Some porous materials have been developed to enhance biologic fusion of the implants to bone in spine fusion surgeries. However, there are several inherent limitations. In this study, a novel biomedical porous tantalum was applied to in vitro and in vivo experiments to test its biocompatibility and osteocompatibility.Bone marrow-derived mesenchymal stem cells (BMSCs) were cultured on porous tantalum implant. Scanning electron microscope (SEM) and Cell Counting Kit-8 assay were used to evaluate the cell toxicity and biocompatibility. Twenty-four rabbits were performed discectomy only (control group), discectomy with autologous bone implanted (autograft group), and discectomy with porous tantalum implanted (tantalum group) at 3 levels: L3-L4, L4-L5, and L5-L6 in random order. All the 24 rabbits were randomly sacrificed at the different post-operative times (2, 4, 6, and 12 months; n = 6 at each time point). Histologic examination and micro-computed tomography scans were done to evaluate the fusion process. Comparison of fusion index scores between groups was analyzed using one-way analysis of variance. Other comparisons of numerical variables between groups were made by Student t test.All rabbits survived and recovered without any symptoms of nerve injury. Radiographic fusion index scores at 12 months post-operatively between autograft and tantalum groups showed no significant difference (2.89 ± 0.32 vs. 2.83 ± 0.38, F = 244.60, P = 0.709). Cell Counting Kit-8 assay showed no significant difference of absorbance values between the leaching liquor group and control group (1.25 ± 0.06 vs. 1.23 ± 0.04, t = -0.644, P = 0.545), which indicated the BMSC proliferation without toxicity. SEM images showed that these cells had irregular shapes with long spindles adhered to the surface of tantalum implant. No implant degradation, wear debris, or osteolysis was observed. Histologic results showed solid fusion in the porous tantalum and autologous bone implanted intervertebral spaces.This novel porous tantalum implant showed a good biocompatibility and osteocompatibility, which could be a valid biomaterial for interbody fusion cages.
To develop and validate a deep-learning classifier trained on voice data extracted from videolaryngostroboscopy recordings, differentiating between three different vocal fold (VF) states: healthy (HVF), unilateral paralysis (UVFP), and VF lesions, including benign and malignant pathologies. Patients with UVFP (n = 105), VF lesions (n = 63), and HVF (n = 41) were retrospectively identified. Voice samples were extracted from stroboscopic videos (Pentax Laryngeal Strobe Model 9400), including sustained /i/ phonation, pitch glide, and /i/ sniff task. Extracted audio files were converted into Mel-spectrograms. Voice samples were independently divided into training (80%), validation (10%), and test (10%) by patient. Pretrained ResNet18 models were trained to classify (1) HVF and pathological VF (lesions and UVFP), and (2) HVF, UVFP, and VF lesions. Both classifiers were further validated on an external dataset consisting of 12 UVFP, 13 VF lesions, and 15 HVF patients. Model performances were evaluated by accuracy and F1-score. When evaluated on a hold-out test set, the binary classifier demonstrated stronger performance compared to the multi-class classifier (accuracy 83% vs. 40%; F1-score 0.90 vs. 0.36). When evaluated on an external dataset, the binary classifier achieved an accuracy of 63% and F1-score of 0.48, compared to 35% and 0.25 for the multi-class classifier. Deep-learning classifiers differentiating HVF, UVFP, and VF lesions were developed using voice data from stroboscopic videos. Although healthy and pathological voice were differentiated with moderate accuracy, multi-class classification lowered model performance. The model performed poorly on an external dataset. Voice captured in stroboscopic videos may have limited diagnostic value, though further studies are needed. 4 Laryngoscope, 2025.
Background Solitary cysticercus granuloma (SCG) is the commonest form of neurocysticercosis in the Indian subcontinent and in travelers. Several different treatment options exist for SCG. We conducted a Bayesian network meta-analysis of randomized clinical trials (RCTs) to identify the best treatment option to prevent seizure recurrence and promote lesion resolution for patients with SCG. Methods and Principal Findings PubMed, EMBASE and the Cochrane Library databases (up to June 1, 2015) were searched for RCTs that compared any anthelmintics or corticosteroids, alone or in combination, with placebo or head to head and reported on seizure recurrence and lesion resolution in patients with SCG. A total of 14 RCTs (1277 patients) were included in the quantitative analysis focusing on four different treatment options. A Bayesian network model computing odds ratios (OR) with 95% credible intervals (CrI) and probability of being best (Pbest) was used to compare all interventions simultaneously. Albendazole and corticosteroids combination therapy was the only regimen that significantly decreased the risk of seizure recurrence compared with conservative treatment (OR 0.32, 95% CrI 0.10–0.93, Pbest 73.3%). Albendazole and corticosteroids alone or in combination were all efficacious in hastening granuloma resolution, but the combined therapy remained the best option based on probability analysis (OR 3.05, 95% CrI 1.24–7.95, Pbest 53.9%). The superiority of the combination therapy changed little in RCTs with different follow-up durations and in sensitivity analyses. The limitations of this study include high risk of bias and short follow-up duration in most studies. Conclusions Dual therapy of albendazole and corticosteroids was the most efficacious regimen that could prevent seizure recurrence and promote lesion resolution in a follow-up period of around one year. It should be recommended for the management of SCG until more high-quality evidence is available.
