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To compare the clinical efficacy of the minimally invasive technique and the open method in the treatment of irreducible unilateral subaxial cervical facet joint dislocation (SCFD).From March 2015 to September 2018, 62 patients with unilateral SCFD were studied. The cases were divided into 2 groups based on different surgery strategies. Thirty-one patients were enrolled in the minimally invasive surgery (MIS) group, and 31 patients were enrolled in the open surgery group. The duration of prone position operation, blood loss, and total hospitalization costs were recorded. The clinical effects were evaluated using visual analogue scale scores, the Oswestry Disability Index, and Japanese Orthopedic Association scores at each follow-up. In addition, the segmental Cobb angle and intervertebral height were recorded and compared.The amount of intraoperative blood loss, prone position operation duration, and total hospital costs in the MIS group were significantly lower than in the open surgery group. The visual analogue scale, Oswestry Disability Index, and Japanese Orthopedic Association scores of the 2 groups significantly improved after the operation. A satisfactory fusion rate was obtained in both groups, and the segmental Cobb angle and intervertebral height scores in both groups improved significantly.Minimally invasive reduction had equal clinical efficacy to posterior open surgery. However, MIS was less invasive and had lower costs. Therefore, it is a potential option in the treatment of SCFD.

Postmenopausal osteoporosis is one of the most prominent worldwide public health problems and the morbidity is increasing with the aging population. It has been demonstrated that early diagnosis and intervention delay the disease progression and improve the outcome. Therefore, searching for biomarkers that are able to identify postmenopausal women at high risk for developing osteoporosis is an effective way to improve the quality of life of patients, and alleviate social and economic burdens. In the present study, a protein array was used to identify potential biomarkers. The bone mineral densities of 10 rats were dynamically measured in an ovariectomized model by micro‑computed tomography assessment, and the early stage of osteoporosis was defined. Through the protein array‑based screening, the expression levels of six serum protein biomarkers in ovariectomized rats were observed to alter at the initiation stage of the postmenopausal osteoporosis. Fractalkine, tissue inhibitor of metalloproteinases‑1 and monocyte chemotactic protein‑1 were finally demonstrated to be increased in the serum of eight enrolled postmenopausal osteoporosis patients using ELISA assay and were correlated with the severity of progressive bone loss. These biomarkers may be explored as potential early biomarkers to readily evaluate and diagnose postmenopausal osteoporosis in the clinic.

Neuron-restrictive silencer factor–induced downregulation of μ-opioid receptor is involved in the reduction of morphine analgesia in sarcoma-induced bone cancer pain., Bone cancer pain has been reported to have unique mechanisms and is resistant to morphine treatment. Recent studies have indicated that neuron-restrictive silencer factor (NRSF) plays a crucial role in modulating the expression of the μ-opioid receptor (MOR) gene. The present study elucidates the regulatory mechanisms of MOR and its ability to affect bone cancer pain. Using a sarcoma-inoculated murine model, pain behaviors that represent continuous or breakthrough pain were evaluated. Expression of NRSF in the dorsal root ganglion (DRG) and spinal dorsal horn was quantified at the transcriptional and translational levels, respectively. Additionally, chromatin immunoprecipitation assays were used to detect NRSF binding to the promoter of MOR. Furthermore, NRSF was genetically knocked out by antisense oligodeoxynucleotide, and the expression of MOR and the effect of morphine were subsequently analyzed. Our results indicated that in a sarcoma murine model, NRSF expression is upregulated in dorsal root ganglion neurons, and the expression of NRSF mRNA is significantly negatively correlated with MOR mRNA expression. Additionally, chromatin immunoprecipitation analysis revealed that NRSF binding to the neuron-restrictive silencer element within the promoter area of the MOR gene is promoted with a hypoacetylation state of histone H3 and H4. Furthermore, genetically knocking down NRSF with antisense oligodeoxynucleotide rescued the expression of MOR and potentiated the systemic morphine analgesia. The present results suggest that in sarcoma-induced bone cancer pain, NRSF-induced downregulation of MOR is involved in the reduction of morphine analgesia. Epigenetically, up-regulation of MOR could substantially improve the effect of system delivery of morphine.

Background: Alendronate has been used to prevent or treat glucocorticoid-induced osteoporosis (GIO), data regarding its efficacy are inconsistent. We conducted the current systematic review and meta-analysis to evaluate both efficacy and safety of alendronate in the treatment of GIO. Methods: PubMed, Embase, the Cochrane Controlled Trials Registry, and the China Academic Journal Network Publishing Databases were searched up through March 1, 2018. Randomized controlled trials (RCTs) involving patients which received alendronate treatment were included. Outcome measures were bone mineral density (BMD) changes, bone fractures, and adverse reactions. Data from the individual studies were pooled using random or fixed effect models based on heterogeneity. Effect size was reported as standardized mean differences (SMD) for continuous outcomes and pooled odds ratios (OR) for dichotomous outcomes, with 95% confidence interval (CI). Results: Overall, 10 studies involving 1002 patients were included in the present investigation. Alendronate treatment significantly increased BMD of the lumbar spine and femoral neck during 6 to 24 months. These beneficial effects were apparent at 12 months after treatment for the lumbar spine but not the femoral neck BMD. Alendronate treatment did not significantly change fracture risk nor induce significant differences in adverse gastrointestinal effects. Conclusion: Alendronate significantly increases BMD of the lumbar spine and femoral neck in patients with GIO, but does not appear to reduce the risk of fractures. As relatively insufficient data regarding the GIO fracture incidence has been reported, more RCTs need to be carried out to determine the efficacy of alendronate in the prevention of GIO fracture.

