Chronic spinal cord lesions (CSCL) which result in irreversible neurologic deficits remain one of the most devastating clinical problems. Its pathophysiological mechanism has not been fully clarified. As a crucial factor in the outcomes following traumatic spinal cord injury (SCI), the blood-spinal cord barrier (BSCB) disruption is considered as an important pathogenic factor contributing to the neurologic impairment in SCI. Vascular endothelial growth factor (VEGF) is a multirole element in the spinal cord vascular event. On one hand, VEGF administrations can result in rise of BSCB permeability in acute or sub-acute periods and even last for chronic process. On the other hand, VEGF is regarded to be correlated with angiogenesis, neurogenesis and improvement of locomotor ability. Hypoxia inducible factor-1 (HIF-1) is a primary regulator of VEGF during hypoxic conditions. Therefore, hypoxia-mediated up-regulation of VEGF may play multiple roles in the BSCB disruption and react on functional restoration of CSCL. The purpose of this article is to further explore the relationship among HIF-1, hypoxia-mediated VEGF and BSCB dysfunction, and investigate the roles of these elements on CSCL.
Animals ; Chronic Disease ; Humans ; Hypoxia-Inducible Factor 1 ; physiology ; Neovascularization, Physiologic ; Neurogenesis ; Spinal Cord ; physiopathology ; Spinal Cord Injuries ; physiopathology ; Vascular Endothelial Growth Factor A ; physiology

Estrogen-related receptor alpha (ERRα) plays an important role in the development of hormone-dependent cancers, but its roles in lung cancer remain elusive. The present study was aimed to investigate the effects of ERRα on the proliferation and metastasis of lung cancer A549 cells. The mRNA and protein levels of ERRα were detected in lung cancer A549 and MCF-7 cells and bronchial epithelial BEAS-2B cells by qRT-PCR and Western blotting, respectively. ERRα plasmid transfection and XCT-790 (an inverse agonist of ERRα) were used to up-regulate or down-regulate ERRα expression in A549 cells, respectively. The viability of A549 cells was measured by cell counting kit-8 (CCK-8) and the motility of A549 cells by wound healing assay and Transwell migration/invasion assay. The epithelial markers E-cadherin (E-Cad) and zona occludin-1 (ZO-1), the mesenchymal markers fibronectin (FN) and vimentin (Vim) and the transcription factors (Snail, Zeb1 Twist and Slug) were further detected at mRNA and protein levels by qRT-PCR and Western blotting, respectively. The results showed that ERRα promoted the growth of lung cancer A549 cells in vitro. XCT-790 significantly inhibited the migration and invasion of A549 cells. Over-expression of ERRα promoted the epithelial-to-mesenchymal transition (EMT) of A549 cells, down-regulated the epithelial makers E-Cad and ZO-1, and up-regulated the mesenchymal makers FN and Vim. Silencing of Slug, but not other transcription factors, significantly abolished the ERRα-induced EMT of A549 cells. It was suggested that ERRα promoted the migration and invasion of A549 cells by inducing EMT, and Slug was involved in the process. Targeting ERRα might be an efficient approach for lung cancer treatment.
Cell Line, Tumor ; Cell Proliferation ; Epithelial-Mesenchymal Transition ; Gene Expression Regulation ; Humans ; Lung Neoplasms ; genetics ; metabolism ; prevention & control ; Neoplasm Metastasis ; Neoplasm Proteins ; biosynthesis ; genetics ; Receptors, Estrogen ; biosynthesis ; genetics

OBJECTIVETo evaluate of the role of transcranial electrical stimulation motor evoked potential (TES-MEP) in combination with cortical somatosensory evoked potential (CSEP) monitoring during the spinal surgery.

METHODSTES-MEP on bilateral anterior tibial muscle and flexor hallucal brevis and CSEP on bilateral posterior tibial nerve were observed simultaneously on 293 patients during spinal surgery from July 2006 to April 2009. Intravenous anesthesia was employed in all the patients, a part of which were added low dose of sevoflurane or muscle relaxant. The results of TES-MEP, CSEP and combined monitoring were analyzed statistically. Pre-operative and post-operative motor and sensory functions of spinal cord were compared.

