Objective Repetitive transcranial magnetic stimulation(rTMS)has demonstrated efficacy in enhancing neurocognitive performance in Alzheimer’s disease(AD),but the neurobiological mechanisms linking synaptic pathology,n...Objective Repetitive transcranial magnetic stimulation(rTMS)has demonstrated efficacy in enhancing neurocognitive performance in Alzheimer’s disease(AD),but the neurobiological mechanisms linking synaptic pathology,neural oscillatory dynamics,and brain network reorganization remain unclear.This investigation seeks to systematically evaluate the therapeutic potential of rTMS as a non-invasive neuromodulatory intervention through a multimodal framework integrating clinical assessments,molecular profiling,and neurophysiological monitoring.Methods In this prospective double-blind trial,12 AD patients underwent a 14-day protocol of 20 Hz rTMS,with comprehensive multimodal assessments performed pre-and postintervention.Cognitive functioning was quantified using the mini-mental state examination(MMSE)and Montreal cognitive assessment(MOCA),while daily living capacities and neuropsychiatric profiles were respectively evaluated through the activities of daily living(ADL)scale and combined neuropsychiatric inventory(NPI)-Hamilton depression rating scale(HAMD).Peripheral blood biomarkers,specifically Aβ1-40 and phosphorylated tau(p-tau181),were analyzed to investigate the effects of rTMS on molecular metabolism.Spectral power analysis was employed to investigate rTMS-induced modulations of neural rhythms in AD patients,while brain network analyses incorporating topological properties were conducted to examine stimulus-driven network reorganization.Furthermore,systematic assessment of correlations between cognitive scale scores,blood biomarkers,and network characteristics was performed to elucidate cross-modal therapeutic associations.Results Clinically,MMSE and MOCA scores improved significantly(P<0.05).Biomarker showed that Aβ1-40 level increased(P<0.05),contrasting with p-tau181 reduction.Moreover,the levels of Aβ1-40 were positively correlated with MMSE and MOCA scores.Post-intervention analyses revealed significant modulations in oscillatory power,characterized by pronounced reductions in delta(P<0.05)and theta bands(P<0.05),while concurrent enhancements were observed in alpha,beta,and gamma band activities(all P<0.05).Network analysis revealed frequency-specific reorganization:clustering coefficients were significantly decreased in delta,theta,and alpha bands(P<0.05),while global efficiency improvement was exclusively detected in the delta band(P<0.05).The alpha band demonstrated concurrent increases in average nodal degree(P<0.05)and characteristic path length reduction(P<0.05).Further research findings indicate that the changes in the clinical scale HAMD scores before and after rTMS stimulation are negatively correlated with the changes in the blood biomarkers Aβ1-40 and p-tau181.Additionally,the changes in the clinical scales MMSE and MoCA scores were negatively correlated with the changes in the node degree of the alpha frequency band and negatively correlated with the clustering coefficient of the delta frequency band.However,the changes in MMSE scores are positively correlated with the changes in global efficiency of both the delta and alpha frequency bands.Conclusion 20 Hz rTMS targeting dorsolateral prefrontal cortex(DLPFC)significantly improves cognitive function and enhances the metabolic clearance ofβ-amyloid and tau proteins in AD patients.This neurotherapeutic effect is mechanistically associated with rTMS-mediated frequency-selective neuromodulation,which enhances the connectivity of oscillatory networks through improved neuronal synchronization and optimized topological organization of functional brain networks.These findings not only support the efficacy of rTMS as an adjunctive therapy for AD but also underscore the importance of employing multiple assessment methods—including clinical scales,blood biomarkers,and EEG——in understanding and monitoring the progression of AD.This research provides a significant theoretical foundation and empirical evidence for further exploration of rTMS applications in AD treatment.展开更多
