The enhanced connectivity between the frontoparietal, somatomotor network and thalamus as the most significant network changes of chronic low back pain.

The prolonged duration of chronic low back pain (cLBP) inevitably leads to changes in the cognitive, attentional, sensory and emotional processing brain regions. Currently, it remains unclear how these alterations are manifested in the interplay between brain functional and structural networks. This study aimed to predict the Oswestry Disability Index (ODI) in cLBP patients using multimodal brain magnetic resonance imaging (MRI) data and identified the most significant features within the multimodal networks to aid in distinguishing patients from healthy controls (HCs). We constructed dynamic functional connectivity (dFC) and structural connectivity (SC) networks for all participants (n = 112) and employed the Connectome-based Predictive Modeling (CPM) approach to predict ODI scores, utilizing various feature selection thresholds to identify the most significant network change features in dFC and SC outcomes. Subsequently, we utilized these significant features for optimal classifier selection and the integration of multimodal features. The results revealed enhanced connectivity among the frontoparietal network (FPN), somatomotor network (SMN) and thalamus in cLBP patients compared to HCs. The thalamus transmits pain-related sensations and emotions to the cortical areas through the dorsolateral prefrontal cortex (dlPFC) and primary somatosensory cortex (SI), leading to alterations in whole-brain network functionality and structure. Regarding the model selection for the classifier, we found that Support Vector Machine (SVM) best fit these significant network features. The combined model based on dFC and SC features significantly improved classification performance between cLBP patients and HCs (AUC=0.9772). Finally, the results from an external validation set support our hypotheses and provide insights into the potential applicability of the model in real-world scenarios. Our discovery of enhanced connectivity between the thalamus and both the dlPFC (FPN) and SI (SMN) provides a valuable supplement to prior research on cLBP.

Hoffmann's sign in cervical spondylotic myelopathy patients: pathological insights from neuroimaging.

OBJECTIVE: Hoffmann's sign testing is a commonly used physical examination in clinical practice for patients with cervical spondylotic myelopathy (CSM). However, the pathophysiological mechanisms underlying its occurrence and development have not been thoroughly investigated. Therefore, the present study aimed to explore whether a positive Hoffmann's sign (PHS) in CSM patients is associated with spinal cord and brain remodeling and to identify potential neuroimaging biomarkers with diagnostic value. METHODS: Seventy-six patients with CSM and 40 sex- and age-matched healthy controls (HCs) underwent multimodal MRI. Based on the results of the Hoffmann's sign examination, patients were divided into two groups: those with a PHS (n = 38) and those with a negative Hoffmann's sign (NHS; n = 38). Quantification of spinal cord and brain structural and functional parameters of the participants was performed using various methods, including functional connectivity analysis, voxel-based morphometry, and atlas-based analysis based on functional MRI and structural MRI data. Furthermore, this study conducted a correlation analysis between neuroimaging metrics and neurological function and utilized a support vector machine (SVM) algorithm for the classification of PHS and NHS. RESULTS: In comparison with the NHS and HC groups, PHS patients exhibited significant reductions in the cross-sectional area and fractional anisotropy (FA) of the lateral corticospinal tract (CST), reticulospinal tract (RST), and fasciculus cuneatus, concomitant with bilateral reductions in the volume of the lateral pallidum. The functional connectivity analysis indicated a reduction in functional connectivity between the left lateral pallidum and the right angular gyrus in the PHS group. The correlation analysis indicated a significant positive association between the CST and RST FA and the volume of the left lateral pallidum in PHS patients. Furthermore, all three variables exhibited a positive correlation with the patients' motor function. Finally, using multimodal neuroimaging metrics in conjunction with the SVM algorithm, PHS and NHS were classified with an accuracy rate of 85.53%. CONCLUSIONS: This research revealed a correlation between structural damage to the pallidum and RST and the presence of Hoffmann's sign as well as the motor function in patients with CSM. Features based on neuroimaging indicators have the potential to serve as biomarkers for assessing the extent of neuronal damage in CSM patients.

Bone mesenchymal stem cell-conditioned medium attenuates the effect of oxidative stress injury on NSCs by inhibiting the Notch1 signaling pathway.

