UNASSIGNED: Non-invasive neuroregulation techniques have been demonstrated to improve certain motor symptoms in Parkinson\'s disease (PD). However, the currently employed regulatory techniques primarily concentrate on stimulating single target points, neglecting the functional regulation of networks and circuits. The supplementary motor area (SMA) has a significant value in motor control, and its functionality is often impaired in patients with PD. The matching SMA-primary motor cortex (M1) paired transcranial magnetic stimulation (TMS) treatment protocol, which benefits patients by modulating the sequential and functional connections between the SMA and M1, was elucidated in this study.
UNASSIGNED: This was a single-center, double-blind, randomized controlled clinical trial. We recruited 78 subjects and allocated them in a 1:1 ratio by stratified randomization into the paired stimulation (n = 39) and conventional stimulation groups (n = 39). Each patient underwent 3 weeks of matching SMA-M1 paired TMS or sham-paired stimulation. The subjects were evaluated before treatment initiation, 3 weeks into the intervention, and 3 months after the cessation of therapy. The primary outcome measure in this study was the Unified Parkinson\'s Disease Rating Scale III, and the secondary outcome measures included non-motor functional assessment, quality of life (Parkinson\'s Disease Questionnaire-39), and objective assessments (electromyography and functional near-infrared spectroscopy).
UNASSIGNED: Clinical protocols aimed at single targets using non-invasive neuroregulation techniques often improve only one function. Emphasizing the circuit and network regulation in PD is important for enhancing the effectiveness of TMS rehabilitation. Pairing the regulation of cortical circuits may be a potential treatment method for PD. As a crucial node in motor control, the SMA has direct fiber connections with basal ganglia circuits and complex fiber connections with M1, which are responsible for motor execution. SMA regulation may indirectly regulate the function of basal ganglia circuits. Therefore, the developed cortical pairing stimulation pattern can reshape the control of information flow from the SMA to M1. The novel neuroregulation model designed for this study is based on the circuit mechanisms of PD and previous research results, with a scientific foundation and the potential to be a means of neuroregulation for PD.Clinical trial registration: ClinicalTrials.gov, identifier [ChiCTR2400083325].

A stroke represents a significant medical condition characterized by the sudden interruption of blood flow to the brain, leading to cellular damage or death. The impact of stroke on individuals can vary from mild impairments to severe disability. Treatment for stroke often focuses on gait rehabilitation. Notably, assessing muscle activation and kinematics patterns using electromyography (EMG) and stereophotogrammetry, respectively, during walking can provide information regarding pathological gait conditions. The concurrent measurement of EMG and kinematics can help in understanding disfunction in the contribution of specific muscles to different phases of gait. To this aim, complexity metrics (e.g., sample entropy; approximate entropy; spectral entropy) applied to EMG and kinematics have been demonstrated to be effective in identifying abnormal conditions. Moreover, the conditional entropy between EMG and kinematics can identify the relationship between gait data and muscle activation patterns. This study aims to utilize several machine learning classifiers to distinguish individuals with stroke from healthy controls based on kinematics and EMG complexity measures. The cubic support vector machine applied to EMG metrics delivered the best classification results reaching 99.85% of accuracy. This method could assist clinicians in monitoring the recovery of motor impairments for stroke patients.

