OBJECTIVES:The osteogenic differentiation ability of bone marrow mesenchymal stem cells (BMSCs) is an important aspect of studying osteoporosis (OP). This study aims to explore the role of SYVN1 in regulating the osteogenic differentiation of BMSCs and to suggest its potential as a treatment for OP. METHODS:BMSCs were differentiated using osteogenic induction. The expression of SYVN1 at different osteogenic induction time points was analyzed by Western blot (WB). The expression levels of osteogenic markers, including RUNX2, ALP, and OCN, were measured by RT-qPCR. EdU staining and colony formation assays were performed to evaluate the impact of SYVN1 on the proliferative ability of BMSCs. The effect of SYVN1 on osteogenic differentiation of BMSCs was assessed by alizarin red staining. The association of SYVN1 with the AMPK/mTOR pathway was confirmed through WB analysis. RESULTS:The expression of SYVN1 decreased as BMSCs differentiation progressed. Overexpression of SYVN1 inhibited the osteogenic differentiation and proliferation of BMSCs, whereas silencing SYVN1 had the opposite effect. Furthermore, SYVN1 overexpression reduced the p-AMPK/AMPK ratio and increased the p-mTOR/mTOR ratio, effects that were reversed by the AMPK activator A-769662. CONCLUSION:SYVN1 overexpression inhibits the osteogenic differentiation and proliferation of BMSCs, potentially through modulation of the AMPK/mTOR pathway.

Spinal cord injury (SCI) is a severe central nervous system injury without effective therapies. PANoptosis is involved in the development of many diseases, including brain and spinal cord injuries. However, the biological functions and molecular mechanisms of PANoptosis-related genes in spinal cord injury remain unclear. In the bioinformatics analysis of public data of SCI, the differentially expressed genes (DEGs) identified by GSE151371 were hybridized with PANoptosis-related genes (PRGs) to obtain differentially expressed PANoptosis-related genes (DE-PRGs). Through three machine learning algorithms, we obtained the hub genes. Then, we constructed functional analysis, drug prediction, regulatory network construction, and immune infiltrating cell analysis. Finally, the expression of the hub gene was verified in GSE93561, GSE45376, and qRT-PCR analysis. Through the above analysis, 14 DE-PRGs were obtained by intersecting 3582 DEGs with 46 PRGs. Five key hub genes, CASP4, GSDMB, NAIP, NLRC4, and NLRP3, were obtained by 3 machine learning algorithms. All five hub genes were enriched in phagocytosis mediated by FC GAMMA R. The 11 immune cells were significantly different between spinal cord injury (SCI) group and human control (HC) group, such as mast cell and gamma delta T cell. The transcription factor (TF)-hub gene network contained 10-nodes (4 hub genes and 6 TFs) and 8-edges. The miRNA-hub gene network consisting of 5-nodes (3 hub genes and 2 miRNAs) and 3-edges was constructed. Moreover, the CASP4 predicted 1 small molecule drug and NLRP3 predicted 9 small molecule drugs. Finally, the expression of 5 hub genes were significantly different in GSE45376 and GSE93561 (SCI vs. HC) and mice SCI model (Sham vs. SCI). Collectively, we identified 5 hub genes (CASP4, GSDMB, NAIP, NLRC4, and NLRP3) associated with PANoptosis, providing potential directions for treating spinal cord injury.

Objective This study aimed to identify surgical, patient-specific, and radiographic risk factors for proximal junctional failure (PJF), a complex complication following adult spinal deformity (ASD) surgery. Methods A systematic literature search was performed using PubMed, Embase, and the Cochrane Library. The literature on the risk factors for PJF after ASD surgery was included. The study patients were diagnosed with ASD and underwent surgery for ASD. PJF is defined as the occurrence of proximal junctional kyphosis, accompanied by one or more of the following characteristics: a fracture of the vertebral body at the upper instrumented vertebra (UIV) or UIV + 1 level, disruption of the posterior ligaments, or dislodgement of the instrumentation at the UIV. proximal junctional kyphosis, on the other hand, is determined by 2 criteria: a proximal junctional sagittal Cobb angle 1) of 10° and 2) at least 10° greater than the preoperative value. Results Our pooled analysis of 11 unique studies (2037 patients) revealed significant differences in several preoperative and postoperative measures between PJF and non-PJF groups. Conclusions In ASD patients, the presence of concurrent osteoporosis or paravertebral muscle wasting significantly increases the risk of developing PJF. The use of bicortical screws, UIV screw angle exceeding 1°, and positioning the UIV in the lower thoracic or lumbar region also further elevate this risk. Lower preoperative SS, higher preoperative PI-LL, higher preoperative pelvic tilt, higher preoperative SVA, higher postoperative LL, and a greater change in LL characterize patients with PJF.