Numerous studies have demonstrated the therapeutic effect of bone mesenchymal stem cells on spinal cord injury (SCI), especially on neural stem cells (NSCs). However, the predominant mechanisms of bone mesenchymal stem cells (BMSCs) are unclear. Recently, some researchers have found that paracrine signaling plays a key role in the therapeutic capacity of BMSCs and emphasized that the protective effect of BMSCs may be due to paracrine factors. In this study, we aimed to investigate the potential mechanisms of BMSCs to protect NSCs. NSCs were identified by immunocytochemistry. The oxidative stress environment was simulated by H2 O2 (50, 100, 200 µM) for 2 h. The apoptotic rate of the NSCs was detected via flow cytometry. Lactate dehydrogenase (LDH), malondialdehyde (MDA), and superoxide dismutase (SOD) activity were evaluated via corresponding assay kits. Western blot was used to detect the expressions of Notch1, HES1, caspase-3, cleave caspase-3, Bax, and Bcl-2. We found that H2 O2 could significantly induce the apoptosis of NSCs, increase LDH, MDA levels, and decrease SOD activity by activating the Notch1 signaling pathway. DAPT (the specific blocker of Notch1) and BMSC-conditioned medium (BMSC-CM) could significantly prevent the apoptotic effect and oxidative stress injury on NSCs that were treated with H2 O2 . We also revealed that BMSC-CM could decrease the expression of Notch1, Hes1, cleave caspase-3, Bax, and increases the expression of Bcl-2 in NSCs, which was induced by H2 O2 . These results have revealed that BMSC-CM can neutralize the effect against oxidative stress injury on the apoptosis of NSCs by inhibiting the Notch1 signaling pathway.

A preliminary study of 3.0-T magnetic resonance diffusion tensor imaging in cervical spondylotic myelopathy.

PURPOSE: To compare diffusion tensor imaging (DTI) parameters of the spinal cord between patients with cervical spondylotic myelopathy (CSM) and normal subjects, and investigate their significance in the clinical diagnosis, surgical planning and post-operative evaluation of CSM. METHODS: Routine sequence magnetic resonance imaging (MRI) and DTI scans were performed in 50 normal subjects and 60 cases of CSM with 3.0-T MR. DTI images, apparent diffusion coefficient (ADC) and fractional anisotropy (FA) colormaps corresponding to spinal cord cross-sections were obtained. The spinal cord function of CSM patients was measured using modified Japanese Orthopaedic Association (mJOA) scoring and Nurick grade at different times. The changes in DTI parameters and their correlation with spinal cord function scores were analysed by SPSS 19. RESULTS: There were significant differences in DTI parameters of the spinal cord between normal subjects and patients with CSM (ADC: 1.119 ± 0.087 vs. 1.395 ± 0.091, P < 0.01; FA: 0.661 ± 0.057 vs. 0.420 ± 0.080, P < 0.01). The FA values at the maximal compression level of the spinal cord in the patients with CSM were significantly associated with the mJOA score pre-operatively, 1 week, and 1, 3 and 6 months post-operatively, with Pearson's correlation coefficients of 0.58 (P < 0.01), 0.53 (P < 0.05), and 0.51 (P < 0.05), 0.54 (P < 0.05) and 0.55 (P < 0.05), respectively. However, the FA values were significantly negatively associated with the Nurick grade, with Pearson's correlation coefficients of - 0.40 (P < 0.05), - 0.39 (P < 0.05), and -0.41 (P < 0.05), - 0.45 (P < 0.05) and - 0.44 (P < 0.05), respectively. CONCLUSIONS: DTI may play a significant role in diagnosing and predicting the development of CSM. These slides can be retrieved under Electronic Supplementary Material.

Transplantation of Neural Stem Cells Loaded in an IGF-1 Bioactive Supramolecular Nanofiber Hydrogel for the Effective Treatment of Spinal Cord Injury.

