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OBJECTIVE The purpose of this study was to validate the Global Alignment and Proportion (GAP) score as a predictor of health-related quality of life (HRQOL) outcomes for patients undergoing adult spinal deformity (ASD) surgery. METHODS This was a retrospective cohort study of patients with ASD undergoing long-segment spine fusions (≥ 5 vertebrae fused) at a single institution over a 2-year period (n = 85). Radiographic parameters were measured at preoperative, 6-week postoperative, 1-year postoperative, and 2-year postoperative visits. GAP scores were calculated using 4 sagittal parameters: relative pelvic version, relative lumbar lordosis, lordosis distribution index, and relative spinopelvic alignment. Patients were stratified into 3 GAP categories at each time point: proportioned (score 0–2), moderately disproportioned (score 3–6), and severely disproportioned (score ≥ 7). HRQOL outcomes were collected at preoperative, 1-year postoperative, and 2-year postoperative visits; these measures included patient self-reported outcome measures (i.e., PROMIS), Scoliosis Research Society-22 spinal deformity questionnaire (SRS-22), and Oswestry Disability Index (ODI) scores. RESULTS Overall, 42% of cases were revision surgeries and 96.5% of patients underwent fusion to the sacrum. The mean preoperative GAP score significantly improved from preoperative (7.84) to immediate postoperative (3.31) assessment (p < 0.001). Similarly, the percentage of patients categorized as proportioned improved from 9.4% at preoperative to 45.9% at immediate postoperative evaluation. The preoperative GAP score or category was not significantly associated with any preoperative HRQOL outcome metrics. The immediate postoperative GAP score was not correlated with any 1-year HRQOL outcomes. However, the immediate postoperative GAP score was significantly associated with 2-year SRS-22 outcomes, including SRS-22 function (r = −0.35, p < 0.01), self-image (r = −0.27, p = 0.044), and subtotal (r = −0.35, p < 0.01) scores. As compared to severely disproportioned patients, proportioned patients had better SRS-22 pain (4.08 vs 3.17, p = 0.04), satisfaction (4.40 vs 3.50, p = 0.02), and subtotal (4.01 vs 3.27, p = 0.036) scores. The immediate postoperative GAP score was also significantly associated with 2-year PROMIS outcomes, including PROMIS pain (r = 0.31, p = 0.023) and physical function (r = −0.35, p < 0.01) scores. As compared to severely disproportioned patients, proportioned patients had better PROMIS pain (53.18 vs 63.60, p = 0.025) and physical function (41.66 vs 34.18, p = 0.017) scores. Postoperative GAP score or category did not predict any ODI outcomes. CONCLUSIONS The postoperative GAP score is a predictor of long-term HRQOL outcomes following ASD surgery, and proportioned patients are more likely to have less pain and be satisfied with their surgery. However, the postoperative GAP score does not predict outcomes as measured by ODI.

OBJECTIVE The objective of this study was to evaluate spinopelvic sagittal alignment and spinal compensatory changes in adult cervical kyphotic deformity. METHODS A database composed of 13 US spine centers was retrospectively reviewed for adult patients who underwent cervical reconstruction with radiographic evidence of cervical kyphotic deformity: C2–7 sagittal vertical axis > 4 cm, chin-brow vertical angle > 25°, or cervical kyphosis (T1 slope [T1S] cervical lordosis [CL] > 15°) (n = 129). Sagittal parameters were evaluated preoperatively and in the early postoperative window (6 weeks to 6 months postoperatively) and compared with asymptomatic control patients. Adult cervical deformity patients were further stratified by degree of cervical kyphosis (severe kyphosis, C2–T3 Cobb angle ≤ −30°; moderate kyphosis, ≤ 0°; and minimal kyphosis, > 0°) and severity of sagittal malalignment (severe malalignment, sagittal vertical axis T3–S1 ≤ −60 mm; moderate malalignment, ≤ 20 mm; and minimal malalignment > 20 mm). RESULTS Compared with asymptomatic control patients, cervical deformity was associated with increased C0–2 lordosis (32.9° vs 23.6°), T1S (33.5° vs 28.0°), thoracolumbar junction kyphosis (T10–L2 Cobb angle −7.0° vs −1.7°), and pelvic tilt (PT) (19.7° vs 15.9°) (p < 0.01). Cervicothoracic kyphosis was correlated with C0–2 lordosis (R = −0.57, p < 0.01) and lumbar lordosis (LL) (R = −0.20, p = 0.03). Cervical reconstruction resulted in decreased C0–2 lordosis, increased T1S, and increased thoracic and thoracolumbar junction kyphosis (p < 0.01). Patients with severe cervical kyphosis (n = 34) had greater C0–2 lordosis (p < 0.01) and postoperative reduction of C0–2 lordosis (p = 0.02) but no difference in PT. Severe cervical kyphosis was also associated with a greater increase in thoracic and thoracolumbar junction kyphosis postoperatively (p = 0.01). Patients with severe sagittal malalignment (n = 52) had decreased PT (p = 0.01) and increased LL (p < 0.01), as well as a greater postoperative reduction in LL (p < 0.01). CONCLUSIONS Adult cervical deformity is associated with upper cervical hyperlordotic compensation and thoracic hypokyphosis. In the setting of increased kyphotic deformity and sagittal malalignment, thoracolumbar junction kyphosis and lumbar hyperlordosis develop to restore normal center of gravity. There was no consistent compensatory pelvic retroversion or anteversion among the adult cervical deformity patients in this cohort.

