Degenerated nucleus pulposus cells derived exosome carrying miR-27a-3p aggravates intervertebral disc degeneration by inducing M1 polarization of macrophages.

BACKGROUND: Intervertebral disc degeneration (IVDD) is a major contributor to spinal disorders. Previous studies have indicated that the infiltration of immunocytes, specifically macrophages, plays a crucial role in the advancement of IVDD. Exosomes (exo) are believed to play a significant role in intercellular communication. This study aims to investigate the role of exosomes derived from degenerated nucleus pulposus (dNPc) in the process of macrophages M1 polarization. METHODS: Nucleus pulposus (NP) tissue and nucleus pulposus cells (NPc) were collected from patients with intervertebral disc degeneration (IVDD) and idiopathic scoliosis. Immunohistochemistry analysis was performed to determine the number of M1 macrophages in NP tissue. Subsequently, exosomes derived from degenerated NP cells (dNPc-exo) and non-degenerated NP cells (nNPc-exo) were collected and co-cultured with M0 macrophages, which were induced from THP-1 cells. The M1 phenotype was assessed using western blot, flow cytometry, immunofluorescence staining, and qRT-PCR. RNA-sequencing analysis was conducted to examine the expression levels of microRNAs in the dNPc-exo and nNPc-exo groups, and qRT-PCR was performed to investigate the effect pf different microRNA to induce macrophage polarization. Furthermore, western blot and qRT-PCR were employed to demonstrate the regulatory effect of microRNAs carried by dNPc-exo on downstream target signaling pathways in macrophages. Finally, an animal model of IVDD was utilized to investigate the impact of dNPc-exo on inducing M1 polarization of macrophages and its role in the IVDD process. RESULTS: In this study, we observed an increase in the number of M1 macrophages as the intervertebral disc (IVD) degraded. Additionally, we discovered that dNPc releases exosomes (dNPc-exo) could promote the polarization of macrophages towards the M1 phenotype. Notably, through RNA-sequencing analysis of dNPc-exo and nNPc-exo groups, we identified miR-27a-3p as a highly expressed miRNA in the dNPc-exo group, which significantly influences the induction of M1 polarization of macrophages. And then, we discovered that dNPc-exo has the ability to transport miR-27a-3p and target the PPARγ/NFκB/PI3K/AKT signaling pathway, thereby influencing the M1 polarization of macrophages. We conducted experiments using rat model of IVDD and observed that the exosomes carrying miR-27a-3p actually induced the M1 polarization of macrophages and exacerbated the degradation of IVD. CONCLUSION: In conclusion, our findings highlight the significant role of dNPc-exo in IVDD process and provide a basis for further investigation into the mechanism of IVDD and the potential of exosome-based therapy.

Insights into Exosome in the Intervertebral Disc: Emerging Role for Disc Homeostasis and Normal Function.

Low back pain (LBP) is a chronic condition that causes great individual suffering and economic burden. The major contributor of LBP is intervertebral disc degeneration (IDD), which is caused by a spectrum of homeostasis alteration, including the apoptosis of nucleus pulposus (NP) and annulus fibrosus (AF) cells, degradation of extracellular matrix (ECM), calcification of cartilaginous endplates (CEP) and so on. Currently, the therapeutic strategy for IDD includes conservative and surgery treatment. Nevertheless, none of them could reverse the progressive destruction of the intervertebral disc. Hence, it is pivotal to pursue a new therapeutic approach. Exosomes, nano-sized substances with diameters of 30-150 nm, can be synthesized and secreted by various types of cells. They play an important role in intercellular communication. Increasing evidence implicates that exosomes could impact the intracellular transcription activities, thereby inhibiting or accelerating the proliferation and apoptosis of cells. Thus, it is a new therapeutic source for IDD. This review chiefly focuses on generalizing and clarifying the roles of exosomes in the onset and deterioration of IDD, and their therapeutic potential.

Effection of monoplanar pedicle screw on facet joint degeneration in thoracolumbar vertebral fractures.