Spinal cord injury (SCI) leads to massive cell death, disruption, and demyelination of axons, resulting in permanent motor and sensory dysfunctions. Stem cell transplantation is a promising therapy for SCI. However, owing to the poor microenvironment that develops following SCI, the bioactivities of these grafted stem cells are limited. Cell implantation combined with biomaterial therapies is widely studied for the development of tissue engineering technology. Herein, an insulin-like growth factor-1 (IGF-1)-bioactive supramolecular nanofiber hydrogel (IGF-1 gel) is synthesized that can activate IGF-1 downstream signaling, prevent the apoptosis of neural stem cells (NSCs), improve their proliferation, and induce their differentiation into neurons and oligodendrocytes. Moreover, implantation of NSCs carried out with IGF-1 gels promotes neurite outgrowth and myelin sheath regeneration at lesion sites following SCI. In addition, IGF-1 gels can enrich extracellular vesicles (EVs) derived from NSCs or from nerve cells differentiated from these NSCs via miRNAs related to axonal regeneration and remyelination, even in an inflammatory environment. These EVs are taken up by autologous endogenous NSCs and regulate their differentiation. This study provides adequate evidence that combined treatment with NSCs and IGF-1 gels is a potential therapeutic strategy for treating SCI.

Butterfly Vertebra: A Retrospective Study of 30 Patients.

BACKGROUND: Butterfly vertebra (BV) is a rare congenital spinal anomaly for which there is a paucity of large-scale retrospective studies and established guidelines for treatment. The objective of this study was to elucidate the clinical characteristics, imaging findings, and therapeutic approaches for BV. METHODS: We conducted a retrospective analysis of 30 patients diagnosed with BV at our hospital from 2009 to 2023, examining clinical data, imaging findings, and clinical interventions. RESULTS: The analysis comprised a cohort of 30 patients, consisting of 15 males and 15 females, with a mean age of 27.63 ± 19.84 years. Imaging studies indicated that the majority of vertebral bodies affected by BV were single-segmented (63.3%, 19/30) and less commonly multi-segmented (36.7%, 11/30). These findings frequently coexisted with other medical conditions, most notably spinal scoliosis (76.7%, 23/30). Furthermore, the study identified a range of spinal abnormalities among patients, including hemivertebral deformity (30.0%, 9/30), spinal cleft (10.0%, 3/30), lumbar disc protrusion or herniation (10.0%, 3/30), vertebral slippage (10.0%, 3/30), thoracic kyphosis deformity (6.67%, 2/30), vertebral fusion deformity (6.67%, 2/30), compressive fractures (3.3%, 1/30), and vertebral developmental anomalies (3.3%, 1/30). Clinical intervention resulted in symptom relief for 23 nonsurgical patients through lifestyle modifications, analgesic use, and physical therapy. Seven surgical patients underwent appropriate surgical procedures, leading to satisfaction and adherence to regular postoperative follow-up appointments. CONCLUSIONS: BV is a rare vertebral anomaly that can be easily misdiagnosed due to its similarity to other diseases. Consequently, it is imperative to enhance vigilance in the differential diagnosis process in order to promptly recognize BV. Furthermore, in cases where patients present with additional associated radiographic findings, a thorough evaluation is typically warranted and timely measures should be taken for treatment.

Contribution of changes in the spinal cord and brain to the onset and progression of hand clumsiness symptoms in cervical spondylotic myelopathy.

OBJECTIVE: Cervical spondylotic myelopathy (CSM) stands as the most prevalent form of spinal cord injury, frequently prompting various changes in both the brain and spinal cord. However, the precise nature of these changes within the brains and spinal cords of CSM patients experiencing hand clumsiness (HCL) symptoms has remained elusive. The authors aimed to scrutinize these alterations and explore potential links between these changes and the onset of HCL symptoms. METHODS: Using the modified Japanese Orthopaedic Association (mJOA) scale, the authors classified CSM patients into two groups: those without HCL and those with HCL. The authors performed voxel-wise z-score transformation amplitude of low-frequency fluctuations (zALFF) and resting-state functional connectivity (FC) evaluations in the brain. Additionally, they used the Spinal Cord Toolbox to calculate the fractional anisotropy (FA) of spinal cord tracts. The analysis also encompassed an examination of the correlation of these measures with improvements in mJOA scores. RESULTS: Significant disparities in zALFF values surfaced in the right calcarine, right cuneus, right precuneus, right middle occipital gyrus (MOG), right superior occipital gyrus (SOG), and right superior parietal gyrus (SPG) between healthy controls (HC), patients without HCL, and patients with HCL, primarily within the visual cortex. In the patient group, patients with HCL displayed reduced FC between the right calcarine, right MOG, right SOG, right SPG, right SFG, bilateral MFG, and left median cingulate and paracingulate gyri when compared with patients without HCL. Moreover, significant differences in FA values of the corticospinal tract (CST) and reticulospinal tract (REST) at the C2 level emerged among HC, patients without HCL, and patients with HCL. Notably, zALFF, FC, and FA values in specific brain regions and spinal cord tracts exhibited correlations with mJOA upper-extremity scores. Additionally, FA values of the CST and REST correlated with zALFF values in the right calcarine, right MOG, right SOG, and right SPG. CONCLUSIONS: Alterations within brain regions associated with the visual cortex, the fronto-parietal-occipital attention network, and spinal cord pathways appear to play a substantial role in the emergence and progression of HCL symptoms. Furthermore, the existence of a potential connection between the spinal cord and the brain suggests that this link might be related to the clinical symptoms of CSM.