Impaired wound healing is a common complication of orthopedic surgery and poses a difficult challenge in the clinic. Fibroblasts are thought to play a significant role in wound healing, and can be positively affected by low concentrations of rapamycin; however, rapamycin is cytotoxic at higher concentrations. To address this issue, a RAPA/PLGA-PEG drug delivery system was constructed in this study to maintain low concentrations of rapamycin. The results showed that the nanoparticles were stable, had good sustained drug release properties and were able to reduce the toxicity of rapamycin to fibroblasts. These findings suggest that RAPA/PLGA-PEG nanoparticles can reduce the cytotoxicity of rapamycin and may be a potential clinical treatment for impaired wound healing.

Thoracolumbar metastases is a difficult disease to deal with in spinal surgery. The aim of this study is to investigate the clinical efficacy of bone-filled mesh vertebroplasty combined with posterior spinal internal fixation in the treatment of thoracolumbar metastases.The clinical data of 68 patients with thoracolumbar vertebral metastases from January 2018 to April 2020 were retrospectively analyzed. A total of 37 cases underwent bone filling mesh pocket vertebroplasty combined with posterior spinal internal fixation as the observation group, and 31 cases underwent routine vertebroplasty combined with posterior spinal internal fixation as the control group. The visual analogue scale (VAS) scores, Oswestry disability index (ODI) scores, Karnofsky performance status (KPS) scores, and the heights of the anterior margin and middle of the diseased vertebra were compared between the 2 groups before and 1 week, 3 months, 6 months, and 1 year after surgery.All cases successfully completed the operation, and there was no pulmonary embolism, paraplegia, or perioperative death in follow-up reported. Intraoperative bone cement leakage occurred in 4 cases with a total of 6 vertebrae in the observation group (leakage rate: 14.29%), and in 8 cases with a total of 11 vertebrae in control group (leakage rate: 31.43%). The differences in VAS scores, ODI scores, KPS scores, and the heights of the anterior margin and middle of the diseased vertebra between preoperative and postoperative periods at 1 week, 3 months, 6 months, and 1 year in both groups were statistically significant (P0.05), while the differences between the 2 groups were not statistically significant (P0.05).The application of bone-filled mesh vertebroplasty combined with posterior internal pedicle screws fixation for the treatment of thoracolumbar metastases can not only reduce the injury of the operation, but also achieve the purpose of relieving pain, controlling local tumor growth to a certain extent, restoring neural function, and rebuilding the stability of the spine, which has important clinical value.

Multimodal intraoperative monitoring (MIOM) is a useful tool to warn surgeons to intervene for intraoperative spinal cord injury in cervical spine surgery. However, the value of MIOM remains controversial before cervical spine surgery.To explore the value of MIOM in early detecting spinal cord injury associated with neck extension before cervical spine surgery.Data of 191 patients receiving cervical spine surgery with the MIOM were enrolled from June 2014 to June 2020. The subjects were divided into a group of evoked potentials (EP) changes and a group of no EP changes for analysis according to the monitoring alerts or not.Five (2.62%) patients showed EP changes associated with neck extension during intubation or positioning. After early different interventions, such as repositioning and timely surgical decompression, none or transient postoperative neurological deficits were observed in four cases, and only one case was with permanent neurological deficits. The average preoperative Japanese Orthopaedic Association (JOA) scores of the group with EP changes were lower than those of the group with no EP changes (P = 0.0370.05). There was no statistical significance in gender, average age, mean Pavlov ratio, and the minimum Palov ratio between the two groups (P0.05).The MIOM could identify spinal cord injury associated with neck extension before cervical spine surgery. Active and effective interventions could prevent or reduce permanent postoperative neurological deficits. Severe spinal cord compression might be a risk factor for EP changes.

As one of the important Power to X technologies, CO2 methanation realizes the storage of green hydrogen and the emission reduction of flue gas CO2. In this study, process modeling was applied for CO2 methanation coupled with CO2 capture and water electrolysis. Aspen Plus and HYSYS models of 400 kW water electrolysis were set up for integration. The heat exchange network and the reaction temperature and catalyst usage of two methanation reactors are optimized. The effects of step-wise evolution of H2 flow on stream flows and reactors are also studied. The results show a system energy efficiency of 42.3% using a high-temperature solid oxide electrolysis cell (SOEC) and 30% monoethanolamide solution (MEA). The heat-exchange network significantly improves the efficiency to 61.5%. Optimizing two-stage methanation reactors realizes 98% CO2 conversion at 10018 h-1 gas hourly space velocity. The optimized reaction temperatures are 390 and 325 °C, respectively. The Aspen HYSYS dynamic modeling shows that the flows reach stability within 10 min under 1 kmol/h step-wise evolution of H2 flow. Longer time is required to approach the stability of the methanation reactor. Sharp evolutions of H2 flow cause higher amplitudes and a longer time to reach stability. The H2 flow lower than 35% of the initial value would result in the unstable behavior of the methanation reactor.