The sludge-based forming thermal reduction can be used to improve the resource utilization ability of sintering dust. This paper discussed the feasibility and mechanism of sewage sludge as a binder and reducing agent to facilitate iron recycling from sintering dust by mixing wet sludge to form and adding dry sludge to reduce. The results showed that a 1.4% ratio of sewage sludge significantly enhanced the strength of metallurgical pellets, and the compressive strength of wet and dry pellets reached 309.5 and 1233.5 N/P. Meanwhile, with the addition of dry sludge (S/Fe = 2.0), the metallization ratio can be up to 88.4%. Sewage sludge has a more efficient reduction potential than other carbon sources as reducing agents. Combined with XRD, XPS, TG-MS, TG-FTIR, and other characterization methods, the reduction phenomenon of iron was confirmed, and the migration and transformation of metals in sintering dust and the segmented volatilization rule of Pb, Zn, K, Na, and other elements were revealed. It is proven that sludge as the disposal route of metallurgical dust cold-pressed forming and reduction is a green and sustainable view and promising research direction.

This study aims to investigate the fusion rate and complications associated with trans-sacral interbody fusion (TSIF) in long fusions to the sacrum for adult spinal deformity (ASD) over a two year follow-up period. Potential predictor variables associated with pseudarthrosis were also examined. A retrospective clinical review was conducted on a consecutive series of ASD patients who underwent long fusions to the sacrum, with TSIF performed as a same-day or staged procedure. Patient demographics, bone mineral density, operative details, perioperative and late complications, and fusion rates were reviewed. Univariate analysis was used to identify the risk factors associated with pseudarthrosis. The study included 43 patients with an average age of 55.3 ± 8.9 years. The perioperative complication rate was 28

Objective: To compare the biomechanical stability of transsacral-transiliac screw fixation and lumbopelvic fixation for “H”- and “U”-type sacrum fractures with traumatic spondylopelvic dissociation. Methods : Finite element models of “H”- and “U”-type sacrum fractures with traumatic spondylopelvic dissociation were created in this study. The models mimicked the standing position of a human. Fixation with transsacral-transiliac screw fixation, lumbopelvic fixation, and bilateral triangular fixation were simulated. Biomechanical tests of instability were performed, and the fracture gap displacement, anteflexion, rotation, and stress distribution after fixation were assessed. Results: For H-type fractures, the three kinds of fixation ranked by stability were bilateral triangular fixation > lumbopelvic fixation > transsacral-transiliac screw fixation in the vertical and anteflexion directions, bilateral triangular fixation > transsacral-transiliac S1 and S2 screw fixation > lumbopelvic fixation in rotation. The largest displacements in the vertical, anteflexion and rotational directions were 0.57234 mm, 0.37923 mm and 0.13076 mm, respectively. For U-type fractures, these kinds of fixation ranked by stability were bilateral triangular fixation > lumbopelvic fixation > transsacral-transiliac S1 and S2 screw fixation > transsacral-transiliac S1 screw fixation in the vertical, anteflexion and rotational directions. The largest displacements in the vertical, anteflexion and rotational directions were 0.38296 mm, 0.33976 mm and 0.05064 mm, respectively. Conclusion: All these kinds of fixation met the mechanical criteria for clinical applications. The biomechanical analysis showed better bilateral balance with transsacral-transiliac screw fixation. The maximal displacement for these types of fixation was less than 1 mm. Percutaneous transsacral-transiliac screw fixation can be considered the best option among these kinds of fracture fixation.

