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Though existing studies had continuously improved the hydrogel printing resolution by facilitating ink solidification, it was literally challenging to exceed the size limit of the printing needle even if there was an ideal ink that could solidify instantaneously. One possible solution to this hurdle is to stretch the hydrogel ink with a high printing speed and try maintaining its deformation without strain recovery. In this study, a gelatin/alginate/hydroxyapatite(HA) ink was printed at multiple temperatures, and a much lower yielding strain occurred at −1 °C than 2–5 °C according to our rheological tests. At −1 °C, the hydrogel ink could be highly stretched to produce an ultrahigh resolution at 81 ± 13 μm while maintaining uniform and continuous. Furthermore, our biological tests found a high scaffold resolution greatly promoted cell adhesion, proliferation, osteogenic differentiation and biomineralization. We stepped further from existing studies, by coming up with a new concept of utilizing ink stress-yielding in improving printing resolution, which would broaden our understanding to the processing-structure-property relationship in hydrogel-based 3D printing.

Abstract Surgical intervention is typically recommended for thoracic ossification of the ligamentum flavum (TOLF). This study aimed to evaluate the efficacy and safety of a novel non-coaxial one-hole split endoscope (OSE) technique for treating TOLF. We performed OSE procedure on 13 patients with TOLF from June 2022 to July 2023. The mean operative time was 117.5 ± 15.4 min. VAS scores for lower limbs decreased from 6.5 ± 0.8 preoperative to 1.6 ± 0.4 at the last follow-up (P

Abstract 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.

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.

Objective This study assessed biomechanical properties of pedicle screws enhanced or revised with 3 materials. We aimed to compare the efficacy of these materials in pedicle augmentation and revision. Methods One hundred twenty human cadaveric vertebrae were utilized for in vitro testing. Vertebrae bone density was evaluated. Allograft bone particles (ABP), calcium phosphate cement (CPC), and demineralized bone matrix (DBM) were used to augment or revise pedicle screw. Post the implantation of pedicle screws, parameters such as insertional torque, pullout strength, cycles to failure and failure load were measured using specialized instruments. Results ABP, CPC, and DBM significantly enhanced biomechanical properties of the screws. CPC augmentation showed superior properties compared to ABP or DBM. ABP-augmented screws had higher cycles to failure and failure loads than DBM-augmented screws, with no difference in pullout strength. CPC-revised screws exhibited similar strength to the original screws, while ABP-revised screws showed comparable cycles to failure and failure loads but lower pullout strength. DBM-revised screws did not match the original screws’ strength. Conclusion ABP, CPC, and DBM effectively improve pedicle screw stability for pedicle augmentation. CPC demonstrated the highest efficacy, followed by ABP, while DBM was less effective. For pedicle revision, CPC is recommended as the primary choice, with ABP as an alternative. However, using DBM for pedicle revision is not recommended.

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.

Abstract 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.

Abstract Background Tryptophan 2,3-dioxygenase (TDO2) is the primary enzyme that catabolizes tryptophan to kynurenine. Numerous studies have suggested that TDO2 is involved in inflammation-related diseases. However, its role in osteoarthritis (OA) has not yet been investigated. The aim of the present study was to explore the levels of TDO2 in the synovium and synovial fluid (SF) of patients with OA and its correlation with clinical manifestations and levels of pro-inflammatory cytokines. Methods Synovium and SF samples were collected from patients with OA and patients with joint trauma (controls) during surgery. An enzyme-linked immunosorbent assay (ELISA) was used to measure TDO2, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) levels in the synovium and SF. Diagnostic performance of TDO2 in the synovium to discriminate between controls and OA patients was assessed using receiver operating characteristic (ROC) curve analysis. Correlations between TDO2 levels, OA clinical features, and pro-inflammatory cytokines were evaluated using Pearson correlation analysis. Effects of IL-1β or TNF-α stimulation on TDO2 expression in OA-fibroblast-like synoviocytes (OA-FLS) were also examined. Results The levels of TDO2, IL-1β, and TNF-α in the synovium of patients with OA were found to be significantly higher than those in controls. ROC curve analysis revealed an area under the curve (AUC) of 0.800 with 64.3% sensitivity and 85.0% specificity of TOD2 in the synovium, which enabled discriminating patients with OA from controls. Moreover, protein expression of TDO2 was upregulated to a greater extent in OA-FLS than in normal synovial fibroblasts (NSF). Furthermore, the levels of TDO2 showed significantly positive correlation with IL-1β and TNF-α levels in the synovium and SF. TDO2 levels in the synovium were also positively correlated with the Kellgren-Lawrence score. Additionally, TDO2 protein expression was significantly increased in IL-1β‒ or TNF-α‒stimulated OA-FLS than in control FLS. Conclusion These data indicate that highTDO2 levels in the synovium can be correlated with pro-inflammatory cytokines and severity of OA.