BACKGROUND: This study aimed to compare the clinical outcomes and effect on instrument-related facet joints between fixed-axis pedicle screw (FAPS) and monoplanar pedicle screw (MPPS). METHODS: 816 pedicle screws of 204 patients with thoracolumbar vertebral fractures (TLVF) who underwent internal fixation surgery were analyzed in this retrospective study. All patients were divided into two groups (FAPS and MPPS). Preoperative, immediate postoperative, and 12-18-months postoperative CT and X-ray, and clinical data, including demographics, preoperative and immediate postoperative Visual Analogue Scale (VAS), blood loss (BL), operation time (OT) and hospital stay time (HST), were collected. Facet joint violation and degeneration grade were evaluated by CT according to Babu's criteria and Weishaupt's criteria respectively, and preoperative, immediate postoperative and 12-18-months postoperative anterior body compression index (ABCI) were measured by X-ray. RESULTS: Postoperative VAS of two groups was lower than preoperative VAS (p < 0.05). BL, OT, and HST were less in MPPS than FAPS, and the difference was statistically significant in BL and HST (p < 0.05) but no in OT (p > 0.05). Immediate postoperative and 12-18-months postoperative ABCI were significantly higher than preoperative (p < 0.05), and the difference of ABCI between immediate postoperative and 12-18-months postoperative were not significant in two groups (p > 0.05). Total violation rate (VR) was about 1.35% (11/816) and FAPS had a lower VR than MPPS, but no significant (p > 0.05). Weishaupt's criteria revealed that average class (AC) was 0.69 in FAPS and 0.67 in MPPS, and the distribution of degenerated facet joints in two groups did not differ preoperatively (p > 0.05). In 12-18 months postoperatively, AC was significantly higher in FAPS than in MPPS, and the distribution of degenerated facet joints in two groups was significantly different (p < 0.05). The comparison of cranial to caudal joints in two groups revealed that cranial joints had more severe degeneration than caudal joints. CONCLUSIONS: The findings suggested that both MPPS and FAPS were effective for patients with TLVF, but MPPS by percutaneous may be a better choice to avoid adjacent segment degeneration, especially the surgery-involved facet joints degeneration.

Clinical efficacy and therapeutic value of delayed surgery in patients with symptomatic old thoracolumbar fractures.

BACKGROUND: To investigate the clinical efficacy and therapeutic value of posterior decompression reduction, bone grafting fusion, and internal fixation for treatment of symptomatic old thoracolumbar fractures. METHOD: Retrospective analysis was conducted for 14 patients (9 men, 5 women; average age 40.1 years) with old thoracolumbar fractures who underwent posterior operation. American Spinal Injury Association (ASIA) scores were used to evaluate neurologic function. Vertebral body height, Cobb angle in the sagittal plane, spinal canal volume ratio (%) and bone graft fusion were analyzed by radiography and computed tomography on different follow-up times. RESULTS: Mean follow-up was 27.1 months (23-36 months). Of three patients with ASIA grade A, 2 had improved postoperative urination and defecation, although no classification change. Preoperative ASIA score for eight patients with incomplete injury was grade B; four patients recovered to grade C at final follow-up. Preoperative ASIA score was C in three patients, increased to D in two patients and returned to normal E in one patient. Preoperative results showed average injured vertebra height loss rate decreased from 50.4 to 8.9%; average Cobb angle on the sagittal plane recovered from 39.6 to 6.9°; and the average spinal canal volume ratio recovered from 33.8 to 5.9%. Bony fusion was achieved; local lumbago and leg pain were relieved to some extent. No patients exhibited loosening of the fracture treated by internal fixation, pseudoarthrosis, or other related serious complications. CONCLUSION: Treatment of old thoracolumbar fractures by posterior decompression reduction, bone grafting fusion, and internal fixation can relieve spinal cord compression, improve neurologic function of some patients (ASIA grades B-C), effectively relieve pain, correct deformity, restore biomechanical stability, and significantly improve quality of life.

Effects of Ginkgo Biloba Extract EGb-761 on Neuropathic Pain in Mice: Involvement of Opioid System.

