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Abstract Background We aimed to compare the difference between the therapeutic effects of percutaneous vertebroplasty (PVP) as well as PVP combined with erector spinae plane blocked (ESPB) in osteoporotic vertebral compression fractures (OVCFs) therapy. Methods After the reception, 100 affected people to OVCFs were randomly divided into the PVP group as a control as well as the PVP + ESPB group as the observation, which included fifty affected people per group. The visual analog scale (VAS) for pain as well as the Oswestry Disability Index (ODI) per group was assessed before the operation, two hours after the operation, and when patients were discharged from the hospital. Operating time was also evaluated on the charged bulk of bone cement during the surgery, blood loss during the surgery, as well as operating costs for each group. Additionally, to assess differences, comparisons have been done among available groups in terms of ambulation as well as defecation or stool after the operation at the earlier time. Results The PVP + ESPB category acquired lower VAS and ODI scores when assessments were processed 2 h after the operation and when they were discharged from a hospital. They also had earlier postoperative ambulation and defecation time than the category of PVP (p

Accelerated population ageing has brought a great burden to the development of society. Repairing senile osteoporosis fractures is a great challenge, but a desirable way to address this issue is by developing multifunctional titanium(Ti) implants with antiaging and pro-osteogenic effects. Herein, to endow TI substrate with an antiaging effect for enhanced bone formation, an exercise-induced myokine(irisin) was loaded on titanium dioxide nanotubes(TNTs) and then a multilayered structure composed of chitosan(Chi) and gelatin(Gel) was constructed on the substrates via a layer-by-layer-assembly technique(TNT-IR-LBL). The surface topography of TNT-IR-LBL was characterized by scanning electron microscopy (SEM), atomic force microscopy(AFM), X-ray photoelectron spectroscopy(XPS) and water contact angle measurements, respectively. As an exercise-induced myokine, the irisin secreted from skeletal muscle exhibits strong activity for against the chronic diseases. The implants synthesized here displayed good biocompatibility towards osteoblasts. Moreover, irisin was sustainably released from TNT-IR-LBL for more than 3 weeks. In vitro studies indicated the TNT-IR-LBL substrates promoted osteoblast differentiation. In addition, compared to bare titanium, TNT-IR-LBL significantly promoted new bone formation around the implant interface in senile osteoporosis rats 4 weeks after implantation. Overall, this study provides a promising candidate to develop Ti-based orthopaedic implants to repair senile osteoporosis fractures.

Osteosarcoma is the most common malignant bone tumour, and the metastasis of osteosarcoma is an important cause of death. Evidence has shown that the mevalonate pathway is highly activated and is expected to be a new target for tumour therapy. In this study, we investigated the effect of mevalonate signalling on osteosarcoma metastasis and its molecular mechanism. First, we found that the key rate-limiting enzyme of mevalonate signalling, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), was highly expressed in osteosarcoma cells, and inhibition of HMGCR with simvastatin significantly inhibited the motility of 143B cells. Next, we found that YAP1 activity was significantly upregulated in osteosarcoma cells and that YAP1 knockdown inhibited the motility of 143B cells. We also found that the mevalonate pathway regulated the motility of 143B cells by modulating YAP1 phosphorylation and cellular localization. Moreover, we found that the activity of YAP1 was regulated by the mevalonate pathway by modulating the cell membrane localization of RhoA. Finally, we demonstrated that inhibition of the mevalonate pathway notably reduced the lung metastasis of 143B cells, as reflected by the decreased incidence and number of metastatic nodules and the increased survival time of the nude mice. Taken together, our findings suggest that the mevalonate pathway can promote the metastasis of osteosarcoma by activating YAP1 via RhoA. Inhibition of the mevalonate pathway may be a promising therapeutic strategy for osteosarcoma metastasis.

Magnesium (Mg) and its alloys have attracted attention as potential biodegradable materials in orthopedics due to their mechanical and physical properties, which are compatible with those of human bone. However, the effect of the mismatch between the rapid material degradation and fracture healing caused by the adverse effect of hydrogen (H2), which is generated during degradation, on surrounding bone tissue has severely restricted the application of Mg and its alloys. Thus, the development of new Mg alloys to achieve ideal degradation rates, H2 evolution and mechanical properties is necessary. Herein, a novel Mg–1Zn–1Sn-xSr (x = 0, 0.2, 0.4, and 0.6 wt%) quaternary alloy was developed, and the microstructure, mechanical properties, corrosion behavior and biocompatibility in vitro/vivo were investigated. The results demonstrated that a minor amount of strontium (Sr) (0.2 wt %) enhanced the corrosion resistance and mechanical properties of Mg–1Zn–1Sn alloy through grain refinement and second phase strengthening. Simultaneously, due to the high hydrogen overpotential of tin (Sn), the H2 release of the alloys was significantly reduced. Furthermore, Sr-containing Mg–1Zn–1Sn-based alloys significantly enhanced the viability, adhesion and spreading of MC3T3-E1 cells in vitro due to their unique biological activity and the ability to spontaneously form a network structure layer with micro/nanotopography. A low corrosion rate and improved biocompatibility were also maintained in a rat subcutaneous implantation model. However, excessive Sr (>0.2 wt %) led to a microgalvanic reaction and accelerated corrosion and H2 evolution. Considering the corrosion resistance, H2 evolution, mechanical properties and biocompatibility in vitro and in vivo, Mg–1Zn–1Sn-0.2Sr alloy has tremendous potential for clinical applications.