Epidural electrical stimulation can restore limb motor function after spinal cord injury by reactivating the surviving neural circuits. In previous epidural electrical stimulation studies, single electrode sites and continuous tetanic stimulation have often been used. With this stimulation, the body is prone to declines in tolerance and locomotion coordination. In the present study, rat models of complete spinal cord injury were established by vertically cutting the spinal cord at the T8 level to eliminate disturbance from residual nerve fibers, and were then subjected to epidural electrical stimulation. The flexible extradural electrode had good anatomical topology and matched the shape of the spinal canal of the implanted segment. Simultaneously, the electrode stimulation site was able to be accurately applied to the L2–3 and S1 segments of the spinal cord. To evaluate the biocompatibility of the implanted epidural electrical stimulation electrodes, GFAP/Iba-1 double-labeled immunofluorescence staining was performed on the spinal cord below the electrodes at 7 days after the electrode implantation. Immunofluorescence results revealed no significant differences in the numbers or morphologies of microglia and astrocytes in the spinal cord after electrode implantation, and there was no activated Iba-1+ cell aggregation, indicating that the implant did not cause an inflammatory response in the spinal cord. Rat gait analysis showed that, at 3 days after surgery, gait became coordinated in rats with spinal cord injury under burst stimulation. The regained locomotion could clearly distinguish the support phase and the swing phase and dynamically adjust with the frequency of stimulus distribution. To evaluate the matching degree between the flexible epidural electrode (including three stimulation contacts), vertebral morphology, and the level of the epidural site of the stimulation electrode, micro-CT was used to scan the thoracolumbar vertebrae of rats before and after electrode implantation. Based on the experimental results of gait recovery using three-site stimulation electrodes at L2–3 and S1 combined with burst stimulation in a rat model of spinal cord injury, epidural electrical stimulation is a promising protocol that needs to be further explored. This study was approved by the Animal Ethics Committee of Chinese PLA General Hospital (approval No. 2019-X15-39) on April 19, 2019.

STUDY DESIGN:Clinical case series. OBJECTIVE:The aim of this study was to describe the treatment of aggressive vertebral hemangiomas (VHs) with neurological deficit treated with total en bloc spondylectomy (TES) in a single institute. SUMMARY OF BACKGROUND DATA:Despite increasing utilization of surgery to treat aggressive VHs, owing to the rarity, the diagnosis and treatment protocols of aggressive VHs are still questionable and disputable. METHODS:All patients with Enneking stage 3 aggressive thoracic or lumbar VHs with neurological deficit and treated with TES from January 2005 to January 2013 were included. Clinical characteristics and surgery outcomes of patients, including Tomita classification, operation time, blood loss, pre- and postoperative American Spinal Injury Association (ASIA) impairment scale, visual analogue score (VAS), and Spinal Instability Neoplastic Score (SINS), were retrospectively reviewed. RESULTS:A total of 23 VHs patients were enrolled in this study, including 17 in the thoracic spine and six in the lumbar spine. All patients suffered neurological deficits caused by direct spinal cord compression with or without associated mechanical instability. The average SINS score was 9.78 ± 1.51. The mean operation time of patients with preoperative embolization was 426.6 ± 104.3 minutes and the mean blood loss was 1883.3 ± 932.1 mL. There were no technical difficulties or serious complications. After surgery, all patients recovered to ASIA-E levels. The VAS pain score decreased from 8.0 ± 0.9 to 2.8 ± 0.8 (P < .05). CONCLUSION:TES is a good treatment option for patients with aggressive VHs with bony destruction and neurological deficit. LEVEL OF EVIDENCE:4.

Risk indicators viral load (ORF1ab Ct), lymphocyte percentage (LYM%), C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT) and lactic acid (LA) in COVID-19 patients have been proposed in recent studies. However, the predictive effects of those indicators on disease classification and prognosis remains largely unknown. We dynamically measured those reported indicators in 132 cases of COVID-19 patients including the moderate-cured (moderated and cured), severe-cured (severe and cured) and critically ill (died). Our data showed that CRP, PCT, IL-6, LYM%, lactic acid and viral load could predict prognosis and guide classification of COVID-19 patients in different degrees. CRP, IL-6 and LYM% were more effective than other three factors in predicting prognosis. For disease classification, CRP and LYM% were sensitive in identifying the types between critically ill and severe (or moderate). Notably, among the investigated factors, LYM% was the only one that could distinguish between the severe and moderate types. Collectively, we concluded that LYM% was the most sensitive and reliable predictor for disease typing and prognosis. During the COVID-19 pandemic, the precise classification and prognosis prediction are critical for saving the insufficient medical resources, stratified treatment and improving the survival rate of critically ill patients. We recommend that LYM% be used independently or in combination with other indicators in the management of COVID-19.

