Bioinformatics analysis of paravertebral muscles atrophy in adult degenerative scoliosis.

Paravertebral muscles (PVM) act as one of the major dynamic factors to maintain human upright activities and play a remarkable role in maintaining the balance of the trunk. Adult degenerative scoliosis (ADS) has become one of the important causes of disability in the elderly population owing to the changes in spinal biomechanics, atrophy and degeneration of PVM, and imbalance of the spine. Previously, many studies focused on the physical evaluation of PVM degeneration. However, the molecular biological changes are still not completely known. In this study, we established a rat model of scoliosis and performed the proteomic analysis of the PVM of ADS. The results showed that the degree of atrophy, muscle fat deposition, and fibrosis of the PVM of rats positively correlated with the angle of scoliosis. The proteomic results showed that 177 differentially expressed proteins were present in the ADS group, which included 105 upregulated proteins and 72 downregulated proteins compared with the PVM in individuals without spinal deformities. Through the construction of a protein-protein interaction network, 18 core differentially expressed proteins were obtained, which included fibrinogen beta chain, apolipoprotein E, fibrinogen gamma chain, thrombospondin-1, integrin alpha-6, fibronectin-1, platelet factor 4, coagulation factor XIII A chain, ras-related protein Rap-1b, platelet endothelial cell adhesion molecule 1, complement C1q subcomponent subunit A, cathepsin G, myeloperoxidase, von Willebrand factor, integrin beta-1, integrin alpha-1, leukocyte surface antigen CD47, and complement C1q subcomponent subunit B. Further analysis of the Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) and immunofluorescence showed that the neutrophil extracellular traps (NETs) formation signaling pathway plays a major role in the pathogenesis of PVM degeneration in ADS. The results of the present study preliminarily laid the molecular biological foundation of PVM atrophy in ADS, which will provide a new therapeutic target for alleviating PVM atrophy and decreasing the occurrence of scoliosis.

Effects of combined adjustable Halo-pelvic fixation brace on cervical spine alignment in patients with severe rigid spinal deformity.

OBJECTIVE: To evaluate the effect of continuous traction with a combined adjustable Halo-pelvic fixation brace on the cervical spine alignment in patients with severe rigid spinal deformity and analyze its related factors. METHODS: We conducted a retrospective cohort study of 21 patients with severe rigid spinal deformity treated in our department between 2015 and 2019. All subjects received combined adjustable Halo-pelvic fixation brace traction before secondary orthopedic surgery. The influence of the Halo-pelvic fixation brace on the cervical spine alignment was evaluated by measuring the parameters of lateral cervical X-ray at three time points: before traction, at the end of traction, and 6 months after orthopedic surgery. The correlation between parameter changes and total traction duration was analyzed to explore factors influencing cervical alignment. RESULTS: The C2L-C7L angle was 22.40 ± 15.91° before traction, which decreased to 5.91 ± 6.78° at the end of traction but increased to 14.51 ± 10.07° after orthopedic surgery (BT vs ET p < 0.005, ET vs AOS p < 0.005, BT vs AOS p < 0.005). Accordingly, C2L-C7U angle, C2L-C6L angle, C2L-C6U angle, C2L-C5L angle, C7 or T1 slope, C2-C7 SVA, SCA, C2-T1 Ha, C0 slope, and C0-C2 angle also changed similarly to C2L-C7L angle. Furthermore, moderate correlation was observed between C2L-C7L angle and total traction volume (r = 0.563, p = 0.008) and SCA and traction duration (r = 0.525, p = 0.015). However, no significant correlation was found between other cervical alignment parameters and total traction volume and traction duration. CONCLUSIONS: The continuous traction of a combined adjustable Halo-pelvic fixation brace can affect the cervical spine alignment of patients with severe rigid spinal deformity and straighten the physiological curvature of the cervical spine. However, the sagittal alignment gradually recovers after the traction, without any adverse effects on the orthopedic surgery and global balance after the operation; therefore, this apparatus is worthy of wide application.