The effective osteointegration of orthopedic implants is a key factor for the success of orthopedic surgery. However, local metabolic imbalance around implants under osteoporosis condition could jeopardize the fixation effect. Inspired by the bone structure and the composition around implants under osteoporosis condition, alendronate (A) was grafted onto methacryloyl hyaluronic acid (H) by activating the carboxyl group of methacryloyl hyaluronic acid to be bonded to inorganic calcium phosphate on trabecular bone, which is then integrated with aminated bioactive glass (AB) modified by oxidized dextran (O) for further adhesion to organic collagen on the trabecular bone. The hybrid hydrogel could be solidified on cancellous bone in situ under UV irradiation and exhibits dual adhesion to organic collagen and inorganic apatite, promoting osteointegration of orthopedic implants, resulting in firm stabilization of the implants in cancellous bone areas. In vitro, the hydrogel was evidenced to promote osteogenic differentiation of embryonic mouse osteoblast precursor cells (MC3T3-E1) as well as inhibit the receptor activator of nuclear factor-κ B ligand (RANKL)-induced osteoclast differentiation of macrophages, leading to the upregulation of osteogenic-related gene and protein expression. In a rat osteoporosis model, the bone-implant contact (BIC) of the hybrid hydrogel group increased by 2.77, which is directly linked to improved mechanical stability of the orthopedic implants. Overall, this organic-inorganic, dual-adhesive hydrogel could be a promising candidate for enhancing the stability of orthopedic implants under osteoporotic conditions.

IntroductionCervical 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.MethodsAccording 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.ResultsWe 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).DiscussionThe 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.

Low back pain is a major cause of disability worldwide that declines the quality of life; it poses a substantial economic burden for the patient and society. Intervertebral disc (IVD) degeneration (IDD) is the main cause of low back pain, and it is also the pathological basis of several spinal degenerative diseases, such as intervertebral disc herniation and spinal stenosis. The current clinical drug treatment of IDD focuses on the symptoms and not their pathogenesis, which results in frequent recurrence and gradual aggravation. Moreover, the side effects associated with the long-term use of these drugs further limit their use. The pathological mechanism of IDD is complex, and oxidative stress and inflammation play an important role in promoting IDD. They induce the destruction of the extracellular matrix in IVD and reduce the number of living cells and functional cells, thereby destroying the function of IVD and promoting the occurrence and development of IDD. Phytochemicals from fruits, vegetables, grains, and other herbs play a protective role in the treatment of IDD as they have anti-inflammatory and antioxidant properties. This article reviews the protective effects of phytochemicals on IDD and their regulatory effects on different molecular pathways related to the pathogenesis of IDD. Moreover, the therapeutic limitations and future prospects of IDD treatment have also been reviewed. Phytochemicals are promising candidates for further development and research on IDD treatment.

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.

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.

