Reversed windshield-wiper effect leads to failure of cement-augmented pedicle screw: Biomechanical mechanism analysis by finite element experiment.

The failure mode of cement-augmented pedicle screw (CAPS) was different from common pedicle screw. No biomechanical study of this failure mode named as "reversed windshield-wiper effect" was reported. To investigate the mechanisms underlying this failure mode, a series of finite element models of CAPS and PS were modified on L4 osseous model. Nine models were created according to the cement volume at 0.5 mL interval (range: 1-5 mL). Pullout load and cranio-caudal loads were applied on the screws. Stress and instantaneous rotation center (IRC) of the vertebra were observed. Under cranio-caudal load, the stress concentrated on the screw tip and pedicle region. The maximal stress (MS) at the screw tip region was +2.143 MPa higher than pedicle region. With cement volume increasing, the maximal stress (MS) at the screw tip region decreased dramatically, while MS at pedicle region was not obviously affected. As dose increased to 1.5 mL, the MS at pedicle region became higher than screw tip region and the maximal stress difference was observed at 3.5 mL. IRC of the vertebra located at the facet joint region in PS model. While IRC in CAPS models shifted anteriorly closer to the vertebral body with the increasing of cement volume. Under axial pull-out load, the maximal stress (MS) of cancellous bone in CAPS models was 29.53-50.04% lower than that 2.228 MPa in PS model. MS in the screw-bone interface did not change significantly with cement volume increasing. Therefore, the possible mechanism is that anterior shift of IRC and the negative difference value of MS between screw tip and pedicle region due to cement augmentation, leading to the screw rotate around the cement-screw complex as the fulcrum point.

Fate of the intervertebral disc and analysis of its risk factors following high-energy traumatic thoracic and lumbar fractures: MRI results of minimum five years after injury.

OBJECTIVE: Disc degenerative disease is regarded as the primary cause of low back pain. The purpose of this study was to clarify the fate of Intervertebral disc (IVD) following the traumatic event through long-term follow-up and to identify the risk factors for irrevocable degeneration. METHODS: 78 non-operative patients who had traumatic fracture of the thoracic or lumbar at minimum 5 years before were enrolled. Disc degeneration was assessed by modified Pfirrmann grading system. The Acceleration of disc degeneration (ADD) was defined as the difference of grade between IVD adjacent to fractured vertebra and their neighbors with increasing grade from 0 to 7. A novel classification of Endplate injury (EPI) with increasing severity from type I to III was proposed based on the injured morphology. The long-term fate of IVD adjacent to fractured vertebra and risk factors for ADD were analyzed. RESULTS: The mean time of last follow-up was 15.4 ± 10.8 years (range 5-49 years) after injury. 138 (68.66%) IVDs were graded 0 of ADD, 44 (21.89%) were 1-3 and 19 (9.45%) were 4-7. Multivariate binary logistic regression analyses showed that injured posterior ligamentous complex (PLC) and EPI type III were independent risk factors for ADD. CONCLUSIONS: Injured PLC and EPI type III were independent risk factors for ADD in patients with traumatic thoracic or lumbar fracture. For such patients without risk factors for ADD, the non-intervertebral fusion should be given a priority if surgery is necessary.

Transplantation of neural stem cells preconditioned with high­mobility group box 1 facilitates functional recovery after spinal cord injury in rats.

Spinal cord injury (SCI) is a devastating disorder that often results in temporary and/or permanent functional impairment below the injured level. To date, few satisfactory therapeutic strategies are available to treat SCI. Hence, exploring novel strategies for SCI is an essential public health concern. Cell transplantation therapy, which is associated with neuroprotection, immunomodulation, axon regeneration, neuronal relay formation and myelin regeneration, provides a promising therapeutic strategy for SCI. The neuronal stem cell (NSC) preconditioning method is an emerging approach, which facilitates NSC survival and neuronal differentiation after implantation. The aim of the present study was to develop a feasible candidate for cell­based therapy following SCI in rats and to investigate the role of high mobility group box­1 (HMGB1) in NSC activation. The results of the present study showed that transplantation of NSCs, preconditioned with 1 ng/ml HMGB1, facilitated functional improvement of injured spinal cords, as indicated by Basso, Beattie and Bresnahan mean scores, mechanical hypersensitivity and cold stimulation. Meanwhile, the histological examination of hematoxylin and eosin staining indicated that engraftment of HMGB1­preconditioned NSCs resulted in decreased atrophy of the injured spinal cord. Meanwhile, the transplantation of HMGB1­preconditioned NSCs resulted in an increased number of functional Nissl bodies in neurons, as detected by Nissl staining, and an increase in the number of ßIII­tubulin+ cells in the epicenter of injured spinal cords in rats with SCI. In addition, the results also demonstrated that 1 ng/ml HMGB1 promoted the differentiation of NSCs into neurons, and that the ERK signaling pathway played an important role in this process. In conclusion, the present data indicated that the preconditioning strategy with 1 ng/ml HMGB1 may present a feasible candidate for cell­based therapy following SCI in rats, which may enlarge the scope of HMGB1 in NSC activation.

