A deep learning model for accurately predicting cancer-specific survival in patients with primary bone sarcoma of the extremity: a population-based study

Purpose Primary bone and joint sarcomas of the long bone are relatively rare neoplasms with poor prognosis. An efficient clinical tool that can accurately predict patient prognosis is not available. The current study aimed to use deep learning algorithms to develop a prediction model for the prognosis of patients with long bone sarcoma. Methods Data of patients with long bone sarcoma in the extremities was collected from the Surveillance, Epidemiology, and End Results Program database from 2004 to 2014. Univariate and multivariate analyses were performed to select possible prediction features. DeepSurv, a deep learning model, was constructed for predicting cancer-specific survival rates. In addition, the classical cox proportional hazards model was established for comparison. The predictive accuracy of our models was assessed using the C-index, Integrated Brier Score, receiver operating characteristic curve, and calibration curve. Results Age, tumor extension, histological grade, tumor size, surgery, and distant metastasis were associated with cancer-specific survival in patients with long bone sarcoma. According to loss function values, our models converged successfully and effectively learned the survival data of the training cohort. Based on the C-index, area under the curve, calibration curve, and Integrated Brier Score, the deep learning model was more accurate and flexible in predicting survival rates than the cox proportional hazards model. Conclusion A deep learning model for predicting the survival probability of patients with long bone sarcoma was constructed and validated. It is more accurate and flexible in predicting prognosis than the classical CoxPH model (AU)

A deep learning model for accurately predicting cancer-specific survival in patients with primary bone sarcoma of the extremity: a population-based study.

PURPOSE: Primary bone and joint sarcomas of the long bone are relatively rare neoplasms with poor prognosis. An efficient clinical tool that can accurately predict patient prognosis is not available. The current study aimed to use deep learning algorithms to develop a prediction model for the prognosis of patients with long bone sarcoma. METHODS: Data of patients with long bone sarcoma in the extremities was collected from the Surveillance, Epidemiology, and End Results Program database from 2004 to 2014. Univariate and multivariate analyses were performed to select possible prediction features. DeepSurv, a deep learning model, was constructed for predicting cancer-specific survival rates. In addition, the classical cox proportional hazards model was established for comparison. The predictive accuracy of our models was assessed using the C-index, Integrated Brier Score, receiver operating characteristic curve, and calibration curve. RESULTS: Age, tumor extension, histological grade, tumor size, surgery, and distant metastasis were associated with cancer-specific survival in patients with long bone sarcoma. According to loss function values, our models converged successfully and effectively learned the survival data of the training cohort. Based on the C-index, area under the curve, calibration curve, and Integrated Brier Score, the deep learning model was more accurate and flexible in predicting survival rates than the cox proportional hazards model. CONCLUSION: A deep learning model for predicting the survival probability of patients with long bone sarcoma was constructed and validated. It is more accurate and flexible in predicting prognosis than the classical CoxPH model.

Using network pharmacology to fabricate crosslinked hyaluronan-chondroitin sulphate-resveratrol composite hydrogels for cartilage regeneration.

Cartilage tissue engineering provides a new approach for the treatment of cartilage damage. The combination of drug system with a tissue scaffold could be highly beneficial. Resveratrol (RES) is a potent anti-inflammatory agent, but its target genes and molecular mechanism of cartilage repair remain to be further studied. We used systems biology and network pharmacology methods to explore the mechanism of RES for chondrocyte and macrophages. Meanwhile, crosslinked hyaluronan-chondroitin sulphate-RES hydrogels (cHA-CS-RES) were constructed based on the target prediction results. Byin vitroandin vivoexperiments, we investigated its anti-inflammatory and pro-chondrogenesis. The results showed there were 12 hub genes potentially interacting in the RES-chondrocyte-macrophage network.In vitroexperiments were used to further verify the validity of the predicted hub genes. The composite hydrogels were successfully fabricated, and maintenance of the characteristic was further confirmed.In vitrostudy, cHA-CS-RES showed high cell viability, anti-inflammatory and pro-chondrogenesis abilities.In vivostudy of cartilage defects confirmed that the cHA-CS-RES groups were significantly better than the control group. Network pharmacology was used to predict and screen the target proteins of RES critical to cartilage tissue engineering. Moreover, cHA-CS-RES composite hydrogel showed good cartilage repair effects, anti-inflammatory and pro-chondrogenesis abilities.

Identification of key biomarkers related to epithelial-mesenchymal transition and immune infiltration in ameloblastoma using integrated bioinformatics analysis.

