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Background Manipulation of neural stem and progenitor cells (NSPCs) is critical for the successful treatment of spinal cord injury (SCI) by NSPC transplantation, since their differentiation into neurons and oligodendrocytes can be inhibited by factors present in inflamed myelin. In this study, we examined the effects of LINGO-1 on spinal cord-derived NSPC (sp-NSPC) differentiation, the underlying mechanisms of action, and the functional recovery of mice after transplantation of manipulated cells. Methods sp-NSPCs were harvested from female adult C57/BL6 mice after SCI induced with an NYU impactor. These cells were infected with lentiviral vectors containing LINGO-1 shRNA sequence or a scrambled control and transplanted into SCI mice. Tuj-1- and GFAP-positive cells were assessed by immunofluorescence staining. Wnt5a, p-JNK, JNK, and β-catenin expression was determined by Western blot and RT-qPCR. miRNAs were sequenced to detect changes in miRNA expression. Motor function was evaluated 0–35 days post-surgery by means of the Basso Mouse Scale (BMS) and by the rotarod performance test. Results We discovered that LINGO-1 shRNA increased neuronal differentiation of sp-NSPCs while decreasing astrocyte differentiation. These effects were accompanied by elevated Wnt5a protein expression, but unexpectedly, no changes in Wnt5a mRNA levels. miRNA-sequence analysis demonstrated that miR-15b-3p was a downstream mediator of LINGO-1 which suppressed Wnt5a expression. Transplantation of LINGO-1 shRNA-treated sp-NSPCs into SCI mice promoted neural differentiation, wound compaction, and motor function recovery. Conclusions LINGO-1 shRNA promotes neural differentiation of sp-NSPCs and Wnt5a expression, probably by downregulating miR-15b-3p. Transplantation of LINGO-1 shRNA-treated NSPCs promotes recovery of motor function after SCI, highlighting its potential as a target for SCI treatment.

Introduction Central poststroke pain (CPSP) develops commonly after stroke, which impairs the quality of life, mood, and social functioning. Current pharmacological approaches for the treatment of CPSP are not satisfactory. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique which has been recommended for the treatment of chronic CPSP. However, few studies have evaluated the analgesic effects of rTMS in patients with acute neuropathic pain after stroke. Methods We evaluated the analgesic effects of rTMS applied over the upper extremity area of the motor cortex (M1) in patients with acute CPSP. Forty patients were randomized to receive either rTMS (10 Hz, 2000 stimuli) (n = 20) or a sham intervention (n = 20) for 3 weeks. The Numeric Rating Scale (NRS), Short-form McGill Pain Questionnaire-2 (SF-MPQ-2, Chinese version), Hamilton Anxiety Scale (HAM-A), Hamilton Depression Scale (HAM-D), brain-derived neurotrophic factor (BDNF) levels, and motor-evoked potentials (MEP) were analyzed at baseline, 3 days, 1 week, 2 weeks, and 3 weeks. Results Significant treatment–time interactions were found for pain intensity. Compared with the sham group, the NRS and SF-MPQ-2 scores were significantly lower on the seventh day of treatment in the rTMS group (P

We used a murine spontaneous osteosarcoma cell line with high metastatic potential, the K7M2 cell line to study the role of Notch signaling in the biological manifestations of osteosarcoma, to understand its underlying mechanism in the regulation of cell proliferation and migration, and to improve patient prognosis in cases of osteosarcoma through the discovery of novel therapeutic targets, First, Notch expression in K7M2 was determined by immunostaining, and the γ-secretase inhibitor N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) was used to inhibit proteolytic cleavage of the Notch intracellular domain (NICD), resulting in the inhibition of Notch activation. By using the Sulforhodamine B assay, colony-forming units assay, Brdu and Ki67 staining, and flow cytometry assays of apoptosis and cell cycle stage, DAPT was found to inhibit K7M2 proliferation in a dose-dependent manner. By using wound healing and transwell migration assays, DAPT was found to inhibit K7M2 migration in a dose-dependent manner as well. By using a combination of micro-Raman spectroscopy and K-means clustering analysis, we found that DAPT inhibit a variety of important cell metabolism-related components in most K7M2 cell structures. Then, DAPT was found to inhibit Notch1ICD expression in a concentration-dependent manner, and this expression was directly correlated with Phospho-Erk1/2 (p-Erk) by using Western blotting. To confirm this finding, we used the Notch signaling ligand Jagged1 to activate the Notch signaling pathway, which in turn up-regulated p-Erk, resulting in increased proliferation and migration of K7M2. Using the Erk pathway inhibitor U0126, we showed that p-Erk was downregulated and the proliferation and migration of K7M2 decreased along with it. Finally, we constructed a K7M2 mouse para-tibial tumor model and lung metastatic model. We found DAPT inhibits p-Erk in vivo, effectively controls tumor growth, reduces angiogenesis, reduces metastasis to the lungs, and improves overall survival. In summary, Notch signaling plays an oncogene role and promotes metastasis in osteosarcoma through p-Erk. DAPT effectively inhibits osteosarcoma proliferation and metastasis in vivo and in vitro by inhibiting Erk phosphorylation. Therefore, the inhibition of Notch activation resulted the down-regulation of phosphorylation of Erk pathway can be used as potential therapeutic targets in clinical treatment to improve osteosarcoma prognosis.