Study Design. Clinical case series. Objective. The aim of this study was to describe the treatment of aggressive vertebral hemangiomas (VHs) with neurological deficit treated with total en bloc spondylectomy (TES) in a single institute. Summary of Background Data. Despite increasing utilization of surgery to treat aggressive VHs, owing to the rarity, the diagnosis and treatment protocols of aggressive VHs are still questionable and disputable. Methods. All patients with Enneking stage 3 aggressive thoracic or lumbar VHs with neurological deficit and treated with TES from January 2005 to January 2013 were included. Clinical characteristics and surgery outcomes of patients, including Tomita classification, operation time, blood loss, pre- and postoperative American Spinal Injury Association (ASIA) impairment scale, visual analogue score (VAS), and Spinal Instability Neoplastic Score (SINS), were retrospectively reviewed. Results. A total of 23 VHs patients were enrolled in this study, including 17 in the thoracic spine and six in the lumbar spine. All patients suffered neurological deficits caused by direct spinal cord compression with or without associated mechanical instability. The average SINS score was 9.78 ± 1.51. The mean operation time of patients with preoperative embolization was 426.6 ± 104.3 minutes and the mean blood loss was 1883.3 ± 932.1 mL. There were no technical difficulties or serious complications. After surgery, all patients recovered to ASIA-E levels. The VAS pain score decreased from 8.0 ± 0.9 to 2.8 ± 0.8 (P < .05). Conclusion. TES is a good treatment option for patients with aggressive VHs with bony destruction and neurological deficit. Level of Evidence: 4

BackgroundThe severity and outcome of COVID-19 cases has been associated with the percentage of circulating lymphocytes (LYM%), levels of C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT), lactic acid (LA), and viral load (ORF1ab Ct). However, the predictive power of each of these indicators in disease classification and prognosis remains largely unclear.MethodsWe retrospectively collected information on the above parameters in 142 patients with COVID-19, stratifying them by survival or disease severity.FindingsCRP, PCT, IL-6, LYM%, and ORF1ab Ct were significantly altered between survivors and non-survivors. LYM%, CRP, and IL-6 were the most sensitive and reliable factors in distinguishing between survivors and non-survivors. These indicators were significantly different between critically ill and severe/moderate patients. Only LYM% levels were significantly different between severe and moderate types. Among all the investigated indicators, LYM% was the most sensitive and reliable in discriminating between critically ill, severe, and moderate types and between survivors and non-survivors.ConclusionsCRP, PCT, IL-6, LYM%, and ORF1ab Ct, but not LA, could predict prognosis and guide classification of COVID-19 patients. LYM% was the most sensitive and reliable predictor for disease typing and prognosis. We recommend that LYM% be further investigated in the management of COVID-19.FundingThis study was supported in part by awards from the National Natural Science Foundation of China, the Foundation and Frontier Research Project of Chongqing, and the Chongqing Youth Top Talent Project.

Minimally invasive surgery has become popular because of the lower incidence of wound complications. However, achieving an anatomic reduction that provides a satisfactory outcome is difficult using minimally invasive surgery. Our study aimed to evaluate the reduction and clinical outcomes of closed reduction and percutaneous fixation treatment using a closed reduction traction device for displaced intra-articular calcaneal fractures compared with traditional open reduction plate fixation using an extended lateral approach. A total of 40 patients and 45 feet with calcaneus fractures from 2012 to 2016 were studied. The open reduction plate fixation group (24 feet) was compared to the closed reduction percutaneous fixation group (21 feet) with a traction device. The reduction assessments included length, width, height, Bohler’s angle, Gissane’s angle, and varus or valgus angle before and after surgery. The clinical outcomes included the American Orthopaedic Foot and Ankle Society hindfoot score and the visual analog score for pain, length of stay, and complication rate. The patients were followed up for an average of 16.53 ± 3.95 months. No significant differences in reduction were observed between the open and closed groups (P > 0.05). The American Orthopaedic Foot and Ankle Society scores of the two groups were 80.29 ± 6.15 and 83.62 ± 6.95 (open versus closed) (P = 0.0957). The visual analog scores of the open and closed groups were 1.50 ± 1.22 and 0.81 ± 0.87 (P = 0.0364). The lengths of stay in the open and closed groups were 9.63 ± 2.72 days and 6.71 ± 1.85 days (P = 0.0002). The complication rates of the open and closed groups were 20.8% (5/24) and 4.8% (1/21) (P < 0.0001). The closed reduction percutaneous fixation with traction device method may provide equivalent reduction results and superior outcomes for the length of stay, VAS score, and complication rate for displaced intra-articular calcaneal fractures.