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 Wiley & Sons, Ltd.

The effects and mechanisms of clinorotation on proliferation and differentiation in bone marrow mesenchymal stem cells.

Data from human and rodent studies have demonstrated that microgravity induces observed bone loss in real spaceflight or simulated experiments. The decrease of bone formation and block of maturation may play important roles in bone loss induced by microgravity. The aim of this study was to investigate the changes of proliferation and differentiation in bone marrow mesenchymal stem cells (BMSCs) induced by simulated microgravity and the mechanisms underlying it. We report here that clinorotation, a simulated model of microgravity, decreased proliferation and differentiation in BMSCs after exposure to 48 h simulated microgravity. The inhibited proliferation are related with blocking the cell cycle in G2/M and enhancing the apoptosis. While alterations of the osteoblast differentiation due to the decreased SATB2 expression induced by simulated microgravity in BMSCs.

Electrical stimulation induces calcium-dependent neurite outgrowth and immediate early genes expressions of dorsal root ganglion neurons.

It has been reported that electrical stimulation (ES) can promote nerve regeneration. One of the key factors leading to the promotion is calcium, which plays a vital role in the regulation on electrical activity of neurons, but the detailed mechanism is still an open question. In this study, ES was used to stimulate cultured dorsal root ganglion neurons (DRGNs) and we've found that ES could greatly promote neurite outgrowth, and calcium signaling was involved in the ES-induced neurite extension in our research. Detailed pharmacological tests indicated that ES-induced elevation of intracellular free calcium concentration ([Ca(2+)] i ) in DRGNs was realized predominately via calcium influx and calcium mobilization, both of which contributed to enhancing neurite outgrowth promoted by ES. Additionally, a calcium-triggered c-fos and brain-derived neurotrophic factor (BDNF) transcription and/or translation were discovered during the ES-induced neurite outgrowth of cultured DRGNs. To our knowledge, this is the first case of detailed snapshots of studying calcium-dependent neurite outgrowth and BDNF and c-fos expressions in DRGNs induced by ES, which may provide experimental evidence for applying ES to promote regeneration of injured nerves and to enhance synthesis of c-fos and BDNF in neurons, and may also help explore the complex molecular cascades underlying the progressive pathophysiological changes in the ES-induced nerve regeneration in future.

Mechanical compression insults induce nanoscale changes of membrane-skeleton arrangement which could cause apoptosis and necrosis in dorsal root ganglion neurons.

In a primary spinal cord injury, the amount of mechanical compression insult that the neurons experience is one of the most critical factors in determining the extent of the injury. The ultrastructural changes that neurons undergo when subjected to mechanical compression are largely unknown. In the present study, using a compression-driven instrument that can simulate mechanical compression insult, we applied mechanical compression stimulation at 0.3, 0.5, and 0.7 MPa to dorsal root ganglion (DRG) neurons for 10 min. Combined with atomic force microscopy, we investigated nanoscale changes in the membrane-skeleton, cytoskeleton alterations, and apoptosis induced by mechanical compression injury. The results indicated that mechanical compression injury leads to rearrangement of the membrane-skeleton compared with the control group. In addition, mechanical compression stimulation induced apoptosis and necrosis and also changed the distribution of the cytoskeleton in DRG neurons. Thus, the membrane-skeleton may play an important role in the response to mechanical insults in DRG neurons. Moreover, sudden insults caused by high mechanical compression, which is most likely conducted by the membrane-skeleton, may induce necrosis, apoptosis, and cytoskeletal alterations.

Non-fusion and growing instrumentation in the correction of congenital spinal deformity associated with split spinal cord malformation: an early follow-up outcome.