Purpose: The purpose of this study is to evaluate the effects of miR-628 on migration and invasion of breast cancer stem cells (CSCs), which are essential for tumor recurrence and metastasis. Materials and methods: Quantitative reverse transcription-polymerase chain reaction was used to determine the expression of microRNAs and mRNAs. A subpopulation of CD44 + /CD24 - breast CSCs were sorted by flow cytometry. Transwell assays were used to evaluate cell migration and invasion. Luciferase reporter assays were performed to verify whether miR-628 targeted SOS Ras/Rac guanine nucleotide exchange factor 1 (SOS1). pcDNA3.1(+)-SOS1 was constructed for overexpressing SOS1 after transfection. Results: Compared with primary breast cancer cells, bone metastatic breast cancer cells showed significant downregulation of miR-628 . The CD44 + /CD24 - breast CSC subpopulations in MDA-MB-231 and MCF-7 cell lines were analyzed and sorted. Transfection with an miR-628 mimic significantly suppressed the migration and invasion of these breast CSCs by targeting SOS1, which plays an essential role in epithelial-to-mesenchymal transition. Overexpression of SOS1 rescued miR-628-mediated migration and invasion by upregulating Snail and vimentin, and downregulating E-cadherin. Conclusion: miR-628 suppressed migration and invasion of breast CSCs of MDA-MB-231 and MCF-7 cells by directly targeting SOS1. Enhancement of miR-628 expression might be an effective strategy for managing breast cancer metastasis. Keywords: breast cancer stem cells, CD44 + /CD24 - , miR-628, SOS1, migration, invasion
En bloc resection is the treatment of choice of myxoid chondrosarcoma. These tumors can produce huge masses. Anatomical constraints limit the possibility to perform en bloc resection in the spine. A very huge myxoid chondrosarcoma (14.2 × 10.8 × 11.4 cm) arising from T2 to T5 and invading the whole higher left pleural cavity was observed. Surgical planning according to WBB staging system was performed. The tumor was successfully submitted to en bloc resection achieving a tumor-free margin as demonstrated by the pathologist’s report. A careful planning and a multidisciplinary collaboration make possible to perform en bloc resection even in apparently impossible cases.
Complexity and heterogeneity increases the difficulty of diagnosis and treatment of bone tumors. We aimed to identify the mutational characterization and potential biomarkers of bone tumors. In this study, a total of 357 bone tumor patients were recruited and the next generation sequencing (NGS)-based YuanSu450 panel, that includes both DNA and RNA sequencing, was performed for genomic alteration identification. The most common mutated genes in bone tumors included TP53, NCOR1, VEGFA, RB1, CCND3, CDKN2A, GID4, CCNE1, TERT, and MAP2K4. The amplification of genes such as NCOR1, VEGFA, and CCND3 mainly occurred in osteosarcoma. Germline mutation analysis reveal a high frequency of HRD related mutations (46.4%, 13/28) in this cohort. With the assistance of RNA sequencing, 16.8% (19/113) gene fusions were independently detected in 20% (16/79) of patients. Nearly 34.2% of patients harbored actionable targeted mutations, of which the most common mutation is CDKN2A deletion. The different mutational characterizations between juvenile patients and adult patients indicated the potential effect of age in bone tumor treatment. According to the genomic alterations, the diagnosis of 26 (7.28%) bone tumors were corrected. The most easily misdiagnosed bone tumor included malignant giant cell tumors of bone (2.8%, 10/357) and fibrous dysplasia of bone (1.7%, 6/357). Meanwhile, we found that the mutations of MUC16 may be a potential biomarker for the diagnosis of mesenchymal chondrosarcomas. Our results indicated that RNA sequencing effectively complements DNA sequencing and increased the detection rate of gene fusions, supporting that NGS technology can effectively assist the diagnosis of bone tumors.
