Noninvasive brain stimulation techniques offer promising therapeutic and regenerative prospects in neurological diseases by modulating brain activity and improving cognitive and motor functions.Given the paucity of kn...Noninvasive brain stimulation techniques offer promising therapeutic and regenerative prospects in neurological diseases by modulating brain activity and improving cognitive and motor functions.Given the paucity of knowledge about the underlying modes of action and optimal treatment modalities,a thorough translational investigation of noninvasive brain stimulation in preclinical animal models is urgently needed.Thus,we reviewed the current literature on the mechanistic underpinnings of noninvasive brain stimulation in models of central nervous system impairment,with a particular emphasis on traumatic brain injury and stroke.Due to the lack of translational models in most noninvasive brain stimulation techniques proposed,we found this review to the most relevant techniques used in humans,i.e.,transcranial magnetic stimulation and transcranial direct current stimulation.We searched the literature in Pub Med,encompassing the MEDLINE and PMC databases,for studies published between January 1,2020 and September 30,2024.Thirty-five studies were eligible.Transcranial magnetic stimulation and transcranial direct current stimulation demonstrated distinct strengths in augmenting rehabilitation post-stroke and traumatic brain injury,with emerging mechanistic evidence.Overall,we identified neuronal,inflammatory,microvascular,and apoptotic pathways highlighted in the literature.This review also highlights a lack of translational surrogate parameters to bridge the gap between preclinical findings and their clinical translation.展开更多
Although previous studies have demonstrated that transcranial focused ultrasound stimulation protects the ischemic brain,clear criteria for the stimulation time window and intensity are lacking.Electrical impedance to...Although previous studies have demonstrated that transcranial focused ultrasound stimulation protects the ischemic brain,clear criteria for the stimulation time window and intensity are lacking.Electrical impedance tomography enables real-time monitoring of changes in cerebral blood perfusion within the ischemic brain,but investigating the feasibility of using this method to assess post-stroke rehabilitation in vivo remains critical.In this study,ischemic stroke was induced in rats through middle cerebral artery occlusion surgery.Transcranial focused ultrasound stimulation was used to treat the rat model of ischemia,and electrical impedance tomography was used to measure impedance during both the acute stage of ischemia and the rehabilitation stage following the stimulation.Electrical impedance tomography results indicated that cerebral impedance increased after the onset of ischemia and decreased following transcranial focused ultrasound stimulation.Furthermore,the stimulation promoted motor function recovery,reduced cerebral infarction volume in the rat model of ischemic stroke,and induced the expression of brain-derived neurotrophic factor in the ischemic brain.Our results also revealed a significant correlation between the impedance of the ischemic brain post-intervention and improvements in behavioral scores and infarct volume.This study shows that daily administration of transcranial focused ultrasound stimulation for 20 minutes to the ischemic hemisphere 24 hours after cerebral ischemia enhanced motor recovery in a rat model of ischemia.Additionally,our findings indicate that electrical impedance tomography can serve as a valuable tool for quantitatively evaluating rehabilitation after ischemic stroke in vivo.These findings suggest the feasibility of using impedance data collected via electrical impedance tomography to clinically assess the effects of rehabilitatory interventions for patients with ischemic stroke.展开更多
Neuromodulation techniques effectively intervene in cognitive function,holding considerable scientific and practical value in fields such as aerospace,medicine,life sciences,and brain research.These techniques utilize...Neuromodulation techniques effectively intervene in cognitive function,holding considerable scientific and practical value in fields such as aerospace,medicine,life sciences,and brain research.These techniques utilize electrical stimulation to directly or indirectly target specific brain regions,modulating neural activity and influencing broader brain networks,thereby regulating cognitive function.Regulating cognitive function involves an understanding of aspects such as perception,learning and memory,attention,spatial cognition,and physical function.To enhance the application of cognitive regulation in the general population,this paper reviews recent publications from the Web of Science to assess the advancements and challenges of invasive and non-invasive stimulation methods in modulating cognitive functions.This review covers various neuromodulation techniques for cognitive intervention,including deep brain stimulation,vagus nerve stimulation,and invasive methods using microelectrode arrays.The non-invasive techniques discussed include transcranial magnetic stimulation,transcranial direct current stimulation,transcranial alternating current stimulation,transcutaneous electrical acupoint stimulation,and time interference stimulation for activating deep targets.Invasive stimulation methods,which are ideal for studying the pathogenesis of neurological diseases,tend to cause greater trauma and have been less researched in the context of cognitive function regulation.Non-invasive methods,particularly newer transcranial stimulation techniques,are gentler and more appropriate for regulating cognitive functions in the general population.These include transcutaneous acupoint electrical stimulation using acupoints and time interference methods for activating deep targets.This paper also discusses current technical challenges and potential future breakthroughs in neuromodulation technology.It is recommended that neuromodulation techniques be combined with neural detection methods to better assess their effects and improve the accuracy of non-invasive neuromodulation.Additionally,researching closed-loop feedback neuromodulation methods is identified as a promising direction for future development.展开更多
Brain lesions,such as those caused by stroke or traumatic brain injury(TBI),frequently result in persistent motor and cognitive impairments that significantly affect the individual patient's quality of life.Despit...Brain lesions,such as those caused by stroke or traumatic brain injury(TBI),frequently result in persistent motor and cognitive impairments that significantly affect the individual patient's quality of life.Despite differences in the mechanisms of injury,both conditions share a high prevalence of motor and cognitive impairments.These deficits show only limited natural recovery.展开更多
Alzheimer's disease is the most common type of cognitive disorder,and there is an urgent need to develop more effective,targeted and safer therapies for patients with this condition.Deep brain stimulation is an in...Alzheimer's disease is the most common type of cognitive disorder,and there is an urgent need to develop more effective,targeted and safer therapies for patients with this condition.Deep brain stimulation is an invasive surgical treatment that modulates abnormal neural activity by implanting electrodes into specific brain areas followed by electrical stimulation.As an emerging therapeutic approach,deep brain stimulation shows significant promise as a potential new therapy for Alzheimer's disease.Here,we review the potential mechanisms and therapeutic effects of deep brain stimulation in the treatment of Alzheimer's disease based on existing clinical and basic research.In clinical studies,the most commonly targeted sites include the fornix,the nucleus basalis of Meynert,and the ventral capsule/ventral striatum.Basic research has found that the most frequently targeted areas include the fornix,nucleus basalis of Meynert,hippocampus,entorhinal cortex,and rostral intralaminar thalamic nucleus.All of these individual targets exhibit therapeutic potential for patients with Alzheimer's disease and associated mechanisms of action have been investigated.Deep brain stimulation may exert therapeutic effects on Alzheimer's disease through various mechanisms,including reducing the deposition of amyloid-β,activation of the cholinergic system,increasing the levels of neurotrophic factors,enhancing synaptic activity and plasticity,promoting neurogenesis,and improving glucose metabolism.Currently,clinical trials investigating deep brain stimulation for Alzheimer's disease remain insufficient.In the future,it is essential to focus on translating preclinical mechanisms into clinical trials.Furthermore,consecutive follow-up studies are needed to evaluate the long-term safety and efficacy of deep brain stimulation for Alzheimer's disease,including cognitive function,neuropsychiatric symptoms,quality of life and changes in Alzheimer's disease biomarkers.Researchers must also prioritize the initiation of multi-center clinical trials of deep brain stimulation with large sample sizes and target earlier therapeutic windows,such as the prodromal and even the preclinical stages of Alzheimer's disease.Adopting these approaches will permit the efficient exploration of more effective and safer deep brain stimulation therapies for patients with Alzheimer's disease.展开更多
