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Abstract This study investigated alterations in functional connectivity (FC) within cortico–basal ganglia–thalamo–cortical (CBTC) circuits and identified critical connections influencing poststroke motor recovery, offering insights into optimizing brain modulation strategies to address the limitations of traditional single‐target stimulation. We delineated individual‐specific parallel loops of CBTC through probabilistic tracking and voxel connectivity profiles‐based segmentation and calculated FC values in poststroke patients and healthy controls, comparing with conventional atlas‐based FC calculation. Support vector machine (SVM) analysis distinguished poststroke patients from controls. Connectome‐based predictive modeling (CPM) used FC values within CBTC circuits to predict upper limb motor function. Poststroke patients exhibited decreased ipsilesional connectivity within the individual‐specific CBTC circuits. SVM analysis achieved 82.8% accuracy, 76.6% sensitivity, and 89.1% specificity using individual‐specific parallel loops. Additionally, CPM featuring positive connections/all connections significantly predicted Fugl‐Meyer assessment of upper extremity scores. There were no significant differences in the group comparisons of conventional atlas‐based FC values, and the FC values resulted in SVM accuracy of 75.0%, sensitivity of 67.2%, and specificity of 82.8%, with no significant CPM capability. Individual‐specific parallel loops show superior predictive power for assessing upper limb motor function in poststroke patients. Precise mapping of the disease‐related circuits is essential for understanding poststroke brain reorganization.

Colorectal cancer (CRC) ranks as the second leading cause of cancer-related deaths globally, trailing only behind lung cancer, and stands as the third most prevalent malignant tumor, following lung and breast cancers. The primary cause of mortality in colorectal cancer (CRC) stems from distant metastasis. Among the various routes of metastasis in CRC, lymph node metastasis predominates, serving as a pivotal factor in both prognostication and treatment decisions for patients. This intricate cascade of events involves multifaceted molecular mechanisms, highlighting the complexity underlying lymph node metastasis in CRC. The cytokines or proteins involved in lymph node metastasis may represent the most promising lymph node metastasis markers for clinical use. In this review, we aim to consolidate the current understanding of the mechanisms and pathophysiology underlying lymph node metastasis in colorectal cancer (CRC), drawing upon insights from the most recent literatures. We also provide an overview of the latest advancements in comprehending the molecular underpinnings of lymph node metastasis in CRC, along with the potential of innovative targeted therapies. These advancements hold promise for enhancing the prognosis of CRC patients by addressing the challenges posed by lymph node metastasis.

Abstract Background The most challenging aspect of rehabilitation is the repurposing of residual functional plasticity in stroke patients. To achieve this, numerous plasticity-based clinical rehabilitation programs have been developed. This study aimed to investigate the effects of motor imagery (MI)-based brain–computer interface (BCI) rehabilitation programs on upper extremity hand function in patients with chronic hemiplegia. Design A 2010 Consolidated Standards for Test Reports (CONSORT)-compliant randomized controlled trial. Methods Forty-six eligible stroke patients with upper limb motor dysfunction participated in the study, six of whom dropped out. The patients were randomly divided into a BCI group and a control group. The BCI group received BCI therapy and conventional rehabilitation therapy, while the control group received conventional rehabilitation only. The Fugl–Meyer Assessment of the Upper Extremity (FMA-UE) score was used as the primary outcome to evaluate upper extremity motor function. Additionally, functional magnetic resonance imaging (fMRI) scans were performed on all patients before and after treatment, in both the resting and task states. We measured the amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), z conversion of ALFF (zALFF), and z conversion of ReHo (ReHo) in the resting state. The task state was divided into four tasks: left-hand grasping, right-hand grasping, imagining left-hand grasping, and imagining right-hand grasping. Finally, meaningful differences were assessed using correlation analysis of the clinical assessments and functional measures. Results A total of 40 patients completed the study, 20 in the BCI group and 20 in the control group. Task-related blood-oxygen-level-dependent (BOLD) analysis showed that when performing the motor grasping task with the affected hand, the BCI group exhibited significant activation in the ipsilateral middle cingulate gyrus, precuneus, inferior parietal gyrus, postcentral gyrus, middle frontal gyrus, superior temporal gyrus, and contralateral middle cingulate gyrus. When imagining a grasping task with the affected hand, the BCI group exhibited greater activation in the ipsilateral superior frontal gyrus (medial) and middle frontal gyrus after treatment. However, the activation of the contralateral superior frontal gyrus decreased in the BCI group relative to the control group. Resting-state fMRI revealed increased zALFF in multiple cerebral regions, including the contralateral precentral gyrus and calcarine and the ipsilateral middle occipital gyrus and cuneus, and decreased zALFF in the ipsilateral superior temporal gyrus in the BCI group relative to the control group. Increased zReHo in the ipsilateral cuneus and contralateral calcarine and decreased zReHo in the contralateral middle temporal gyrus, temporal pole, and superior temporal gyrus were observed post-intervention. According to the subsequent correlation analysis, the increase in the FMA-UE score showed a positive correlation with the mean zALFF of the contralateral precentral gyrus (r = 0.425, P

Abstract Background The volumes of the hippocampal subfields are related to poststroke cognitive dysfunctions. However, it remains unclear whether contralesional hippocampal subfield volume contributes to cognitive impairment. This study aimed to investigate the volumetric differences in the contralesional hippocampal subfields between patients with left and right hemisphere strokes (LHS/RHS). Additionally, correlations between contralesional hippocampal subfield volumes and clinical outcomes were explored. Methods Fourteen LHS (13 males, 52.57 ± 7.10 years), 13 RHS (11 males, 51.23 ± 15.23 years), and 18 healthy controls (11 males, 46.94 ± 12.74 years) were enrolled. Contralesional global and regional hippocampal volumes were obtained with T1‐weighted images. Correlations between contralesional hippocampal subfield volumes and clinical outcomes, including the Montreal Cognitive Assessment (MoCA) and Mini‐Mental State Examination (MMSE), were analyzed. Bonferroni correction was applied for multiple comparisons. Results Significant reductions were found in contralesional hippocampal as a whole (adjusted p = .011) and its subfield volumes, including the hippocampal tail (adjusted p = .005), cornu ammonis 1 (CA1) (adjusted p = .002), molecular layer (ML) (adjusted p = .004), granule cell and ML of the dentate gyrus (GC‐ML‐DG) (adjusted p = .015), CA3 (adjusted p = .009), and CA4 (adjusted p = .014) in the RHS group compared to the LHS group. MoCA and MMSE had positive correlations with volumes of contralesional hippocampal tail (p = .015, r = .771; p = .017, r = .763) and fimbria (p = .020, r = .750; p = .019, r = .753) in the LHS group, and CA3 (p = .007, r = .857; p = .009, r = .838) in the RHS group, respectively. Conclusion Unilateral stroke caused volumetric differences in different hippocampal subfields contralesionally, which correlated to cognitive impairment. RHS leads to greater volumetric reduction in the whole contralesional hippocampus and specific subfields (hippocampal tail, CA1, ML, GC‐ML‐DG, CA3, and CA4) compared to LHS. These changes are correlated with cognitive impairments, potentially due to disrupted neural pathways and interhemispheric communication.

Tongue coating affects cognition, and cognitive decline at early stage also showed relations to functional and structural remodeling of superior temporal sulcus (STS) in amnestic mild cognitive impairment (aMCI). The potential correlation between disparate cognitive manifestations in aMCI patients with different tongue coatings, and corresponding mechanisms of STS remodeling remains uncharted. In this case-control study, aMCI patients were divided into thin coating (n = 18) and thick coating (n = 21) groups. All participants underwent neuropsychological evaluations and multimodal magnetic resonance imaging. Group comparisons were conducted in clinical assessments and neuroimaging measures of banks of the STS (bankssts). Generalized linear models were constructed to explore relationships between neuroimaging measures and cognition. aMCI patients in the thick coating group exhibited significantly poorer immediate and delayed recall and slower information processing speed (IPS) (P < 0.05), and decreased functional connectivity (FC) of bilateral bankssts with frontoparietal cortices (P < 0.05, AlphaSim corrected) compared to the thin coating group. It was found notable correlations between cognition encompassing recall and IPS, and FC of bilateral bankssts with frontoparietal cortices (P < 0.05, Bonferroni's correction), as well as interaction effects of group × regional homogeneity (ReHo) of right bankssts on the first immediate recall (P < 0.05, Bonferroni's correction). aMCI patients with thick coating exhibited poor cognitive performance, which might be attributed to decreased FC seeding from bankssts. Our findings strengthen the understanding of brain reorganization of STS via which tongue coating status impacts cognition in patients with aMCI.