Abstract Solid fusion at the bone-implant interface (BII) is considered one of the indicators of a satisfactory clinical outcome for spine surgery. Although the mechanical and physical properties of nanohydroxyapatite/polyamide66 (n-HA/PA66) offers many advantages, the results of long-term follow-up for BIIs remain limited. This study aimed to improve the BII of n-HA/PA66 by applying plasma-sprayed titanium (PST) and assessing the mechanical and histological properties. After the PST coating was applied to n-HA/PA66 implants, the coating had uneven, porous surfaces. The compression results were not significantly different between the two groups. The micro-CT results demonstrated that at 6 weeks and 12 weeks, the bone volume (BV), BV/tissue volume (TV) and trabecular number (Tb.N) values of the n-HA/PA66-PST group were significantly higher than those of the n-HA/PA66 group. The results of undecalcified bone slicing showed that more new bone appeared to form around n-HA/PA66-PST implant than around n-HA/PA66 implant. The bone-implant contact (BIC) and push-out test results of the n-HA/PA66-PST group were better than those of the n-HA/PA66 group. In conclusion, after PST coating, direct and additional new bone-to-implant bonding could be achieved, improving the BII of n-HA/PA66 implants. The n-HA/PA66-PST implants could be promising for repair purposes.

Abstract Objective To explore the clinical efficacy of posterior LFF for cervical OPLL with radicular pain of upper limbs Methods Between January 2014 and January 2018, 48 OPLL patients with radicular pain symptoms of upper limbs who underwent a one-stage posterior laminectomy and instrumented fusion with/without foraminotomy were reviewed retrospectively and divided into two groups: LF group (laminectomy with instrumented fusion without foraminotomy) and LFF group (laminectomy with instrumented fusion and foraminotomy). Clinical data were assessed and compared between the two groups. The radicular pain of upper limbs and neck was measured using the visual analog scale (VAS). The neurological function was evaluated with the American Spinal Injury Association (ASIA) scale. Changes of sagittal alignment were investigated by postoperative plain x-ray or computed tomography (CT). Moreover, the decompression of the spinal cord was evaluated based on postoperative MRI. Results All the 48 patients were followed up for 24–42 months with an average follow-up time of 31.1±5.3 months. A total of 56 cervical intervertebral foramens were enlarged in 48 patients, including 40 cases (83.3%) with 1 intervertebral foramen enlargement and 8 cases (16.7%) with 2 intervertebral foramen enlargements. There were no significant differences in intraoperative blood loss, postoperative drainage amount, Japanese Orthopaedic Association (JOA) scores, JOA recovery rates, VAS scores for neck pain, and ASIA grade between two groups. The mean operative time was shorter in the LF group compared with the LFF group. The VAS score for arm pain was significantly lower while the surgical duration was longer in group B. No statistical difference was observed between the two groups in terms of C2–C7 SVA, cervical lordosis, focal angulation at the foraminotomy segment, and local spinal cord angle. Compared with the LF group, there was no segmental kyphosis or instability where the additional posterior foraminotomy was performed in the LFF group. Conclusions One-stage posterior LFF can achieve satisfied clinical efficacy in improving neurological function and relieving the radicular pain of the upper limbs for OPLL patients with radiculopathy symptoms.

Abstract To compare the surgical outcomes of autogenous spinous process with iliac bone graft in managing single segment lumbar pyogenic spondylitis (PS) after posterior debridement and instrumentation. We performed a retrospective study for adult patients with single level lumbar PS. 60 patients with single segment lumbar PS underwent one-stage posterior debridement, autogenous bone graft and instrumentations. The patients were divided into Group A (autogenous iliac bone) and Group B (autogenous spinous process). Preoperative Charlson comorbidity index (CCI) was analyzed to assess the comorbidity. Low back pain was evaluated using the visual analog scale (VAS). Neurological status was assessed with the American Spinal Injury Association (ASIA) scale. Clinical infection index including the C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) was also reviewed. Moreover, fusion and changes of sagittal alignment were investigated radiologically. There was a significantly longer operative time, hospital stay and greater blood loss in group A. The VAS scores improved significantly at each follow-up interval and post-operative VAS score was significantly lower in group B. At the last follow-up, ESR and CRP returned to normal for all patients. There was at least one grade level improvement in ASIA score. No statistical difference in corrected rate, loss of sagittal angle and lumbar lordosis was found between the two groups. There was no significant difference in fusion rate, mean fusion time and complications between the two groups. Compared with iliac bone graft, the autogenous spinous process bone graft can be less invasive and painful for the single segment lumbar PS. One-stage posterior debridement, autogenous spinous process bone graft and instrumentation can provide satisfactory results for appropriate cases.