The outcome of spinal cord injury (SCI) is determined by both neural cell-intrinsic survival pathways and tissue microenvironment-derived signals. Macrophages dominating the inflammatory responses in SCI possess both destructive and reparative potentials, according to their activation status. Notch signaling is involved in both cell survival and macrophage-mediated inflammation, but a comprehensive role of Notch signaling in SCI has been elusive. In this study, we compared the effects of general Notch blockade by a pharmaceutical γ-secretase inhibitor (GSI) and myeloid-specific Notch signal disruption by recombination signal binding protein Jκ (RBP-J) knockout on SCI. The administration of Notch signal inhibitor GSI resulted in worsened hind limb locomotion and exacerbated inflammation. However, mice lacking RBP-J, the critical transcription factor mediating signals from all four mammalian Notch receptors, in myeloid lineage displayed promoted functional recovery, attenuated glial scar formation, improved neuronal survival and axon regrowth, and mitigated inflammatory response after SCI. These benefits were accompanied by enhanced AKT activation in the lesion area after SCI. These findings demonstrate that abrogating Notch signal in myeloid cells ameliorates inflammation response post-SCI and promotes functional recovery, but general pharmaceutical Notch interception has opposite effects. Therefore, clinical intervention of Notch signaling in SCI needs to pinpoint myeloid lineage to avoid the counteractive effects of global inhibition.

Aims To investigate the effect of locally slow-released rapamycin (RAPA) from bionic peripheral nerve stent to reduce the incidence of neuropathic pain or mitigate the degree of pain after nerve injury. Main methods We constructed a neural tissue engineering scaffold with sustained release of RAPA to repair 20 mm defects in rat sciatic nerves. Four presurgical and postsurgical time windows were selected to monitor the changes in the expression of pain-related dorsal root ganglion (DRG) voltage-gated sodium channels 1.3 (Nav1.3), 1.7 (Nav1.7), and 1.8 (Nav1.8) through immunohistochemistry (IHC) and Western Blot, along with the observation of postsurgical pathological pain in rats by pain-related behavior approaches. Key findings Relatively small upregulation of DRG sodium channels was observed in the experimental group (RAPA + poly(lactic-co-glycolic acid) (PLGA) + stent) after surgery, along with low degrees of neuropathic pain and anxiety, which were similar to those in the Autologous nerve graft group. Significance Autoimmune inflammatory response plays a leading role in the occurrence of post-traumatic neuropathic pain, and that RAPA significantly inhibits the abnormal upregulation of sodium channels to reduce pain by alleviating inflammatory response.

Long‑term glucocorticoid therapy results in various side effects, including a high incidence of glucocorticoid‑induced osteoporosis (GIOP), which is the most common form of secondary osteoporosis. Excess glucocorticoids reduce the viability of bone marrow‑derived mesenchymal stem cells (BMSCs) and prolong osteoclast survival. These two types of cell are essential in the balance between bone formation and resorption. Tetramethylpyrazine (TMP), the pharmacologically active component extracted from Chuanxiong, has been reported to protect BMSCs from glucocorticoid‑induced apoptosis. In the present study, the protective effects of TMP on BMSC differentiation and osteoclasts maturation in GIOP were investigated in vivo and in vitro. The immunostaining of osterix (OSX) and tartrate‑resistant acid phosphatase (TRAP) staining indicated that TMP promoted osteogenesis and inhibited osteoclastogenesis in a rat model of GIOP. Treatment with 10‑6 M dexamethasone (Dex) significantly inhibited BMSC differentiation and increased TRAP‑positive cells in vitro. However, different concentrations of TMP (50, 100 and 200 µM) ameliorated the negative effects of Dex by promoting the activity of alkaline phosphatase (ALP) and the calcium mineralization of BMSCs following osteogenic induction, which increased the expression levels of osteogenic genes, including ALP, collagen type I α1, osteocalcin and OSX, and decreased osteoclastogenesis‑related genes, including TRAP, nuclear factor of T‑cells cytoplasmic 1 and cathepsin K. In addition, it was found that the inhibition of receptor activator of nuclear factor‑κB ligand and intereleukin‑6 in BMSCs may be a possible mechanism for the protective effects of TMP against glucocorticoid‑induced osteoclastogenesis. These results are the first, to the best of our knowledge, to demonstrate that TMP promotes BMSC differentiation and inhibits osteoclastogenesis to ameliorate bone mass change in GIOP.