BackgroundLumbosacral muscle strain (LMS) is common in Chinese elite trampoline athletes. Advanced lumbar muscle activation is necessary for postural control before upper extremity voluntary movements, called anticipatory postural adjustment to reduce internal postural interference (IPI). The potential of delayed lumbar muscle activation has been reported in patients with non-specific LBP (NLBP) in response to IPI. However, it remains unknown whether this effect exists in elite trampoline athletes. There is also limited literature reporting the rehabilitation of LMS in this population. This study first aimed to explore whether elite trampoline athletes with LMS experience delayed activation of lumbar muscles under IPI. The secondary aim was to preliminarily evaluate an integrative rehabilitation program's effectiveness.Materials and methodsTen elite trampoline athletes with LMS were recruited and received 10 sessions of integrative rehabilitation, including extracorporeal shock wave therapy, acupuncture, Tui-na, and spine function exercises. At baseline and after all sessions, the relative activation time of the lumbar muscles under IPI in a modified rapid arm-rise test was used as a primary outcome measure. The secondary measures included a visual analog scale (VAS) and a questionnaire to assess low back pain (LBP) and athletic training performance.ResultsThe relative activation time of the lumbar muscles under IPI was delayed at baseline, but significantly decreased after the intervention (P 0.05).ConclusionsElite trampoline athletes with LMS had delayed activation in their lumbar muscles under IPI. Integrative rehabilitation was effective in LBP relief and neuromuscular control of the lumbar muscles, and impacted positively on training performance. Future studies with a larger sample size, a control group, and long-term follow-ups are needed to further examine the efficacy of integrative rehabilitation in elite trampoline athletes with LMS. Additionally, the application of this approach in athletes with LMS or LBP in other sports, particularly those involving IPI, should be explored.

Background: Stroke remains a leading cause of disability globally and movement impairment is the most common complication in stroke patients. Resting-state electroencephalography (EEG) microstate analysis is a non-invasive approach of whole-brain imaging based on the spatiotemporal pattern of the entire cerebral cortex. The present study aims to investigate microstate alterations in stroke patients. Methods: Resting-state EEG data collected from 24 stroke patients and 19 healthy controls matched by age and gender were subjected to microstate analysis. For four classic microstates labeled as class A, B, C and D, their temporal characteristics (duration, occurrence and coverage) and transition probabilities (TP) were extracted and compared between the two groups. Furthermore, we explored their correlations with clinical outcomes including the Fugl-Meyer assessment (FMA) and the action research arm test (ARAT) scores in stroke patients. Finally, we analyzed the relationship between the temporal characteristics and spectral power in frequency bands. False discovery rate (FDR) method was applied for correction of multiple comparisons. Results: Microstate analysis revealed that the stroke group had lower occurrence of microstate A which was regarded as the sensorimotor network (SMN) compared with the control group (p = 0.003, adjusted p = 0.036, t = –2.959). The TP from microstate A to microstate D had a significant positive correlation with the Fugl-Meyer assessment of lower extremity (FMA-LE) scores (p = 0.049, r = 0.406), but this finding did not survive FDR adjustment (adjusted p = 0.432). Additionally, the occurrence and the coverage of microstate B were negatively correlated with the power of delta band in the stroke group, which did not pass adjustment (p = 0.033, adjusted p = 0.790, r = –0.436; p = 0.026, adjusted p = 0.790, r = –0.454, respectively). Conclusions: Our results confirm the abnormal temporal dynamics of brain activity in stroke patients. The study provides further electrophysiological evidence for understanding the mechanism of brain motor functional reorganization after stroke.

Abstract Background Electroacupuncture (EA) has been shown to facilitate brain plasticity‐related functional recovery following ischemic stroke. The functional magnetic resonance imaging technique can be used to determine the range and mode of brain activation. After stroke, EA has been shown to alter brain connectivity, whereas EA's effect on brain network topology properties remains unclear. An evaluation of EA's effects on global and nodal topological properties in rats with ischemia reperfusion was conducted in this study. Methods and results There were three groups of adult male Sprague‐Dawley rats: sham‐operated group (sham group), middle cerebral artery occlusion/reperfusion (MCAO/R) group, and MCAO/R plus EA (MCAO/R + EA) group. The differences in global and nodal topological properties, including shortest path length, global efficiency, local efficiency, small‐worldness index, betweenness centrality (BC), and degree centrality (DC) were estimated. Graphical network analyses revealed that, as compared with the sham group, the MCAO/R group demonstrated a decrease in BC value in the right ventral hippocampus and increased BC in the right substantia nigra, accompanied by increased DC in the left nucleus accumbens shell (AcbSh). The BC was increased in the right hippocampus ventral and decreased in the right substantia nigra after EA intervention, and MCAO/R + EA resulted in a decreased DC in left AcbSh compared to MCAO/R. Conclusion The results of this study provide a potential basis for EA to promote cognitive and motor function recovery after ischemic stroke.

BackgroundLong-term skill learning can lead to structure and function changes in the brain. Different sports can trigger neuroplasticity in distinct brain regions. Volleyball, as one of the most popular team sports, heavily relies on individual abilities such as perception and prediction for high-level athletes to excel. However, the specific brain mechanisms that contribute to the superior performance of volleyball athletes compared to non-athletes remain unclear.MethodWe conducted a study involving the recruitment of ten female volleyball athletes and ten regular female college students, forming the athlete and novice groups, respectively. Comprehensive behavioral assessments, including Functional Movement Screen and audio-visual reaction time tests, were administered to both groups. Additionally, resting-state magnetic resonance imaging (MRI) data were acquired for both groups. Subsequently, we conducted in-depth analyses, focusing on the amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo), and functional connectivity (FC) in the brain for both the athlete and novice groups.ResultsNo significant differences were observed in the behavioral data between the two groups. However, the athlete group exhibited noteworthy enhancements in both the ALFF and ReHo within the visual cortex compared to the novice group. Moreover, the functional connectivity between the visual cortex and key brain regions, including the left primary sensory cortex, left supplementary motor cortex, right insula, left superior temporal gyrus, and left inferior parietal lobule, was notably stronger in the athlete group than in the novice group.ConclusionThis study has unveiled the remarkable impact of volleyball athletes on various brain functions related to vision, movement, and cognition. It indicates that volleyball, as a team-based competitive activity, fosters the advancement of visual, cognitive, and motor skills. These findings lend additional support to the early cultivation of sports talents and the comprehensive development of adolescents. Furthermore, they offer fresh perspectives on preventing and treating movement-related disorders. Trial registrationRegistration number: ChiCTR2400079602. Date of Registration: January 8, 2024.

Abstract Background Ischemic stroke is a severe type of stroke with high disability and mortality rates. In recent years, microglial exosome-derived miRNAs have been shown to be promising candidates for the treatment of ischemic brain injury and exert neuroprotective effects. Mechanisms underlying miRNA dysregulation in ischemic stroke are still being explored. Here, we aimed to verify whether miRNAs derived from exosomes exert effects on functional recovery. Methods MiR-212-5p agomir was employed to upregulate miR-212-5p expression in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) as well as an oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro. Western blot analysis, qRT–PCR and immunofluorescence staining and other methods were applied to explore the underlying mechanisms of action of miR-212-5p. Results The results of our study found that intervention with miR-212-5p agomir effectively decreased infarct volume and restored motor function in MCAO/R rats. Mechanistically, miR-212-5p agomir significantly reduced the expression of PlexinA2 (PLXNA2). Additionally, the results obtained in vitro were similar to those achieved in vivo. Conclusion In conclusion, the present study indicated that PLXNA2 may be a target gene of miR-212-5p, and miR-212-5p has great potential as a target for the treatment and diagnosis of ischemic stroke.

Background: Brachial plexus injury is a common severe peripheral nerve injury with high disability. At present, the bibliometric analysis of brachial plexus injury is basically unknown. Methods: This article analyzes the data retrieved to the web of science and uses the R language (version 4.2), Citespace (version 6.1.R3 Advanced), Vosviewer (Lei deng university) to make a scientific map. Specifically, we analyze the main publication countries, institutions, journals where the article is published, and the cooperative relationship between different institutions, the relationship between authors, main research directions in this field, and current research hotspots. Results: From 1980 to 2022, the total number of publications is 1542. In terms of countries where articles were published, 551 records were published in the United States, accounting for 35% of the total. With 74 articles, Fudan University ranks first in the world in terms of the number of articles issued by the institution, followed by 72 articles from Mayo Clinic. The magazine with the largest number of articles is JOURNAL OF HAND SURGERY-AMERICAN VOLUME, which has published 87 articles in total. GU YD (Gu Yu-Dong) team (Fudan University) and spinner RJ (Robert J Spinner) team (Mayo clinic) are in a leading position in this field. Nerve transfer and nerve reconstruction have been a hot topic of brachial plexus injury. ''Spinal nerve root repair and reimplantation of avulsed ventral roots into the spinal cord after brachial plexus injury'' has the strongest citation bursts. Conclusion: Research on brachial plexus injury shows a trend of increasing heat. At present, there is a lack of communication and cooperation between scholars from different countries. Nerve transfer and nerve reconstruction are the current and future research directions in the treatment of brachial plexus injury.