Measurement of volume-occupying rate of cervical spinal canal and its role in cervical spondylotic myelopathy.

PURPOSE: To compare volume-occupying rate of cervical spinal canal between patients with cervical spondylotic myelopathy (CSM) and normal subjects, and to investigate its significance in cervical spine disease. METHODS: Spiral computed tomography (CT) scan (C4-C6 cervical spine unit) was performed in 20 normal subjects and 36 cases of CSM at a neutral position, and data were transferred to the Advantage Workstation Version 4.2 for assessment. Bony canal area and fibrous canal area in each cross section, and sagittal diameters of cervical spinal canal and cervical spinal body were measured. Volume-occupying rate of cervical spinal canal was calculated using MATLAB. Cervical spinal canal ratio and effective cervical spinal canal ratio were calculated, and Japanese Orthopaedic Association score was used to assess cervical spinal cord function. RESULTS: Volume-occupying rate of cervical spinal canal at a neutral position was significantly higher in CSM patients as compared to normal subjects (P < 0.01). There was no correlation between cervical spinal canal ratio and JOA score in CSM patients, with a Pearson's correlation coefficient of 0.171 (P > 0.05). However, sagittal diameter of secondary cervical spinal canal, effective cervical spinal canal ratio and volume-occupying rate of cervical spinal canal were significantly associated to JOA score, with Pearson's coefficient correlations of 0.439 (P < 0.05), 0.491 (P < 0.05) and -0.613 (P < 0.01), respectively. CONCLUSIONS: Volume-occupying rate of cervical spinal canal is an objective reflection of compression on cervical spine and spinal cord, and it is associated with cervical spinal cord function. These suggest that it may play a significant role in predicting the development of CSM.

Inflammation Modifies miR-21 Expression Within Neuronal Extracellular Vesicles to Regulate Remyelination Following Spinal Cord Injury.

Cell‒cell communication following spinal cord injury (SCI) plays a key role in remyelination and neurological recovery. Although communication between neuron-neural stem cells (NSCs) affects remyelination, its precise mechanism remains unclear. The present study investigated the biological effects of extracellular vesicles (EVs) derived from neurons on the differentiation of NSCs and the remyelination of axons in a rat model for SCI. We found that that EVs derived from neurons promoted the differentiation of NSCs into oligodendrocytes and the remyelination of axons in SCI rats. However, neuron-derived EVs lost their biological effects after inflammatory stimulation of these neurons from which they originate. Further analysis demonstrated that the inflammatory stimulation on neurons upregulated miR-21 within EVs, which targeted SMAD 7 and upregulated the TGF-ß/SMAD2 signaling pathway, resulting in an excess of astrocytic scar boundaries and in remyelination failure. Moreover, these effects could be abolished by miR-21 inhibitors/antagomirs. Considered together, these results indicate that inflammatory stimulation of neurons prevents remyelination following SCI via the upregulation of miR-21 expression within neuron-derived EVs, and this takes place through SMAD 7-mediated activation of the TGF-ß/SMAD2 signaling pathway. Graphical Astract.

Inflammatory stimulation of astrocytes affects the expression of miRNA-22-3p within NSCs-EVs regulating remyelination by targeting KDM3A.