CO2 methanation shows advantages in Power-to-Gas technologies using renewable energy. In this article, Sm doped Ce x Sm y Zr1−x−y O2-δ complex is prepared using a one-pot hydrolysis method and is used as support for the Ru-Ni catalyst. The CO2 methanation activity at high temperature, GHSV, and thermal stability is tested. The results show that Sm doping is unfavorable for low-temperature methanation activity, but improves the thermal stability with Sm doping amount of 10 mol%. The Sm doping significantly enhances the performance at high temperatures (>400 °C ) and high GHSV (> 10000 h−1). Five reaction rate equations with different adsorption expressions are applied for kinetic analysis. Low activation energies ranging between 50.1 kJ/mol and 53.2 kJ/mol are observed for different models, which are lower than reported Ni-based catalysts. The equation considering both CO2 and H2O adsorption achieves the best-fitting results.

OBJECTIVEThe aim of this work was to investigate the effects of methylprednisolone on the proliferation of endogenous neural stem cells (ENSCs) in nonhuman primates with spinal cord injury (SCI).METHODSA total of 14 healthy cynomolgus monkeys (Macaca fascicularis) (4–5 years of age) were randomly divided into 3 groups: the control group (n = 6), SCI group (n = 6), and methylprednisolone therapy group (n = 2). Only laminectomy was performed in the control animals at T-10. SCI was induced in monkeys using Allen’s weight-drop method (50 mm × 50 g) to injure the posterior portion of the spinal cord at T-10. In the methylprednisolone therapy group, monkeys were intravenously infused with methylprednisolone (30 mg/kg) immediately after SCI. All animals were intravenously infused with 5-bromo-2-deoxyuridine (BrdU) (50 mg/kg/day) for 3 days prior to study end point. The small intestine was dissected for immunohistochemical examination. After 3, 7, and 14 days, the spinal cord segments of the control and SCI groups were dissected to prepare frozen and paraffin sections. The proliferation of ENSCs was evaluated using BrdU and nestin immunofluorescence staining.RESULTSHistological examination showed that a larger number of mucosa epithelial cells in the small intestine of all groups were BrdU positive. Nestin-positive ependymal cells are increased around the central canal after SCI. After 3, 7, and 14 days of SCI, BrdU-positive ependymal cells in the SCI group were significantly increased compared with the control group, and the percentage of BrdU-positive cells in the left/right ventral horns and dorsal horn was significantly higher than that of the control group. Seven days after SCI, the percentages of both BrdU-positive ependymal cells around the central canal and BrdU– and nestin–double positive cells in the left/right ventral horns and dorsal horn were significantly lower in the methylprednisolone therapy group than in the SCI group.CONCLUSIONSWhile ENSCs proliferate significantly after SCI in nonhuman primates, methylprednisolone can inhibit the proliferation of ependymal cells after SCI.

The aim of this study is to evaluate the influences of different bone graft heights on the size of the intervertebral foramen, which will help determine the optimal graft height in clinical practice. Six fresh adult cadavers were used, with the C5-C6 vertebral column segment defined as the functional spinal unit (FSU). After discectomy, the C5/6 intervertebral height was set as the baseline height (normal disc height). We initially used spiral computed tomography (CT) to scan and measure the middle area of the intervertebral foramen when at the baseline height. Data regarding the spatial relationship of C5-C6 were subsequently collected with a laser scanner. Grafting with four different sized grafts, namely, grafts of 100, 130, 160, and 190% of the baseline height, was implanted. Moreover, we scanned to display the FSU in the four different states using Geomagic8.0 studio software. Multiple planar dynamic measurements (MPDM) were adopted to measure the intervertebral foramen volume, middle area, and areas of internal and external opening. MPDM with a laser scanner precisely measured the middle area of the intervertebral foramen as spiral CT, and it is easy to simulate the different grafts implanted. With the increase of the bone graft height, the size of the intervertebral foramen began to decrease after it increased to a certain point, when grafts of 160% of the baseline height implanted. MPDM of the intervertebral foramens with laser scanning three-dimensional (3D) reconstitution are relatively objective and accurate. The recommended optimal graft height of cervical spondylosis is 160% of the mean height of adjacent normal intervertebral spaces.