Background: Spinal cord injury (SCI) is currently not completely curable. Exosomes have been widely used in preclinical studies of spinal cord injury. Here, in this meta-analysis, we focused on evaluating the overall efficacy of therapies based on miRNA-modified exosomes on functional recovery in animal models of SCI.Methods: PubMed, embase and Web of Science library databases were searched. Relevant literature was included, and the random effects model was used to assess the overall effect of the intervention, with outcomes expressed as SMD. The primary outcome included motor function scores. Risk of bias (ROB) was assessed using the ROB tool of the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE). R version 4.1.1software and Review Manager software were used for meta-analysis.Results: A total of 11 preclinical studies were included. The meta-analysis revealed that miRNA-modified exosome therapy was effective in improving motor function scores compared with exosomes alone or control therapy (standardized mean difference: 4.21; 95% confidence interval: 3.39–5.04). There was significant asymmetry in the funnel plot, and trim-and-fill analysis revealed four unpublished studies of motor scores. The quality of all included studies was evaluated with SYRCLE’s ROB tool. The SCI model, administration time and dose had an impact on the effect of the treatment.Conclusion: MiRNA-modified exosomes have shown great potential in the treatment of SCI. Moreover, the efficacy of miRNA-modified exosomes was superior to that of exosomes alone.

Background. Although direct pars repair using a pedicle screw-rod-hook system has achieved satisfactory results in patients with spondylolysis, its application in adults with low-grade isthmic spondylolisthesis is rarely reported. Objective. To assess the surgical effect of reduction and direct repair surgery with a pedicle screw-rod-hook system combined with autogenous bone grafts in adult patients with low-grade isthmic spondylolisthesis. Methods. Sixty-four adult patients with low-grade isthmic spondylolisthesis underwent reduction and direct repair using a pedicle screw-rod-hook system in our department from September 2009 to April 2018. The clinical efficacy was evaluated by clinical and radiological assessments. Results. The average follow-up was 52.15 ± 9.96 months. The visual analog scale (VAS) scores (VAS-lumbar and VAS-leg) and Oswestry Disability Index (ODI) at the final follow-up (FFU) were significantly lower than the preoperative levels P

Abstract Background The application of nano-hydroxyapatite/polyamide 66(n-HA/PA66) struts has become reliable in anterior cervical corpectomy and fusion (ACCF) as a source of sufficient segmental stability. This was a retrospective and long-term imaging evaluation of the n-HA/PA66 strut in 1-level ACCF. Methods The patients between June 2006 and December 2014, who underwent 1-level ACCF using an n-HA/PA66 strut, were reviewed. The neurological status was assessed using the Japanese Orthopedic Association (JOA) score and axial pain was evaluated using a Visual Analogue Scale (VAS) score and the radiographic parameters were determined by X-ray and 3-D CT examinations when necessary for the evaluation of bone fusion using the Brantigan scale and imaging characteristics. Results A total of 520 patients underwent one-level ACCF, with a mean follow-up (FU) duration of 72.38 ± 24.56 months. The level of surgery was C4 in 58 cases, C5 in 173 cases, C6 in 208 cases, and C7 in 81 cases. According to the Brantigan scale, on X-ray examination, the bony fusion rate was observed to be 40%, 70%, 93%, and 98% at 3 months, 6 months, 1 year and the final FU. An interesting radiographic appearance of the bone graft growth pattern was classified into three types. 95% of the patients accounted for types a and b. No significant differences were observed in age, hospitalization duration, surgical haemorrhage volume, or fusion rate among the types except in the percentage and sex of the patients among the types. Type a had better cervical lordosis, and less subsidence than types b and c (P

The number and spatial configuration of the screws will affect the stability and prognosis of the fractures. In our study, we assessed the biomechanical effects of the double-head cannulated compression screw (DhCCS) and ordinary cannulated compression screw (OCCS) for the treatment of femoral neck fractures by using computer finite element analysis. The original digital imaging and communications in medicine (DICOM)data of a proximal femur were imported into Materialise's interactive medical image control system (MIMICS)software for modeling. Both DhCCS and OCCS 3D-models were obtained by using the 3D scan technique. Using the fracture model and internal fixation assembly model with an inverted triangle, two horizontal and vertical distribution were established in UG software. Next, the displacement and stress distribution were calculated in ANSYS software. The displacement value of the femoral head in the DhCCS group was smaller than that in the OCCS group, and the displacement value in the two horizontal groups was smaller than that in the vertical group. The stress distribution in the DhCCS group was concentrated on the screw rod at the fracture block and thread end, while only at the fracture block in the OCCS group. The stress in the horizontal group was more dispersed on the screws than that in the vertical group. DhCCS has reliable stability for the fixation of femoral neck fractures and applied in the clinical work and 2 horizontal fixation can be used when two screws are selected.

