Survival Prediction in High-grade Osteosarcoma Using Radiomics of Diagnostic Computed Tomography.

The poor 5-year survival rate in high-grade osteosarcoma (HOS) has not been increased significantly over the past 30 years. This work aimed to develop a radiomics nomogram for survival prediction at the time of diagnosis in HOS. In this retrospective study, an initial cohort of 102 HOS patients, diagnosed from January 2008 to March 2011, was used as the training cohort. Radiomics features were extracted from the pretreatment diagnostic computed tomography images. A radiomics signature was constructed with the lasso algorithm; then, a radiomics score was calculated to reflect survival probability by using the radiomics signature for each patient. A radiomics nomogram was developed by incorporating the radiomics score and clinical factors. A clinical model was constructed by using clinical factors only. The models were validated in an independent cohort comprising 48 patients diagnosed from April 2011 to April 2012. The performance of the nomogram was assessed with respect to its calibration, discrimination, and clinical usefulness. Kaplan-Meier survival analysis was performed. The radiomics nomogram showed better calibration and classification capacity than the clinical model with AUC 0.86 vs. 0.79 for the training cohort, and 0.84 vs. 0.73 for the validation cohort. Decision curve analysis demonstrated the clinical usefulness of the radiomics nomogram. A significant difference (p-value <.05; log-rank test) was observed between the survival curves of the nomogram-predicted survival and non-survival groups. The radiomics nomogram may assist clinicians in tailoring appropriate therapy.

Bone transport for reconstruction of large bone defects after tibial tumor resection: a report of five cases.

This study was performed to explore the clinical efficacy of bone transport using external fixation for treatment of large bone defects after tibial tumor resection in five patients. Bone transport started 14 days postoperatively at 1 mm/day and was adjusted according to the callus-to-diameter ratio. The bone transport time, bone graft fusion, relapse, and metastasis were recorded. Clinical efficacy was evaluated using the Musculoskeletal Tumor Society (MSTS) scoring system. The tumors included osteosarcoma (n=2), Ewing sarcoma (n=1), malignant schwannoma (n=1), and hemangioma (n=1). The average bone defect length after resection was 11.6 cm. The five patients were followed up for an average of 50.8 months, and the average bone transport time was 15.5 months. Three patients who underwent postoperative chemotherapy were followed for 22.7 months, and two who did not undergo chemotherapy were followed for 4.75 months. Four patients underwent iliac bone grafting, and one underwent vascular pedicle fibular transplantation. The average MSTS score was 21.2 (19.3 for patients who underwent chemotherapy and 24.0 for patients who did not). No relapse or metastasis was observed. Bone transport is effective for reconstruction of large bone defects after tibial tumor resection as well as tibial malignancies with high doses of chemotherapy.

Upshifting the Ipsilateral Proximal Femur May Provide Satisfactory Reconstruction of Periacetabular Pelvic Bone Defects After Tumor Resection.

BACKGROUND: Pelvic ring reconstruction after resection of pelvic malignancies or aggressive benign tumors remains challenging, especially when the tumor invades periacetabular bone, resulting in a Type II resection as classified by Enneking and Dunham (removal of part or all of the acetabulum). Although numerous treatment approaches are in use, none is clearly superior to the others. An alternative involving use of the ipsilateral proximal femur as an autograft has not been well characterized, so we present our preliminary experience with this approach. QUESTIONS/PURPOSES: (1) What were the oncologic outcomes after using an ipsilateral proximal femur autograft for reconstruction after Type II pelvic resection in a small series of patients who underwent this reconstructive approach? (2) What were the Musculoskeletal Tumor Society (MSTS) scores after this reconstruction? (3) What complications were observed? METHODS: Between October 2006 and May 2016, we treated 67 patients with Type II malignant or aggressive benign tumors of the ilium. Of those, we used an ipsilateral proximal femur and a prosthesis as a reconstruction method for 11 patients with pelvic tumors. In general, we performed this approach in young or middle-aged patients with primary malignant or aggressive benign tumors involving pelvic area II and in whom the tumor did not invade the hip. The method used for resection of pelvic tumors included osteotomy of the femoral shaft, harvesting the proximal femur as a graft. The length of the femoral graft was determined by the extent of the pelvic defect. The proper placement was selected after a comparison of the proximal femur and the pelvic defect. A curved reconstruction plate and cancellous bone screws were used for pelvic fixation. The operative duration and total blood loss were recorded. Of the 11 patients who underwent this approach, all but one had at least 2 years of followup unless death occurred earlier, and all but one have been seen within the last year for evaluation. Functional outcomes were assessed using the MSTS scoring system. Local recurrence, metastases, and deaths were recorded as were complications including infection, bone nonunion, mechanical failure and sciatic nerve palsy. RESULTS: The followup was a mean of 37 months (range, 13-96 months). One patient was lost to followup. Three patients died of disease owing to local recurrence or lung metastasis. The other seven patients lived without evidence of tumor. The main complications included mechanical failure in two patients, nonunion in one patient, infection in two patients, and sciatic nerve palsy in one patient. The median MSTS function score was 70% (21 of 30 points; range, 11-25 points). CONCLUSIONS: Our preliminary results show that this technique of using the ipsilateral proximal femur may be an alternative method for reconstruction of pelvic bone defects after tumor resection. Even with this short followup, complications were common, but short-term function appears to be comparable to studies of other options. Longer term followup with more patients is necessary to confirm our results. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Effects of a bone graft substitute consisting of porous gradient HA/ZrO2 and gelatin/chitosan slow-release hydrogel containing BMP-2 and BMSCs on lumbar vertebral defect repair in rhesus monkey.