STUDY DESIGN: A hospital-based retrospective epidemiological study. OBJECTIVE: To examine the demographic and epidemiological characteristics of patients with TSCI in Guangdong to help health-related institutions develop measures to determine the best allocation of medical resources. SUMMARY OF BACKGROUND DATA: Traumatic spinal cord injury (TSCI) is a highly disabling and deadly injury. Currently, there is little information regarding the epidemiological characteristics for TSCI in Guangdong. METHODS: We retrospectively reviewed the medical records of partial second-grade class-A hospitals (mainly capturing general city and county hospitals and some large-scale affiliated hospitals) in Guangdong province according to the International Classification of Disease Version 10 (ICD-10) and diagnostic code of TSCI. RESULTS: The study included the medical records of 1,340 patients with TSCI, and the annual number of TSCI admissions increased during the 2003-2011 period. The male-to-female ratio was approximately 3.5:1. The major causes of spinal cord injuries were high falls (41.0%) and traffic accidents (37.8%). The most common injury among patients with TSCI was cervical injury (818 cases). In addition, 62.9% of the patients had spinal fractures, 24.0% had other fractures, and 13.7% had brain injuries. Furthermore, 25.1% (337/1,340) of the patients experienced clinical complications. The differences in the number of patients with and without complete injury who accepted surgery and hyperbaric oxygen therapy were statistically significant (P CONCLUSIONS: The epidemiological characteristics of TSCI in Guangdong has its own characteristics, and preventive measures should focus on high-risk populations, such as adult men. LEVEL OF EVIDENCE: 3. Language: en

This study tried to quantify spinal cord perfusion by using contrast-enhanced ultrasound (CEUS) in rhesus monkey models with acute spinal cord injury. Acute spinal cord perfusion after injury was detected by CEUS, coupling with conventional ultrasound (US) and Color Doppler US (CDFI). Time-intensity curves and perfusion parameters were obtained by autotracking contrast quantification (ACQ) software in the epicenter and adjacent regions of injury, respectively. Neurological and histological examinations were performed to confirm the severity of injury. US revealed spinal cords were hypoechoic and homogeneous, whereas dura maters, pia maters, and cerebral aqueducts were hyperechoic. After spinal cord contusion, the injured spinal cord was hyperechoic on US, and intramedullary vessels of adjacent region of injury were increased and dilated on CDFI. On CEUS hypoperfusion were found in the epicenter of injury, while hyperperfusion in its adjacent region. Quantitative analysis showed that peak intensity (PI) decreased in epicenters of injury but significantly increased in adjacent regions at all time points (p < 0.05). Functional evaluation demonstrated significant deterioration compared to pre-contusion (p < 0.05). Quantitative analysis with CEUS is a promising method for monitoring perfusion changes of spinal cord injury in overall views and real-time.

To describe the retroperitoneoscopic debridement technique and evaluate the clinical outcome of internal fixation for the treatment of lumbar tuberculosis. Twenty-eight patients were performed conventional laparoendoscopic technique (n = 17) or laparoendoscopic single-site technique (n = 11). Antituberculosis chemotherapy and thoracolumbosacral orthosis were given to all patients. The clinical outcomes were evaluated with preoperative and postoperative Visual Analog Scale, and radiographs with respect to sagittal angle and fusion status. Average time of the 28 procedures was 220.6 ± 50.9 min (180–365 min). The average intraoperative blood loss was 108.6 ± 95.3 mL (50–400 mL). All patients showed significant improvement of their Visual Analog Scale back pain score at follow-up and were classified as having a radiographic fusion in this study. The mean sagittal angle was 11.2 ± 3.6° before operation, significantly improved to 3.7 ± 2.4° after operation. There were no recurrent infections during the follow-up period. Complications included loosening of anterior fixation and temporary deficit of the sympathetic nerve. Retroperitoneal laparoscopic approach with CO2 insufflation technique is a challenging but safe and effective procedure for lumbar spine tuberculosis. Retroperitoneal laparoendoscopic single-site can be used for anterior lumbar spine surgery, offer exposure for L1 through L5.

Purpose To access the feasibility and efficacy of percutaneous endoscopic debridement (PED) combined with percutaneous pedicle screw fixation (PPSF) in the treatment of lumbar pyogenic spondylodiscitis. Methods Forty-five patients diagnosed as pyogenic spondylodiscitis underwent PPSF followed by PED. A drainage catheter was left in place for negative pressure drainage. Adequate systematic antibiotics were administered empirically or based on bacterial culture results. Clinical outcomes were assessed by physical examination, regular serologic testing, visual analog scale (VAS), Oswestry Disability Index (ODI), and imaging studies. Results The mean operative time was 110.1 ± 21.2 minutes (range 80–165 minutes), with intra-operative blood loss 47.8 ± 21.0 ml (range 20–120 ml). All patients reported relief of back pain, able to sit up, and partially ambulate the next day. Causative pathogens were identified in 32 of 45 biopsy specimens, staphylococcal bacteria being the most prevalent strain. However, there were 13 patients with post-operative complications. During 6–12 months’ follow-up, inflammatory markers showed infection controlled. VAS and ODI values were significantly improved. Discussion Satisfactory clinical and functional outcomes were achieved in our patients post-operatively. It is recommended that PED plus PPSF can be another alternative for spondylodiscitis. Conclusion PED supplementing PPSF offers a valid option in treating spondylodiscitis, as it is minimally invasive, shortens hospital stay, and avoids prolonged bed rest with an optimistic outcome.