RESULTSSuccess rate of TES-MEP, CSEP and combined monitoring was 90.8%, 96.9% and 100% respectively. For the judgment of motor function of spinal cord, the sensitivity of TES-MEP and CSEP was 100% and 89.3% respectively and the specificity of 98.4% and 96.9%. The Youden index of the two methods was 0.984 and 0.862. For sensory function, the sensitivity of them was 76.7% and 93.3% respectively and the specificity of 98.7% and 98.0%. The Youden index was 0.754 and 0.913. The sensitivity of combined monitoring was 100%, with the specificity of 96.9%. The Youden index was 0.969.

CONCLUSIONSThe precision of monitoring motor function of spinal cord with TES-MEP is higher than that with CSEP, however, for sensory function, CSEP is more precise. The sensitivity and precision of combined monitoring for spinal cord function were apparently better than that of unitary TES-MEP or CSEP. The combined TES-MEP and CSEP monitoring is a relatively ideal method.

Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Evoked Potentials, Motor ; physiology ; Evoked Potentials, Somatosensory ; physiology ; Female ; Humans ; Infant ; Male ; Middle Aged ; Monitoring, Intraoperative ; methods ; Retrospective Studies ; Sensitivity and Specificity ; Spinal Cord ; physiology ; Spine ; surgery ; Young Adult

OBJECTIVETo investigate the molecular mechanism of TFE (total flavone of epimedium) in the treatment of osteoporosis, and then provide experimental evidence for modernization and further development of TFE as an traditional Chinese medicine.

METHODSSixty healthy female SD rats with aged 4 months were randomly divided into three groups (including control group in which rats received sham surgery, OVX group in which ovariectomized rats didn't give any medicine after the removal of ovaries and TFE group in which ovariectomized rats administrated TFE), 20 rats in each group. Compared bone mineral density (BMD) between before operation and at 4th week after operation in order to verify the establishment of osteoporotic model (criteria: BMD decreased more than 20% at 4th week after operation). The rats in TEF group were administrated total flavone of epimedium(concentration 30 mg/ml, 10 ml/kg, qd) orally for 4 weeks. After this, killed rats to harvest the lower part of the femur and detected BMD again. Applying the reverse transcriptase-polymerase chain reaction technique (RT-PCR) to detect expression of OPG, OPGL mRNA in bone tissue.

RESULTS(1) At 4th week after ovariectomy, the mean BMD of lumbar vertebra in TFE group fell to (0.084 +/- 0.020) g/cm2. Administrated with TFE for 4 weeks,the BMD increased to (0.112 +/- 0.009) g/cm2. There was significant improvement compare with the OVX group (P < 0.05). (2) Compared between OVX group and TFE group, The OPG mRNA expression of TFE group obviously enhanced. There was significant difference in statistics (P < 0.05). However,the promotion for OPGL mRNA expression were detected between OVX group and TFE group,there was no significant difference in statistics (P > 0.05).

CONCLUSIONThis study showed that TFE could inhibit differentiation and maturation of osteoclast through enhancing OPG mRNA expression, accordingly,to treat osteoporosis.

Animals ; Bone Density ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Epimedium ; chemistry ; Female ; Flavones ; Flavonoids ; pharmacology ; Gene Expression Regulation ; drug effects ; Osteoblasts ; drug effects ; metabolism ; physiology ; Osteoprotegerin ; genetics ; Ovariectomy ; RANK Ligand ; genetics ; RNA, Messenger ; genetics ; metabolism ; Rats

OBJECTIVETo evaluate the efficacy of hBMP-4 gene modified tissue engineered bone graft in the enhancement of rabbit spinal fusion and find an ideal kind of substitute for the autograft bone.