Comparison of unilateral and bilateral polymethylmethacrylate-augmented cannulated pedicle screw fixation for the management of lumbar spondylolisthesis with osteoporosis.

BACKGROUND: Cannulated pedicle screw (CPS) augmented by polymethylmethacrylate (PMMA) can achieve satisfactory clinical efficacy in the treatment of lumbar spondylolisthesis with osteoporosis. However, accurate application of CPSs will help to avoid the difficulty of screw revision and reduce the incidence of PMMA-related complications. This study aimed to investigate the mid-term efficacy of CPS compared to unilateral and bilateral applications in this common lumbar degenerative disease. METHODS: May 2011 and May 2018, 50 patients with lumbar spondylolisthesis with osteoporosis who underwent posterior fixation and fusion using traditional pedicle screws or CPSs were included in the study. Patients were divided into two groups based on the application: the unilateral PMMA-augmented CPS group (UC, n = 29) and the bilateral PMMA-augmented CPS group (BC, n = 21). Operation time, blood loss, average hospitalization time, PMMA leakage, and other complications were recorded. The visual analog scale (VAS) and Oswestry disability index (ODI) scores were used to evaluate symptom recovery. Radiographic results were compared for intervertebral fusion and screw loosening. RESULTS: There were no significant differences in the baseline data of the two groups. The VAS and ODI scores improved significantly after surgery (P < 0.05), with no significant differences between the groups (P > 0.05). The operation time and blood loss in the UC group were significantly lower than those in the BC group (P < 0.05). However, the loss of intervertebral disk height and Taillard index did not differ significantly between the groups. The rates of PMMA leakage in the UC and BC groups were 7.0% and 11.9%, respectively (P < 0.05). Bony fusion was achieved in all groups without screw loosening at the last follow-up. Only one patient experienced superficial infection in both groups, while cerebrospinal fluid leakage was observed in two patients in the BC group. CONCLUSIONS: Unilateral application of PMMA-augmented CPS may provide adequate clinical safety and effectiveness in the surgical treatment of lumbar spondylolisthesis with osteoporosis.

Clinical efficacy of Bone Cement-injectable Cannulated Pedicle Screw Short Segment Fixation for Lumbar Spondylolisthesis with Osteoporosise.

Many clinical studies have shown a satisfactory clinical efficacy using bone cement-augmented pedicle screw in osteoporotic spine, however, few studies have involved the application of this type of screw in lumbar spondylolisthesis. This study aims to investigate the mid-term clinical outcome of bone cement-injectable cannulated pedicle screw (CICPS) in lumbar spondylolisthesis with osteoporosis. From 2011 to 2015, twenty-three patients with transforminal lumbar interbody fusion (TLIF) using CICPS for lumbar spondylolisthesis were enrolled in the study. Oswestry Disability Index (ODI) and Visual Analogue Scale (VAS) were used to evaluate faunctional recovery and physical pain; and operation time, blood loss and hospitalization time were recorded, respectively. Radiograph and computed tomography of lumbar spine was performed to assess loss of the intervertebral disc space height, fixation loosening, and the rate of bony fusion. The average follow-up time of 23 patients was 22.5 ± 10.2 months (range, 6-36 months). According to VAS and ODI scores, postoperative pain sensation and activity function were significantly improved (p < 0.05). The height of the intervertebral disc space was reduced by 0.4 ± 1.1 mm, and the bone graft fusion rate was 100%. No cases of internal fixation loosening or screw pullout was observed. CICPS using cement augmentation may suggest as a feasible surgical technique in osteoporotic patients with lumbar spondylolisthesis.

LRRFIP1 expression triggers platelet agglutination by enhancing αIIbß3 expression.