To meet the growing demand for antibacterial implants for bone-implant-associated infection therapy and avoid the adverse effects of secondary surgery, a degradable platform with pH responsiveness and ion-associated antibacterial properties was constructed. A small amount of Sn added to Mg-1Zn alloy reduces the biocorrosion rate, which can be attributed to Sn participation in outer-layer film formation, significantly reducing the biocorrosion rate and hydrogen evolution rate after implantation in vivo. These Mg alloys, which are susceptible to degradation in the acidic bacterial microenvironment, degrade by releasing Mg, Zn and Sn, producing favorably alkaline and antibacterial conditions. Samples with the composition of Mg-1Zn-0.5Sn were found to be beneficial for promoting initial cell adhesion and proliferation, resulting in improved biocompatibility and biosafety. The biocompatibility of this alloy was confirmed by the healthy behavior of animals and the absence of acute or chronic toxicity in the liver, spleen, and kidneys. Our results demonstrate that Mg-1Zn-0.5Sn is safe for biological systems, enabling its efficacious use in biomedical applications.

Abstract Background Diffusion tensor imaging (DTI) is an effective method to identify subtle changes to normal-appearing white matter (WM). Here we analyzed the DTI data with other examinations, including motor evoked potentials (MEPs), histopathological images, and behavioral results, to reflect the lesion development in different degrees of spinal cord injury (SCI) in acute and subacute stages. Method Except for 2 Sprague -Dawley rats which died from the anesthesia accident, the rest 42 female rats were randomized into 3 groups: control group (n = 6), moderate group (n = 18), and severe group (n = 18). Moderate (a 50-g aneurysm clip with 0.4-mm thickness spacer) or severe (a 50-g aneurysm clip with no spacer) contusion SCI at T8 vertebrae was induced. Then the electrophysiological assessments via MEPs, behavioral deterioration via the Basso, Beattie, and Bresnaha (BBB) scores, DTI data, and histopathology examination were analyzed. Results In this study, we found that the damage of WM myelin, MEPs amplitude, BBB scores and the decreases in the values of fractional anisotropy (FA) and axial diffusivity (AD) were more obvious in the severe injury group than those of the moderate group. Additionally, the FA and AD values could identify the extent of SCI in subacute and early acute SCI respectively, which was reflected in a robust correlations with MEPs and BBB scores. While the values of radial diffusivity (RD) showed no significant changes. Conclusions Our data confirmed that DTI was a valuable in ex vivo imaging tool to identify damaged white matter tracts after graded SCI in rat, which may provide useful information for the early identification of the severity of SCI.

Abstract Background Large segmental bone defects are still one of the challenges for orthopaedic surgeons. Although 3D-printed porous titanium is a potential bone substitute material because of its porous structure simulating natural bone, the titanium surface has low bioactivity, integrates with bone tissue through the simple mechanical interlock. The study aims to investigate the capability and osteogenesis of 3D-printed porous titanium (3D PPT)-coated polydopamine (PDA) for repairing bone defects. Methods Fifteen 6-month New Zealand white rabbits were implanted with PDA-3D PPT to repair 6 mm × 10 mm defects on the femoral condyle compared with the group of 3D PPT and comparing with the blank group. After 6 weeks and 12 weeks, micro-CT and histological examination were performed to observe bone growth. Results All the PDA-3D PPT group, the 3D PPT group and the blank group recovered in good condition. The images showed that the boundaries between the implant area and the surrounding area were obscure in the three groups. The results of micro-CT demonstrated that at 6 weeks and 12 weeks, the bone volume (BV) values of PDA-3D PPT implants group were significantly higher than those of the 3D PPT implants group and blank group (P < 0.05), the BV/tissue volume (TV) and the trabecular number (Tb.N) of PDA-3D PPT implants were significantly higher than those of the 3D PPT group and blank group (P < 0.05). The results of un-decalcified bone slicing showed that ore new bone appeared to form around the PDA-3D PPT than that of 3D PPT and blank group. The bone-implant contact (BIC) of PDA-3D PPT was better (P < 0.05) than that of 3D PPT group. Conclusion PDA-3D PPT could improve the bioactivity and promote the growth and healing of bone tissue and can be a promising repairing material.