OBJECTIVE: The rehabilitation work for patients with motor dysfunction after stroke is crucial. However, there is currently a lack of summarized evidence regarding the rehabilitation management of stroke patients in rehabilitation wards, communities, and at home. This study aims to compile relevant evidence on the rehabilitation management of patients with motor dysfunction after stroke, providing a reference for clinical and community health professionals to carry out rehabilitation interventions.
METHODS: A systematic search was conducted in BMJ Best Practice, UpToDate, National Guidebook Clearinghouse, American Heart Association/American Stroke Association, Canadian Medical Association, National Institute for Health and Clinical Excellence, United States Department of Veterans Affairs/ Department of Defense, Registered Nurses Association of Ontario, JBI Evidence-Based Healthcare Center Database, The Cochrane Library, PubMed, Web of Science, Embase, CINAHL, CNKI, Wanfang Database, SinoMed, and other databases for all literature on the rehabilitation management of patients with motor dysfunction after stroke. This included clinical decision-making, guidelines, expert consensuses, recommended practices, systematic reviews, and evidence summaries, with the search period spanning from the establishment of each database to October 2023. Two researchers independently evaluated the quality of the literature.
RESULTS: A total of twenty-one documents were included, consisting of 11 guidelines, 2 expert consensus, and 8 systematic reviews. Evidence was extracted and integrated from the included literature, summarizing forty-five pieces of evidence across nine areas: rehabilitation management model, rehabilitation institutions, rehabilitation teams, timing of rehabilitation interventions, rehabilitation assessment, rehabilitation programs, rehabilitation duration and frequency, rehabilitation intensity, and rehabilitation support These covered comprehensive rehabilitation management content for stroke patients in the early, subacute, and chronic phases.
CONCLUSIONS: The best evidence summarized in this study for the rehabilitation management of patients with motor dysfunction after stroke is comprehensive and of high quality. It provides important guidance for clinical and community healthcare professionals in carrying out rehabilitation interventions. When applying the evidence, it is recommended to consider the current condition of the stroke patient, the extent of motor dysfunction, environmental factors, and the patient\'s preferences. Then, select the most appropriate rehabilitation plan, and adjust the type and intensity of training according to each patient\'s specific needs and preferences.
目的: 脑卒中运动功能障碍患者康复工作的开展至关重要，然而目前缺少脑卒中患者在康复病房、社区以及家庭康复管理的相关证据总结。本研究旨在汇总脑卒中运动功能障碍患者康复管理的相关证据，为临床和社区医护人员开展康复干预提供参考依据。方法: 系统检索BMJ Best Practice、UpToDate、美国国立指南库、美国心脏协会/美国卒中协会、加拿大医学会、英国国家卫生与临床优化研究所、美国退伍军人事务部/国防部、加拿大安大略注册护士协会、JBI循证卫生保健中心数据库、The Cochrane Library、PubMed、Web of Science、Embase、CINAHL、中国知网、万方数据库、维普数据库、中国生物医学文献系统中关于脑卒中运动功能障碍患者康复管理的所有文献，包括临床决策、指南、专家共识、推荐实践、系统评价、证据总结，检索时限为建库至2023年10月。由2名研究者独立对文献进行质量评价。结果: 共纳入21篇文献，包括11篇指南、2篇专家共识和8篇系统评价。通过对纳入文献的证据进行提取与整合，从康复管理模式、康复机构、康复团队、康复介入时机、康复评估、康复项目、康复时间和频率、康复强度和康复支持9个领域中汇总45条证据，涵盖了脑卒中患者早期、亚急性期和慢性期全病程的三级康复管理的相关内容。结论: 本研究汇总的脑卒中运动功能障碍患者康复管理的最佳证据较为全面，证据质量较高，对临床和社区医护人员开展康复干预具有重要指导意义。建议应用证据时，综合考虑脑卒中患者当前病情、运动功能受损情况、环境因素和患者的意愿，然后选择最适合的康复方案，并根据每位患者的具体需求和喜好调整训练的种类和强度。.

UNASSIGNED: This study aims to utilize latent growth model (LGM) to explore the developmental trajectory of motor dysfunction in Parkinson\'s disease (PD) patients and investigate the relationship between depression and motor dysfunction.
UNASSIGNED: Four-year follow-up data from 389 PD patients were collected through the Parkinson\'s Progression Marker Initiative (PPMI). Firstly, a univariate LGM was employed to examine the developmental trajectory of motor dysfunction in PD patients. Subsequently, depression levels were introduced as covariates into the model, and depression was further treated as a parallel growth latent variable to study the longitudinal relationship between motor dysfunction and depression.
UNASSIGNED: In the trajectory analysis of motor dysfunction, the fit indices for the quadratic growth LGM model were χ2 = 7.419, df = 6, CFI = 0.998, TLI = 0.997, SRMR = 0.019, and RMSEA = 0.025, indicating that the growth trend of motor dysfunction follows a quadratic curve rather than a simple linear pattern. Introducing depression symptoms as time-varying covariates to explore their effect on motor dysfunction revealed significant positive correlations (β = 0.383, p = 0.026; β = 0.675, p < 0.001; β = 0.385, p = 0.019; β = 0.415, p = 0.014; β = 0.614, p = 0.003), suggesting that as depression levels increase, motor dysfunction scores also increase. Treating depression as a parallel developmental process in the LGM, the regression coefficients for depression intercept on motor dysfunction intercept, depression slope on motor dysfunction slope, and depression quadratic factor on motor dysfunction quadratic factor were 0.448 (p = 0.046), 1.316 (p = 0.003), and 1.496 (p = 0.038), respectively. These significant regression coefficients indicate a complex relationship between depression and motor dysfunction, involving not only initial level associations but also growth trends over time and possible quadratic effects.
UNASSIGNED: This study indicates a quadratic growth trajectory for motor dysfunction in PD, suggesting a continuous increase in severity with a gradual deceleration in growth rate. The relationship between depression and motor dysfunction is complex, involving initial associations, evolving trends over time, and potential quadratic effects. Exacerbation of depressive symptoms may coincide with motor function deterioration.

