Clinical exploration of the international society of limb salvage classification of endoprosthetic failure using Henderson in the application of 3D-printed pelvic tumor prostheses.

Background: The use of 3D-printed pelvic prosthesis for postoperative reconstruction after pelvic tumor resection has become one of the primary reconstruction methods the incidence of complications related to postoperative prosthesis reconstruction is high. Drawing on the failure of the type of bone tumor reconstruction in Henderson,the occurrence of postoperative complications was explored to take advantage of the design improvement of the 3D-printed prosthesis of subsequent pelvic tumors. Methods: The data for patients who underwent 3D-printed pelvic tumor prostheses in the Department of Bone and Soft Tissue Surgery at the Affiliated Cancer Hospital of Guangxi Medical University from January 2019 to October 2022 were collected and analyzed. Results: The median follow-up time for all patients was 15.99 months (1.33-31.16 months). At the most recent follow-up,all patients were alive,with an average Musculoskeletal Tumor Society (MSTS) score of 21.46 (17 to 26 points). Local recurrence occurred in two cases (15.3%), metastasis in four cases (30.7%), and complications in 10 cases (76.9%). Early complications after surgery were primarily local wound fissure, deep tissue infection, and postoperative neuralgia. Later complications included loose dissolution of internal fixation, postoperative prosthetic dislocation, and postoperative gluteal middle muscle gait. Conclusion: 3D printing personalized design pelvic tumor prosthesis is an effective way to reconstruct, and designing pelvic 3D printed tumor prosthesis with the help of Henderson's bone tumor reconstruction failure concept may help bone tumor surgeons develop better pelvic tumor prosthesis.

LncRNA UCA1 accelerates osteosarcoma progression via miR-145 and Wnt/ß-catenin pathway.

Long non-coding (lnc) urothelial cancer associated 1 (UCA1) has been confirmed to participate in osteosarcoma (OS), but its specific mechanism is still under investigation. The study was designed to reveal the interaction between UCA1 and its downstream effector molecules, so as to determine whether there is any interaction of regulating physiological processes in tumor cells. Here, we studied the signaling cascade involving UCA1, miR-145, and HMGA1. The expression of UCA1 and miR-145 levels was interfered to assess their effects on physiological processes of tumor cells. The relationship between UCA1 and miR-145 as well as between HMGA1 and miR-145 was identified by the dual-luciferase reporter (DLR) assay, and the in vivo effect of UCA1 was estimated in nude mouse xenografts. As a result, a negative association was found between UCA1 and miR-145 in OS cells. Both UCA1 knockout and miR-145 over-expression inhibited malignant progression and induced apoptosis in MG-63 and U2OS cells. UCA1 knockout led to an increase in miR-145 and decreases in HMGA1, p-ß-catenin and cyclin D1. In addition, UCA1 upregulation promoted tumor growth in vitro and changed miR-145 and HMGA1 levels in vivo. Moreover, the DLR assay and RNA immunoprecipitation (RIP) showed that UCA1 was likely to regulate HMGA1 levels by sponging miR-145. Overall, the inhibition of UCA1 increases miR-145 levels and decreases HMGA1 levels, thereby exerting an anti-tumor role in OS.

Anti-neoplastic characteristics and potential targets of calycosin against bisphenol A-related osteosarcoma: bioinformatics analysis.

Environmentally, bisphenol A (BPA) is a well-known pollutant caused human health risk, including osteosarcoma (OS). OS, a deadly bone neoplasia, may occur in children and adults. However, the anti-OS pharmacotherapy prescribes limitedly in clinical practice. Interestingly, previous experimental evidences indicate calycosin-exerting potential anti-OS actions. Thus, in this report, we aimed to further characterize and detail the therapeutic targets and molecular mechanisms of calycosin-anti-BPA-related OS by using network pharmacology and molecular docking analyses. In results, the bioinformatics data disclosed all mapped, core targets, biological functions, molecular pathways of calycosin to treat BPA-related OS. The computational analysis using molecular docking indicated that potential binding ability of core targets in calycosin to treat BPA-related OS was identified. Moreover, detailed biological functions and optimal pathways of calycosin-anti-BPA-related OS were revealed, as shown in integrated network maps. Taken together, these network pharmacology and structural biology findings illustrate the core biotargets, pharmacological functions and pathways of calycosin-anti-BPA-related OS. Potentially, these core targets identified by molecular docking may attribute to the potential clinical application of calycosin against BPA-related OS.[Formula: see text].

