Uric acid(UA)is a naturally antioxidant that is strongly associated with the development and progression of Parkinson's disease(PD).The purine diet is an important exogenous pathway that modulates blood UA levels....Uric acid(UA)is a naturally antioxidant that is strongly associated with the development and progression of Parkinson's disease(PD).The purine diet is an important exogenous pathway that modulates blood UA levels.Deep brain stimulation(DBS)is an important tool for PD treatment.This study aimed to explore the effects of preoperative purine diet on the prognosis of patients with PD after DBS.Sixty-four patients with PD who underwent DBS were included in this study,and their clinical data,blood UA levels,and daily purine intake.Patients were followed up for improvement 1 year after surgery.We found that patient higher purine intake was strongly associated with the rate of improvement after DBS and was a protective factor for patient prognosis.Daily purine intake from meat and seafood was significantly higher in the responsive patients than in the lessresponsive patients.Mediation analysis showed that UA mediated 78%of the effect of purine intake on motor symptom improvement after DBS.In summary,we observed that purine intake is strongly associated with the rate of improvement in motor symptoms after subthalamic nucleus-DBS in patients with PD.This study provides a reference for preoperative diet planning in patients with PD undergoing DBS.展开更多
Background Although 15 mA transcranial alternating current stimulation(tACS)has a therapeutic effect on depression,the activations of brain structures in humans accounting for this tACS configuration remain largely un...Background Although 15 mA transcranial alternating current stimulation(tACS)has a therapeutic effect on depression,the activations of brain structures in humans accounting for this tACS configuration remain largely unknown.Aims To investigate which intracranial brain structures are engaged in the tACS at 77.5 Hz and 15 mA,delivered via the forehead and the mastoid electrodes in the human brain.Methods Actual human head models were built using the magnetic resonance imagings of eight outpatient volunteers with drug-naïve,first-episode major depressive disorder and then used to perform the electric field distributions with SimNIBS software.Results The electric field distributions of the sagittal,coronal and axial planes showed that the bilateral frontal lobes,bilateral temporal lobes,hippocampus,cingulate,hypothalamus,thalamus,amygdala,cerebellum and brainstem were visibly stimulated by the 15 mA tACS procedure.Conclusions Brain-wide activation,including the cortex,subcortical structures,cerebellum and brainstem,is involved in the 15 mA tACS intervention for first-episode major depressive disorder.Our results indicate that the simultaneous involvement of multiple brain regions is a possible mechanism for its effectiveness in reducing depressive symptoms.展开更多
Background Postoperative sleep disturbance(PSD)is a common and serious postoperative complication and is associated with poor postoperative outcomes.Aims This study aimed to investigate the effect of transcranial dire...Background Postoperative sleep disturbance(PSD)is a common and serious postoperative complication and is associated with poor postoperative outcomes.Aims This study aimed to investigate the effect of transcranial direct current stimulation(tDCS)on PSD in older patients undergoing lower limb major arthroplasty.Methods In this prospective,double-blind,pilot,randomised,sham-controlled trial,patients 65 years and over undergoing lower limb major arthroplasty were randomly assigned to receive active tDCS(a-tDCS)or sham tDCS(s-tDCS).The primary outcomes were the objective sleep measures on postoperative nights(N)1 and N2.Results 116 inpatients were assessed for eligibility,and a total of 92 patients were enrolled;47 received a-tDCS and 45 received s-tDCS.tDCS improved PSD by altering the following sleep measures in the a-tDCS and s-tDCS groups;the respective comparisons were as follows:the promotion of rapid eye movement(REM)sleep time on N1(64.5(33.5-105.5)vs 19.0(0.0,45.0)min,F=20.10,p<0.001)and N2(75.0(36.0-120.8)vs 30.0(1.3-59.3)min,F=12.55,p<0.001);the total sleep time on N1(506.0(408.0-561.0)vs 392.0(243.0-483.5)min,F=14.13,p<0.001)and N2(488.5(455.5-548.5)vs 346.0(286.5-517.5)min,F=7.36,p=0.007);the deep sleep time on N1(130.0(103.3-177.0)vs 42.5(9.8-100.8)min,F=24.4,p<0.001)and N2(103.5(46.0-154.8)vs 57.5(23.3-106.5)min,F=8.4,p=0.004);and the percentages of light sleep and REM sleep on N1 and N2(p<0.05 for each).The postoperative depression and anxiety scores did not differ significantly between the two groups.No significant adverse events were reported.Conclusion In older patients undergoing lower limb major arthroplasty,a single session of anodal tDCS over the left dorsolateral prefrontal cortex showed a potentially prophylactic effect in improving postoperative short-term objective sleep measures.However,this benefit was temporary and was not maintained over time.展开更多
To the editor:Insomnia disorder has a serious and widespread detrimental effect on humans with comorbidity with other mental or physical health problems.In recent years,noninvasive brain stimulation(NIBS)techniques,es...To the editor:Insomnia disorder has a serious and widespread detrimental effect on humans with comorbidity with other mental or physical health problems.In recent years,noninvasive brain stimulation(NIBS)techniques,especially transcranial magnetic stimulation(TMS)and transcranial electrical stimulation,have been increasingly used for the treatment of brain diseases,including insomnia disorder.展开更多
Background Structural imaging holds great potential for precise targeting and stimulation for deep brain stimulation(DBS).The anatomical information it provides may serve as potential biomarkers for predicting the eff...Background Structural imaging holds great potential for precise targeting and stimulation for deep brain stimulation(DBS).The anatomical information it provides may serve as potential biomarkers for predicting the efficacy of DBS in treatment-resistant depression(TRD).Aims The primary aim is to identify preoperative imaging biomarkers that correlate with the efficacy of DBS in patients with TRD.Methods Preoperative imaging parameters were estimated and correlated with the 6-month clinical outcome of patients with TRD receiving combined bed nucleus of the stria terminalis(BNST)-nucleus accumbens(NAc)DBS.White matter(WM)properties were extracted and compared between the response/non-response and remission/non-remission groups.Structural connectome was constructed and analysed using graph theory.Distances of the volume of activated tissue(VAT)to the main modulating tracts were also estimated to evaluate the correlations.Results Differences in fibre bundle properties of tracts,including superior thalamic radiation and reticulospinal tract,were observed between the remission and nonremission groups.Distance of the centre of the VAT to tracts connecting the ventral tegmental area and the anterior limb of internal capsule on the left side varied between the remission and non-remission groups(p=0.010,t=3.07).The normalised clustering coefficient(γ)and the small-world property(σ)in graph analysis correlated with the symptom improvement after the correction of age.Conclusions Presurgical structural alterations in WM tracts connecting the frontal area with subcortical regions,as well as the distance of the VAT to the modulating tracts,may influence the clinical outcome of BNST-NAc DBS.These findings provide potential imaging biomarkers for the DBS treatment for patients with TRD.展开更多
