Multi-omics Analysis to Identify Key Immune Genes for Osteoporosis based on Machine Learning and Single-cell Analysis.

OBJECTIVE: Osteoporosis is a severe bone disease with a complex pathogenesis involving various immune processes. With the in-depth understanding of bone immune mechanisms, discovering new therapeutic targets is crucial for the prevention and treatment of osteoporosis. This study aims to explore novel bone immune markers related to osteoporosis based on single-cell and transcriptome data, utilizing bioinformatics and machine learning methods, in order to provide novel strategies for the diagnosis and treatment of the disease. METHODS: Single cell and transcriptome data sets were acquired from Gene Expression Omnibus (GEO). The data was then subjected to cell communication analysis, pseudotime analysis, and high dimensional WGCNA (hdWGCNA) analysis to identify key immune cell subpopulations and module genes. Subsequently, ConsensusClusterPlus analysis was performed on the key module genes to identify different diseased subgroups in the osteoporosis (OP) training set samples. The immune characteristics between subgroups were evaluated using Cibersort, EPIC, and MCP counter algorithms. OP's hub genes were screened using 10 machine learning algorithms and 113 algorithm combinations. The relationship between hub genes and immunity and pathways was established by evaluating the immune and pathway scores of the training set samples through the ESTIMATE, MCP-counter, and ssGSEA algorithms. Real-time fluorescence quantitative PCR (RT-qPCR) testing was conducted on serum samples collected from osteoporosis patients and healthy adults. RESULTS: In OP samples, the proportions of bone marrow-derived mesenchymal stem cells (BM-MSCs) and neutrophils increased significantly by 6.73% (from 24.01% to 30.74%) and 6.36% (from 26.82% to 33.18%), respectively. We found 16 intersection genes and four hub genes (DND1, HIRA, SH3GLB2, and F7). RT-qPCR results showed reduced expression levels of DND1, HIRA, and SH3GLB2 in clinical blood samples of OP patients. Moreover, the four hub genes showed positive correlations with neutrophils (0.65-0.90), immature B cells (0.76-0.92), and endothelial cells (0.79-0.87), while showing negative correlations with myeloid-derived suppressor cells (negative 0.54-0.73), T follicular helper cells (negative 0.71-0.86), and natural killer T cells (negative 0.75-0.85). CONCLUSION: Neutrophils play a crucial role in the occurrence and development of osteoporosis. The four hub genes potentially inhibit metabolic activities and trigger inflammation by interacting with other immune cells, thereby significantly contributing to the onset and diagnosis of OP.

pH-Responsive Mesoporous Silica Nanoparticles Loaded with Naringin for Targeted Osteoclast Inhibition and Bone Regeneration.

Background: It is well-established that osteoclast activity is significantly influenced by fluctuations in intracellular pH. Consequently, a pH-sensitive gated nano-drug delivery system represents a promising therapeutic approach to mitigate osteoclast overactivity. Our prior research indicated that naringin, a natural flavonoid, effectively mitigates osteoclast activity. However, naringin showed low oral availability and short half-life, which hinders its clinical application. We developed a drug delivery system wherein chitosan, as gatekeepers, coats mesoporous silica nanoparticles loaded with naringin (CS@MSNs-Naringin). However, the inhibitory effects of CS@MSNs-Naringin on osteoclasts and the underlying mechanisms remain unclear, warranting further research. Methods: First, we synthesized CS@MSNs-Naringin and conducted a comprehensive characterization. We also measured drug release rates in a pH gradient solution and verified its biosafety. Subsequently, we investigated the impact of CS@MSNs-Naringin on osteoclasts induced by bone marrow-derived macrophages, focusing on differentiation and bone resorption activity while exploring potential mechanisms. Finally, we established a rat model of bilateral critical-sized calvarial bone defects, in which CS@MSNs-Naringin was dispersed in GelMA hydrogel to achieve in situ drug delivery. We observed the ability of CS@MSNs-Naringin to promote bone regeneration and inhibit osteoclast activity in vivo. Results: CS@MSNs-Naringin exhibited high uniformity and dispersity, low cytotoxicity (concentration≤120 µg/mL), and significant pH sensitivity. In vitro, compared to Naringin and MSNs-Naringin, CS@MSNs-Naringin more effectively inhibited the formation and bone resorption activity of osteoclasts. This effect was accompanied by decreased phosphorylation of key factors in the NF-κB and MAPK signaling pathways, increased apoptosis levels, and a subsequent reduction in the production of osteoclast-specific genes and proteins. In vivo, CS@MSNs-Naringin outperformed Naringin and MSNs-Naringin, promoting new bone formation while inhibiting osteoclast activity to a greater extent. Conclusion: Our research suggested that CS@MSNs-Naringin exhibited the strikingly ability to anti-osteoclasts in vitro and in vivo, moreover promoted bone regeneration in the calvarial bone defect.