Metabolic reprogramming in tumor-associated macrophages (TAM) is associated with cancer development, however, the role of macrophage triglyceride metabolism in cancer metastasis is unclear. Here, we showed that TAMs exhibited heterogeneous expression of abhydrolase domain containing 5 (ABHD5), an activator of triglyceride hydrolysis, with migratory TAMs expressing lower levels of ABHD5 compared with the nonmigratory TAMs. ABHD5 expression in macrophages inhibited cancer cell migration in vitro in xenograft models and in genetic cancer models. The effects of macrophage ABHD5 on cancer cell migration were dissociated from its metabolic function as neither triglycerides nor ABHD5-regulated metabolites from macrophages affected cancer cell migration. Instead, ABHD5 deficiency in migrating macrophages promoted NFκB p65-dependent production of matrix metalloproteinases (MMP). ABHD5 expression negatively correlated with MMP expression in TAMs and was associated with better survival in patients with colorectal cancer. Taken together, our findings show that macrophage ABHD5 suppresses NFκB-dependent MMP production and cancer metastasis and may serve as a prognostic marker in colorectal cancer. SIGNIFICANCE: These findings highlight the mechanism by which reduced expression of the metabolic enzyme ABHD5 in macrophages promotes cancer metastasis.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/21/5513/F1.large.jpg.

Previous studies have reported age-specific pathological and functional outcomes in young and aged patients suffering spinal cord injury, but the mechanisms remain poorly understood. In this study, we examined mice with spinal cord injury. Gene expression profiles from the Gene Expression Omnibus database (accession number GSE93561) were used, including spinal cord samples from 3 young injured mice (2–3-months old, induced by Impactor at Th9 level) and 3 control mice (2–3-months old, no treatment), as well as 2 aged injured mice (15–18-months old, induced by Impactor at Th9 level) and 2 control mice (15–18-months old, no treatment). Differentially expressed genes (DEGs) in spinal cord tissue from injured and control mice were identified using the Linear Models for Microarray data method, with a threshold of adjusted P < 0.05 and |logFC(fold change)| > 1.5. Protein–protein interaction networks were constructed using data from the STRING database, followed by module analysis by Cytoscape software to screen crucial genes. Kyoto encyclopedia of genes and genomes pathway and Gene Ontology enrichment analyses were performed to investigate the underlying functions of DEGs using Database for Annotation, Visualization and Integrated Discovery. Consequently, 1,604 and 1,153 DEGs were identified between injured and normal control mice in spinal cord tissue of aged and young mice, respectively. Furthermore, a Venn diagram showed that 960 DEGs were shared among aged and young mice, while 644 and 193 DEGs were specific to aged and young mice, respectively. Functional enrichment indicates that shared DEGs are involved in osteoclast differentiation, extracellular matrix–receptor interaction, nuclear factor-kappa B signaling pathway, and focal adhesion. Unique genes for aged and young injured groups were involved in the cell cycle (upregulation of PLK1) and complement (upregulation of C3) activation, respectively. These findings were confirmed by functional analysis of genes in modules (common, 4; aged, 2; young, 1) screened from protein–protein interaction networks. Accordingly, cell cycle and complement inhibitors may be specific treatments for spinal cord injury in aged and young mice, respectively.