Dense biomaterial plays an important role in bone replacement. However, it fails to induce bone cell migration into graft material. In the present study, a novel bone graft substitute (BGS) consisting of porous gradient hydroxyapatite/zirconia composite (PGHC) and gelatin/chitosan slow-release hydrogel containing bone morphogenetic protein 2 and bone mesenchymal stem cells was designed and prepared to repair lumbar vertebral defects. The morphological characteristics of the BGS evaluated by a scanning electron microscope showed that it had a three-dimensional network structure with uniformly distributed chitosan microspheres on the surfaces of the graft material and the interior of the pores. Then, BGS (Group A), PGHC (Group B), or autologous bone (Group C) was implanted into lumbar vertebral body defects in a total of 24 healthy rhesus monkeys. After 8 and 16 weeks, anteroposterior and lateral radiographs of the lumbar spine, microcomputed tomography, histomorphometry, biomechanical testing, and biochemical testing for bone matrix markers, including Type I collagen, osteocalcin, osteopontin, basic fibroblast growth factor, alkaline phosphatase, and vascular endothelial growth factor, were performed to examine the reparative efficacy of the BGS and PGHC. The BGS displayed excellent ability to repair the lumbar vertebral defect in rhesus monkeys. Radiography, microcomputed tomography scanning, and histomorphological characterization showed that the newly formed bone volume in the interior of the pores in the BGS was significantly higher than in the PGHC. The results of biomechanical testing indicated that the vertebral body compression strength of the PGHC implant was lower than the other implants. Reverse-transcription polymerase chain reaction and western blot analyses showed that the expression of bone-related proteins in the BGS implant was significantly higher than in the PGHC implant. The BGS displayed reparative effects similar to autologous bone. Therefore, BGS use in vertebral bone defect repair appears promising.

VEGF165 induces differentiation of hair follicle stem cells into endothelial cells and plays a role in in vivo angiogenesis.

Within the vascular endothelial growth factor (VEGF) family of five subtypes, VEGF165 secreted by endothelial cells has been identified to be the most active and widely distributed factor that plays a vital role in courses of angiogenesis, vascularization and mesenchymal cell differentiation. Hair follicle stem cells (HFSCs) can be harvested from the bulge region of the outer root sheath of the hair follicle and are adult stem cells that have multi-directional differentiation potential. Although the research on differentiation of stem cells (such as fat stem cells and bone marrow mesenchymal stem cells) to the endothelial cells has been extensive, but the various mechanisms and functional forms are unclear. In particular, study on HFSCs' directional differentiation into vascular endothelial cells using VEGF165 has not been reported. In this study, VEGF165 was used as induction factor to induce the differentiation from HFSCs into vascular endothelial cells, and the results showed that Notch signalling pathway might affect the differentiation efficiency of vascular endothelial cells. In addition, the in vivo transplantation experiment provided that HFSCs could promote angiogenesis, and the main function is to accelerate host-derived neovascularization. Therefore, HFSCs could be considered as an ideal cell source for vascular tissue engineering and cell transplantation in the treatment of ischaemic diseases.

Reconstruction of Kuwada grade IV chronic achilles tendon rupture by minimally invasive technique.