Platelets primarily participate in hemostasis and antimicrobial host defense. The present study aimed to investigate the effects of leucine-rich repeat flightless-interacting protein-1 (LRRFIP1) on platelet agglutination. The bacterial strain of LRRFIP1 was used to synthesize the recombinant protein and a mouse model of LRRFIP1 gene knockout was established. Platelets were isolated from the mice and divided into the different trial groups according to their treatment with collagen, thrombin receptor SFLLRN, anti-wild-type (w)LRRFIP1monoclonal antibodies and the model of LRRFIP1 gene knockout. The platelets were prepared and platelet agglutination was examined using platelet aggregation apparatus. The active αIIbß3 integrin was examined by flow cytometry. The results revealed that the combined wLRRFIP1 protein was successfully expressed. wLRRFIP1 treatment significantly triggered platelet agglutination of collagen, thrombin and monoclonal antibody treated platelets. wLRRFIP1 knockout significantly decreased αIIbß3 levels compared with the wild-type. Platelet agglutination was also significantly inhibited in the LRRFIP1-/-mouse model compared with the wild-type. LRRFIP1 knockout significantly decreased the αIIbß3 levels in platelets undergoing convulxin treatment. In conclusion, LRRFIP1 treatment triggered platelet agglutination and LRRFIP1 gene knockout inhibited platelet agglutination. In addition, LRRFIP1 gene knockout significantly decreased the levels of αIIbß3. This suggests that LRRFIP1 my be applied to patients in a clinical setting to trigger platelet agglutination in inflammatory diseases and atherothrombotic diseases.

Expressions of some neurotrophins and neurotrophic cytokines at site of spinal cord injury in mice after vaccination with dendritic cells pulsed with homogenate proteins.

OBJECTIVE: Immune cells are key mediators of secondary damage following spinal cord injury (SCI), and dendritic cell (DC)-based vaccines have received considerable interest for treatment of SCI. We previously showed that vaccination with DCs pulsed with homogenate proteins of the spinal cord (hpDCs) promotes functional recovery from SCI in mice. However, the underlying molecular mechanisms remain unclear. Here, changes of neurotrophins, cytokines and T cells at the site of SCI in mice after vaccination with hpDCs were investigated and correlated with recovery from SCI. METHODS: hpDCs, DCs (control) or PBS (control) were injected intraperitoneally into injured mouse spinal cords. Functional recovery of the spinal cord was measured weekly using the Basso Mouse Scale (BMS) and confirmed by histological and immunohistochemical analysis. Brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), interleukin-4 (IL-4) and interferon-γ (IFN-γ) levels in T cell culture supernatants and spinal cord tissues were determined by ELISA. RESULTS: Eighty-four days after immunization, the BMS score of the hpDCs group (6.92 ± 0.20) was significantly higher than those of the DCs and PBS groups (p < 0.01). Meanwhile, the injury area and number of cysts in the hpDCs group decreased significantly compared with control groups. BDNF, NT-3, IL-4 and IFN-γ levels at the injured site as well as BDNF and NT-3 levels in the supernatant of cultured T cells from the hpDCs group were significantly higher than in control groups (p < 0.05). CONCLUSION: These results reveal that vaccination with hpDCs can promote SCI repair potentially by upregulating BDNF, NT-3, IL-4 and IFN-γ at the injury site.

Spinal trauma in mainland China from 2001 to 2007: an epidemiological study based on a nationwide database.

STUDY DESIGN: Descriptive epidemiological study. OBJECTIVE: To determine the epidemiological characteristics of spinal trauma in Mainland China. SUMMARY OF BACKGROUND DATA: To date, a large-scale epidemiological analysis of spinal trauma in Mainland China has not been undertaken. METHODS: Data were acquired from Chinese Database of Traumas. Patients with International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) coding of 805.x and 806.x (spinal column fracture with and without spinal cord injury) from 2001 to 2007 were identified. Variables assessed included patient demographics, etiology, segmental distribution, and outcomes. RESULTS: A total of 82,720 patients with spinal trauma were identified, accounting for 4.58% of all trauma patients in the study period. Spinal cord injuries (SCIs) and fracture-dislocations accounted for 16.87% and 7.17% of spinal trauma and 0.74% and 0.32% of all traumas in the same period, respectively. The male-to-female ratio was 2.33:1. About 79.32% of spinal trauma occurred in patients between 20 and 60 years of age. There was an annual increase in incidence during the study period. A total of 64,630 patients (78.13%) had a definitive cause, with motor vehicle accidents identified as the leading etiological factor (33.61%), followed by high falls (31.25%) and trivial falls (23.23%). Lumbar spine was most frequently involved (56.09%), followed by thoracic spine (23.77%), cervical spine (17.75%), and sacrococcygeal vertebrae (2.39%). Fracture-dislocation occurred most frequently in the cervical and lumbar spines, whereas spinal cord injury occurred most frequently in the cervical and thoracic spines. Children younger than 10 years of age were prone to cervical spine injury, whereas adults older than 60 years were more prone to osteoporotic thoracic and lumbar fractures. Overall rate of conservative treatment (55.88%) was higher than that of operative treatment (44.12%). Overall combined cure and improvement rates exceeded 90%. The male mortality rate was twice that of the female population. Lumbar spine injury was the most curable, whereas cervical spine injury was associated with the worst prognosis and the highest medical costs. CONCLUSION: This is the first large-scale epidemiological study of spinal injury in Mainland China. The results obtained have important implications for future public health care planning, public safety, and resource allocation.