Analysis of cartilage loading and injury correlation in knee varus deformity.

Knee varus (KV) deformity leads to abnormal forces in the different compartments of the joint cavity and abnormal mechanical loading thus leading to knee osteoarthritis (KOA). This study used computer-aided design to create 3-dimensional simulation models of KOA with varying varus angles to analyze stress distribution within the knee joint cavity using finite element analysis for different varus KOA models and to compare intra-articular loads among these models. Additionally, we developed a cartilage loading model of static KV deformity to correlate with dynamic clinical cases of cartilage injury. Different KV angle models were accurately simulated with computer-aided design, and the KV angles were divided into (0°, 3°, 6°, 9°, 12°, 15°, and 18°) 7 knee models, and then processed with finite element software, and the Von-Mises stress distribution and peak values of the cartilage of the femoral condyles, medial tibial plateau, and lateral plateau were obtained by simulating the human body weight in axial loading while performing the static extension position. Finally, intraoperative endoscopy visualization of cartilage injuries in clinical cases corresponding to KV deformity subgroups was combined to find cartilage loading and injury correlations. With increasing varus angle, there was a significant increase in lower limb mechanical axial inward excursion and peak Von-Mises stress in the medial interstitial compartment. Analysis of patients' clinical data demonstrated a significant correlation between varus deformity angle and cartilage damage in the knee, medial plateau, and patellofemoral intercompartment. Larger varus deformity angles could be associated with higher medial cartilage stress loads and increased cartilage damage in the corresponding peak stress area. When the varus angle exceeds 6°, there is an increased risk of cartilage damage, emphasizing the importance of early surgical correction to prevent further deformity and restore knee function.

Reversing Ferroptosis Resistance in Breast Cancer via Tailored Lipid and Iron Presentation.

Ferroptotic cancer therapy is promising in many scenarios where traditional cancer therapies show a poor response. However, certain types of cancers lack the long-chain acyl-CoA synthetase 4 (ACSL4), a key modulator of ferroptosis, resulting in therapy resistance and tumor relapse. Because ACSL4 is in charge of the synthesis of ferroptotic lipids (e.g., arachidonoylphosphatidylethanolamine/PE-AA), we postulated that direct delivery of PE-AA may reverse ferroptosis resistance induced by ACSL4 deficiency. To further increase the ferroptosis sensitivity, we employed the ferrocene-bearing polymer micelles to co-load PE-AA with an FDA-approved redox modulator, auranofin (Aur), targeting the thioredoxin reductase. The presence of ferrocene enabled triggered cargo release and iron production, which can sensitize ferroptosis by boosting autoxidation-mediated PE-AA peroxidation. The micellar system could impair redox homeostasis and induce lipid peroxidation in ACSL4-deficient MCF-7 cells. Moreover, the tailored micelles potently induced ferroptosis in MCF-7 tumors in vivo, suppressed tumor growth, and increased the mice's survival rate. The current work provides a facile means for reversing the ferroptosis resistance in ACSL4-deficient tumors.

Brain structural correlates of postoperative axial pain in degenerative cervical myelopathy patients following posterior cervical decompression surgery: a voxel-based morphometry study.