The regressive biological function of human bone marrow‑derived mesenchymal stem cells (hBMSCs) is one of the key factors resulting in the decrease of bone mass in senile osteoporosis. MicroRNAs (miRs) are non‑coding small RNAs involved in various gene regulation processes. Whether any miR(s) are involved in the progression of osteoporosis by regulating the biological function of hBMSCs remains to be elucidated. The present study aimed to compare the expression levels of miR‑125b in hBMSCs derived from senile osteoporotic patients with that of control (normal) subjects. A significantly upregulated expression of miR‑125b in osteoporotic hBMSCs was detected. To elucidate the biological function of miR‑125b in senile osteoporosis, the effects of miR‑125b expression on proliferation and osteogenic differentiation of hBMSCs were assessed using gain‑ and loss‑of‑function studies. It was evident that the overexpression of a miR‑125b mimic was able to suppress the proliferative and osteogenic differentiation of senile hBMSCs. In contrast, repression of the function of miR‑125b by transfection of an miR‑125b inhibitor promoted the proliferation and osteogenic differentiation of hBMSCs. Furthermore, the potential target gene of miR‑125b, osterix (Osx), was examined. The results of the present study strongly suggested that miR‑125b may regulate osteogenic differentiation of hBMSCs through the modulation of Osx expression.

Neuropathic pain is considered as one of the most difficult types of pain to manage with conventional analgesics. EGb-761 is extracted from leaves of Ginkgo biloba and has analgesia and anti-inflammatory properties. This study aimed to examine the effect of EGb-761 on chronic constriction injury (CCI)-induced neuropathic pain behaviors, including thermal hyperalgesia and mechanical allodynia, and to explore the possible mechanisms underlying this action. To this end, CCI mice were intraperitoneally injected with EGb-761 (10, 20, 40, and 80 mg/kg), and thermal hyperalgesia, mechanical allodynia, cytokines, and mu-opioid receptor expression were measured. Results showed that EGb-761 attenuated thermal hyperalgesia and mechanical allodynia dose-dependently and the best delivery time window was from day 7 to day 14 after CCI. Additionally, EGb-761 treatment significantly decreased pro-inflammatory cytokines and enhanced mu opioid receptor (MOR) expression in the sciatic nerve. Moreover, the opioid antagonist naloxone prevented the effect of EGb-761 on thermal hyperalgesia and mechanical allodynia but did not influence the effect of EGb-761 on inflammatory cytokines. In conclusion, this study suggests that the potential of EGb-761 as a new analgesic for neuropathic pain treatment, and opioid system may be involved in the EGb-761-induced attenuation of thermal hyperalgesia and mechanical allodynia. Copyright © 2016 John WileySons, Ltd.

Study design A multicenter cross-cultural study to re-evaluate the reliability and validity of the simplified Chinese version of Scoliosis Research Society-22 (SRS-22) Patient Questionnaire. Objective To assess the concurrent validity and reliability of this instrument in mainland China. Summary of background data The SRS-22 Questionnaire was developed to assess the health-related quality of life for patients with scoliosis in the United States. More recently, the reliability and validity analyses of traditional and simplified Chinese versions of this questionnaire were performed, respectively. However, with respect to the diversity of population and large proportion of rural patients in China, a multicenter study might be necessary to re-evaluate its adaptation. Methods The original English version of the SRS-22 Questionnaire was translated into simplified Chinese. Considering the different health care systems in mainland China, the question 15 was modified; the respondent might be the parent if the patient was younger than 18 years. This multicenter study was performed by 13 scoliosis surgeons involving seven spine centers. The SRS-22 Questionnaire and a previously validated 36-Item Short-Form Health Survey Questionnaire were given to 391 patients with idiopathic scoliosis or congenital scoliosis without neurologic deficits. Of those, 136 patients were randomly selected for a second identical SRS-22 Questionnaire filled 1 week later and mailed back with a stamped return envelope. Results A total of 333 patients fully completed both SRS-22 and 36-Item Short-Form Health Survey Questionnaires. Good consistency was observed for all the five domains of the SRS-22. Poorer internal consistency was found in questions 15 and 18. If question 15 was excluded, the α coefficient would increase to 0.68. The pain domain of SRS-22 had a high ceiling effect being 67.5%. The test-retest reproducibility was observed "good" in the pain domain and "excellent" for the remaining domains of SRS-22 Questionnaire. Good (10 domains) and moderate (23 domains) correlations were demonstrated while seven domains had poor correlation. Conclusion The simplified Chinese version of the SRS-22 Questionnaire was re-evaluated by a multicenter study to respect the diversity of population and cultural differences in mainland China, which showed good internal consistency and satisfactory test-retest reproducibility. It might be useful for clinical evaluation of Chinese adolescents and young adults with scoliosis treated with bracing or surgery, although it also encountered previously reported difficulties with some of the items related to different cultures and health care systems.

Spondylolysis is a fracture in part of the vertebra with a reported prevalence of about 3–6% in the general population. Genetic etiology of this disorder remains unknown. The present study was aimed at identifying genomic mutations in patients with dysplastic spondylolysis as well as the potential pathogenesis of the abnormalities. Whole-exome sequencing and functional analysis were performed for patients with spondylolysis. We identified a novel heterozygous mutation (c.2286A > T; p.D673V) in the sulfate transporter gene SLC26A2 in five affected subjects of a Chinese family. Two additional mutations (e.g., c.1922A > G; p.H641R and g.18654T > C in the intron 1) in the gene were identified by screening a cohort of 30 unrelated patients with the disease. In situ hybridization analysis showed that SLC26A2 is abundantly expressed in the lumbosacral spine of the mouse embryo at day 14.5. Sulfate uptake activities in CHO cells transfected with mutant SLC26A2 were dramatically reduced compared with the wild type, confirming the pathogenicity of the two missense mutations. Further analysis of the gene–disease network revealed a convergent pathogenic network for the development of lumbosacral spine. To our knowledge, our findings provide the first identification of autosomal dominant SLC26A2 mutations in patients with dysplastic spondylolysis, suggesting a new clinical entity in the pathogenesis of chondrodysplasia involving lumbosacral spine. The analysis of the gene–disease network may shed new light on the study of patients with dysplastic spondylolysis and spondylolisthesis as well as high-risk individuals who are asymptomatic.

