Malicious Tumor? Pathological Fracture of the Femur in Children Caused by Myelolipoma: A Case Report and Review of Literatures.

Myelolipoma is a kind of benign lipoma containing myeloid cells. It is a rare type of tumor that typically presents as an occasional adrenal tumor, generally manifesting as a nonfunctional adrenal mass. Although it can occur in extra-adrenal tissues, its occurrence in bone tissue is extremely rare. Most cases are discovered accidentally during physical examinations of adults, and there are currently no reports of cases with pathological fractures as the main symptoms. We present a case of a 15-year-old teenager who developed a pathological fracture caused by femoral myelolipoma. The diagnosis of the specific type of bone tumor of the patient was determined through pathology and imaging. To treat the condition, we utilized a technique known as the "soft drill" to fully access the tumor space, remove the bone septum, and scrape away the diseased tissue. The fracture was then stabilized using a hybrid external fixation. After a 2-year follow-up period, there was no recurrence of the bone tumor. This case is the first case of intraosseous myelolipoma that occurred in a minor with the initial symptom of pathological fracture, filling the gap in our existing body of knowledge and providing a reference for the treatment of this type of intraosseous myelolipoma.

Analysis of the associated factors in postoperative wound infection following open reduction and internal fixation for elbow fracture.

Postoperative wound infections (PWIs) following open reduction and internal fixation (ORIF) for elbow fractures can significantly affect patient outcomes. Identifying associated risk factors is crucial for improving clinical practices and patient care. A retrospective analysis (June 2020-June 2023) at our institution involved 90 patients who underwent elbow ORIF. Thirty patients developed PWIs (case group), compared to 60 who did not (control group). Variables like anaemia, operation duration, hospital stay, blood loss, body mass index (BMI), age, hypoalbuminemia, smoking status, diabetes mellitus and open fractures were examined. Univariate and multivariate analyses determined the impact of these variables on PWI incidence, with statistical significance set at p < 0.05. The main pathogens identified were Escherichia coli among Gram-negative bacteria (59.46%) and Staphylococcus aureus among Gram-positive bacteria (40.54%). In the univariate analysis, hypoalbuminemia, anaemia, and lifestyle factors such as smoking showed higher prevalence in patients with PWIs. However, age and length of hospital stay did not significantly influence infection rates. The multivariate analysis further elucidated that anaemia, smoking, diabetes mellitus and open fractures were independent, significant predictors of PWIs. These findings highlight the complexity of factors influencing infection risk post-ORIF, underscoring the importance of both individual health conditions and surgical complications in patient outcomes. Anaemia, smoking, diabetes mellitus and open fractures significantly increase the risk of PWI after elbow ORIF. Early identification and management of these risk factors are imperative to reduce infection rates and improve postoperative recovery.

TiRobot-Assisted Percutaneous Cannulated Screw Fixation for Elderly Patients with Fragility Fractures of the Pelvis: A Retrospective Study.

OBJECTIVE: The incidence of fragility fractures of the pelvis (FFPs) is increasing in the elderly population, and FFPs that require fixation are a challenge for orthopedic surgeons. The insertion of implants is not risk free due to the complex anatomical and osteoporotic bones and requires a steep learning curve. This study aimed to investigate the clinical efficacy of TiRobot-assisted percutaneous cannulated screw fixation in the treatment of elderly FFP patients. METHOD: The clinical data of 46 elderly FFP patients who had been treated with percutaneous cannulated screw fixation from May 2020 to September 2022 were retrospectively analyzed. Twenty-four patients were treated with percutaneous cannulated screw fixation assisted by the TiRobot (TiRobot-assisted group) and 22 patients were treated with conventional freehand surgery (freehand group). Postoperative outcomes, including Matta value, excellent and good rate (EGR) of fracture reduction, and accuracy of screw placement (ASP), were compared. Changes in the Visual analog scale (VAS) pain score and the Majeed score were recorded and compared between groups before and after surgery and during the 24-week follow-up. Repeated-measures analysis of variance (ANOVA) and effect sizes were used as analysis methods. RESULTS: A total of 90 screws were implanted, 51 screws in the TiRobot-assisted group and 39 screws in the freehand group. The operation time of the two groups was 34.1 ± 2.67 min versus 64.5 ± 4.19 min (p < 0.001). There were no screw-related complications or revision surgeries in any group. The Matta value of the TiRobot-assisted group was 5.13 ± 3.52, which was significantly lower than that of the freehand group (9.00 ± 3.68, p < 0.001), while the EGR was 91.67% versus 72.73%, with statistical significance (p < 0.001). The ASP was 100% in the TiRobot-assisted group, better than that in the freehand group, where it was 85.7% (p = 0.043). At each timepoint in the early postoperative period, the VAS score of the TiRobot-assisted group was significantly lower than that of the freehand group and was close to consistent by the last follow-up; the Majeed score of the former was significantly higher than that of the latter at each timepoint of follow-up, with statistical significance (p < 0.001). CONCLUSION: TiRobot-assisted percutaneous cannulated screw fixation of elderly FFP patients is advantageous over conventional freehand surgery, with less invasion, more accurate screw placement, better fracture reduction, early pain relief, and rapid recovery, suggesting that Freehand method to stabilize FFP in the elderly population.