BACKGROUND: Endogenous neural stem cells (NSCs) are critical for the remyelination of axons following spinal cord injury (SCI). Cell-cell communication plays a key role in the regulation of the differentiation of NSCs. Astrocytes act as immune cells that encounter early inflammation, forming a glial barrier to prevent the spread of destructive inflammation following SCI. In addition, the cytokines released from astrocytes participate in the regulation of the differentiation of NSCs. The aim of this study was to investigate the effects of cytokines released from inflammation-stimulated astrocytes on the differentiation of NSCs following SCI and to explore the influence of these cytokines on NSC-NSC communication. RESULTS: Lipopolysaccharide stimulation of astrocytes increased bone morphogenetic protein 2 (BMP2) release, which not only promoted the differentiation of NSCs into astrocytes and inhibited axon remyelination in SCI lesions but also enriched miRNA-22-3p within extracellular vesicles derived from NSCs. These miRNA-22 molecules function as a feedback loop to promote NSC differentiation into oligodendrocytes and the remyelination of axons following SCI by targeting KDM3A. CONCLUSIONS: This study revealed that by releasing BMP2, astrocytes were able to regulate the differentiation of NSCs and NSC-NSC communication by enriching miRNA-22 within NSC-EVs, which in turn promoted the regeneration and remyelination of axons by targeting the KDM3A/TGF-beta axis and the recovery of neurological outcomes following SCI.

Remodeling of the brain correlates with gait instability in cervical spondylotic myelopathy.

Introduction: Cervical spondylotic myelopathy (CSM) is a common form of non-traumatic spinal cord injury (SCI) and usually leads to remodeling of the brain and spinal cord. In CSM with gait instability, the remodeling of the brain and cervical spinal cord is unclear. We attempted to explore the remodeling of these patients' brains and spinal cords, as well as the relationship between the remodeling of the brain and spinal cord and gait instability. Methods: According to the CSM patients' gait, we divided patients into two groups: normal gait patients (nPT) and abnormal gait patients (aPT). Voxel-wise z-score transformation amplitude of low-frequency fluctuations (zALFF) and resting-state functional connectivity (rs-FC) were performed for estimating brain changes. Cross-sectional area (CSA) and fractional anisotropy (FA) of the spinal cord were computed by Spinal cord toolbox. Correlations of these measures and the modified Japanese Orthopedic Association (mJOA) score were analyzed. Results: We found that the zALFF of caudate nucleus in aPT was higher than that in healthy controls (HC) and lower than that in nPT. The zALFF of the right postcentral gyrus and paracentral lobule in HC was higher than those of aPT and nPT. Compared with the nPT, the aPT showed increased functional connectivity between the caudate nucleus and left angular gyrus, bilateral precuneus and bilateral posterior cingulate cortex (PCC), which constitute a vital section of the default mode network (DMN). No significantly different FA values or CSA of spinal tracts at the C2 level were observed between the HC, nPT and aPT groups. In CSM, the right paracentral lobule's zALFF was negatively correlated with the FA value of fasciculus gracilis (FCG), and the right caudate zALFF was positively correlated with the FA value of the fasciculus cuneatus (FCC). The results showed that the functional connectivity between the right caudate nucleus and DMN was negatively correlated with the CSA of the lateral corticospinal tract (CST). Discussion: The activation of the caudate nucleus and the strengthening functional connectivity between the caudate nucleus and DMN were associated with gait instability in CSM patients. Correlations between spinal cord and brain function might be related to the clinical symptoms in CSM.

Dysregulated neural activity between the thalamus and cerebral cortex mediates cortical reorganization in cervical spondylotic myelopathy.

Neuroimaging research has revealed significant changes in brain structure and function in patients with cervical spondylotic myelopathy(CSM). The thalamus plays a crucial role in this process, although its mechanisms of action remain incompletely understood. This study aimed to investigate whether spinal cord compression leads to alterations in the functional connectivity between the thalamus and the cerebral cortex, and to determine if such changes are associated with structural and functional remodeling of the brain in patients with CSM, and to identify potential neuroimaging biomarkers for classification. The study included 40 patients with CSM and 34 healthy controls(HCs) who underwent resting-state functional magnetic resonance imaging(fMRI) and structural MRI scans. Brain structural and functional metrics were quantified using functional connectivity(FC), fractional amplitude of low-frequency fluctuations(fALFF), surface-based morphometry(SBM), and independent component analysis(ICA) based on functional and structural MRI. Patients with CSM exhibited significantly reduced fALFF in the bilateral lateral lingual gyrus, bilateral calcarine fissure, left precentral gyrus and postcentral gyrus, left middle and superior occipital gyrus, left superior marginal gyrus, left inferior parietal gyrus, and right Rolandic operculum. ICA results revealed weakened functional connectivity between the sensorimotor network (SMN) and the left and right frontoparietal network(FPN), and lateral visual network (lVN), along with decreased connectivity between lVN and rFPN, and increased connectivity between lFPN and rFPN. Patients with CSM also had decreased sulcus depth in the bilateral insula, left precentral and postcentral gyrus, and right lingual gyrus and calcarine fissure. Furthermore, cervical spondylotic myelopathy patients showed decreased functional connectivity between the left ventral posterolateral nucleus (VPL) of the thalamus and the right middle occipital gyrus (MOG). Finally,multimodal neuroimaging with support vector machine(SVM) classified patients with CSM and healthy controls with 86.00% accuracy. Our study revealed that the decrease in functional connectivity between the thalamus and cortex mediated by spinal cord compression leads to structural and functional reorganization of the cortex. Features based on neuroimaging markers have the potential to become neuroimaging biomarkers for CSM.