METHODSRabbit BMSCs were cultured and transfected with AAV-hBMP-4 using different MOI value. The optimal MOI value were determined by observing cell's morphology change. BMSCs were then transfected with AAV-hBMP4 and AAV-EGFP respectively, following which the transfected cells were evenly suspended in a collagen sponge I, and implanted to either side of the L5,6 intertransverse spaces posterolateral in the New Zealand rabbits to induce spinal fusion. Fourteen rabbits were randomly divided into 2 groups. Group 1: AAV-hBMP-4 transfected BMSCs in the right side (hBMP-4 side) and autograft bone in the left side. Group 2: AAV-hBMP-4 transfected BMSCs in the right side (hBMP-4 side) and AAV-EGFP transfected BMSCs in the left side (EGFP side). Radiographs and three-dimensional CT of the spine, manual palpation, gross and histological examination of the fusion masses for all the animals were performed subsequent to animals having been sacrificed at 12 weeks after surgery.

RESULTSEvaluation has been taken in 12 New Zealand rabbits delivered into 2 groups which meet the criterion after operation. Eleven in 12 implemented sides involved hBMP-4 achieved bony fusion, to which 5 in 6 autografted sides was similar. But only 2 in 6 sides in EGFP-group achieved bony fusion meanwhile. Three-dimensional CT scan and palpation also evidenced the results. Bone formation was observed obviously on specimen both in hBMP4 sides and autografted ones. EGFP-group also got bony integration, but the quantity was small.

CONCLUSIONTissue-engineered bone graft constructed from application of hBMP4 is a fine substitute for autograft. Effective enhancement of bony integration in spinal fusion surgery has been evidenced in vivo.

Animals ; Bone Morphogenetic Protein 4 ; genetics ; Bone Regeneration ; Bone Substitutes ; Bone Transplantation ; methods ; Genetic Vectors ; Lentivirus ; genetics ; Male ; Myeloid Progenitor Cells ; Rabbits ; Random Allocation ; Spinal Fusion ; methods ; Stromal Cells ; Tissue Engineering ; Transfection

OBJECTIVETo compare the surgical results of two kinds of posterior approach for osteoporotic thoracolumbar Kvmmell's disease.

METHODSClinical and radiographic results of 1-segmental pedicle screw fixation combined with vertebroplasty (Group A, n equal to 12) or posterior shortening osteotomy (Group B, n equal to 16) for osteoporotic thoracolumbar Kvmmell's disease were analyzed retrospectively. Japanese orthopedic association (JOA) and visual analogue scale (VAS) scores were used for clinical evaluation. Neurological status was judged by Frankel grades. X-ray was used to evaluate the radiographic results. Complications related to operation and devices were also considered.

RESULTSThe follow-up period was 12-54 months (average 29 months). Pre-and post-operative VAS were 9.3 and 3.2 in Group A, 8.9 and 2.5 in Group B, respectively. The mean JOA score at the final follow-up was significantly higher than that of pre-operation (t equal to 5.306, P less than 0.001). There was no significant difference between Groups A and B (t equal to 0.618, P larger than 0.05). The kyphosis were corrected from preoperative 33.9 degree A)/37.3 degree B) to postoperative 10.3 degree A)/6.5 degree B), and 15.3 degree (A)/13.7 degree B) at the final follow-up. There was a significant difference between the two groups at the final follow-up. Frankel grade was improved from grade C preoperatively to postoperatively grade D or E in 7 cases of Group A and 5 cases of Group B, from grade D to E in 5 cases of Group A and 11 cases of Group B. The mean improvement was 1.6 and 1.7 grades for Groups A and B, respectively. There were no serious complications related to internal fixation.

CONCLUSIONSThe similar clinical results can be obtained by the two kinds of posterior surgical methods for osteoporotic Kvmmell's disease. Posterior spinal shortening is a better choice for patients with serious kyphosis combined with neurological deficit than the other.

Aged ; Bone Screws ; Female ; Follow-Up Studies ; Humans ; Kyphosis ; surgery ; Lumbar Vertebrae ; injuries ; surgery ; Male ; Middle Aged ; Osteoporosis ; complications ; Osteotomy ; Retrospective Studies ; Spinal Fractures ; surgery ; Thoracic Vertebrae ; injuries ; surgery ; Vertebroplasty

OBJECTIVETo build sub-endplate microcirculation disturbance animal model and to investigate the potential pathogenesis of intervertebral disc degeneration (IVDD).