OBJECTIVE: To investigate the brain structural correlates of postoperative axial pain (PAP) in degenerative cervical myelopathy (DCM) following posterior cervical decompression surgery. METHODS: Structural images with high-resolution T1 weighting were collected from 62 patients with DCM and analyzed, in addition to 42 age/gender matched subjects who were healthy. Voxel-based morphometry (VBM) was analyzed, grey matter volume (GMV) was computed. One-way ANOVA was performed to reveal the GMV differences among DCM patients with PAP, patients without PAP and healthy controls (HC). Post-hoc analyses were conducted to identify the pair-wise GMV differences among these three groups. Analyses of correlations were conducted to uncover the link between clinical measurements and GMV variations. Last, support vector machine (SVM) was conducted to test the utility of GMV for classifying PAP and nPAP DCM patients. RESULTS: Three main findings were observed: [1] Compared to healthy controls, DCM patients showed a significantly lower GMV in the precuneus preoperatively. DCM patients with PAP also exhibited a lower GMV within precuneus than those without; [2] In DCM patients with PAP, the precuneus GMV was inversely related to the postoperative pain intensity; [3] Moreover, successful classification between PAP and nPAP were observed via SVM based on precuneus GMV as features. CONCLUSION: In summary, our results indicate that precuneus GMV may be linked to PAP in DCM, and could be employed to forecast the emergence of PAP in DCM patients.

Surface modification techniques of titanium and titanium alloys for biomedical orthopaedics applications: A review.

Biomedical alloys have an important share in orthopedic applications. Among them, titanium and its titanium alloys are widely used as implant materials because of their excellent mechanical properties and non-cytotoxicity. However, its disadvantages such as its biological inertness and poor antibacterial properties inhibit its further development. Therefore, the surface properties of titanium are crucial in the implantation process and determine the success of the implant. The main purpose of this review is to provide a comprehensive and detailed description of the modification techniques used for the surface modification of titanium implants. In this paper, the corresponding technical methods are introduced systematically from four aspects: mechanical method, physical surface modification, chemical surface modification and electrochemical technique to understand the experimental mechanism of each modification technique, and the above methods can indeed improve the various properties of titanium and its alloys. With the increasing demand for implants in the future, the requirements for surface properties will also increase. Therefore, the development of new coating materials with higher performance by combining various advantages of existing modification technologies is the main trend of future research on surface modification of titanium alloys.

Alterations in the microenvironment and the effects produced of TRPV5 in osteoporosis.

The pathogenesis of osteoporosis involves multiple factors, among which alterations in the bone microenvironment play a crucial role in disrupting normal bone metabolic balance. Transient receptor potential vanilloid 5 (TRPV5), a member of the TRPV family, is an essential determinant of the bone microenvironment, acting at multiple levels to influence its properties. TRPV5 exerts a pivotal influence on bone through the regulation of calcium reabsorption and transportation while also responding to steroid hormones and agonists. Although the metabolic consequences of osteoporosis, such as loss of bone calcium, reduced mineralization capacity, and active osteoclasts, have received significant attention, this review focuses on the changes in the osteoporotic microenvironment and the specific effects of TRPV5 at various levels.

SCIMP: A Novel Targeted Gene for Postmenopausal Osteoporosis Progression.