Multisensory enhancement,as a facilitation phenomenon,is responsible for superior behavioral performance when an individual is responding to cross-modal versus modality-specific stimuli.However,the event-related poten...Multisensory enhancement,as a facilitation phenomenon,is responsible for superior behavioral performance when an individual is responding to cross-modal versus modality-specific stimuli.However,the event-related potential（ERP） counterparts of behavioral multisensory enhancement are not well known.We recorded ERPs and behavioral data from 14 healthy volunteers with three types of target stimuli（modality-specific,bimodal,and trimodal） to examine the spatio-temporal electrophysiological characteristics of multisensory enhancement by comparing behavioral data with ERPs.We found a strong correlation between P3 latency and behavioral performance in terms of reaction time（RT）（R = 0.98,P ＆lt;0.001）,suggesting that P3 latency constitutes a temporal measure of behavioral multisensory enhancement.In addition,a fast RT and short P3 latency were found when comparing the modality-specific visual target with the modality-specific auditory and somatosensory targets.Our results indicate that behavioral multisensory enhancement can be identified by the latency and source distribution of the P3 component.These findings may advance our understanding of the neuronal mechanisms of multisensory enhancement.展开更多
A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigati...A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and progression.Nonetheless,nonpharmacological interventions aimed at inducing adult neurogenesis are currently limited.Although individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully explored.In this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 months.Amyloid deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease progressed.However,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus decreased.These findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 mice.Furthermore,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice following multifactor stimulation,as evidenced by Morris water maze,novel object recognition,forced swimming test,and tail suspension test results.Notably,the efficacy of multifactor stimulation in consolidating immature neurons persisted for at least 2weeks after treatment cessation.At the molecular level,multifactor stimulation upregulated the expression of neuron-related proteins(NeuN,doublecortin,postsynaptic density protein-95,and synaptophysin),anti-apoptosis-related proteins(Bcl-2 and PARP),and an autophagyassociated protein(LC3B),while decreasing the expression of apoptosis-related proteins(BAX and caspase-9),in the hippocampus of amyloid precursor protein/presenilin 1 mice.These observations might be attributable to both the brain-derived neurotrophic factor-mediated signaling pathway and antioxidant pathways.Furthermore,serum metabolomics analysis indicated that multifactor stimulation regulated differentially expressed metabolites associated with cell apoptosis,oxidative damage,and cognition.Collectively,these findings suggest that multifactor stimulation is a novel non-invasive approach for the prevention and treatment of Alzheimer's disease.展开更多
Alzheimer’s disease is a neurodegenerative disease resulting from deficits in synaptic transmission and homeostasis.The Alzheimer’s disease brain tends to be hyperexcitable and hypersynchronized,thereby causing neur...Alzheimer’s disease is a neurodegenerative disease resulting from deficits in synaptic transmission and homeostasis.The Alzheimer’s disease brain tends to be hyperexcitable and hypersynchronized,thereby causing neurodegeneration and ultimately disrupting the operational abilities in daily life,leaving patients incapacitated.Repetitive transcranial magnetic stimulation is a cost-effective,neuro-modulatory technique used for multiple neurological conditions.Over the past two decades,it has been widely used to predict cognitive decline;identify pathophysiological markers;promote neuroplasticity;and assess brain excitability,plasticity,and connectivity.It has also been applied to patients with dementia,because it can yield facilitatory effects on cognition and promote brain recovery after a neurological insult.However,its therapeutic effectiveness at the molecular and synaptic levels has not been elucidated because of a limited number of studies.This study aimed to characterize the neurobiological changes following repetitive transcranial magnetic stimulation treatment,evaluate its effects on synaptic plasticity,and identify the associated mechanisms.This review essentially focuses on changes in the pathology,amyloidogenesis,and clearance pathways,given that amyloid deposition is a major hypothesis in the pathogenesis of Alzheimer’s disease.Apoptotic mechanisms associated with repetitive transcranial magnetic stimulation procedures and different pathways mediating gene transcription,which are closely related to the neural regeneration process,are also highlighted.Finally,we discuss the outcomes of animal studies in which neuroplasticity is modulated and assessed at the structural and functional levels by using repetitive transcranial magnetic stimulation,with the aim to highlight future directions for better clinical translations.展开更多
Objective:To study the effect of repetitive peripheral magnetic stimulation(rPMS)combined with conventional rehabilitation measures on shoulder dysfunction in early stroke.Methods:60 patients with shoulder dysfunction...Objective:To study the effect of repetitive peripheral magnetic stimulation(rPMS)combined with conventional rehabilitation measures on shoulder dysfunction in early stroke.Methods:60 patients with shoulder dysfunction in early stroke were selected,and all of them were admitted to our hospital from August 2021 to August 2023.The patients were randomly grouped into a control group(conventional rehabilitation measures intervention,30 cases)and an intervention group(rPMS and conventional rehabilitation measures intervention,30 cases)according to the lottery method.The pain scores,shoulder mobility,and motor function scores of the two groups were compared.Results:The pain score was lower in the intervention group,and the shoulder mobility and motor function scores were higher in the intervention group(P<0.05)as compared to that of the control group.Conclusion:The effect of combining rPMS and conventional rehabilitation measures in treating shoulder dysfunction in early stroke was remarkable and should be popularized.展开更多
Transcutaneous electrical acupoint stimulation(TEAS)is a kind of physical therapy that use electric cur-rent through the electrodes placed on the surface of acupoints to produce clinical effects in the human body,whic...Transcutaneous electrical acupoint stimulation(TEAS)is a kind of physical therapy that use electric cur-rent through the electrodes placed on the surface of acupoints to produce clinical effects in the human body,which is characterized by less adverse reaction and convenient operation.It has been widely used in the treatment of various diseases.This review introduces six major clinical applications of TEAS,named analgesia,regulation of gastrointestinal function,improvement of reproductive function,enhancement of cognitive function,promotion of limb function recovery and relief of fatigue.Besides,TEAS has been ap-plied to the treatment of other chronic diseases such as hypertension and diabetes,achieving satisfactory clinical effects.However,two crucial challenges are encountered in the development of TEAS.One is the lack of standardization in the selection of parameters such as waveform,frequency,intensity and stimula-tion duration.The other is the limitation on the flexibility in the acupoint selection.This review analyzes key issues that need to be addressed in the current clinical application of TEAS,such as the selection of parameters and acupoints,and this review provides a certain reference value for optimizing regimens of TEAS and promoting its development and application.展开更多
The critical role of patient-reported outcome measures(PROMs)in enhancing clinical decision-making and promoting patient-centered care has gained a profound significance in scientific research.PROMs encapsulate a pati...The critical role of patient-reported outcome measures(PROMs)in enhancing clinical decision-making and promoting patient-centered care has gained a profound significance in scientific research.PROMs encapsulate a patient's health status directly from their perspective,encompassing various domains such as symptom severity,functional status,and overall quality of life.By integrating PROMs into routine clinical practice and research,healthcare providers can achieve a more nuanced understanding of patient experiences and tailor treatments accordingly.The deployment of PROMs supports dynamic patient-provider interactions,fostering better patient engagement and adherence to tre-atment plans.Moreover,PROMs are pivotal in clinical settings for monitoring disease progression and treatment efficacy,particularly in chronic and mental health conditions.However,challenges in implementing PROMs include data collection and management,integration into existing health systems,and acceptance by patients and providers.Overcoming these barriers necessitates technological advancements,policy development,and continuous education to enhance the acceptability and effectiveness of PROMs.The paper concludes with recommendations for future research and policy-making aimed at optimizing the use and impact of PROMs across healthcare settings.展开更多