OBJECTIVE: This study aimed to elucidate the underlying mechanisms of ameloblastoma (AM) through integrated bioinformatics analysis. METHODS: We downloaded two microarrays of AMs from the GEO database and identified differentially expressed genes (DEGs) by integrated bioinformatics analysis. The enrichment analysis of DEGs was conducted to characterize GO and KEGG pathways. Protein-protein interaction (PPI) network and hub genes were screened via STRING and Cytoscape. CIBERSORT algorithm was utilized to analyze immune infiltration in AMs. We also verified the diagnostic and therapeutic value of hub genes. RESULTS: Overall, 776 DEGs were identified in AMs through bioinformatics analysis. The function enrichment analysis shed light on pathways involved in AMs. Subsequently, we screened six hub genes via PPI network. Furthermore, we evaluated immune infiltration in AMs and found that macrophages may be participating in the progression of AMs. The upregulated expression of FN1 was related to the macrophages M2 polarization. Finally, ROC analysis indicated that six hub genes had high diagnostic value for AMs and 11 drugs interacted with upregulated hub genes were identified by screening the DGIdb database. CONCLUSION: This study revealed the underlying mechanisms of pathogenesis and biological behavior of AMs and provided candidate targets for the diagnosis and treatment of AMs.

Comparison of customized 3D-printed prosthesis and screw-rod-cage system reconstruction following resection of periacetabular tumors.

Background and purpose: Various operative methods are used for reconstructing pelvic girdle after resection of primary malignant periacetabular tumor has been reported. The objective of this study was to evaluate the accuracy, effectiveness, and safety of customized three dimensional-printed prosthesis (3DP) in the reconstruction of bone defects compared with conventional reconstruction using the screw-rod-cage system. Methods: A retrospective case-control analysis of 40 patients who underwent pelvic tumor resection and reconstruction with a customized 3D-printed prosthesis (3DP), or screw-rod-cage system (SRCS) between January 2010 and December 2019 was performed. The minimum follow-up time for patients alive was 2 years. Blood loss, operation time, complications, surgical margin, local recurrence, distant metastases, status at time of latest follow-up, MSTS-93 score, Harris hip score, and postoperative radiographic parameters were recorded. Moreover, overall survival, tumor-free survival, and prosthesis survival rates in both groups were compared. Results: Customized 3DP reconstruction was performed in 15 patients, and SRCS reconstruction was done in 25 patients. The group of patients treated with customized 3DP reconstruction had significantly shorter operation time (323.7 ± 83.7 vs. 393.6 ± 98.8 min; P = 0.028) and more precise (all P < 0.05) radiographic reconstruction parameters than patients in the SRCS group. Fewer complications (P = 0.026), better MSTS score (P = 0.030), and better Harris hip score (P = 0.016) were achieved in the 3DP group. Furthermore, the survival rate of prosthesis was also significantly better in the 3DP group (P = 0.039). However, blood loss, surgical margin, local recurrence, distant metastases, and status at time of latest follow-up had no significant difference between two groups. Conclusion: Compared with the screw-rod-cage system reconstruction, the customized 3D-printed prosthesis reconstruction is equally safe and effective, but it is more accurate and time-saving and is associated with fewer complications.

Customized three dimensional printed prosthesis as a novel intercalary reconstruction for resection of extremity bone tumours: a retrospective cohort study.

AIMS: The 3D-printed prosthesis (3DP) is a novel treatment for massive bone defect reconstruction after tumor resection. This study was aiming to explore the clinical efficacy of customized 3DP for intercalary reconstruction by comparing the clinical outcomes after implanting customized 3DP or conventional allograft in limb salvage surgery. METHODS: A total of 28 patients with extremity bone tumors who underwent customized 3DP or conventional allograft reconstruction between 2011 and 2018 at our institution were analyzed retrospectively. Among them, 14 cases received customized 3DP reconstruction (3DP group), and 14 cases received conventional allograft reconstruction (control group). Demographics, surgical outcomes, radiographical assessments, limb functions, and post-operative complications between these two groups were collected to evaluate clinical outcomes. RESULTS: No significant difference was observed in the demographics, mean intra-operative blood loss, MOSI scores, and MSTS scores between the two groups. Patients in 3DP group had a shorter operative time (157.9 vs 199.6 min, p = 0.03) and lesser number of fluoroscopy (4.1 vs 8.1, p < 0.001) compared to control group. The mean time to osseointegration at bone-implant interfaces in 3DP group was significantly earlier than that in control group (6.1 vs 12.2 months, p < 0.001). Moreover, the 3DP group had a significantly lower post-operative complication rate than the control group (7% vs 50%, p = 0.03). CONCLUSIONS: The customized 3DP might provide a promising strategy for intercalary reconstruction in limb salvage surgery with more precise reconstruction, higher surgical efficiency, and comparable satisfactory clinical outcomes.

Effect of electrohydrodynamic printing scaffold with different spacing on chondrocyte dedifferentiation.