OBJECTIVE: The literature suggests that not all postmenopausal women suffer from osteoporosis, and the occurrence of postmenopausal osteoporosis is closely related to the genetic susceptibility of genes in the population and the cellular pathways of related genes. To systematically understand the functions of SCIMP gene for osteoporosis, both in vitro and in vivo experiments were analyzed in depth in this integrated study. METHODS: The significantly differentially expressed genes of postmenopausal osteoporosis (PMOP) patients from GEO database were selected. Meanwhile, the primary target gene was also confirmed in clinically recruited individuals using ELISA method; 50 postmenopausal osteoporosis patients with a T-score of -2.5 were randomly enrolled; postmenopausal women with a T-score > -2.5 were included in the non-osteoporotic group (including osteopenia and normal bone mineral density). The associated processes and signaling pathways were deeply investigated with GO and KEGG enrichment analysis. The downstream signaling factors including Erk-1/2, Akt, and IkB-related signaling pathways for the potential gene were evaluated using MG-63 cell line; the MTT, CCK-8, and flow cytometry assays were performed to exam MG-63 cell viability, proliferation, as well as apoptosis, respectively, under different treatments. RESULTS: Based on the differentially expressed gene analysis for GEO database, PMOP patients displayed 845 differentially expressed genes, including 709 down-regulated and 136 up-regulated ones. Ten genes including SCIMP were significantly differentially expressed (at least three-fold difference). SCIMP was the most markedly decreased in PMOP patients' specimens. Using clinical recruited individuals, the concentration of SCIMP was 96.6 ± 20.8 ng/µL in the PMOP group compared with 168.8 ± 23.5 ng/µL in the control group (p < 0.05). At the same time, the osteoclast differentiation signaling pathway was significantly up-regulated while hedgehogs as well as other signaling pathways were down-regulated based on the KEGG analysis. The phosphorylation level of Akt was markedly blocked in si-SCIMP treatment. Up-regulation of SCIMP increased cell proliferation, inhibited cell apoptosis, and enhanced cell viability in MG-63 cells, which was markedly rescued by AKT phosphorylation inhibitor. Finally, in vivo experiments also confirmed that the upregulation of SCIMP enhanced the structural parameters of rat trabecular bone and the osteogenic activity of bone tissue. CONCLUSION: SCIMP plays a critical role in the pathogenesis of postmenopausal osteoporosis in women. SCIMP influences osteoclasts function through an akt-dependent molecular pathway, and subsequently influences the equilibrium process of bone metabolism. This provides a new insight into the pathogenesis of postmenopausal osteoporosis as well as the clinical treatment of osteoporosis.

The Osteoarthritis Natural Progress and Changes in Intraosseous Pressure of the Guinea Pig Model in Different Degeneration Stages.

OBJECTIVE: Articular cartilage and subchondral bone changes during the pathological progress of knee osteoarthritis (KOA) is a key event marking the development of the disease. The age varying alteration patterns within entire osteochondral unit remains poorly understood. The purpose of this study was to find a reasonable age range of the Dunkin-Hartley guinea pig model for the studying of KOA pathological process, and to investigate Intraosseous pressure (IOP) in the process during different degeneration stages of KOA. METHODS: Male Dunkin-Hartley guinea pigs were selected and divided into groups of 3, 6, 9, 12, 18 months old by age, 10 in each group. All knees underwent imaging examination including X-ray, Micro-CT and MRI. Observed the imaging findings with the use of Kellgren-Lawrence (K-L) classification and knee osteoarthritis MRI scores. Measured the IOP of distal femur (DF) and proximal tibia (PT) in each group, and observed the differences of bilateral tibiofemoral articular cartilage in histological and immunohistochemistry, staining results were evaluated by using Mankin's score. Analysis of variance (ANOVA) and t-tests were used to compare the differences indicators between groups. RESULTS: With the increase of age, changes in X-ray, Micro-CT and MRI imaging findings and pathological staining results of articular cartilage in all stages were consistent with the changing of degenerative KOA process. The IOP of DF and PT increased gradually with age, and reached its peak in 12-month age group, and then gradually decreased, there was a statistically significant difference of IOP between each group. The IOP of DF was slightly higher than that of PT, but the difference was not statistically significant. CONCLUSION: Dunkin-Hartley guinea pigs can be used as an animal model to study different pathological stages of KOA. There might be a correlation between the changes of IOP and the pathological progress of articular cartilage and subchondral bone in DF and PT.

Successful outcomes of unilateral vs bilateral pedicle screw fixation for lumbar interbody fusion: A meta-analysis with evidence grading.