In this paper,a new micro-creep model of salt rock is proposed based on a linear parallel bonded model(LPBM)using the two-dimensional particle flow code(PFC2D).The power function weakening form is assumed to describe ...In this paper,a new micro-creep model of salt rock is proposed based on a linear parallel bonded model(LPBM)using the two-dimensional particle flow code(PFC2D).The power function weakening form is assumed to describe the variation of the parallel bonded diameter(PBD)over time.By comparing with the parallel-bonded stress corrosion(PSC)model,a smaller stress fluctuation and smoother creep strain−time curves can be obtained by this power function model at the same stress level.The validity and adaptability of the model to simulate creep deformation of salt rock are verified through comparing the laboratory creep test curves and the Burgers model fitting result.The numerical results reveal that this model can be capable of capturing the creep deformation and damage behavior from the laboratory observations.展开更多
The development of the socialist market economy demands the furtherintensification of the reform of the management operating system (MOS)of the state-owned assets, the strengthening of the efficiency in the man-agemen...The development of the socialist market economy demands the furtherintensification of the reform of the management operating system (MOS)of the state-owned assets, the strengthening of the efficiency in the man-agement of state-owned assets,and the improvement of the operating bene-展开更多
文章以幂函数变换为研究对象,从背景值误差和还原误差的角度分析了幂函数变换对GM(1,1)模型建模精度的影响,论证了幂函数变换的GM(1,1)模型(PFNGM(1,1)模型)具有逼近无偏性,能在可忽略的误差范围内实现对白指数序列的预测无偏性。实例...文章以幂函数变换为研究对象,从背景值误差和还原误差的角度分析了幂函数变换对GM(1,1)模型建模精度的影响,论证了幂函数变换的GM(1,1)模型(PFNGM(1,1)模型)具有逼近无偏性,能在可忽略的误差范围内实现对白指数序列的预测无偏性。实例应用结果表明,其建模精度和预测效果均优于无偏GM(1,1)模型和离散GM(1,1)模型。为将适宜建模序列拓展至近似非齐次指数序列和季节波动序列,同时保留幂函数变换可以有效降低背景值误差对建模精度影响的优势,将幂函数变换与平移变换相结合构建了PFNGM(1,1)模型,将幂函数变换与季节性GM(1,1)模型(SGM(1,1)模型)相结合构建了PFSGM(1,1)模型。实例应用结果表明,PFNGM(1,1)模型的建模精度和预测效果均优于背景值改进的NGM(1,1, k )模型和ONGM(1,1, k,c )模型,PFSGM(1,1)模型的建模精度和预测效果均优于SGM(1,1)模型,验证了两种模型的有效性。展开更多
文摘Objective Repetitive transcranial magnetic stimulation(rTMS)has demonstrated efficacy in enhancing neurocognitive performance in Alzheimer’s disease(AD),but the neurobiological mechanisms linking synaptic pathology,neural oscillatory dynamics,and brain network reorganization remain unclear.This investigation seeks to systematically evaluate the therapeutic potential of rTMS as a non-invasive neuromodulatory intervention through a multimodal framework integrating clinical assessments,molecular profiling,and neurophysiological monitoring.Methods In this prospective double-blind trial,12 AD patients underwent a 14-day protocol of 20 Hz rTMS,with comprehensive multimodal assessments performed pre-and postintervention.Cognitive functioning was quantified using the mini-mental state examination(MMSE)and Montreal cognitive assessment(MOCA),while daily living capacities and neuropsychiatric profiles were respectively evaluated through the activities of daily living(ADL)scale and combined neuropsychiatric inventory(NPI)-Hamilton depression rating scale(HAMD).Peripheral blood biomarkers,specifically Aβ1-40 and phosphorylated tau(p-tau181),were analyzed to investigate the effects of rTMS on molecular metabolism.Spectral power analysis was employed to investigate rTMS-induced modulations of neural rhythms in AD patients,while brain network analyses incorporating topological properties were conducted to examine stimulus-driven network reorganization.Furthermore,systematic assessment of correlations between cognitive scale scores,blood biomarkers,and network characteristics was performed to elucidate cross-modal therapeutic associations.Results Clinically,MMSE and MOCA scores improved