Micro-RNA let-7a-5p Derived From Mesenchymal Stem Cell-Derived Extracellular Vesicles Promotes the Regrowth of Neurons in Spinal-Cord-Injured Rats by Targeting the HMGA2/SMAD2 Axis.

Spinal cord injury (SCI) often causes neuronal and axonal damage, resulting in permanent neurological impairments. Mesenchymal stem cells (MSCs) and extracellular vesicles (EVs) are promising treatments for SCI. However, the underlying mechanisms remain unclear. Herein, we demonstrated that EVs from bone marrow-derived MSCs promoted the differentiation of neural stem cells (NSCs) into the neurons and outgrowth of neurites that are extending into astrocytic scars in SCI rats. Further study found that let-7a-5p exerted a similar biological effect as MSC-EVs in regulating the differentiation of NSCs and leading to neurological improvement in SCI rats. Moreover, these MSC-EV-induced effects were attenuated by let-7a-5p inhibitors/antagomirs. When investigating the mechanism, bioinformatics predictions combined with western blot and RT-PCR analyses showed that both MSC-EVs and let-7a-5p were able to downregulate the expression of SMAD2 by inhibiting HMGA2. In conclusion, MSC-EV-secreted let-7a-5p promoted the regrowth of neurons and improved neurological recovery in SCI rats by targeting the HMGA2/SMAD2 axis.

Efficacy and Safety of Establishing an Optimal Path Through Unilateral Pedicle Under the Assistance of Surgical Robot in Percutaneous Kyphoplasty.

BACKGROUND: Despite percutaneous kyphoplasty (PKP) being widely used to treat osteoporotic vertebral compression fractures (OVCFs), the details of puncture are still controversial. With the development of surgical robots in spine surgery, robotic-assisted PKP surgery will become a promising treatment strategy. OBJECTIVES: To evaluate the efficacy and safety of establishing an optimal working path through a unilateral pedicle approach to improve bone cement distribution under the assistance of a surgical robot in percutaneous kyphoplasty. STUDY DESIGN: Experimental and prospective study. METHODS: PKP surgery under the assistance of the TINAVI robot was performed on 78 patients with osteoporotic vertebral compression fractures (OVCFs) from May 2018 to January 2020 in a single spine center. During the operation, the optimal path of the working channel made through unilateral pedicle puncture was designed according to the details of the fractured vertebral body under the guidance of the TINAVI surgical robot. Visual analog scale (VAS) scores of back pain, intraoperative blood loss, surgical time, and complications were recorded and evaluated. Postoperative fluoroscopy and 3D-CT were used to evaluate the distribution of bone cement. RESULTS: We have successfully performed 78 PKP surgeries under the assistance of the TINAVI robot. The mean procedure time was 13.9 ± 2.6 minutes from the beginning of C-arm scan to finish the injection of bone cement, and the intraoperative blood loss was 5.4 ± 2.8 mL. Pain of all cases was relieved immediately and significantly after PKP surgery; the VAS score was 7.5 ± 2.3 before surgery and 1.4 ± 0.8 post-surgery. The mean volume of bone cement was 4.7 ± 1.9 mL, and bone cement leakage occurred at the anterior edge of the fractured vertebral body in 2 patients, with no neurological and vascular injury in any of the cases. Postoperative fluoroscopy and 3D-CT showed that a good bone cement distribution evenly through unilateral pedicle puncture in the fractured vertebral body in all cases except the bone cement leakage in 2 patients. LIMITATIONS: More cases are needed to evaluate the efficacy and stability of robot-assisted PKP surgery. A control group of PKP performed freehand should be included in this study. CONCLUSIONS: Robotic-assisted PKP surgery through the unilateral approach to establishing an optimal working channel is a safe and available procedure for treating OVCFs in terms of better distribution of bone cement, high accuracy, good repeatability, and less surgical trauma.

