Frozen inactivated autograft replantation for bone and soft tissue sarcomas.

Background: The frozen inactivation of autologous tumor bones using liquid nitrogen is an important surgical method for limb salvage in patients with sarcoma. At present, there are few research reports related to frozen inactivated autograft replantation. Methods: In this study, we retrospectively collected the clinical data of patients with bone and soft tissue sarcoma treated with liquid nitrogen-frozen inactivated tumor bone replantation, and analyzed the safety and efficacy of this surgical method. The healing status of the frozen inactivated autografts was evaluated using the International Society of Limb Salvage (ISOLS) scoring system. Functional status of patients was assessed using the Musculoskeletal Tumor Society (MSTS) scale. Results: This study included 43 patients. The average length of the bone defect after tumor resection is 16.9 cm (range 6.3-35.3 cm). Patients with autograft not including the knee joint surface had significantly better healing outcomes (ISOLS scores) (80.6% ± 15% vs 28.2% ± 4.9%, P<0.001) and limb function (MSTS score) (87% ± 11.6% vs 27.2% ± 4.4%, P<0.001) than patients with autografts including the knee joint surface. The healing time of the end of inactivated autografts near the metaphyseal was significantly shorter than that of the end far away from the metaphyseal (9.8 ± 6.3 months vs 14.9 ± 6.3 months, P=0.0149). One patient had local recurrence, one had an autograft infection, five (all of whom had an autograft including the knee joint surface) had joint deformities, and seven had bone non-union. Conclusion: Frozen inactivated autologous tumor bone replantation is safe and results in good bone healing. But this method is not suitable for patients with autograft involving the knee joint surface.

The application of custom 3D-printed prostheses with ultra-short stems in the reconstruction of bone defects: a single center analysis.

Objective: Considering the advantages and widespread presence of 3D-printing technology in surgical treatments, 3D-printed porous structure prostheses have been applied in a wide range of the treatments of bone tumor. In this research, we aimed to assess the application values of the 3D-printed custom prostheses with ultra-short stems for restoring bone defects and maintaining arthrosis in malignant bone tumors of lower extremities in children. Methods: Seven cases of pediatric patients were included in this study. In all cases, the prostheses were porous titanium alloy with ultra-short stems. MSTS 93 (Musculoskeletal Tumor Society) scores were recorded for the functional recovery of the limbs. VAS (Visual analogue scale) scores were utilized to assess the degree of painfulness for the patients. X-ray and MRI (magnetic resonance imaging) were applied to evaluate the bone integration, prostheses aseptic loosening, prostheses fracture, wound healing, and tumor recurrence during follow-up. Results: During follow-up, none of the patients developed any postoperative complications, including prostheses aseptic loosening, prostheses fracture, or tumor recurrence. Radiological examinations during the follow-up showed that prostheses implanted into the residual bone were stably fitted and bone defects were effectively reconstructed. The MSTS 93 scores were 24.9 ± 2.9 (20-28). VAS scores were decreased to 5.8 ± 1.2 (4.0-7.0). No statistically significant differences in leg length discrepancy were observed at the time of the last follow-up. Conclusion: 3D-printing technology can be effectively applied throughout the entire surgical treatment procedures of malignant bone tumors, offering stable foundations for the initial stability of 3D-printed prostheses with ultra-short stems through preoperative design, intraoperative precision operation, and personalized prosthesis matching. With meticulous postoperative follow-up, close monitoring of postoperative complications was ensured. These favorable outcomes indicate that the utilization of 3D-printed custom prostheses with ultra-short stems is a viable alternative for reconstructing bone defects. However, further investigation is warranted to determine the long-term effectiveness of the 3D-printing technique.

Apatinib plus chemotherapy for non-metastatic osteosarcoma: a retrospective cohort study.