BACKGROUND: Whether it's better to adopt unilateral pedicle screw (UPS) fixation or to use bilateral pedicle screw (BPS) one for lumbar degenerative diseases is still controversially undetermined. AIM: To make a comparison between UPS and BPS fixation as to how they work efficaciously and safely in patients suffering from lumbar degenerative diseases. METHODS: We have searched a lot in the databases through 2020 with index terms such as "unilateral pedicle screw fixation" and "bilateral pedicle screw fixation." Only randomized controlled trials and some prospective cohort studies could be found, yielding 15 studies. The intervention was unilateral pedicle screw fixation; Primarily We've got outcomes of complications and fusion rates. Secondarily, we've achieved outcomes regarding total blood loss, operative time, as well as length of stay. Softwares were installed and utilized for subgroup analysis, analyzing forest plots, sensitivity, heterogeneity, forest plots, publication bias, and risk of bias. RESULTS: Fifteen previous cases of study including 992 participants have been involved in our meta-analysis. UPS had slightly lower effects on fusion rate [relative risk (RR) = 0.949, 95%CI: 0.910 to 0.990, P = 0.015], which contributed mostly to this meta-analysis, and similar complication rates (RR = 1.140, 95%CI: 0.792 to 1.640, P = 0.481), Δ visual analog scale [standard mean difference (SMD) = 0.178, 95%CI: -0.021 to 0.378, P = 0.080], and Δ Oswestry disability index (SMD = -0.254, 95%CI: -0.820 to 0.329, P = 0.402). In contrast, an obvious difference has been observed in Δ Japanese Orthopedic Association (JOA) score (SMD = 0.305, 95%CI: 0.046 to 0.563, P = 0.021), total blood loss (SMD = -1.586, 95%CI: -2.182 to -0.990, P = 0.000), operation time (SMD = -2.831, 95%CI: -3.753 to -1.909, P = 0.000), and length of hospital stay (SMD = -0.614, 95%CI: -1.050 to -0.179, P = 0.006). CONCLUSION: Bilateral fixation is more effective than unilateral fixation regarding fusion rate after lumbar interbody fusion. However, JOA, operation time, total blood loss, as well as length of stay were improved for unilateral fixation.

Effects and mechanisms of microenvironmental acidosis on osteoclast biology.

Due to continuous bone remodeling, the bone tissue is dynamic and constantly being updated. Bone remodeling is precisely regulated by the balance between osteoblast-induced bone formation and osteoclast-induced bone resorption. As a giant multinucleated cell, formation and activities of osteoclasts are regulated by macrophage colony-stimulating factor (M-CSF), receptor activator of nuclear factor-kappaB ligand (RANKL), and by pathological destabilization of the extracellular microenvironment. Microenvironmental acidosis, as the prime candidate, is a driving force of multiple biological activities of osteoclast precursor and osteoclasts. The mechanisms involved in these processes, especially acid-sensitive receptors/channels, are of great precision and complicated. Recently, remarkable progress has been achieved in the field of acid-sensitive mechanisms of osteoclasts. It is important to elucidate the relationship between microenvironmental acidosis and excessive osteoclasts activity, which will help in understanding the pathophysiology of diseases that are associated with excess bone resorption. This review summarizes physiological consequences and in particular, potential mechanisms of osteoclast precursor or osteoclasts in the context of acidosis microenvironments.

Romosozumab versus Teriparatide for the Treatment of Postmenopausal Osteoporosis: A Systematic Review and Meta-analysis through a Grade Analysis of Evidence.