Abstract Introduction : Brain has a spontaneous recovery after stroke, reflecting the plasticity of the brain. Currently, TMS is used for studies of single-target brain region modulation, which lacks consideration of brain networks and functional connectivity. Cortico-cortical paired associative stimulation (ccPAS) promotes recovery of motor function. Multisensory effects in primary visual cortex(V1) directly influence behavior and perception, which facilitate motor functional recovery in stroke patients. Therefore, in this study, dual-targeted precise stimulation of V1 and primary motor cortex(M1) on the affected hemisphere of stroke patients will be used for cortical visuomotor multisensory integration to improve motor function. Method This study is a randomized, double-blind controlled clinical trial over a 14-week period. 69 stroke subjects will be enrolled and divided into sham stimulation group, ccPAS low frequency group, and ccPAS high frequency group. All groups will receive conventional rehabilitation. The intervention lasted for two weeks, five times a week. Assessments will be performed before the intervention, at the end of the intervention, and followed up at 6 and 14 weeks. The primary assessment indicator is the ‘Fugl-Meyer Assessment of the Upper Extremity ’, secondary outcomes were ‘The line bisection test’, ‘Modified Taylor Complex Figure’, ‘NIHSS’ and neuroimaging assessments. All adverse events will be recorded. Discussion Currently, ccPAS is used for the modulation of neural circuits. Based on spike-timing dependent plasticity theory, we can precisely intervene in the connections between different cortices to promote the recovery of functional connectivity on damaged brain networks after stroke. We hope to achieve the modulation of cortical visuomotor interaction by combining ccPAS with the concept of multisensory integration. We will further analyze the correlation between analyzing visual and motor circuits and explore the alteration of neuroplasticity by the interactions between different brain networks. This study will provide us with a new clinical treatment strategy to achieve precise rehabilitation for patient with motor dysfunction after stroke. Trial registration This trial was registered in the Chinese Clinical Trial Registry with code ChiCTR2300067422 and was approved on January 16, 2023.

Abstract Background Connectome mapping may reveal new treatment targets for patients with neurological and psychiatric diseases. However, the long-term delayed recall based-network with structural and functional connectome is still largely unknown. Our objectives were to (1) identify the long-term delayed recall-based cortex-hippocampus network with structural and functional connectome and (2) investigate its relationships with various cognitive functions, age, and activities of daily living. Methods This case-control study enrolled 131 subjects (73 amnestic mild cognitive impairment [aMCI] patients and 58 age- and education-matched healthy controls [HCs]). All subjects completed a neuropsychological battery, activities of daily living assessment, and multimodal magnetic resonance imaging. Nodes of the cortical-hippocampal network related to long-term delayed recall were identified by probabilistic fiber tracking and functional connectivity (FC) analysis. Then, the main and interaction effects of the network on cognitive functions were assessed by a generalized linear model. Finally, the moderating effects of the network on the relationships between long-term delayed recall and clinical features were analyzed by multiple regression and Hayes’ bootstrap method. All the effects of cortex-hippocampus network were analyzed at the connectivity and network levels. Results The result of a generalized linear model showed that the bilateral hippocampus, left dorsolateral superior frontal gyrus, right supplementary motor area, left lingual gyrus, left superior occipital gyrus, left superior parietal gyrus, left precuneus, and right temporal pole (superior temporal gyrus) are the left and right cortex-hippocampus network nodes related to long-term delayed recall (P < 0.05). Significant interaction effects were found between the Auditory Verbal Learning Test Part 5 (AVLT 5) scores and global properties of the left cortex-hippocampus network [hierarchy, clustering coefficient, characteristic path length, global efficiency, local efficiency, Sigma and synchronization (P < 0.05 Bonferroni corrected)]. Significant interaction effects were found between the general cognitive function/executive function/language and global properties of the left cortex-hippocampus network [Sigma and synchronization (P < 0.05 Bonferroni corrected)]. Conclusion This study introduces a novel symptom-based network and describes relationships among cognitive functions, brain function, and age. The cortex–hippocampus network constrained by the structural and functional connectome is closely related to long-term delayed recall.

Abstract Introduction Tuina is currently one of the popular complementary and alternative methods of rehabilitation therapy. Tuina can improve patients' pain and mobility function. However, the underlying physiological mechanism remains largely unknown, which might limit its further popularization in clinical practice. The aim of this study is to explore the short‐term and long‐term changes in brain functional activity following Tuina intervention for peripheral nerve injury repair. Methods A total of 16 rats were equally divided into the intervention group and the control group. Rats in the intervention group received Tuina therapy applying on the gastrocnemius muscle of the right side for 4 months following sciatic nerve transection and immediate repair, while the control group received nerve transection and repair only. The block‐design functional magnetic resonance imaging scan was applied in both groups at 1 and 4 months after the surgery. During the scan, both the injured and intact hindpaw was electrically stimulated according to a “boxcar” paradigm. Results When stimulating the intact hindpaw, the intervention group exhibited significantly lower activation in the somatosensory area, limbic/paralimbic areas, pain‐regulation areas, and basal ganglia compared to the control group, with only the prefrontal area showing higher activation. After 4 months of sciatic nerve injury, the control group exhibited decreased motor cortex activity compared to the activity observed at 1 month, and the intervention group demonstrated stronger bilateral motor cortex activity compared to the control group. Conclusion Tuina therapy on the gastrocnemius muscle of rats with sciatic nerve injury can effectively alleviate pain and maintain the motor function of the affected limb. In addition, Tuina therapy reduced the activation level of pain‐related brain regions and inhibited the decreased activity of the motor cortex caused by nerve injury, reflecting the impact of peripheral stimulation on brain plasticity.

BackgroundBrain–computer interface (BCI) has been widely used for functional recovery after stroke. Understanding the brain mechanisms following BCI intervention to optimize BCI strategies is crucial for the benefit of stroke patients.MethodsForty-six patients with upper limb motor dysfunction after stroke were recruited and randomly divided into the control group or the BCI group. The primary outcome was measured by the assessment of Fugl–Meyer Assessment of Upper Extremity (FMA-UE). Meanwhile, we performed resting-state functional magnetic resonance imaging (rs-fMRI) in all patients, followed by independent component analysis (ICA) to identify functionally connected brain networks. Finally, we assessed the topological efficiency of both groups using graph-theoretic analysis in these brain subnetworks.ResultsThe FMA-UE score of the BCI group was significantly higher than that of the control group after treatment (p = 0.035). From the network topology analysis, we first identified seven subnetworks from the rs-fMRI data. In the following analysis of subnetwork properties, small-world properties including γ (p = 0.035) and σ (p = 0.031) within the visual network (VN) decreased in the BCI group. For the analysis of the dorsal attention network (DAN), significant differences were found in assortativity (p = 0.045) between the groups. Additionally, the improvement in FMA-UE was positively correlated with the assortativity of the dorsal attention network (R = 0.498, p = 0.011).ConclusionBrain–computer interface can promote the recovery of upper limbs after stroke by regulating VN and DAN. The correlation trend of weak intensity proves that functional recovery in stroke patients is likely to be related to the brain’s visuospatial processing ability, which can be used to optimize BCI strategies.Clinical Trial RegistrationThe trial is registered in the Chinese Clinical Trial Registry, number ChiCTR2000034848. Registered 21 July 2020.

Abstract Background Upper limb motor dysfunction is a common sequela of stroke, and its clinical efficacy needs to be improved. This protocol describes a trial to verify the clinical efficacy of robot-assisted virtual reality mirror therapy (RAVRMT) in improving upper limb motor dysfunction in stroke patients, and to explore the central mechanism by using functional magnetic resonance imaging (fMRI). Methods This trial will be a single-center, assessor-blinded, randomized controlled clinical study. Thirty-two eligible patients will be randomly divided into 2 groups according to the ratio of 1:1, namely virtual reality mirror therapy (VRMT) group and robot-assisted virtual reality mirror therapy (RAVRMT) group. The interventions will be performed once a day for 4 weeks. Primary outcome is Fugl–Meyer motor function assessment-Upper Extremity (FMA-UE), secondary outcomes are the Montreal Cognitive Assessment (MoCA), activities of daily living (ADL), quality of life (QOL), the pain visual analogue scale (VAS-pain) and fMRI. Adverse events will be recorded, and severe adverse events will be used as criteria to discontinue the intervention. Discussion Combined application of robot-assisted therapy and virtual reality mirror therapy could theoretically activate mirror neuron system and reward circuits to a greater extent, but further high-quality research is needed. The results of this trial will determine whether RAVRMT could better improve upper limb motor dysfunction after stroke and explore its central mechanism using fMRI. Trial registration This trial was prospectively registered at ClinicalTrials.gov (ChiCTR2200061721; 01 July 2022).