The present study aimed to investigate the biomechanical comparison of channel-assisted minimally invasive restoration and three common Achilles tendon restoration techniques in an in vitro model via a progressive rehabilitation program. The 42 porcine tendons were randomly assigned to the following six groups of tendons (n=7/group): Achillon, percutaneous Achilles repair system (PARS), Krackow, channel-assisted minimally invasive repair (CAMIR), CAMIR augmentation (CAMIR(+)), CAMIR-5 (repair with No. 5 Ethibond suture). There was no significant difference in elongation among groups following the first 10 loading cycles, which consisted of 20-100 N at 1 Hz. The elongation of the CAMIR group (7.51 +/- 1.77 mm) was significantly longer than the Achillon group (3.19 +/- 0.57 mm) and PARS group (3.73 +/- 0.66 mm; P<0.05) following 1,000 cycles. However, the CAMIR group exhibited no significant difference vs. the Krackow (7.32 +/- 1.09 mm) and CAMIR(+) groups (7.11 +/- 1.50 mm) following 1,000 cycles. Following 2,000 cycles, there was no significant difference between the CAMIR-5 (7.99 +/- 1.68 mm) group, and the Achillon (3.19 +/- 0.57 mm) and PARS groups (3.73 +/- 0.66 mm). At the point of restoration construct failure, the total cycles of the CAMIR group (median, 1,000; range, 1,000-1,000) were significantly less than the Achillon group (median, 2,000; range, 2,000-2,013) and PARS group (median, 2,000; range, 2,000-2,010; P<0.05), but had no significant difference compared with the Krackow group (median, 1,000; range, 1,000-1,000) and CAMIR(+) group 1,000 (median, 1,000; range, 1,000-1,004). There was also no significant difference between the CAMIR-5 group (median, 2,000; range, 2,000-2,000), and the Achillon group (median, 2,000; range, 2,000-2,013) and PARS group (median, 2,000; range, 2,000-2,010). Restricted by the strength of suture, the one-suture CAMIR restoration technique was weaker than the three-suture Achillon and PARS restoration techniques, but there was no significant difference with the open Krackow restoration technique, which provides a reliable mechanical strength for repairing. CAMIR has an advantage of reducing the risk of suture reactivity.

Background and objectives: Spinal cord injury is an irreversible pathological process. Clinical findings in recent years have demonstrated that dural sac decompression can scavenge subdural hematoma and necrotic tissue, alleviate compression of the injured spinal cord, create a favorable microenvironment for regeneration of nerve repair, and promote recovery of neurological function. Therefore, this trial aims to examine the effect of dural sac decompression and spinal cord untethering for treating obsolete spinal cord injury. Design: This is a prospective, multicenter cohort study. Methods: Seventy-two patients with obsolete spinal cord injury from four clinical sites in China will be assigned to the trial group (n = 36) or control group (n = 36) according to therapeutic methods. Patients in the trial group will receive dural sac decompression and spinal cord untethering. Patients in the control group will undergo conservative treatment. All patients were followed up for 24 months. Outcome measures: The difference in American Spinal Injury Association scores between 3 months after treatment and before treatment is the primary outcome measure. For secondary outcome measures, the autonomic nervous scoring scale, the Visual Analog Scale, an electromyogram below the injured plane, somatosensory evoked potential, motor evoked potential, functional independent measure, the ID pain self-rating scale, the modified Ashworth Scale for grading spasticity, and the Penn Spasm Frequency Scale will be applied 3 months before treatment, and 1, 3, 6, 9, 12, 18, and 24 months after treatment. Urodynamic testing will be performed. Discussion: This trial is expected to provide an experimental basis for dural sac decompression and spinal cord untethering in patients with obsolete spinal cord injury. Ethics and dissemination: The protocols were approved by the Ethics Committee of Chinese PLA General Hospital on May 11th, 2016 (approval No. S2016-024-01). The study design was finished in April 2016. Recruitment of patients began in April 2017. Follow-up will be completed in December 2018. Data analysis will be completed in December 2019. The results of the trial will be published in a peer-reviewed journal and will be disseminated via various forms of media. Trial registration: This trial has been registered in the Chinese Clinical Trial Registry (registration No. ChiCTR-ONC-17010479) on January 19th, 2017. Recruitment of patients is ongoing.