Background: Giant cell tumor of bone (GCT) is a potentially malignant tumor. CD147 is a multifunctional protein, which expresses itself in many tumors. In this study, we have investigated the correlation between CD147 and PCNA, VEGF, MMPs expression in giant cell tumor of bones. We have also explored the relationship between its clinical pathology and prognosis. Results: A significant difference of the expression level of CD147, MMPs was found in cases of GCT with Jaffe grading and prognosis (P

Background Neuropathic pain (NP) continues to be challenging to treat due to lack of effective drugs. Accumulating evidence elucidated that glia-mediated inflammatory reactions play a pivotal role in the introduction and development of NP. Besides, activation of the c-Jun N-terminal kinase (JNK)/monocyte chemoattractant protein-1 (MCP-1) pathway in astrocytes has been reported to be critical for spinal astrocytic activation and neuropathic pain development after spinal nerve ligation (SNL). Tanshinone IIA, a major active component of a traditional Chinese drug, Danshen, possesses potent immuno-suppressive activities. The present study was undertaken to assess whether intraperitoneal administration of tanshinone IIA sulfonate (TIIAS) has analgesic effect on SNL-induced neuropathic pain and whether the inhibition of astrocytic activation and JNK/MCP-1 pathway is involved in the analgesic effect of TIIAS. Methods The effects of TIIAS on SNL-induced mechanical allodynia were assessed by behavioral testing. Immunofluorescence histochemical staining was used to detect changes of spinal astrocytes and spinal pJNK expression and localization. Immunofluorescence histochemistry and Western blot analysis were used to quantify the SNL-induced spinal pJNK expression after TIIAS administration. Enzyme-linked immunosorbent assay (ELISA) was used to detect the SNL-induced spinal expression of pro-inflammatory cytokines and MCP-1. Results Our results indicated that intraperitoneal TIIAS up-regulated the mechanical paw withdrawal threshold (PWT) of NP, while astrocytic activation was suppressed and accompanied by the down-regulation of IL-1β and TNF-α expression, as well as JNK phosphorylation in the spinal dorsal horn. Additionally, the release of MCP-1 was dose dependently decreased. After co-treatment with TIIAS and JNK inhibitor (SP600125), no significant increases in mechanical PWT and MCP-1 expression were observed compared with the TIIAS-treated group. Conclusions The present results suggest that the analgesic effects of TIIAS in neuropathic pain are mainly mediated by the down-regulation of SNL-induced astrocytic activation, which is via the inhibition of JNK/MCP-1 pathway.

Tissue engineering has become a promising way of treating growth plate injuries. In this study, we attempted investigating the role of the autologous tissue-engineered composite in the treatment of rabbit growth plate injuries. Growth plate chondrocytes from iliac crest epiphyseal cartilage of immature New Zealand rabbits were obtained by dissection and sequential digestion with 0.2% collagenase (type II). After proliferating in monolayer culture in vitro for 3 weeks, the cells were harvested and seeded onto the demineralized bone matrix (DBM) scaffold to construct the composite. The autologous tissue-engineered composites were finally implanted into the proximal right tibia defects of the growth plate created in 12 rabbits (group A underwent the operation after obtaining chondrocytes 3 weeks beforehand), another 12 rabbits were implanted with only the DBM scaffold (group B), and the defects in group C (12 rabbits) were not implanted. The left tibias of all animals were left undone as the normal control. Two weeks after the operation, severe shortness and angulation deformity of the right tibia evaluated by X-ray were gradually observed in groups B and C. However, there were no obvious changes in group A and there were significant differences between group A and groups B and C (p < 0.05) at the 4-, 8-, and 16-weeks time points. 16 weeks after operation, histological examination revealed that the defects of the right tibias in group A had restored to almost the normal columnar structure of the growth plate. The results demonstrate that tissue-engineered composite established by combination of autologous growth plate chondrocytes and DBM can prevent the formation of a bone bridge and restore the growth of damaged growth plate.

Although there have been numerous studies aimed at determining the effects and safety of early vs. late surgical decompression for traumatic cervical spinal cord injury, controversies still exist regarding the optimal timing of surgery for this serious spinal trauma. This study was conducted to evaluate the effectiveness and safety of early vs. late surgical decompression for lower cervical spine trauma associated with spinal cord injury. A retrospective review of was performed on consecutive patients who underwent surgical decompression for lower cervical (C3–C7) spine trauma associated with spinal cord injury at six institutions across China from January 2007 to January 2012. These patients were analysed according to the timing of surgical intervention. The early group comprised patients who underwent surgery within the first 72 hours after being injured, whilst the late group comprised patients who underwent surgery after the first 72 hours. For analysis of neurologic improvement, patients who had completed a follow-up of at least six months were assessed. Other outcomes analysed were hospitalisation periods, complications and mortality. A total of 595 patients were identified (456 men and 139 women at an average age of 41.4 years), with 212 in the early group and 383 in the late group. Patients in both groups had made a significant neurologic improvement in the final follow-up, but no statistically significant difference was noted between groups. Patients in the early group had a significantly shorter hospital stay (15.4 vs. 18.3 days, p