Background: Effective adjuvant therapy for osteosarcoma is necessary for improved outcomes. Previous studies demonstrated that apatinib plus doxorubicin-based chemotherapy may improve the efficacy of neoadjuvant therapy. This study aimed to clarify the effectiveness and safety of apatinib plus doxorubicin and cisplatin (AP) as neoadjuvant therapy for osteosarcoma. Methods: The clinical data of osteosarcoma patients who underwent neoadjuvant therapy and surgery between August 2016 and April 2022 were retrospectively collected and analyzed. Patients were divided into two groups: the apatinib plus AP (apatinib + AP) group and the methotrexate, doxorubicin, and cisplatin (MAP) group. Results: This study included 42 patients with nonmetastatic osteosarcoma (19 and 23 patients in the apatinib + AP and MAP groups, respectively). The 1- and 2-year disease-free survival rates in the apatinib + AP group were higher than those in the MAP group, but the difference was not significant (P=0.165 and 0.283, respectively). Some adverse events were significantly more common in the apatinib + AP group than in the MAP group, including oral mucositis (grades 3 and 4) (52.6% vs. 17.4%, respectively, P=0.023), limb edema (47.4% vs. 17.4%, respectively, P=0.049), hand-foot syndrome (31.6% vs. 0%, respectively, P=0.005), proteinuria (26.3% vs. 0%, respectively, P=0.014), hypertension (21.1% vs. 0%, respectively, P=0.035), and hypothyroidism (21.1% vs. 0%, respectively, P=0.035). No drug-related deaths occurred. There was no statistically significant difference in the incidence of postoperative complications between the groups (P>0.05). Conclusion: The present study suggests that apatinib + AP may be a promising candidate for neoadjuvant therapy for osteosarcoma, warranting further validation in prospective randomized controlled clinical trials with long-term follow-up.

Gemcitabine Plus Anlotinib Is Effective and Safe Compared to Gemcitabine Plus Docetaxel in Advanced Soft Tissue Sarcoma.

Objective: The aim of this study is to compare gemcitabine (G) plus docetaxel (D) versus G plus anlotinib (A) for advanced soft tissue sarcoma (STS). Methods: We retrospectively investigated 122 patients with locally advanced or metastatic STS who were treated with either G+D or G+A between July 2016 and October 2021 and compared the efficacy and toxicity of G+D and G+A. The primary endpoints were median progression-free survival (PFS) and the proportion of patients with grade ≥3 adverse events. We also analyzed differences in the clinical efficacy of G+D and G+A in leiomyosarcoma, and the differences in the clinical efficacy of G+D and G+A as first-line therapy. Results: Overall, 122 patients were included (81 patients receiving G+D and 41 patients receiving G+A) with a median age of 55 years. The main histological types are leiomyosarcoma, undifferentiated pleomorphic sarcoma, and liposarcoma. After a median follow-up of 25 months, PFS did not differ between patients treated with G+D and those treated with G+A (median PFS: 5.8 months and 6.8 months, p = 0.39), and overall survival (OS) was similar (median OS: 14.7 vs. 13.3 months, p = 0.75) with a similar objective response rate (18.5% vs. 14.6%, p = 0.17), whereas the proportion of patients with grade ≥3 adverse events treated with G+D was significantly higher than those treated with G+A (68% vs. 44%, p < 0.05). Subgroup analysis of leiomyosarcoma patients (47.5% of the patients) and first-line treatment patients (46.7% of the patients) shows that PFS was not significantly different between the two groups (LMS: median PFS: 6.5 months vs. 7.5 months, p = 0.08; first-line treatment: median PFS: 6.2 months vs. 7.1 months, p = 0.51). Conclusion: Compared with gemcitabine plus docetaxel for advanced STS, gemcitabine plus anlotinib achieved a similar response rate on median PFS and OS, but lower toxicity. These results suggest that gemcitabine plus anlotinib may be an effective and safe strategy for advanced STS.

Osteosarcoma Cell-Derived Exosomal ELFN1-AS1 Mediates Macrophage M2 Polarization via Sponging miR-138-5p and miR-1291 to Promote the Tumorgenesis of Osteosarcoma.

Background: Exosomes play an important role in cell-cell communication by transferring genetic materials such as long non-coding RNAs (lncRNAs) between cancer cells and tumor-associated macrophages (TAMs) in the tumor microenvironment (TME). Recent studies revealed that lncRNA ELFN1-AS1 could function as an oncogene in many human cancers. However, the role of extracellular lncRNA ELFN1-AS1 in cell-to-cell communication of osteosarcoma (OS) has not been fully investigated. Methods: Functional studies, including CCK-8, EdU staining and transwell assay were performed to investigate the role of ELFN1-AS1 in the progression of OS. 143B via xenograft mouse model was established to assess the role of ELFN1-AS1 in vivo. In addition, transmission electron microscopy (TEM) and real-time quantitative PCR (RT-qPCR) assay were used to verify the existence of exosomal ELFN1-AS1. Results: The level of ELFN1-AS1 was markedly upregulated in patients with advanced OS and in OS cells. In addition, overexpression of ELFN1-AS1 significantly promoted the proliferation, migration and invasion of OS cells, while knockdown of ELFN1-AS1 exhibited the opposite effects. Meanwhile, ELFN1-AS1 could be transferred from OS cells to macrophages via exosomes. Exosomal ELFN1-AS1 from 143B cells was able to promote macrophage M2 polarization, and M2 macrophage in return facilitated OS progression. Mechanistically, overexpression of ELFN1-AS1 upregulated CREB1 level via sponging miR-138-5p and miR-1291 in macrophage via. Conclusion: OS cell-derived exosomal ELFN1-AS1 was able to induce macrophage M2 polarization via sponging miR-138-5p and miR-1291, and M2 macrophage notably facilitated the progression of OS. These data suggested that ELFN1-AS1 might serve as a potential therapeutic target for osteosarcoma.