MSC secreted extracellular vesicles carrying TGF-beta upregulate Smad 6 expression and promote the regrowth of neurons in spinal cord injured rats.

Mesenchymal stem cells (MSCs) constitute a promising therapy for spinal cord injury (SCI) because they can provide a favorable environment for the regrowth of neurons by inhibiting receptor-regulated Smads (R-Smads) expression in endogenous neural stem cells (NSCs). However, their mechanism of action and effect on the expression of inhibitory Smads (I-Smads) remain unclear. Herein, we demonstrated that extracellular vesicles (EVs) from MSCs were able to upregulate the Smad 6 expression by carrying TGF-ß, and the Smad 6 knockdown in NSCs partially weakened the bone marrow MSC (BMSC)-EV-induced effect on neural differentiation. We found that the expression of Smad 6 did not reduced owing to the TGF-ß type I receptor kinase inhibitor, SB 431,542, treatment in the acute phase of injury in rats with SCI, thereby indicating that the Smad 6 expression was not only mediated by TGF-ß, but also by the inflammatory factors and bone morphogenetic proteins (BMPs) as well. However, in the later phase of SCI, the Smad 6 expression decreased by the addition of SB 431,542, suggesting that TGF-ß plays a key role in the mediation of Smad 6 expression in this phase. In addition, immunohistochemistry staining; hematoxylin-eosin staining; and the Basso, Beattie, and Bresnahan (BBB) scores revealed that the early inhibition of TGF-ß did not increase neuron regrowth. However, this inhibition increased the cavity and the caspase-3 expression at 24 h post-injury, leading to a worse functional outcome. Conversely, the later treatment with the TGF-ß inhibitor promoted the regrowth of neurons around the cavity, resulting in a better neurological outcome. Together, these results indicate that Smad 6 acts as a feedback regulator to prevent the over-differentiation of NSCs to astrocytes and that BMSC-EVs can upregulate Smad 6 expression by carrying TGF-ß.

Degeneration of the Sensorimotor Tract in Degenerative Cervical Myelopathy and Compensatory Structural Changes in the Brain.

Degenerative cervical myelopathy is a progressive neurodegenerative disease, that has become increasingly prevalent in the aging population worldwide. The current study determined the factors affecting degeneration in the sensorimotor tract with degenerative cervical myelopathy and its relationship with brain structure. We divided patients into hyperintensity (HS) and non-hyperintensity (nHS) groups and measured the fractional anisotropy and apparent diffusion coefficients of the lateral corticospinal tract (CST), fasciculus gracilis and fasciculus cuneatus (FGC). Voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) techniques were used to estimate brain structure changes. Correlation of the modified Japanese Orthopaedic Association (mJOA) score, light touch, pinprick, motor score, and fractional anisotropy (FA) ratios of the CST at different levels were analyzed. Compared to healthy controls, the FA ratios of CST in the HS and nHS groups were decreased at all levels, and the apparent diffusion coefficient (ADC) ratio was increased only at C4/5 levels in the HS group. The FA ratio of FGC was decreased at the C3/4 and C4/5 levels in the HS group and only decreased at the C4/5 level in the nHS group. The ADC ratio was decreased only at the C4/5 level in the HS group. VBM analysis revealed that the volume of the precentral gyrus, postcentral gyrus, and paracentral lobule increased in patients compared to controls. TBSS analysis found no statistical significance between the sensory and motor tracts in white matter. The volume of clusters in HS and nHS groups negatively correlated with the C1/2 FA ratio of the CST. The results showed that the degeneration distance of the CST was longer than the FGC, and the degeneration distance was related to the degree of compression and spinal cord damage. Structural compensation and the neurotrophin family may lead to enlargement of the brain.

Sleep Deprivation Disturbs Immune Surveillance and Promotes the Progression of Hepatocellular Carcinoma.