It is essential to make sure patients be actively involved in motor training using robot-assisted rehabilitation to achieve better rehabilitation outcomes. This paper introduces an attention-controlled wrist rehabilitation method using a low-cost EEG sensor. Active rehabilitation training is realized using a threshold of the attention level measured by the low-cost EEG sensor as a switch for a flexible wrist exoskeleton assisting wrist flexion/extension and radial/ulnar deviation. We present a prototype implementation of this active training method and provide a preliminary evaluation. The feasibility of the attention-based control was proven with the overall actuation success rate of 95%. The experimental results also proved that the visual guidance was helpful for the users to concentrate on the wrist rehabilitation training: two types of visual guidance, namely, looking at the hand motion shown on a video and looking at the user's own hand had no significant performance difference. A general threshold of a certain group of users can be utilized in the wrist robot control rather than a customized threshold to simplify the procedure.

Objectives Central neuropathic pain (CNP) often appears following spinal cord injury (SCI), but current treatments are not always successful. In this study, we evaluated the analgesic effects of repetitive transcranial magnetic stimulation (rTMS) applied over the hand area of the motor cortex in patients with acute CNP after SCI. Methods A total of 48 patients with complete or incomplete SCI and acute CNP participated in this study and were randomized to receive either rTMS (10 Hz, 1,500 stimuli; N = 24) or a sham intervention (N = 24) for three weeks. The numeric rating scale (NRS) and Short-Form McGill Pain Questionnaire-2 (Chinese Edition; SF-MPQ-2-CN) were analyzed to assess the degree of pain. Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were collected to explore expression influenced by rTMS. Motor-evoked potential (MEP) latency and maximal amplitude were measured to determine neurophysiological changes. The assessments were carried out at baseline (T0), three days (T1), one week (T2), two weeks (T3), and three weeks (T4) after onset of treatment. Results The analysis showed significant treatment–time interactions for the quality and intensity of pain, as measured by NRS (P < 0.001, η2 = 0.441) and SF-MPQ-2 (P < 0.001, η2 = 0.590). Compared with the sham group, the NRS and SF-MPQ2-CN scores were significantly lower on the third day (P < 0.001, Cohen’s d = 1.135; P = 0.006, Cohen’s d = 0.616) and after one week (P < 0.001, Cohen’s d = 0.846; P = 0.012, Cohen’s d = 0.557) of treatment. In addition, the serum levels of BDNF and NGF were significantly higher in the treated group after three weeks (P = 0.015, Cohen’s d = 0.539; P = 0.009, Cohen’s d = 0.580), and the MEP amplitude increased by 109.59% (P = 0.033, Cohen’s d = 0.464). Conclusions These findings indicate that 10 Hz rTMS over the hand area of the motor cortex could alleviate acute CNP in the early phase of SCI and could enhance MEP parameters and modulate BDNF and NGF secretion.