Vagus nerve stimulation(VNS)and stroke:Stroke is the second leading cause of death and the third leading cause of disability worldwide(Baig et al.,2023).There have been significant paradigm shifts in the management of...Vagus nerve stimulation(VNS)and stroke:Stroke is the second leading cause of death and the third leading cause of disability worldwide(Baig et al.,2023).There have been significant paradigm shifts in the management of acute ischemic stroke through mechanical thrombectomy.In chronic ischemic stroke,invasive VNS paired with rehabilitation is associated with a significant increase in upper limb motor recovery and is FDA-approved(Baig et al.,2023).There are no treatments of similar efficacy in acute intracerebral hemorrhage(ICH)where several promising trials,e.g.,TICH-2,STOP-AUST,and TRAIGE did not show improvements in functional outcomes(Puy et al.,2023).展开更多
Coal measures are significant hydrocarbon source rocks and reservoirs in petroliferous basins.Many large gas fields and coalbed methane fields globally are originated from coal-measure source rocks or accumulated in c...Coal measures are significant hydrocarbon source rocks and reservoirs in petroliferous basins.Many large gas fields and coalbed methane fields globally are originated from coal-measure source rocks or accumulated in coal rocks.Inspired by the discovery of shale oil and gas,and guided by“the overall exploration concept of considering coal rock as reservoir”,breakthroughs in the exploration and development of coal-rock gas have been achieved in deep coal seams with favorable preservation conditions,thereby opening up a new development frontier for the unconventional gas in coal-rock reservoirs.Based on the data from exploration and development practices,a systematic study on the accumulation mechanism of coal-rock gas has been conducted.The mechanisms of“three fields”controlling coal-rock gas accumulation are revealed.It is confirmed that the coal-rock gas is different from CBM in accumulation process.The whole petroleum systems in the Carboniferous–Permian transitional facies coal measures of the eastern margin of the Ordos Basin and in the Jurassic continental facies coal measures of the Junggar Basin are characterized,and the key research directions for further developing the whole petroleum system theory of coal measures are proposed.Coal rocks,compared to shale,possess intense hydrocarbon generation potential,strong adsorption capacity,dual-medium reservoir properties,and partial or weak oil and gas self-sealing capacity.Additionally,unlike other unconventional gas such as shale gas and tight gas,coal-rock gas exhibits more complex accumulation characteristics,and its accumulation requires a certain coal-rock play form lithological and structural traps.Coal-rock gas also has the characteristics of conventional fractured gas reservoirs.Compared with the basic theory and model of the whole petroleum system established based on detrital rock formations,coal measures have distinct characteristics and differences in coal-rock reservoirs and source-reservoir coupling.The whole petroleum system of coal measures is composed of various types of coal-measure hydrocarbon plays with coal(and dark shale)in coal measures as source rock and reservoir,and with adjacent tight layers as reservoirs or cap or transport layers.Under the action of source-reservoir coupling,coal-rock gas is accumulated in coal-rock reservoirs with good preservation conditions,tight oil/gas is accumulated in tight layers,conventional oil/gas is accumulated in traps far away from sources,and coalbed methane is accumulated in coal-rock reservoirs damaged by later geological processes.The proposed whole petroleum system of coal measures represents a novel type of whole petroleum system.展开更多
Temporal interference(TI)is a form of stimulation that epitomizes an innovative and non-invasive approach for profound neuromodulation of the brain,a technique that has been validated in mice.Yet,the thin cranial bone...Temporal interference(TI)is a form of stimulation that epitomizes an innovative and non-invasive approach for profound neuromodulation of the brain,a technique that has been validated in mice.Yet,the thin cranial bone structure of mice has a marginal influence on the effect of the TI technique and may not effectively showcase its effectiveness in larger animals.Based on this,we carried out TI stimulation experiments on rats.Following the TI intervention,analysis of electrophysiological data and immunofluorescence staining indicated the generation of a stimulation focus within the nucleus accumbens(depth,8.5 mm)in rats.Our findings affirm the viability of the TI methodology in the presence of thick cranial bones,furnishing efficacious parameters for profound stimulation with TI administered under such conditions.This experiment not only sheds light on the intervention effects of TI deep in the brain but also furnishes robust evidence in support of its prospective clinical utility.展开更多
In the practice of healthcare,patient-reported outcomes(PROs)and PRO measures(PROMs)are used as an attempt to observe the changes in complex clinical situations.They guide us in making decisions based on the evidence ...In the practice of healthcare,patient-reported outcomes(PROs)and PRO measures(PROMs)are used as an attempt to observe the changes in complex clinical situations.They guide us in making decisions based on the evidence regarding patient care by recording the change in outcomes for a particular treatment to a given condition and finally to understand whether a patient will benefit from a particular treatment and to quantify the treatment effect.For any PROM to be usable in health care,we need it to be reliable,encapsulating the points of interest with the potential to detect any real change.Using structured outcome measures routinely in clinical practice helps the physician to understand the functional limitation of a patient that would otherwise not be clear in an office interview,and this allows the physician and patient to have a meaningful conver-sation as well as a customized plan for each patient.Having mentioned the rationale and the benefits of PROMs,understanding the quantification process is crucial before embarking on management decisions.A better interpretation of change needs to identify the treatment effect based on clinical relevance for a given condition.There are a multiple set of measurement indices to serve this effect and most of them are used interchangeably without clear demarcation on their differences.This article details the various quantification metrics used to evaluate the treatment effect using PROMs,their limitations and the scope of usage and implementation in clinical practice.展开更多
There are various types of natural gas resources in coal measures,making them major targets for natural gas exploration and development in China.In view of the particularity of the whole petroleum system of coal measu...There are various types of natural gas resources in coal measures,making them major targets for natural gas exploration and development in China.In view of the particularity of the whole petroleum system of coal measures and the reservoir-forming evolution of natural gas in coal,this study reveals the formation,enrichment characteristics and distribution laws of coal-rock gas by systematically reviewing the main types and geological characteristics of natural gas in the whole petroleum system of coal measures.First,natural gas in the whole petroleum system of coal measures is divided into two types,conventional gas and unconventional gas,according to its occurrence characteristics and accumulation mechanism,and into six types,distal detrital rock gas,special rock gas,distal/proximal tight sandstone gas,inner-source tight sandstone gas,shale gas,and coal-rock gas,according to its source and reservoir lithology.The natural gas present in coal-rock reservoirs is collectively referred to as coal-rock gas.Existing data indicate significant differences in the geological characteristics of coal-rock gas exploration and development between shallow and deep layers in the same area,with the transition depth boundary generally 1500-2000 m.Based on the current understanding of coal-rock gas and respecting the historical usage conventions of coalbed methane terminology,coal-rock gas can be divided into deep coal-rock gas and shallow coalbed methane according to burial depth.Second,according to the research concept of“full-process reservoir formation”in the theory of the whole petroleum system of coal measures,based on the formation and evolution of typical coal-rock gas reservoirs,coal-rock gas is further divided into four types:primary coal-rock gas,regenerated coal-rock gas,residual coal-rock gas,and bio coal-rock gas.The first two belong to deep coal-rock gas,while the latter two belong to shallow coal-rock gas.Third,research on the coal-rock gas reservoir formation and evolution shows that shallow coal-rock gas is mainly residual coal-rock gas or bio coal-rock gas formed after geological transformation of primary coal-rock gas,with the reservoir characteristics such as low reservoir pressure,low gas saturation,adsorbed gas in dominance,and gas production by drainage and depressurization,while deep coal-rock gas is mainly primary coal-rock gas and regenerated coal-rock gas,with the reservoir characteristics such as high reservoir pressure,high gas saturation,abundant free gas,and no or little water.In particular,the primary coal-rock gas is wide in distribution,large in resource quantity,and good in reservoir quality,making it the most favorable type of coal-rock gas for exploration and development.展开更多