ObjectiveAging has great influence on the clinical treatment effect of cerebrovascular diseases, and evidence suggests that the effect may be associated with age-related brain plasticity. Electroacupuncture is an effective alternative treatment for traumatic brain injury (TBI). In the present study, we aimed to explore the effect of aging on the cerebral metabolic mechanism of electroacupuncture to provide new evidence for developing age-specific rehabilitation strategies.MethodsBoth aged (18 months) and young (8 weeks) rats with TBI were analyzed. Thirty-two aged rats were randomly divided into four groups: aged model, aged electroacupuncture, aged sham electroacupuncture, and aged control group. Similarly, 32 young rats were also divided into four groups: young model, young electroacupuncture, young sham electroacupuncture, and young control group. Electroacupuncture was applied to “Bai hui” (GV20) and “Qu chi” (LI11) for 8 weeks. CatWalk gait analysis was then performed at 3 days pre- and post-TBI, and at 1, 2, 4, and 8 weeks after intervention to observe motor function recovery. Positron emission computed tomography (PET/CT) was performed at 3 days pre- and post-TBI, and at 2, 4, and 8 weeks after intervention to detect cerebral metabolism.ResultsGait analysis showed that electroacupuncture improved the forepaw mean intensity in aged rats after 8 weeks of intervention, but after 4 weeks of intervention in young rats. PET/CT revealed increased metabolism in the left (the injured ipsilateral hemisphere) sensorimotor brain areas of aged rats during the electroacupuncture intervention, and increased metabolism in the right (contralateral to injury hemisphere) sensorimotor brain areas of young rats.ResultsThis study demonstrated that aged rats required a longer electroacupuncture intervention duration to improve motor function than that of young rats. The influence of aging on the cerebral metabolism of electroacupuncture treatment was mainly focused on a particular hemisphere.

Abstract Background Osteoarthritis (OA) is the most prevalent degenerative joint disease. In vitro experiments are an intuitive method used to investigate its early pathogenesis. Chondrocyte inflammation models in rats and mice are often used as in vitro models of OA. However, similarities and differences between them in the early stages of inflammation have not been reported. Objective This paper seeks to compare the chondrocyte phenotype of rats and mice in the early inflammatory state and identify chondrocytes suitable for the study of early OA. Methods Under similar conditions, chondrocytes from rats and mice were stimulated using the same IL-1β concentration for a short period of time. The phenotypic changes of chondrocytes were observed under a microscope. The treated chondrocytes were subjected to RNA-seq to identify similarities and differences in gene expression. Chondrocytes were labelled with EdU for proliferation analysis. Cell proliferation-associated proteins, including minichromosome maintenance 2 (MCM2), minichromosome maintenance 5 (MCM5), Lamin B1, proliferating cell nuclear antigen (PCNA), and Cyclin D1, were analysed by immunocytochemical staining, cell immunofluorescence, and Western blots to verify the RNA-seq results. Results RNA-seq revealed that the expression patterns of cytokines, chemokines, matrix metalloproteinases, and collagen were similar between the rat and mouse chondrocyte inflammation models. Nonetheless, the expression of proliferation-related genes showed the opposite pattern. The RNA-seq results were further verified by subsequent experiments. The expression levels of MCM2, MCM5, Lamin B1, PCNA, and Cyclin D1 were significantly upregulated in rat chondrocytes (P

Pain is one of the manifestations of hip disorder and has been proven to lead to the remodeling of somatotopic map plasticity in the cortex. However, most studies are volume-based which may lead to inaccurate anatomical positioning of functional data. The methods that work on the cortical surface may be more sensitive than those using the full brain volume and thus be more suitable for map plasticity study. In this prospective cross-sectional study performed in Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, China, 20 patients with osteonecrosis of the femoral head (12 males and 8 females, aged 56.80 ± 13.60 years) and 20 healthy controls (9 males and 11 females, aged 54.56 ± 10.23 years) were included in this study. Data of resting-state functional magnetic resonance imaging were collected. The results revealed that compared with healthy controls, compared with the healthy controls, patients with osteonecrosis of the femoral head (ONFH) showed significantly increased surface-based regional homogeneity (ReHo) in areas distributed mainly in the left dorsolateral prefrontal cortex, frontal eye field, right frontal eye field, and the premotor cortex and decreased surface-based ReHo in the right primary motor cortex and primary sensory cortex. Regions showing significant differences in surface-based ReHo values between the healthy controls and patients with ONFH were defined as the regions of interests. Seed-based functional connectivity was performed to investigate interregional functional synchronization. When the areas with decreased surface-based ReHo in the frontal eye field and right premotor cortex were used as the regions of interest, compared with the healthy controls, the patients with ONFH displayed increased functional connectivity in the right middle frontal cortex and right inferior parietal cortex and decreased functional connectivity in the right precentral cortex and right middle occipital cortex. Compared with healthy controls, patients with ONFH showed significantly decreased cortical thickness in the para-insular area, posterior insular area, anterior superior temporal area, frontal eye field and supplementary motor cortex and reduced volume of subcortical gray matter nuclei in the right nucleus accumbens. These findings suggest that hip disorder patients showed cortical plasticity changes, mainly in sensorimotor- and pain-related regions. This study was approved by the Medical Ethics Committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine (approval No. 2018-041) on August 1, 2018.

Electroacupuncture (EA) has been widely used for functional restoration after stroke. However, its role in post-stroke rehabilitation and the associated regulatory mechanisms remain poorly understood. In this study, we applied EA to the Zusanli (ST36) and Quchi (LI11) acupoints in rats with middle cerebral artery occlusion and reperfusion. We found that EA effectively increased the expression of brain-derived neurotrophic factor and its receptor tyrosine kinase B, synapsin-1, postsynaptic dense protein 95, and microtubule-associated protein 2 in the ischemic penumbra of rats with middle cerebral artery occlusion and reperfusion. Moreover, EA greatly reduced the expression of myelin-related inhibitors Nogo-A and NgR in the ischemic penumbra. Tyrosine kinase B inhibitor ANA-12 weakened the therapeutic effects of EA. These findings suggest that EA can improve neurological function after middle cerebral artery occlusion and reperfusion, possibly through regulating the activity of the brain-derived neurotrophic factor/tyrosine kinase B signal pathway. All procedures and experiments were approved by the Animal Research Committee of Shanghai University of Traditional Chinese Medicine, China (approval No. PZSHUTCM200110002) on January 10, 2020.

Introduction Improving lower extremity motor function is the focus and difficulty of post-stroke rehabilitation treatment. More recently, robot-assisted and virtual reality (VR) training are commonly used in post-stroke rehabilitation and are considered feasible treatment methods. Here, we developed a rehabilitation system combining robot motor assistance with neural circuit-based VR (NeuCir-VR) rehabilitation programme involving procedural lower extremity rehabilitation with reward mechanisms, from muscle strength training, posture control and balance training to simple and complex ground walking training. The study aims to explore the effectiveness and neurological mechanisms of combining robot motor assistance and NeuCir-VR lower extremity rehabilitation training in patients after stroke.Methods and analysis This is a single-centre, observer-blinded, randomised controlled trial. 40 patients with lower extremity hemiparesis after stroke will be recruited and randomly divided into a control group (combined robot assistance and VR training) and an intervention group (combined robot assistance and NeuCir-VR training) by the ratio of 1:1. Each group will receive five 30 min sessions per week for 4 weeks. The primary outcome will be Fugl-Meyer assessment of the lower extremity. Secondary outcomes will include Berg Balance Scale, Modified Ashworth Scale and functional connectivity measured by resting-state functional MRI. Outcomes will be measured at baseline (T0), post-intervention (T1) and follow-ups (T2–T4).Ethics, registration and dissemination The trial was approved by the Ethics Committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Chinese Traditional Medicine (Grant No. 2019–014). The results will be submitted to a peer-reviewed journal or at a conference.Trial registration number ChiCTR2100052133.

BackgroundSpinal stretch reflex (SSR) hyperexcitability reflected by the H-reflex has been reported in more strongly affected extremities after stroke. The H-reflex in the lower extremities is modulated by body position normally and alternatively modulated post-stroke.ObjectiveThis study aimed to preliminarily explore how upper extremity (UE) H-reflexes are modulated by body position after stroke, which remains unknown.Materials and methodsThree patients after stroke with hemiparesis/hemiplegia were included. Bilateral flexor carpi radialis (FCR) H-reflexes were examined in the supine position while standing. Other clinical evaluations include the modified Ashworth scale (MAS) and postural stability measurement.ResultsThe three cases herein showed that (1) SSR excitability was higher in more strongly affected UEs than less-affected UEs, (2) down-modulation of SSR excitability occurred in less-affected UEs in static standing compared with the supine position, but modulation of SSR excitability in more-affected UEs varied, and (3) bilateral UE SSR excitability in case 3 was down-modulated the most. Moreover, case 3 showed no difference in muscle tone of the more affected UE between supine and standing positions, and case 3 showed the best postural stability.ConclusionSpinal stretch reflex hyperexcitability in strongly affected UEs could commonly occur in different phases of recovery after stroke. Down-modulation of SSR excitability could occur in less-affected UEs in the standing position compared with the supine position, while modulation of SSR excitability might be altered in strongly affected UEs and vary in different phases of recovery. There could be some correlation between postural control and UE SSR hyperexcitability. The H-reflex may help to offer a new perspective on rehabilitation evaluation and interventions to promote UE motor control after stroke.