Integrative findings indicate anti-tumor biotargets and molecular mechanisms of calycosin against osteosarcoma.

Calycosin is reportedly evidenced with pharmacologically treating bone cells. However, the comprehensive anti-osteosarcoma (OS) mechanisms of calycosin have not been uncovered. By using a systemic method of network pharmacology, the present study aimed to reveal potential anti-OS biotargets and molecular mechanisms played by calycosin. Moreover, human and animal experiments were conducted to verify the core biotargets of calycosin against OS. As results, all primary and core biotargets, biological processes, molecular pathways of calycosin against OS were revealed. Additionally, top 20 biological processes and pathways of calycosin against OS were identified. In human study, the OS sections resulted in reduced expressions of tumor protein p53 (TP53), Caspase-3 (CASP3), and elevated X-linked inhibitor of apoptosis protein (XIAP) expression in comparison with OS-free controls. As shown in cell culture study, calycosin-treated OS cells showed reduced cell proliferation, and promoted cell apoptosis. In TUNEL stains, calycosin resulted in elevated apoptotic cells. As showed in immunostaining, calycosin-treated OS cells exhibited intracellular up-regulation of TP53, CASP3 expressions, and decreased XIAP expressions. Taken together, the biological informational findings manifest the candidate and core biotargets, molecular functions and pathways of calycosin against OS. Attractively, these core biotargets may be used for effectively detecting and treating human OS.

miR-17-5p Regulates Heterotopic Ossification by Targeting ANKH in Ankylosing Spondylitis.

Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized with heterotopic ossification of the axis joints ligaments, resulting in joint disability. MicroRNAs (miRNAs) are regulators of mRNAs that play a crucial role in the AS pathological process. Here, we showed that the level of miR-17-5p was significantly higher in fibroblasts and ligament tissues from AS patients as compared to the non-AS individuals. Knockdown of the miR-17-5p from the fibroblasts derived from AS patients exhibited decreased osteogenic differentiation and ossification. On the other hand, AS patient-derived fibroblasts overexpressing miR-17-5p displayed the increased osteogenesis. Furthermore, inhibition of miR-17-5p ameliorated osteophyte formation, and the sacroiliitis phenotype in AS rats received emulsified collagen. Mechanistically, miR-17-5p regulated osteogenic differentiation by targeting the 3' UTR of ankylosis protein homolog (ANKH). Also, downregulation of miR-17-5p slowed AS progression through regulation of cytokines, such as dickkopf-1 (DKK1) and vascular endothelial growth factor (VEGF). In conclusion, our findings reveal a role of the miR-17-5p-ANKH axis in the regulation of heterotopic ossification, which is essential for therapeutic intervention in heterotopic ossification in AS.

Risk of hip fracture in patients on dialysis or kidney transplant: a meta-analysis of 14 cohort studies.

PURPOSE: We aimed to conduct a meta-analysis of published cohort studies to evaluate the risk of hip fracture in patients undergoing dialysis or kidney transplantation (KT). METHODS: We identified relevant studies by searching PubMed, EMBASE and Google Scholar databases from their inception to December 31, 2017. Cohort studies evaluating risk of hip fractures in patients undergoing dialysis or KT were considered included. The methodological quality of the cohort studies was assessed using the modified Newcastle-Ottawa scale. RESULTS: In our meta-analysis of 14 retrospective cohort studies, a total of more than 1.5 million patients undergoing dialysis or KT were included, of whom more than 30,000 had hip fractures. After the merger, the proportion of hip fractures was 1.92% (95% CI, 1.38%-2.46%) with significant heterogeneity (I 2=99.9%, P=0.000) in all patients, and the incidence rate of hip fractures (per 1,000 person-years) was 8.95 (95% CI, 4.05-13.85) with significant heterogeneity (I 2=99.9%, P=0.000). The pooled relative risks (RR) value for dialysis patients compared with the general population were 6.35 (95% CI, 4.53-8.88) for male and 5.57 (95% CI, 4.44-6.99) for female. The pooled RR value for hemodialysis (HD) patients compared with peritoneal dialysis (PD) patients was 1.39 (95% CI, 1.13-1.70) with no heterogeneity (I 2=0.0%, P=0.763). CONCLUSION: In conclusion, the present meta-analysis reveals that about 2% of dialysis or KT patients go on to sustain a hip fracture during follow-up, with the overall hip fracture incidence rates being 8.95 per 1,000 person-years. The overall risk of hip fracture was more than 5-fold higher in dialysis patients than in the general population. Among patients on PD, HD, and KT, HD and KT patients had the highest and the lowest risk of hip fractures, respectively.