Backgroud: A variety of extrapedicular puncture methods have been successfully used in percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty (PKP). Currently, there are no reviews on extrapedicular puncture. Authors reviewed the puncture methods in different extrapedicular approaches and recommend appropriate extrapedicular puncture methods for thoracolumbar PVP (PKP). Methods: All the published research available in English and Chinese up to January 2020 from Web of Science, PubMed, Embase, China National Knowledge Internet (CNKI), and the Wanfang Database were included. The subject areas included “percutaneous vertebroplasty, percutaneous kyphoplasty, vertebral augmentation” and “extrapedicular, parapedicular, bilateral, and unilateral”. Articles met the selection criteria if they contained the details of the puncture method of the extrapedicular approach. Results: We searched 118 studies, and after careful reading, 9 studies introduced 10 types of extrapedicular punctures in detail: the transcostovertebral approach, extrapedicular approach, unilateral extrapedicular approach, far-lateral extrapedicular approach, parapedicular access, lumbar extrapedicular approach, thoracic infrapedicular approach, extrapedicular modified inferior endplate access, extrapedicular approach along the predetermined individualized puncture route, and Kambin triangle approach. Conclusions: In thoracic vertebrae, the extrapedicular approach could be a better puncture method. In the upper lumbar vertebrae, the unilateral extrapedicular and far-lateral extrapedicular approach are recommended as the extrapedicular puncture methods. In L4-5, extrapedicular puncture is not recommended because of the high risk of injury to the lumbar artery.

Background: To compare the clinical efficacy of granular bone grafts and transverse process bone grafts for single-segmental thoracic tuberculosis (TB).Methods: The clinical records of 52 patients who were diagnosed with single-segmental thoracic TB and treated by one stage posterior debridement, bone graft fusion, and internal fixation in our department from 2015 to 2018 were retrospectively analyzed. Among them, 25 cases were in the granular bone graft group and 27 cases in the transverse processes bone graft group. Outcomes including the visual analog scale (VAS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), neurological function, operative time, operative blood loss, hospital stay, Cobb angle, bone graft fusion time, and postoperative complications were all recorded and analyzed.Results: There were no significant differences in operative time, operative blood loss, and hospital stay between the two groups (P > 0.05). With an average follow-up of 18–33 months, all patients in the two groups showed significant improvement in VAS score, ESR, CRP, and neurological function compared with preoperative measurements (P < 0.05), however, no significant differences were found for the last follow-up (P > 0.05). The two groups showed similar Cobb angle correction (P > 0.05), but the granular bone graft group had a larger Cobb angle loss than the transverse processes bone graft group (P < 0.05). The bone graft fusion time of the granular bone graft group was shorter than that of the transverse processes bone graft group (P < 0.05). No significant difference was found in the postoperative complications rate between the two groups (P > 0.05).Conclusion: Granular bone grafts and transverse process bone grafts may achieve comparable clinical efficacy for single-segmental thoracic TB, but the former method had a shorter bone fusion time.

The mechanical properties and bio-corrosion behaviors of as-extruded Mg–4Zn alloys after Sn addition were investigated, systematically. A small amount of Sn addition to Mg–4Zn alloy slightly improved the mechanical properties for solid solution strengthening, and significantly controlled the bio-corrosion rates. Sn participating in the outer layer film formation as SnO/SnO2 resisted the bio-corrosion proceeding. Especially, Mg–4Zn–1.5Sn alloy, with a weight loss rate of 0.45 mm/y and hydrogen evolution rate of 0.099 mL/cm2/day, showed cytotoxicity grade of 0 to MC3T3-E1 cells. The perfect alliance of cytocompatibility, suitable mechanical properties and low bio-corrosion rate demonstrates that this Mg–4Zn–1.5Sn alloy is a promising biodegradable magnesium alloy for orthopedic implants. Keywords: Magnesium alloy, Polarization, Immersion, Bio-corrosion behavior, Cytocompatibility

Context: Caragana pruinosa Kom. (Fabaceae), a commonly used folk medicine, has been found to possess antitumor effects. However, the antiproliferative effect of 2,4-dihydroxy-3′-methoxy-4′-ethoxychalcone (DMEC) derived from C. pruinosa against multiple myeloma (MM) has never been investigated. Objective: This study systematically evaluates the antiproliferative effect of DMEC against MM cells. Materials and methods: The antiproliferative effect of DMEC (1, 2, 4, 8, 16, 32, and 64 μM) on MM cells lines, including RPMI8226, MM.1S, and U266, was examined using Cell counting kit-8 (CCK-8) assay after 24 h incubation. The proapoptotic effect of DMEC (20 μM) was determined using fluorescent microscope and flow cytometer, and its possible underlying mechanisms were further studied by using western blotting analysis. Results: The half maximal inhibitory concentrations (IC50) of DMEC on RPMI8226, MM.1S, and U266 cells were calculated as 25.97, 18.36, and 15.02 μM, respectively. The inhibitory effect of DMEC on MM cells was related to mitochondria-mediated apoptosis via upregulation of the cleaved-caspase-3 (C-3), cleaved-caspase-9 (C-9), Bad, and cytochrome C (Cyto C), but downregulation of the Bcl-2 and poly ADP-ribose polymerase (PARP). Furthermore, DMEC (5, 10, and 20 μM) reduced the expression of phosphatidylinositol-3-kinase (PI3K), phosphorylated (p)-protein kinase B (Akt), and p-mammalian target of rapamycin (p-mTOR), which were further evidenced by pretreatment with IGF-1, a PI3K activator. Conclusion: Collectively, our results indicate that the DMEC could be treated as a new candidate for treatment of multiple myeloma in the future. Also, an in vivo study is warranted in the future.