Chemoattractant receptors as pharmacological targets for elimination of glioma stem-like cells.

Malignant tumors are thought to be initiated by a small population of cells that display stem cell properties, including the capacity of self-renewal, multipotent differentiation, initiation of tumor tissues and resistance to therapy. Cancer stem cells (CSCs) have also been identified in gliomas in which they are named as glioma stem-like cells (GSLCs), or glioma stem cells. In xenograft transplantation models, GSLCs propagate tumor and promote tumor progression. The tumorigenesis of GSLCs depends not only on their autonomous proliferation but also on interaction with microenvironment components. Among these components, G protein coupled chemoattractant receptors (GPCRs) and their agonists have attracted much attention for their capacity to mediate leukocyte infiltration, angiogenesis, tumor invasion and metastasis. Chemoattractant GPCRs are widely expressed by tumor cells and stromal cells and recognize agonists present in the tumor microenvironment. Such GPCRs have been found to be expressed also by CSCs including GSLCs. In this brief review, we will summarize the recent development in the studies of the function, regulation and signal transduction of chemoattractant GPCRs in GSLCs in hope to promote a better understanding of the mechanistic basis of the progression of gliomas and the identification of molecular targets for the novel anti-glioma therapy.

Osteoinductive activity of demineralized bone matrix and deprotenized bone derived from human avascular necrotic femoral head.

OBJECTIVE: To observe the osteoinductive activity of demineralized bone matrix (DBM) and deproteinized bone (DPB) made from human avascular necrotic femoral head. METHODS: The femoral head was cut into pieces with the size of 3 mm x 3 mm x 5 mm, which were made into DBM and DPB. These two kinds of biomaterials were cocultured with human bone mesenchymal stem cells (hBMSCs). Monolayer cells without biomaterials were cultured as control. Proliferative activity of hBMSCs was evaluated on days 1, 3, 5, 7 and 14. The concentration of alkaline phosphatase (ALP), osteocalcin (OC), and Ca(2+) were detected on days 1, 7, 14 and 21. RESULTS: Cells cultured in DBM showed higher proliferative activity than did in DPB and monolayer cells (F =39.773, P <0.01). DBM and DPB also had osteoinductive activity. The concentrations of ALP (F=93.162, P <0.01), OC (F =236.852, P < 0.01), Ca(2+)(F =80.711, P <0.01) of DBM group were significantly higher than that of DPB and control groups. CONCLUSIONS: In vitro, DBM and DPB made from avascular necrotic femoral head have osteoinductive activity when cocultured with hBMSCs, and the former is stronger than the latter.

[Measurement of cerebrovascular reserve of patients with symptomatic middle cerebral artery ischemia by perfusion CT and combined with CO2 test].

OBJECTIVE: To investigate the feasibility of assessment of the cerebrovascular reserve (CVR) by perfusion CT combined with CO(2) test in patients with symptomatic middle cerebral artery ischemia. METHODS: 38 healthy volunteers and 32 symptomatic middle artery ischemia inhaled mixed gas of 5% CO(2) and 95% O(2), and the changes of CO(2) concentration by the end of inhalation were measured among as pretest. Ten-row CT was with round area 24 mm in diameter at bilateral blood supply areas of middle cerebral artery as ROI. Forty patients with symptomatic middle cerebral artery ischemia underwent perfusion CT with 5% carbon dioxide and 95% oxygen. The end-expiratory CO(2) content after inhalation of mixture gas was tested in 36 volunteers and 32 patients with symptomatic middle cerebral artery ischemia. RESULTS: After inhalation of a gas mixture with 5% CO(2) and 95% oxygen the end-expiratory CO(2) content increased by 0.93% +/- 0.31% in the volunteers and 0.89% +/- 0.23% in the patients with symptomatic middle cerebral artery ischemia (P < 0.05). The CVR of the patients with symptomatic middle cerebral artery ischemia could be bigger than 20%. The CVR of middle cerebral artery supply area was correlated with the collateral circulation number and scale, but not with the stenosis degree of M1 segment of middle cerebral artery. CONCLUSION: It is safe and feasible to assess CVR with dynamic computer tomography and gas mixture with 5% CO(2) and 95% oxygen in the patients with symptomatic middle cerebral artery ischemia.