The transdifferentiation of bone and fat is a new insight in studying the increasingly bone marrow fat in the process of osteoporosis of elderly or menopause crowd which is increasing in prevalence. The loss of bone mass in osteoporosis is multifactorially determined and includes genetic, hormonal and environmental determinants. Although it has long been considered whether the transdifferentiation process does exist in vivo and whether it could be find in the same individual, interaction between skeleton and adipose tissue has been proved pre-clinically and clinically by increasing evidence. Here we focus on the current understanding of the transdifferentiation between bone and fat, the molecular interactions and future clinical implications of recent studies linking the transdifferentiation to bone metabolism diseases. Furthermore, a set of recommendations of bone and fat transdifferentiation on bone metabolism are also presented to facilitate evaluation of this magic process.

Glucocorticoid‑induced osteoporosis (GIOP) is a widespread clinical complication following glucocorticoid therapy. This irreversible damage to bone‑forming and ‑resorbing cells is essential in the pathogenesis of osteoporosis. Autophagy is a physiological process involved in the regulation of cells and their responses to diverse stimuli, however, the role of autophagy in glucocorticoid‑induced damage to bone marrow mesenchymal stem cells (BMSCs) remains unclear. The current study confirmed that glucocorticoid administration impaired the proliferation of BMSCs. Transmission electron microscopy, immunohistochemistry and western blot analysis detected autophagy in vitro and in GIOP model rats (in vivo). With the addition of the autophagy inhibitor 3‑methyladenine, the proliferative ability of BMSCs was further reduced, while the number of apoptotic BMSCs was significantly increased. The data suggests that in response to glucocorticoid administration, induced autophagy aids to maintain proliferation and prevent apoptosis of BMSCs. Thus, it is hypothesized that autophagy may be a novel target in the treatment or prevention of osteoporosis.

The study aimed for addressing the expression of soluble Fas (sFas) and soluble Fas Ligand (sFasL) in human nucleus pulposus (NP) and its attendant relationship with disc degeneration. Human NP samples were collected from patients with disc degeneration and cadavers as degenerate and normal groups, respectively. Subsequently, NP cells were cultured in monolayer. ELISA was performed to identify the expression levels of sFas and sFasL in the supernatant of NP cell cultures in vitro. Quantitative real-time PCR was used to detect the expression of sFas and sFasL in human NP cells in mRNA solution. The study comprised 12 degenerate and 8 normal cadaveric NP samples. The concentration value of sFas in the supernatant was significantly higher from degenerate NP than that from normal NP at each time point. In contrast, sFasL was significantly lower at each time point. Moreover, the expression of sFas and sFasL reached the peak at various early stages of cell cultures and decreased thereafter. Furthermore, the mRNA level of Fas in degenerate NP cells was significantly higher than that in normal cells; whereas FasL showed an opposite pattern. The study is the first addressing the expression of sFas and sFasL in human NP cell cultures. Moreover, the expression of sFas and sFasL varies with culture time in vitro with different levels in degenerate and normal settings. These findings indicate that sFas and sFasL might play a role in intervertebral disc degeneration.

The unique structural hallmark of the intervertebral disc has made its central composition, the nucleus pulposus (NP), excluded from the immunologic tolerance. Consequently, the intervertebral disc is identified as an immune-privileged organ. Traditionally, local detrimental immune activities caused by NP at the lesion sites of the disc are noted as a significant factor contributing to disc degeneration. However, given the beneficial activities of immune cells in other immune-privileged sites on basis of current evidence, the degenerate disc might need the assistance of a subpopulation of immune cells to restore its structure and lessen inflammation. In addition, the beneficial impact of immune cells can be seen in the absorption of the herniated NP, which is an important factor causes the mechanical compression of nerve roots. Consequently, a modulated immune network in degenerate disc is essential for the restoration of this immune-privileged organ. Until now, the understandings of immune response in disc degeneration still rest on the harmful aspect. Further studies are needed to explore its beneficial influence. Accordingly, there are no absolutely the pros and cons in terms of immune reactions caused by NP.

Biologic and cellular treatment strategies aiming for curing intervertebral disc degeneration (IDD) have been proposed recently. Given the convenient availability and expansion potential, adipose-derived stromal cells (ADSCs) might be an ideal cell candidate. However, the interaction between ADSCs and nucleus pulposus (NP) cells still remains ambiguous, especially in direct co-cultures of the two types of cells. Nevertheless, NP markers in ADSCs after co-cultures were unidentified. Here, we addressed the interaction of human ADSCs and NP cells in a direct co-culture system for the first time. As a result, ADSCs could differentiate to the NP cell phenotype with a significant up-regulated expression of multiple genes and proteins in extracellular matrix (ECM) (SOX9, COL2A1, ACAN, and COL6A2), relative NP markers (FOXF1, PAX1, CA12, and HBB) and pertinent growth factors (CDMP-1, TGF-β1, IGF-1, and CTGF). Moreover, the gene expression of COL2A1, ACAN, and COL6A2 of degenerate NP cells was also up-regulated. Collectively, these results suggest that direct co-cultures of ADSCs and NP cells may exert a reciprocal impact, that is, both stimulating ADSCs differentiation to the NP cell phenotype and inducing NP cells to regain functional phenotype. Accordingly, ADSCs might be a potential candidate in the development of cellular treatment strategies for IDD.