Bone-Targeted Biomimetic Nanogels Re-Establish Osteoblast/Osteoclast Balance to Treat Postmenopausal Osteoporosis.

Insufficient bone formation and excessive bone resorption caused by estrogen deficiency are the major factors resulting in the incidence of postmenopausal osteoporosis (PMOP). The existing drugs usually fail to re-establish the osteoblast/osteoclast balance from both sides and generate side-effects owing to the lack of bone-targeting ability. Here, engineered cell-membrane-coated nanogels PNG@mR&C capable of scavenging receptor activator of nuclear factor-κB ligand (RANKL) and responsively releasing therapeutic PTH 1-34 in the bone microenvironment are prepared from RANK and CXCR4 overexpressed bone mesenchymal stem cell (BMSC) membrane-coated chitosan biopolymers. The CXCR4 on the coated-membranes confer bone-targeting ability, and abundant RANK effectively absorb RANKL to inhibit osteoclastogenesis. Meanwhile, the release of PTH 1-34 triggered by osteoclast-mediated acid microenvironment promote osteogenesis. In addition, the dose and frequency are greatly reduced due to the smart release property, prolonged circulation time, and bone-specific accumulation. Thus, PNG@mR&C exhibits satisfactory therapeutic effects in the ovariectomized (OVX) mouse model. This study provides a new paradigm re-establishing the bone metabolic homeostasis from multitargets and shows great promise for the treatment of PMOP.

LncRNA MSTRG.22719.16 mediates the reduction of enoxaparin sodium high-viscosity bone cement-induced thrombosis by targeting the ocu-miR-326-5p/CD40 axis.

OBJECTIVE: Polymethylmethacrylate (PMMA) bone cement promotes the development of local thrombi. Our study found that a novel material, ES-PMMA bone cement, can reduce local thrombosis. We used a simple and reproducible animal model to confirm the reduction in local thrombosis and explored the associated molecular mechanism. METHODS: New Zealand rabbits, which were used to model thrombosis using extracorporeal carotid artery shunts, were divided into the following two groups, with 3 rabbits in each group: the PMMA bone cement group and the ES-PMMA bone cement group. Four hours after modelling, experimental samples, including thrombotic and vascular tissues, were collected. Thrombotic samples from the PMMA group and ES-PMMA group were subjected to lncRNA sequencing, and a lncRNA microarray was used to screen the differentially expressed lncRNAs. The expression of thrombomodulin in endothelial cells was quantified in vascular tissue samples. Differences in the lncRNA expression profiles between the thrombotic samples of the PMMA group and ES-PMMA group were assessed by base-to-base alignment in the intergenic regions of genomes. The lncRNA-miRNA-mRNA competitive endogenous RNA (ceRNA) network was established in light of ceRNA theory. Thrombosis was observed in the PMMA group and ES-PMMA group. RESULTS: The thrombotic weight was 0.00706 ± 0.00136 g/cm in the PMMA group and 0.00551 ± 0.00115 g/cm in the ES-PMMA group. Quantitative real-time polymerase chain reaction (RT-q-CR) and Western blotting revealed that the expression of CD40, which can regulate thrombosis in vascular endothelial cells, was significantly lower in the ES-PMMA group than in the PMMA group. High-throughput sequencing was used to identify 111 lncRNAs with lower expression in the ES-PMMA group than in the PMMA group. Through bioinformatics investigation, lncRNA MSTRG22719.16/ocu-miR-326-5p/CD40 binding sites were selected. Fluorescent in situ RNA hybridization (FISH) was performed to verify the lower expression of lncRNA MSTRG.22719.16 in vascular tissues from the ES-PMMA group. A dual-luciferase reporter gene assay was applied to verify that ocu-miR-326-5p binds the CD40 3'-UTR and targets lncRNA MSTRG.22719.16. CONCLUSION: Compared with PMMA bone cement, ES-PMMA bone cement can reduce thrombosis through the lncRNA MSTRG.22719.16/ocu-miR-326-5p/CD40 axis.

ATF2-driven osteogenic activity of enoxaparin sodium-loaded polymethylmethacrylate bone cement in femoral defect regeneration.