BackgroundProgression of freezing of gait (FOG), a common pathological gait in Parkinson’s disease (PD), has been shown to be an important risk factor for falls, loss of independent living ability, and reduced quality of life. However, previous evidence indicated poor efficacy of medicine and surgery in treating FOG in patients with PD. Music-based movement therapy (MMT), which entails listening to music while exercising, has been proposed as a treatment to improve patients’ motor function, emotions, and physiological activity. In recent years, MMT has been widely used to treat movement disorders in neurological diseases with promising results. Results from our earlier pilot study revealed that MMT could relieve FOG and improve the quality of life for patients with PD.ObjectiveTo explore the effect of MMT on FOG in patients with PD.Materials and methodsThis was a prospective, evaluator-blinded, randomized controlled study. A total of 81 participants were randomly divided into music-based movement therapy group (MMT, n = 27), exercise therapy group (ET, n = 27), and control group (n = 27). Participants in the MMT group were treated with MMT five times (1 h at a time) every week for 4 weeks. Subjects in the ET group were intervened in the same way as the MMT group, but without music. Routine rehabilitation treatment was performed on participants in all groups. The primary outcome was the change of FOG in patients with PD. Secondary evaluation indicators included FOG-Questionnaire (FOG-Q) and the comprehensive motor function.ResultsAfter 4 weeks of intervention, the double support time, the cadence, the max flexion of knee in stance, the max hip extension, the flexion moment of knee in stance, the comprehensive motor function (UPDRS Part III gait-related items total score, arising from chair, freezing of gait, postural stability, posture, MDS-UPDRS Part II gait-related items total score, getting out of bed/a car/deep chair, walking and balance, freezing), and the FOG-Q in the MMT group were lower than that in the control group and ET group (p < 0.05). The gait velocity, the max ankle dorsiflexion in stance, ankle range of motion (ROM) during push-off, ankle ROM over gait cycle, the knee ROM over gait cycle, and the max extensor moment in stance (ankle, knee) in the MMT group were higher than that in the control group and ET group (p < 0.05). However, no significant difference was reported between the control group and ET group (p > 0.05). The stride length and hip ROM over gait cycle in the MMT group were higher than that in the control group (p < 0.05), and the max knee extension in stance in the MMT group was lower than that in the control group (p < 0.05). Nevertheless, there was no significant difference between the ET group and MMT group (p > 0.05) or control group (p > 0.05).ConclusionMMT improved gait disorders in PD patients with FOG, thereby improving their comprehensive motor function.

Background: Transforaminal endoscopic lumbar discectomy (TELD) has been widely used for lumbar disc herniation. However, in some challenging cases such as very highly migrated disc herniation (VHMDH), traditional TELD is difficult to access the pathology. Methods: From January 2016 to December 2019, 63 patients with single-level VHMDH underwent TELD using targeted puncture and foraminotomy techniques were included. All patients were followed up for 26.5 months on average (range, 24–48 months). Operative time, length of hospital stay, visual analog scale (VAS) score, Oswestry Disability Index (ODI), modified MacNab criteria and surgical complications were evaluated. Results: The operative time was 40–120 min (56.8 on average). The length of hospitalization was 2.5 days (range, 2–4 d). VAS score decreased significantly from 5.5 ± 1.3 preoperatively to 1.9 ± 1.30 (p < 0.001) 1 day postoperatively, and to 0.9 ± 0.8 (p < 0.001) at the final follow-up. ODI score improved significantly from 23.5 ± 3.2 preoperatively to 13.4 ± 3.0 (p < 0.001) 1 day postoperatively; and 3.1 ± 1.2 (p < 0.001) at the final follow-up. According to the modified MacNab criteria, 40 patients (63.5%) showed excellent results, 20 patients (31.7%) were rated as good, 2 patients (3.2%) were rated as fine, and 1 patient (1.6%) was rated as bad at the final follow-up. No residual fragments, nerve root or cauda equina injury was shown in this series. One recurrent case was resolved by open surgery. Conclusions: With modified targeted puncture and foraminotomy techniques, VHMDH can be accessed safely and effectively, and satisfactory clinical outcomes can be obtained for these patients.

Motor dysfunction is the major sequela of ischemic stroke. Motor recovery after stroke has been shown to be associated with remodeling of large-scale brain networks, both functionally and structurally. Electroacupuncture (EA) is a traditional Chinese medicine application that has frequently been recommended as an alternative therapy for ischemic stroke and is reportedly effective for alleviating motor symptoms in patients. In the present study, the effect of EA on the alterations of functional resting state networks (RSNs) was explored after middle cerebral artery occlusion/reperfusion (MCAO/R) injury using resting-state functional MRI. Rats were randomly assigned to three groups, including the sham group, MCAO/R group and MCAO/R+EA group. The ladder rung walking test was conducted prior to and after modeling to assess behavioral changes. RSNs were identified based on the independent component analysis (ICA) performed on the fMRI data from groups. EA treatment effectively reduced the occurrence of contralateral forelimb foot faults. Furthermore, our results suggested the disrupted function of the whole-brain network following ischemic stroke and the modulatory effect of acupuncture. The sensorimotor network (SMN), interoceptive network (IN), default mode network (DMN) and salience network (SN) were related to the therapeutic effect of EA on stroke recovery. Collectively, our findings confirmed the effect of EA on motor function recovery after cerebral ischemia reperfusion and shed light on the assessment of EA intervention-induced effects on brain networks. This study provides neuroimaging evidence to explain the therapeutic effects of EA in ischemic stroke and will lay the groundwork for further studies.

Post-stroke depression (PSD) is a serious complication of stroke that significantly restricts rehabilitation. The use of immersive virtual reality for stroke survivors is promising. Herein, we investigated the effects of a novel immersive virtual reality training system on PSD and explored induced effective connectivity alterations in emotional networks using multivariate Granger causality analysis (GCA). Forty-four patients with PSD were equally allocated into an immersive-virtual reality group and a control group. In addition to their usual rehabilitation treatments, the participants in the immersive-virtual reality group participated in an immersive-virtual reality rehabilitation program, while the patients in the control group received 2D virtual reality rehabilitation training. The Hamilton Depression Rating Scale, modified Barthel Index (MBI), and resting-state functional magnetic resonance imaging (rsfMRI) data were collected before and after a 4-week intervention. rsfMRI data were analyzed using multivariate GCA. We found that the immersive virtual reality training was more effective in improving depression in patients with PSD but had no statistically significant improvement in MBI scores compared to the control group. The GCA showed that the following causal connectivities were strengthened after immersive virtual reality training: from the amygdala, insula, middle temporal gyrus, and caudate nucleus to the dorsolateral prefrontal cortex; from the insula to the medial prefrontal cortex; and from the thalamus to the posterior superior temporal sulcus. These causal connectivities were weakened after treatment in the control group. Our results indicated the neurotherapeutic use of immersive virtual reality rehabilitation as an effective non-pharmacological intervention for PSD; the alteration of causal connectivity in emotional networks might constitute the neural mechanisms underlying immersive-virtual reality rehabilitation in PSD.

Characterized by high morbidity, mortality, and disability, stroke usually causes symptoms of cerebral hypoxia due to a sudden blockage or rupture of brain vessels, and it seriously threatens human life and health. Rehabilitation is the essential treatment for post-stroke patients suffering from functional impairments, through which hemiparesis, aphasia, dysphagia, unilateral neglect, depression, and cognitive dysfunction can be restored to various degrees. Noninvasive brain stimulation (NIBS) is a popular neuromodulatory technology of rehabilitation focusing on the local cerebral cortex, which can improve clinical functions by regulating the excitability of corresponding neurons. Increasing evidence has been obtained from the clinical application of NIBS, especially repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). However, without a standardized protocol, existing studies on NIBS show a wide variation in terms of stimulation site, frequency, intensity, dosage, and other parameters. Its application for neurorehabilitation in post-stroke patients is still limited. With advances in neuronavigation technologies, functional near-infrared spectroscopy, and functional MRI, specific brain regions can be precisely located for stimulation. On the basis of our further understanding on neural circuits, neuromodulation in post-stroke rehabilitation has also evolved from single-target stimulation to co-stimulation of two or more targets, even circuits and the network. The present study aims to review the findings of current research, discuss future directions of NIBS application, and finally promote the use of NIBS in post-stroke rehabilitation.

Facial synkinesis is a troublesome sequelae of facial nerve malfunction. It is difficult to recover from synkinesis, despite improved surgical techniques for isolating the peripheral facial nerve branches. Furthermore, it remains unclear whether long-term dysfunction of motor control can lead to irreversible plasticity-induced structural brain changes. This case-control study thus investigated the structural brain alterations associated with facial synkinesis. The study was conducted at Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, China. Twenty patients with facial synkinesis (2 male and 18 female, aged 33.35 ± 6.97 years) and 19 healthy volunteers (2 male and 17 female, aged 33.21 ± 6.75 years) underwent magnetic resonance imaging, and voxel-based and surface-based morphometry techniques were used to analyze data. There was no significant difference in brain volume between patients with facial synkinesis and healthy volunteers. Patients with facial synkinesis exhibited a significantly reduced cortical thickness in the contralateral superior and inferior temporal gyri and a reduced sulcal depth of the ipsilateral precuneus compared with healthy volunteers. In addition, sulcal depth of the ipsilateral precuneus was negatively correlated with the severity of depression. These findings suggest that there is a structural remodeling of gray matter in patients with facial synkinesis after facial nerve malfunction. This study was approved by the Ethics Review Committee of the Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, China (approval No. 2017-365-T267) on September 13, 2017, and was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR1800014630) on January 25, 2018.