OBJECTIVE: To provide a systematic review about the efficacy and safety of romosozumab and teriparatide for the treatment of postmenopausal osteoporosis. METHOD: Randomized controlled trials (RCTs) were searched from electronic databases, including PubMed (1996 to June 2019), Embase (1980 to June 2019), Cochrane Library (CENTRAL, June 2019), Web of Science (1998 to June 2019), and others. The primary outcomes included the following: the percentage change in bone mineral density of lumbar spine and total hip from baseline at month 6 and month 12 in each group. The secondary outcomes included the following: the percentage change in bone mineral density of femoral neck from baseline at month 6 and month 12 in each group and the incidence of adverse events at month 12 in each group. RESULTS: Four studies containing 1304 patients met our selection criteria. The result of our analysis indicated that romosozumab showed better effects in improving BMD of lumbar spine (month 6: MD = 3.54, 95% CI [3.13, 3.94], P<0.001; month 12: MD = 4.93, 95% CI [4.21, 5.64], P<0.001), total hip (month 6: MD = 2.27, 95% CI [0.62, 3.91], P = 0.007; month 12: MD = 3.17, 95% CI [2.68, 3.65], P<0.001), and femoral neck (month 6: MD = 2.30, 95% CI [0.51, 4.08], P = 0.01; month 12: MD = 3.04, 95% CI [2.29, 3.78], P<0.001). Also, the injection-site reaction was less (month 12: RR = 2.84, 95% CI [1.22, 6.59], P = 0.02), but there were no significant difference in the incidence of serious adverse events (month 12: RR = 0.78, 95% CI [0.46, 1.33], P = 0.37) and death (month 12: RR = 0.61, 95% CI [0.08, 4.62], P = 0.63). CONCLUSION: Based on the available studies, our current results demonstrate that romosozumab was better than teriparatide both in terms of efficacy and side effects.

Investigation of Diagnostic Biomarkers for Osteoporosis Based on Differentially Expressed Gene Profile with QCT and mDixon-Quant Techniques.

OBJECTIVE: To develop a comprehensive differential expression profile for osteoporosis based on two independent data sources. METHODS: Using a hindlimb unloading (HLU) rat model to mimic osteoporosis syndrome in humans (animal experiments), the significant differentially expressed mRNAs in osteoporosis were analyzed using RNA-seq. The enriched GO terms as well as KEGG signaling pathways were also deeply investigated. Using clinical specimens to verify the functions of potential hub genes (biomarkers) for osteoporosis (clinical experiments), 128 suspected cases for osteoporosis from January 2019 to December 2020 were randomly selected and analyzed by quantitative computed tomography (QCT) as well as modified Dixon quantification (mDixon-Quant) techniques in the Tianjin hospital. Among these, 80 patients out of 128 suspected cases were finally diagnosed as the osteoporosis group. Meanwhile, 48 patients were selected for osteopenia group. There was no significant age and gender difference across participant subgroups. The protein levels of potential hub genes (FST, CCL3, and RAPGEF4) were determined by ELISA double antibody sandwich method for osteopenia and osteoporosis groups from peripheral blood. RESULT: In the RNA-seq analysis, compared with control group, a total of 803 differentially expressed mRNAs were identified, including 288 up-regulated and 515 down-regulated mRNAs. Of these, FST, CCL3, CPE, RAPGEF4, IL6, MDFI, PDZD2, and GATM were primary hub genes (biomarkers) for osteoporosis. These differentially expressed genes were significantly enriched in GO terms related to extracellular matrix process and KEGG signaling pathways including osteoclast differentiation. In the functional experiments, the protein expression level of FST, CCL3, and RAPGEF4 displayed a specific expression pattern between osteoporosis patients and control group. The protein concentration of FST was 23.63 ± 6.39 ng/mL in osteoporosis patients compared as 48.36 ± 9.12 ng/mL in osteopenia group (P < 0.01). Meanwhile, CCL3 was 1.03 ± 0.64 ng/mL in osteoporosis patients vs 0.56 ± 0.24 in osteopenia group (P < 0.01) and RAPGEF4 was 53.58 ± 11.42 ng/mL in osteoporosis patients vs 66.47 ± 13.28 ng/mL in osteopenia group (P < 0.05), respectively. CONCLUSION: This study has identified potential gene biomarkers (the genes with most significantly differential expression and useful for distinguishing osteoporosis from other bone disorders) and established a differential expression profile for osteoporosis, which is a valuable reference for future clinical research.

Application of rib surface positioning ruler combined with volumetric CT measurement technique in endoscopic minimally invasive thoracic wall fixation surgery.