Abstract Background The combination of phytochemicals with chemotherapy drugs is an emerging new strategy for cancer therapy to increase antitumor responses. Methods The present study investigates the effect of the combination of capsaicin (CAP) with cisplatin (DDP) and the potential underlying anticancer mechanisms in osteosarcoma (OS) cells in vitro and in vivo. Results Cell viability assays and isobolographic analyses demonstrated that the combination of CAP and DDP showed synergistic cytotoxic effects on OS cells. We chose relatively low concentrations of CAP (100 μM) and DDP (16.7 μM) for subsequent experiments. Generally, the combination of CAP and DDP had significant effects on apoptosis induction, cell cycle arrest and cell invasion inhibition in OS cells compared with the individual-treatment groups and the control group. Moreover, cotreatment with CAP and DDP triggered prosurvival autophagy through reactive oxygen species (ROS)/JNK and p-AKT/mTOR signaling in OS cells. The combination regimen of CAP and DDP also inhibited tumor growth in an OS xenograft model. Conclusion These results suggest that the combination of CAP and DDP has strong inhibitory effects on OS cells and identify CAP as a promising agent for supplementing standard chemotherapy and possible future targeted therapy in OS.

We prepared the superparamagnetic chitosan nanoparticles (SPCIONPs) to study the application of them as gene vectors using a magnetic transfection system for the targeted treatment of lung metastasis of osteosarcoma. The SPCIONPs were characterized by transmission electron microscopy, Fourier transform infrared spectrometry, superconducting quantum interference device and atomic force microscopy. Their biosafety was determined by cell counting kit-8 (CCK8) and live–dead staining assays. The transfection in vitro was detected by laser confocal microscopy. SPCIONPs, which can bind closely to plasmids and protect them from DNA enzyme degradation, were prepared with an average particle size of approximately 22 nm and zeta potential of 11.3 mV. The results of the CCK8 and live–dead staining assays showed that superparamagnetic chitosan nanoparticles loaded with insulin-like growth factor-binding protein 5 (SPCIONPs/pIGFBP5) induced no significant cytotoxicity compared to the control group. The result of transfection in vitro suggested that pIGFBP5 emitted a greater amount of red fluorescence in the SPCIONPs/pIGFBP5 group than that in the chitosan-loaded IGFBP5 (CS/pIGFBP5) group. In conclusion, the prepared SPCIONPs had good biosafety and could be effectively used to transfer pIGFBP5 into 143B cells, and they thus have good application prospects for the treatment of lung metastasis of osteosarcoma.

Objective This study was performed to evaluate the surgical indications, clinical efficacy, and preliminary experiences of nonstructural bone grafts for lumbar tuberculosis (TB). Methods Thirty-four patients with lumbar TB who were treated with nonstructural bone grafts were retrospectively assessed. The operative time, operative blood loss, hospital stay, bone graft fusion time, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) concentration, visual analog scale (VAS) score, Oswestry Disability Index (ODI), American Spinal Injury Association (ASIA) impairment grade, and Cobb angle were recorded and analyzed. Results The mean operative time, operative blood loss, hospital stay, Cobb angle correction, and Cobb angle loss were 192.59 ± 42.16 minutes, 385.29 ± 251.82 mL, 14.91 ± 5.06 days, 9.02° ± 3.16°, and 5.54° ± 1.09°, respectively. During the mean follow-up of 27.53 ± 8.90 months, significant improvements were observed in the ESR, CRP concentration, VAS score, ODI, and ASIA grade. The mean bone graft fusion time was 5.15 ± 1.13 months. Three complications occurred, and all were cured after active treatment. Conclusions Nonstructural bone grafts may achieve satisfactory clinical efficacy for appropriately selected patients with lumbar TB.

Objective. To compare the effect of decompression of the spinal canal with or without discectomy on the clinical efficacy of Dynesys dynamic fixation treatment in lumbar degenerative diseases. Methods. A total of 62 patients treated for single-segment lumbar degenerative disease from October 2010 to November 2017 were retrospectively analyzed. All patients underwent decompression of the spinal canal with Dynesys dynamic fixation and were divided into two groups. Twenty-seven patients in group A did not undergo discectomy, and 35 patients in group B underwent discectomy. The intervertebral height, range of motion, Pfirrmann grade of the surgical segment and the upper adjacent segment, function scores, and operation information were compared. Results. All patients were followed up for an average of 30.7 ± 11.5 months. At the final follow-up, the intervertebral height and range of motion of the surgical segment decreased significantly in both group A and B (p0.05) and range of motion (p