Significance of circulating tumor cells in osteosarcoma patients treated by neoadjuvant chemotherapy and surgery.

PURPOSE: By examining and identifying circulating tumor cell (CTC) counts and subtypes of peripheral blood in osteosarcoma patients, we evaluated the relationship between CTCs and characteristics of osteosarcoma patients, as well as CTC changes after neoadjuvant chemotherapy and surgery. METHODS: CanPatrol™ CTC technology was used to detect CTCs in peripheral blood before and after treatment in 32 osteosarcoma patients. Peripheral blood samples from 10 healthy volunteers were included as controls and examined for the presence of CTCs. RESULTS: Of the 32 osteosarcoma patients, CTCs were detected in 30 patients before treatment, and the average CTC count was 14.06±9.08. No CTCs were detected in the 10 healthy volunteers. The detected CTCs were divided into epithelial CTCs, mesenchymal CTCs (M-CTCs), and biophenotypic epithelial/mesenchymal CTCs. The average number of pretreatment CTCs was higher in stage III patients than in stage IIB patients (P=0.012). Twenty-eight patients were screened for changes in CTC count at 1 week after neoadjuvant chemotherapy and at 4 weeks after surgery. We divided these 28 patients into two groups according to the changes in the percentage of M-CTCs before and after treatment, and the results showed that the disease-free survival (DFS) was significantly shorter in the M-CTC percentage-increased group than in the M-CTC percentage-decreased or no-change group (P=0.032). Five patients with stage II osteosarcoma were examined for CTCs at the appearance of lung metastases, and the total number of CTCs was found to be higher at the appearance of lung metastases than before treatment in these patients. CONCLUSION: The rate of presence of CTCs in the peripheral blood of osteosarcoma patients is high, and patients with an increased percentage of M-CTCs after treatment have a shorter DFS. The dynamic monitoring of changes in CTC counts after treatment has clinical significance for the timely detection of recurrence or metastasis.

A Human Chondrocyte-Derived In Vitro Model of Alcohol-Induced and Steroid-Induced Femoral Head Necrosis.

BACKGROUND Worldwide, femoral head necrosis (FHN), which is also known as avascular necrosis of the femoral head or osteonecrosis of the femoral head, affects millions of people. Excess alcohol intake and steroid use are two common associations with FHN, but their pathogenesis remains unknown. The aim of this study was to develop an in vitro model using human chondrocytes to study alcohol-induced and steroid-induced FHN. MATERIAL AND METHODS In this study, the in vitro model used a monolayer culture of articular chondrocytes derived from patients with non-traumatic FHN (Ficat and Arlet, Stage III). Normal chondrocytes were obtained from patients with femoral neck fracture resulting from road traffic accident (Garden, Stage IV). Alcohol-stimulated and steroid-stimulated articular chondrocytes were evaluated by a cell proliferation assay, measurement of calcium levels (alizarin red), measurement of alkaline phosphatase (ALP) levels, detection of glycosaminoglycan (GAG) secretion using safranin O histochemical staining, and analysis of cartilage-specific genes, ACAN, SOX9, OPG, TGF-ß, RANKL, and RUNX2, using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS Both alcohol and steroids, but especially steroids, accelerated the degradation of cartilage by suppression of chondrogenesis while promoting chondrocyte hypertrophy and activating osteogenic differentiation, as assessed by cell proliferation assay, detection of glycosaminoglycan (GAG) secretion, and analysis of cartilage-specific genes. CONCLUSIONS A human chondrocyte-derived in vitro model of alcohol-induced and steroid-induced FHN demonstrated chondrocyte hypertrophy and activated osteogenic differentiation.