Background: Osteoarthritis (OA) is a common degenerative disease. Chondrocyte dedifferentiation can accelerate the progress of OA. Three-dimensional printing (3DP) is widely used in tissue regeneration applications. A three-dimensional (3D) culture system with 3D printed scaffolds could reduce the dedifferentiation of chondrocytes during passages, which would be a potential method for chondrocyte expansion. Methods: The viability and proliferation of chondrocytes on scaffolds and effects of scaffolds with 100, 150, 200, 250 or 300 µm spacing on chondrocyte dedifferentiation were analyzed in vitro. The morphology of scaffolds and cell/scaffold constructs was observed by scanning electron microscopy (SEM). Glycosaminoglycan (GAG) was evaluated by Alcian blue staining. The effects of different spacing on chondrocyte dedifferentiation were evaluated by the messenger RNA (mRNA) and protein levels of cartilage-related genes. Results: With more binding sites, the proliferation and viability of chondrocytes on scaffolds with 100 and 150 µm spacing were better than those with 200, 250 and 300 µm spacing on day 1, but this advantage diminished over time. The histology and quantitative real-time polymerase chain reaction (qRT-PCR) results showed that 200 µm spacing inhibits chondrocyte dedifferentiation better. Conclusions: 3D printed scaffolds with 200 µm spacing can inhibit chondrocyte dedifferentiation, providing a basis for the future study of 3D printed scaffolds as an effective method for chondrocyte expansion.

Clinical application of 3D-printed patient-specific guide plate combined with computer navigation in acetabular reconstruction following resection of periacetabular tumors.

Background: The precise acetabular reconstruction has historically been a challenging procedure. 3D-printed patient-specific guide (PSG) and computer navigation (CN) technologies have been used to assist acetabular component positioning and pelvic reconstruction. This precise reconstruction approach may translate into clinical benefit. Methods: The clinical data of 84 patients who underwent periacetabular malignant tumor resection and screw-rod-acetabular cage system reconstruction in our center from January 2013 to December 2020 were retrospectively analyzed. Patients were divided into four groups: free hand (FH) group, PSG group, CN group, and PSG combined with computer navigation (PSG + CN) group. The operation time, intraoperative blood loss, and number of fluoroscopy views were recorded. The oncological prognosis, radiographic measurements of the acetabulum, limb function data, and postoperative complications were compared among groups. And finally, we evaluated the risk factors for mechanical failure of the prosthesis. Results: The postoperative X-ray and computed tomography (CT) scan revealed that the vertical offset discrepancy (VOD) between affected side and contralateral side was 8.4±1.9, 5.9±2.2, 4.1±1.3, and 2.4±1.2 mm in each groups; the horizontal offset discrepancy (HOD) was 9.0±1.9, 6.1±2.2, 3.2±1.3, and 2.1±1.2 mm, correspondingly; the abduction angle discrepancy (ABAD) was 8.6°±1.8°, 5.6°±2.0°, 2.5°±1.3°, and 1.8°±0.9°, respectively; the anteversion angle discrepancy (ANAD) was 5.9°±1.6°, 3.6°±1.7°, 2.9°±1.6°, and 1.9°±0.9°, correspondingly. Statistical results show that the PSG + CN group was superior to the FH group and the PSG group in terms of acetabular position and limb function (P<0.05). Body mass index (P=0.040) and resection type (P=0.042) were found to be the high-risk factors for mechanical failure of the prosthesis. Conclusions: PSG + CN has potential advantages in improving the accuracy and safety of acetabular positioning and reconstruction.

Reconstruction with customized, 3D-printed prosthesis after resection of periacetabular Ewing's sarcoma in children using "triradiate cartilage-based" surgical strategy:a technical note.

BACKGROUND: Surgery for Ewing sarcoma involving acetabulum in children is challenging. Considering the intrinsic structure of immature pelvis, trans-acetabular osteotomy through triradiate cartilage might be applied. The study was to describe the surgical technique and function outcomes of trans-acetabular osteotomy through triradiate cartilage and reconstruction with customized, 3D-printed prosthesis. METHODS: Two children with periacetabular ES were admitted to our hospital. The pre-operative imaging showed the triradiate cartilage was not penetrated or wholly affected by tumor. After neoadjuvant chemotherapy, the tumor was excised by trans-acetabular osteotomy basing on "triradiate cartilage strategy" and the acetabulum was reconstructed with the customized, 3D-printed prosthesis. The prosthesis was designed in Mimics software basing on the images from CT, optimized by topology technique, and examined in FE model. After implantation, the oncological and functional outcomes were evaluated with radiography, CT, and MSTS score. RESULTS: The operation time and intra-operative blood loss in these two children were 3.5h, 2.5h and 300 ml, 600 ml, respectively. The postoperative specimen showed the tumor was en bloc removed with safe margin. In the latest follow-up (48 months and 24 months), both patients were free of disease and had satisfactory function according to MSTS score. The radiography indicated the prosthesis fit the defect well without loosening. CONCLUSION: The customized, 3D-printed prosthesis could provide optimal reconstruction of pelvic ring and satisfactory hip function after trans-acetabular osteotomy in children. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: This study provides promising results of implantation of customized 3D printing prosthesis in children's pelvic sarcoma, which may bring a new design method for orthopaedic implants.