To the editor:Affective disorders,including major depressive disorder(MDD)and bipolar disorder,have emerged as the primary cause of adolescent suicide.Moreover,suicide mostly occurs in the major depressive episode(MDE...To the editor:Affective disorders,including major depressive disorder(MDD)and bipolar disorder,have emerged as the primary cause of adolescent suicide.Moreover,suicide mostly occurs in the major depressive episode(MDE)of affective disorders.Suicidal ideation(SI)has been identified as an immediate precursor to suicide,such that reducing its severity is conducive to suicide prevention in adolescents.展开更多
To the editor:Transcranial magnetic stimulation(TMS)is a non-invasive brain modulation technique.One important usage of TMS is the transient interruption of cognitive brain function(also named virtual lesion)for inves...To the editor:Transcranial magnetic stimulation(TMS)is a non-invasive brain modulation technique.One important usage of TMS is the transient interruption of cognitive brain function(also named virtual lesion)for investigating precisely where and when a specific cortical region contributes to a specific cognitive function.1 A more important usage of TMS is the treatment of brain disorders by repetitive TMS(rTMS).展开更多
To the editor:It is commonly reported that people with insomnia often experience comorbid emotional disorders,such as mood and anxiety disorders.12 A study found that fragmented rapid eye movement(REM)sleep in individ...To the editor:It is commonly reported that people with insomnia often experience comorbid emotional disorders,such as mood and anxiety disorders.12 A study found that fragmented rapid eye movement(REM)sleep in individuals with insomnia is associated with higher Beck Depression Inventory(BDI)scores.3 REM sleep architecture disruption is a typical symptom of insomnia.展开更多
INTRODUCTION Repetitive transcranial magnetic stimulation(rTMS)is a neuroplasticity-enhancing technique that modifies brain responsiveness to various therapeutic modalities in clinical psychiatric and neurological app...INTRODUCTION Repetitive transcranial magnetic stimulation(rTMS)is a neuroplasticity-enhancing technique that modifies brain responsiveness to various therapeutic modalities in clinical psychiatric and neurological applications. Furthermore,its effect can be attributed to long-term potentiation(LTP)or longterm depression(LTD)-like neuroplasticity.However,responsiveness to rTMS is largely variable in healthy and pathological brains and is mediated by complex biological mechanisms.Metaplasticity refers to a higher-order plasticity mechanism in which the direction and magnitude of synaptic plasticity are modified by prior neuronal activity and is believed to be a significant factor leading to the response variability of rTMs.展开更多
Background Previous studies havedemonstrated that excitatory repetitive transcranial magnetic stimulation(rTMS)can improve the cognitive function of patients with Alzheimer's disease(AD).Intermittent theta burst s...Background Previous studies havedemonstrated that excitatory repetitive transcranial magnetic stimulation(rTMS)can improve the cognitive function of patients with Alzheimer's disease(AD).Intermittent theta burst stimulation(iTBS)is a novel excitatory rTMS protocol for brain activity stimulation with the ability to induce long-term potentiation-like plasticity and represents a promising treatment for AD.However,the long-term effects of iTBS on cognitive decline and brain structure in patients with AD areunknown.Aims We aimed to explore whether repeating accelerated iTBS every three months could slow down the cognitive decline in patients with AD.Methods In this randomised,assessor-blinded,controlled trial,iTBS was administered to the left dorsolateral prefrontal cortex(DLPFC)of 42 patients with AD for 14days every 13weeks.Measurements included the Montreal Cognitive Assessment(MoCA),a comprehensive neuropsychological battery,and the grey matter volume(GMV)of the hippocampus.Patients were evaluated at baseline and after follow-up.The longitudinal pipeline of the Computational Anatomy Toolbox for SPM was used to detect significant treatment-related changes over time.Results The iTBS group maintained MoCA scores relative to the control group(t=3.26,p=0.013)and reduced hippocampal atrophy,which was significantly correlated with global degeneration scale changes.The baseline Mini-Mental State Examination(MMSE)score,apolipoprotein E genotype and Clinical Dementia Rating were indicative of MoCA scores at follow-up.Moreover,the GMV of the left(t=0.08,p=0.996)and right(t=0.19,p=0.977)hippocampus were maintained in the active group but significantly declined in the control group(left:t=4.13,p<0.001;right:t=5.31,p<0.001).GMV change in the left(r=0.35,p=0.023)and right(r=0.36,p=0.021)hippocampus across the intervention positively correlated with MoCA changes;left hippocampal GMV change was negatively correlated with global degeneration scale(r=-0.32,p=0.041)changes.Conclusions DLPFC-iTBS maybe a feasible and easy-to-implement non-pharmacological intervention to slow down the progressive decline of overall cognition and quality of life in patients with AD,providing a new AD treatment option.Trial registration number NCT04754152.展开更多
Viscoelastic surfactants(VES)are often used as viscous diverters in acidizing stimulation to prolong the acid consumption time and maximize zonal coverage of the acid for improving well productivity.However,the ceilin...Viscoelastic surfactants(VES)are often used as viscous diverters in acidizing stimulation to prolong the acid consumption time and maximize zonal coverage of the acid for improving well productivity.However,the ceiling temperature of commercial VES cannot exceed 120℃in practical use because of the poor thermal stability and fragile molecular structure,hindering their implementation in hightemperature oil reservoirs,i.e.,≥150℃.Here we synthesized a novel C22-tailed diamine,N-erucaminopropyl-N,N-dimethylamine(EDPA),and examined comparatively its rheological behavior,assemblies morphology and molecular stability in 20 wt%HCl with a commercial VES,erucyl dimethyl amidopropyl betaine(EDAB).The feasibility of EDPA for acidizing stimulation was assessed by acid etching of carbonate rock with its HCl solution at 150℃.Rheological results showed that the 2.5 wt%EDPA—20 wt%HCl solution maintains stable viscosity of 90 m Pa s at 150℃for 60 min,while that of 2.0 wt%EDAB HCl solution is just 1 m Pa s under identical conditions.1H NMR spectra and cryo-TEM observations revealed that the chemical structure and self-assembled architectures of EDPA remained intact in such context,but the EDAB suffered from degradation due to the hydrolysis of the amide group,accounting for the poor heat-resistance and acid-tolerance.The reaction rate of 2.5 wt%EDPA HCl solution with carbonate rock was one order of magnitude lower than that of 20 wt%HCl solution at 150℃,underpinning the potential of EDPA to be used in the high-temperature reservoirs acidizing.This work improved the thermal tolerance of VES in highly concentrated HCl solution,paving a feasible way for the acidization of high-temperature reservoir environments(~150℃).展开更多