LncRNA PCBP1-AS1-mediated AR/AR-V7 deubiquitination enhances prostate cancer enzalutamide resistance.

The refractory of castration-resistant prostate cancer (CRPC) is mainly reflected in drug resistance. The current research on the resistance mechanism of CRPC is still in its infancy. In this study, we revealed for the first time the key role of LncRNA PCBP1-AS1 in CRPC drug resistance. Through detailed in vivo and in vitro studies, we found that PCBP1-AS1 may enhance the deubiquitination of AR/AR-V7 by stabilizing the USP22-AR/AR-V7 complex, thereby preventing AR/AR-V7 from being degraded through the ubiquitin-proteasome pathway. Targeting PCBP1-AS1 can significantly restore the drug sensitivity of enzalutamide-resistant tumors in vivo and in vitro. Our research further expands the function of LncRNA in castration-resistant prostate cancer, which may provide new potential for clinical diagnosis and targeted therapy.

Microwave breast tumor localization using wavelet feature extraction and genetic algorithm-neural network.

PURPOSE: Ultra-Wide Band (UWB) microwave breast cancer detection is a promising new technology for routine physical examination and home monitoring. The existing microwave imaging algorithms for breast tumor detection are complex and the effect is still not ideal, due to the heterogeneity of breast tissue, skin reflection, and fibroglandular tissue reflection in backscatter signals. This study aims to develop a machine learning method to accurately locate breast tumor. METHODS: A microwave-based breast tumor localization method is proposed by time-frequency feature extraction and neural network technology. First, the received microwave array signals are converted into representative and compact features by 4-level Discrete Wavelet Transform (DWT) and Principal Component Analysis (PCA). Then, the Genetic Algorithm-Neural Network (GA-NN) is developed to tune hyper-parameters of the neural network adaptively. The neural network embedded in the GA-NN algorithm is a four-layer architecture and 10-fold cross-validation is performed. Through the trained neural network, the tumor localization performance is evaluated on four datasets that are created by FDTD simulation method from 2-D MRI-derived breast models with varying tissue density, shape, and size. Each dataset consists of 1000 backscatter signals with different tumor positions, in which the ratio of training set to test set is 9:1. In order to verify the generalizability and scalability of the proposed method, the tumor localization performance is also tested on a 3-D breast model. RESULTS: For these 2-D breast models with unknown tumor locations, the evaluation results show that the proposed method has small location errors, which are 0.6076 mm, 3.0813 mm, 2.0798 mm, and 3.2988 mm, respectively, and high accuracy, which is 99%, 80%, 94%, and 85%, respectively. Furthermore, the location error and the prediction accuracy of the 3-D breast model are 3.3896 mm and 81%. CONCLUSIONS: These evaluation results demonstrate that the proposed machine learning method is effective and accurate for microwave breast tumor localization. The traditional microwave-based breast cancer detection method is to reconstruct the entire breast image to highlight the tumor. Compared with the traditional method, our proposed method can directly get the breast tumor location by applying neural network to the received microwave array signals, and circumvent any complicated image reconstruction processing.

Precise detection of early breast tumor using a novel EEMD-based feature extraction approach by UWB microwave.

The accurate detection of early breast cancer is of great significance to each patient. In recent years, breast cancer non-invasive detection technology based on Ultra-Wideband (UWB) microwave has been proposed and developed extensively, which is complementary to the existing methods. In this paper, a novel approach is proposed for tumor existence detection based on feature extraction algorithm. Firstly, the breast features are obtained by Ensemble Empirical Mode Decomposition (EEMD) and valid correlation Intrinsic Mode Function (IMF) selection. Secondly, raw feature datasets are constructed and then simplified by Principal Component Analysis (PCA) or Recursive Feature Elimination (RFE). Finally, the detection is realized by Support Vector Machines (SVM). The influence of different kernel functions and feature selection methods on detection results is compared. In this study, 11,232 sets of backscatter signals from simulation results of four different categories' breast models are utilized. And feature dataset is constructed by 24 specific features from each signal's four valid components. The results demonstrate that the proposed method can extract representative features and detect the early breast cancer effectively with the accuracy of 84.8%.