Background: Traumatic brain injury (TBI) produces lasting neurological deficits that plague patients and physicians. To date, there is no effective method to combat the source of this problem. Here, we utilized a mild, closed head TBI model to determine the modulatory effects of a natural dietary compound, astaxanthin (AST). AST is centrally active following oral administration and is neuroprotective in experimental brain ischemia/stroke and subarachnoid hemorrhage (SAH) models. We examined the effects of oral AST on the long-term neurological functional recovery and histological outcomes following moderate TBI in a mice model.Methods: Male adult ICR mice were divided into 3 groups: (1) Sham + olive oil vehicle treated, (2) TBI + olive oil vehicle treated, and (3) TBI + AST. The olive oil vehicle or AST were administered via oral gavage at scheduled time points. Closed head brain injury was applied using M.A. Flierl weight-drop method. NSS, Rotarod, ORT, and Y-maze were performed to test the behavioral or neurological outcome. The brain sections from the mice were stained with H&E and cresyl-violet to test the injured lesion volume and neuronal loss. Western blot analysis was performed to investigate the mechanisms of neuronal cell survival and neurological function improvement.Results: AST administration improved the sensorimotor performance on the Neurological Severity Score (NSS) and rotarod test and enhanced cognitive function recovery in the object recognition test (ORT) and Y-maze test. Moreover, AST treatment reduced the lesion size and neuronal loss in the cortex compared with the vehicle-treated TBI group. AST also restored the levels of brain-derived neurotropic factor (BDNF), growth-associated protein-43 (GAP-43), synapsin, and synaptophysin (SYP) in the cerebral cortex, which indicates the promotion of neuronal survival and plasticity.Conclusion: To the best of our knowledge, this is the first study to demonstrate the protective role and the underlining mechanism of AST in TBI. Based on these neuroprotective actions and considering its long-standing clinical use, AST should be considered for the clinical treatment of TBI. (C) 2017 Elsevier B.V. All rights reserved.

Atrophic non-union is a serious complication of fractures. The underlying biological mechanisms involved in its pathogenesis are not yet completely understood. MicroRNAs (miRNAs or miRs) are a type of endogenous small non-coding RNA, which participate in various physiological and pathophysiological processes. In this study, differentially expressed miRNAs were screened in patients with atrophic nonunion. In total, 4 miRNAs (miR-149*, miR-221, miR-628-3p and miR-654-5p) were upregulated and 7 miRNAs (let-7b*, miR-220b, miR-513a-3p, miR-551a, miR-576-5p, miR-1236 and kshv-miR-K12-6-5p) were downregulated at the fracture sites in patients with atrophic non-union. Among the upregulated miRNAs, miR-628-3p and miR-654-5p expression was found to be persistently decreased during osteoblast differentiation, indicating their possible inhibitory effect on osteogenesis. Gain-of-function experiment demonstrated that miR-628-3p, but not miR-654-5p, attenuated osteoblast differentiation. Further, in silico analysis revealed that runt-related transcription factor 2 (RUNX2), the master transcript factor for osteoblast differentiation, was the target of miR-628-3p, which had two binding site-condense regions in the 3' untranslated region. The exact binding site of miR-628-3p was further identified with luciferase reporter assay. In addition, the overexpression of miR-628-3p appeared to be associated with the suppression of RUNX2 expression at both the mRNA and protein level, suggesting that miR-628-3p inhibits osteoblast differentiation via RUNX2. On the whole, the findings of this study provide evidence of the upregulation of miR-628-3p in patients with atrophic non-union and that miR-628-3p may exert an inhibitory effect on osteogenesis via the suppression of its target gene, RUNX2. The study provides valuable insight into the pathogenesis of atrophic non-union and suggests new potential therapeutic targets for the treatment of this disorder.

Currently, there are 3 kinds of biomaterials used for treatment of spinal cord injury: Guidance Channels and Scafolds, Hydrogels, Nanoparticles. Each material is made of different chemical materials and has different uses and biocompatibility. Biomaterials are used not only to assist in the transportation and regulation of drug release, but also to provide physical support for the regeneration of injured tissues. Although biological materials have broad prospects in the treatment of spinal cord injury, there is no consistent conclusion to prove which material is the best choice for the repair of spinal cord injury. A series of problems need to be further studied, which include how long treatment measures should persist based on different materials, how long the in vivo half-life is and how is the biological activity of materials when placed in injury of spinal cord in order to obtain the best therapeutic effects and so on.

OBJECTIVE:To review the in vivo imaging research progress of two-photon microscopy (TPM) in spinal cord.METHODS:The recent literature concerning in vivo two-photon imaging of axon, microglia, and calcium in transgenic mice spinal cord was extensively consulted and reviewed.RESULTS:In vivo two-photon imaging of spinal cord provide dynamic information about axonal degeneration and regeneration, microglial accumulation, and calcium influx after spinal cord injury.CONCLUSIONS:TPM in vivo imaging study on spinal cord will provide theoretical foundation for pathophysiologic process of spinal cord injury.