Massage therapy is an alternative treatment for chronic pain that is potentially related to brain plasticity. However, the underlying mechanism remains unclear. We established a peripheral nerve injury model in rats by unilateral sciatic nerve transection and direct anastomosis. The experimental rats were treated over the gastrocnemius muscle of the affected hindlimb with a customized massage instrument (0.45 N, 120 times/min, 10 minutes daily, for 4 successive weeks). Resting-state functional magnetic resonance imaging revealed that compared with control rats, the amplitude of low-frequency fluctuations in the sensorimotor cortex contralateral to the affected limb was significantly lower after sciatic nerve transection. However, amplitudes were significantly higher in the massage group than in a sham-massage group. These findings suggest that massage therapy facilitated adaptive change in the somatosensory cortex that led to the recovery of peripheral nerve injury and repair. This study was approved by the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine of China (approval No. 201701001) on January 12, 2017.

Normal aging causes profound changes of structural degeneration and glucose hypometabolism in the human brain, even in the absence of disease. In recent years, with the extensive exploration of the topological characteristics of the human brain, related studies in rats have begun to investigate. However, age-related alterations of topological properties in individual brain metabolic network of rats remain unknown. In this study, a total of 48 healthy female Sprague–Dawley (SD) rats were used, including 24 young rats and 24 aged rats. We used Jensen-Shannon Divergence Similarity Estimation (JSSE) method for constructing individual metabolic networks to explore age-related topological properties and rich-club organization changes. Compared with the young rats, the aged rats showed significantly decreased clustering coefficient (Cp) and local efficiency (Eloc) across the whole-brain metabolic network. In terms of changes in local network measures, degree (D) and nodal efficiency (Enod) of left posterior dorsal hippocampus, and Enod of left olfactory tubercle were higher in the aged rats than in the young rats. About the rich-club analysis, the existence of rich-club organization in individual brain metabolic networks of rats was demonstrated. In addition, our findings further confirmed that rich-club connections were susceptible to aging. Relative to the young rats, the overall strength of rich-club connections was significantly reduced in the aged rats, while the overall strength of feeder and local connections was significantly increased. These findings demonstrated the age-related reorganization principle of the brain structure and improved our understanding of brain alternations during aging.

BackgroundMotor imagery training might be helpful in stroke rehabilitation. This study explored if a specific modulation of movement-related regions is related to motor imagery (MI) ability.MethodsTwenty-three patients with subcortical stroke and 21 age-matched controls were recruited. They were subjectively screened using the Kinesthetic and Visual Imagery Questionnaire (KVIQ). They then underwent functional magnetic resonance imaging (fMRI) while performing three repetitions of different motor tasks (motor execution and MI). Two separate runs were acquired [motor execution tasks (ME and rest) and motor imagery (MI and rest)] in a block design. For the different tasks, analyses of cerebral activation and the correlation of motor/imagery task-related activity and KVIQ scores were performed.ResultsDuring unaffected hand (UH) active grasp movement, we observed decreased activations in the contralateral precentral gyrus (PreCG), contralateral postcentral gyrus (PoCG) [p < 0.05, family wise error (FWE) corrected] and a positive correlation with the ability of FMA-UE (PreCG: r = 0.46, p = 0.028; PoCG: r = 0.44, p = 0.040). During active grasp of the affected hand (AH), decreased activation in the contralateral PoCG was observed (p < 0.05, FWE corrected). MI of the UH induced significant activations of the contralateral superior frontal gyrus, opercular region of the inferior frontal gyrus, and ipsilateral ACC and deactivation in the ipsilateral supplementary motor area (p < 0.05, AlphaSim correction). Ipsilateral anterior cingulate cortex (ACC) activity negatively correlated with MI ability (r = =–0.49, p = 0.022). Moreover, we found significant activation of the contralesional middle frontal gyrus (MFG) during MI of the AH.ConclusionOur results proved the dominant effects of MI dysfunction that exist in stroke during the processing of motor execution. In the motor execution task, the enhancement of the contralateral PreCG and PoCG contributed to reversing the motor dysfunction, while in the MI task, inhibition of the contralateral ACC can increase the impaired KVIQ ability. The bimodal balance recovery model can explain our results well. Recognizing neural mechanisms is critical to helping us formulate precise strategies when intervening with electrical or magnetic stimulation.

BackgroundInterhemispheric and intrahemispheric long-range synchronization and information communication are crucial features of functional integration between the bilateral hemispheres. Previous studies have demonstrated that disrupted functional connectivity (FC) exists in the bilateral hemispheres of patients with carpal tunnel syndrome (CTS), but they did not clearly clarify the phenomenon of central dysfunctional connectivity. This study aimed to further investigate the potential mechanism of the weakened connectivity of primary somatosensory cortex (S1) based on a precise template.MethodsPatients with CTS (n = 53) and healthy control subjects (HCs) (n = 23) participated and underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning. We used FC to investigate the statistical dependency of the whole brain, effective connectivity (EC) to analyze time-dependent effects, and voxel-mirrored homotopic connectivity (VMHC) to examine the coordination of FC, all of which were adopted to explore the change in interhemispheric and intrahemispheric S1.ResultsCompared to the healthy controls, we significantly found a decreased strength of the two connectivities in the interhemispheric S1hand, and the results of EC and VMHC were basically consistent with FC in the CTS. The EC revealed that the information output from the dominant hemisphere to the contralateral hemisphere was weakened.ConclusionThis study found that maladjusted connections between and within the bilateral S1 revealed by these methods are present in patients with CTS. The dominant hemisphere with deafferentation weakens its effect on the contralateral hemisphere. The disturbance in the bilateral S1 provides reliable evidence to understand the neuropathophysiological mechanisms of decreased functional integration in the brains of patients with CTS.

Objectives To evaluate the incidence and risk factors of heterotopic ossification (HO) after arthroscopic elbow release. Methods The present study included 101 elbows, with arthroscopic release performed on 98 patients over the 5‐year period from November 2011 to December 2015. Patients were divided into three groups: group 1, with elbow arthritis, including 46 elbows in 43 patients; group 2, with posttraumatic extrinsic elbow stiffness (without intraarticular adhesion), including 23 elbows in 23 patients; and group 3, with intrinsic contractures (with intraarticular adhesion), including 32 elbows in 32 patients. Arthroscopic elbow release was performed under general anesthesia. For intrinsic stiffness, a radiofrequency device was applied to release intraarticular scar tissue and create work space, which was rarely necessary in groups 1 and 2. In the postoperative period, X‐rays and CT scans were assessed at follow up to determine if there was HO formation, which was diagnosed when new calcifications were identified. The functional recovery was evaluated by comparing the range of motion (ROM) and pain relief preoperativley and postoperatively in each group. Other complications were also assessed postoperatively. Results The patients’ mean age was 38.6 years (range, 12–66), with 57 males and 41 females. Mean follow‐up was 21 months (range, 4–56). The active ROM and Mayo elbow performance index (MEPS) were improved from 93° ± 8.3° to 126° ± 12.4° (P

Gut-brain crosstalk has been demonstrated previously. However, brain metabolic patterns of colorectal cancer and chronic enteritis remain unclear. A better understanding of gut-brain crosstalk from a radiological perspective is necessary. We conducted a retrospective study in which we acquired 18F-fluorodeoxyglucose positron emission tomography in 45 colorectal cancer cases, 45 age- and sex-matched chronic enteritis patients, and 45 age- and sex-matched healthy controls. We calculated a scaled sub-profile pattern based on principal component analysis and metabolic connectivity to explore the brain metabolic model and analyzed correlations between various brain regions and cancer to identify potential neuroimaging markers for non-pharmaceutical therapies. We found a characteristic cerebral metabolic pattern in colorectal cancer patients, which mainly involved visceral sensation and both affective and cognitive psychological processes. The metabolic patterns of patients with colorectal cancer and chronic enteritis were similar but not identical. The metabolic connectivity of the postcentral gyrus and paracentral lobule was found to be significantly different between the controls and patients with colorectal cancer (p < 0.05, false discovery rate correction). The maximal standard uptake value of the cancer focus in colorectal cancer patients was negatively correlated with the dorsolateral superior frontal gyrus (p < 0.05). Patients with colorectal cancer may show abnormal glucose cerebral metabolism characterized by “point-line-surface.” This preliminary study revealed the cerebral metabolic characteristics and neurobiological mechanisms of colorectal cancer and chronic enteritis (ChiCTR2000041020; registered December 16, 2020).