Effective immobilization and transportation are vital to the life-saving acute medical care needed when treating critically injured people. However, the most common types of stretchers used today are wrought with problems that can lead to further medical complications, difficulty in employment and rescue, and ineffective transitions to hospital treatment. Here we report a novel first aid stretcher called the "emergency carpet", which solves these problems with a unique design for spine injured patients. Polyurethane composite material, obtained by a novel process of manually mixing isocyanate and additives, can be poured into a specially designed fabric bag and allowed to harden to form a rigid human-shaped stretcher. The effectiveness of the emergency carpet was examined in the pre-hospital management of victims with spinal fractures. Additionally, it was tested on flat ground and complex terrain as well as in the sea and air. We demonstrated that the emergency carpet can be assembled and solidified on the scene in 5 minutes, providing effective immobilization to the entire injured body. With the protection of the emergency carpet, none of the 20 patients, who were finally confirmed to have spinal column fracture or dislocation, had any neurological deterioration during transportation. Furthermore, the carpet can be handled and transported by multiple means under differing conditions, without compromising immobilization. Finally, the emergency carpet allows the critically injured patient to receive multiple examinations such as X-ray, CT, and MRI without being removed from the carpet. Our results demonstrate that the emergency carpet has ideal capabilities for immobilization, extrication, and transportation of the spine injured patients. Compared with other stretchers, it allows for better mobility, effective immobilization, remarkable conformity to the body, and various means for transportation. The emergency carpet is promising for its intrinsic advantages in the pre-hospital management of accident victims.

Objective: To explore the influence of pedicle screw insertion through the neurocentral cartilage (NCC) on the development of vertebrae and spinal canal in an animal experiment. Methods: Sixteen dogs were randomly assigned to three groups: in group 1, posterior muscles at the surgery site were dissected; in group 2, the pedicles were drilled through the NCC by screws; in group 3, screws were placed in the pedicles through the NCC. Vertebrae of T8, T10, T12, L2, L4 and L6 were studied with the average data of the adjacent two vertebrae serving as controls. Spiral computerized tomography (CT) was used to assess the morphologic parameters of studied vertebrae and their controls. Measurements were made by an independent radiologist on the first post‐operative day and 3 months after operation. Paired Student's t‐tests of studied vertebrae and their controls were performed to evaluate the effect of pedicle screw insertion. Results: In group 3, 3 months after operation the area, transverse diameter and anterior‐posterior diameter of the vertebral canal and length of pedicle of studied vertebrae were significantly smaller than those of control vertebrae (P < 0.05). There were no significant differences in morphologic parameters between the studied vertebrae and the control vertebrae in groups 1 and 2 (P > 0.05). Conclusion: (i) Pedicle screw placement has a significant impact on the growth of the canine vertebra canal, and may lead to iatrogenic spinal stenosis, but their placement has no significant effect on the vertebral bodies; and (ii) the NCC can repair itself automatically. Drilling pedicle bone through the NCC with a screw and then removing the screw has no obvious impact on the growth of vertebrae.

The bone marrow-derived mesenchymal stem cells or mesenchymal stromal cells (MSCs), with pluripotent differentiation capacity, present an ideal source for cell transplantation or tissue engineering therapies, but exact understanding of regulating mechanism underling MSC proliferation and differentiation remains a critical issue in securing their safe and efficient clinical application. This review outlines current knowledge regarding MSC cell surface biomarkers and molecular mechanisms of MSC differentiation and proliferation with emphasis on Wnt/β-catenin signaling, Notch signaling pathway, bone morphogenesis proteins and various growth factors functioning in regulation of differentiation and proliferation of MSCs. Possible relation of oncogene and immunosuppressive activities of MSCs with tumorigenicity or tumor generation is also addressed for safe translational clinical application. Fast increase of MSC knowledge and techniques has led to some successful clinical trials and helped devising new tissue engineering therapies for bone and cartilage diseases that severely afflict human health. Production of adult MSC-derived functional neurons can further extend their therapeutic application in nerve injury and neurodegenerative diseases. It is promising that MSCs shall overcome ethical and immunorejection problems appeared in human embryonic stem cells, and specific molecular targeting manipulation may result in practical MSC therapy for personalized treatment of various diseases in the regeneration medicine.