BACKGROUND: Polymethylmethacrylate (PMMA) bone cement loaded with enoxaparin sodium (PMMA@ES) has been increasingly highlighted to affect the bone repair of bone defects, but the molecular mechanisms remain unclear. We addressed this issue by identifying possible molecular mechanisms of PMMA@ES involved in femoral defect regeneration based on bioinformatics analysis and network pharmacology analysis. METHODS: The upregulated genes affecting the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) were selected through bioinformatics analysis, followed by intersection with the genes of ES-induced differentiation of BMSCs identified by network pharmacology analysis. PMMA@ES was constructed. Rat primary BMSCs were isolated and cultured in vitro in the proliferation medium (PM) and osteogenic medium (OM) to measure alkaline phosphatase (ALP) activity, mineralization of the extracellular matrix, and the expression of RUNX2 and OCN using gain- or loss-of-function experiments. A rat femoral bone defect model was constructed to detect the new bone formation in rats. RESULTS: ATF2 may be a key gene in differentiating BMSCs into osteoblasts. In vitro cell assays showed that PMMA@ES promoted the osteogenic differentiation of BMSCs by increasing ALP activity, extracellular matrix mineralization, and RUNX2 and OCN expression in PM and OM. In addition, ATF2 activated the transcription of miR-335-5p to target ERK1/2 and downregulate the expression of ERK1/2. PMMA@ES induced femoral defect regeneration and the repair of femoral defects in rats by regulating the ATF2/miR-335-5p/ERK1/2 axis. CONCLUSION: The evidence provided by our study highlighted the ATF2-mediated mechanism of PMMA@ES in the facilitation of the osteogenic differentiation of BMSCs and femoral defect regeneration.

Enoxaparin sodium bone cement displays local anti-inflammatory effects by regulating the expression of IL-6 and TNF-α.

Objective: To explore the roles of Enoxaparin Sodium-Polymethyl methacrylate bone cement on inflammatory factors Interleukin-6 and Tumour Necrosis Factor-α in a rabbit knee replacement model. As well as the mechanisms underlying its potential effects on lipopolysaccharide-induced endothelial cell injury. Methods: A knee replacement model was established using New Zealand rabbits. Forty rabbits were randomly divided into four groups: PMMA, ES-PMMA, sham-operated, and blank control groups (n = 10 in each group). Local tissues around the incision were taken at the 30th, 60th, and 90th minute after the surgical implantation of the corresponding bone cement. Immunohistochemistry in the surgical field was used to measure the expression of local inflammatory factors IL-6 and TNF-α. In the in vitro experiments, 1 cm3 of bone cement was immersed in 3 mL of the medium for 24 h. The bone cement was discarded and diluted to 25% with normal medium. Pre-experiments were screened for the best LPS-inducing concentration of 100 mg/mL, and the most compatible LPS concentration was used for subsequent experiments simulating the primary cultures of rats' Inferior Vena Cava Endothelial Cells. The experiments were divided into four groups: blank control group, LPS induction group, PMMA + LPS group, and ES-PMMA + LPS group. The apoptosis rate was detected by flow cytometry, and the expression levels of TNF-α and IL-6 in the cells and supernatant were measured by ELISA, western blotting, and immunofluorescence. Results: According to immunohistochemical results, IL-6-positive cells were concentrated in the tissue interstitial space. In the PMMA and sham-operated groups, the number of IL-6-positive cells gradually increased over time. At all time points, IL-6 expression in the ES-PMMA group was much lower than in the PMMA and sham-operated groups. At 30 min, TNF-α positive cells in the ES-PMMA group expressed less than those in the PMMA and sham-operated groups, with no discernible difference between the PMMA and ES-PMMA groups at 60 or 90 min. Using ELISA and flow cytometry, the expression levels of IL-6 and TNF-α were improved and the apoptosis rate was magnified in the LPS-induced group (***P < 0.001) in contrast with the blank control group. Additionally, the expression levels of IL-6 and TNF-α were reduced in the ES-PMMA + LPS group compared with the LPS-induced group (*P < 0.05) and the apoptosis rate was reduced (***P < 0.001), with statistically significant variations. Western blotting and immunofluorescence analysis confirmed that IL-6 and TNF-α protein expression in cells was upregulated in the LPS-induced group compared to the blank control group (***P < 0.001), and the mean fluorescence intensity was enlarged (***P < 0.001). Meanwhile, IL-6 and TNF-α expression in the ES-PMMA + LPS group were down-regulated (**P < 0.01 or *P < 0.05) compared with the LPS-induced group and PMMA + LPS crew protein expression, and the average fluorescence intensity of IL-6 and TNF-α was lowered in the ES-PMMA + LPS group compared to the LPS-induced group (***P < 0.001). Conclusions: ES-PMMA bone cement reduced the expression levels of local inflammatory factors IL-6 and TNF-α in a rabbit knee model. ES-PMMA bone cement reduced the rate of LPS-induced endothelial cell apoptosis and diminished local inflammatory damage by regulating the secretion of inflammatory factors TNF-α and IL-6.

Enoxaparin sodium bone cement plays an anti-inflammatory immunomodulatory role by inducing the polarization of M2 macrophages.