Application value of rib surface positioning ruler combined with volumetric CT measurement in selection of the incision for minimally invasive internal fixation of rib fracture was investigated. A total of 80 patients who received internal fixation of rib fractures in Tianjin Hospital Affiliated to Tianjin University (Tianjin, China) from May 2018 to April 2019 were selected. Patients were treated with the rib surface positioning ruler combined with volumetric CT measurement method (n=42) or traditional positioning method (n=38). The following parameters were compared between the two groups: Preset incision accuracy, operation incision length, operation time, intraoperative bleeding volume, postoperative wound drainage volume and postoperative pain score. Compared with the traditional positioning method, rib surface positioning ruler combined with volumetric CT measurement method can improve preset incision accuracy, reduce operation time, incision length, intraoperative bleeding volume, postoperative wound drainage volume, and postoperative pain score, with statistically significant differences (P<0.05). In conclusion, the application of rib surface positioning ruler combined with volumetric CT measurement technique has obvious effect on the selection of incision for internal fixation of rib fracture, and is an effective method worth promoting.

Upregulation of miR-211 Promotes Chondrosarcoma Development via Targeting Tumor Suppressor VHL.

INTRODUCTION: miR-211 has been demonstrated to be aberrantly expressed and plays a pivotal role in human cancers. However, its expression profiles and potential roles in chondrosarcoma development remain still elusive. This study aims to determine the clinical values and underlying roles of miR-211 in chondrosarcoma. METHODS: miR-211 expression was analyzed by qRT-PCR in chondrosarcoma specimens and the matched adjacent non-tumor tissues. The relationships among miR-211 expression, clinicopathological factors and overall survival were also evaluated. Cell viability, colony formation, migration and invasion were further investigated in chondrosarcoma cells. Potential target of miR-211 was predicted using bioinformatics to delineate the molecular mechanisms. RESULTS: miR-211 was remarkably increased in chondrosarcoma compared with the matched adjacent non-tumor tissues. High miR-211 level was identified as 66.7% in chondrosarcoma specimens, which were significantly associated with histological grade and MSTS stage. miR-211 had significant influences on the prognosis of chondrosarcoma patients. Multivariate analysis demonstrated that miR-211 was an independent prognostic factor for overall survival of chondrosarcoma patients. We also found that overexpression or inhibitor of miR-211 promotes or suppresses chondrosarcoma cell proliferation, migration and invasion, respectively. Mechanistically, miR-211 binds to the 3'-UTR of Von Hippel-Lindau (VHL) and suppresses its expression, while restoration of VHL suppressed the potentiated function of miR-211 on proliferation and invasion of chondrosarcoma cells. CONCLUSION: miR-211 is identified as a potent oncogenic function in chondrosarcoma development, which can serve as a novel biomarker to predict the survival of chondrosarcoma patients. miR-211 potentiates chondrosarcoma growth via targeting VHL, highlighting a novel attractive target for chondrosarcoma treatment.

Correction to: Finite element analysis of two cephalomedullary nails in treatment of elderly reverse obliquity intertrochanteric fractures: zimmer natural nail and proximal femoral nail antirotation-ΙΙ.

In the original publication of this article [1], Chinese text of the Figs. 3, 4, 5 has not been converted to English.

Biomechanical efficacy of four different dual screws fixations in treatment of talus neck fracture: a three-dimensional finite element analysis.

BACKGROUND: Current there are different screws fixation methods used for fixation of the talar neck fracture. However, the best method of screws internal fixation is still controversial. Few relevant studies have focused on this issue, especially by finite element analysis. The purpose of this study was to explore the mechanical stability of dual screws internal fixation methods with different approaches and the best biomechanical environment of the fracture section, so as to provide reliable mechanical evidence for the selection of clinical internal fixation. METHODS: The computed tomography (CT) image of the healthy adult male ankle joint was used for three-dimensional reconstruction of the ankle model. Talus neck fracture and screws were constructed by computer-aided design (CAD). Then, 3D model of talar neck fracture which fixed with antero-posterior (AP) parallel dual screws, antero-posterior (AP) cross dual screws, postero-anterior (PA) parallel dual screws, and postero-anterior (PA) cross dual screws were simulated. Finally, under the condition of 2400N vertical load, finite element analysis (FEA) were carried out to compare the outcome of the four different internal fixation methods. The results of Von Mises stress, displacement of four groups which contain talus fracture fragments and screws internal fixations were analyzed. RESULTS: Compared with the other three groups, postero-anterior (PA) parallel dual screws had better results in the stress peak, stress distribution, and displacement of talus and internal fixation. CONCLUSIONS: To sum up, the Von Mises stress of fracture section was the smallest, the stress distribution of screws were the most scattered, and the peak value was the smallest in posterior to anterior parallel double screws fixation, which was obviously better than that in the other three groups. When using screws internal fixation, the method of posterior to anterior screws fixation is better than that of anterior to posterior screws fixation, and the peak value and stress distribution of parallel double screws fixation is better than that of cross double screws fixation. Thus, for the talar neck fracture, the use of posterior to anterior parallel double screws fixation is recommended in clinical surgery.