Assessment of isokinetic trunk muscle strength and its association with health-related quality of life in patients with degenerative spinal deformity.

BACKGROUND: A considerable portion of the elderly population are increasingly afflicted by degenerative spinal deformity (DSD), which seriously affects patient health-related quality of life (HRQoL). HRQoL index is used across many studies to show correlations between radio-graphical alignment, disability, and pain in patients with DSD. However, imaged structural deformity represents only one aspect for consideration, namely, the disability effect of DSD. We assessed the isokinetic strength of trunk muscle in patients with degenerative spinal deformity (DSD), and investigated its relationship with HRQoL. METHODS: In total, 38 patients with DSD (DSD group) and 32 healthy individuals (control group) were recruited. Both groups were homogeneous for age, weight, height and body mass index (BMI). Assessments were performed using the isokinetic dynamometer IsoMed-2000; trunk extensor, flexor strength and flexion/extension (F/E) ratios were explored concentrically at speeds of 30°, 60° and 120° per second. The grip strength of both hands was measured using a hand-held dynamometer. Visual analogue scale (VAS) scores, the Oswestry Disability Index (ODI), a Roland-Morris disability questionnaire (RDQ), and a 36-item Short Form Health Survey (SF-36) evaluated patient HRQoL. Correlations between trunk strength and HRQoL were analyzed. RESULTS: When compared with the control group, the DSD group showed lower trunk extensor strength at three velocity movements, and higher F/E ratios at 60° and 120°/s (p < 0.05). Both groups exhibited similar trunk flexor strength and grip strength (p > 0.05). In DSD group, trunk extensor strength at 60°/s was negatively associated with ODI and RDQ (p < 0.05). A negative relationship between trunk flexor strength at 120°/s and ODI was also recorded (p < 0.05). In addition, trunk extensor strength at 60°/s and trunk flexor strength at 120°/s were positively correlated with physical functioning and role-physical scores according to the SF-36 (p < 0.05). CONCLUSIONS: We identified isolated trunk extensor myopathy in DSD, which causes an imbalance in trunk muscle strength. Isokinetic trunk extensor strength at 60°/s and trunk flexor strength at 120°/s can predict disability, and decrease physical HRQoL in DSD patients.

Periostin promotes ectopic osteogenesis of CTLA4-modified bone marrow mesenchymal stem cells.

The improved ectopic osteogenesis of cytotoxic T-lymphocyte-associated antigen 4-Ig-modified bone marrow mesenchymal stem cells (MSCs-CTLA4) has been demonstrated but the mechanisms involved remain to be determined. The extracellular matrix (ECM) has recently been reported to play a vital role in bone formation and periostin (POSTN) has been suggested as a key member in constructing the ECM in bone tissue. We found that POSTN expression in the MSCs-CTLA4 group is significantly enhanced compared with that in the MSCs group, not only in tissue-engineered bone (TEB) with femur heterotopic transplantation in vivo but also under the immune activation condition in vitro. This ectopic osteogenesis effect is in accordance with POSTN expression. We also found that the soluble POSTN treatment up-regulates osteogenic marker expression in MSCs, including runt-related transcription factor 2, collagen 1, osteocalcin, osterix, and alkaline phosphatase and calcium nodule formation. These effects are diminished when the soluble POSTN is neutralized. Our results demonstrate that POSTN promotes the osteogenic differentiation of MSCs and that CTLA4 enhances the ectopic osteogenesis of MSCs-CTLA4-based TEB, potentially by maintaining POSTN expression in xenotransplantation.

The effects of back extensor strength in different body positions on health-related quality of life in patients with degenerative spinal deformity.