OBJECTIVE: The implantation of PMMA bone cement results in an immune response and the release of PMMA bone cement particles causes an inflammatory cascade. Our study discovered that ES-PMMA bone cement can induce M2 polarization of macrophages, which has an anti-inflammatory immunomodulatory effect. We also delved into the molecular mechanisms that underlie this process. METHODS: In this study, we designed and prepared samples of bone cement. These included PMMA bone cement samples and ES-PMMA bone cement samples, which were implanted into the back muscles of rats. At 3, 7, and 14 days after the operation, we removed the bone cement and a small amount of surrounding tissue. We then performed immunohistochemistry and immunofluorescence to observe the polarization of macrophages and the expression of related inflammatory factors in the surrounding tissues. The RAW264.7 cells were exposed to lipopolysaccharide (LPS) for 24 h to establish the macrophage inflammation model. Then, each group was treated with enoxaparin sodium medium, PMMA bone cement extract medium, and ES-PMMA bone cement extract medium, respectively, and cultured for another 24 h. We collected cells from each group and used flow cytometry to detect the expressions of CD86 and CD206 in macrophages. Additionally, we performed RT-qPCR to determine the mRNA levels of three markers of M1 macrophages (TNF-α, IL-6, iNOS) and two M2 macrophage markers (Arg-1, IL-10). Furthermore, we analyzed the expression of TLR4, p-NF-κB p65, and NF-κB p65 through Western blotting. RESULTS: The immunofluorescence results indicate that the ES-PMMA group exhibited an upregulation of CD206, an M2 marker, and a downregulation of CD86, an M1 marker, in comparison to the PMMA group. Additionally, the immunohistochemistry results revealed that the levels of IL-6 and TNF-α expression were lower in the ES-PMMA group than in the PMMA group, while the expression level of IL-10 was higher in the ES-PMMA group. Flow cytometry and RT-qPCR analyses revealed that the expression of M1-type macrophage marker CD86 was significantly elevated in the LPS group compared to the NC group. Additionally, M1-type macrophage-related cytokines TNF-α, IL-6, and iNOS were also found to be increased. However, in the LPS + ES group, the expression levels of CD86, TNF-α, IL-6, and iNOS were decreased, while the expression of M2-type macrophage markers CD206 and M2-type macrophage-related cytokines (IL-10, Arg-1) were increased compared to the LPS group. In comparison to the LPS + PMMA group, the LPS + ES-PMMA group demonstrated a down-regulation of CD86, TNF-α, IL-6, and iNOS expression levels, while increasing the expression levels of CD206, IL-10, and Arg-1. Western blotting results revealed a significant decrease in TLR4/GAPDH and p-NF-κB p65/NF-κB p65 in the LPS + ES group when compared to the LPS group. Additionally, the LPS + ES-PMMA group exhibited a decrease in TLR4/GAPDH and p-NF-κB p65/NF-κB p65 levels when compared to the LPS + PMMA group. CONCLUSION: ES-PMMA bone cement is more effective than PMMA bone cement in down-regulating the expression of the TLR4/NF-κB signaling pathway. Additionally, it induces macrophages to polarize towards the M2 phenotype, making it a crucial player in anti-inflammatory immune regulation.

Lateral locking plate plus antero-posterior lag screws techniques for the management of posterolateral tibial plateau fracture: preliminary clinical results and biomechanical study.

INTRODUCTION: To date, there is no consensus on the optimal surgical strategy for the treatment of posterolateral tibial plateau fracture (PLF). This study introduced a novel, simple technique for treating PLF with a lateral locking plate plus antero-posterior lag screws (LPpLS). METHODS: We conducted a retrospective case series of 42 patients (Female/Male 19/23) with PLF treated with LPpLS between 1 July 2016 and 30 June 2019. Several pre- and postoperative outcomes were recorded, including operative time, intraoperative blood loss, CT findings, HSS, and ROM. For biomechanical studies, seventy synthetic tibiae with a simulated posterolateral split fracture were divided into seven groups. The biomechanical evaluation included displacement measurement at axial compression and fatigue testing. RESULTS: Forty-two eligible patients were followed up for an average of 18 months (range 14-21 months). Postoperative radiographs and CT showed good positioning of plates and screws, no fracture fragment loss, and normal articular surfaces in all 42 cases. The biomechanical study showed that the axial stiffness of LPpLS was in the same fashion as the posterior buttress plate and better than the other fixation methods (P < 0.05). Additionally, the LPpLS group had a smaller displacement of fracture fragments along the X-axis (medial to lateral direction) than the BP group (P < 0.01). CONCLUSIONS: The LPpLS technique could implement good reconstruction of the PLF, showing satisfactory therapeutic effect. The biomechanical evaluation demonstrated that the LPpLS had better stability in three-dimensional directions for PLF than other fixation strategies.

Cement Leakage in Vertebral Compression Fractures Between Unilateral and Bilateral Percutaneous Vertebral Augmentation: A Meta-Analysis.