Various hydrogels have been studied for nucleus pulposus regeneration. However, they failed to overcome the changes in the acidic environment during intervertebral disc degeneration. Therefore, a new functionalized peptide RAD/SA1 was designed by conjugating Sa12b, an inhibitor of acid-sensing ion channels, onto the C-terminus of RADA16-I. Then, the material characteristics and biocompatibility of RAD/SA1, and the bioactivities and mechanisms of degenerated human nucleus pulposus mesenchymal stem cells (hNPMSCs) were evaluated. Atomic force microscopy (AFM) and scanning electron microscopy (SEM) confirmed that RAD/SA1 self-assembling into three-dimensional (3D) nanofiber hydrogel scaffolds under acidic conditions. Analysis of the hNPMSCs cultured in the 3D scaffolds revealed that both RADA16-I and RAD/SA1 exhibited reliable attachment and extremely low cytotoxicity, which were verified by SEM and cytotoxicity assays, respectively. The results also showed that RAD/SA1 increased the proliferation of hNPMSCs compared to that in culture plates and pure RADA16-I. Quantitative reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, and western blotting demonstrated that the expression of collagen I was downregulated, while collagen II, aggrecan, and SOX-9 were upregulated. Furthermore, Ca2+ concentration measurement and western blotting showed that RAD/SA1 inhibited the expression of p-ERK through Ca2+-dependent p-ERK signaling pathways. Therefore, the functional self-assembling peptide nanofiber hydrogel designed with the short motif of Sa12b could be used as an excellent scaffold for nucleus pulposus tissue engineering. Moreover, RAD/SA1 exhibits great potential applications in the regeneration of mildly degenerated nucleus pulposus.

The expansion and maintenance of the NPMSC (nucleus pulposus mesenchymal stem cell) phenotype are considered as potential therapeutic tools for clinical applications in intervertebral disc tissue engineering and regenerative medicine. However, the harsh microenvironment within the intervertebral disc is the main limitation of its regeneration. The osmolarity of the intervertebral disc is higher than that of other tissues, which has an important influence on the biological characteristics of NPMSCs. In this study, we observed the effect of different osmolarities on the biological characteristics of human normal NPMSCs cultured in vitro and explored the role of osmolarity in intervertebral disc degeneration. Our data demonstrated that the change in osmotic pressure has an important effect on the biological activity of NPMSCs, and this effect may occur through the P16INK4A/Rb pathway. This study provides a theoretical basis for the future treatment of intervertebral disc degeneration.

Abstract 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.

Abstract Background The leukocyte esterase (LE) strip is considered as a helpful method to detect infection, which might be influenced by other inflammatory diseases. This study aims to explore whether the centrifugation of synovial fluid could influence the positive result of LE strip caused by inflammatory arthritis during the diagnosis of periprosthetic joint infection (PJI). Methods From March 2016 to December 2018, 64 patients who were diagnosed as PJI or aseptic arthritis and another 20 patients with inflammatory arthritis were enrolled in our study. After synovial fluid samples were obtained, the LE strip test was performed with and without centrifugation. Then clinicians read the color changes 3 min after the samples were dropped and classify the results based on the instruction of strip. The differences between septic and aseptic arthritis patients and septic and inflammatory arthritis patients were analyzed. Results Among the included 21 PJI samples, 19 of them showed positive results (++) of LE strip before centrifugation. After centrifugation, two samples changed from two-positive (++) to one-positive (+), which is also considered as positive. Before centrifugation, 29 of the LE strip tests in the aseptic arthritis group (43 samples included) were ++ or +. After centrifugation, 16 of the samples yielded negative results. Among 20 samples with inflammatory arthritis, LE strip of 18 samples were positive (++ or +) before centrifugation, among which only 3 samples remained as positive after centrifugation. Conclusion LE strip test results could be influenced by inflammatory arthritis during the diagnosis of PJI. Centrifugation should be performed for LE strip tests to determine whether the result is a true positive or a false positive influenced by inflammatory arthritis.

Abstract Background Cortical bone trajectory (CBT) has been well-known in spine surgery for obtaining improved fixation while minimizing soft tissue dissection. This study was designed to compare the bone mineral density (BMD) between the CBT and traditional trajectory (TT) by using Hounsfield unit (HU) values and identify the ideal decades of patients and the suitable lumbar segments using this CBT technology from a radiological standpoint. Methods Patients were selected randomly from an institutional database based on age (evenly distributed by a decade of life) and gender. A total of 240 healthy patients had a computed tomography (CT) scan of the chest, abdomen, and pelvis. For each patient, axial slices of every vertebra were cut in two planes: one horizontal to the pedicle representing the plane wherein pedicle screws were inserted using the TT and the other in a caudocranial plane representing the plane wherein pedicle screws were inserted using the CBT. For each trajectory, a region of interest (ROI) was selected within the area wherein the screws were inserted. A CT number (HU values) was then calculated within each ROI to represent bone density. Results HU values measured at the ROI of CBT were significantly greater than those of the traditional pedicle screw in all age groups, and the specific value (ratio of the HU values of CBT/the HU values of TT) between CBT and TT was 1.92. A significant difference was observed between male and female. The HU values of CBT and TT of males were generally higher than those of females (males: CBT/TT 1.89 ± 0.45; Females: CBT/TT 1.95 ± 0.47). The specific value in HU values significantly increased with increasing age (p = 0.000) and cauda lumbar level (p = 0.000) in males and females. Conclusion BMD, as measured by HU values for the ROI of the CBT screw, was significantly greater than that of the traditional pedicle screw, especially in old patients and cauda lumbar segments.