Recently, a new promising type of marine shale gas reservoir, carbonate-rich shale, has been discovered.But the mechanical properties of this type of shale were still unrevealed and the corresponding reservoir stimula...Recently, a new promising type of marine shale gas reservoir, carbonate-rich shale, has been discovered.But the mechanical properties of this type of shale were still unrevealed and the corresponding reservoir stimulation design was lack of guidance. Using the deep downhole cores of an exploratory carbonate-rich shale gas well, the physical and mechanical parameters and failure mechanism of the whole reservoir section were acquired and evaluated systematically, by performing XRD, tri-axial compression, Brazilian splitting, and fracture toughness tests. A new model was established to evaluate the reservoir brittleness based on fracture morphology and stress-strain curve. Recommended strategy for reservoir stimulation was discussed. Results showed that(1) Carbonate-rich shale possessed high compressive strength and high Young's modulus, which were improved by 10.74% and 3.37% compared to that of siliceous shale. It featured high tensile strength and fracture toughness, with insignificant anisotropy.(2) With the content of carbonate minerals increasing, the shear failure morphology transformed from sparse and wide brittle fractures to diffusely distributed and subtle plastic cracks.(3) The brittleness index order was: siliceous shale, clay-rich shale, carbonate-rich shale, and limestone.(4) The special properties of carbonate-rich shale were rooted in the inherent feature of carbonate minerals(high strength, high elastic modulus,and cleavage structure), resulting in greater challenge in reservoirs stimulation. The above findings would promote the understanding of carbonate-rich shale reservoirs and provide reference for the optimum design of reservoir stimulation.展开更多
The cyclic hydraulic stimulation(CHS) has proven as a prospective technology for enhancing the permeability of unconventional formations such as coalbeds. However, the effects of CHS on the microstructure and gas sorp...The cyclic hydraulic stimulation(CHS) has proven as a prospective technology for enhancing the permeability of unconventional formations such as coalbeds. However, the effects of CHS on the microstructure and gas sorption behavior of coal remain unclear. In this study, laboratory tests including the nuclear magnetic resonance(NMR), low-temperature nitrogen sorption(LTNS), and methane sorption isotherm measurement were conducted to explore changes in the pore structure and methane sorption characteristics caused by CHS on an anthracite coal from Qinshui Basin, China. The NMR and LTNS tests show that after CHS treatment, meso- and macro-pores tend to be enlarged, whereas micropores with larger sizes and transition-pores may be converted into smaller-sized micro-pores. After the coal samples treated with 1, 3, 5 and 7 hydraulic stimulation cycles, the total specific surface area(TSSA)decreased from 0.636 to 0.538, 0.516, 0.505, and 0.491 m^(2)/g, respectively. Fractal analysis based on the NMR and LTNS results show that the surface fractal dimensions increase with the increase in the number of hydraulic stimulation cycles, while the volume fractal dimensions exhibit an opposite trend to the surface fractal dimensions, indicating that the pore surface roughness and pore structure connectivity are both increased after CHS treatment. Methane sorption isothermal measurements show that both the Langmuir volume and Langmuir pressure decrease significantly with the increase in the number of hydraulic stimulation cycles. The Langmuir volume and the Langmuir pressure decrease from 33.47 cm^(3)/g and 0.205 MPa to 24.18 cm^(3)/g and 0.176 MPa after the coal samples treated with 7 hydraulic stimulation cycles, respectively. The increments of Langmuir volume and Langmuir pressure are positively correlated with the increment of TSSA and negatively correlated with the increments of surface fractal dimensions.展开更多
Transcranial Hall-effect stimulation（THS） is a new stimulation method in which an ultrasonic wave in a static magnetic field generates an electric field in an area of interest such as in the brain to modulate neuron...Transcranial Hall-effect stimulation（THS） is a new stimulation method in which an ultrasonic wave in a static magnetic field generates an electric field in an area of interest such as in the brain to modulate neuronal activities. However, the biophysical basis of simulating the neurons remains unknown. To address this problem, we perform a theoretical analysis based on a passive cable model to investigate the THS mechanism of neurons. Nerve tissues are conductive; an ultrasonic wave can move ions embedded in the tissue in a static magnetic field to generate an electric field（due to Lorentz force）.In this study, a simulation model for an ultrasonically induced electric field in a static magnetic field is derived. Then,based on the passive cable model, the analytical solution for the voltage distribution in a nerve tissue is determined. The simulation results showthat THS can generate a voltage to stimulate neurons. Because the THS method possesses a higher spatial resolution and a deeper penetration depth, it shows promise as a tool for treating or rehabilitating neuropsychiatric disorders.展开更多
In recent years, rapid progress in the use of high pressure water jets （HPWJ） has been made in oil and gas well drilling, completion, and stimulation; and good results have been achieved in field applications. Advan...In recent years, rapid progress in the use of high pressure water jets （HPWJ） has been made in oil and gas well drilling, completion, and stimulation; and good results have been achieved in field applications. Advances in technologies and developments of well completion and stimulation with hydrajet are reviewed in this paper. Experiments were conducted to study the characteristics of abrasive water jetting and to optimize jet parameters, which can provide methods for the well completion and hydrajet fracturing. Deep-penetrating hydrajet perforating can create a 2-3 m clean hole with a diameter of 20-35 mm. Multilayer hydrajet fracturing is a process whereby multiple layers are stimulated in a single run without using mechanical packers, thereby reducing operation procedure and risk. Multilateral radial wells can be drilled using hydraulic jetting up to 100 m in length. The technique to remove sand particles and plugs with rotating self-resonating cavitating water jets in horizontal wellbores has been developed and oilfield-tested, which shows promising, cost effective prospects.展开更多
We investigate transcranial magneto–acoustical stimulation（TMAS） for noninvasive brain neuromodulation in vivo.TMAS as a novel technique uses an ultrasound wave to induce an electric current in the brain tissue in ...We investigate transcranial magneto–acoustical stimulation（TMAS） for noninvasive brain neuromodulation in vivo.TMAS as a novel technique uses an ultrasound wave to induce an electric current in the brain tissue in the static magnetic field. It has the advantage of high spatial resolution and penetration depth. The mechanism of TMAS onto a neuron is analyzed by combining the TMAS principle and Hodgkin–Huxley neuron model. The anesthetized rats are stimulated by TMAS, resulting in the local field potentials which are recorded and analyzed. The simulation results show that TMAS can induce neuronal action potential. The experimental results indicate that TMAS can not only increase the amplitude of local field potentials but also enhance the effect of focused ultrasound stimulation on the neuromodulation. In summary, TMAS can accomplish brain neuromodulation, suggesting a potentially powerful noninvasive stimulation method to interfere with brain rhythms for diagnostic and therapeutic purposes.展开更多