AIM: Cement leakage remains a significant clinical problem associated with vertebroplasty and kyphoplasty procedures, with uncontrolled cement flow in the posterior direction causing leakage into the vertebral veins or spinal canal that leads to potentially serious clinical complications. This meta-analysis compared the incidences of cement leakage between unilateral and bilateral percutaneous vertebral augmentation (PVA) in the treatment of osteoporosis vertebral compression fractures. MATERIAL AND METHODS: Pertinent studies were identified by a search of the PubMed, Embase, and Web of Science databases up to December 2020. The risk ratio (RR) or weighted mean difference (WMD) was applied to combine the results, and a random-effects or a fixed-effects model was used to pool the results depending on the heterogeneity among studies. Publication bias was estimated using Egger's regression asymmetry test. RESULTS: A total of 16 trials (including 9 RCTs and 7 cohort studies) met the inclusion criteria and were included in this meta-analysis. The incidences of cement leakage were similar between the bilateral PVA and unilateral PVA groups (RR = 0.80, 95%CI: 0.57, 1.11; P = 0.182) but unilateral PVA required less cement volume (WMD = -1.34 ml, 95%CI: -1.87, -0.81; P 0.001). Subgroup analysis revealed that the incidence of cement leakage was significantly lower in the unilateral PKP group than in the bilateral PKP group (RR = 0.65, 95%CI: 0.44, 0.97; P = 0.034). CONCLUSION: The incidences of cement leakage were similar between unilateral and bilateral PVA, but unilateral PVA required less cement. More large-scale studies are needed to verify our findings.

Bone healing study of alendronate combined with enoxaparin sodium bone cement in rabbits with bone defects.

BACKGROUND: To observe the effect of enoxaparin sodium-polymethyl methacrylate (ES-PMMA) bone cement supplemented with alendronate (AN) on bone repair of bone defects in New Zealand rabbits. METHODS: Twenty-seven New Zealand rabbits were randomly divided into ES/AN, ES-PMMA and PMMA groups, with a total of 27 New Zealand rabbits. The drugs loaded in 40 g bone cement powder were as follows: ES/AN group 8000 AxaIU enoxaparin (ES) and 200 mg alendronate (AN), ES-PMMA group 8000 AxaIU enoxaparin (ES), PMMA group without drugs. A bone defect model with a length of 10 mm and a diameter of 5 mm was made from the left tibia of rabbits, and the prepared bone cement was placed in the tibia defect. At 4 weeks, 8 weeks and 12 weeks after the operation, 3 rabbits in each group were sacrificed, and left tibia samples were collected for histological scoring, HE staining and Masson staining. Bone mineral density and new bone volume were measured by imaging, and the related data were processed by one-way ANOVA and least significance difference (LSD) post hoc test. RESULTS: (1) Bone mineral density (BMD, mg/mm3) around the bone defect: at the 4th week, BMD in the ES/AN group was higher than that in the PMMA group; at the 8th week, the BMD in the ES/AN group was significantly higher than that in the other two groups; and at the 12th week, the BMD in the ES/AN group was significantly higher than that in the other two groups. (2) New bone volume (BV, mm3): at the 4th week, BV in the ES/AN group was significantly higher than that in the other two groups, BV in the ES/AN group was significantly higher than that in the other two groups at the 8th and 12th weeks, and BV in the ES-PMMA group was higher than that in the PMMA group. (3) Histological score: at the 4th and 8th weeks, the histological score of the ES/AN group was higher than that of the PMMA group, and at the 12th week, the histological score of the ES/AN group was higher than that of the other two groups. (4) Cortical bone thickness (µm): at the 4th, 8th and 12th weeks, the cortical bone thickness in the ES/AN group was higher than that in the other two groups, and the cortical bone thickness in the ES-PMMA group was higher than that in the PMMA group. (5) The percentage of mature area of new bone in the ES/AN group was higher than that in the other two groups at the 4th week, and at the 8th and 12th weeks, the percentage of mature area of new bone in the ES/AN group and ES-PMMA group was significantly higher than that in the PMMA group. CONCLUSION: (1) Enoxaparin sodium bone cement supplemented with alendronate was superior to enoxaparin sodium bone cement and PMMA bone cement in promoting bone repair of tibial bone defects in New Zealand rabbits. (2) Enoxaparin sodium bone cement is superior to PMMA bone cement in promoting bone repair, showing a certain osteogenic potential.

Bioinspired Nanovesicles Convert the Skeletal Endothelium-Associated Secretory Phenotype to Treat Osteoporosis.

Recently, bone marrow endothelial cells (BMECs) were found to play an important role in regulating bone homeostasis. However, few studies utilized BMECs to treat bone metabolic diseases including osteoporosis. Here, we reported bioinspired nanovesicles (BNVs) prepared from human induced pluripotent stem cells-derived endothelial cells under hypoxia culture through an extrusion approach. Abundant membrane C-X-C motif chemokine receptor 4 conferred these BNVs bone-targeting ability and the endothelial homology facilitated the BMEC tropism. Due to their unique endogenous miRNA cargos, these BNVs re-educated BMECs to secret cytokines favoring osteogenesis and anti-inflammation. Owing to the conversion of secretory phenotype, the osteogenic differentiation of bone mesenchymal stem cells was facilitated, and the M1-macrophage-dominant pro-inflammatory microenvironment was ameliorated in osteoporotic bones. Taken together, this study proposed BMEC-targeting nanovesicles treating osteoporosis via converting the skeletal endothelium-associated secretory phenotype.