Investigating the protective effect of tanshinone IIA against chondrocyte dedifferentiation: a combined molecular biology and network pharmacology approach.

BACKGROUND: Osteoarthritis (OA) is a common degenerative disease with multifactorial etiology. The dedifferentiation of chondrocytes can accelerate the progress of OA. Tanshinone IIA (TIIA) has been widely used to treat OA for many years and has proved to be effective in inhibiting chondrocyte dedifferentiation. Until now, the precise mechanism of TIIA's effect against dedifferentiation has not been well understood. METHODS: The targets of TIIA were explored from public databases using various methods. The related targets of OA were obtained from the GeneCards database and the Online Mendelian Inheritance in Man (OMIM) database. The potential targets and signaling pathways were determined using protein-protein interaction (PPI), Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Cell viability, proliferation, and metabolic activity were analyzed in vitro. The effects of TIIA on chondrocyte dedifferentiation were evaluated by assessing morphological changes, glycosaminoglycan (GAG) production, and messenger RNA (mRNA) levels of cartilage-related genes. After 48 hours of culture in medium with 100 µg/mL TIIA, chondrocytes/hydrogel spheres were implanted to repair cartilage defects in a rat model. The harvested specimens were examined with hematoxylin and eosin (H&E) staining and immunohistochemistry to evaluate cartilage regeneration. RESULTS: The results showed that there were 28 genes potentially interacting in the TIIA-chondrocyte dedifferentiation network, and nine hub genes were identified. In vitro experiments showed an inhibitory effect of TIIA on chondrocyte dedifferentiation. The proliferation and viability of chondrocytes were promoted by TIIA at a concentration of 100-200 µg/mL, but inhibited by TIIA at 400 µg/mL. Furthermore, the histology results showed that chondrocyte/hydrogel spheres pre-treated with TIIA had better cartilage repair. CONCLUSIONS: This study revealed a systematic network pharmacology approach and provided a basis for the future study of TIIA as an effective treatment for cartilage regeneration. Moreover, in vitro and in vivo results confirmed the protective effects of TIIA against chondrocyte dedifferentiation.

Broad distribution of Ranavirus in free-ranging Rana dybowskii in Heilongjiang, China.

Ranaviruses have been associated with die-offs in cultured amphibians in China, but their presence in wild amphibians has not yet been assessed. We sampled free-ranging Rana dybowskii at seven sites throughout Heilongjiang Province to determine the presence and prevalence of ranaviruses in this region. Our results revealed an overall infection prevalence of 5.7% (18/315) for adults and 42.5% (51/120) for tadpoles by PCR. PCR-amplified product showed a high degree of homology with several members of the Iridoviridae, mostly with those belonging to the genus Ranavirus. The results indicate that ranaviruses are broadly distributed throughout Heilongjiang Province and could have important implications for the health of native wildlife. Additional sampling and management strategies should be urgently adopted to address the prevalence and health consequences of ranaviruses throughout China.

Early-spring survey for Batrachochytrium dendrobatidis in wild Rana dybowskii in Heilongjiang Province, China.

Batrachochytrium dendrobatidis has been investigated worldwide because of its importance in population declines in multiple species of amphibians; however, little is known regarding the disease status of all native amphibian species in China. The present study is the first survey of chytridiomycosis in free-ranging amphibian populations in China, and it examined the possible presence of B. dendrobatidis in Rana dybowskii in northeastern China (Heilongjiang Province). R. dybowskii is mainly distributed in the northeast part of China and is intensively hunted for human consumption, making populations vulnerable to extirpation in the event of additional stresses from disease epidemics. The survey was performed in early spring of 2008, using a PCR assay, histological examination of skin samples, and zoospore culture. In total, 191 frogs were examined; thus, a 95% confidence limit for prevalence of 1.57% was selected. Our results demonstrate that R. dybowskii is currently free from chytridiomycosis in Heilongjiang, even though the natural conditions of the sampling sites are suitable for the occurrence of B. dendrobatidis. Central and local governments should implement strict management measures to prevent the escape of non-native commercial amphibian species into this area, which might endanger local populations of native species.