Depression is a common mental disorder, which attributes to significant morbidity, disability and burden of care. A significant number of patients with depression still remain symptomatic after adequate trials of anti...Depression is a common mental disorder, which attributes to significant morbidity, disability and burden of care. A significant number of patients with depression still remain symptomatic after adequate trials of antidepressant treatment as well as psychotherapy, which is often referred to as treatment-resistant depression. Neuromodulation techniques—like electroconvulsive therapy, vagus nerve stimulation, transcranial magnetic stimulation (TMS) and transcranial direct current stimulation, may be useful augmenting techniques in depression, mostly recommended for treatment-resistant cases. Robust evidence exists regarding the efficacy of electroconvulsive therapy in the management of treatment-resistant depression;however, other techniques are understudied. TMS has been increasingly studied in various psychiatric disorders including depression. It has been approved by the US Food and Drug Administration for use in major depressive disorder. Over the past two decades, TMS has been studied in diverse groups of the population with depression using several research designs. This article gives an overview of the efficacy of repetitive TMS in treatment-resistant depression with the recent evidence.展开更多
By reviewing the development history of shale oil reservoir stimulation technology of PetroChina Company Limited(PetroChina),we have systematically summarized the main progress of shale oil reservoir stimulation techn...By reviewing the development history of shale oil reservoir stimulation technology of PetroChina Company Limited(PetroChina),we have systematically summarized the main progress of shale oil reservoir stimulation technology of CNPC in five aspects:reservoir stimulation mechanism,fracture-controlled fracturing,geological-engineering integrated reservoir stimulation design platform,low-cost materials,and large well-pad three-dimensional development mode.It is made clear that the major stimulation technology for shale oil reservoir is the high density multi-cluster and fracture-controlled staged fracturing aiming to increase fracture-controlled reserves,lower operation costs and increase economic benefits.Based on comprehensive analysis of the challenges shale oil reservoir stimulation technology faces in three-dimensional development,stimulation parameter optimization for fracture-controlled fracturing,refracturing and low-cost stimulation technology,we proposed five development directions of the stimulation technology:(1)Strengthen the research on integration of geology and engineering to make full use of reservoir stimulation.(2)Deepen the study on fracture-controlled fracturing to improve reserves development degree.(3)Promote horizontal well three-dimensional development of shale oil to realize the production of multiple layers vertically.(4)Research refracturing technology of shale oil reservoir through horizontal well to efficiently tap the remaining reserves between fractures.(5)Develop low-cost stimulation supporting technology to help reduce the cost and increase economic benefit of oilfield development.展开更多
Emotional factors and motivations should be taken into considerations,and combine grammar,rules with practical skills in communications,the stimulation of children's English learning at the initial stage must take...Emotional factors and motivations should be taken into considerations,and combine grammar,rules with practical skills in communications,the stimulation of children's English learning at the initial stage must take effect and lead to good results.展开更多
Background Pharmacological and conventional nonpharmacological treatments are only moderately effective in treatingeneralised anxiety disorder(GAD).Recently,repetitive transcranial magnetic stimulation(rTMS)has attrac...Background Pharmacological and conventional nonpharmacological treatments are only moderately effective in treatingeneralised anxiety disorder(GAD).Recently,repetitive transcranial magnetic stimulation(rTMS)has attracted interest because of its potential therapeutic value.Aim To investigate the efficacy and safety of rTMS treatment for GAD.Methods Literature studies published in English or Chinese were screened in 10 electronic databases up to 5 December 2018.The included studies'bias risk was assessed using Cochrane risk of bias assessment tool.Meta-analysis was performed to compute the standardised mean difference(SMD)and risk ratio(RR)along with its 95%Cis through using RevMan V.5.3.Heterogeneity was inspected by I2 and the χ2 test.We performed subgroup analysis and meta-regression to investigate heterogeneity.We used funnel plot to assess publication bias.We used the GRADE approach to assess the whole quality of evidence.Results Twenty-one studies,with a total sample size of 1481,were analysed.The risk of bias in most studies included is moderate,the majority of which are lacking of blinding methods of treatment allocation.The treatment had beneficial effects in the rTMS group compared with the control group in mean anxiety score(SMD=-0.68;95%Cl-0.89 to-0.46).None of the 21 studies included here reported severe adverse events.As for dropout rates,there are no statistically significant differences between the two groups(RR 1.14,95%Cl 0.72 to 1.82)or adverse events(RR 0.95,95%Cl 0.77 to 1.18).No particular influence on the heterogeneity of any variable was observed.The risk of publication bias was low.According to the GRADE approach,the evidence levels of primary outcome(treatment effects)and secondary outcomes(acceptability and safety)were rated as‘medium’.Conclusion The use of rTMS combined with medication treatment may have a significant positive anti-anxiety effect on patients with GAD.However,we should interpret the results cautiously due to the relatively high heterogeneity of the meta-analysis.Future high-quality clinical trials are needed to confirm our results.展开更多
文摘Uric acid(UA)is a naturally antioxidant that is strongly associated with the development and progression of Parkinson's disease(PD).The purine diet is an important exogenous pathway that modulates blood UA levels.Deep brain stimulation(DBS)is an important tool for PD treatment.This study aimed to explore the effects of preoperative purine diet on the prognosis of patients with PD after DBS.Sixty-four patients with PD who underwent DBS were included in this study,and their clinical data,blood UA levels,and daily purine intake.Patients were followed up for improvement 1 year after surgery.We found that patient higher purine intake was strongly associated with the rate of improvement after DBS and was a protective factor for patient prognosis.Daily purine intake from meat and seafood was significantly higher in the responsive patients than in the lessresponsive patients.Mediation analysis showed that UA mediated 78%of the effect of purine intake on motor symptom improvement after DBS.In summary,we observed that purine intake is strongly associated with the rate of improvement in motor symptoms after subthalamic nucleus-DBS in patients with PD.This study provides a reference for preoperative diet planning in patients with PD undergoing DBS.