BACKGROUND: Transfer of a flexor hallucis longus (FHL) tendon can not only reconstruct the Achilles tendon but also provide ischemic tendinous tissues with a rich blood supply to enhance wound healing. This retrospective study aims to investigate clinical outcomes in patients who underwent repair of Kuwada grade IV chronic Achilles tendon rupture with long hallucis longus tendons harvested using a minimally invasive technique. MATERIALS AND METHODS: 35 patients who were treated for Kuwada grade IV Achilles tendon injuries from July 2006 to June 2011 were included in this retrospective study. The age ranged between 23 and 71 years. The duration from primary injury to surgery ranged from 29 days to 34 months (mean value, 137.6 days). All 35 patients had difficulties in lifting their calves. Thirty two were followed up for a mean 32.2 months (range 18-72 months), whereas three were lost to followup. Magnetic resonance imaging (MRI) showed that the tendon rupture gap ranged from 6.0 to 9.2 cm. During surgery, a 2.0 cm minor incision was made vertically in the medial plantar side of the midfoot, and a 1.5 cm minor transverse incision was made in the plantar side of the interphalangeal articulation of the great toe to harvest the FHL tendon, and the tendon was fixed to the calcaneus with suture anchors. Postoperative appearance and function were evaluated by physiotherapists based American Orthopedic Foot and Ankle Society-ankle and hindfoot score (AOFAS-AH), and Leppilahti Achilles tendon ratings. RESULTS: Results were assessed in 32 patients. Except for one patient who suffered complications because of wound disruption 10 days after the operation, all other patients had primary wound healing, with 28 of 32 able to go up on their toes at last followup. The AOFAS-AH score was increased from preoperative (51.92 ± 7.08) points to (92.56 ± 6.71) points; Leppilahti Achilles tendon score was increased from preoperative (72.56 ± 7.43) to (92.58 ± 5.1). There were statistically significant differences. The result of the total excellent and good rate was 93.8% (30/32). MRI of Achilles tendon showed even signal without evidence of tear or cystic degeneration. CONCLUSION: Reconstruction of a chronic Achilles tendon rupture with an FHL tendon harvested using a minimally invasive technique showed good outcomes.

Reconstruction of large tibial bone defects following osteosarcoma resection using bone transport distraction: A report of two cases.

The clinical efficiency of bone transport distraction osteogenesis in the reconstruction of large tibial defects following resection of osteosarcoma remains unclear. The current study presents two cases of large tibial defects treated with bone transport distraction using an Orthofix external fixator. Case 1 was a 29-year-old man with a tibial defect 11 cm in length, while case 2 was a 16-year-old girl with a 15-cm-long defect. Bone transport distraction osteogenesis was initiated for the both cases on day 14 following resection of the tibial osteosarcoma. Bone transport distraction in case 1 and 2 was continued for 16 and 28 months, respectively, and the patients were followed up for 51 and 56 months, respectively. The two patients did not exhibit any signs of tumor recurrence or tumor metastasis during the follow-up period. The Musculoskeletal Tumor Society functional scores at final follow-up visits were 22 and 18 for case 1 and 2, respectively. Based on the experience gained in these 2 cases, a bone transport is a viable option for the reconstruction of large tibial defects following osteosarcoma resection.

Evaluation of a Novel HA/ZrO2-Based Porous Bioceramic Artificial Vertebral Body Combined with a rhBMP-2/Chitosan Slow-Release Hydrogel.

