Neuromuscular electrical stimulation(NMES)is a well-established therapeutic approach for chronic wounds.Conventionally,NMES involves direct electrode contact with wounds or adjacent healthy skin;however,it is limited ...Neuromuscular electrical stimulation(NMES)is a well-established therapeutic approach for chronic wounds.Conventionally,NMES involves direct electrode contact with wounds or adjacent healthy skin;however,it is limited by the need for wound exposure and by increased pain.Our preliminary study demonstrated the innovative application of remote NMES(rNMES)to the skeletal muscle of the distal calf,which showed the potential to accelerate wound healing in remote areas.rNMES was effective in human clinical trials in our previous work,although the underlying mechanisms remain unclear.As rNMES is often used to stimulate muscle contraction in long-term bedridden patients,we analyzed data from the Gene Expression Omnibus(GEO)database and found that exercise promotes midkine(MDK)expression in muscle.MDK is a small secreted heparin-binding protein that interacts with multiple cell surface receptors to promote growth.In the present study,we found that MDK significantly enhanced macrophage efferocytosis in a low-density lipoprotein receptor-related protein 1(LRP1)-dependent manner.Our findings demonstrate that rNMES upregulates MDK expression in skeletal muscles through the AMPK-ERK axis,facilitating its delivery to wounds through the circulatory system and promoting LRP1-mediated efferocytosis of apoptotic cells,thereby expediting wound healing.展开更多
Machado-Joseph disease,or spinocerebellar ataxia type 3(SCA3),represents the most common autosomal dominant cerebellar ataxia worldwide.Despite its progressive and debilitating nature,disease-modifying therapies remai...Machado-Joseph disease,or spinocerebellar ataxia type 3(SCA3),represents the most common autosomal dominant cerebellar ataxia worldwide.Despite its progressive and debilitating nature,disease-modifying therapies remain elusive.Repetitive transcranial magnetic stimulation(rTMS)has emerged as a promising non-invasive intervention;however,its clinical application has been hindered by inconsistent protocols and a lack of mechanistic understanding.A recent landmark study published in Brain Stimulation by Chen et al.addressed these challenges by combining a high-dose intermittent theta-burst stimulation(iTBS)protocol with concurrent transcranial magnetic stimulation-electroencephalography(TMS-EEG).This commentary provides an in-depth analysis of their findings,highlighting the restoration of cerebello-cortical inhibition(CBI)as a key therapeutic mechanism.Furthermore,we discuss the broader implications of this work,proposing that future translational research should integrate accelerated iTBS(aiTBS)paradigms,cortical response measurements(CRM),and individualized neuro-navigation to establish a new era of precision neuromodulation for ataxia.展开更多
目的:通过Meta分析系统性评估间歇性Theta刺激改善脑卒中患者下肢运动功能、平衡功能以及日常活动能力的效果。方法:检索Cochrane Library、Scopus、PubMed、Embase、ProQuest、Web of Science、中国知网、中国生物医学、维普和万方数据...目的:通过Meta分析系统性评估间歇性Theta刺激改善脑卒中患者下肢运动功能、平衡功能以及日常活动能力的效果。方法:检索Cochrane Library、Scopus、PubMed、Embase、ProQuest、Web of Science、中国知网、中国生物医学、维普和万方数据库,选择各数据库建库至2024年11月期间间歇性Theta刺激治疗脑卒中的随机对照试验。其中,试验组接受小脑/M1区间歇性Theta刺激,对照组进行常规康复治疗。采用RevMan 5.3和Stata 16.0进行Meta分析。结果:共纳入12篇文献,444例患者。Meta分析表明,间歇性Theta刺激有助于提高脑卒中患者下肢Fugl-Meyer量表评分[WMD=2.87,95%CI(1.77,3.98),P<0.00001]、Berg平衡量表评分[WMD=5.79,95%CI(3.80,7.79),P<0.00001]以及改良Barthel指数[WMD=6.32,95%CI(4.02,8.44),P<0.00001]。亚组分析结果显示,相较于600脉冲刺激,1200脉冲刺激更有利于改善下肢Fugl-Meyer量表评分[WMD=4.31,95%CI(2.91,5.71),P<0.00001]、Berg平衡量表评分[WMD=8.12,95%CI(5.27,10.98),P<0.00001]和改良Barthel指数[WMD=8.50,95%CI(6.55,10.45),P<0.00001]。结论:间歇性Theta刺激能够提高脑卒中患者的下肢运动能力、平衡功能及日常生活能力评分。其中,1200脉冲间歇性Theta刺激在改善下肢运动能力、平衡功能和日常生活能力方面,可能具有更大益处。展开更多
基金supported by the National Natural Science Foundation of China(Grant No.82271252 to W.L.,No.8217091029 to T.W.and No.82204542 to L.H.)the Key Medical Research Projects of Jiangsu Health and Health Commission(Grant No.K2023066 to L.Z.)the Taishan Industrial Talent Project(Grant No.2020-371722-73-03-097290 to W.L.).
文摘Neuromuscular electrical stimulation(NMES)is a well-established therapeutic approach for chronic wounds.Conventionally,NMES involves direct electrode contact with wounds or adjacent healthy skin;however,it is limited by the need for wound exposure and by increased pain.Our preliminary study demonstrated the innovative application of remote NMES(rNMES)to the skeletal muscle of the distal calf,which showed the potential to accelerate wound healing in remote areas.rNMES was effective in human clinical trials in our previous work,although the underlying mechanisms remain unclear.As rNMES is often used to stimulate muscle contraction in long-term bedridden patients,we analyzed data from the Gene Expression Omnibus(GEO)database and found that exercise promotes midkine(MDK)expression in muscle.MDK is a small secreted heparin-binding protein that interacts with multiple cell surface receptors to promote growth.In the present study,we found that MDK significantly enhanced macrophage efferocytosis in a low-density lipoprotein receptor-related protein 1(LRP1)-dependent manner.Our findings demonstrate that rNMES upregulates MDK expression in skeletal muscles through the AMPK-ERK axis,facilitating its delivery to wounds through the circulatory system and promoting LRP1-mediated efferocytosis of apoptotic cells,thereby expediting wound healing.
基金supported by grants from the Open Research Fund of the Zhejiang Key Laboratory of Precision Psychiatry(2025A2)the Natural Science Foundation of Zhejiang Province(LY23C090002)。
文摘Machado-Joseph disease,or spinocerebellar ataxia type 3(SCA3),represents the most common autosomal dominant cerebellar ataxia worldwide.Despite its progressive and debilitating nature,disease-modifying therapies remain elusive.Repetitive transcranial magnetic stimulation(rTMS)has emerged as a promising non-invasive intervention;however,its clinical application has been hindered by inconsistent protocols and a lack of mechanistic understanding.A recent landmark study published in Brain Stimulation by Chen et al.addressed these challenges by combining a high-dose intermittent theta-burst stimulation(iTBS)protocol with concurrent transcranial magnetic stimulation-electroencephalography(TMS-EEG).This commentary provides an in-depth analysis of their findings,highlighting the restoration of cerebello-cortical inhibition(CBI)as a key therapeutic mechanism.Furthermore,we discuss the broader implications of this work,proposing that future translational research should integrate accelerated iTBS(aiTBS)paradigms,cortical response measurements(CRM),and individualized neuro-navigation to establish a new era of precision neuromodulation for ataxia.