Cervical degenerative disease is one of the most common spinal disorders worldwide, especially in older people. Anterior cervical corpectomy and fusion (ACCF) is a useful method for the surgical treatment of multi-level cervical degenerative disease. Anterior cervical disc replacement (ACDR) is considered as an alternative surgical method. However, both methods have drawbacks, particularly the neck motion decrease observed after arthrodesis, and arthroplasty should only be performed on patients presenting with cervical disc disease but without any vertebral body disease. Therefore, we designed a non-fusion cervical joint system, namely an artificial cervical vertebra and intervertebral complex (ACVC), to provide a novel treatment for multi-level cervical degenerative disease. To enhance the long-term stability of ACVC, we applied a hydroxyapatite (HA) biocoating on the surface of the artificial joint. Thirty-two goats were randomly divided into four groups: a sham control group, an ACVC group, an ACVC-HA group, and an ACCF group (titanium and plate fixation group). We performed the prosthesis implantation in our previously established goat model. We compared the clinical, radiological, biomechanical, and histological outcomes among these four different groups for 24 weeks post surgery. The goats successfully tolerated the entire experimental procedure. The kinematics data for the ACVC and ACVC-HA groups were similar. The range of motion (ROM) in adjacent level increased after ACCF but was not altered after ACVC or ACVC-HA implantation. Compared with the control group, no significant difference was found in ROM and neutral zone (NZ) in flexion-extension or lateral bending for the ACVC and ACVC-HA groups, whereas the ROM and NZ in rotation were significantly greater. Compared with the ACCF group, the ROM and NZ significantly increased in all directions. Overall, stiffness was significantly decreased in the ACVC and ACVC-HA groups compared with the control group and the ACCF group. Similar results were found after a fatigue test of 5,000 repetitions of axial rotation. The histological results showed more new bone formation and better bone implant contact in the ACVC-HA group than the ACVC group. Goat is an excellent animal model for cervical spine biomechanical study. Compared with the intact state and the ACCF group, ACVC could provide immediate stability and preserve segmental movement after discectomy and corpectomy. Besides, HA biocoating provide a better bone ingrowth, which is essential for long-term stability. In conclusion, ACVC-HA brings new insight to treat cervical degenerative disease.

Dual-task performance is strongly affected by the direction of attentional focus. This study investigated neural control of a postural–suprapostural procedure when postural focus strategy varied. Twelve adults concurrently conducted force-matching and maintained stabilometer stance with visual feedback on ankle movement (visual internal focus, VIF) and on stabilometer movement (visual external focus, VEF). Force-matching error, dynamics of ankle and stabilometer movements, and event-related potentials (ERPs) were registered. Postural control with VEF caused superior force-matching performance, more complex ankle movement, and stronger kinematic coupling between the ankle and stabilometer movements than postural control with VIF. The postural focus strategy also altered ERP temporal-spatial patterns. Postural control with VEF resulted in later N1 with less negativity around the bilateral fronto-central and contralateral sensorimotor areas, earlier P2 deflection with more positivity around the bilateral fronto-central and ipsilateral temporal areas, and late movement-related potential commencing in the left frontal-central area, as compared with postural control with VIF. The time–frequency distribution of the ERP principal component revealed phase-locked neural oscillations in the delta (1–4 Hz), theta (4–7 Hz), and beta (13–35 Hz) rhythms. The delta and theta rhythms were more pronounced prior to the timing of P2 positive deflection, and beta rebound was greater after the completion of force-matching in VEF condition than VIF condition. This study is the first to reveal the neural correlation of postural focusing effect on a postural–suprapostural task. Postural control with VEF takes advantage of efficient task-switching to facilitate autonomous postural response, in agreement with the “constrained-action” hypothesis.

Resection of the odontoid process and anterior arch of the atlas results in atlantoaxial instability, which if left uncorrected may lead to severe neurological complications. Currently, such atlantoaxial instability is corrected by anterior and/or posterior C1–C2 fusion. However, this results in considerable loss of rotation function of the atlantoaxial complex. From the viewpoint of retaining the rotation function and providing stability, we designed an artificial atlanto-odontoid joint based on anatomical measurements of 50 pairs of dry atlantoaxial specimens by digital calipers and 10 fresh cadaveric specimens by microsurgical techniques. The metal-on-metal titanium alloy joint has an arc-shaped atlas component, and a hollow cylindrical bushing into which fits a rotation axle of an inverted v-shaped axis component and is implanted through a transoral approach. After the joint was implanted onto specimens with anterior decompression, biomechanical tests were performed to compare the stability parameters in the intact state, after decompression, after artificial joint replacement, and after fatigue test. Compared to the intact state, artificial joint replacement resulted in a significant decrease in the range of motion (ROM) and neutral zone (NZ) during flexion, extension, and lateral bending (P