UNASSIGNED: Limb motor dysfunction is one of the challenges in rehabilitation after cerebral ischemic stroke (CIS) and greatly affects the quality of life of patients. This study aims to investigate the central mechanisms of the curative effect with multimodal magnetic resonance imaging (MRI), which will provide additional evidence to support the application of Xingnao Kaiqiao (XNKQ) acupuncture.
UNASSIGNED: This trial is a randomized controlled trial. Patients who meet the criteria will be recruited and randomly divided into 2 groups. One group will receive acupuncture treatment and another group will not receive acupuncture treatment. Both groups will receive conventional treatment. In addition, 20 healthy individuals will be recruited who will not receive any treatment. The total course of treatment is 14 days. The primary outcome is multimodal MRI analysis. For safety assessment, adverse events will be observed and recorded.
UNASSIGNED: The study involving human subjects was reviewed and approved by the Ethics Committee of IRB of The First Teaching Hospital of Tianjin University of TCM (TYLL2023[K]031). This study complied with the Declaration of Helsinki. Written informed consent about this study was provided by the participants. The results of this study will be published in a peer-reviewed journal.
UNASSIGNED: Chinese Clinical Trial Registration Center (ChiCTR2300078315) https://www.chictr.org.cn/.

BACKGROUND: Parkinson\'s disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the brain. Despite existing treatments, there remains an unmet need for therapies that can halt or reverse disease progression. Gene therapy has been tried and tested for a variety of illnesses, including PD. The goal of this systematic review is to assess gene therapy techniques\' safety and effectiveness in PD clinical trials.
METHODS: Online databases PubMed/Medline, and Cochrane were used to screen the studies for this systematic review. The risk of bias of the included studies was assessed using standard tools.
RESULTS: Gene therapy can repair damaged dopaminergic neurons from the illness or deal with circuit anomalies in the basal ganglia connected to Parkinson\'s disease symptoms. Rather than only treating symptoms, this neuroprotective approach alters the illness itself. Medication for gene therapy is currently administered at the patient\'s bedside. It can hyperactivate specific brain circuits associated with motor dysfunction. PD therapies are developing quickly, and there aren\'t enough head-to-head trials evaluating the safety and effectiveness of available treatments. When choosing an advanced therapy, patient-specific factors should be considered in addition to the effectiveness and safety of each treatment option.
CONCLUSIONS: In comparison to conventional therapies, gene therapy may be advantageous for PD. It may minimize side effects, relieve symptoms, and offer dependable dopamine replacement.

Parkinson\'s disease (PD) is a neurodegenerative disorder commonly accompanied by gut dysfunction. EA has shown anti-inflammatory and neuroprotective effects. Here, we aim to explore whether EA can treat Parkinson\'s disease by restoring the intestinal barrier and modulating NLRP3 inflammasome. We applied 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to establish a PD mouse model and EA at the GV16, LR3, and ST36 for 12 consecutive days. The open-field test results indicated that EA alleviated depression and behavioral defects, upregulated the expressions of tyrosine hydroxylase (TH) and brain-derived neurotrophic factor (BDNF), and blocked the accumulation of α-synuclein (α-syn) in the midbrain. Moreover, EA blocked the damage to intestinal tissues of PD mice, indicative of suppressed NLRP3 inflammasome activation and increased gut barrier integrity. Notably, the antibiotic-treated mouse experiment validated that the gut microbiota was critical in alleviating PD dyskinesia and intestinal inflammation by EA. In conclusion, this study suggested that EA exhibited a protective effect against MPTP-induced PD by alleviating behavioral defects, reversing the block of motor dysfunction, and improving the gut barrier by modulating intestinal NLRP3 inflammasome. Above all, this study could provide novel insights into the pathogenesis and therapy of PD.