An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease prog...An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease progression,demonstrating the need for novel approaches in PD.Repetitive transcranial magnetic stimulation is a non-invasive approach that has been shown to improve motor and non-motor symptoms of Parkinson's disease.However,the underlying mechanisms of the beneficial effects of repetitive transcranial magnetic stimulation remain unknown.The purpose of this study is to investigate the extent to which the beneficial effects of prolonged intermittent theta burst stimulation in the 6-hydroxydopamine model of experimental parkinsonism are based on modulation of adenosine-mediated signaling.Animals with unilateral 6-hydroxydopamine lesions underwent intermittent theta burst stimulation for 3 weeks and were tested for motor skills using the Rotarod test.Immunoblot,quantitative reverse transcription polymerase chain reaction,immunohistochemistry,and biochemical analysis of components of adenosine-mediated signaling were performed on the synaptosomal fraction of the lesioned caudate putamen.Prolonged intermittent theta burst stimulation improved motor symptoms in 6-hydroxydopamine-lesioned animals.A 6-hydroxydopamine lesion resulted in progressive loss of dopaminergic neurons in the caudate putamen.Treatment with intermittent theta burst stimulation began 7 days after the lesion,coinciding with the onset of motor symptoms.After treatment with prolonged intermittent theta burst stimulation,complete motor recovery was observed.This improvement was accompanied by downregulation of the e N/CD73-A_(2A)R pathway and a return to physiological levels of A_(1)R-adenosine deaminase 1 after 3 weeks of intermittent theta burst stimulation.Our results demonstrated that 6-hydroxydopamine-induced degeneration reduced the expression of A_(1)R and elevated the expression of A_(2A)R.Intermittent theta burst stimulation reversed these effects by restoring the abundances of A_(1)R and A_(2A)R to control levels.The shift in ARs expression likely restored the balance between dopamine-adenosine signaling,ultimately leading to the recovery of motor control.展开更多
BACKGROUND Although gastroscopy is a commonly used diagnostic and therapeutic technique,postoperative gastrointestinal dysfunction is prone to occur.Traditional Chinese medicine theory suggests that postoperative gast...BACKGROUND Although gastroscopy is a commonly used diagnostic and therapeutic technique,postoperative gastrointestinal dysfunction is prone to occur.Traditional Chinese medicine theory suggests that postoperative gastrointestinal disorders are related to spleen and stomach weakness.This study hypothesizes that the combination of acupoint application at the Ziwu Liuzhu acupoint and percutaneous acupoint electrical stimulation can promote postoperative gastrointestinal function recovery and alleviate stress reactions.AIM To investigate the effects of acupoint application of Ziwu Liuzhu combined with percutaneous acupoint electrical stimulation on postoperative gastrointestinal function recovery and stress response in patients undergoing gastrointestinal endoscopy surgery.METHODS A total of 120 patients who underwent gastroscopy surgery were selected and treated between October 2024 and January 2025.This study used a stratified block randomization method,and then allocated groups using computer-generated random number sequences(SAS 9.4 software).The groups were divided into two groups:A control group of 60 patients who received routine postoperative intervention measures,and an observation group of 60 patients who received acupuncture point application combined with transcutaneous acupoint electrical CONCLUSION The combination of percutaneous acupoint electrical stimulation in gastroscopy patients has been demonstrated to be both highly safe and effective.The benefits of this approach include the promotion of postoperative gastrointestinal function,the reduction of stress response,the attainment of optimal results,and the enhancement of patient satisfaction.展开更多
Objective To evaluate the association of GGN repeat polymorphism of androgen receptor(AR)with ovarian reserve and ovarian response in controlled ovarian stimulation(COS).Methods This genetic association study was cond...Objective To evaluate the association of GGN repeat polymorphism of androgen receptor(AR)with ovarian reserve and ovarian response in controlled ovarian stimulation(COS).Methods This genetic association study was conducted among a total of 361 women aged≤40 years with basal FSH≤12 U/L undergoing the GnRH-agonist long protocol for COS in a university affiliated IVF center.GGN repeat in the AR gene was analyzed with Sanger sequencing.The primary endpoint was the number of antral follicle counts(AFCs),and the secondary endpoints were stimulation days,total dose of gonadotropin(Gn)used,total number of retrieved oocytes,ovarian sensitivity index,and follicular output rate.Results The GGN repeat in exon 1 of the AR gene ranged from 13 to 24,and the median repeat length was 22.Based on the genotypes(S for GGN repeats<22,L for GGN repeats≥22),the patients were divided into 3 groups:SS,SL,and LL.Generalized regression analysis indicated that the number of AFCs in group SS was significantly lower than those in group SL(adjusted β=1.8,95%CI:0.2-3.4,P=0.024)and group LL(adjusted β=1.5,95%CI:0.2-2.7,P=0.021).No significant difference was observed in the number of AFCs between group SL and group LL(P>0.05).Generalized regression analysis indicated no significant differences in ovarian stimulation parameters among the 3 groups,either before or after adjusting for confounding factors(P>0.05).Conclusion GGN repeat length on the AR gene is associated with AFC but not with ovarian response in Chinese women,indicating that AR gene polymorphisms may affect ovarian reserve.展开更多
Due to the numerous variables to take into account as well as the inherent ambiguity and uncertainty,evaluating educational institutions can be difficult.The concept of a possibility Pythagorean fuzzy hypersoft set(pP...Due to the numerous variables to take into account as well as the inherent ambiguity and uncertainty,evaluating educational institutions can be difficult.The concept of a possibility Pythagorean fuzzy hypersoft set(pPyFHSS)is more flexible in this regard than other theoretical fuzzy set-like models,even though some attempts have been made in the literature to address such uncertainties.This study investigates the elementary notions of pPyFHSS including its set-theoretic operations union,intersection,complement,OR-and AND-operations.Some results related to these operations are also modified for pPyFHSS.Additionally,the similarity measures between pPyFHSSs are formulated with the assistance of numerical examples and results.Lastly,an intelligent decision-assisted mechanism is developed with the proposal of a robust algorithm based on similarity measures for solving multi-attribute decision-making(MADM)problems.A case study that helps the decision-makers assess the best educational institution is discussed to validate the suggested system.The algorithmic results are compared with the most pertinent model to evaluate the adaptability of pPyFHSS,as it generalizes the classical possibility fuzzy set-like theoretical models.Similarly,while considering significant evaluating factors,the flexibility of pPyFHSS is observed through structural comparison.展开更多
基金funded by the Deutsche Forschungsgemeinschaft(DFG,German Research Foundation):project ID 431549029-SFB 1451the Marga-und-Walter-Boll-Stiftung(#210-10-15)(to MAR)a stipend from the'Gerok Program'(Faculty of Medicine,University of Cologne,Germany)。
文摘Noninvasive brain stimulation techniques offer promising therapeutic and regenerative prospects in neurological diseases by modulating brain activity and improving cognitive and motor functions.Given the paucity of knowledge about the underlying modes of action and optimal treatment modalities,a thorough translational investigation of noninvasive brain stimulation in preclinical animal models is urgently needed.Thus,we reviewed the current literature on the mechanistic underpinnings of noninvasive brain stimulation in models of central nervous system impairment,with a particular emphasis on traumatic brain injury and stroke.Due to the lack of translational models in most noninvasive brain stimulation techniques proposed,we found this review to the most relevant techniques used in humans,i.e.,transcranial magnetic stimulation and transcranial direct current stimulation.We searched the literature in Pub Med,encompassing the MEDLINE and PMC databases,for studies published between January 1,2020 and September 30,2024.Thirty-five studies were eligible.Transcranial magnetic stimulation and transcranial direct current stimulation demonstrated distinct strengths in augmenting rehabilitation post-stroke and traumatic brain injury,with emerging mechanistic evidence.Overall,we identified neuronal,inflammatory,microvascular,and apoptotic pathways highlighted in the literature.This review also highlights a lack of translational surrogate parameters to bridge the gap between preclinical findings and their clinical translation.