The endogenous spinal cord ependymal cells (SCECs), which form the central canal (CC), are critically involved in proliferation, differentiation and migration after spinal cord injury (SCI) and represents a repair cell source in treating SCI. Previously, we reported that BAF45D is expressed in the SCECs and the spinal cord neurons in adult mice and knockdown of BAF45D fail to induce expression of PAX6, a neurogenic fate determinant, during early neural differentiation of human embryonic stem cells. However, the effects of SCI on expression of BAF45D have not been reported. The aim of this study is to explore the expression and potential role of BAF45D in rat SCI model. In this study, adult rats were randomly divided into intact, sham, and SCI groups. We first explored expression of BAF45D in the SCECs in intact adult rats. We then explored SCI-induced loss of motor neurons and lesion of neurites in the anterior horns induced by the SCI. We also investigated whether the SCI-induced lesions in SCECs are accompanied by the motor neuron lesions. Finally, we examined the effect of BAF45D knockdown on cell growth in neuro2a cells. Our data showed that BAF45D is expressed in SCECs, neurons, and oligodendrocytes but not astrocytes in the spinal cords of intact adult rats. After SCI, the structure of CC was disrupted and the BAF45D-positive SCEC-derivatives were decreased. During the early stages of SCI, when shape of CC was affected but there was no disruption in circular structure of the SCECs, it was evident that there was a significant reduction in the number of neurites and motor neurons in the anterior horns compared with those of intact rats. In comparison, a complete loss of SCECs accompanied by further loss of motor neurons but not neurites was observed at the later stage. BAF45D knockdown was also found to inhibit cell growth in neuro2a cells. These results highlight the decreased expression of BAF45D in SCI-injured SCECs and the potential role of BAF45D downregulation in development of neuronal lesion after SCI in adult rats.

Adult neurogenesis is important for the development of regenerative therapies for human diseases of the central nervous system (CNS) through the recruitment of adult neural stem cells (NSCs). NSCs are characterized by the capacity to generate neurons, astrocytes, and oligodendrocytes. To identify key factors involved in manipulating the adult NSC neurogenic fate thus has crucial implications for the clinical application. Here, we report that BAF45D is expressed in the subgranular zone (SGZ) of the dentate gyrus, the subventricular zone (SVZ) of the lateral ventricle, and the central canal (CC) of the adult spinal cord. Coexpression of BAF45D with glial fibrillary acidic protein (GFAP), a radial glial like cell marker protein, was identified in the SGZ, the SVZ and the adult spinal cord CC. Quantitative analysis data indicate that BAF45D is preferentially expressed in the neurogenic zone of the LV and the neurons of the adult CNS. Furthermore, during the neuroectoderm differentiation of H9 cells, BAF45D is required for the expression of PAX6, a neuroectoderm determinant that is also known to regulate the self-renewal and neuronal fate specification of adult neural stem/progenitor cells. Together, our results may shed new light on the expression of BAF45D in the adult neurogenic zones and the contribution of BAF45D to early neural development.