Abstract Background Crohn's disease (CD) is a chronic recurrent intestinal inflammatory disease, often accompanied by poor adaptation and excessive stress response. However, the potential neurological mechanisms of these symptoms have not yet been studied in‐depth. Objective To investigate alterations in brain activity in patients with Crohn's disease and study the relationship between altered regions and clinical indices. Methods A total of 15 CD patients and 26 matched healthy controls were recruited. All participants underwent fMRI scans. The amplitude of low‐frequency fluctuations (ALFF) and regional homogeneity (ReHo) assessed differences in spontaneous regional brain activity. Differences between the groups were selected as seeds for functional connectivity (FC) analyses. Correlations between disease duration and ALFF/ReHo/FC values in abnormal regions were analyzed. Results Patients with CD had significantly higher ALFF values in the left superior frontal gyrus, anterior cingulate cortex, and supplementary motor area, and lower values in the left hippocampus. They also had higher ReHo values in the left anterior cingulate cortex, supplementary motor area, putamen, and the bilateral superior frontal gyri. FC strength in the left precentral and middle temporal gyri was found to be increased when the left superior frontal gyrus was used as the seed point. FC strength was also observed to be increased in the left postcentral, middle frontal gyri, inferior frontal orbital cortex, and right rolandic operculum when the left anterior cingulate cortex was used as the seed point. Conclusion CD demonstrated abnormal neural activity and FC in various regions primarily associated with emotional, pain and cognitive‐related functions, which provides more information to further understand the neural mechanisms of the disease.

Neuropathic pain has been found to be related to profound reorganization in the function and structure of the brain. We previously demonstrated changes in local brain activity and functional/metabolic connectivity among selected brain regions by using neuroimaging methods. The present study further investigated large-scale metabolic brain network changes in 32 Sprague–Dawley rats with right brachial plexus avulsion injury (BPAI). Graph theory was applied in the analysis of 2-deoxy-2-[18F] fluoro-D-glucose (18F-FDG) PET images. Inter-subject metabolic networks were constructed by calculating correlation coefficients. Global and nodal network properties were calculated and comparisons between pre- and post-BPAI (7 days) status were conducted. The global network properties (including global efficiency, local efficiency and small-world index) and nodal betweenness centrality did not significantly change for all selected sparsity thresholds following BPAI (p > 0.05). As for nodal network properties, both nodal degree and nodal efficiency measures significantly increased in the left caudate putamen, left medial prefrontal cortex, and right caudate putamen (p < 0.001). The right entorhinal cortex showed a different nodal degree (p < 0.05) but not nodal efficiency. These four regions were selected for seed-based metabolic connectivity analysis. Strengthened connectivity was found among these seeds and distributed brain regions including sensorimotor area, cognitive area, and limbic system, etc. (p < 0.05). Our results indicated that the brain had the resilience to compensate for BPAI-induced neuropathic pain. However, the importance of bilateral caudate putamen, left medial prefrontal cortex, and right entorhinal cortex in the network was strengthened, as well as most of their connections with distributed brain regions.

Abstract Background Mesenchymal stem cell (MSC)-derived exosomes have been recognized as new candidate agents for treating critical-sized bone defects; they promote angiogenesis and may be an alternative to cell therapy. In this study, we evaluated whether exosomes derived from bone marrow-derived MSCs (BMSCs) preconditioned with a low dose of dimethyloxaloylglycine (DMOG), DMOG-MSC-Exos, exert superior proangiogenic activity in bone regeneration and the underlying mechanisms involved. Methods To investigate the effects of these exosomes, scratch wound healing, cell proliferation, and tube formation assays were performed in human umbilical vein endothelial cells (HUVECs). To test the effects in vivo, a critical-sized calvarial defect rat model was established. Eight weeks after the procedure, histological/histomorphometrical analysis was performed to measure bone regeneration, and micro-computerized tomography was used to measure bone regeneration and neovascularization. Results DMOG-MSC-Exos activated the AKT/mTOR pathway to stimulate angiogenesis in HUVECs. This contributed to bone regeneration and angiogenesis in the critical-sized calvarial defect rat model in vivo. Conclusions Low doses of DMOG trigger exosomes to exert enhanced proangiogenic activity in cell-free therapeutic applications.

Purpose. This study is aimed at investigating brain structural changes and structural network properties in complete spinal cord injury (SCI) patients, as well as their relationship with clinical variables. Materials and Methods. Structural MRI of brain was acquired in 24 complete thoracic SCI patients (38.50±11.19 years, 22 males) within the first postinjury year, while 26 age- and gender-matched healthy participants (38.38±10.63 years, 24 males) were enrolled as control. The voxel-based morphometry (VBM) approach and graph theoretical network analysis based on cross-subject grey matter volume- (GMV-) based structural covariance networks (SCNs) were conducted to investigate the impact of SCI on brain structure. Partial correlation analysis was performed to explore the relationship between the GMV of structurally changed brain regions and SCI patients’ clinical variables, including injury duration, injury level, Visual Analog Scale (VAS), American Spinal Injury Association Impairment Scale (AIS), International Classification of Functioning, Disability and Health (ICF) scale, Self-rating Depression Scale (SDS), and Self-rating Anxiety Scale (SAS), after removing the effects of age and gender. Results. Compared with healthy controls, SCI patients showed higher SDS score (t=4.392 and p0.05). Conclusions. SCI patients would experience depressive and/or anxious feelings at the early stage. Their GMV reduction mainly involved psychology-cognition related rather than sensorimotor brain regions. The efficiency of regional information transmission in psychology-cognition regions increased. Greater GMV reduction in psychology region was related with more severe depressive feelings. Therefore, early neuropsychological intervention is suggested to prevent psychological and cognitive dysfunction as well as irreversible brain structure damage.

Objective. We evaluated the effects and mechanisms of GDC0623 on osteogenic differentiation of osteoblasts induced by IL-1β. Methodology. Osteoblasts were treated with 20 ng/ml IL-1β and 0.1 µM GDC0623. Cell proliferation levels were evaluated by the cell counting kit 8 (CCK8), EdU assay, and western blotting [proliferating cell nuclear antigen (PCNA) and Cyclin D1]. Osteoblasts were cultured in an osteogenic induction medium for 1–3 weeks after which their differentiations were assessed by alkaline phosphatase (ALP) staining, Alizarin Red staining, calcium concentration, immunocytochemistry staining, real-time quantitative PCR (RT-qPCR), and immunofluorescence staining. The osteogenesis-associated mechanisms were further evaluated by western blotting using appropriate antibodies. Results. Relative to the control group, IL-1β induced the rapid proliferation of osteoblasts and suppressed their osteogenic differentiations by upregulating the activities of MEK-Erk1/2 as well as Jak-Stat3 pathways and by elevating MMP13 and MMP9 levels. However, blocking of the MEK-Erk1/2 signaling pathway by GDC0623 treatment reversed these effects. Conclusion. Inhibition of Jak-Stat3 pathway by C188-9 downregulated the expression levels of MMP9 and MMP13, activated MEK-Erk1/2 pathway, and inhibited osteogenic differentiation.

In recent years, bone repair biomaterials that combine cells and bioactive factors are superior to autologous and allogeneic bone implants. However, neither natural nor synthetic biomaterials can possess all desired qualities such as strength, porosity, and biological activity. In this study, we used poly (glycerol sebacate) (PGS), a synthetic material with great osteogenic potential that has attracted more attention in the field of tissue (such as bone tissue) regeneration owing to its good biocompatibility and high elasticity. It also has the advantage of being regulated by material synthesis to match the bone tissue's strength and can be easily modified to become functional. However, pure PGS lacks functional groups and hydrophilicity. Therefore, we used PGS as the substrate to graft the adhesive ligands RGD and vascular endothelial growth factor mimetic peptide. The bone repair scaffold can be prepared through photo crosslinking, as it not only improves hydrophobicity but also promotes vascularization and accelerates osteogenesis. Simultaneously, we improved the preparation method of hydrogels after freeze-drying and crosslinking to form a sponge-like structure and to easily regenerate blood vessels. In summary, a bone repair scaffold was prepared to meet the structural and biological requirements. It proved to serve as a potential bone-mimicking scaffold by enhancing tissue regenerative processes such as cell infiltration and vascularization and subsequent replacement by the native bone tissue.