BACKGROUND: Degenerative spinal deformity (DSD) is believed to originate from degeneration of the discs and facet joints and vertebral wedging. Currently, the nosogeny of DSD is not yet fully clarified and there has been no systematic study on the impact of their lower back muscle strength on quality of life. OBJECTIVE: To determine the characteristics of back extensor strength (BES) in different body positions and examine their correlations with health-related quality of life (HQOL) in degenerative spinal deformity (DSD) patients. METHODS: Participants comprised 60 DSD patients and 40 healthy volunteers. Maximal isometric BES was evaluated by dynamometers with the subject in three different positions (standing, prone, sitting). The visual analogue scale (VAS) score, Oswestry Disability Index (ODI), Roland-Morris Disability Questionnaire (RMQ), and 36-item Short Form Health Survey (SF-36) score were used to evaluate patient HQOL. Correlations between the BES in different body positions and HQOL were analysed. RESULTS: The BES values in three body positions were significantly smaller in DSD patients than healthy subjects (P< 0.05). The standing BES was found to be negatively associated with ODI and RMQ (R= 0.313, p< 0.05 and R= 0.422, p< 0.01, respectively). A negative relationship between sitting BES and RMQ was also seen (R= 0.271, p< 0.05). In addition, the standing and prone BES were positively correlated with the physical functioning score of the SF-36 (R= 0.471, p< 0.01 and R= 0.289, p< 0.05, respectively), and the sitting BES was positively correlated with the role-physical score of the SF-36 (R= 0.436, p< 0.01). CONCLUSION: The results indicate that the back extensor muscle is compromised in DSD patients and there are differences in predicting the severity of disability and physical HQOL scores with BES in different positions. Standing BES was the most reliable contributor to HQOL among three body positions.

Isokinetic strength assessment of trunk muscle and its relationship with spinal-pelvic parameters in patients with degenerative spinal deformity.

BACKGROUND: The incidence rate of degenerative spinal deformity (DSD) has gradually increased in the elderly. Currently, the relationship between the functional status of trunk muscle and the spinal-pelvic parameters of DSD patients remains unclear. OBJECTIVE: This paper aims to explore the relationship between the two factors and provide new clues for exploring the mechanism of the occurrence and development of DSD. METHODS: A total of 41 DSD patients treated in our hospital (DSD group) and 35 healthy volunteers (control group) were selected. Muscle strength was evaluated using an IsoMed-2000 isokinetic dynamometer, and the trunk flexor and extensor peak torque (PT) of subjects was measured at a low, medium, and high angular velocity of 30∘/s, 60∘/s, and 120∘/s, respectively. Hand grip strength (HGS) was assessed using an electronic grip dynamometer and Surgimap software was used to measure the spinal-pelvic parameters, including the sagittal vertical axis (SVA), thoracic kyphosis (TK), lumbar lordosis (LL), sacral slope (SS), pelvic tilt (PT), pelvic incidence rate (PI), and PI-LL, and the relationship between trunk muscle function and various parameters was analyzed. RESULTS: Under the three angular velocities, the flexor and extensor PT values in the DSD group were lower than those in the control group, and only the extensor PT showed a statistically significant difference (P< 0.05). There was no significant difference in HGS between the two groups (P> 0.05). In the DSD group, the extensor PT at 30∘/s was significantly negatively correlated with SVA (P< 0.05). At 60∘/s and 120∘/s, the extensor PT was significantly negatively correlated with SVA and PT (P< 0.05). CONCLUSION: Trunk extensor strength is significantly lower in DSD patients than in normal controls. The decline in trunk extensor strength in DSD patients is a type of local muscle dysfunction more closely related to the deformity, which is likely involved in the compensatory mechanism of DSD and may reflect the overall imbalance of the trunk.

HVEM Promotes the Osteogenesis of allo-MSCs by Inhibiting the Secretion of IL-17 and IFN-γ in Vγ4T Cells.