基金supported by the Fundamental Research Funds for the Central Universities,Nos.G2021KY05107,G2021KY05101the National Natural Science Foundation of China,Nos.32071316,32211530049+1 种基金the Natural Science Foundation of Shaanxi Province,No.2022-JM482the Education and Teaching Reform Funds for the Central Universities,No.23GZ230102(all to LL and HH).
文摘Although previous studies have demonstrated that transcranial focused ultrasound stimulation protects the ischemic brain,clear criteria for the stimulation time window and intensity are lacking.Electrical impedance tomography enables real-time monitoring of changes in cerebral blood perfusion within the ischemic brain,but investigating the feasibility of using this method to assess post-stroke rehabilitation in vivo remains critical.In this study,ischemic stroke was induced in rats through middle cerebral artery occlusion surgery.Transcranial focused ultrasound stimulation was used to treat the rat model of ischemia,and electrical impedance tomography was used to measure impedance during both the acute stage of ischemia and the rehabilitation stage following the stimulation.Electrical impedance tomography results indicated that cerebral impedance increased after the onset of ischemia and decreased following transcranial focused ultrasound stimulation.Furthermore,the stimulation promoted motor function recovery,reduced cerebral infarction volume in the rat model of ischemic stroke,and induced the expression of brain-derived neurotrophic factor in the ischemic brain.Our results also revealed a significant correlation between the impedance of the ischemic brain post-intervention and improvements in behavioral scores and infarct volume.This study shows that daily administration of transcranial focused ultrasound stimulation for 20 minutes to the ischemic hemisphere 24 hours after cerebral ischemia enhanced motor recovery in a rat model of ischemia.Additionally,our findings indicate that electrical impedance tomography can serve as a valuable tool for quantitatively evaluating rehabilitation after ischemic stroke in vivo.These findings suggest the feasibility of using impedance data collected via electrical impedance tomography to clinically assess the effects of rehabilitatory interventions for patients with ischemic stroke.
基金supported by STI 2030-Major Projects,No.2021ZD0201603(to JL)the Joint Foundation Program of the Chinese Academy of Sciences,No.8091A170201(to JL)+1 种基金the National Natural Science Foundation of China,Nos.T2293730(to XC),T2293731(to XC),T2293734(to XC),62471291(to YW),62121003(to XC),61960206012(to XC),62333020(to XC),and 62171434(to XC)the National Key Research and Development Program of China,Nos.2022YFC2402501(to XC),2022YFB3205602(to XC).
文摘Neuromodulation techniques effectively intervene in cognitive function,holding considerable scientific and practical value in fields such as aerospace,medicine,life sciences,and brain research.These techniques utilize electrical stimulation to directly or indirectly target specific brain regions,modulating neural activity and influencing broader brain networks,thereby regulating cognitive function.Regulating cognitive function involves an understanding of aspects such as perception,learning and memory,attention,spatial cognition,and physical function.To enhance the application of cognitive regulation in the general population,this paper reviews recent publications from the Web of Science to assess the advancements and challenges of invasive and non-invasive stimulation methods in modulating cognitive functions.This review covers various neuromodulation techniques for cognitive intervention,including deep brain stimulation,vagus nerve stimulation,and invasive methods using microelectrode arrays.The non-invasive techniques discussed include transcranial magnetic stimulation,transcranial direct current stimulation,transcranial alternating current stimulation,transcutaneous electrical acupoint stimulation,and time interference stimulation for activating deep targets.Invasive stimulation methods,which are ideal for studying the pathogenesis of neurological diseases,tend to cause greater trauma and have been less researched in the context of cognitive function regulation.Non-invasive methods,particularly newer transcranial stimulation techniques,are gentler and more appropriate for regulating cognitive functions in the general population.These include transcutaneous acupoint electrical stimulation using acupoints and time interference methods for activating deep targets.This paper also discusses current technical challenges and potential future breakthroughs in neuromodulation technology.It is recommended that neuromodulation techniques be combined with neural detection methods to better assess their effects and improve the accuracy of non-invasive neuromodulation.Additionally,researching closed-loop feedback neuromodulation methods is identified as a promising direction for future development.
基金supported by the Defitech Foundation(Morges,CH)to FCHthe Bertarelli Foundation-Catalyst program(Gstaad,CH)to FCH+2 种基金the Wyss Center for Bio and Neuroengineering the Lighthouse Partnership for AI-guided Neuromodulation to FCHthe Fonds de recherche du Quebec-Sante(FRQS#342969)to CEPthe Neuro X Postdoctoral Fellowship Program to CEP。
文摘Brain lesions,such as those caused by stroke or traumatic brain injury(TBI),frequently result in persistent motor and cognitive impairments that significantly affect the individual patient's quality of life.Despite differences in the mechanisms of injury,both conditions share a high prevalence of motor and cognitive impairments.These deficits show only limited natural recovery.
基金supported by the Capital Fund for Health Improvement and Research,No.2022-2-2048(to WZ)the National Natural Science Foundation of China,No.81970992(to WZ)+3 种基金Capital Clinical Characteristic Application Research,No.Z121107001012161(to WZ)the Natural Science Foundation of Beijing,No.7082032(to WZ)the Key Technology R&D Program of Beijing Municipal Education Commission,No.KZ201610025030(to WZ)Project of Scientific and Technological Development of Traditional Chinese Medicine in Beijing,No.JJ2018-48(to WZ)。
文摘Alzheimer's disease is the most common type of cognitive disorder,and there is an urgent need to develop more effective,targeted and safer therapies for patients with this condition.Deep brain stimulation is an invasive surgical treatment that modulates abnormal neural activity by implanting electrodes into specific brain areas followed by electrical stimulation.As an emerging therapeutic approach,deep brain stimulation shows significant promise as a potential new therapy for Alzheimer's disease.Here,we review the potential mechanisms and therapeutic effects of deep brain stimulation in the treatment of Alzheimer's disease based on existing clinical and basic research.In clinical studies,the most commonly targeted sites include the fornix,the nucleus basalis of Meynert,and the ventral capsule/ventral striatum.Basic research has found that the most frequently targeted areas include the fornix,nucleus basalis of Meynert,hippocampus,entorhinal cortex,and rostral intralaminar thalamic nucleus.All of these individual targets exhibit therapeutic potential for patients with Alzheimer's disease and associated mechanisms of action have been investigated.Deep brain stimulation may exert therapeutic effects on Alzheimer's disease through various mechanisms,including reducing the deposition of amyloid-β,activation of the cholinergic system,increasing the levels of neurotrophic factors,enhancing synaptic activity and plasticity,promoting neurogenesis,and improving glucose metabolism.Currently,clinical trials investigating deep brain stimulation for Alzheimer's disease remain insufficient.In the future,it is essential to focus on translating preclinical mechanisms into clinical trials.Furthermore,consecutive follow-up studies are needed to evaluate the long-term safety and efficacy of deep brain stimulation for Alzheimer's disease,including cognitive function,neuropsychiatric symptoms,quality of life and changes in Alzheimer's disease biomarkers.Researchers must also prioritize the initiation of multi-center clinical trials of deep brain stimulation with large sample sizes and target earlier therapeutic windows,such as the prodromal and even the preclinical stages of Alzheimer's disease.Adopting these approaches will permit the efficient exploration of more effective and safer deep brain stimulation therapies for patients with Alzheimer's disease.
