Jianer Chen

Objective: To investigate the effects of sequential electroacupuncture (EA) combined with augmented reality (AR) gait training on walking function and neuromuscular control in patients with subacute stroke (onset 1–6 mo). Design: A single-blind, randomized controlled trial allocating 40 patients with subacute stroke to an experimental (EA+AR, n=20) or control group (AR alone, n=20) for 4 weeks. The primary outcome was gait speed. Results: Generalized estimating equations (GEE) analyses revealed that the experimental group demonstrated significantly greater improvement in gait speed (Wald χ²=6.509, P =0.011) compared with controls. Significant improvements were also observed in stride length, gait symmetry, FMA-LE, BBS, and CCI (all P 0.05). No adverse events occurred. Conclusion: The sequential EA-AR protocol significantly improved gait speed—the primary outcome—as well as stride length, gait symmetry, motor function, balance, and neuromuscular control. These findings suggest that temporally structured EA prior to AR training may facilitate motor relearning, potentially through transient neuromodulatory states induced by EA, though this mechanistic interpretation requires further confirmation.

The treatment of Alzheimer's disease (AD) is severely hampered by the blood‐brain barrier (BBB), which limits the delivery of therapeutic agents like donepezil (DPZ), an acetylcholinesterase inhibitor. While DPZ has multi‐faceted benefits, its clinical efficacy is constrained by poor BBB penetration, requiring high doses that lead to significant side effects. To overcome this, we developed a brain‐targeted nanotherapeutic utilizing apoferritin (AFn) nanoparticles loaded with DPZ (AFn‐DPZ). We demonstrate that this platform, by binding to the EphB1 receptor on the blood–brain barrier, enables transient and reversible opening of the blood–brain barrier, thereby facilitating efficient and targeted drug delivery. Following intravenous administration in an AD mouse model, AFn‐DPZ exhibited enhanced brain accumulation and sustained release of DPZ. This targeted delivery inhibited acetylcholinesterase activity, reduced amyloid plaque burden, alleviated neuroinflammation, attenuated oxidative damage, restored mitochondrial function, and upregulated the expression of brain‐derived neurotrophic factor (BDNF). Consequently, AFn‐DPZ treatment significantly improved cognitive performance compared to free DPZ. Our findings establish EphB1‐mediated facilitation of BBB traversal as a promising strategy for enhancing nanotherapeutic delivery to the brain, offering a potent approach to address the complex pathology of AD.

The blood-brain barrier (BBB) is a sophisticated structure composed of brain capillary endothelial cells, basement membrane, and neuroglial membrane, which strictly regulates substance exchange between the blood and brain tissue. While maintaining the homeostasis of the central nervous system, it blocks the entry of over 98% of small-molecule drugs and nearly all macromolecular drugs into the brain parenchyma, posing a significant challenge for the treatment of neurodegenerative diseases (NDs). Owing to their unique hollow architecture, favorable biocompatibility, reversible self-assembly properties, intrinsic targeting capability, and surface modifiability, natural ferritin nanocages have garnered substantial attention in the fields of biomedicine and nanotechnology. This review outlines the pathological mechanisms of NDs, the structure and function of the BBB, as well as its transport mechanisms. It highlights the advantages of ferritin nanocages in crossing the BBB—attributed to their natural nanostructure, brain-targeting potential, and capacity for functionalized surface modification—along with their drug loading capacity, antioxidant activity, and favorable biosafety profile. Recent advances in the application of natural ferritin nanocages for the diagnosis and therapy of NDs are also summarized. However, it is important to note that the evidence supporting their application in NDs remains more limited compared to their extensive research in cancer therapeutics. Finally, current challenges and future prospects of ferritin-based nanoplatforms are discussed, providing valuable insights for developing ferritin nanocage-based strategies in the diagnosis and treatment of NDs.

This randomized controlled trial investigated the effects of motor imagery training (MIT) monitored by functional near-infrared spectroscopy (fNIRS) on upper limb motor function and cortical activation in stroke patients. Seventy participants were allocated to either an MI group, which received conventional rehabilitation therapy (CRT) supplemented with visual and kinesthetic-based MIT, or a control group (CON group), which received CRT alone. The CRT intervention consisted of 30-min sessions administered four times per day over a 4-week period. The MI group underwent an additional daily 25-min session of MIT, whereas the CON group watched neutral nature documentaries (landscapes and animals) for an equivalent duration. Functional outcomes were assessed using the Fugl-Meyer Assessment for Upper Extremity (FMA-UE) and the modified Barthel Index (MBI). Additionally, fNIRS was used to monitor changes in oxyhemoglobin (HbO₂) levels in the motor cortex before and after the intervention in the MI group. Sixty-three participants completed the study (MI group: n = 32, CON group: n = 31). Both groups showed significant improvements in FMA-UE and MBI scores after the intervention (P < 0.05). The MI group demonstrated significantly greater improvement in MBI compared with the CON group (P < 0.05), although between-group differences in FMA-UE were not significant (P > 0.05). fNIRS revealed increased cortical activation in the MI group, specifically showing enhanced activation intensity in the supplementary motor area (channel 3) and sensorimotor cortex (channels 18, 19, 21) (P < 0.05). These findings suggest that functional improvements may be mediated through neural plasticity changes. The combined application of MIT and CRT appears to enhance motor cortex activation and promote functional recovery in stroke rehabilitation.