Bone defects are a common orthopaedic concern, and an increasing number of tissue-engineered bones (TEBs) are used to repair bone defects. Allogeneic mesenchymal stem cells (allo-MSCs) are used as seed cells in many approaches to develop TEB constructs, but the immune response caused by allogeneic transplantation may lead to transplant failure. V gamma 4 T (Vγ4T) cells play an important role in mediating the immune response in the early stage after transplantation; therefore, we wanted to verify whether suppressing Vγ4T cells by herpesvirus entry mediator (HVEM)/B and T lymphocyte attenuator (BTLA) signalling can promote MSCs osteogenesis in the transplanted area. In vitro experiments showed that the osteogenic differentiation of MSCs and Vγ4T cells was weakened after co-culture, and an increase in interleukin-17 (IL-17) and interferon-γ (IFN-γ) levels was detected in the culture supernatant. HVEM-transfected MSCs (MSCs-HVEM) still exhibited osteogenic differentiation activity after co-culture with Vγ4T cells, and the levels of IL-17 and IFN-γ in the co-culture supernatant were significantly reduced. In vivo experiments revealed that inflammation in the transplanted area was reduced and osteogenic repair was enhanced after Vγ4T cells were removed. MSCs-HVEM can also consistently contribute to reduced inflammation in the transplanted area and enhanced bone repair in wild-type (WT) mice. Therefore, our experiments verified that HVEM can promote the osteogenesis of allo-MSCs by inhibiting IL-17 and IFN-γ secretion from Vγ4T cells.

Laminin alpha 4 promotes bone regeneration by facilitating cell adhesion and vascularization.

Selective cell retention (SCR) has been widely used as a bone tissue engineering technique for the real-time fabrication of bone grafts. The greater the number of mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) retained in the scaffold, the better the osteoinductive and angiogenic properties of the scaffold's microenvironment. Improved bioscaffold properties in turn lead to improved bone graft survival, bone regeneration, and angiogenesis. Laminin plays a key role in cell-matrix adhesion, cell proliferation, and differentiation. We designed a collagen-binding domain (CBD) containing the core functional amino acid sequences of laminin α4 (CBD-LN peptide) to supplement the functional surface of a collagen-based decalcified bone matrix (DBM) scaffold. This scaffold promoted MSCs and EPCs early cell adhesion through up-regulating the expression of integrin α5ß1 and integrin αvß3 respectively, thus accelerated the following cell spreading, proliferation, and differentiation. Interestingly, it promoted the retention of MSCs (CD90+/CD105+ cells) and EPCs (CD31+ cells) in the scaffold following the use of clinical SCR technology. Furthermore, the DBM/CBD-LN scaffold induced the formation of type H vessels through the activation of the HIF-1α signaling pathway. The DBM/CBD-LN scaffold displayed rapid bone formation and angiogenesis in vivo, suggesting that it might be used as a new biomaterial in bone tissue engineering. STATEMENT OF SIGNIFICANCE: Selective cell retention technology (SCR) has been utilized in clinical settings to manufacture bioactive bone grafts. Specifically, demineralized bone matrix (DBM) is a widely-used SCR clinical biomaterial but it displays poor adhesion performance and angiogenic activity. In this work, we designed a collagen-binding domain (CBD) containing the core functional amino acid sequences of laminin α4 to supplement the functional surface of a collagen-based DBM scaffold. This bioscaffold promoted SCR-mediated MSCs and EPCs early cell adhesion, thus accelerated the following cell spreading, proliferation, and differentiation. Our results indicate this bioscaffold greatly induced osteogenesis and angiogenesis in vivo. In general, this bioscaffold has a good prospect for SCR application and may provide highly bioactive bone implant in clinical environment.

Clinical evaluation of a bone cement-injectable cannulated pedicle screw augmented with polymethylmethacrylate: 128 osteoporotic patients with 42 months of follow-up.