The aim of this study is to study the relationship between the degree of lumbar disc degeneration and the height of the disc in patients with pain in the lower back and determine whether there is a dose-response relationship between the two. Eighty-2ve patients were examined by magnetic resonance imaging (MRI). The grade of lumbar degeneration was determined by the P2rrmann grading system, and the intervertebral height and VAS pain scores were measured. The height difference of intervertebral discs with different degeneration levels was measured by the F test. This difference was correlated and further quantified by regression analysis. Finally, the differences intervertebral disc heights with a VAS score of 0-6 and 7-10 were observed by an independent sample t-test. The higher degree of disc degeneration in each lumbosacral segment, the lower the intervertebral disc height (p ≤ 0.011). When discs with grade 1 and grade 5 degeneration were excluded, the results remained the same (p ≤ 0.034). To quantify correlations, at each lumbar level, the disc height was reduced for each level of lumbosacral disc degeneration, and the height of disc was reduced after adjusting according to age, sex, and BMI (# range: -1.25mmto -1.76 mm, 95% CI: -0.83 to -2.29, all p ≤ 0.002). Subjects with a VAS score of 7-10 had a lower intervertebral disc height than those with a VAS score of 0-6, especially with respect to total height levels at L4/5, L5/S1, and L1-S1 (p ≤ 0.04). This study showed a relationship between increased degree of intervertebral disc degeneration and decreased the disc height in patients with pain in the low back. Although the assessment of lumbar and lumbosacral level disc degeneration involves many qualitative measurements, these statistical data confirm the effectiveness of lumbosacral disc height as a continuous data measure and quantification in clinical trials and epidemiological studies. [ABSTRACT FROM AUTHOR]

Neural stem cells (NSCs) have emerged as a promising treatment for spinal cord injuries. However, the increasing expression of bone morphogenetic proteins (BMPs) in spinal cord injury lesion sites seems to have contributed to the limited oligodendroglial differentiation and the majority of the astroglial differentiation of NSCs. In the present study, we demonstrate that BMPs promote NSCs differentiation toward astrocytes and prevent them from differentiating into oligodendrocytes. This effect is accompanied by the increasing expression of Id2 and the reduction in Oilg1/2 expression. Treatment with bone marrow stromal cells (BMSCs) can enhance the development of oligodendrocytes in the presence of BMPs. The analysis of Id2, as well as Olig1 and Olig2 gene expression, reveals that the effect of BMPs on these gene expressions is reversed with the addition of BMSCs. In sum, these data strongly suggest that BMSCs can promote the differentiation of NSCs into oligodendrocytes through mediating Id2 and Olig1/2 expression by blocking the BMP/Smad signaling pathway. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Tryptophan 2,3-dioxygenase (TDO2) is the primary enzyme that catabolizes tryptophan to kynurenine. Numerous studies have suggested that TDO2 is involved in inflammation-related diseases. However, its role in osteoarthritis (OA) has not yet been investigated. The aim of the present study was to explore the levels of TDO2 in the synovium and synovial fluid (SF) of patients with OA and its correlation with clinical manifestations and levels of pro-inflammatory cytokines.  METHODS : Synovium and SF samples were collected from patients with OA and patients with joint trauma (controls) during surgery. An enzyme-linked immunosorbent assay (ELISA) was used to measure TDO2, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) levels in the synovium and SF. Diagnostic performance of TDO2 in the synovium to discriminate between controls and OA patients was assessed using receiver operating characteristic (ROC) curve analysis. Correlations between TDO2 levels, OA clinical features, and pro-inflammatory cytokines were evaluated using Pearson correlation analysis. Effects of IL-1β or TNF-α stimulation on TDO2 expression in OA-fibroblast-like synoviocytes (OA-FLS) were also examined.Results: The levels of TDO2, IL-1β, and TNF-α in the synovium of patients with OA were found to be significantly higher than those in controls. ROC curve analysis revealed an area under the curve (AUC) of 0.800 with 64.3% sensitivity and 85.0% specificity of TOD2 in the synovium, which enabled discriminating patients with OA from controls. Moreover, protein expression of TDO2 was upregulated to a greater extent in OA-FLS than in normal synovial fibroblasts (NSF). Furthermore, the levels of TDO2 showed significantly positive correlation with IL-1β and TNF-α levels in the synovium and SF. TDO2 levels in the synovium were also positively correlated with the Kellgren-Lawrence score. Additionally, TDO2 protein expression was significantly increased in IL-1β‒ or TNF-α‒stimulated OA-FLS than in control FLS.Conclusion: These data indicate that highTDO2 levels in the synovium can be correlated with pro-inflammatory cytokines and severity of OA. [ABSTRACT FROM AUTHOR]