METHODSTwenty four New Zealand white rabbits were divided into treatment group (Group A) and control group (Group B). In Group A, animals received endotoxin and corticosteroid application to build sub-endplate microcirculation disturbance animal model, validated by microthrombus staining. In Group B, animals were given no drug, but standard feeding. After 3 month, the extent of IVDD was evaluated by the water content, biochemistry analysis, and morphology.

RESULTSSub-endplate microthrombus staining confirmed the exist of microcirculation disturbance. The water content and biochemistry components content of disc in Group A were lower than those of disc in Group B, and IVDD was observed in morphology.

CONCLUSIONSub-endplate microcirculation disturbance can directly contribute to IVDD, the nutrients diffusion barrier is the potential pathogenesis of IVDD.

Animals ; Disease Models, Animal ; Female ; Intervertebral Disc ; blood supply ; metabolism ; pathology ; Male ; Microcirculation ; Rabbits ; Random Allocation ; Thrombosis ; complications ; metabolism ; pathology

OBJECTIVETo biomechanically compare the stability of the short and long iliac screw fixation constructs in lumbo-iliac reconstruction.

METHODSSeven adult human embalmed cadavers (L(3)-pelvis) were used. Using posterior spinal fixation system, L(4)-S(1) pedicle screw fixation was performed. This was defined as intact state of the sacroiliac joint. After the intact test, total sacrum resection and L(4)-L(5)-pelvis reconstruction by pedicle screw and iliac screw with different lengths were performed as follow: short screw group (as the length of exceeding 2 mm over ischial notch) and long screw group (as the length of exceeding 2 mm over anterior inferior iliac spine). Using the 858 MTS material testing machine, biomechanical testing was performed under 800 N compression and 7 Nm torsion loading modes. At last, the axial pullout test of two iliac screws was executed. Construct stiffness in compression and torsion test, and maximum pullout force were analyzed.

RESULTSInsertion lengths of the short and long iliac screw were (70 +/- 2) mm and (138 +/- 4) mm respectively. The lumbo-pelvic reconstruction using short and long iliac screw, respectively restored 53.3% +/- 13.6% and 57.6% +/- 16.2% of the initial stiffness in compression testing, and respectively harvested 55.1% +/- 11.9% and 62.5% +/- 9.2% of the initial stiffness in torsion testing. No significant difference was detected between the two reconstructions (P > 0.05), however, the compressive and torsional stiffness of the two techniques were markedly less than the intact condition (P < 0.05). The maximum pullout strength of long iliac screw was significantly higher than short screw (P < 0.05).

CONCLUSIONSUnder the physical loading, lumbo-pelvic fixation construct using the short iliac screw may obtain mechanical stability comparable to that by long iliac screw. The short iliac screw is only the half of the long iliac screw by length, could reduce the implantation risk. However, the long iliac screw behaves greater axial pullout force, should be applied as far as possible in the osteoporosis patient. The lumbo-pelvic reconstruction utilizing any length of iliac screw is difficult to restore the local stability.

Adult ; Aged ; Biomechanical Phenomena ; Bone Screws ; Female ; Humans ; Ilium ; surgery ; Lumbar Vertebrae ; surgery ; Male ; Middle Aged ; Pelvic Bones ; surgery ; Sacrum ; surgery ; Spinal Fusion ; methods

BACKGROUNDPercutaneous kyphoplasty (PKP) using balloon expander has been proved to be effective in the treatment of painful vertebral compression fractures. Recently, Sky-bone expander, an alternative bone expander for PKP has been developed. The purpose of this study was to show our preliminary clinical outcomes of PKP with Sky-bone expander.