Biomechanical evaluation of percutaneous cement discoplasty by finite element analysis.

BACKGROUND: Percutaneous cement discoplasty (PCD) is a minimally invasive treatment for degenerative lumbar spine disease, but the relationship between decompression effect on the nerve root and different doses of bone cement is uncertain. PURPOSE: To investigate the indirect decompression effect of cement with different doses on nerve roots and the biomechanical changes on the spine during PCD using finite element analysis (FEA). METHODS: FEA was adapted to analyze the mechanical changes in the lumbar vertebrae before and after the application of PCD.CT scan images of adult males were utilized to establish a finite element model of the lumbar vertebral body using mimics and Pro/E software. The images were divided into four models: the normal model (normal, model N), the disc degeneration model (high, model H), the intervertebral disc injected with 3 mL of bone cement (model H1), and the intervertebral disc injected with 5 mL of bone cement (model H2). All models were analyzed using the ABAQUS6.14.2 software. The normal physiological movements were simulated, and the mechanical changes in the lumbar vertebrae were observed prior to and after the cement filling application. RESULTS: The stress of the nerve root in model H was the largest. The nerve root stress in the model H2 was the smallest during flexion, extension, left bending, right bending, left rotation, and right rotation at 90%, 44%, 25%, 56%, 56%, and 51% of the normal benchmark, respectively. After the injection of bone cement, the nerve root stress is reduced. The greater the amount of cement, the lesser the nerve root stress. The motion was reduced in models H, H1, and H2, and there were differences between models H1 and H2. Cartilage endplate stress was less in model H2 than in model H1. CONCLUSIONS: The nerve root stress increased after degeneration and decreased after intervertebral height recovery through cement injection, resulting in a significant indirect decompression effect.The stress of the nerve root decreased with the increase in the amount of cement injection.

The mechanism by which enoxaparin sodium-high-viscosity bone cement reduces thrombosis by regulating CD40 expression in endothelial cells.

OBJECTIVE: PMMA bone cement leads to the development of local thrombi. Our study found that ES-PMMA bone cement, a novel material, can reduce local thrombosis. We used a simple and reproducible animal model to confirm the reduction in local thrombosis and preliminarily explored the associated molecular mechanism. METHODS: New Zealand rabbits, which were used to model thrombosis using extracorporeal carotid artery shunts, were divided into the following three groups, with 10 rabbits in each group: the sham group, PMMA group and ES-PMMA group. Four hours after modelling, experimental samples were collected, and the degree of thrombosis was compared between the groups. The expression of thrombomodulin in endothelial cells was quantified in vascular tissues samples. RESULTS: Thrombosis was observed in the PMMA group and ES-PMMA group but not in the sham group. The thrombosis weight was 0.00732 ± 0.00089 g/cm in the PMMA group and 0.00554 ± 0.00077 g/cm in the ES-PMMA group (P < 0.001). Quantitative real-time polymerase chain reaction (RT-qPCR) and Western blotting revealed that the expression of CD40, which can regulate thrombosis in vascular endothelial cells, was significantly lower in the ES-PMMA group than in the PMMA group. CONCLUSION: Compared with PMMA bone cement, ES-PMMA bone cement can reduce local thrombosis by decreasing the expression of the thrombus-associated regulatory protein CD40 in vascular endothelial cells.

Impact of sarcopenia and sagittal parameters on the residual back pain after percutaneous vertebroplasty in patients with osteoporotic vertebral compression fracture.

OBJECTIVE: The objective of this study was to explore the impact of sarcopenia and sagittal parameters on the residual back pain (RBP) after percutaneous vertebroplasty (PVP) for treatment of osteoporotic vertebral compression fracture (OVCF). METHODS: This retrospective study included elderly patients (age range 60-90 years) with OVCF treated with PVP from January 2015 and December 2020 in our hospital. The skeletal muscle mass index (SMI) was calculated by dividing the T12 pedicle level muscle cross-sectional area by the square of body height from chest CT to diagnose sarcopenia. The radiological parameters for measuring the sagittal alignment were included: C7-sagittal vertical axis (SVA), T1 pelvic angle (TPA), lumbar lordosis (LL), thoracic kyphosis (TK), pelvic tilt (PT), sacral slope (SS), pelvic incidence (PI). RESULT: According to whether the VAS score > 4, patients were divided into RBP group (56 patients) and Control group (100 patients). There was no difference in age, gender, body mass index, BMD, surgical segment, bone cement usage between the groups (P > 0.05). The SMI in RBP group (27.3 ± 5.1) was significantly lower compared to that in Control group (36.8 ± 3.2) (P < 0.05). Sarcopenia was present in 19 patients (20.3%) in RBP group, which was significantly more than that in Control group (P < 0.05). C7-SVA and TPA was significantly larger in the RBP group than in the Control group (P < 0.05). PI and LL was significantly smaller in the RBP group compared to the Control group (P < 0.05). However, no significant differences between the two groups with respect to TK, SS and PT (P > 0.05). CONCLUSION: Poor sagittal parameters and sarcopenia in OVCF patients after PVP were more prone to residual back pain. Larger C7-SVA, TPA and PI-LL mismatch could increase the incidence of RBP in elderly patients with single-segment osteoporotic compression fractures.