significantly(P<0.05).Biomarker showed that Aβ1-40 level increased(P<0.05),contrasting with p-tau181 reduction.Moreover,the levels of Aβ1-40 were positively correlated with MMSE and MOCA scores.Post-intervention analyses revealed significant modulations in oscillatory power,characterized by pronounced reductions in delta(P<0.05)and theta bands(P<0.05),while concurrent enhancements were observed in alpha,beta,and gamma band activities(all P<0.05).Network analysis revealed frequency-specific reorganization:clustering coefficients were significantly decreased in delta,theta,and alpha bands(P<0.05),while global efficiency improvement was exclusively detected in the delta band(P<0.05).The alpha band demonstrated concurrent increases in average nodal degree(P<0.05)and characteristic path length reduction(P<0.05).Further research findings indicate that the changes in the clinical scale HAMD scores before and after rTMS stimulation are negatively correlated with the changes in the blood biomarkers Aβ1-40 and p-tau181.Additionally,the changes in the clinical scales MMSE and MoCA scores were negatively correlated with the changes in the node degree of the alpha frequency band and negatively correlated with the clustering coefficient of the delta frequency band.However,the changes in MMSE scores are positively correlated with the changes in global efficiency of both the delta and alpha frequency bands.Conclusion 20 Hz rTMS targeting dorsolateral prefrontal cortex(DLPFC)significantly improves cognitive function and enhances the metabolic clearance ofβ-amyloid and tau proteins in AD patients.This neurotherapeutic effect is mechanistically associated with rTMS-mediated frequency-selective neuromodulation,which enhances the connectivity of oscillatory networks through improved neuronal synchronization and optimized topological organization of functional brain networks.These findings not only support the efficacy of rTMS as an adjunctive therapy for AD but also underscore the importance of employing multiple assessment methods—including clinical scales,blood biomarkers,and EEG——in understanding and monitoring the progression of AD.This research provides a significant theoretical foundation and empirical evidence for further exploration of rTMS applications in AD treatment.
基金Projects(51621006,51874274)supported by the National Natural Science Foundation of ChinaProject(2018YFC0808401)supported by the National Key Research and Development Program of China
文摘In this paper,a new micro-creep model of salt rock is proposed based on a linear parallel bonded model(LPBM)using the two-dimensional particle flow code(PFC2D).The power function weakening form is assumed to describe the variation of the parallel bonded diameter(PBD)over time.By comparing with the parallel-bonded stress corrosion(PSC)model,a smaller stress fluctuation and smoother creep strain−time curves can be obtained by this power function model at the same stress level.The validity and adaptability of the model to simulate creep deformation of salt rock are verified through comparing the laboratory creep test curves and the Burgers model fitting result.The numerical results reveal that this model can be capable of capturing the creep deformation and damage behavior from the laboratory observations.
文摘The development of the socialist market economy demands the furtherintensification of the reform of the management operating system (MOS)of the state-owned assets, the strengthening of the efficiency in the man-agement of state-owned assets,and the improvement of the operating bene-
文摘文章以幂函数变换为研究对象,从背景值误差和还原误差的角度分析了幂函数变换对GM(1,1)模型建模精度的影响,论证了幂函数变换的GM(1,1)模型(PFNGM(1,1)模型)具有逼近无偏性,能在可忽略的误差范围内实现对白指数序列的预测无偏性。实例应用结果表明,其建模精度和预测效果均优于无偏GM(1,1)模型和离散GM(1,1)模型。为将适宜建模序列拓展至近似非齐次指数序列和季节波动序列,同时保留幂函数变换可以有效降低背景值误差对建模精度影响的优势,将幂函数变换与平移变换相结合构建了PFNGM(1,1)模型,将幂函数变换与季节性GM(1,1)模型(SGM(1,1)模型)相结合构建了PFSGM(1,1)模型。实例应用结果表明,PFNGM(1,1)模型的建模精度和预测效果均优于背景值改进的NGM(1,1, k )模型和ONGM(1,1, k,c )模型,PFSGM(1,1)模型的建模精度和预测效果均优于SGM(1,1)模型,验证了两种模型的有效性。