A new HA/ZrO2-based porous bioceramic artificial vertebral body (AVB), carried a recombinant human bone morphogenetic protein-2 (rhBMP-2)/chitosan slow-release hydrogel was prepared to repair vertebral bone defect in beagles. An ionic cross-linking was used to prepare the chitosan hydrogel (CS gel) as the rhBMP-2 slow-release carrier. The vertebral body defects were implanted with the rhBMP-2-loaded AVB in group A, or a non-drug-loaded AVB in group B, or autologous iliac in group C. The encapsulation rate of rhBMP-2 in rhBMP-2-loaded CS gel was 91.88±1.53%, with a drug load of 39.84±2.34 ng/mg. At 6, 12, 24 weeks postoperatively, radiography showed that the bone calluses gradually increased with time in group A, where the artificial vertebral body had completely fused with host-bone at 24 weeks after surgery. In group C, an apparent bone remodeling was occurred in the early stages, and the graft-bone and host-bone had also fused completely at 24 weeks postoperatively. In group B, fusion occurred less than in groups A and C. At 24 weeks after surgery, micro-computed tomography (Micro-CT) revealed that the volume of newly-formed bone in group A was significantly more than in group B (p<0.05). At 24 weeks after surgery, ultra-compressive strengths of the operated segments were 14.03±1.66 MPa in group A, 8.62±1.24 MPa in group B, and 13.78±1.43 MPa in group C. Groups A and C were both significantly higher than group B (p < 0.05). At 24 weeks postoperatively, the hard tissue sections showed that the AVB of group A had tightly fused with host bone, and that pores of the AVB had been filled with abundant nearly mature bone, and that the new bone structured similarly to a trabecular framework, which was similar to that in group C. In contrast, implant fusion of the AVB in group B was not as apparent as group A. In conclusion, the novel HA/ZrO2-based porous bioceramic AVB carried the rhBMP-2-loaded CS gel can promote the repair of bony defect, and induce bone tissue to grow into the pores, which may replace iliac bone grafts as commonly applied in clinical practice.

The study of traditional Chinese medical elongated-needle therapy promoting neurological recovery mechanism after spinal cord injury in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Acupuncture is a key part of traditional Chinese medicine, shown to induce favorable neuroplasticity for injuries in the central and peripheral nervous systems. Recent studies report elongated needle therapy (ENT) with BL54 and ST28 may restore acute spinal cord injury (ASCI). However, the precise mechanism for this has not been elucidated. AIM OF THE STUDY: In our current study, we investigated the effects of ENT on inflammation and neuronal apoptosis induced by ASCI, and whether PI3K/Akt and MAPK/ERK signaling pathways are involved in the ENT restoration effect. MATERIALS AND METHODS: Rat models of moderate SCI were established in accordance with the modified Allen's method and were treated with ENT continuously for 7 days. Spontaneous activities were evaluated by the Basso Beattie and Bresnahan locomotor scale. Levels of inflammatory cytokines, such as tumor necrosis factor alpha, interleukin-6, IL-1ß, and nuclear factor kappa-ß, were determined by enzyme-linked immunosorbent assay. Cell apoptosis was examined by the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The proportions of cells with positive Bcl-2 and Bax expression were determined by immunohistochemical assays, whilst the expression profiles of p-AKT and p-ERK in spinal cord tissues were evaluated by western blotting. Furthermore, the expression profiles of Cytochrome-C (Cyt-C) and caspase-3 in vivo were analyzed by reverse transcription polymerase chain reaction. The potential inhibitory effects downstream of the Akt and ERK signaling pathways were examined by administration of specific inhibitors LY294002 and PD98059 in vivo. RESULTS: As indicated by this study, inflammation as well as PI3K/Akt- and MAPK/ERK signaling pathway-mediated neuronal apoptosis were involved in the course of SCI in rats. The neuro-protective effect of ENT was associated with reduced Bax protein-positive neurons and increased Bcl-2 protein-positive neurons. ENT enhanced recovery of rat activities. Activation of p-Akt and p-ERK in the PI3K/Akt and MAPK/ERK signaling pathways, inhibited expression of the critical component Cyt-C. Cyt-C is required for the mitochondrial apoptosis pathway and cascade of caspase-3, which is involved in activation of neuronal apoptosis through down-regulation of Bax protein and up-regulation of Bcl-2, as determined by TUNEL. The administration of PI3K/Akt and MAPK/ERK signaling pathway specific inhibitors, LY294002 and PD98059, suppressed expression of both p-Akt and p-ERK. CONCLUSION: ENT with BL54 and ST28 points can promote the recovery of ASCI. And the neuro-protective effect of ENT during the restoration of SCI may be associated with the suppression of both inflammation and activation of PI3K/Akt and MAPK/ERK signaling pathways, resulting from down-regulation of Bax protein, up-regulation of Bcl-2, and inhibition of the mitochondrial apoptosis pathway.

Treatment of Calcified Insertional Achilles Tendinopathy by the Posterior Midline Approach.