Release characteristics of enoxaparin sodium-loaded polymethylmethacrylate bone cement.

BACKGROUND: This study aimed to prepare the polymethylmethacrylate (PMMA) bone cement release system with different concentrations of enoxaparin sodium (ES) and to investigate the release characteristics of ES after loading into the PMMA bone cement. METHODS: In the experimental group, 40 g Palacos®R PMMA bone cement was loaded with various amount of ES 4000, 8000, 12,000, 16,000, 20,000, and 24,000 AXaIU, respectively. The control group was not loaded with ES. Scanning electron microscopy (SEM) was used to observe the surface microstructure of the bone cement in the two groups. In the experiment group, the mold was extracted continuously with pH7.4 Tris-HCL buffer for 10 days. The extract solution was collected every day and the anti-FXa potency was measured. The experiment design and statistical analysis were conducted using a quantitative response parallel line method. RESULTS: Under the SEM, it was observed that ES was filled in the pores of PMMA bone cement polymer structure and released from the pores after extraction. There was a burst effect of the release. The release amount of ES on the first day was 0.415, 0.858, 1.110, 1.564, 1.952, and 2.513, respectively, from the six groups with various ES loading amount of 4000, 8000, 12,000, 16,000, 20,000, and 24,000 AXaIU, all reaching the peak of release on the first day. The release decreased rapidly on the next day and entered the plateau phase on the fourth day. CONCLUSION: The prepared ES-PMMA bone cement has high application potential in orthopedic surgery. ES-PMMA bone cement shows good drug release characteristics. The released enoxaparin sodium has a local anti-coagulant effect within 24 h after application, but it will not be released for a long time, which is complementary to postoperative anti-coagulation therapy.

Lumbar degenerative disease after oblique lateral interbody fusion: sagittal spinopelvic alignment and its impact on low back pain.

BACKGROUND: We determined the incidence and risk factors of low back pain (LBP) in patients with lumbar degenerative disease after single-level oblique lateral interbody fusion (OLIF). METHODS: We retrospectively reviewed 120 lumbar degenerative disease patients who underwent single-level OLIF. We compared preoperative and postoperative radiographic parameters, including segmental lordosis (SL), lumbar lordosis (LL), disk height (DH), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), thoracic kyphosis (TK), and C7-sagittal vertical axis (SVA). Clinical outcomes were evaluated using the Oswestry Disability Index (ODI) scores and visual analog scale (VAS) scores for back and leg pain. All patients were followed up for at least 2 years. RESULTS: Thirty-eight patients had postoperative LBP (VAS score for back pain ≥3; LBP group); the remaining 82 patients were in the non-LBP group. Age (P = 0.082), gender (P = 0.425), body mass index (P = 0.138), diagnosis (degenerative spondylolisthesis vs. lumbar spinal stenosis; P = 0.529), surgical level (P = 0.651), blood loss (P = 0.889), and operative time (P = 0.731) did not differ between the groups. In both groups, the ODI and VAS scores for back pain and leg pain significantly improved at the final follow-up compared with the preoperative scores (P = 0.003). Except for the VAS score for back pain (P = 0.000), none of the scores significantly differed between the two groups at the final follow-up (P > 0.05). In the non-LBP group, LL, SL, DH, TK, and SS significantly improved, while PT and C7-SVA significantly decreased at the final follow-up as compared with the preoperative values. In both groups, DH significantly improved postoperatively, with no significant between-group difference (P = 0.325). At the final follow-up, LL, PI-LL mismatch, PT, and C7-SVA showed significantly greater improvement in the non-LBP group than in the LBP group (P < 0.05). Multivariate analysis identified PT, PI-LL mismatch, and C7-SVA as significant risk factors for LBP after OLIF. CONCLUSION: OLIF for single-level lumbar degenerative disease had satisfactory clinical outcomes. PT, PI-LL mismatch, and C7-SVA were significant risk factors for postoperative LBP. Patients with appropriately decreased PT, improved C7-SVA, and PI-LL match experienced less LBP.

Role of miR-199a-5p in osteoblast differentiation by targeting TET2.