Abstract Background Numerous studies have demonstrated the important roles of tumor-associated macrophages (TAMs) in osteosarcoma metastasis. In osteosarcoma, higher levels of HMGB1 correlate with osteosarcoma progression. However, whether HMGB1 is involved in the polarization of M2 macrophages into M1 macrophages in osteosarcoma still remains largely unknown. Methods HMGB1 and CD206 mRNA expression was measured by qRT-PCR in osteosarcoma tissues and cells. HMGB1 and RAGE protein expression was measured by western blotting. Osteosarcoma migration was measured using a Transwell and wound-healing assay. Osteosarcoma invasion was measured using a Transwell assay. Macrophage subtypes were detected using flow cytometry. Results HMGB1 is aberrantly overexpressed in osteosarcoma, and positively correlates with the TNM III & IV stages, lymph node metastasis, and distant metastasis. Silencing HMGB1 inhibits migration, invasion, and metastasis-related proteins in osteosarcoma cells. Furthermore, the reduced HMGB1 expression in the conditioned media derived from osteosarcoma cells also induces the polarization of M2 TAMs to M1 TAMs. In addition, silencing HMGB1 inhibits the liver and lung metastases of osteosarcoma and reduces the expression of HMGB1, CD163, and CD206 in vivo experiments. HMGB1 regulates macrophage polarization through RAGE. Interestingly, the polarized M2 macrophages could induce osteosarcoma migration and invasion, which in turn results in activation of HMGB1 expression in osteosarcoma cells to form a positive feedback loop. Conclusions HMGB1 and M2 macrophages enhance osteosarcoma migration, invasion, and metastasis capability through positive feedback regulation. These findings reveal the significance of tumor cell and TAM interaction in the metastatic microenvironment.
To evaluate the clinical outcomes of the wide resection and the functional reconstruction for treating malignant tumors of the proximal femur.The clinical data were analysed from 62 patients with malignant tumors of the proximal femur treated between January 1987 and December 2007. There were 29 males and 33 females with a median age of 35 years (range, 14-73 years). In 41 patients with primary malignant tumors having a disease course of 0.5-14.0 months, there were 16 cases of osteosarcoma, 7 cases of fibrosarcoma, 6 cases of chondrosarcoma, 6 cases of malignant fibrous histiocytoma, 4 cases of mesenchymal sarcoma,1 case of Ewing sarcoma, and 1 case of angiosarcoma, including 3 cases of type IB, 2 cases of type IIA, 35 cases of type IIB, and 1 case of type III according to Enneking stage. In 21 patients with metastatic tumors, 16 had a malignant tumor history; the disease course was 0.1-28.0 months (3.4 months on average). Radical resection was performed in 9 cases, extensive resection in 39 cases, and marginal resection in 14 cases. After resection, 39 cases underwent reconstruction with prostheses (prostheses group) and 14 cases underwent reconstruction with allograft-prosthetic composites (APC, APC group).All incision healed by first intention. Twenty-six cases died of tumor metastasis, their postoperative survive time was 16-56 months (28 months on average). The average follow-up time was 64 months (range, 28-221 months) in 36 survival patients. The local recurrence rate of primary malignant tumors was 4.88% (2/41). In prostheses group, dislocation of femoral head occurred in 2 cases, fracture of prosthetic stem in 1 case, hip pain in 3 cases, acetabular wear in 3 cases, and stem loosening in 5 cases. In APC group, nonunion of APC occurred in 3 cases and acetabular wear in 1 case. At last follow-up, the average Musculoskeletal Tumor Society (MSTS) functional scores were 77.69% +/- 6.50% in prostheses group and 85.71% +/- 7.45% in APC group, showing significant difference (P < 0.001).When the wide resection is performed for malignant tumors of the proximal femur, better local control could be achieved. Compared with reconstruction of the prosthesis, the APC reconstruction can provide better function.
Background: Recent studies have reported the vital roles of circular RNAs (circRNAs) in tumor progression. However, the function and expression profile of most circRNAs in osteosarcoma remain unclear. Methods: We examined the expression of circEPSTI1, a circRNA, in 50 paired adjacent normal tissues and osteosarcoma tissues by qRT-PCR. Then, we further explored the function of circEPSTI1 in osteosarcoma progression in vitro and in vivo. For example, cell proliferation and migration were examined. Some experiments were performed to explore the regulatory function of circEPSTI1 in miRNA and to investigate the potential role of circEPSTI1 in osteosarcoma. Results: We found that circEPSTI1 was significantly upregulated in osteosarcoma. Inhibition of circEPSTI1 suppressed the osteosarcoma cancer cell proliferation and migration in vitro. Dual luciferase reporter assay showed that circEPSTI1 and MCL1 (myeloid cell leukaemia 1) could bind to miR-892b and that MCL1 and circEPSTI1 were targets of miR-892b. Conclusion: Thus, the circEPSTI1-miR-892b-MCL1 axis affected osteosarcoma progression through the miRNA sponging mechanism. circEPSTI1 may serve as a target and biomarker for osteosarcoma treatment.
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