This study evaluated the usefulness of a single-stage, free-fibular vascularized osteoseptocutaneous flap transfer for Type III open tibial shaft fractures with segmental bone loss for the reconstruction of combined bone and soft tissue defects.Nonrandomized retrospective study.University Level I trauma center.All Gustilo Type III open tibial shaft fractures with segmental bone loss that were treated at one institution between 2000 and 2007 were identified from a trauma registry. The study group consisted of 28 patients with Type III open tibial fractures: 27 were Gustilo-Anderson Type IIIB and one was Grade IIIC. The cause of tibial injury included eight industrial accidents, seven motor vehicle accidents, five crushing injuries caused by heavy objects, five falls from a height, and three motorcycle crashes. The lengths of the preoperative segmental tibial bone loss ranged from 9 to 17 cm and the size of the associated soft tissue defects ranged from 8 × 6 cm to 15 × 7 cm.The free fibular vascularized osteoseptocutaneous flap was used to graft and reconstruct combined bone and soft tissue defects. The radical wound débridement, soft tissue and bone revision, fracture stabilization, and early soft tissue coverage were achieved by this technique in a one-stage procedure. The average duration from injury to one-stage reconstruction was 15.8 hours (range, 5.3 hours to 6.5 days).Radiographic and functional evaluation of the lower extremity.All free fibular osteoseptocutaneous flaps survived completely. The average time to overall union for the entire group was 32 weeks after surgery (range, 26-41 weeks). None of the patients in this series had a nonunion. Acceptable radiographic alignment, defined as 5° of angulation in any plane, was obtained in 22 patients (78.6%). Malunion affected six (21.4%) fractures. According to the lower extremity functional assessment, excellent and good results were achieved for 82.1% (23 of 28), fair results were seen in 14.3 % (four of 28), and a poor result occurred in one case (3.5%).The free fibular vascularized osteoseptocutaneous flap grafting is an effective alternative in management of Type III open tibial fractures using a one-stage procedure. The grafted fibula offers good fracture stabilization plus a vascularized bone graft, and the fibular flap can also provide a large piece of mobile skin to cover the soft tissue defect in Type III open tibial fractures. The free osteoseptocutaneous flap also serves as a visible monitor of the adequacy of the circulation of the grafted fibula.

The present study examined the protective effect of hyperbaric oxygen preconditioning (HBO-PC) and the role of thioredoxin reductase (TrxR) in a post-traumatic stress disorder (PTSD)-induced rat model by using single prolonged stress (SPS). Rats were randomly divided into Sham, HBO, SPS and HBO + SPS groups. HBO-PC was conducted by exposing rats to 100% oxygen at 2.5 atm absolute for 1 h each day for 5 consecutive days. SPS was performed 24 h after the last HBO-PC conditioning event. At 1 h, 6 h, 12 h, 24 h and 72 h after SPS, TrxR mRNA expression was analyzed in the hippocampus; Nissl and TUNEL staining were performed at 72 h after SPS. The results indicated that HBO-PC was able to significantly preserve viable neurons in the CA1 subfield of hippocampus following SPS exposure, as evidenced by reduced amounts of CA1 neuronal apoptosis. Furthermore, HBO-PC upregulate the expression of TrxR-1 and TrxR-2 mRNA in the hippocampus at 6 h and 12 h after SPS exposure and ameliorated anxiety-like behavior and cognitive impairments normally induced by SPS. Taken together, these findings suggest that HBO-PC is beneficial for the improvement of anxiety-like behavior and cognitive impairments induced by SPS exposure, and this effect might be associated with inhibition of neuronal apoptosis via upregulation of TrxR in stressed rats.

Intervertebral disc degeneration (IDD) pertains to the loss of extracellular matrix (ECM), particularly the early loss of aggrecan, the turnover of which is regulated by ADAMTSs. Amongst the etiological factors of IDD, mechanical stress plays an important role in the physiological and pathological processes of nucleus pulposus (NP) cells. However, the role of ADAMTSs and their inhibitor in human NP cells under mechanical stress has not been elucidated to date. The purpose of this study was to investigate the role of ADAMTSs and TIMP-3 in NP cells under mechanical stress. Human NP cells isolated from non-degenerative and degenerative discs were subjected to dynamic compressive load. The expression of ADAMTSs, aggrecan, and TIMP-3 was detected by quantitative real-time PCR and/or Western blot. Consequently, the gene expression of ADAMTS-1, 4, and 5 increased significantly in loaded NP cells compared with not-loaded cells from either non-degenerative or degenerative discs, whereas the gene expression of aggrecan decreased significantly. Moreover, Western blot indicated increased protein levels of ADAMTSs-1, 4, and 5. However, the expression of TIMP-3 altered insignificantly. Together, this study is the first addressing the underlying mechanisms of compressive load as a contributing factor to IDD in terms of ADAMTSs. Our results suggest that compressive load leads to the increase in ADAMTS-1, 4, and 5 that contributes to the decrease of aggrecan and IDD via TIMP-3 independent machinery.

BACKGROUND Olfactory ensheathing cells (OECs) can promote many kinds of neuron growth and axonal extension. The aim of the study was to investigate the effects of co-culturing with OECs on neuron apoptosis in vitro. METHODS Apoptosis was induced by treatment of cultured dorsal root ganglion neurons with 1 mmol/L hydrogen peroxide (H(2)O(2)). Cells were randomly arranged into the following treatment groups. In group 1, OECs at different density (10(4)/ml to 8 x 10(5)/ml) were added immediately after H(2)O(2) treatment and cells were co-cultured for 24 hours. In group 2, OECs were added at different time points (0, 4, 8, 12 and 24 hours) after H(2)O(2) treatment. Apoptotic cell death was determined by Hoechst 33258 staining and flow cytometry (FCM). Cell viability was determined by using methyl thiazoleterazolium (MTT) assays. RESULTS The results showed in the Hoechest 33258 staining, FCM and MTT that OECs have both the density-dependent protection and time-dependent protection on neuron apoptosis. The apoptosis decreased and the dorsal root ganglion neuron viability increased, when the density of OECs was increased in co-culture groups. But further increasing OEC density above 2 x 10(5)/ml (i.e. 8 x 10(5)/ml) failed to exert additional protection. As the interval between adding H(2)O(2) and adding OECs was increased, the amounts of apoptosis cells were also increased. When OECs were added 24 hours after H(2)O(2), no significant protection was observed. CONCLUSION These results indicated that OECs could protect dorsal root ganglion neurons from apoptosis induced by H(2)O(2) in a density- and time-dependent manner.