OBJECTIVES: To evaluate the safety and efficacy of a novel bone cement-injectable cannulated pedicle screw augmented with polymethylmethacrylate in osteoporotic spinal surgery. METHODS: This study included 128 patients with osteoporosis (BMD T-score -3.2±1.9; range, -5.4 to -2.5) who underwent spinal decompression and instrumentation with a polymethylmethacrylate-augmented bone cement-injectable cannulated pedicle screw. Postoperative Visual Analogue Scale scores and the Oswestry Disability Index were compared with preoperative values. Postoperative plain radiographs and computed tomography (CT) scans were performed immediately after surgery; at 1, 3, 6, and 12 months; and annually thereafter. RESULTS: The mean follow-up time was 42.4±13.4 months (range, 23 to 71 months). A total of 418 polymethylmethacrylate-augmented bone cement-injectable cannulated pedicle screws were used. Cement extravasations were detected in 27 bone cement-injectable cannulated pedicle screws (6.46%), mainly in cases of vertebral fracture, without any clinical sequela. The postoperative low back and lower limb Visual Analogue Scale scores were significantly reduced compared with the preoperative scores (<0.01), and similar results were noted for the Oswestry Disability Index score (p<0.01). No significant screw migration was noted at the final follow-up relative to immediately after surgery (p<0.01). All cases achieved successful bone fusion, and no case required revision. No infection or blood clots occurred after surgery. CONCLUSIONS: The polymethylmethacrylate-augmented bone cement-injectable cannulated pedicle screw is safe and effective for use in osteoporotic patients who require spinal instrumentation.

Bioactivity, pharmacokinetics, and immunogenicity assays in preclinical and clinical trials for recombinant human endostatin.

AIM: To determine the in vitro and in vivo bioactivity of recombinant human endostatin (rhEndostatin) and to analyze its pharmacokinetics and immunogenicity in rhesus monkeys and patients. METHODS: The physical chemical characteristics of rhEndostatin were detected according to Pharmacopoeia of the People's Republic of China (2005 edition, part III). Its in vitro and in vivo bioactivities were assayed via proliferation-inhibition on human umbilical vein endothelial cells and their inhibitory effect on tumor-bearing mice models. Serum concentrations of rhEndostatin in monkeys and patients were determined by an enzyme immunoassay method. RESULTS: The corresponding specific in vitro activities of rhEndostatin obtained from the cell counting method, 3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and lactate dehydrogenase assay, respectively, were 6.4 x 10(7), 6.7 x 10(7), and 3.8 x 10(8) U/mg, and the in vivo antitumoral potency was 4.04 x 10(7) U/mg. In rhesus monkeys, there were no gender differences in all pharmacokinetic parameters. Serum anti-rhEndostatin immunoglobulin (Ig)G antibodies were generated quickly after intravenous (iv) administration and decreased rapidly when therapy was stopped. In phase I clinical trials, linearity in the pharmacokinetics of rhEndostatin was indicated by dose-proportionate increases in the area under the curve and the maximum serum concentration. Serum rhEndostatin reached a steady-state level after 7 d of successive administration with the average concentration at a steady state of 272.44+/-91.98 ng/mL. Neither IgG nor IgM antibodies against rhEndostatin were observed in patients. CONCLUSION: RhEndostatin exhibited a definite proliferation- inhibition effect on HUVEC, and significant antitumoral activity in mice. The immunoreactivity of rhesus monkeys to rhEndostatin is common, and rhEndostatin showed no immunogenicity in patients in this trial. The results provide a basis for further clinical trials.

Application of Cement-Injectable Cannulated Pedicle Screw in Treatment of Osteoporotic Thoracolumbar Vertebral Compression Fracture (AO Type A): A Retrospective Study of 28 Cases.