Stroke survivors often experience residual motor dysfunction in their limbs. Additional physical rehabilitation therapies may further improve patients̵

The therapeutic effect and underlying mechanism of combining transcranial direct current stimulation (tDCS) with robot-assisted gait training (RAGT) for stroke patients remain unclear. The goal of this study is to examine whether anodal tDCS can augment the beneficial effects of RAGT on motor function of the lower limbs in stroke survivors. Furthermore, the study aims to explore the brain motor function network underlying regulation mechanism of this integrated therapeutic approach.The patients were randomly assigned to two groups: the anode tDCS + RAGT group (n = 22) and the RAGT group (n = 21). In the experimental group, patients underwent a 20-minute session of anodal tDCS followed by a 20-minute RAGT session. Conversely, the control group patients only received 20 min of RAGT. These sessions were conducted 5 days a week for a duration of 4 weeks. Hemoglobin alterations in the primary motor cortex (M1) and pre-motor cortex/supplementary motor cortex area (PMC/SMA) of patients at rest were measured using Functional Near Infrared Spectroscopy (fNIRS). Additionally, the Fugl-Meyer Lower Extremity Assessment (FMA-LE) was utilized to evaluate the functionality of the lower extremities. A total of 38 stroke patients successfully completed the study. Significant improvements were observed in the FMA-LE scores of both groups following treatment. Notably, the anode tDCS + RAGT group demonstrated a remarkable enhancement in FMA-LE compared to the control group. Furthermore, the combination of anodal tDCS + RAGT strengthened the functional connectivity between LM1-RPMC/SMA. The combination of anodal tDCS and RAGT can enhance lower limb motor function in stroke patients, while also modulating the connectivity within the motor network. Additionally, the elevation of functional connectivity between the bilateral cerebral hemispheres, quantifiable through fNIRS, could potentially serve as a valuable biomarker in stroke patients. This study has been registered in the Chinese Clinical Trial Registry (no. ChiCTR2400088222). This article has been registered on August 13th, 2024, and it was registered retrospectively.

Robot-assisted gait training is more effective in improving lower limb function and walking ability in stroke patients compared to conventional rehabilitation, but the neural mechanisms remain unclear. This study aims to explore the effects of robot-assisted gait training on lower limb motor dysfunction in stroke patients and its impact on neural activity in the motor cortex, providing objective evidence for clinical application. Forty-two stroke patients meeting the inclusion criteria were randomly assigned to either the experimental group receiving robot-assisted gait training or the control group receiving conventional overground walking training. Assessments were conducted at baseline and after four weeks of treatment. Primary outcome measures included cortical activation measured by functional near-infrared spectroscopy (fNIRS), power ratio index (PRI), and delta/alpha power ratio (DAR) measured by quantitative electroencephalography (QEEG), and their correlation with the Fugl-Meyer Assessment (FMA) for lower limb motor function. Secondary outcome measures included FMA and Functional Ambulation Category (FAC). Data from 36 patients (18 in each group) after four weeks of treatment were analyzed. The fNIRS results indicated better activation in the premotor and supplementary motor cortices in the robot-assisted gait training group compared to the control group. QEEG analysis showed reduced PRI and DAR in the premotor, supplementary motor, and primary motor cortices in the robot-assisted gait training group, suggesting improved motor function recovery in stroke patients. Clinical scale analysis revealed superior motor function recovery in the robot-assisted gait training group compared to the control group. Robot-assisted gait training significantly enhances activation in the primary motor cortex and supplementary motor area, potentially aiding stroke patients in recovering their ability to plan. PRI and DAR, particularly PRI, are valuable clinical indicators for assessing motor function recovery in stroke patients. Chinese Clinical Trial Registry (ChiCTR2200060668). Registered on June 6, 2022; https://www.chictr.org.cn/showproj.html?proj=171610 .

This study aimed to explore the neuroimaging basis of motor imagery (MI) in stroke rehabilitation, particularly focusing on the brain activation patterns during MI tasks. Additionally, this study may provide insights into clinical rehabilitation strategies. A total of 40 right‐handed stroke patients from Zhejiang Rehabilitation Medical Center were assigned to either the right‐sided or left‐sided cerebral infarction group. They were right‐handed and recruited from Zhejiang Rehabilitation Medical Center. A portable near‐infrared brain function imaging system was used to detect changes in oxyhemoglobin concentration in the bilateral sensorimotor cortex, premotor cortex, and supplementary motor area during the MI task. Activated channels and intensity changes in brain regions under the MI state were observed and analyzed. In patients with right‐sided cerebral infarction, brain activation was left‐lateralized during both left‐ and right‐limb MI. Patients with left‐sided cerebral infarction exhibited left lateralization during right‐limb MI and right lateralization during left‐limb MI. Functional near‐infrared spectroscopy was utilized to investigate the activation of motor‐related brain regions during MI after stroke. These regions of interest were associated with hand motor tasks and were successfully activated during the MI task. Following infarction, the activation of the MI cortex was asymmetric. When imagining movements on the dominant‐hand side, MI becomes more vivid and activates bilateral motor cortex areas.