The present study investigated the clinical outcomes of the posterior midline approach in the treatment of 34 patients with significantly calcified insertional Achilles tendinopathy. The posterior midline approach was applied for the surgical treatment of 34 patients with chronic significantly calcified insertional Achilles tendinopathy after failed conservative treatment. Gastrocnemius recession was performed simultaneously for patients with gastrocnemius contracture. The Fowler-Philip angle and parallel pitch lines were measured before surgery, and the visual analog scale, Tegner score, and Victorian Institute of Sport tendon study group score were recorded before and after surgery. The mean follow-up period was 45.2 ± 17.7 (range 24 to 84) months. After surgery, the visual analog scale score had decreased notably, and the Tegner score and Victorian Institute of Sport tendon study group score had increased significantly. The posterior midline approach can achieve satisfactory outcomes in the treatment of significantly calcified insertional Achilles tendinopathy, and gastrocnemius recession (Strayer procedure) should be performed for patients with gastrocnemius contracture to improve the surgical outcome.

Evaluation of porous gradient hydroxyapatite/zirconia composites for repair of lumbar vertebra defect in dogs.

OBJECTIVE: To evaluate the effects of porous gradient composites with hydroxyapatite/zirconia and autologous iliac in repair of lumbar vertebra body defects in dogs. METHODS: (1) New porous gradient hydroxyapatite/zirconia composites were prepared using foam immersion, gradient compound and high temperature sintering; (2) A total of 18 adult beagle dogs, aged five to eight months and weighted 10-13 kg, were randomly assigned into two subgroups, which were implanted with new porous gradient hydroxyapatite/zirconia composites (subgroup A in 12) or autologous iliac bone (subgroup B in 6); (3) The post-operative data were analyzed and compared between the subgroups to repair the vertebral body defect by roentgenoscopy, morphology and biomechanics. RESULTS: The porosity of new porous gradient hydroxyapatite/zirconia composites is at 25 poles per inch, and the size of pores is at between 150 and 300 µm. The post-operative roentgenoscopy displayed that new-bone formation is increased gradually, and the interface between composites and host-bone becomes became blur, and the new-bone around the composites were integrated into host-bone at 24 weeks postoperatively in subgroup A. As to subgroup B, the resorption and restructure were found at six weeks after the surgery, and the graft-bone and host-bone have been integrated completely without obvious boundary at 24 weeks postoperatively. Histomorphologic study showed that the amount of bone within pores of the porous gradient hydroxyapatite/zirconia composites increased continuously with a prolonged implantation time, and that partial composites were degradated and replaced by new-bone trabeculae. There was no significant difference between subgroups (P > 0.05) in the ultimate compressive strengths. CONCLUSION: New porous gradient hydroxyapatite/zirconia composites can promote the repair of bony defect, and induce bone tissue to ingrow into the pores, which may be applied widely to the treatment of bony defect in the future.

Gelatin-chondroitin-6-sulfate-hyaluronic acid scaffold seeded with vascular endothelial growth factor 165 modified hair follicle stem cells as a three-dimensional skin substitute.

INTRODUCTION: In the field of skin tissue engineering, gelatin-chondroitin-6-sulfate-hyaluronic acid (Gel-C6S-HA) stents are a suitable bio skin substitute. The purpose was to investigate the effect of genetically-modified hair follicle stem cells (HFSCs), combined with Gel-C6S-HA scaffolds, on the vascularization of tissue-engineered skin. METHODS: Three-dimensional (3D) Gel-C6S-HA scaffolds were prepared by freeze-drying. Vascular endothelial growth factor (VEGF) 165 gene-modified rat HFSCs (rHFSCs) were inoculated into the scaffolds and cultured for 7 days. Two bilateral full-thickness skin defects were created on the back of 18 Sprague-Dawley rats. Rats were randomly divided into four groups: Group A, HFSCs transduced with VEGF165 seeded onto Gel-C6S-HA scaffolds; Group B, HFSCs transduced with empty vector seeded onto Gel-C6S-HA scaffolds; Group C, Gel-C6S-HA scaffold only; Group D, Vaseline gauze dressing. These compositions were implanted onto the defects and harvested at 7, 14 and 21 days. Wound healing was assessed and compared among groups according to hematoxylin-eosin staining, CD31 expression, alpha smooth muscle actin (α-SMA) and major histocompatibility complex class I (MHC-I) immunohistochemistry, and microvessel density (MVD) count, to evaluate the new blood vessels. RESULTS: SEM revealed the Gel-C6S-HA scaffold was spongy and 3D, with an average pore diameter of 133.23 ± 43.36 µm. Cells seeded on scaffolds showed good adherent growth after 7 days culture. No significant difference in rHFSC morphology, adherence and proliferative capacity was found before and after transfection (P >0.05). After 14 and 21 days, the highest rate of wound healing was observed in Group A (P <0.05). Histological and immunological examination showed that after 21 days, MVD also reached a maximum in Group A (P <0.05). Therefore, the number of new blood vessels formed within the skin substitutes was greatest in Group A, followed by Group B. In Group C, only trace amounts of mature subcutaneous blood vessels were observed, and few subcutaneous tissue cells migrated into the scaffolds. CONCLUSIONS: Tissue-engineered skin constructs, using 3D Gel-C6S-HA scaffolds seeded with VEGF165-modified rHFSCs, resulted in promotion of angiogenesis during wound healing and facilitation of vascularization in skin substitutes. This may be a novel approach for tissue-engineered skin substitutes.