Finite element analysis of two cephalomedullary nails in treatment of elderly reverse obliquity intertrochanteric fractures: zimmer natural nail and proximal femoral nail antirotation-ΙΙ.

BACKGROUND: More elderly patients are suffering from intertrochanteric fractures. However, the choice of internal fixation is still controversial, especially in the treatment of unstable intertrochanteric fracture; thus, previous implants continue to be improved, and new ones are being developed. The purpose of our study was to compare the biomechanical advantages between the zimmer natural nail (ZNN) and proximal femoral nail antirotation-II (PFNA-II) in the treatment of elderly reverse obliquity intertrochanteric fractures. METHODS: A three-dimensional finite element was applied for reverse obliquity intertrochanteric fracture models (AO31-A3.1) fixed with the ZNN or PFNA-II. The distribution, peak value and position of the von Mises stress and the displacement were the criteria for comparison between the two groups. RESULTS: The stresses of the internal fixation and femur in the ZNN model were smaller than those in the PFNA-II model, and the peak values of the two groups were 364.8 MPa and 171.8 MPa (ZNN) and 832.3 MPa and 1795.0 MPa (PFNA-II). The maximum amount of displacement of the two groups was similar, and their locations were the same, i.e., in the femoral head vertex (3.768 mm in the ZNN model and 3.713 mm in the PFNA-II model). CONCLUSIONS: The displacement in the two models was similar, but the stresses in the implant and bone were reduced with the ZNN. Therefore, the ZNN implant may provide biomechanical advantages over PFNA-II in reverse obliquity intertrochanteric fractures, as shown through the finite element analysis. These findings from our study may provide a reference for the perioperative selection of internal fixations.

The effect of tail suspension and treadmill exercise on LRP6 expression, bone mass and biomechanical properties of hindlimb bones in SD rats.

Purpose: To investigate whether mechanical load regulates LRP6 expression and whether different intensities of treadmill exercise have different effects on LRP6 expression and the biomechanical properties of hindlimb bones in Sprague-Dawley (SD) rats. Methods: Fifty-six three-month-old virgin female SD rats were randomly divided into seven groups (n=8). Each group was subjected to tail suspension, free physiological activity or different intensities of treadmill exercise according to the experimental design for four or eight weeks. Rats were sacrificed after the intervention based on experimental design, and fresh femurs, tibias and fibulas were harvested for molecular biological analysis, biomechanical testing and micro-CT analysis. Results: LRP6 expression and the Wnt/ß-catenin pathway activity decreased, and bone mass and biomechanical properties decreased after loss of mechanical stimulation. For disuse osteoporosis, even physiological activity could improve LRP6 expression, Wnt/ß-catenin pathway activity, bone mass and biomechanical properties. Compared with physiological activity, treadmill exercise had better and faster effects on bone recovery. Compared with the Low intensity Exercise Group (LE group), the Medium intensity Exercise Group (ME group) and High intensity Exercise Group (HE group) had higher LRP6 expression, bone mass and biomechanical properties, while there were no significant difference between the ME group and HE group. Conclusions: Mechanical load appears to be a regulator of LRP6 expression, and it further affects the Wnt/ß-catenin pathway activity and bone mass. The LRP6 expression, bone mass and biomechanical properties gradually improve as treadmill exercise intensity increases, while there is no significant difference between the ME group and HE group.