Self-assembled peptide scaffolds based on D-RADA16 are an important matrix for controlled drug release and three-dimensional cell culture. In this work, D-RADA16 peptide hydrogels were coated on artificial bone composed of nano-hydroxyapatite/polyamide 66 (nHA/PA66) to obtain a porous drug-releasing structure for treating bone defects. The developed materials were characterized via transmission electron microscopy and scanning electron microscopy. The proliferation and adhesion of bone mesenchymal stem cells (BMSCs) were examined by confocal laser microscopy and CCK-8 experiments. The osteogenic ability of the porous materials towards bone BMSCs was examined in vitro by staining with Alizarin Red S and alkaline phosphatase, and bioactivity was evaluated in vivo. The results revealed that nHA/PA66/D-RADA16/bFGF reduces the degradation rate of D-RADA16 hydrogels and prolongs sustained release of bFGF, which would promote BMSCs proliferation, adhesion and osteogenesis in vitro and bone repair in vivo. Thus, it deserves more attention and is worthy of further research.

Mg-Zn-Sn-based alloys are widely used in the industrial field because of their low-cost, high-strength and heat-resistant characteristics. However, their application in the biomedical field has been rarely reported. In the present study, biodegradable Mg-1Zn-1Sn and Mg-1Zn-1Sn-0.2Sr alloys were fabricated. Their microstructure, surface characteristics, mechanical properties and bio-corrosion properties were carried out using an optical microscope (OM), X-ray diffraction (XRD), electron microscopy (SEM), mechanical testing, electrochemical and immersion test. The cell viability and morphology were studied by cell counting kit-8 (CCK-8) assay, live/dead cell assay, confocal laser scanning microscopy (CLSM) and SEM. The osteogenic activity was systematically investigated by alkaline phosphatase (ALP) assay, Alizarin Red S (ARS) staining, immunofluorescence staining and quantitative real time-polymerase chain reaction (qRT-PCR). The results showed that a small amount of strontium (Sr) (0.2 wt.%) significantly enhanced the corrosion resistance of the Mg-1Zn-1Sn alloy by grain refinement and decreasing the corrosion current density. Meanwhile, the mechanical properties were also improved via the second phase strengthening. Both Mg-1Zn-1Sn and Mg-1Zn-1Sn-0.2Sr alloys showed excellent biocompatibility, significantly promoted cell proliferation, adhesion and spreading. Particularly, significant increases in ALP activity, ARS staining, type I collagen (COL-I) expression as well as the expressions of three osteogenesis-related genes (runt-related transcription factor 2 (Runx2), osteopontin (OPN), and osteocalcin (Bglap)) were observed for the Mg-1Zn-1Sn-0.2Sr group. In summary, this study demonstrated that Mg-Zn-Sn-based alloy has great application potential in orthopedics and Sr is an ideal alloying element of Mg-Zn-Sn-based alloy, which optimizes its corrosion resistance, mechanical properties and osteoinductive activity.

Resveratrol shows potent anti-tumor therapeutic properties in various tumors. However, the exact effect of resveratrol on osteosarcoma cells, especially cancer stem cells, remains unclear. In this study, we examined the effect of resveratrol on osteosarcoma stem cells and explored the underlying molecular mechanisms. Resveratrol inhibited cell viability, self-renewal ability and tumorigenesis of osteosarcoma cells, whereas showed no significant inhibition effects to normal osteoblast cells. Mechanically, resveratrol treatment decreased cytokines synthesis and inhibited JAK2/STAT3 signaling, which was consistent with the decline of cancer stem cells marker, CD133. Exogenous STAT3 activation attenuated the cancer stem cell elimination effects of resveratrol treatment. Our results demonstrated that resveratrol inhibited osteosarcoma cell proliferation and tumorigenesis ability, which was correlated with cytokines inhibition related JAK2/STAT3 signaling blockage. Resveratrol may be a promising therapeutic agent for osteosarcoma management.

To evaluate the association of acromial morphology and subacromial impingement.Bilateral shoulder computed tomography was performed in 138 patients who received shoulder arthroscopy. Measured parameters included: acromial tilt (AT), modified acromial tilt (mAT), acromial slope (AS), acromiohumeral interval (AHI), lateral acromial angle (LAA), acromial index (AI), critical shoulder angle (CSA), acromial anterior protrusion (AAP), and acromial inferior protrusion (AIP). Acromial morphological characteristics were compared between groups. Side-to-side differences were assessed between affected and non-affected shoulders. Intra- and inter-observer agreements for each parameter were calculated.AT (25.90 vs. 29.41°), mAT (18.88 vs. 22.64°), and AHI (5.46 vs. 6.47 mm) were significantly smaller in impinged patients. The impingement group demonstrated significantly larger AI (63.50 vs. 59.84%), CSA (31.78 vs. 28.74°), AAP (7.13 vs. 5.32 mm), and AIP (5.51 vs. 4.04 mm). Regarding side-to-side comparison, the acromial morphology was significantly different between the affected and non-affected shoulders in impinged patients, while the difference was slight and insignificant in control patients. All, except AS and LAA, measured parameters demonstrated good intra- and inter-observer agreements.Three-dimensional reconstructed CT scan is a reliable method to measure shoulder morphology. The acromial morphological variation is related with sub acromial impingement, however, the causal relationship of them should be further explored.