Short- and long-term effects of vertebroplastic bone cement on cancellous bone.

Vertebroplasty using poly(methyl methacrylate) (PMMA) bone cement is the most common method to treat osteoporotic vertebral fractures. However, several questions of interest remain to be clarified, including how does PMMA affect the cement-bone interface area and surrounding bone tissue, can damaged bone tissues be repaired, how will PMMA change the bone interface over the long-term, and what happens to PMMA itself? The purpose of this study is to investigate these concerns and provide a basis for clinical evaluation. We made bone defects in the lumbar vertebrae of New Zealand rabbits as a model of osteoporosis and injected them with bone cement. A mechanical testing machine was used to perform axial compression, three-point bending, and twisting resistance tests to observe and investigate the short- and long-term biomechanical properties of PMMA after implantation. Optical, fluorescence, scanning electron microscopy, and nanoindentation were used to observe the changes in the interface microstructure. PMMA can rapidly establish the strong support with stable function in the near future. Biomechanical experiments showed that biomechanical property of bone cement group was significantly higher than those in the other two groups (P<0.05) biomechanical property of bone cement group may decline with the time, but it's still better than that of OP in the control group (P<0.05). Histomorphological observation result shows that under osteoporosis state the bone grows slower, also bone's rebuilding time extended. And in the later period, main bone's continuous osteoporosis has some impact on the interface. Nano-indentation testing shows that the young modulus and stiffness of the interface among bone, material and interface were significantly differences (P<0.05). Bone cement had gave the best nano indentation hardness, then was interface and bone tissue. PMMA bone cement was able to quickly support and stabilize the defect in the short term, and bone growth restarted at the bone interface and was tightly integrated. However, over the long-term, fluorescent signal was weakened, osteoclasts appeared, the mechanical indicators for both the interface and the whole vertebra decreased, and bone resorption was eventually greater than bone formation, resulting in bone loss. Therefore, vertebroplasty is not the end of treatment, and we need to further study ways to improve the bone cement material, which is crucial for long-term vertebroplasty efficacy, to better treat osteoporosis.

A brief analysis of traditional chinese medical elongated needle therapy on acute spinal cord injury and its mechanism.

Acute spinal cord injury is one of the most common and complicated diseases among human spinal injury. We aimed to explore the effect of point-through-point acupuncture therapy with elongated needles on acute spinal cord injury in rabbits and its possible mechanism. Adult rabbits were randomly divided into a model group, elongated needle therapy group, and blank group. Immunohistochemical staining showed that the protein levels of Fas and caspase-3 in the model group were significantly higher than those in the blank group at each time point (P < 0.05) and significantly lower than those in the elongated needle therapy group on the 3rd and 5th days after operation (P < 0.05). RT-PCR showed that Fas and caspase-3 mRNA levels in the model group and elongated needle therapy group were significantly higher than those in the blank group (P < 0.05, 0.01). The mRNA levels of Fas and caspase-3 in the elongated needle therapy group were significantly lower than those in model group on the 3rd day (P < 0.05, 0.01). Therefore, we confirmed that elongated needle therapy has an obvious effect on acute spinal cord injury in rabbits. Its mechanism is made possible by inhibiting the expression of the Fas→caspase-3 cascade, thereby inhibiting cell apoptosis after spinal cord injury.

Study on the genotoxicity of HA/ZrO2 composite particles in vitro.