The nuclear receptor corepressor (N-CoR) is involved in the regulation of diverse transcription factors. We previously found that N-CoR could regulate adipogenic differentiation of rat mesenchymal stem cells (MSCs), but whether it modulated osteogenic differentiation of this type of cells was uncertain. Therefore, in the present study, we investigated the effect and mechanism of N-CoR on osteogenic differentiation of rat MSCs. The results showed that MSCs cultured in osteogenic medium successfully differentiated into osteogenic cells. Overexpression of N-CoR decreased cell proliferation, alkaline phosphatase (ALP) activity, calcium accumulation, mRNA expression of genes including bone sialoprotein (BSP), osteocalcin (OCN), osteopontin (OPN), Osterix and Runx2, and protein expression of phosphor-Akt (pAkt). Conversely, knocking down cellular N-CoR by small interfering RNA (siRNA) promoted pAkt activity and cell differentiation. Overexpression or knockdown of N-CoR had no significant influences on the protein expression of pyruvate dehydrogenase kinase isozyme 1 (PDK1), phosphatidylinositol 3-kinase (PI3K) and total Akt, indicating that N-CoR regulated the changes in the PI3K/Akt signaling pathway by targeting pAkt. To further prove the function of the PI3K/Akt signaling in N-CoR-regulated osteogenic differentiation, we used the PI3K inhibitor (LY294002) to block the activation of the PI3K/Akt pathway and found that overexpression of N-CoR showed no effects on ALP activity, calcium level and mRNA expression of BSP, osteocalcin OCN, OPN, Osterix and Runx2 in rat MSCs following the inhibition of the PI3K/Akt pathway. These findings suggest that N-CoR regulates osteogenic differentiation of rat MSCs through suppression of the PI3K/Akt signaling pathway. Key words : N-CoR; MSCs; osteogenic differentiation; PI3K; Akt Received: September 1, 2015; Revised: October 16, 2015; Accepted: October 21, 2015; Published online: April 27, 2016

The present study aimed to investigate candidate genes involved in the development and metastasis of osteosarcoma. Candidate genes were screened preliminarily from the Gene Expression Omnibus database and then validated using actual tumor tissues collected from patients with osteosarcoma. The cells were prepared and transfected with specific gene-targeted small interfering RNA followed by an MTS assay for cell viability detection and Transwell assays for cell migration and invasion capacity detection. The cell apoptosis was determined by flow cytometry and the protein level of the genes was detected by western blot analysis. An in vivo nude model was used and injected with cells to detect the functions of the genes. Transcriptome sequencing was performed to verify the regulation network, followed by reverse transcription-quantitative polymerase chain reaction and western blot analyses for validation. Increased tripartite motif-containing protein 2 (TRIM2) was detected in the osteosarcoma tumor tissues compared with normal tissues. The inhibition of TRIM2 induced lower cell viability and cell invasion capacity, and increased the rate of cell apoptosis. Decreased TRIM2 also inhibited the development and metastasis of osteosarcoma in the nude mouse models. The transcriptome sequencing revealed that the regulation of TRIM2 may be correlated with genes, Sirtuin 4, DNA damage inducible transcript 3, cAMP responsive element binding protein 5, G protein-coupled receptor 65 (GPR65) and ADP-ribosyltransferase 5. Western blot analysis indicated that TRIM2 regulated the development and metastasis of osteosarcoma via the phosphoinositide 3-kinase/protein kinase B signaling pathway. Therefore, TRIM2 performs important functions in regulating the development and metastasis of osteosarcoma.

Background context The understanding of vascular supply to the spinal cord is important given that the evolution of surgical approaches to the spine may bring along the potential for more frequent complications, especially a rare but devastating complication: that of spinal cord ischemia or infarction. To maximally avoid this complication, the relationship between the spinal cord vascularity and the anterior spine surgical approach needs further study. Purpose To provide a theoretical basis that will allow the spinal surgeon to take appropriate steps to avoid spinal cord ischemia during anterior spinal surgery through anatomic means. Study design Spinal cord vascular casting assessment with cadaveric specimen. Methods Twenty adult cadaveric specimens (11 men and 9 women) were obtained for the latex perfusion and vessel dissection. In addition, nine patients (seven men and two women) underwent superselective angiography of the spinal cord. The segmental arterial anastomosis and radiculomedullary vessels in the thoracolumbar region were shown and reviewed. Results There were approximately 21 pairs of segmental arteries in the thoracolumbar region. Adjacent segmental arteries were networked with each other. The latex infusion specimens demonstrated 72 anterior radiculomedullary arteries and 177 posterior radiculomedullary arteries in all 20 samples. The anterior and posterior spinal arteries were also networked with each other at several levels. Superselective spinal angiography was consistent with the latex infusion specimens showing. Conclusions The variety of anatomy of spinal cord arterial networks is shown, and the relation between the blood supply of certain spinal levels and the potential ischemic complications during the anterior surgical approach is discussed. It is hopefully of benefit to surgeons, after fully understanding the anatomy of these spinal vascular supply structures, that there may be even greater avoidance of vascular compromise in these challenging operations.