基金The study was partly funded by the National Natural Science Foundation of China(82371490)the National Key R&D Program of China(2022YFC2503900,2022YFC2503901)+1 种基金Beijing Hundred,Thousand and Ten Thousand Talents Project(2017-CXYF-09)Beijing Health System Leading Talent Grant(2022-02-10).
文摘Background Although 15 mA transcranial alternating current stimulation(tACS)has a therapeutic effect on depression,the activations of brain structures in humans accounting for this tACS configuration remain largely unknown.Aims To investigate which intracranial brain structures are engaged in the tACS at 77.5 Hz and 15 mA,delivered via the forehead and the mastoid electrodes in the human brain.Methods Actual human head models were built using the magnetic resonance imagings of eight outpatient volunteers with drug-naïve,first-episode major depressive disorder and then used to perform the electric field distributions with SimNIBS software.Results The electric field distributions of the sagittal,coronal and axial planes showed that the bilateral frontal lobes,bilateral temporal lobes,hippocampus,cingulate,hypothalamus,thalamus,amygdala,cerebellum and brainstem were visibly stimulated by the 15 mA tACS procedure.Conclusions Brain-wide activation,including the cortex,subcortical structures,cerebellum and brainstem,is involved in the 15 mA tACS intervention for first-episode major depressive disorder.Our results indicate that the simultaneous involvement of multiple brain regions is a possible mechanism for its effectiveness in reducing depressive symptoms.
基金This study was supported in part by grants from the National Key R&D Program of China(2021ZD0203100 to JC)National Natural Science Foundation of China(NSFC81720108013,NSFC31771161 and NSFC81230025 to JC,NSFC81300957 and NSFC82171227 to HL,NSFC81771453 and NSFC31970937 to HZ)+6 种基金Jiangsu Provincial Special Program of Medical Science(BL2014029 to JC)Basic and Clinical Research Center in Anesthesiology of Jiangsu Provincial'Science and Education for Health'Project(JC),Zhejiang Provincial Natural Science Foundation(LY22H090019 to HL)Jiangsu Provincial Natural Science Foundation(BK20190047 to HZ)the Priority Academic Program Development of Jiangsu Higher Education Institutions(19KJA610005 to HZ)Distinguished Professor Program of Jiangsu(HZ),Jiangsu Province Innovative and Entrepreneurial Talent Program and Jiangsu Province Innovative and Entrepreneurial Team Program(HZ),Xuzhou Medical University start-up grant for excellent scientist(D2018010 and D2019025D to HZ)the Natural Science Foundation of Shanghai(21ZR1411300 to YH)Shenkang Clinical Study Foundation of Shanghai(SHDC2020CR4061 to YH).
文摘Background Postoperative sleep disturbance(PSD)is a common and serious postoperative complication and is associated with poor postoperative outcomes.Aims This study aimed to investigate the effect of transcranial direct current stimulation(tDCS)on PSD in older patients undergoing lower limb major arthroplasty.Methods In this prospective,double-blind,pilot,randomised,sham-controlled trial,patients 65 years and over undergoing lower limb major arthroplasty were randomly assigned to receive active tDCS(a-tDCS)or sham tDCS(s-tDCS).The primary outcomes were the objective sleep measures on postoperative nights(N)1 and N2.Results 116 inpatients were assessed for eligibility,and a total of 92 patients were enrolled;47 received a-tDCS and 45 received s-tDCS.tDCS improved PSD by altering the following sleep measures in the a-tDCS and s-tDCS groups;the respective comparisons were as follows:the promotion of rapid eye movement(REM)sleep time on N1(64.5(33.5-105.5)vs 19.0(0.0,45.0)min,F=20.10,p<0.001)and N2(75.0(36.0-120.8)vs 30.0(1.3-59.3)min,F=12.55,p<0.001);the total sleep time on N1(506.0(408.0-561.0)vs 392.0(243.0-483.5)min,F=14.13,p<0.001)and N2(488.5(455.5-548.5)vs 346.0(286.5-517.5)min,F=7.36,p=0.007);the deep sleep time on N1(130.0(103.3-177.0)vs 42.5(9.8-100.8)min,F=24.4,p<0.001)and N2(103.5(46.0-154.8)vs 57.5(23.3-106.5)min,F=8.4,p=0.004);and the percentages of light sleep and REM sleep on N1 and N2(p<0.05 for each).The postoperative depression and anxiety scores did not differ significantly between the two groups.No significant adverse events were reported.Conclusion In older patients undergoing lower limb major arthroplasty,a single session of anodal tDCS over the left dorsolateral prefrontal cortex showed a potentially prophylactic effect in improving postoperative short-term objective sleep measures.However,this benefit was temporary and was not maintained over time.
基金the National Natural Science Foundation of China(81871426,81871430,82260359,U22A20303)Hebei Provincial Natural Science Foundation(H2020206263,H2020206625)STI2030-Major Projects Program(2022ZD0214500).
文摘To the editor:Insomnia disorder has a serious and widespread detrimental effect on humans with comorbidity with other mental or physical health problems.In recent years,noninvasive brain stimulation(NIBS)techniques,especially transcranial magnetic stimulation(TMS)and transcranial electrical stimulation,have been increasingly used for the treatment of brain diseases,including insomnia disorder.
基金supported by an unrestricted,investigator-initiated research grant by Scenery(BS),which provided the devices used.The project was sponsored by SJTU Trans-med Awards Research(2019015 to BS)Shanghai Clinical Research Centre for Mental Health(19MC191100 to BS)+3 种基金sponsored by the National Natural Science Foundation of China(81771482)supported by the Guangci Professorship Programme of Ruijin Hospital(N/A)and a Medical Research Council Senior Clinical Fellowship(MR/P008747/1)sponsored by the National Natural Science Foundation of China(82101546)the Shanghai Sailing Program(21YF1426700).The funding sources were not involved in the design and conduct of the study。
文摘Background Structural imaging holds great potential for precise targeting and stimulation for deep brain stimulation(DBS).The anatomical information it provides may serve as potential biomarkers for predicting the efficacy of DBS in treatment-resistant depression(TRD).Aims The primary aim is to identify preoperative imaging biomarkers that correlate with the efficacy of DBS in patients with TRD.Methods Preoperative imaging parameters were estimated and correlated with the 6-month clinical outcome of patients with TRD receiving combined bed nucleus of the stria terminalis(BNST)-nucleus accumbens(NAc)DBS.White matter(WM)properties were extracted and compared between the response/non-response and remission/non-remission groups.Structural connectome was constructed and analysed using graph theory.Distances of the volume of activated tissue(VAT)to the main modulating tracts were also estimated to evaluate the correlations.Results Differences in fibre bundle properties of tracts,including superior thalamic radiation and reticulospinal tract,were observed between the remission and nonremission groups.Distance of the centre of the VAT to tracts connecting the ventral tegmental area and the anterior limb of internal capsule on the left side varied between the remission and non-remission groups(p=0.010,t=3.07).The normalised clustering coefficient(γ)and the small-world property(σ)in graph analysis correlated with the symptom improvement after the correction of age.Conclusions Presurgical structural alterations in WM tracts connecting the frontal area with subcortical regions,as well as the distance of the VAT to the modulating tracts,may influence the clinical outcome of BNST-NAc DBS.These findings provide potential imaging biomarkers for the DBS treatment for patients with TRD.