OBJECTIVE: miR-199a-5p was increased during osteoblast differentiation, which may target and regulate TET2, a gene attracted a lot of attention in the osteoblast differentiation in the past few years. However, the role of miR-199a-5p in osteoblast differentiation by targeting TET2 is not established. METHODS: The correlation between miR-199a-5p and TET2 was verified through dual luciferase reporter assay, and their expressions in human bone marrow stromal cells (hBMSCs) during the osteoblast differentiation were detected. hBMSCs were transfected with TET2 siRNA, miR-199a-5p mimic or/and TET2 CRISPR activation plasmid., and then prepared for the induction of osteoblast differentiation, followed by alkaline phosphatase (ALP) and alizarin red staining, qRT-PCR and Western blotting. In vivo, ovariectomized (OVX) mice were injected with agomir-miR-199a-5p, antagomiR-199a-5p or/and TET2 siRNA to calculate the BMD and BV/TV ratio of mice, as well as to measure the expressions of osteogenesis-related genes in bone tissues. RESULTS: A gradual increase of miR-199a-5p was observed in hBMSCs during the induction of osteoblast differentiation, while TET2 expression was decreased. Besides, miR-199a-5p was reduced in the bone tissue of OVX mice, while TET2 was up-regulated. In addition, overexpression of miR-199a-5p and inhibition of TET2 augmented ALP activity in hBMSCs, with the enhanced calcification and the up-regulated expressions of Runx2, OSX and OCN, which also increased the quality of bone in OVX mice accompanying the enhancement BV/TV ratio, BMD and osteogenesis-related genes. CONCLUSION: MiR-199a-5p may promote the osteoblast differentiation and prevent OVX-induced osteoporosis by targeting TET2.

CCL28 promotes locomotor recovery after spinal cord injury via recruiting regulatory T cells.

BACKGROUND: Chemokines play a key role in post-traumatic inflammation and secondary injury after spinal cord injury (SCI). CCL28, the chemokine CC-chemokine ligand 28, is involved in the epithelial and mucosal immunity. However, whether CCL28 participates in the physiopathologic processes after SCI remains unclear. RESULTS: CCL28 is upregulated in the spinal cord after SCI. In addition, neutralizing antibodies against IL-1ß or TNF-α, or treatment of ML120B, a selective inhibitor of IKK-ß, remarkably decrease CCL28 upregulation, suggesting that CCL28 upregulation relies on NF-κB pathway activated by IL-1ß and TNF-α after SCI. Moreover, CD4+CD25+FOXP3+ regulatory T (Treg) cells that express CCR10, a receptor of CCL28, are enriched in the spinal cord after SCI. We further demonstrate that the spinal cord recruits Treg cells through CCL28-CCR10 axis, which in turn function to suppress immune response and promote locomotor recovery after SCI. In contrast, neutralizing CCL28 or CCR10 reduces Treg cell recruitment and delays locomotor recovery. METHODS: The neutralizing antibodies and recombinant CCL28 were injected intraspinally into the mice prior to SCI, which was established via hemitransection. RT-qPCR analysis was performed to determine transcript level, and Western blot analysis and ELISA assay were used to detect protein expression. Immune cells were analyzed by flow cytometry and visualized by immunofluorescence. The chemotaxis was assessed by in vitro transwell migration assay. The mouse locomotor activity was assessed via the Basso Mouse Scale (BMS) system. CONCLUSIONS: These results indicate that NF-κB pathway-regulated CCL28 production plays a protective role after SCI through recruiting CCR10-expressing and immunosuppressive Treg cells, and suggest that interfering CCL28-CCR10 axis might be of potential clinical benefit in improving SCI recovery.

Benefits and Risks of Subsection Laminectomy with Pedicle Screw Fixation for Ossification of the Ligamentum Flavum of the Thoracic Spine: A Retrospective Study of 30 Patients.

BACKGROUND This study aimed to evaluate the effectiveness of subsection laminectomy with pedicle screw fixation (SLPF) for the treatment of ossification of the ligamentum flavum of the thoracic spine. MATERIAL AND METHODS Thirty patients (age, 40-71 years) with ossification of the ligamentum flavum of the thoracic spine underwent SLPF (13 men, 17 women). Operative time, intraoperative blood loss, preoperative and postoperative change in thoracic kyphosis, and perioperative complications were recorded. The Japanese Orthopedic Association (JOA) score for severity of myelopathy and the American Spinal Injury Association (ASIA) motor and sensory impairment scale were used before and after surgery. RESULTS Mean operative time for SLPF was 208.4±38.3 min and mean intraoperative blood loss was 689.3±171.7 ml. The mean JOA score significantly increased from 5.7±1.9 before surgery to 8.8±2.2 at one month after surgery and 9.3±2.7 at the last follow-up (P<0.01). Postoperative improvement in neurological function increased by 68.3±14.4%. The postoperative ASIA grades significantly improved compared with the preoperative grades (P<0.01). The mean local Cobb angle significantly decreased from 17.8±4.3° before surgery to 15.4±3.6° at one month after surgery and 15.8±3.8° at the last follow-up (P<0.01). Three patients (10%) had operative cerebrospinal fluid (CSF) leak. Postoperatively, one patient had neurological deterioration, two patients had deep venous thrombosis (DVT), and one patient developed a wound infection. CONCLUSIONS SLPF was an effective procedure for the treatment of ossification of the ligamentum flavum of the thoracic spine.