STUDY DESIGN: A retrospective case review. INTRODUCTION: To evaluate the safety and efficacy of the non-fusion technique in achieving and maintaining the proper correction for congenital spinal deformity (CSD) and allowing normal spinal growth in patients with split spinal cord malformation (SSCM). MATERIALS AND METHODS: Seven patients who had CSD and SSCM were adopted, with a mean age of 8 years. All the patients in this study received Halo-gravity traction (HGT) prior to expansion of the spine and instrumentation with vertical expandable titanium prosthetic rib, growing rod or their hybrid. Five of them underwent opening wedge thoracoplasty simultaneously. And the two patients with type I SSCM underwent bony spur excision in the initial surgery before corrective manipulation. Then all the patients received a lengthened operation every six months. Changes of their major curve and length of T1-S1 spine were measured, and complications, neurological status were recorded. All the patients were followed up with an average of 32.6 months. RESULTS: Their mean major curve improved from 90.1° to 58.6° with a correction rate of 34.9 %. The T1-S1 length increased from 26.3 to 34.7 cm at final follow-up. Especially, one of the type I SSCM patients whose neurological deterioration was found preoperatively was significantly improved. CONCLUSION: Preoperative Halo-gravity traction followed by non-fusion and growing instrumentation may be effective and safe for young children of CSD associated with SSCM. But it is an ongoing study and additional large multicenter studies are necessary to further assess the safety and efficacy of non-fusion and growing instrumentation.

Staged corrective surgery for complex adolescent kyphoscoliosis caused by back scalding during the childhood period.

INTRODUCTION: Adolescent scar contracture kyphoscoliosis is a very rare disease. METHODS AND RESULTS: Here, we present the case of a 21-year-old man who was scalded due to ebullient water when he was 10 years old. Moreover, kyphoscoliosis was found when he was 12 years old and developed rapidly. Thereafter, no management was proposed before his consultation at our center. On examination, kyphoscoliosis was detected in thoracolumbar, the trunk deviated to the right on standing view, extensive contractured scar presented on the right side of the back, abdomen, chest wall, hip, right thighs and armpit anterior, especially in the right flank. A one-stage correction was deemed too risky, we therefore released contractured scar during the first stage with the defect of soft tissue protected by vacuum sealing drainage and then performed skeletal traction with halo and bilateral femoral pins. A reasonable correction was achieved without any neurological deficits 1 month after traction. Next, a second-stage operation was taken to translate a free anterolateral thigh myocutaneous flap to overlay the extensive defect of soft tissue. 1.5 months later, a third posterior segmental pedicle screw instrumented fusion with Smith-Peterson osteotomy between T9 and L2 was performed. Postoperative recovery was uneventful and as there were no complications, he was discharged 10 days after the third surgery. At 2-year follow-up the patient's outcome is excellent with balance and correction of the deformity. CONCLUSION: Based this grand round case and relevant literature, we discuss the different options for the treatment of adolescent scar contracture scoliosis.

Comparison of the Clinical Efficacy of Two Reduction Methods for the Treatment of Irreducible Unilateral Subaxial Cervical Facet Joint Dislocation.

OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Comparing Clinical and Radiographic Outcomes Between the Self-locking Stand-alone Cage and Conventional Cage-plate Construct: A Five-year Retrospective Cohort Study.

STUDY DESIGN/SETTING: A retrospective cohort study. OBJECTIVE: To evaluate the clinical efficacy of the self-locking stand-alone (SA) cage and conventional cage-plate construct (CPC) in treating degenerative cervical spondylosis with a five-year follow-up. SUMMARY OF BACKGROUND DATA: The SA approach was designed to reduce complications associated with traditional anterior cervical discectomy and fusion. These techniques have been shown to have satisfactory short-term clinical outcomes. Literature describing the mid-term clinical outcomes of SA cage is limited. MATERIALS AND METHODS: We retrospectively analyzed patients with cervical spondylosis who had received an SA device or CPC between 2014 and 2016 at the Xijing Hospital. Participants were matched for sex, age, and operative level. Differences in clinical and radiographic outcomes and the occurrence of postoperative complications between the two groups were analyzed. RESULTS: In total, 207 patients were included (101 with SA and 106 with CPC), the median follow-up for both groups were 60.2 and 60.9 months. Both groups exhibited significant improvements in all measured values compared with the preoperative values. The SA group had a shorter operation time, less intraoperative blood loss, and a significantly lower incidence of dysphagia after surgery than the CPC group ( P <0.05). At the last visit, cage subsidence was 6.9% and 3.8% in the SA and CPC groups, respectively ( P =0.365). The radiographic adjacent segment degeneration (ASD) was significantly lower in the SA group than in the CPC group (6.9% vs. 27.4%, P <0.01). No symptomatic ASD was observed in the SA group, and six (5.7%) cases occurred in the CPC group ( P =0.029). CONCLUSIONS: In this study, the SA cage showed similar efficacy to that of the conventional CPC in treating cervical spondylosis using anterior cervical discectomy and fusion, with a significant reduction in the incidence of immediate postoperative dysphagia and mid-term ASD.