OBJECTIVE: To evaluate safety and effectiveness of the novel polymethyl methacrylate-augmented bone cement-injectable cannulated pedicle screw (CICPS) in patients with thoracolumbar vertebral compression fractures (AO type A) associated with osteoporosis. METHODS: We conducted a retrospective cohort study of 28 patients treated for osteoporosis-related thoracolumbar vertebral body compression fracture at our facility between 2011 and 2015. Treatment involved posterior thoracolumbar fusion or lumbar fusion using CICPS. Treatment effectiveness was evaluated using visual analog scale and Oswestry Disability Index scores, degree of fracture reduction, and correction of kyphosis. The safety of CICPS was mainly assessed in terms of intraoperative and postoperative complications. Radiography, computed tomography, and magnetic resonance imaging outcomes were also assessed. RESULTS: All 28 patients had severe osteoporosis. The visual analog scale score at final follow-up (0.50 ± 0.69) was significantly (P < 0.001) lower compared with before surgery (4.93 ± 1.30). The Oswestry Disability Index score had also decreased from 57.39% ± 14.46% to 6.83% ± 15.38% at final follow-up (P < 0.001). Radiologic evaluation of vertebral height and Cobb angle showed good fracture reduction and satisfactory correction of kyphosis (preoperative vs. final follow-up, P < 0.001). There were no instances of screw loosening or symptomatic complications except for a few cases of cement leakage from CICPS (10.3%; cement leakage most common in AO type A3.3). CONCLUSIONS: The use of CICPS and polymethyl methacrylate is an effective and safe surgical technique for management of osteoporosis-related vertebral fractures (AO type A), with good clinical outcomes and low complications rates.

Improved Osteogenesis by HVEM-Expressing Allogenic Bone Marrow-Derived Mesenchymal Stem Cells in an Immune Activation Condition and Mouse Femoral Defect Model.

Use of allogeneic mesenchymal stem cells (allo-MSCs) in bone tissue engineering strategies can overcome the limitations associated with autologous MSCs, but unfortunately, the immunogenicity of allo-MSCs leads to a high rate of rejection, unless immunosuppressive agents are used. B and T lymphocyte attenuator (BTLA) is a newly discovered immunoglobulin superfamily inhibitory receptor, and Herpesvirus-entry mediator (HVEM), a member of the tumor necrosis factor receptor family, is the only ligand of BTLA. Both BTLA and HVEM are widely expressed in B and T lymphocytes and other immune cells and play significant roles in the negative regulation of an immunoreaction. Therefore, we hypothesized that MSCs could be modified to maintain their bone differentiation ability through negative regulation of the immune response, and to test this hypothesis, we generated HVEM-expressing MSCs and tested their potential for osteogenic differentiation and bone repair in a simulated immune activation condition in vitro and in a mice femoral defect model. We found that osteogenic differentiation of allo-MSCs was decreased significantly in the activated immune microenvironment and that HVEM expression by allo-MSCs inhibited the immune response, resulting in improved osteogenic differentiation in vitro and new bone formation by allo-MSCs in a mouse femoral defect model. Our results also preliminarily suggested that the mechanism by which HVEM-expressing allo-MSCs overcome inflammation and enhance osteogenesis may be related to inhibition of interleukin-17. Overall, the data obtained in the present study provide support for the further development of HVEM-modified allo-MSCs as potentially ideal seed cells for bone tissue engineering applications.

A quantitative method for measuring the antitumor potency of recombinant human endostatin in vivo.

Recombinant human endostatin (rhEndostatin) has been shown to inhibit tumor growth, but the variable antitumor activity of different rhEndostatin preparations has necessitated the development of an accurate, reproducible in vivo bioassay for evaluating the rhEndostatin activity. To assess the in vivo antitumor efficacy of rhEndostatin, H22 tumor-bearing mice received three doses of rhEndostatin and the potency of rhEndostatin preparations in inhibiting tumor growth was determined by ED(50)-potency assay and validated by dose-response parallel-line assay. There was a consistent and highly reproducible linear regression relationship between rhEndostatin dosage and tumor growth inhibition rate. The ED(50) values were determined from dose-response regression lines for seven rhEndostatin preparations with high reproducibility. On the basis of the current study, the potency of rhEndostatin preparations was assigned a value of 6.09 x 10(5) U/ampoule and a 95% confidence limit of 5.96 x 10(5)-6.22 x 10(5). We consider that this procedure can be served as a potential candidate pharmacopoeial method for potency measurement of different rhEndostatin preparations.

Periostin Upregulates Wnt/ß-Catenin Signaling to Promote the Osteogenesis of CTLA4-Modified Human Bone Marrow-Mesenchymal Stem Cells.

