the mechanisms of Trakl action remain unclear and the pathogenic effects of Trakl mutation are unknown. Here we report that Trakl has a crucial function in regulation of mitochondrial fusion. Depletion of Trakl inhibits mitochondrial fusion, result- ing in mitochondrial fragmentation, whereas overex- pression of Trakl elongates and enlarges mitochondria. Our analyses revealed that Trakl interacts and colocal- izes with mitofusins on the outer mitochondrial mem- brane and functions with mitofusins to promote mitochondrial tethering and fusion. Furthermore, Trakl is required for stress-induced mitochondrial hyperfu- sion and pro-survival response. We found that hyper- tonia-associated mutation impairs Trakl mitochondrial localization and its ability to facilitate mitochondrial tethering and fusion. Our findings uncover a novel function of Trakl as a regulator of mitochondrial fusion and provide evidence linking dysregulated mitochon- drial dynamics to hypertonia pathogenesis.
文摘目的:观察盆底磁刺激联合内脏松弛术在剖宫产术后盆底肌高张中的疗效。方法:本次临床研究拟选取2023年1月—2025年1月就诊于上饶市人民医院的剖宫产术后盆底肌高张患者80例作为研究对象,按随机数字表法将其分为对照组(n=40)和观察组(n=40),其中对照组给予盆底磁刺激治疗,观察组在对照组的基础上联合应用内脏松弛术治疗。对比两组盆底肌及盆骨带VAS评分、Ⅰ和Ⅱ类肌纤维肌力、盆底功能情况(前后静息电位、快慢肌收缩肌电位)、女性性功能指数量表(female sexual function index,FSFI)评分及最大尿流率(maximum urinary flow rate,Qmax)和排尿后残余尿量(post-void residual urine volume,PVR)水平。结果:治疗3个月后,相较于对照组,观察组的盆底肌及骨盆带VAS评分均较低(P<0.05);相较于对照组,观察组Ⅰ、Ⅱ类肌纤维肌力水平均较高(P<0.05);在盆底表面肌电方面,治疗3个月后两组均有明显改善(P<0.05),相较于对照组,观察组治疗3个月后的前、后静息电位均较低(P<0.05);两组快、慢肌收缩电位差异无统计学意义(P>0.05);治疗3个月后,相较于对照组,观察组FSFI中性欲、性唤起、阴道湿润度、性高潮、性生活满意度、性交疼痛评分水平均较高(P<0.05);相较于对照组,治疗3个月后,观察组Qmax水平较高,PVR较低(P<0.05);两组患者均未发现并发症。结论:盆底磁刺激联合内脏松弛术治疗剖宫产术后盆底肌高张能够有效缓解盆底肌及盆骨带疼痛程度、提升肌纤维肌力及改善盆底肌电静息电位及排尿情况,并且在性功能改善方面也更具优势,安全性良好。