Electrical stimulation induces calcium-dependent release of NGF from cultured Schwann cells.

Production of nerve growth factor (NGF) from Schwann cells (SCs) progressively declines in the distal stump, if axonal regeneration is staggered across the suture site after peripheral nerve injuries. This may be an important factor limiting the outcome of nerve injury repair. Thus far, extensive efforts are devoted to modulating NGF production in cultured SCs, but little has been achieved. In the present in vitro study, electrical stimulation (ES) was attempted to stimulate cultured SCs to release NGF. Our data showed that ES was capable of enhancing NGF release from cultured SCs. An electrical field (1 Hz, 5 V/cm) caused a 4.1-fold increase in NGF release from cultured SCs. The ES-induced NGF release is calcium dependent. Depletion of extracellular or/and intracellular calcium partially/ completely abolished the ES-induced NGF release. Further pharmacological interventions showed that ES induces calcium influx through T-type voltage-gated calcium channels and mobilizes calcium from 1, 4, 5-trisphosphate-sensitive stores and caffeine/ryanodine-sensitive stores, both of which contributed to the enhanced NGF release induced by ES. In addition, a calcium-triggered exocytosis mechanism was involved in the ES-induced NGF release from cultured SCs. These findings show the feasibility of using ES in stimulating SCs to release NGF, which holds great potential in promoting nerve regeneration by enhancing survival and outgrowth of damaged nerves, and is of great significance in nerve injury repair and neuronal tissue engineering.

Detection and characterization of side population in Ewing's sarcoma SK-ES-1 cells in vitro.

Dye exclusion is a valuable technique to isolate cancer stem cells (CSCs) based on an ability of stem cell to efflux fluorescent DNA-binding dye, especially for tumors without unique surface markers. It has been proven that side population (SP) cells that exclude Hoechst 33342 dye are enriched with stem-like cells in several cancer cell lines. In this study, we isolated and characterized SP cells from human Ewing's sarcoma cell line SK-ES-1 in vitro. SP cells were detected in SK-ES-1 and comprised 1.2% of total cell population. Only SP cells had the capacity to regenerate both SP and non-SP cells. The proliferation rates were similar between SP and non-SP cells. However, the clonogenicity and invasiveness of SP cells were significantly higher than that of non-SP cells. Further characterization of this SP phenotype presented other properties. SP cells exhibited increased multi-drug resistance and the ATP binding cassette protein (ABC) transporters were up-regulated in SP population. These findings suggest that SP cells derived from Ewing's sarcoma play the critical role in tumor metastasis and recurrence and might be an ideal target for clinical therapy.

[A clinical follow-up study on treatment of adolescent idiopathic scoliosis with brace].