基金This study was funded by the National Key R&D Program of China(2022YFB4500600)National Natural Science Foundation of China(82271564)+1 种基金Science and Technology Projects of Guangzhou(202201010568,202201020047,2023B03J1300,2024A04J4178)Medical Scientific Research Foundation of Guangdong Province,China(A2023137).
文摘To the editor:Affective disorders,including major depressive disorder(MDD)and bipolar disorder,have emerged as the primary cause of adolescent suicide.Moreover,suicide mostly occurs in the major depressive episode(MDE)of affective disorders.Suicidal ideation(SI)has been identified as an immediate precursor to suicide,such that reducing its severity is conducive to suicide prevention in adolescents.
基金Ministry Key Project(JW0890006)Key Realm R&D Program of Guangdong Province(2019B030335001)+1 种基金Department of Science and Technology of Sichuan Province(2022NSFSC0808)Key Medical Discipline of Hangzhou,The Cultivation Project of the Province-leveled Preponderant Characteristic Discipline of Hangzhou Normal University(18JYXK046,20JYXK004).
文摘To the editor:Transcranial magnetic stimulation(TMS)is a non-invasive brain modulation technique.One important usage of TMS is the transient interruption of cognitive brain function(also named virtual lesion)for investigating precisely where and when a specific cortical region contributes to a specific cognitive function.1 A more important usage of TMS is the treatment of brain disorders by repetitive TMS(rTMS).
基金This work is supported by the National Natural Science Foundation of China(grant/award numbers:81871430,81871426,U22A20303,82260359)Hebei Provincial Natural Science Foundation(grant/award numbers:H2020206263,H2020206625)STI2030-Major Projects Program(grant/award number:2022ZD0214500).
文摘To the editor:It is commonly reported that people with insomnia often experience comorbid emotional disorders,such as mood and anxiety disorders.12 A study found that fragmented rapid eye movement(REM)sleep in individuals with insomnia is associated with higher Beck Depression Inventory(BDI)scores.3 REM sleep architecture disruption is a typical symptom of insomnia.
基金the Shanghai Municipal Health Commission Clinical ResearchProgram(20224Y0220)to ZBStart-up Fundfor RAPs under the Strategic Hiring Scheme(P0048866)and JJZ.
文摘INTRODUCTION Repetitive transcranial magnetic stimulation(rTMS)is a neuroplasticity-enhancing technique that modifies brain responsiveness to various therapeutic modalities in clinical psychiatric and neurological applications. Furthermore,its effect can be attributed to long-term potentiation(LTP)or longterm depression(LTD)-like neuroplasticity.However,responsiveness to rTMS is largely variable in healthy and pathological brains and is mediated by complex biological mechanisms.Metaplasticity refers to a higher-order plasticity mechanism in which the direction and magnitude of synaptic plasticity are modified by prior neuronal activity and is believed to be a significant factor leading to the response variability of rTMs.
基金the National Natural Science Foundation of China(No.82101498 to XW)STI2030-Major Prjects of China(No.20212D0201801 to PH)+1 种基金National Natural Science Foundation of China(No.82171917 to PH,No.82090034 and 31970979 to KW and 32071054 to YT)the 2021 Youth Foundation Training Program of the First Affiliated Hospital of Anhui Medical University(No.2021kj19 to XW).
文摘Background Previous studies havedemonstrated that excitatory repetitive transcranial magnetic stimulation(rTMS)can improve the cognitive function of patients with Alzheimer's disease(AD).Intermittent theta burst stimulation(iTBS)is a novel excitatory rTMS protocol for brain activity stimulation with the ability to induce long-term potentiation-like plasticity and represents a promising treatment for AD.However,the long-term effects of iTBS on cognitive decline and brain structure in patients with AD areunknown.Aims We aimed to explore whether repeating accelerated iTBS every three months could slow down the cognitive decline in patients with AD.Methods In this randomised,assessor-blinded,controlled trial,iTBS was administered to the left dorsolateral prefrontal cortex(DLPFC)of 42 patients with AD for 14days every 13weeks.Measurements included the Montreal Cognitive Assessment(MoCA),a comprehensive neuropsychological battery,and the grey matter volume(GMV)of the hippocampus.Patients were evaluated at baseline and after follow-up.The longitudinal pipeline of the Computational Anatomy Toolbox for SPM was used to detect significant treatment-related changes over time.Results The iTBS group maintained MoCA scores relative to the control group(t=3.26,p=0.013)and reduced hippocampal atrophy,which was significantly correlated with global degeneration scale changes.The baseline Mini-Mental State Examination(MMSE)score,apolipoprotein E genotype and Clinical Dementia Rating were indicative of MoCA scores at follow-up.Moreover,the GMV of the left(t=0.08,p=0.996)and right(t=0.19,p=0.977)hippocampus were maintained in the active group but significantly declined in the control group(left:t=4.13,p<0.001;right:t=5.31,p<0.001).GMV change in the left(r=0.35,p=0.023)and right(r=0.36,p=0.021)hippocampus across the intervention positively correlated with MoCA changes;left hippocampal GMV change was negatively correlated with global degeneration scale(r=-0.32,p=0.041)changes.Conclusions DLPFC-iTBS maybe a feasible and easy-to-implement non-pharmacological intervention to slow down the progressive decline of overall cognition and quality of life in patients with AD,providing a new AD treatment option.Trial registration number NCT04754152.