基金partly supported by the National Natural Science Foundation of China(81271685)Key Project of Science and Technology Fund of Tianjin Municipality,China(10JCZDJC16100)+1 种基金the China Postdoctoral Science Foundation(2012M510754)the Independent Innovative Fund of Tianjin University,Tianjin Municipality,China(1102)
文摘Multisensory enhancement,as a facilitation phenomenon,is responsible for superior behavioral performance when an individual is responding to cross-modal versus modality-specific stimuli.However,the event-related potential（ERP） counterparts of behavioral multisensory enhancement are not well known.We recorded ERPs and behavioral data from 14 healthy volunteers with three types of target stimuli（modality-specific,bimodal,and trimodal） to examine the spatio-temporal electrophysiological characteristics of multisensory enhancement by comparing behavioral data with ERPs.We found a strong correlation between P3 latency and behavioral performance in terms of reaction time（RT）（R = 0.98,P ＆lt;0.001）,suggesting that P3 latency constitutes a temporal measure of behavioral multisensory enhancement.In addition,a fast RT and short P3 latency were found when comparing the modality-specific visual target with the modality-specific auditory and somatosensory targets.Our results indicate that behavioral multisensory enhancement can be identified by the latency and source distribution of the P3 component.These findings may advance our understanding of the neuronal mechanisms of multisensory enhancement.
基金supported by the National Natural Science Foundation of China,No.82001155(to LL)the Natural Science Foundation of Zhejiang Province,No.LY23H090004(to LL)+5 种基金the Natural Science Foundation of Ningbo,No.2023J068(to LL)the Fundamental Research Funds for the Provincial Universities of Zhejiang Province,No.SJLY2023008(to LL)the College Students'Scientific and Technological Innovation Project(Xin Miao Talent Plan)of Zhejiang Province,No.2022R405A045(to CC)the Student ResearchInnovation Program(SRIP)of Ningbo University,Nos.20235RIP1919(to CZ),2023SRIP1938(to YZ)the K.C.Wong Magna Fund in Ningbo University。
文摘A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and progression.Nonetheless,nonpharmacological interventions aimed at inducing adult neurogenesis are currently limited.Although individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully explored.In this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 months.Amyloid deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease progressed.However,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus decreased.These findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 mice.Furthermore,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice following multifactor stimulation,as evidenced by Morris water maze,novel object recognition,forced swimming test,and tail suspension test results.Notably,the efficacy of multifactor stimulation in consolidating immature neurons persisted for at least 2weeks after treatment cessation.At the molecular level,multifactor stimulation upregulated the expression of neuron-related proteins(NeuN,doublecortin,postsynaptic density protein-95,and synaptophysin),anti-apoptosis-related proteins(Bcl-2 and PARP),and an autophagyassociated protein(LC3B),while decreasing the expression of apoptosis-related proteins(BAX and caspase-9),in the hippocampus of amyloid precursor protein/presenilin 1 mice.These observations might be attributable to both the brain-derived neurotrophic factor-mediated signaling pathway and antioxidant pathways.Furthermore,serum metabolomics analysis indicated that multifactor stimulation regulated differentially expressed metabolites associated with cell apoptosis,oxidative damage,and cognition.Collectively,these findings suggest that multifactor stimulation is a novel non-invasive approach for the prevention and treatment of Alzheimer's disease.
基金supported by the Hefei Comprehensive National Science Center Hefei Brain Project(to KW)the National Natural Science Foundation of China,Nos.31970979(to KW),82101498(to XW)the STI2030-Major Projects,No.2021ZD0201800(to PH).
文摘Alzheimer’s disease is a neurodegenerative disease resulting from deficits in synaptic transmission and homeostasis.The Alzheimer’s disease brain tends to be hyperexcitable and hypersynchronized,thereby causing neurodegeneration and ultimately disrupting the operational abilities in daily life,leaving patients incapacitated.Repetitive transcranial magnetic stimulation is a cost-effective,neuro-modulatory technique used for multiple neurological conditions.Over the past two decades,it has been widely used to predict cognitive decline;identify pathophysiological markers;promote neuroplasticity;and assess brain excitability,plasticity,and connectivity.It has also been applied to patients with dementia,because it can yield facilitatory effects on cognition and promote brain recovery after a neurological insult.However,its therapeutic effectiveness at the molecular and synaptic levels has not been elucidated because of a limited number of studies.This study aimed to characterize the neurobiological changes following repetitive transcranial magnetic stimulation treatment,evaluate its effects on synaptic plasticity,and identify the associated mechanisms.This review essentially focuses on changes in the pathology,amyloidogenesis,and clearance pathways,given that amyloid deposition is a major hypothesis in the pathogenesis of Alzheimer’s disease.Apoptotic mechanisms associated with repetitive transcranial magnetic stimulation procedures and different pathways mediating gene transcription,which are closely related to the neural regeneration process,are also highlighted.Finally,we discuss the outcomes of animal studies in which neuroplasticity is modulated and assessed at the structural and functional levels by using repetitive transcranial magnetic stimulation,with the aim to highlight future directions for better clinical translations.
文摘Objective:To study the effect of repetitive peripheral magnetic stimulation(rPMS)combined with conventional rehabilitation measures on shoulder dysfunction in early stroke.Methods:60 patients with shoulder dysfunction in early stroke were selected,and all of them were admitted to our hospital from August 2021 to August 2023.The patients were randomly grouped into a control group(conventional rehabilitation measures intervention,30 cases)and an intervention group(rPMS and conventional rehabilitation measures intervention,30 cases)according to the lottery method.The pain scores,shoulder mobility,and motor function scores of the two groups were compared.Results:The pain score was lower in the intervention group,and the shoulder mobility and motor function scores were higher in the intervention group(P<0.05)as compared to that of the control group.Conclusion:The effect of combining rPMS and conventional rehabilitation measures in treating shoulder dysfunction in early stroke was remarkable and should be popularized.
基金Supported by Shanghai 2020“Science and Technology Innovation Action Plan”Medical Innovation Research Special Program:20Y21902800Shanghai Municipal Health Commission Shanghai Three-Year Action Plan to Further Accelerate the Development of Traditional Chinese Medicine Inheritance and Innovation:ZY(2021-2023)−0302)+1 种基金Shanghai Key Specialty(Acupuncture)Construction Project:shslczdzk04701Shanghai 2024"Science and Technology Innovation Action Plan"star cultivation(Sail special):24YF2740600.
文摘Transcutaneous electrical acupoint stimulation(TEAS)is a kind of physical therapy that use electric cur-rent through the electrodes placed on the surface of acupoints to produce clinical effects in the human body,which is characterized by less adverse reaction and convenient operation.It has been widely used in the treatment of various diseases.This review introduces six major clinical applications of TEAS,named analgesia,regulation of gastrointestinal function,improvement of reproductive function,enhancement of cognitive function,promotion of limb function recovery and relief of fatigue.Besides,TEAS has been ap-plied to the treatment of other chronic diseases such as hypertension and diabetes,achieving satisfactory clinical effects.However,two crucial challenges are encountered in the development of TEAS.One is the lack of standardization in the selection of parameters such as waveform,frequency,intensity and stimula-tion duration.The other is the limitation on the flexibility in the acupoint selection.This review analyzes key issues that need to be addressed in the current clinical application of TEAS,such as the selection of parameters and acupoints,and this review provides a certain reference value for optimizing regimens of TEAS and promoting its development and application.