Sleep disturbance is common in patients with cancer and is associated with poor prognosis. However, the effects of sleep deprivation (SD) on immune surveillance during the development of hepatocellular carcinoma (HC) and the underlying mechanisms are not known. This was investigated in the present study using mouse models of SD and tumorigenesis. We determined that acute and chronic sleep deprivation (CSD) altered the relative proportions of various immune cell types in blood and peripheral organs. CSD increased tumor volume and weight, an effect that was enhanced with increasing CSD time. Expression of the cell proliferation marker Ki-67 was elevated in tumor tissues, and tumor cell infiltration into adjacent muscles was enhanced by CSD. Multicolor flow cytometry analysis revealed that CSD significantly reduced the numbers of antitumor CD3+ T cells and natural killer (NK) cells and increased that of immunosuppressive CD11b+ cells infiltrating into the tumor microenvironment from the spleen via the peripheral blood. These results indicate that CSD impairs immune surveillance mechanisms and promotes immunosuppression in the tumor microenvironment to accelerate tumor growth, underscoring the importance of alleviating sleep disturbance in HC patients in order to prevent HC progression.

The role of hepatocyte growth factor in mesenchymal stem cell-induced recovery in spinal cord injured rats.

BACKGROUND: Mesenchymal stem cells (MSCs) have become a promising treatment for spinal cord injury (SCI) due to the fact that they provide a favorable environment. Treatment using MSCs results in a better neurological functional improvement through the promotion of nerve cell regeneration and the modulation of inflammation. Many studies have highlighted that the beneficial effects of MSCs are more likely associated with their secreted factors. However, the identity of the factor that plays a key role in the MSC-induced neurological functional recovery following SCI as well as its molecular mechanism still remains unclear. METHODS: A conditioned medium (collected from the MSCs) and hepatocyte growth factor (HGF) were used to test the effects on the differentiation of neural stem cells (NSCS) in the presence of BMP4 with or without a c-Met antibody. In SCI rats, Western blot, ELISA, immunohistochemistry, and hematoxylin-eosin staining were used to investigate the biological effects of MSC-conditioned medium and HGF on nerve cell regeneration and inflammation with or without the pre-treatment using a c-Met antibody. In addition, the possible molecular mechanism (cross-talk between HGF/c-Met and the BMP/Smad 1/5/8 signaling pathway) was also detected by Western blot both in vivo and in vitro. RESULTS: The conditioned medium from bone marrow-derived MSCs (BMSCs) was able to promote the NSC differentiation into neurons in vitro and the neurite outgrowth in the scar boundary of SCI rats by inhibiting the BMP/Smad signaling pathway as well as reduces the secondary damage through the modulation of the inflammatory process. The supplementation of HGF showed similar biological effects to those of BMSC-CM, whereas a functional blocking of the c-Met antibody or HGF knockdown in BMSCs significantly reversed the functional improvement mediated by the BMSC-CM. CONCLUSIONS: The MSC-associated biological effects on the recovery of SCI rats mainly depend on the secretion of HGF.

Elevated plasma BDNF levels are correlated with NK cell activation in patients with traumatic spinal cord injury.

BACKGROUND: The precise role of innate immune responses in the early stage of traumatic spinal cord injury (SCI), especially those mediated by natural killer (NK) cells, is poorly understood. METHODS: The frequency and phenotype of NK cells from traumatic SCI patients and healthy controls were assessed by flow cytometry. ELISA assay was used to detect the production of a series of cytokines, neurotrophins, and neurohormones in plasma samples. In vitro cell culture was performed to observe brain-derived neurotrophic factor (BDNF)-induced NK cell activation. RESULTS: A significant increase in the NK cell frequency and the presence of NK cells with the activated phenotype was observed, as reflected by the enhanced expression of CD69, HLA-DR, NKG2D, and NKp30 on the NK cells, in traumatic SCI patients within 24 h of injury, compared to case for the healthy controls. Meanwhile, a higher level of BDNF, a member of the neurotrophin family, was observed in the plasma samples of the SCI patients; the elevated level of BDNF was strongly and positively correlated with the percentage of NK cells during the early stage of traumatic SCI. Furthermore, the expression of CD69 and NKp30 on the NK cells increased following stimulation with BDNF for 24 h in vitro, which is consistent with the in vivo observation in SCI patients. CONCLUSION: Collectively, our findings demonstrate the activation of NK cells within 24 h after traumatic SCI, and reveal a novel role of BDNF in regulating NK cell activation.