OBJECTIVE: To evaluate clinical outcomes of bracing and analyze related factors that influence curative effects in adolescents with idiopathic scoliosis, and to investigate indications of bracing. METHODS: Seventy-nine patients with AIS who had no history of prior therapy were treated with a brace. Several parameters were consecutive measured and documented during the period of follow-up including Cobb's angles, curve patterns, menarche status, sitting heights, standing heights, Risser sign, apical vertebral rotation, and so on. RESULTS: The average period of followed-up was 30 months (12 months to 60 months). Twenty-one patients (26.6%) presented curve deterioration, 40 patients have no obvious curve change, 18 patients (22.8%) got a curve improvement. There was significantly lower percentage of curve progression and higher percentage of curve improvement in cases with Cobb's angle less than 35 degrees at the first visit (P < 0.05). The percentage of curve progression was significantly greater in the cases with apical vertebral rotation beyond grade III while the percentage of curve improvement was lower (P < 0.05). Curve patterns, Risser sign and other parameters were found to make their effects on the percentage of curve progression and improvement, which, however, was not statistically significant (P > 0.05). CONCLUSION: Bracing can limit or improve mild and moderate curve of idiopathic scoliosis effectively, especially in cases with initial curve magnitude ranging from 20 degrees to 35 degrees . Risser sign is not a reliable parameter for measuring the outcome of bracing treatment for idiopathic scoliosis. Surgery is advised as soon as possible for the cases with initial Cobb's angles greater than 45 degrees and initial apical vertebral rotation beyond grade III early while bracing did not work.

Novel Screw Head Design of Pedicle Screw for Reducing the Correction Loss in the Patients With Thoracolumbar Vertebral Fractures: A Biomechanical Study.

STUDY DESIGN: A biomechanical study. OBJECTIVE: To study the different biomechanical property among fixed-axis, monoplanar and polyaxial screws in the static and dynamic tests. SUMMARY OF BACKGROUND DATA: Correction loss is a common phenomenon in the patients with thoracolumbar vertebral fractures who underwent the posterior pedicle screw fixation. The incidence varies with the kinds of fixation instrumentation used. There is higher incidence in polyaxial pedicle screws group than in fixed-axis pedicle screws. Monoplanar pedicle screws, which are mobile in the axial plane but fixed in the sagittal plane, can be a better fixation instrumentation for thoracolumbar vertebral fractures in theory. METHODS: A total of 30 porcine spinal units (L2-L4) were used for the static and dynamic tests, which were randomized into six groups (A1, A2, A3, B1, B2, and B3). Static test was performed in A1, A2, and A3. In this test, fixed-axis, monoplanar, and polyaxial screws were performed in A1, A2, and A3, respectively. The ultimate load was noted after tested. In addition, dynamic test was performed in B1, B2, and B3, used fixed-axis, monoplanar, and polyaxial screws, respectively. Correction loss (head-shank angle shift and anterior vertebral body height shift) was obtained and analyzed in each mode. RESULTS: In static test, fixed-axis and monoplanar screws had significantly higher ultimate load than polyaxial screws (P < 0.05) and fixed-axis screws had a little higher ultimate load than monoplanar screws (P < 0.05). In dynamic test, correction loss was minimal in fixed-axis screws, medium in monoplanar screws, and maximal in polyaxial screws. However, the differences were statistically significant in all comparisons but not in the comparison of fixed-axis and monoplanar screws (P > 0.05). CONCLUSION: The findings from the current study suggest that monoplanar screws can significantly increase the stiffness in axial direction compared with polyaxial screws, and reduce the risks of correction loss. For thoracolumbar vertebral fractures, monoplanar screw is a better optional instrumentation for minimally invasive surgery. LEVEL OF EVIDENCE: N/A.

[Effects of Yunnan Baiyao on peri-operative bleeding of patients undergoing cervical open-door laminoplasty: a multi-center randomized double-blind placebo-control trial].

OBJECTIVE: To investigate the effects of Yunnan Baiyao on peri-operative bleeding of the patients undergoing cervical open-door laminoplasty. METHODS: 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. RESULTS: 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, P < 0.05). There were no statistical differences in the amount of postoperative bleeding and side effect rate between the two groups. CONCLUSION: Yunnan Baiyao is effective and safe in reducing the amount of intra-operative bleeding of cervical open-door laminoplasty.

CaMKII-Mediated CREB Phosphorylation Is Involved in Ca2+-Induced BDNF mRNA Transcription and Neurite Outgrowth Promoted by Electrical Stimulation.