文摘The critical role of patient-reported outcome measures(PROMs)in enhancing clinical decision-making and promoting patient-centered care has gained a profound significance in scientific research.PROMs encapsulate a patient's health status directly from their perspective,encompassing various domains such as symptom severity,functional status,and overall quality of life.By integrating PROMs into routine clinical practice and research,healthcare providers can achieve a more nuanced understanding of patient experiences and tailor treatments accordingly.The deployment of PROMs supports dynamic patient-provider interactions,fostering better patient engagement and adherence to tre-atment plans.Moreover,PROMs are pivotal in clinical settings for monitoring disease progression and treatment efficacy,particularly in chronic and mental health conditions.However,challenges in implementing PROMs include data collection and management,integration into existing health systems,and acceptance by patients and providers.Overcoming these barriers necessitates technological advancements,policy development,and continuous education to enhance the acceptability and effectiveness of PROMs.The paper concludes with recommendations for future research and policy-making aimed at optimizing the use and impact of PROMs across healthcare settings.
基金supported by on Association of British Neurologists Fellowship(Stroke Association/Berkeley Foundation)supported by the NIHR Sheffield Biomedical Research Centre。
文摘Vagus nerve stimulation(VNS)and stroke:Stroke is the second leading cause of death and the third leading cause of disability worldwide(Baig et al.,2023).There have been significant paradigm shifts in the management of acute ischemic stroke through mechanical thrombectomy.In chronic ischemic stroke,invasive VNS paired with rehabilitation is associated with a significant increase in upper limb motor recovery and is FDA-approved(Baig et al.,2023).There are no treatments of similar efficacy in acute intracerebral hemorrhage(ICH)where several promising trials,e.g.,TICH-2,STOP-AUST,and TRAIGE did not show improvements in functional outcomes(Puy et al.,2023).
基金Supported by the PetroChina Basic Project(2024DJ23)CNPC Science Research and Technology Development Project(2021DJ0101)。
文摘Coal measures are significant hydrocarbon source rocks and reservoirs in petroliferous basins.Many large gas fields and coalbed methane fields globally are originated from coal-measure source rocks or accumulated in coal rocks.Inspired by the discovery of shale oil and gas,and guided by“the overall exploration concept of considering coal rock as reservoir”,breakthroughs in the exploration and development of coal-rock gas have been achieved in deep coal seams with favorable preservation conditions,thereby opening up a new development frontier for the unconventional gas in coal-rock reservoirs.Based on the data from exploration and development practices,a systematic study on the accumulation mechanism of coal-rock gas has been conducted.The mechanisms of“three fields”controlling coal-rock gas accumulation are revealed.It is confirmed that the coal-rock gas is different from CBM in accumulation process.The whole petroleum systems in the Carboniferous–Permian transitional facies coal measures of the eastern margin of the Ordos Basin and in the Jurassic continental facies coal measures of the Junggar Basin are characterized,and the key research directions for further developing the whole petroleum system theory of coal measures are proposed.Coal rocks,compared to shale,possess intense hydrocarbon generation potential,strong adsorption capacity,dual-medium reservoir properties,and partial or weak oil and gas self-sealing capacity.Additionally,unlike other unconventional gas such as shale gas and tight gas,coal-rock gas exhibits more complex accumulation characteristics,and its accumulation requires a certain coal-rock play form lithological and structural traps.Coal-rock gas also has the characteristics of conventional fractured gas reservoirs.Compared with the basic theory and model of the whole petroleum system established based on detrital rock formations,coal measures have distinct characteristics and differences in coal-rock reservoirs and source-reservoir coupling.The whole petroleum system of coal measures is composed of various types of coal-measure hydrocarbon plays with coal(and dark shale)in coal measures as source rock and reservoir,and with adjacent tight layers as reservoirs or cap or transport layers.Under the action of source-reservoir coupling,coal-rock gas is accumulated in coal-rock reservoirs with good preservation conditions,tight oil/gas is accumulated in tight layers,conventional oil/gas is accumulated in traps far away from sources,and coalbed methane is accumulated in coal-rock reservoirs damaged by later geological processes.The proposed whole petroleum system of coal measures represents a novel type of whole petroleum system.
基金supported by the National Key Research and Development Program Project(2021YFC2400203)the Shaanxi Province Key Research and Development Program Project(2023-YBSF-120)+1 种基金the Shandong Provincial Natural Science Foundation(ZR2024QF287)the National Natural Science Foundation of China(31972907).
文摘Temporal interference(TI)is a form of stimulation that epitomizes an innovative and non-invasive approach for profound neuromodulation of the brain,a technique that has been validated in mice.Yet,the thin cranial bone structure of mice has a marginal influence on the effect of the TI technique and may not effectively showcase its effectiveness in larger animals.Based on this,we carried out TI stimulation experiments on rats.Following the TI intervention,analysis of electrophysiological data and immunofluorescence staining indicated the generation of a stimulation focus within the nucleus accumbens(depth,8.5 mm)in rats.Our findings affirm the viability of the TI methodology in the presence of thick cranial bones,furnishing efficacious parameters for profound stimulation with TI administered under such conditions.This experiment not only sheds light on the intervention effects of TI deep in the brain but also furnishes robust evidence in support of its prospective clinical utility.
文摘In the practice of healthcare,patient-reported outcomes(PROs)and PRO measures(PROMs)are used as an attempt to observe the changes in complex clinical situations.They guide us in making decisions based on the evidence regarding patient care by recording the change in outcomes for a particular treatment to a given condition and finally to understand whether a patient will benefit from a particular treatment and to quantify the treatment effect.For any PROM to be usable in health care,we need it to be reliable,encapsulating the points of interest with the potential to detect any real change.Using structured outcome measures routinely in clinical practice helps the physician to understand the functional limitation of a patient that would otherwise not be clear in an office interview,and this allows the physician and patient to have a meaningful conver-sation as well as a customized plan for each patient.Having mentioned the rationale and the benefits of PROMs,understanding the quantification process is crucial before embarking on management decisions.A better interpretation of change needs to identify the treatment effect based on clinical relevance for a given condition.There are a multiple set of measurement indices to serve this effect and most of them are used interchangeably without clear demarcation on their differences.This article details the various quantification metrics used to evaluate the treatment effect using PROMs,their limitations and the scope of usage and implementation in clinical practice.
基金Supported by the National Science and Technology Major Project for New Oil and Gas Exploration and Development(2025ZD1404200)Forward-looking and Fundamental Project of PetroChina Company Limited(2024DJ23)Scientific Research and Technology Development Project of PetroChina Research Institute of Petroleum Exploration&Development(2024vzz).