To evaluate the genotoxicity of the HA/ZrO2 composite particles by using the micronucleus test (MNT) in vitro. HA/ZrO2 composite particles prepared by sintering at high temperature and pressure, that used powder of HA and ZrO2 of different proportions, were compared with pure HA particles and pure ZrO2 particles. The effect of the composite particles on cell proliferation of rabbit mesenchymal stem cells, and its the genotoxicity to rabbit mesenchymal stem cells were detected by MNT method. The MTT test showed that both pure HA particles and composite particles which contained HA promoted cell proliferation of rabbit mesenchymal stem cells, while pure ZrO2 particles did not, and there was a significant difference (P<0.05). The MNT test showed no significant difference between the HA group and the negative control group (P>0.05), but a significant difference between the HA group and the positive control group (P<0.05). The difference between the ZrO2 group and the negative control group was significant (P<0.01), while the difference between the ZrO2 group and the positive control group was insignificant (P>0.05). The genotoxicity of the HA/ZrO2 composite particle increased with a higher proportion of ZrO2 and an increase in the concentration of the composite, and the 30 wt.% HA/70% ZrO2 composite with 200 µg/mL concentration showed significant genotoxicity (P<0.01).

Effects of combined c-myc and Bmi-1 siRNAs on the growth and chemosensitivity of MG-63 osteosarcoma cells.

Osteosarcoma is the most common form of primary malignant bone tumor. Patients who are insensitive to chemotherapy treatment often have a poor prognosis. According to our previous study, recombinant adenovirus (Myc-AS) in combination with caffeine enhances the induction of apoptosis and the chemotherapeutic effects of cisplatin (CDDP) in MG-63 osteosarcoma cells. The present study aimed to investigate the combinational effects of the small interfering RNAs (siRNAs) c-myc and Bmi-1 on the growth and chemosensitivity of MG-63 osteosarcoma cells. The results indicated that the cell growth inhibition rates of MG-63 cells gradually increased with increasing concentrations of CDDP (P<0.05). This observation was consistent in the single and combined siRNA groups. At a concentration of 5.0 µg/ml CDDP, the growth inhibition rates were 53.3±5.2, 42.7±6.3 and 40.9±4.7% in the combined, c-myc and Bmi-1 siRNA groups, respectively. The cell growth inhibition rate in the combined siRNA group was higher than that observed in the two single siRNA groups (P<0.05). The cell apoptotic rate was 37.3±4.9% in the combined siRNA group, which was significantly higher than that observed in the c-myc (24.8±5.6%) and Bmi-1 siRNA groups (22.7±6.1%; P<0.05). These results suggest that the chemosensitivity of MG-63 cells to CDDP may be markedly enhanced in the siRNA combination group. A decrease in cell proliferation and increased cell apoptosis were also observed in the siRNA combination group. The present study may provide novel insights to further elucidate the pathogenesis and drug resistance mechanisms involved in osteosarcoma. It may also improve our understanding of the underlying mechanisms involved in chemotherapeutic sensitivity, and thus aid the development of future therapeutic strategies for the treatment of osteosarcoma.

Valgus osteotomy in combination with dynamic hip screw fixation for fibrous dysplasia with shepherd's crook deformity.

BACKGROUND AND OBJECTIVES: The treatment of fibrous dysplasia with shepherd's crook deformity is a big challenge. The purpose of this study was to investigate the clinical effect of valgus osteotomy in combination with dynamic hip screw (DHS) fixation to treat fibrous dysplasia with shepherd's crook deformity. METHOD: Twenty-one clinical cases of femoral fibrous dysplasia with shepherd's crook deformity treated between April 2001 and May 2010 were retrospectively analyzed. The valgus osteotomy and internal fixation were performed for these patients. Six patients underwent DHS and trochanter stabilizing plate internal fixation, and the other 15 cases were stabilized by DHS fixation. RESULTS: Patients were followed for 19-128 months. The neck-shaft angle was corrected from 89° (range 65°-107°) preoperatively to 129° (range 119°-140°) postoperatively. Limb-length discrepancy was corrected from 3.0 (range 1.8-4.5) cm preoperatively to 0.7 (range 0-1.9) cm postoperatively. All osteotomies had healed at the final follow-up examination. The clinical scores, which were evaluated by the modified criteria of Guille, improved from an average of 2.9 (range 1-7) to 8.5 (range 6-10). CONCLUSION: Our results demonstrate that valgus osteotomy in combination with DHS internal fixation is an easy and effective method for the treatment of fibrous dysplasia with shepherd's crook deformity. It can restore the neck-shaft angle and re-establish the mechanical alignment of the femur to improve function.

Multicentric epithelioid angiosarcoma of bone.