Electrical stimulation (ES)-triggered up-regulation of brain-derived neurotrophic factor (BDNF) and neurite outgrowth in cultured rat postnatal dorsal root ganglion neurons (DRGNs) is calcium (Ca2+)-dependent. The effects of increased Ca2+ on BDNF up-regulation and neurite outgrowth remain unclear. We showed here that ES increased phosphorylation of the cAMP-response element binding protein (CREB). Blockade of Ca2+ suppressed CREB phosphorylation and neurite outgrowth. Down-regulation of phosphorylated (p)-CREB reduced BDNF transcription and neurite outgrowth triggered by ES. Furthermore, blockade of calmodulin-dependent protein kinase II (CaMKII) using the inhibitors KN93 or KN62 reduced p-CREB, and specific knockdown of the CaMKIIα or CaMKIIß subunit was sufficient to suppress p-CREB. Recombinant BDNF or hyperforin reversed the effects of Ca2+ blockade and CaMKII knockdown. Taken together, these data establish a potential signaling pathway of Ca2+-CaMKII-CREB in neuronal activation. To our knowledge, this is the first report of the mechanisms of Ca2+-dependent BDNF transcription and neurite outgrowth triggered by ES. These findings might help further investigation of complex molecular signaling networks in ES-triggered nerve regeneration in vivo.

Effects of mechanical force on cytoskeleton structure and calpain-induced apoptosis in rat dorsal root ganglion neurons in vitro.

BACKGROUND: A sudden mechanical insult to the spinal cord is usually caused by changing pressure on the surface of the spinal cord. Most of these insults are mechanical force injuries, and their mechanism of injury to the spinal cord is largely unknown. METHODS: Using a compression-driven instrument to simulate mechanical force, we applied mechanical pressure of 0.5 MPa to rat dorsal root ganglion (DRG) neurons for 10 min to investigate cytoskeletal alterations and calpain-induced apoptosis after the mechanical force injury. RESULTS: The results indicated that mechanical forces affect the structure of the cytoskeleton and cell viability, induce early apoptosis, and affect the cell cycle of DRG neurons. In addition, the calpain inhibitor PD150606 reduced cytoskeletal degradation and the rate of apoptosis after mechanical force injury. CONCLUSION: Thus, calpain may play an important role in DRG neurons in the regulation of apoptosis and cytoskeletal alterations induced by mechanical force. Moreover, cytoskeletal alterations may be substantially involved in the mechanotransduction process in DRG neurons after mechanical injury and may be induced by activated calpain. To our knowledge, this is the first report to demonstrate a relationship between cytoskeletal degradation and apoptosis in DRG neurons.

Oral administration of quercetin inhibits bone loss in rat model of diabetic osteopenia.

Diabetic osteopenia can result in an increased incidence of bone fracture and a delay in fracture healing. Quercetin, one of the most widely distributed flavonoids in plants, possesses antioxidant property and beneficial effect on osteoporosis in ovariectomized mice. All these properties make quercetin a potential candidate for controlling the development of diabetic osteopenia. Therefore, the present study was designed to investigate the putative beneficial effect of quercetin on diabetic osteopenia in rats. Diabetes mellitus was induced by streptozotocin. The diabetic rats received daily oral administration of quercetin (5mg/kg, 30 mg/kg and 50mg/kg) for 8 weeks, which was started at 4 weeks after streptozotocin injection. Quercetin at 5mg/kg showed little effect on diabetic osteopenia, while quercetin at 30 mg/kg and 50mg/kg could increase the decreased serum osteocalcin, serum alkaline phosphatase activity, and urinary deoxypyridinoline in diabetic rats. In addition, quercetin (30 mg/kg and 50mg/kg) could partially reverse the decreased biomechanical quality and the impaired micro-architecture of the femurs in diabetic rats. Histomorphometric analysis showed that both decreased bone formation and resorption were observed in diabetic rats, which was partially restored by quercetin (30 mg/kg and 50mg/kg). Further investigations showed that quercetin significantly lowered the oxidative DNA damage level, up-regulated the total serum antioxidant capability and the activity of serum antioxidants in diabetic rats. All those findings indicate the beneficial effect of quercetin on diabetic osteopenia in rats, and raise the possibility of developing quercetin as potential drugs or an ingredient in diet for controlling diabetic osteopenia.