Abstract Introduction Numerous treatments suggest that brain plasticity changes after peripheral nerve injury (PNI), and most studies examining functional magnetic resonance imaging focused on abnormal changes in specific brain regions. However, it is the large‐scale interaction of neuronal networks instead of isolated brain regions contributed to the functional recovery after PNI. In the present study, we examined the intra‐ and internetworks alterations between the related functional resting‐state networks (RSNs) in a sciatic nerve injury rat model. Methods Ninety‐six female rats were divided into a control and model group. Unilateral sciatic nerve transection and direct anastomosis were performed in the latter group. We used an independent component analysis (ICA) algorithm to observe the changes in RSNs and assessed functional connectivity between different networks using the functional networks connectivity (FNC) toolbox. Results Six RSNs related to PNI were identified, including the basal ganglia network (BGN), sensorimotor network (SMN), salience network (SN), interoceptive network (IN), cerebellar network (CN), and default mode network (DMN). The model group showed significant changes in whole‐brain FC changes within these resting‐state networks (RSNs), but four of these RSNs exhibited a conspicuous decrease. The interalterations performed that significantly decreased FNC existed between the BGN and SMN, BGN and IN, and BGN and DMN (p

Objective: The present study aimed to investigate the analgesic effect of electroacupuncture (EA) in neuropathic pain due to brachial plexus avulsion injury (BPAI) and related changes in the metabolic brain connectivity.Methods: Neuropathic pain model due to BPAI was established in adult female Sprague–Dawley rats. EA stimulations (2/15 Hz, 30 min/day, 5-day intervention followed by 2-day rest in each session) were applied to the fifth–seventh cervical “Jiaji” acupoints on the noninjured side from 1st to 12th weeks following BPAI (EA group, n = 8). Three control groups included sham EA (nonelectrical acupuncture applied to 3 mm lateral to the real “Jiaji” acupoints), BPAI-only, and normal rats (no particular intervention; eight rats in each group). Thermal withdrawal latency (TWL) of the noninjured forepaw was regularly tested to evaluate the threshold of thermalgesia. Small animal [fluorine-18]-fluoro-2-deoxy-D-glucose (18F-FDG) PET/CT scans of brain were conducted at the end of 4th, 12th, and 16th weeks to explore metabolic alterations of brain.Results: In the EA group, the TWL of the noninjured forepaw significantly decreased following BPAI and then increased following EA stimulation, compared with sham EA (P < 0.001). The metabolic brain connectivity among somatosensory cortex (SC), motor cortex (MC), caudate putamen (Cpu), and dorsolateral thalamus (DLT) in bilateral hemispheres decreased throughout the 16 weeks’ observation in the BPAI-only group, compared with the normal rats (P < 0.05). In the EA group, the strength of connectivity among the above regions were found to be increased at the end of 4th week following BPAI modeling, decreased at 12th week, and then increased again at 16th week (P < 0.05). The changes in metabolic connectivity were uncharacteristic and dispersed in the sham EA group.Conclusion: The study revealed long-term and extensive changes of metabolic brain connectivity in EA-treated BPAI-induced neuropathic pain rats. Bilateral sensorimotor and pain-related brain regions were mainly involved in this process. It indicated that modulation of brain metabolic connectivity might be an important mechanism of analgesic effect in EA stimulation for the treatment of neuropathic pain.

Background. Neuropathic pain after brachial plexus avulsion remained prevalent and intractable currently. However, the neuroimaging study about neural mechanisms or etiology was limited and blurred. Objective. This study is aimed at investigating the effect of electroacupuncture on effective connectivity and neural response in corticolimbic circuitries during implicit processing of nociceptive stimulus in rats with brachial plexus pain. Methods. An fMRI scan was performed in a total of 16 rats with brachial plexus pain, which was equally distributed into the model group and the electroacupuncture group. The analysis of task-dependent data determined pain-related activation in each group. Based on those results, several regions including AMY, S1, and h were recruited as ROI in dynamic causal modeling (DCM) analysis comparing evidence for different neuronal hypotheses describing the propagation of noxious stimuli in regions of interest and horizontal comparison of effective connections between the model and electroacupuncture groups. Results. In both groups, DCM revealed that noxious stimuli were most likely driven by the somatosensory cortex, with bidirectional propagation with the hypothalamus and amygdala and the interactions in them. Also, the 3-month intervention of acupuncture reduced effective connections of h-S1 and AMY-S1. Conclusions. We showed an evidence that a full connection model within the brain network of brachial plexus pain and electroacupuncture intervention reduces effective connectivity from h and AMY to S1. Our study for the first time explored the relationship of involved brain regions with dynamic causal modeling. It provided novel evidence for the feature of the organization of the cortical-limbic network and the alteration caused by acupuncture.

Abstract Central neurologic injury (CNI) causes dysfunctions not only in limbs but also in cognitive ability. We applied a novel peripheral nerve rewiring (PNR) surgical procedure to restore limb function. Here, we conducted a prospective study to develop estimates for the extent of preattentive processes to cognitive function changes in CNI patients after PNR. Auditory mismatch negativity (MMN) was measured in CNI patients who received the PNR surgery plus conventional rehabilitation treatment. During the 2-year follow-up, the MMN was enhanced with increased amplitude in the PNR plus rehabilitation group compared to the rehabilitation-only group as the experiment progressed, and progressive improvement in behavioural examination tests was also observed. Furthermore, we found a significant correlation between the changes in Fugl-Meyer assessment scale scores and in MMN amplitudes. These results suggested that PNR could affect the efficiency of pre-attention information processing synchronously with the recovery of motor function in the paralyzed arm of the in chronic CNI patients. Such electroencephalographic measures might provide a biological approach with which to distinguish patient subgroups after surgery, and the change in MMN may serve as an objective auxiliary index, indicating the degree of motor recovery and brain cognitive function.

Objective. Facial synkinesis is a severe sequelae of facial nerve malfunction. Once the synkinesis is established, it is extremely difficult for patients to recover. Given that the restoration of motor or sensory function after peripheral nerve injury was closely related with cortical plasticity, we investigated cortical plasticity in facial synkinesis patients by the frequency-specific data which remains largely uncharacterized. Materials and Methods. Resting-state fMRI was conducted in 20 facial synkinesis patients and 19 healthy controls, and the amplitude of low-frequency fluctuation (ALFF) in five different frequency bands (slow-6: 0-0.01 Hz; slow-5: 0.01-0.027 Hz; slow-4: 0.027-0.073 Hz; slow-3: 0.073-0.167 Hz; and slow-2: 0.167-0.25 Hz) was calculated, respectively. And the relationship between ALFF and clinical outcomes was also analyzed. Results. Comparing with the healthy controls, facial synkinesis patients showed significantly different ALFF values, mainly in the sensorimotor areas. Furthermore, increased ALFF of the ipsilateral insula in the slow-6 band was significantly related with better facial nerve function. Conclusion. Increased ALFF values in the ipsilateral insula might reflect an abnormal state of hypercompensation in motor control of facial synkinesis patients. It provided valuable spatial information about the functionally aberrant regions, which implied the possible involvement of motor control system in facial synkinesis.

Objective. Neuropathic pain after brachial plexus injury remains an increasingly prevalent and intractable disease due to inadequacy of satisfactory treatment strategies. A detailed mapping of cortical regions concerning the brain plasticity was the first step of therapeutic intervention. However, the specific mapping research of brachial plexus pain was limited. We aimed to provide some localization information about the brain plasticity changes after brachial plexus pain in this preliminary study. Methods. 24 Sprague-Dawley rats received complete brachial plexus avulsion with neuropathic pain on the right forelimb successfully. Through functional imaging of both resting-state and block-design studies, we compared the amplitude of low-frequency fluctuations (ALFF) of premodeling and postmodeling groups and the changes of brain activation when applying sensory stimulation. Results. The postmodeling group showed significant decreases on the mechanical withdrawal threshold (MWT) in the bilateral hindpaws and thermal withdrawal latency (TWL) in the left hindpaw than the premodeling group (P

Although some patients have successful peripheral nerve regeneration, a poor recovery of hand function often occurs after peripheral nerve injury. It is believed that the capability of brain plasticity is crucial for the recovery of hand function. The supplementary motor area may play a key role in brain remodeling after peripheral nerve injury. In this study, we explored the activation mode of the supplementary motor area during a motor imagery task. We investigated the plasticity of the central nervous system after brachial plexus injury, using the motor imagery task. Results from functional magnetic resonance imaging showed that after brachial plexus injury, the motor imagery task for the affected limbs of the patients triggered no obvious activation of bilateral supplementary motor areas. This result indicates that it is difficult to excite the supplementary motor areas of brachial plexus injury patients during a motor imagery task, thereby impacting brain remodeling. Deactivation of the supplementary motor area is likely to be a serious problem for brachial plexus injury patients in terms of preparing, initiating and executing certain movements, which may be partly responsible for the unsatisfactory clinical recovery of hand function.

In this paper, we designed a hemiplegic upper limb rehabilitation training system, which allowed both single degree of freedom and composite degrees of freedom for the training of shoulder and elbow. The system contained an upper limb rehabilitation robot, a pattern recognition system and a motion control system. Firstly, we designed a novel upper limb rehabilitation robot with three degrees of freedom, with the motor and reducer innovatively placed centrally in the shoulder of the mechanical limb arm. The movement is more stable because the inertia of each joint movement is reduced. The design makes simultaneously training both the left and right arm possible. In the control system design, the movement coupling problem is solved through the inverse operation of the target action. Lastly, to further enrich information of the single feature vector, a method integrating the AR model coefficients and wavelet coefficients was proposed. A method combining the Particle Swarm Optimization Algorithm and Levenberg-Marquardt (LM) was used to optimize the BP networks, addressing the problems associated with lower convergence speed and local minimum of standard BP networks. The experiments showed that the convergence speed of the network and the recognition rate of the target action were effectively improved, which demonstrated the effectiveness of the training system.