基金the financial support from the National Natural Science Foundation of China(Nos:21773161,22172108)。
文摘Viscoelastic surfactants(VES)are often used as viscous diverters in acidizing stimulation to prolong the acid consumption time and maximize zonal coverage of the acid for improving well productivity.However,the ceiling temperature of commercial VES cannot exceed 120℃in practical use because of the poor thermal stability and fragile molecular structure,hindering their implementation in hightemperature oil reservoirs,i.e.,≥150℃.Here we synthesized a novel C22-tailed diamine,N-erucaminopropyl-N,N-dimethylamine(EDPA),and examined comparatively its rheological behavior,assemblies morphology and molecular stability in 20 wt%HCl with a commercial VES,erucyl dimethyl amidopropyl betaine(EDAB).The feasibility of EDPA for acidizing stimulation was assessed by acid etching of carbonate rock with its HCl solution at 150℃.Rheological results showed that the 2.5 wt%EDPA—20 wt%HCl solution maintains stable viscosity of 90 m Pa s at 150℃for 60 min,while that of 2.0 wt%EDAB HCl solution is just 1 m Pa s under identical conditions.1H NMR spectra and cryo-TEM observations revealed that the chemical structure and self-assembled architectures of EDPA remained intact in such context,but the EDAB suffered from degradation due to the hydrolysis of the amide group,accounting for the poor heat-resistance and acid-tolerance.The reaction rate of 2.5 wt%EDPA HCl solution with carbonate rock was one order of magnitude lower than that of 20 wt%HCl solution at 150℃,underpinning the potential of EDPA to be used in the high-temperature reservoirs acidizing.This work improved the thermal tolerance of VES in highly concentrated HCl solution,paving a feasible way for the acidization of high-temperature reservoir environments(~150℃).
基金sponsored by the “National Natural Science Foundation of China” (No. U22B6003), (No. 52104010), and (No. 52104046)。
文摘Recently, a new promising type of marine shale gas reservoir, carbonate-rich shale, has been discovered.But the mechanical properties of this type of shale were still unrevealed and the corresponding reservoir stimulation design was lack of guidance. Using the deep downhole cores of an exploratory carbonate-rich shale gas well, the physical and mechanical parameters and failure mechanism of the whole reservoir section were acquired and evaluated systematically, by performing XRD, tri-axial compression, Brazilian splitting, and fracture toughness tests. A new model was established to evaluate the reservoir brittleness based on fracture morphology and stress-strain curve. Recommended strategy for reservoir stimulation was discussed. Results showed that(1) Carbonate-rich shale possessed high compressive strength and high Young's modulus, which were improved by 10.74% and 3.37% compared to that of siliceous shale. It featured high tensile strength and fracture toughness, with insignificant anisotropy.(2) With the content of carbonate minerals increasing, the shear failure morphology transformed from sparse and wide brittle fractures to diffusely distributed and subtle plastic cracks.(3) The brittleness index order was: siliceous shale, clay-rich shale, carbonate-rich shale, and limestone.(4) The special properties of carbonate-rich shale were rooted in the inherent feature of carbonate minerals(high strength, high elastic modulus,and cleavage structure), resulting in greater challenge in reservoirs stimulation. The above findings would promote the understanding of carbonate-rich shale reservoirs and provide reference for the optimum design of reservoir stimulation.
基金financially supported by the National Natural Science Foundation of China (51904319)the Fundamental Research Funds for the Central Universities (21CX06029A)。
文摘The cyclic hydraulic stimulation(CHS) has proven as a prospective technology for enhancing the permeability of unconventional formations such as coalbeds. However, the effects of CHS on the microstructure and gas sorption behavior of coal remain unclear. In this study, laboratory tests including the nuclear magnetic resonance(NMR), low-temperature nitrogen sorption(LTNS), and methane sorption isotherm measurement were conducted to explore changes in the pore structure and methane sorption characteristics caused by CHS on an anthracite coal from Qinshui Basin, China. The NMR and LTNS tests show that after CHS treatment, meso- and macro-pores tend to be enlarged, whereas micropores with larger sizes and transition-pores may be converted into smaller-sized micro-pores. After the coal samples treated with 1, 3, 5 and 7 hydraulic stimulation cycles, the total specific surface area(TSSA)decreased from 0.636 to 0.538, 0.516, 0.505, and 0.491 m^(2)/g, respectively. Fractal analysis based on the NMR and LTNS results show that the surface fractal dimensions increase with the increase in the number of hydraulic stimulation cycles, while the volume fractal dimensions exhibit an opposite trend to the surface fractal dimensions, indicating that the pore surface roughness and pore structure connectivity are both increased after CHS treatment. Methane sorption isothermal measurements show that both the Langmuir volume and Langmuir pressure decrease significantly with the increase in the number of hydraulic stimulation cycles. The Langmuir volume and the Langmuir pressure decrease from 33.47 cm^(3)/g and 0.205 MPa to 24.18 cm^(3)/g and 0.176 MPa after the coal samples treated with 7 hydraulic stimulation cycles, respectively. The increments of Langmuir volume and Langmuir pressure are positively correlated with the increment of TSSA and negatively correlated with the increments of surface fractal dimensions.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.61273063 and 61503321)the China Postdoctoral Science Foundation(Grant No.2013M540215)+1 种基金the Natural Science Foundation of Hebei Province,China(Grant No.F2014203161)the Youth Research Program of Yanshan University,China(Grant No.02000134)
文摘Transcranial Hall-effect stimulation（THS） is a new stimulation method in which an ultrasonic wave in a static magnetic field generates an electric field in an area of interest such as in the brain to modulate neuronal activities. However, the biophysical basis of simulating the neurons remains unknown. To address this problem, we perform a theoretical analysis based on a passive cable model to investigate the THS mechanism of neurons. Nerve tissues are conductive; an ultrasonic wave can move ions embedded in the tissue in a static magnetic field to generate an electric field（due to Lorentz force）.In this study, a simulation model for an ultrasonically induced electric field in a static magnetic field is derived. Then,based on the passive cable model, the analytical solution for the voltage distribution in a nerve tissue is determined. The simulation results showthat THS can generate a voltage to stimulate neurons. Because the THS method possesses a higher spatial resolution and a deeper penetration depth, it shows promise as a tool for treating or rehabilitating neuropsychiatric disorders.