BackgroudGluteal muscle contracture (GMC) is a multi-factor human chronic fibrotic disease of the gluteal muscle. Fibrotic tissue is characterized by excessive accumulation of collagen in the muscle's extracellular matrix. Transforming growth factor (TGF)-β1 and -β2 are thought to play an important role in fibrogenesis, while TGF-β3 is believed to have an anti-fibrotic function. We hypothesize that the expression of collagen and TGF-βs would be up-regulated in GMC patients.MethodsThe expression of collagen type I, type III and TGF-βs were studied in 23 fibrotic samples and 23 normal/control samples in GMC patients using immunohistochemistry, reverse transcription and polymerase chain reaction (RT-PCR) and western bolt analysis.ResultsCompared to the unaffected adjacent muscle, increased expression of TGF-β1 and -β3 was associated with deposition of collagen type I and type III in the fibrotic muscle of the GMC patients at the mRNA level. Strong up-regulation of these proteins in fibrotic muscle was confirmed by immunohistochemical staining and western blot analysis. TGF-β2 was not up-regulated in relation to GMC.ConclusionThis study confirmed our hypothesis that collagen types I, III, TGF-β1 and TGF-β3 were up-regulated in biopsy specimens obtained from patients with GMC. Complex interaction of TGF-β1 with profibrotic function and TGF-β3 with antifibrotic function may increase synthesis of collagens and thereby significantly contribute to the process of gluteal muscle scarring in patients with GMC.

Study Design. An in vitro biomechanical study. Objective. To determine the initial stability and function of a new artificial joint in a cadaveric cervical spine model by comparing it with a conventional method. Summary of Background Data. Resection of the odontoid and anterior arch of the atlas results in atlantoaxial instability, which if left uncorrected may lead to severe neurologic complications. Currently, such atlantoaxial instability is corrected by anterior and/or posterior C1–C2 fusion. Methods. There were 24 fresh human cadaveric cervical spines (C0–C3) randomly divided into 2 groups: group 1, resection of the odontoid with artificial atlanto-odontoid joint (AAOJ); and group 2, resection of the odontoid with Harms anterior atlantoaxial plate (Harms). For each specimen, the intact and resection of the odontoid underwent a flexibility test first, followed by the instrumented construct. Rotational angles of the C0–C3 segment were measured to study the immediate stability and function of resection of the odontoid and AAOJ, compared with the intact and resection of the odontoid and Harms. Results. Compared with the intact state, resection of the odontoid and AAOJ resulted in a significant decrease in the range of motion (ROM) and neutral zone during flexion, extension, and lateral bending (P 0.05). Compared with resection of the odontoid and Harms, resection of the odontoid and AAOJ during flexion, extension, and lateral bending, there was no significant difference in ROM (P > 0.05). Conclusion. We have designed a new type of AAOJ for correcting atlantoaxial instability arising from C1 to C2 anterior decompression procedures. The unique aspect of this joint is that it restores, to a great extent, the C1–C2 axial rotation that is lost during current stabilization procedures.

Background Gluteal muscle contracture (GMC) is a clinical syndrome due to multiple etiologies in which hip movements may be severely limited. The aim of this study was to propose a detailed classification of GMC and evaluate the statistical association between outcomes of different management and patient conditions. Methods One hundred fifty-eight patients, who were treated between January 1995 and December 2004, were reviewed at a mean duration of follow-up of 4.8 years. Statistical analyses were performed using X2 and Fisher's exact tests. Results Non-operative management (NOM), as a primary treatment, was effective in 19 of 49 patients (38.8%), while operative management was effective in all 129 patients, with an excellence rating of 83.7% (108/129). The outcome of NOM in level I patients was significantly higher than in level II and III patients (P < 0.05). The results of NOM and operative management in the child group were better than the adolescent group (P < 0.05). Complications in level III were more than in level II. Conclusion NOM was more effective in level I patients than in level II and III patients. Operative management was effective in patients at all levels, with no statistical differences between levels or types. We recommend NOM as primary treatment for level I patients and operative management for level II and III patients. Either NOM or operative management should be carried out as early as possible.