Osteocyte apoptosis has been reported to play a central role in bone remodeling. In addition to apoptosis, other mechanisms may be involved in osteocyte loss. This study aimed to investigate the effect of necroptosis on osteocytes in ovariectomized (OVX) rats. Ninety-six female Sprague-Dawley rats were randomly divided into an OVX group and a sham group. At 0, 4, 8 and 12 weeks after surgery, specimens from each group (n = 12 each) were harvested. Bone mineral density (BMD) and body weight were measured. Transmission electron microscopy (TEM) and micro-CT were used to observe the changes in cellular morphology and bone microarchitecture induced by estrogen deficiency. Osteocyte apoptosis and necroptosis were evaluated via TUNEL and immunofluorescence staining for active caspase-3. At 8 weeks after ovariectomy, a greater number of osteocytes with typical necrotic morphological features were TUNEL positive but negative for active caspase-3. Western blotting, quantitative real-time PCR and immunofluorescence assessments demonstrated that the levels of receptor-interacting serine/threonine protein kinase 1 (RIP1) and RIP3 in osteocytes were significantly increased at 8 weeks after ovariectomy. These data are the first to suggest that necroptosis accelerates osteocyte loss under conditions of estrogen deficiency-induced osteoporosis in OVX rats. These findings provide evidence of a potential mechanism through which osteocyte necroptosis is associated with postmenopausal osteoporosis.

OBJECTIVE: To retrospectively compare the efficacy of the titanium mesh cage (TMC) and the nano-hydroxyapatite/polyamide66 cage (n-HA/PA66 cage) for 1- or 2-level anterior cervical corpectomy and fusion (ACCF) to treat multilevel cervical spondylotic myelopathy (MCSM). METHODS: A total of 117 consecutive patients with MCSM who underwent 1- or 2-level ACCF using a TMC or an n-HA/PA66 cage were studied retrospectively at a mean follow-up of 45.28 ± 12.83 months. The patients were divided into four groups according to the level of corpectomy (1- or 2-level corpectomy) and cage type used (TMC or n-HA/PA66 cage). Clinical and radiological parameters were used to evaluate outcomes. RESULTS: At the one-year follow-up, the fusion rate in the n-HA/PA66 group was higher, albeit non-significantly, than that in the TMC group for both 1- and 2-level ACCF, but the fusion rates of the procedures were almost equal at the final follow-up. The incidence of cage subsidence at the final follow-up was significantly higher in the TMC group than in the n-HA/PA66 group for the 1-level ACCF (24% vs. 4%, p = 0.01), and the difference was greater for the 2-level ACCF between the TMC group and the n-HA/PA66 group (38% vs. 5%, p = 0.01). Meanwhile, a much greater loss of fused height was observed in the TMC group compared with the n-HA/PA66 group for both the 1- and 2-level ACCF. All four groups demonstrated increases in C2-C7 Cobb angle and JOA scores and decreases in VAS at the final follow-up compared with preoperative values. CONCLUSION: The lower incidence of cage subsidence, better maintenance of the height of the fused segment and similar excellent bony fusion indicate that the n-HA/PA66 cage may be a superior alternative to the TMC for cervical reconstruction after cervical corpectomy, in particular for 2-level ACCF.

In this study, we prepared nano-hydroxyapatite/polyamide 66/glass fibre (n-HA/PA66/GF) bioactive bone screws. The microstructure, morphology and coating of the screws were characterised, and the adhesion, proliferation and viability of MC3T3-E1 cells on n-HA/PA66/GF scaffolds were determined using scanning electron microscope, CCK-8 assays and cellular immunofluorescence analysis. The results confirmed that n-HA/PA66/GF scaffolds were biocompatible and had no negative effect on MC3T3-E1 cells in vitro. To investigate the in vivo biocompatibility, internal fixation properties and osteogenesis of the bioactive screws, both n-HA/PA66/GF screws and metallic screws were used to repair intercondylar femur fractures in dogs. General photography, CT examination, micro-CT examination, histological staining and biomechanical assays were performed at 4, 8, 12 and 24 weeks after operation. The n-HA/PA66/GF screws exhibited good biocompatibility, high mechanical strength and extensive osteogenesis in the host bone. Moreover, 24 weeks after implantation, the maximum push-out load of the bioactive screws was greater than that of the metallic screws. As shown by their good cytocompatibility, excellent biomechanical strength and fast formation and ingrowth of new bone, n-HA/PA66/GF screws are thus suitable for orthopaedic clinical applications.