基金The authors express their appreciation to the National Natural Science Foundation of China (No.50774089)the High-tech Research and Development Program of China (No.2007AA09Z315) for the fi nancial support of this work
文摘In recent years, rapid progress in the use of high pressure water jets （HPWJ） has been made in oil and gas well drilling, completion, and stimulation; and good results have been achieved in field applications. Advances in technologies and developments of well completion and stimulation with hydrajet are reviewed in this paper. Experiments were conducted to study the characteristics of abrasive water jetting and to optimize jet parameters, which can provide methods for the well completion and hydrajet fracturing. Deep-penetrating hydrajet perforating can create a 2-3 m clean hole with a diameter of 20-35 mm. Multilayer hydrajet fracturing is a process whereby multiple layers are stimulated in a single run without using mechanical packers, thereby reducing operation procedure and risk. Multilateral radial wells can be drilled using hydraulic jetting up to 100 m in length. The technique to remove sand particles and plugs with rotating self-resonating cavitating water jets in horizontal wellbores has been developed and oilfield-tested, which shows promising, cost effective prospects.
基金supported by the National Natural Science Foundation of China(Grant Nos.61503321 and 61273063)the Natural Science Foundation of Hebei Province,China(Grant No.F2014203161)
文摘We investigate transcranial magneto–acoustical stimulation（TMAS） for noninvasive brain neuromodulation in vivo.TMAS as a novel technique uses an ultrasound wave to induce an electric current in the brain tissue in the static magnetic field. It has the advantage of high spatial resolution and penetration depth. The mechanism of TMAS onto a neuron is analyzed by combining the TMAS principle and Hodgkin–Huxley neuron model. The anesthetized rats are stimulated by TMAS, resulting in the local field potentials which are recorded and analyzed. The simulation results show that TMAS can induce neuronal action potential. The experimental results indicate that TMAS can not only increase the amplitude of local field potentials but also enhance the effect of focused ultrasound stimulation on the neuromodulation. In summary, TMAS can accomplish brain neuromodulation, suggesting a potentially powerful noninvasive stimulation method to interfere with brain rhythms for diagnostic and therapeutic purposes.
文摘Depression is a common mental disorder, which attributes to significant morbidity, disability and burden of care. A significant number of patients with depression still remain symptomatic after adequate trials of antidepressant treatment as well as psychotherapy, which is often referred to as treatment-resistant depression. Neuromodulation techniques—like electroconvulsive therapy, vagus nerve stimulation, transcranial magnetic stimulation (TMS) and transcranial direct current stimulation, may be useful augmenting techniques in depression, mostly recommended for treatment-resistant cases. Robust evidence exists regarding the efficacy of electroconvulsive therapy in the management of treatment-resistant depression;however, other techniques are understudied. TMS has been increasingly studied in various psychiatric disorders including depression. It has been approved by the US Food and Drug Administration for use in major depressive disorder. Over the past two decades, TMS has been studied in diverse groups of the population with depression using several research designs. This article gives an overview of the efficacy of repetitive TMS in treatment-resistant depression with the recent evidence.
基金Supported by the National Science and Technology Major Project(2016ZX05023,2017ZX05013-005)。
文摘By reviewing the development history of shale oil reservoir stimulation technology of PetroChina Company Limited(PetroChina),we have systematically summarized the main progress of shale oil reservoir stimulation technology of CNPC in five aspects:reservoir stimulation mechanism,fracture-controlled fracturing,geological-engineering integrated reservoir stimulation design platform,low-cost materials,and large well-pad three-dimensional development mode.It is made clear that the major stimulation technology for shale oil reservoir is the high density multi-cluster and fracture-controlled staged fracturing aiming to increase fracture-controlled reserves,lower operation costs and increase economic benefits.Based on comprehensive analysis of the challenges shale oil reservoir stimulation technology faces in three-dimensional development,stimulation parameter optimization for fracture-controlled fracturing,refracturing and low-cost stimulation technology,we proposed five development directions of the stimulation technology:(1)Strengthen the research on integration of geology and engineering to make full use of reservoir stimulation.(2)Deepen the study on fracture-controlled fracturing to improve reserves development degree.(3)Promote horizontal well three-dimensional development of shale oil to realize the production of multiple layers vertically.(4)Research refracturing technology of shale oil reservoir through horizontal well to efficiently tap the remaining reserves between fractures.(5)Develop low-cost stimulation supporting technology to help reduce the cost and increase economic benefit of oilfield development.
文摘Emotional factors and motivations should be taken into considerations,and combine grammar,rules with practical skills in communications,the stimulation of children's English learning at the initial stage must take effect and lead to good results.
基金Shanghai Science and Technology Committee(18411952400,19411968600,16411965000)Shanghai Municipal Natural Science Foundation(18ZR1432600)+1 种基金Shanghai Municipal Commission of Health and Family Planning Foundation(20164Y0215,20174Y0021)SHSMU-ION Research Centre for Brain Disorders(2015NKX004).
文摘Background Pharmacological and conventional nonpharmacological treatments are only moderately effective in treatingeneralised anxiety disorder(GAD).Recently,repetitive transcranial magnetic stimulation(rTMS)has attracted interest because of its potential therapeutic value.Aim To investigate the efficacy and safety of rTMS treatment for GAD.Methods Literature studies published in English or Chinese were screened in 10 electronic databases up to 5 December 2018.The included studies'bias risk was assessed using Cochrane risk of bias assessment tool.Meta-analysis was performed to compute the standardised mean difference(SMD)and risk ratio(RR)along with its 95%Cis through using RevMan V.5.3.Heterogeneity was inspected by I2 and the χ2 test.We performed subgroup analysis and meta-regression to investigate heterogeneity.We used funnel plot to assess publication bias.We used the GRADE approach to assess the whole quality of evidence.Results Twenty-one studies,with a total sample size of 1481,were analysed.The risk of bias in most studies included is moderate,the majority of which are lacking of blinding methods of treatment allocation.The treatment had beneficial effects in the rTMS group compared with the control group in mean anxiety score(SMD=-0.68;95%Cl-0.89 to-0.46).None of the 21 studies included here reported severe adverse events.As for dropout rates,there are no statistically significant differences between the two groups(RR 1.14,95%Cl 0.72 to 1.82)or adverse events(RR 0.95,95%Cl 0.77 to 1.18).No particular influence on the heterogeneity of any variable was observed.The risk of publication bias was low.According to the GRADE approach,the evidence levels of primary outcome(treatment effects)and secondary outcomes(acceptability and safety)were rated as‘medium’.Conclusion The use of rTMS combined with medication treatment may have a significant positive anti-anxiety effect on patients with GAD.However,we should interpret the results cautiously due to the relatively high heterogeneity of the meta-analysis.Future high-quality clinical trials are needed to confirm our results.