Endogenous neural stem cells (NSCs) are the most promising sources for replacing cells lost after spinal cord injury (SCI). We have previously shown that substance P (SP), a neuropeptide, improves functional recovery after SCI and increases the numbers of cells in lesion sites, but how this occurs is unclear. Here, we investigate whether SP regulates the neurogenesis of resident NSCs as well as exerting a beneficial effect on functional improvement. We found that SP (5nmol/kg) treatment markedly improved functional recovery and elicited robust activation of endogenous NSCs and boosted the number of EdU+ proliferating cells differentiating into neurons, but it reduced astroglial differentiation in the lesion sites. Consistently, treatment with SP (10nM) in vitro significantly increased the proliferation of NSCs via activating the Erk1/2 signaling pathway and promoted neuronal differentiation but not astroglial differentiation. These results suggest that SP may represent a potential therapeutic agent for SCI via enhancing endogenous neurogenesis.

Nonhuman primate models of spinal cord injury (SCI) have been widely used in evaluation of the efficacy and safety of experimental restorative interventions before clinical trials. However, no objective methods are currently available for the evaluation of neural function in nonhuman primates. In our long-term clinical practice, we have used evoked potential (EP) for neural function surveillance during operation and accumulated extensive experience. In the present study, a nonhuman primate model of SCI was established in 6 adult cynomologus monkeys through spinal cord contusion injury at T8–T9. The neural function before SCI and within 6 months after SCI was evaluated based on EP recording. A scoring system including somatosensory evoked potentials (SSEPs) and transcranial electrical stimulation-motor evoked potentials (TES-MEPs) was established for the evaluation of neural function of nonhuman primates with SCI. We compared the motor function scores of nonhuman primates before and after SCI. Our results showed that the EP below the injury level significantly changed during the 6 months after SCI. In addition, a positive correlation was identified between the EP scores and motor function. The EP-based scoring system is a reliable approach for evaluating the motor function changes in nonhuman primates with SCI.

miR-223 inhibits the advanced glycation end product (AGE)-promoted apoptosis in osteoblasts., Advanced glycation end products (AGEs) have been confirmed to induce bone quality deterioration in diabetes mellitus (DM), and to associate with abnormal expression of miRNAs in DM patients or in vitro. Recently, miRNAs have been recognized to mediate the onset or progression of DM. In the present study, we investigated the regulation on miR-223 level by AGE-BSA treatment in osteoblast-like MC3T3-E1 cells, with real-time quantitative PCR assay. And then we examined the inhibition of insulin-like growth factor 1 receptor (IGF-1R) expression by miR-223, via targeting of the 3′ UTR of IGF-1R with real-time quantitative PCR, western blotting and luciferase reporter assay. Then we explored the regulation of miR-223 and IGF-1R levels, via the lentivirus-mediated miR-223 inhibition and IGF-1R overexpression in the AGE-BSA-induced apoptosis in MC3T3-E1 cells. It was demonstrated that AGE-BSA treatment with more than 100 μg/ml significantly up-regulated miR-223 level, whereas down-regulated IGF-1R level in MC3T3-E1 cells. And the up-regulated miR-223 down-regulated IGF-1R expression in both mRNA and protein levels, via targeting the 3′ UTR of IGF-1R. Moreover, though the AGE-BSA treatment promoted apoptosis in MC3T3-E1 cells, the IGF-1R overexpression or the miR-223 inhibition significantly attenuated the AGE-BSA-promoted apoptosis in MC3T3-E1 cells. In summary, our study recognized the promotion of miR-223 level by AGE-BSA treatment in osteoblast-like MC3T3-E1 cells. The promoted miR-223 targeted IGF-1R and mediated the AGE-BSA-induced apoptosis in MC3T3-E1 cells. It implies that miR-223 might be an effective therapeutic target to antagonize the AGE-induced damage to osteoblasts in DM.

The aim of this study was to test the sensitivity and specificity of diffusion-weighted MRI for the detection of acute spinal cord injury. Forty female New Zealand white rabbits were randomly divided into four groups: the mild, moderate and severe injury groups, and the control (sham operation) group. Contusion of the spinal cord was induced using a weight-drop impactor. All animals were imaged using T1-weighted, T2-weighted, and diffusion-weighted imaging (DWI) sequences at 30 minutes, 6 hours, and 24 hours after injury. One animal from each group was killed at each time point for histologic examination of the spinal cord. DWI had a sensitivity of 100% at all time points, whereas T2-weighted MRI had a sensitivity of 43.33% at 30 minutes after injury, 81.48% at 6 hours after injury, and 95.83% at 24 hours after injury. Conversely, the specificity of DWI was lower than that of T2-weighted MRI at all time points. One animal in the control group had a non-specific high signal on DWI. Significant systematic differences were seen between DWI and T2-weighted MRI at both 30 minutes and 6 hours after injury. The apparent diffusion coefficient values of the lesion were lower than those of adjacent unaffected regions in the mild and moderate injury groups, but higher than adjacent unaffected regions in the severe injury group. The histological findings were reliably correlated with the magnetic resonance findings. We found that DWI has a higher sensitivity, but a lower specificity, than conventional MRI for the detection of early pathological changes after contusive injury.