Accurate construction of 3-D numerical breast models with anatomical information through MRI scans.

The realistic numerical breast model is an important tool for verifying algorithms, improving design concepts, and exploring new technologies related to microwave breast cancer detection. Recently, several numerical breast models have been developed. However, these models do not include the real breast boundary and the chest region, which causes the electromagnetic wave propagation in the breast models to deviate from the actual situation. The proposed breast models in this paper overcome the significant deficiencies of the recent breast models in terms of structure completeness and authenticity. The model construction based on magnetic resonance imaging (MRI) scans is a multistep approach. Firstly, intensity inhomogeneity in MRI images is corrected by an improved nonparametric nonuniform intensity normalization (N4) algorithm. Then, a dual threshold and morphological transformation (DTMT) method is developed to segment the real breast region. Subsequently, a modified maximum inter-class variance (MICV) method is employed to automatically divide the breast region into the fat and the fibroglandular clusters with desired complexity. Finally, the dielectric properties of breast tissues are calculated by a piecewise weighted mapping method. The applicability and effectiveness of the proposed method are verified by constructing four breast models with varying tissue density, shape, and size. The constructed models in this study are significant to achieve reliable and precise effects for microwave breast cancer detection due to the accurate expression of the breast anatomical information and electromagnetic characteristics.

Tantalum boride as a biocompatible coating to improve osteogenesis of the bionano interface.

A proper biological microenvironment conducive to tissue repair and regeneration, while the bioimplant interface directly affects the local microenvironment. In this study, to improve the biological microenvironment, a nanosized tantalum boride (Ta-B) was coated on a titanium alloy substrate (Ti6Al4V, TC4) using magnetron cosputtering. The sample surface was characterized by X-ray diffraction (XRD) and transmission electron microscopy (TEM). To investigate the effects of tantalum boride coating on the microenvironment, rabbit bone marrow stromal cells (BMSCs), and RAW 264.7 cells were respectively seeded on the sample surface and relevant experiments were conducted in vitro. The pure tantalum coating (Ta) and naked TC4 were prepared as controls. Our results showed that the Ta-B coating enhanced cell proliferation and adhesion and inhibited the inflammatory response. Findings of alkaline phosphatase (ALP) staining, alizarin red staining and real-time PCR for osteoblastic gene expression indicated that Ta-B and Ta coating improve the osteogenesis, in which Ta-B coating showed higher osteogenesis than Ta coating. Thus, this study suggests that Ta-B coating with excellent biocompatibility could have new applications for wound healing in bone tissue engineering.

Potential antibacterial mechanism of silver nanoparticles and the optimization of orthopedic implants by advanced modification technologies.

Infection, as a common postoperative complication of orthopedic surgery, is the main reason leading to implant failure. Silver nanoparticles (AgNPs) are considered as a promising antibacterial agent and always used to modify orthopedic implants to prevent infection. To optimize the implants in a reasonable manner, it is critical for us to know the specific antibacterial mechanism, which is still unclear. In this review, we analyzed the potential antibacterial mechanisms of AgNPs, and the influences of AgNPs on osteogenic-related cells, including cellular adhesion, proliferation, and differentiation, were also discussed. In addition, methods to enhance biocompatibility of AgNPs as well as advanced implants modifications technologies were also summarized.

Fabrication of bioactive 3D printed porous titanium implants with Sr ion-incorporated zeolite coatings for bone ingrowth.

Functionalization of porous titanium alloy implants with bioactive coatings to improve bone regeneration performance is hotly pursued in recent decade. Here we demonstrate a facile strategy to design bioactive 3D printed porous titanium implants with strontium (Sr) ion incorporated zeolite coatings (SZCs). The SZCs can be uniformly fabricated on the 3D porous scaffolds using an in situ hydrothermal crystal growth method to improve their osteogenesis and osteointegration capacity. In vitro experiments of SZCs on a TC4 disk show that Sr ions can slowly release in the simulated body fluid by means of ion-exchange, thus can drastically improve apatite forming ability, biocompatibility, corrosion resistance, and alkaline phosphatase (ALP) activity. In vivo evaluation on a rabbit model with 3D printed titanium implants shows that the SZCs could significantly induce new bone formation both in and around the porous implants within four weeks. This work may open up a new method for the development of bioactive customized porous implants by functionalization with zeolite coatings for orthopedic applications.