Automatic Breast Volume Scanner and B-Ultrasound-Based Radiomics Nomogram for Clinician Management of BI-RADS 4A Lesions.

RATIONALE AND OBJECTIVES: To develop and validate a nomogram for predicting the risk of malignancy of breast imaging reporting and data system (BI-RADS) 4A lesions to reduce unnecessary invasive examinations. MATERIALS AND METHODS: From January 2017 to July 2021, 190 cases of 4A lesions included in this study were divided into training and validation sets in a ratio of 8:2. Radiomics features were extracted from sonograms by Automatic Breast Volume Scanner (ABVS) and B-ultrasound. We constructed the radiomics model and calculated the rad-scores. Univariate and multivariate logistic regressions were used to assess demographics and lesion elastography values (virtual touch tissue image, shear wave velocity) and to develop clinical model. A clinical radiomics model was developed using rad-score and independent clinical factors, and a nomogram was plotted. Nomogram performance was evaluated using discrimination, calibration, and clinical utility. RESULTS: The nomogram included rad-score, age, and elastography, and showed good calibration. In the training set, the area under the receiver operating characteristic curve (AUC) of the clinical radiomics model (0.900, 95% confidence interval (CI): 0.843-0.958) was superior to that of the radiomics model (0.860, 95% CI: 0.799-0.921) and clinical model (0.816, 95% CI: 0.735-0.958) (p = 0.024 and 0.008, respectively). The decision curve analysis showed that the clinical radiomics model had the highest net benefit in most threshold probability ranges. CONCLUSION: ABVS and B-ultrasound-based radiomics nomograms have satisfactory performance in differentiating benign and malignant 4A lesions. This can help clinicians make an accurate diagnosis of 4A lesions and reduce unnecessary biopsy.

Wnt3a enhances bone morphogenetic protein 9-induced osteogenic differentiation of C3H10T1/2 cells.

BACKGROUND: Bone morphogenetic protein 9 (BMP9) and Wnt/ß-catenin signaling pathways are able to induce osteogenic differentiation of mesenchymal stem cells (MSCs), but the role of Wnt/ß-catenin signaling pathway in BMP9-induced osteogenic differentiation is not well understood. Thus, our experiment was undertaken to investigate the interaction between BMP9 and Wnt/ß-catenin pathway in inducing osteogenic differentiation of MSCs. METHODS: C3H10T1/2 cells were infected with recombinant adenovirus expressing BMP9, Wnt3a, and BMP9+Wnt3a. ALP, the early osteogenic marker, was detected by quantitative and staining assay. Later osteogenic marker, mineral calcium deposition, was determined by Alizarin Red S staining. The expression of osteopotin (OPN), osteocalcin (OC), and Runx2 was analyzed by Real time PCR and Western blotting. In vivo animal experiment was carried out to further confirm the role of Wnt3a in ectopic bone formation induced by BMP9. RESULTS: The results showed that Wnt3a enhanced the ALP activity induced by BMP9 and increased the expressions of OC and OPN, with increase of mineral calcium deposition in vitro and ectopic bone formation in vivo. Furthermore, we also found that Wnt3a increased the level of Runx2, an important nuclear transcription factor of BMP9. CONCLUSION: Canonical Wnt/ß-catenin signal pathway may play an important role in BMP9-induced osteogenic differentiation of MSCs, and Runx2 may be a linkage between the two signal pathways.

Smads, p38 and ERK1/2 are involved in BMP9-induced osteogenic differentiation of C3H10T1/2 mesenchymal stem cells.

Although previous studies have demonstrated that BMP9 is highly capable of inducing osteogenic differentiation of mesenchymal stem cells, the molecular mechanism involved remains to be fully elucidated. In this study, we showed that BMP9 simultaneously promotes the activation of Smad1/5/8, p38 and ERK1/2 in C3H10T1/2 cells. Knockdown of Smad4 with RNA interference reduced nuclear translocation of Smad1/5/8, and disrupted BMP9-induced osteogenic differentiation. BMP9-induced osteogenic differentiation was blocked by p38 inhibitor SB203580, whereas enhanced by ERK1/2 inhibitor PD98059. SB203580 decreased BMP9-activated Smads singling, and yet PD98059 stimulated Smads singling in C3H10T1/2 cells. The effects of inhibitor were reproduced with adenovirus expressing siRNA targeted p38 and ERK1/2, respectively. Taken together, our findings revealed that Smads, p38 and ERK1/2 are involved in BMP9-induced osteogenic differentiation. Also, it is noteworthy that p38 and ERK1/2 may play opposing regulatory roles in mediating BMP9-induced osteogenic differentiation of C3H10T1/2 cells.