Polymethylmethacrylate (PMMA) bone cement, which is used as a filler material in vertebroplasty, is one of the major sources of pulmonary embolism in patients who have undergone vertebroplasty. In the present study, we established and evaluated two animal models of pulmonary embolism by injecting PMMA or biphasic calcium composite (BCC) bone cement with a negative surface charge. A total of 12 adults and healthy Wuzhishan minipigs were randomly divided into two groups, the PMMA and BBC groups, which received injection of PMMA bone cement and BBC bone cement with a negative surface charge in the circulation system through the pulmonary trunk, respectively, to construct animal models of pulmonary embolism. The hemodynamics, arterial blood gas, and plasma coagulation were compared between these two groups. In addition, morphological changes of the lung were examined using three-dimensional computed tomography. The results showed that both PMMA and BCC injections induced pulmonary embolisms in minipigs. Compared to the PMMA group, the BCC group exhibited significantly lower levels of arterial pressure, pulmonary artery pressure, blood oxygen pressure, blood carbon dioxide pressure, blood bicarbonate, base excess, antithrombin III and D-dimer. In conclusion, BCC bone cement with a negative surface charge is a promising filler material for vertebroplasty.

To evaluate the clinical outcomes of total en-bloc spondylectomy (TES) in recurrence spinal tumor.The study was a retrospective study of recurrence spinal tumor from January 2010 to October 2013. A total of 6 patients with recurrent spinal tumor underwent TES procedures, with 5 cases located in thoracic spine and 1 case located in L1. There were 3 male and 3 female patients, with a mean age of 33.2 years. Pathological diagnosis included giant cell tumor of bone in 3 cases, breast cancer, lung cancer and nasopharyngeal carcinoma with 1 case in each. The operation time, bleeding loss, resected segments, cutting edge, spinal cord function and complications was evaluated.Single segment resected in 1 case, 2 segments resected in 2 cases and 3 segments resected in 3 cases. The average operation time was 8.9 hours (7.5 to 12.0 hours). The average blood loss was 3 116 ml (2 500 to 4 500 ml). The average follow-up period was 23.2 months (12 to 47 months) without recurrence. There was no spinal cord injury during operation. The neurologic function was significantly improved in 2 cases (American Spinal Injury Association (ASIA) grade C to grade D), unchanged in 1 cases (ASIA grade B) and no deteriorated case in 3 cases (ASIA grade E). There was no perioperative deaths case. Complications included 2 cases pleural rupture, 1 case dural tear and 1 case massive haemothorax. No peri-operation death case.Some of the recurrent spinal tumors are still suitable for en-bloc resection and TES procedure with the extent of its applicability under strict control.

Transplanted primates' neural stem cells (NSCs) tissue engineering complex into spinal cord injury (SCI) model rats, analyze and evaluate the long-term effects of repairing.Primate NSCs were cultured in self-assembling peptide nanofiber scaffolds to repair SCI.Sun Yat-sen Memorial Hospital, Guangzhou, China.Primate NSCs were isolated and cultured in self-assembling peptide nanofiber scaffolds. T10 SCI model was established; the rats were randomly divided into four groups: NSC plus self-assembling peptide scaffold group; NSC group; self-assembling peptide scaffold group; and control group. Immunohistochemical staining and electronic microscope were used to investigate the growth and differentiation of transplanted NSCs. The motor function of the hind limbs of rats was evaluated (P0.05 was considered as statistically significant).NSCs and NSCs cultured in self-assembling peptide nanofiber scaffolds could be induced to differentiation into neurons, glial cells and oligodendrocytes in vitro. The primate NSC culture was established in self-assembling peptide scaffolds. No significant difference was seen in the differentiation rate between primate NSCs cultured in self-assembling peptide nanofiber scaffolds and primate NSCs cultured in regular medium. The motor function of the hind limbs in the NSC plus self-assembling peptide scaffold group was significantly better than that of the other three groups. In addition, the NSCs of the NSC group mainly differentiated into astrocytes.Transplantation of primate NSCs cultured in self-assembling peptide scaffolds is efficient for repairing the injured spinal cord and for improving the motor function of spinal cord in rats.The National Natural Science Foundation of China; Science and Technology Office of Guangdong Province.