文摘There are various types of natural gas resources in coal measures,making them major targets for natural gas exploration and development in China.In view of the particularity of the whole petroleum system of coal measures and the reservoir-forming evolution of natural gas in coal,this study reveals the formation,enrichment characteristics and distribution laws of coal-rock gas by systematically reviewing the main types and geological characteristics of natural gas in the whole petroleum system of coal measures.First,natural gas in the whole petroleum system of coal measures is divided into two types,conventional gas and unconventional gas,according to its occurrence characteristics and accumulation mechanism,and into six types,distal detrital rock gas,special rock gas,distal/proximal tight sandstone gas,inner-source tight sandstone gas,shale gas,and coal-rock gas,according to its source and reservoir lithology.The natural gas present in coal-rock reservoirs is collectively referred to as coal-rock gas.Existing data indicate significant differences in the geological characteristics of coal-rock gas exploration and development between shallow and deep layers in the same area,with the transition depth boundary generally 1500-2000 m.Based on the current understanding of coal-rock gas and respecting the historical usage conventions of coalbed methane terminology,coal-rock gas can be divided into deep coal-rock gas and shallow coalbed methane according to burial depth.Second,according to the research concept of“full-process reservoir formation”in the theory of the whole petroleum system of coal measures,based on the formation and evolution of typical coal-rock gas reservoirs,coal-rock gas is further divided into four types:primary coal-rock gas,regenerated coal-rock gas,residual coal-rock gas,and bio coal-rock gas.The first two belong to deep coal-rock gas,while the latter two belong to shallow coal-rock gas.Third,research on the coal-rock gas reservoir formation and evolution shows that shallow coal-rock gas is mainly residual coal-rock gas or bio coal-rock gas formed after geological transformation of primary coal-rock gas,with the reservoir characteristics such as low reservoir pressure,low gas saturation,adsorbed gas in dominance,and gas production by drainage and depressurization,while deep coal-rock gas is mainly primary coal-rock gas and regenerated coal-rock gas,with the reservoir characteristics such as high reservoir pressure,high gas saturation,abundant free gas,and no or little water.In particular,the primary coal-rock gas is wide in distribution,large in resource quantity,and good in reservoir quality,making it the most favorable type of coal-rock gas for exploration and development.
基金supported by a grant from Ministry of Science,Technological Development and Innovation,Serbia,No.451-03-68/2022-14/200178(to NN)University of Defence,No.MFVMA/02/22-24(to MN)。
文摘An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease progression,demonstrating the need for novel approaches in PD.Repetitive transcranial magnetic stimulation is a non-invasive approach that has been shown to improve motor and non-motor symptoms of Parkinson's disease.However,the underlying mechanisms of the beneficial effects of repetitive transcranial magnetic stimulation remain unknown.The purpose of this study is to investigate the extent to which the beneficial effects of prolonged intermittent theta burst stimulation in the 6-hydroxydopamine model of experimental parkinsonism are based on modulation of adenosine-mediated signaling.Animals with unilateral 6-hydroxydopamine lesions underwent intermittent theta burst stimulation for 3 weeks and were tested for motor skills using the Rotarod test.Immunoblot,quantitative reverse transcription polymerase chain reaction,immunohistochemistry,and biochemical analysis of components of adenosine-mediated signaling were performed on the synaptosomal fraction of the lesioned caudate putamen.Prolonged intermittent theta burst stimulation improved motor symptoms in 6-hydroxydopamine-lesioned animals.A 6-hydroxydopamine lesion resulted in progressive loss of dopaminergic neurons in the caudate putamen.Treatment with intermittent theta burst stimulation began 7 days after the lesion,coinciding with the onset of motor symptoms.After treatment with prolonged intermittent theta burst stimulation,complete motor recovery was observed.This improvement was accompanied by downregulation of the e N/CD73-A_(2A)R pathway and a return to physiological levels of A_(1)R-adenosine deaminase 1 after 3 weeks of intermittent theta burst stimulation.Our results demonstrated that 6-hydroxydopamine-induced degeneration reduced the expression of A_(1)R and elevated the expression of A_(2A)R.Intermittent theta burst stimulation reversed these effects by restoring the abundances of A_(1)R and A_(2A)R to control levels.The shift in ARs expression likely restored the balance between dopamine-adenosine signaling,ultimately leading to the recovery of motor control.
基金Supported by Zhejiang Province Traditional Chinese Medicine Science and Technology Plan Project,No.2023ZL230。
文摘BACKGROUND Although gastroscopy is a commonly used diagnostic and therapeutic technique,postoperative gastrointestinal dysfunction is prone to occur.Traditional Chinese medicine theory suggests that postoperative gastrointestinal disorders are related to spleen and stomach weakness.This study hypothesizes that the combination of acupoint application at the Ziwu Liuzhu acupoint and percutaneous acupoint electrical stimulation can promote postoperative gastrointestinal function recovery and alleviate stress reactions.AIM To investigate the effects of acupoint application of Ziwu Liuzhu combined with percutaneous acupoint electrical stimulation on postoperative gastrointestinal function recovery and stress response in patients undergoing gastrointestinal endoscopy surgery.METHODS A total of 120 patients who underwent gastroscopy surgery were selected and treated between October 2024 and January 2025.This study used a stratified block randomization method,and then allocated groups using computer-generated random number sequences(SAS 9.4 software).The groups were divided into two groups:A control group of 60 patients who received routine postoperative intervention measures,and an observation group of 60 patients who received acupuncture point application combined with transcutaneous acupoint electrical CONCLUSION The combination of percutaneous acupoint electrical stimulation in gastroscopy patients has been demonstrated to be both highly safe and effective.The benefits of this approach include the promotion of postoperative gastrointestinal function,the reduction of stress response,the attainment of optimal results,and the enhancement of patient satisfaction.
文摘Objective To evaluate the association of GGN repeat polymorphism of androgen receptor(AR)with ovarian reserve and ovarian response in controlled ovarian stimulation(COS).Methods This genetic association study was conducted among a total of 361 women aged≤40 years with basal FSH≤12 U/L undergoing the GnRH-agonist long protocol for COS in a university affiliated IVF center.GGN repeat in the AR gene was analyzed with Sanger sequencing.The primary endpoint was the number of antral follicle counts(AFCs),and the secondary endpoints were stimulation days,total dose of gonadotropin(Gn)used,total number of retrieved oocytes,ovarian sensitivity index,and follicular output rate.Results The GGN repeat in exon 1 of the AR gene ranged from 13 to 24,and the median repeat length was 22.Based on the genotypes(S for GGN repeats<22,L for GGN repeats≥22),the patients were divided into 3 groups:SS,SL,and LL.Generalized regression analysis indicated that the number of AFCs in group SS was significantly lower than those in group SL(adjusted β=1.8,95%CI:0.2-3.4,P=0.024)and group LL(adjusted β=1.5,95%CI:0.2-2.7,P=0.021).No significant difference was observed in the number of AFCs between group SL and group LL(P>0.05).Generalized regression analysis indicated no significant differences in ovarian stimulation parameters among the 3 groups,either before or after adjusting for confounding factors(P>0.05).Conclusion GGN repeat length on the AR gene is associated with AFC but not with ovarian response in Chinese women,indicating that AR gene polymorphisms may affect ovarian reserve.
基金supported by the Deanship of Graduate Studies and Scientific Research at Qassim University(QU-APC-2024-9/1).
文摘Due to the numerous variables to take into account as well as the inherent ambiguity and uncertainty,evaluating educational institutions can be difficult.The concept of a possibility Pythagorean fuzzy hypersoft set(pPyFHSS)is more flexible in this regard than other theoretical fuzzy set-like models,even though some attempts have been made in the literature to address such uncertainties.This study investigates the elementary notions of pPyFHSS including its set-theoretic operations union,intersection,complement,OR-and AND-operations.Some results related to these operations are also modified for pPyFHSS.Additionally,the similarity measures between pPyFHSSs are formulated with the assistance of numerical examples and results.Lastly,an intelligent decision-assisted mechanism is developed with the proposal of a robust algorithm based on similarity measures for solving multi-attribute decision-making(MADM)problems.A case study that helps the decision-makers assess the best educational institution is discussed to validate the suggested system.The algorithmic results are compared with the most pertinent model to evaluate the adaptability of pPyFHSS,as it generalizes the classical possibility fuzzy set-like theoretical models.Similarly,while considering significant evaluating factors,the flexibility of pPyFHSS is observed through structural comparison.