Bone epithelioid angiosarcoma is rare and generally shows positive immunostaining for epithelial markers. Multicentric bone epithelioid angiosarcoma is easily misdiagnosed as carcinoma, including metastatic carcinoma, multiple myeloma, and multiple lymphoma of bone. This article describes a case of multicentric bone epithelioid angiosarcoma. The patient was first misdiagnosed as having metastatic carcinoma. Examination showed osteolytic lesions in the bilateral heels and the lower left humerus. The diagnosis was confirmed postoperatively and corrected after immunohistochemical analysis of the biopsy. The immunohistochemical analysis revealed that the tumor mass was strongly positive for CD31, factor VIII, vimentin, and neuron-specific enolase. The patient refused chemotherapy and died of lung metastasis 4 months postoperatively.Most bone epithelioid angiosarcomas are immunopositive for epithelial markers (ie, keratin, cytokeratin, high-molecular-weight keratin, and epithelial membrane antigen), vascular endothelial markers (ie, CD31, CD34, and von Willebrand factor), and factor VIII-associated antigen. Bone epithelioid angiosarcoma shows a relatively high degree of malignancy. Patients often die of distant metastasis, including those found in the lung and lymph node tissue. A wide excision of epithelioid angiosarcoma should be performed during the operation of the primary tumor. A better understanding of the clinicopathologic features of this disease may help to clarify the confusion, provide better treatment, and improve the clinical prognosis.

Multivariate analysis of the prognosis of 37 chondrosarcoma patients.

OBJECTIVE: The current study aimedto screen for possible factors which affect prognosis of chondrosarcoma. METHODS: Thirty seven cases were selected and analyzed statistically. The patients received surgical treatment at our hospital between December 2005 and March 2008. All of them had complete follow-up data. The survival rates were calculated by univariate analysis using the Kaplan-Meier method and tested by Log-rank. χ2 or Fisher exact tests were carried out for the numeration data. The significant indexes after univariate analysis were then analyzed by multivariate analysis using COX regression model. Based on the literature, factors of gender, age, disease course, tumor location, Enneking grades, surgical approaches, distant metastasis and local recurrence were examined. RESULTS: Univariate analysis showed that there were significant differences in Enneking grades, surgical approaches and distant metastasis related to the patients' 3-year survival rate after surgery (P<0.001). No significant difference was not found in gender, age, disease course, tumor location or local recurrence (P>0.05). Multivariate analysis showed that Enneking grade (P=0.007) and surgical approaches (P=0.010) were independent factors affecting the prognosis of chondrosarcoma, but distant metastasis was not (P=0.942). CONCLUSION: Enneking grades, surgical approaches and distant metastasis are risk factors for prognosis of chondrosarcoma, among which the former two are independent factors.

Difference of adherence, proliferation and osteogenesis of mesenchymal stem cells cultured on different HA/ZrO2 composites.

OBJECTIVE: To study the adherence, proliferation and osteogenesis of mesenchymal stem cells (MSCs) cultured on different HA/ZrO2 composites. METHODS: The simplex and graded HA/ZrO2 compo-sites were prepared using dry-laid method. The surface topography of the composites was observed by scanning electron microscope (SEM). The MSCs were isolated from rabbits and cultured on experimental groups (simplex HA/ZrO2 composite, graded HA/ZrO2 composite, pure HA or pure ZrO2 coatings respectively) and control group (ordinary culture plate). Then, we observed the adherence, proliferation and osteogenesis of the MSCs, detected the cellular alkaline phosphatase (ALP) activities, extracted total RNA and detected the mRNA expression of collagen I, osteocalcin and osteopontin using the reverse transcription and polymerase chain reaction (RT-PCR) method. RESULTS: The SEM images confirmed that the surface of the simplex HA/ZrO2 composite was coverd by discon-tiguous HA layer with clear visualization of the partial ZrO2 matrix, while the surface of the graded HA/ZrO2 composite was fairly rough with porosity. X-ray diffraction showed that after high temperature sintering, the ZrO2 phase still remained, while the HA phase was transformed to beta-Ca3(PO4)2 , alpha-Ca3(PO4)2 and CaZrO3 phases on the surface of both composites. Cell culture indicated that the HA/ZrO2 composites supported cell attachment. Neither ALP expression nor mRNA expression of collagen I, osteocalcin or osteopontin from RT-PCR results showed significant deviation among four groups. CONCLUSION: Among these four composites, the graded HA/ZrO2 composite promotes the MSCs proliferation and the osteogenic differentiation to a certain extent.