Our objective was to evaluate the feasibility, safety, and efficacy of intravenous (IV) infusion of allogenic mesenchymal stem cells (MSCs) in ankylosing spondylitis (AS) patients who are refractory to or cannot tolerate the side effects of nonsteroidal anti-inflammatory drugs (NSAIDs). AS patients enrolled in this study received four IV infusions of MSCs on days 0, 7, 14, and 21. The percentage of ASAS20 responders (the primary endpoint) at the fourth week and the mean ASAS20 response duration (the secondary endpoint) were used to assess treatment response to MSC infusion and duration of the therapeutic effects. Ankylosing Spondylitis Disease Activity Score Containing C-reactive Protein (ASDAS-CRP) and other preestablished evaluation indices were also adopted to evaluate the clinical effects. Magnetic resonance imaging (MRI) was performed to detect changes of bone marrow edema in the spine. The safety of this treatment was also evaluated. Thirty-one patients were included, and the percentage of ASAS20 responders reached 77.4% at the fourth week, and the mean ASAS20 response duration was 7.1 weeks. The mean ASDAS-CRP score decreased from 3.6 ± 0.6 to 2.4 ± 0.5 at the fourth week and then increased to 3.2 ± 0.8 at the 20th week. The average total inflammation extent (TIE) detected by MRI decreased from 533,482.5 at baseline to 480,692.3 at the fourth week ( p > 0.05) and 400,547.2 at the 20th week ( p < 0.05). No adverse effects were noted. IV infusion of MSCs is a feasible, safe, and promising treatment for patients with AS.

The pathogenesis of dysfunctional immunoregulation of mesenchymal stem cells (MSCs) in ankylosing spondylitis (AS) is thought to be a complex process that involves multiple genetic alterations. In this study, MSCs derived from both healthy donors and AS patients were cultured in normal media or media mimicking an inflammatory environment. Whole genome expression profiling analysis of 33,351 genes was performed and differentially expressed genes related to AS were analyzed by GO term analysis and KEGG pathway analysis. Our results showed that in normal media 676 genes were differentially expressed in AS, 354 upregulated and 322 downregulated, while in an inflammatory environment 1767 genes were differentially expressed in AS, 1230 upregulated and 537 downregulated. GO analysis showed that these genes were mainly related to cellular processes, physiological processes, biological regulation, regulation of biological processes, and binding. In addition, by KEGG pathway analysis, 14 key genes from the MAPK signaling and 8 key genes from the TLR signaling pathway were identified as differentially regulated. The results of qRT-PCR verified the expression variation of the 9 genes mentioned above. Our study found that in an inflammatory environment ankylosing spondylitis pathogenesis may be related to activation of the MAPK and TLR signaling pathways.

BACKGROUND: Spinal cord injuries are highly disabling and deadly injuries. Currently, few studies focus on non-traumatic spinal cord injuries, and there is little information regarding the risk factors for complete injuries. This study aims to describe the demographics and the injury characteristics for both traumatic and non-traumatic spinal cord injuries and to explore the risk factors for complete spinal cord injuries. METHODS: A retrospective study was performed by reviewing the medical records of 3,832 patients with spinal cord injuries who were first admitted to the sampled hospitals in Guangdong, China. The demographics and injury characteristics of the patients were described and compared between the different groups using the chi-square test. Logistic regression was conducted to analyze the risk factors for complete spinal cord injuries. RESULTS: The proportion of patients increased from 7.0% to 14.0% from 2003 to 2011. The male-to-female ratio was 3.0∶1. The major cause of spinal cord injuries was traffic accidents (21.7%). Many of the injured were workers (36.2%), peasants (22.8%), and unemployed people (13.9%); these occupations accounted for 72.9% of the total sample. A multivariate logistic regression model revealed that the OR (95% CI) for male gender compared to female gender was 1.25 (1.07-1.89), the OR (95%CI) for having a spinal fracture was 1.56 (1.35-2.60), the OR (95%CI) for having a thoracic injury was 1.23 (1.10-2.00), and the OR (95%CI) for having complications was 2.47 (1.96-3.13). CONCLUSION: The proportion of males was higher than the proportion of females. Workers, peasants and the unemployed comprised the high-risk occupational categories. Male gender, having a spinal fracture, having a thoracic injury, and having complications were the major risk factors for a complete injury. We recommend that preventive measures should focus on high-risk populations, such as young males. Language: en

The objectives of this study were to describe our surgical management with a modified total en bloc spondylectomy (TES) and to evaluate the clinical effects in patients with thoracolumbar tumors.Sixteen consecutive patients with thoracolumbar neoplasms underwent a modified TES via single posterior approach followed by dorsoventral reconstruction from December 2008 to July 2011. Details of the modified technique were described and the patients' clinical information was retrospectively reviewed and analyzed.Significant improvements in neurological function were achieved in most of the patients. Local pain or radicular leg pain was relieved postoperatively. The mean operation time was 7.2 h, with an average blood loss of 2,300 ml. No major complications, instrumentation failure or local recurrence was found at the final follow-up. Five patients died of the disease during mean 14-month (3.0-23) follow-up.The modified TES with a single posterior approach is feasible, safe and effective for thoracolumbar spine tumors.

Some of the universities or special libraries will have special requirements for the information query. According to some of the special requirements, a multi-agent coalition inter database retrieval system architecture is constructed to support unified access to multiple databases. This paper gives the details about the model structure of collaborative agent and the collaborative mechanism in the system.