Considerable research efforts have been directed toward the symptom relief of Parkinson\'s disease (PD) by attenuating dopamine (DA) depletion. One common feature of these existing therapies is their unavailability of preventing the neurodegenerative process of dopaminergic neurons. (+)-Borneol, a natural highly lipid-soluble bicyclic monoterpene, has been reported to regulate the levels of monoamine neurotransmitters in the central nervous system and exhibit neuroprotective effects. However, the effect of (+)-borneol on the dopaminergic neuronal loss of methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice is not defined. Herein, we first report that 30 mg/kg (+)-borneol significantly attenuated the motor deficits of PD mice, which benefits from markedly increasing the level of DA and decreasing the metabolic rate of DA in the striatum of conscious and freely moving mouse detected by ultraperformance liquid chromatography tandem mass spectrometry online combined with in vivo brain microdialysis sampling. It is worth noting that the enhanced level of DA by (+)-borneol was enabled by the reduction in loss of tyrosine hydroxylase-immunoreactive dopaminergic neurons in the substantia nigra and striatum and promotion of reserpine- or nomifensine-induced DA release in PD mice. Interestingly, (+)-borneol evidently inhibited the decreased expression levels of DA transporter (DAT) and vesicular monoamine transporter 2 (VMAT2) on the MPTP mouse model of PD. Moreover, (+)-borneol suppressed the neuroinflammation by inhibiting the production of IL-1β, IL-6, and TNF-α and attenuated oxidative stress by decreasing the level of MDA and increasing the activities of SOD and GSH-px in PD mice. These findings demonstrate that (+)-borneol protects DA neurons by inhibiting neuroinflammation and oxidative stress. Further research work for the neuroprotection mechanism of (+)-borneol will focus on reactive oxygen species-mediated apoptosis. Therefore, (+)-borneol is a potential therapeutic candidate for retarding the neurodegenerative process of PD.

Hemorrhage-induced injury of the corticospinal tract (CST) in the internal capsule (IC) causes severe neurological dysfunction in both human patients and rodent models of intracerebral hemorrhage (ICH). A nuclear receptor Nurr1 (NR4A2) is known to exert anti-inflammatory and neuroprotective effects in several neurological disorders. Previously we showed that Nurr1 ligands prevented CST injury and alleviated neurological deficits after ICH in mice. To prove direct effect of Nurr1 on CST integrity, we examined the effect of Nurr1 overexpression in neurons of the primary motor cortex on pathological consequences of ICH in mice. ICH was induced by intrastriatal injection of collagenase type VII, where hematoma invaded into IC. Neuron-specific overexpression of Nurr1 was induced by microinjection of synapsin I promoter-driven adeno-associated virus (AAV) vector into the primary motor cortex. Nurr1 overexpression significantly alleviated motor dysfunction but showed only modest effect on sensorimotor dysfunction after ICH. Nurr1 overexpression also preserved axonal structures in IC, while having no effect on hematoma-associated inflammatory events, oxidative stress, and neuronal death in the striatum after ICH. Immunostaining revealed that Nurr1 overexpression increased the expression of Ret tyrosine kinase and phosphorylation of Akt and ERK1/2 in neurons in the motor cortex. Moreover, administration of Nurr1 ligands 1,1-bis(3\'-indolyl)-1-(p-chlorophenyl)methane or amodiaquine increased phosphorylation levels of Akt and ERK1/2 as well as expression of glial cell line-derived neurotrophic factor and Ret genes in the cerebral cortex. These results suggest that the therapeutic effect of Nurr1 on striatal ICH is attributable to the preservation of CST by acting on cortical neurons.

Neuronal loss is the central issue in Alzheimer\'s disease (AD), yet no treatment developed so far can halt AD-associated neurodegeneration. Here, we developed a monoclonal antibody (mAb2A7) against 217 site-phosphorylated human tau (p-tau217) and observed that p-tau217 levels positively correlated with brain atrophy and cognitive impairment in AD patients. Intranasal administration efficiently delivered mAb2A7 into male PS19 tauopathic mouse brain with target engagement and reduced tau pathology/aggregation with little effect on total soluble tau. Further, mAb2A7 treatment blocked apoptosis-associated neuronal loss and brain atrophy, reversed cognitive deficits, and improved motor function in male tauopathic mice. Proteomic analysis revealed that mAb2A7 treatment reversed alterations mainly in proteins associated with synaptic functions observed in murine tauopathy and AD brain. An antibody (13G4) targeting total tau also attenuated tau-associated pathology and neurodegeneration but impaired the motor function of male tauopathic mice. These results implicate p-tau217 as a potential therapeutic target for AD-associated neurodegeneration.