Objective To investigate the efficient method which can culture and induce embryonic stem cells to neurocyte in vitro. Methods Isolate the blastula of 3.5 d from BALB/c species mouse. Culture the cells from inner cell mass (ICM) which were isolated by mechanical method on the mouse embryonic fibroblaste cell (MEF) feeder layer or 0.1% gelatin coated dishes. The stem cells were identified by characterized morphology, alkaline phosphatase stain, differential potency in vivo and immunochemistry stain. The isolated cells were differentiated by serial induction method that mimicking the intrinsic developmental process of the neural system. Results The isolated cells were positive for alkaline phosphatatse and SSEA-1 (stage specific embryonic antigen 1). Moreover they were identified pluripotent by differentiation in vivo. Therefore the isolated cells presented the characters of ESCs. Then the isolated cells were able to differentiate into neurocytes in vitro. Conclusion Mouse embryonic stem cells isolation, culture and differentiation system has been established.

To investigate the effects of Yunnan Baiyao on peri-operative bleeding of the patients undergoing cervical open-door laminoplasty.197 patients undergoing cervical open-door laminoplasty were randomly divided into 2 groups Yunnan Baiyao group (receiving Yunnan Baiyao 500 mg three times daily for 5 days) and placebo group. The amounts of intra-operative and post-operative bleeding were compared, and the side effect of Yunnan Baiyao was also analyzed.Statistical analysis showed that the amount of intra-operative bleeding of the Yunnan Baiyao was 350 ml +/- 190 ml, significantly lower than that of the placebo group (443 ml +/- 266 ml, P0.05). There were no statistical differences in the amount of postoperative bleeding and side effect rate between the two groups.Yunnan Baiyao is effective and safe in reducing the amount of intra-operative bleeding of cervical open-door laminoplasty.

Tissue engineering has become a promising way of treating growth plate injuries. In this study, we attempted investigating the role of the autologous tissue-engineered composite in the treatment of rabbit growth plate injuries. Growth plate chondrocytes from iliac crest epiphyseal cartilage of immature New Zealand rabbits were obtained by dissection and sequential digestion with 0.2% collagenase (type II). After proliferating in monolayer culture in vitro for 3 weeks, the cells were harvested and seeded onto the demineralized bone matrix (DBM) scaffold to construct the composite. The autologous tissue-engineered composites were finally implanted into the proximal right tibia defects of the growth plate created in 12 rabbits (group A underwent the operation after obtaining chondrocytes 3 weeks beforehand), another 12 rabbits were implanted with only the DBM scaffold (group B), and the defects in group C (12 rabbits) were not implanted. The left tibias of all animals were left undone as the normal control. Two weeks after the operation, severe shortness and angulation deformity of the right tibia evaluated by X-ray were gradually observed in groups B and C. However, there were no obvious changes in group A and there were significant differences between group A and groups B and C (p0.05) at the 4-, 8-, and 16-weeks time points. 16 weeks after operation, histological examination revealed that the defects of the right tibias in group A had restored to almost the normal columnar structure of the growth plate. The results demonstrate that tissue-engineered composite established by combination of autologous growth plate chondrocytes and DBM can prevent the formation of a bone bridge and restore the growth of damaged growth plate.

To observe the treating effect of collage-heparin sulfate after the 10 mm rat sciatic nerve defect was bridged by it.A new kind of nervous tissue engineering scaffold was produced by freeze-drying technique from collagen-heparin sulfate. Thirty-two SD rats were randomly divided into A, B, C and D groups. Sciatic nerve defect in group A was bridged by collagen-heparin sulfate. In group B, sciatic nerve was bridged by auto-nerve transplantation. Group C was the blank control group. Animals in group D were normal. And 10 mm sciatic nerve defect was bridged in the experiment. Thirty-six weeks after the operation, the experimental animals were detected by HRP labeled retrograde trace, HE staining, toluidine staining, silvering staining, S100, GAP-43 and NF immunohistological staining, MBP immunofluorescence staining and transmission electron microscope to observe the nerve regeneration inducing effect of this new scaffold.Nine months after operation, the collage-heparin sulfate scaffold was replaced by newly regenerated nerve. The number of HRP labeled spinal cord anterior horn cells and the area of sensation nerve fiber at the posterior horn were similar with that was repaired by auto-nerve. GAP-43, NF and S100 labeled regenerated nerve fiber had passed the total scaffold and entered the distal terminal. The regenerated nerve fibers were paralleled, lineage arranged, coincide with the prearranged regenerating "channel" in the collagen-heparin sulfate scaffold. MBP immunofluorescence staining also proved that the newly regenerated nerve fiber could be ensheathed. In the experimental group, the area of myelinated nerve fiber and the thickness of the myelin sheath had no obvious difference with that of the group repaired by auto-nerve, except that the density of the regenerated myelinated sheath fiber was lower than that of the control group.Nervous tissue engineering scaffold produced by collagen-heparin sulfate can guide the regeneration of nerve fibers. The nerve function recovers fine. This kind of material has great application potential.