Effect of metformin on ossification and inflammation of fibroblasts in ankylosing spondylitis: An in vitro study.

Ankylosing spondylitis (AS) is an autoimmune disease characterized by fibroblasts ossification. However, effective drug therapy for AS is lacking. As an antidiabetic drug, metformin has demonstrated an antiosteogenic effect on osteoblasts in vitro. And it is also a kind of specific agonists for adenosine 5'-monophosphate activated protein kinase (AMPK), which is blocked in the process of AS. Given the role in antiosteogenesis and AMPK activating, metformin was investigated of its effect on fibroblasts harvested from capsular ligament of patients with femoral neck fracture and AS. Osteogenic specific makers (Alp, Bglap, Runx2, Bmp2, and Col1) in fibroblasts administered with metformin (20 µg/mL) were detected by ALP staining, alizarin red staining, qPCR, and Western blotting after 7 and 14 days of culture. Inflammation genes (il1-ß and il6) and pathway (Pi3k, Akt, and Ampk) associated markers were also evaluated. Our results showed that osteogenic specific markers were greatly downregulated and ossification was effectively inhibited in AS fibroblasts after addition of metformin. Levels of inflammation markers were also decreased by metformin. Thus, metformin exerts potent effect on suppression of ossification and inflammation in AS fibroblasts via the activation of Pi3k/Akt and AMPK pathways, which may be developed as a potential agent for treatment of AS.

Effect of NGF From Venom of Chinese Cobra (Naja Atra)on Chondrocytes Proliferation and Metabolism In Vitro.

Autologous chondrocyte implantation (ACI) is promising strategy for cartilage repair. However, chondrocyte phenotype is easily lost when expanded in vitro which defined as "dedifferentiation." To ensure successful therapy, an effective pro-chondrogenic agent is necessary to overcome the obstacle of limited cell numbers in the restoration process, and dedifferentiation is a prerequisite. In the present study, we investigated the chondro-protective effect of NGF from Chinese cobra venom on human chondrocytes by determination of its specific effect on cell viability, proliferation, morphology, GAG production, and cartilage specific gene expression. The results suggested that NGF showed no cytotoxicity to chondrocytes below the concentration of 16 µg/mL. DNA and glycosaminoglycan (GAG) content were, respectively, improved in NGF groups comparing to the control (P < 0.05). NGF up-regulate the gene expression of ACAN, SOX9, and COL2A1 while down-regulate the expression level of COL1A1 (P < 0.05). Moreover, the results of viability assay, hematoxylin-eosin, safranin O, and immunohistochemical staining also suggested better performances in NGF groups. NGF of 6 µg/mL shown lower cytotoxicity on chondrocytes, more glycosaminoglycans (GAGs) synthesis and up-regulated chondrogenic gene expression. This study may provide a basis for the development of a novel agent for the treatment of articular cartilage defects. J. Cell. Biochem. 118: 4308-4316, 2017. © 2017 Wiley Periodicals, Inc.

[Treatment of children with femoral subtrochanteric fracture with advanced elastic intramedullary nail technology].

OBJECTIVE: To explore curative effects of advanced elastic intramedullary nail technology in treating children with femoral subtrochanteric fracture. METHODS: Form March 2009 to December 2010, 16 children with femoral subtrochanteric fracture were treated with advanced elastic intramedullary nail technology. There were 12 males and 4 females ranging in age from 7 to 15 years old with a mean of 9.8 years old. According to fracture classification, 9 cases were stable fractures (traverse or short oblique type) and 7 cases were unstable fractures (comminuted or long oblique type). Radiographs and complications were retrospectively reviewed. Fracture healing were evaluated according to Flynn criteria. RESULTS: All children were followed up from 11 to 32 months with an average of 21 months. No incision infecton,bone nonunion and breakage of screw occurred. The fracture healing time was from 8 to 16 weeks with an average of 10.1 weeks. According to Flynn criteria, 14 cases got excellent results, 1 moderate and 1 poor. CONCLUSION: Advanced elastic intramedullary nail technology for the treatment of children with femoral subtrochanteric fracture is a safe and effective fixation, which is good for early mobilization, shorter the duration of hospital stays and reduce complications.