METHODSPKP with Sky-bone expander was performed in 25 patients (30 vertebrae). The operation time, bleeding volume, cement volume injected were recorded. The pain and functional activities of the patients before and after the operation were compared using Wilcoxon signed-rank test. The cement distribution in the vertebrae, vertebral height restoration, and kyphosis correction after the procedure were evaluated by radiography. The pre- and post-operative absolute values of the vertebral height and kyphotic angle were compared by paired-sample t test. All the patients were followed up by telephone or clinic consulting after being discharged from our hospital.

RESULTSThe procedure was performed successfully in all the patients. Bipedicular injection was used in 2 of the patients, and unipedicular injection was made in the others. The operation time ranged from 25 to 120 minutes (45 minutes per vertebra on average). The average bleeding volume was about 20 ml. Polymethylmethacrylate 1.5-5.0 ml (mean, (3.15+/-0.78) ml) was injected through each pedicle into all the patients except one, who received calcium sulphate 3.5 ml instead. The patients were followed up for 12-15 months (13.5 months on average). The mean visual analogue scale (VAS) score, Oswestry Disability Index, anterior, midline, and posterior vertebral height, and kyphotic angle of the patients were improved significantly at the end of the follow-up compared with those before the operation. (2.5+/-1.3, 35.1%, (20.94+/-6.15) mm, (20.26+/-4.59) mm, (26.72+/-3.49) mm, and 8.2 degrees vs. 8.5+/-1.9, 61.2%, (19.11+/-6.72) mm, (15.88+/-5.73) mm, (25.78+/-3.67) mm, and 17.3 degrees; all P<0.05). The cement distribution with unipedicular injection was mostly limited within the injection site in the vertebral body. Cement extravasation was seen at ten levels (33.3%).

CONCLUSIONSPKP with Sky-bone expander is an effective and relatively safe alternative to the PKP using balloon expander. It can relieve pain, improve physical function, and restore the height of the collapsed vertebrae, but the cement extravasation is unsolved.

Adult ; Aged ; Bone Cements ; Female ; Fractures, Compression ; surgery ; Humans ; Male ; Middle Aged ; Prospective Studies ; Spinal Fractures ; surgery ; Spine ; surgery ; Tissue Expansion Devices ; Treatment Outcome

OBJECTIVETo compare the clinical results of balloon percutaneous kyphoplasty (PKP) and "Sky-bone expander" PKP.

METHODSFrom October 2004 to February 2006, 25 cases (57 vertebrae) balloon PKP and 24 cases (29 vertebrae) "Sky-bone expander" PKP procedures were performed. The operation time, bleeding volume, cement injected volume were recorded during operation. The patients' pain relief and functional activities recovery were evaluated after operation. The distribution of the cement and the restoration of vertebral height were also observed post-operation. All these patients were followed-up by telephone or clinic consults after discharged.

RESULTSAll cases were successfully experienced procedures. There are no significant differences in operative time, bleeding volume and cost of every vertebrae in these two group (P > 0.05). The balloon group had larger cement injected volume per pedicle than Sky group (4.27 +/- 1.08) ml vs. (3.15 +/- 0.78) ml (P < 0.05). The VAS and ODI scoring of these two groups were both decreased significantly after operation. The vertebral height were restored in both two groups with anterior height and midline height restored significantly in balloon group and midline height restored significantly in Sky group. The cement distribution of "Sky-bone expander" PKP with unipediclar injection mostly limited in the injective side of the vertebral body, but most of the balloon PKP vertebrae with unipediclar injection can be seen a cross-midline cement distribution in the anterior-posterior position X ray film.

CONCLUSIONSBoth balloon PKP and "Sky-bone expander" PKP are efficacious and safety in the treatment of vertebral compression fractures. "Sky-bone expander" PKP is more suitable for single level compressive fracture while balloon PKP is especially suitable for multiple level compressive fractures.

Aged ; Aged, 80 and over ; Catheterization ; instrumentation ; Female ; Follow-Up Studies ; Fractures, Compression ; etiology ; surgery ; Humans ; Male ; Middle Aged ; Osteoporosis ; complications ; Spinal Fractures ; etiology ; surgery ; Tissue Expansion Devices ; Vertebroplasty ; instrumentation ; methods