The enhanced osteogenesis of mesenchymal stem cells (MSCs) modified by expression of cytotoxic T lymphocyte-associated antigen 4 (CTLA4) has been shown in previous studies, but the mechanism remains unknown. Here we found that the bone repair effect of CTLA4-modified MSCs in demineralized bone matrix (DBM) in a rabbit radius defect model was significantly better than that observed for unmodified MSCs in DBM or DBM alone, and the periostin (POSTN) expression in CTLA4-modified MSCs was significantly higher than that in unmodified MSCs both in vivo and in vitro. In addition, we also found that treatment of CTLA4-modified MSCs with soluble POSTN could inhibit the glycogen synthase kinase-3ß activity and increase ß-catenin expression through up-regulation of lipoprotein-related protein-6 phosphorylation to promote osteogenic differentiation, but blocking of integrin αvß3, a receptor of POSTN, could suppress these effects. Our data demonstrated that POSTN expressed in response to CTLA4 can promote the osteogenesis of xenotransplanted MSCs through interaction with Wnt/ß-catenin pathway.

Effects of site-specific polyethylene glycol modification of recombinant human granulocyte colony-stimulating factor on its biologic activities.

BACKGROUND: Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is a long-chain cytokine that is administered to stimulate the production of white blood cells (WBCs) to reduce the risk of serious infection in immunocompromized patients. However, to achieve sustained stimulation of WBC production, rhG-CSF must be administered frequently, thus limiting its clinical use. METHODS: We conjugated rhG-CSF with linear monomethoxy-polyethylene glycol (PEG) maleimide at amino acid residue Cys(17) to test our hypothesis that this could extend the in vivo half-life of rhG-CSF in blood. RESULTS: The mono-PEG rhG-CSF became more stable to pH, temperature, and enzyme degradation in vitro, and had granulopoietic activity that was superior to the unmodified form in vivo. The granulopoietic activity of PEG-G-CSF was 2.82-fold greater than that of unmodified G-CSF. CONCLUSIONS: These results indicate that the thiol-specific PEGylation remarkably prolonged the half-life of rhG-CSF and represents a novel strategy to address the more clinically acceptable therapeutic application of hemopoietic growth factor.

Clinical evaluation of a bone cement-injectable cannulated pedicle screw augmented with polymethylmethacrylate: 128 osteoporotic patients with 42 months of follow-up

OBJECTIVES: To evaluate the safety and efficacy of a novel bone cement-injectable cannulated pedicle screw augmented with polymethylmethacrylate in osteoporotic spinal surgery. METHODS: This study included 128 patients with osteoporosis (BMD T-score −3.2±1.9; range, −5.4 to -2.5) who underwent spinal decompression and instrumentation with a polymethylmethacrylate-augmented bone cement-injectable cannulated pedicle screw. Postoperative Visual Analogue Scale scores and the Oswestry Disability Index were compared with preoperative values. Postoperative plain radiographs and computed tomography (CT) scans were performed immediately after surgery; at 1, 3, 6, and 12 months; and annually thereafter. RESULTS: The mean follow-up time was 42.4±13.4 months (range, 23 to 71 months). A total of 418 polymethylmethacrylate-augmented bone cement-injectable cannulated pedicle screws were used. Cement extravasations were detected in 27 bone cement-injectable cannulated pedicle screws (6.46%), mainly in cases of vertebral fracture, without any clinical sequela. The postoperative low back and lower limb Visual Analogue Scale scores were significantly reduced compared with the preoperative scores (<0.01), and similar results were noted for the Oswestry Disability Index score (p<0.01). No significant screw migration was noted at the final follow-up relative to immediately after surgery (p<0.01). All cases achieved successful bone fusion, and no case required revision. No infection or blood clots occurred after surgery. CONCLUSIONS: The polymethylmethacrylate-augmented bone cement-injectable cannulated pedicle screw is safe and effective for use in osteoporotic patients who require spinal instrumentation.