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TNBC is characterized by high incidence of visceral metastasis and lacks effective clinical targets. This study aims to delineate the molecular mechanisms of SENP1 in TNBC invasion and metastasis. By using IHC to test the SENP1 expression in TNBC tissues, we analyzed the relationship between SENP1 expression and TNBC prognosis. We showed that SENP1 expression was higher in TNBC tumor tissues and related to TNBC prognosis, supporting SENP1 as an independent risk factor. High expression of SENP1 was significantly associated with histologic grade and tumor lymph node invasion. Intriguingly, the expression levels of SENP1 in TNBC tumors were significantly correlated with that of CSN5, GATA1 and ZEB1. Importantly, SENP1 promoted TNBC cell migration and invasion by regulating ZEB1 deubiquitination and expression through CSN5. Further studies showed that deSUMOylation at lysine residue K137 of GATA1 enhanced the binding of GATA1 to the CSN5 promoter and transactivated CSN5 expression. In addition, we showed that ZEB1 is deubiquitinated at lysine residue K1108. Our in vivo studies also indicated that reduction in SENP1 expression upregulated GATA1 SUMOylation, and thus resulted in decreased expression of CSN5 and ZEB1 in the tumor microenvironment, which decelerated TNBC progression and metastasis. SENP1 promoted CSN5-mediated ZEB1 protein degradation via deSUMOylation of GATA1, and thus influenced TNBC progression. These findings suggest that SENP1 could be utilized as a potential target for blockade of TNBC development and thus provide a totally new approach for TNBC treatment.

Objective: Adolescent idiopathic scoliosis (AIS) is a three‐dimensional structural deformity of the spine caused by the disruption of the biomechanical balance of the spine. However, the current biomechanical modeling and analysis methods of scoliosis cannot really describe the real state of the spine. This study aims to propose a high‐precision biomechanical modeling and analysis method that can reflect the spinal state under gravity and provide a theoretical basis for therapeutics. Methods: Combining CT and X‐ray images of AIS patients, this study constructed an adjusted three‐dimensional model and FE model of the spine corresponding to the patient's gravity position, including vertebral bodies, intervertebral discs, ribs, costal cartilage, ligaments, and facet cartilage. Then, the displacement and stress of the spine under gravity were analyzed. Results: A model of the T1‐Sacrum with 1.7 million meshes was constructed. After adding the gravity condition, the maximum displacement point was at T1 of thoracic vertebra (20.4 mm). The analysis indicates that the stress on the lower surface of the vertebral body in thoracolumbar scoliosis tended to be locally concentrated, especially on the concave side of the primary curvature's vertebral body (the maximum stress on the lower surface of T9 is 32.33 MPa) and the convex side of the compensatory curvature's vertebral body (the maximum stress on the lower surface of L5 is 41.97 MPa). Conclusion: This study provides a high‐precision modeling and analysis method for scoliosis with full consideration of gravity. The reliability of the method was verified based on patient data. This model can be used to analyze the biomechanical characteristics of patients in the treatment plan design stage. [ABSTRACT FROM AUTHOR]

The dual mobility hip implant has been introduced recently and increasingly used in total hip replacement to maintain the stability and reduce the risk of post-surgery dislocation. However, the kinematics and contact mechanisms of dual mobility hip implants have not been investigated in detail in the literature. Therefore, finite element method was adopted in this study to investigate dynamics and contact mechanics of a typical metal-on-polymer dual mobility hip implant under different friction coefficient ratios between the inner and the outer articulations and clearances/interferences between the ultra-high-molecular-weight polyethylene liner and the metal back shell. A critical ratio of friction coefficients between the two pairs of contact interfaces was found to mainly determine the rotating surfaces. Furthermore, an initial clearance between the liner and the back shell facilitated the rotation of the liner while an initial interference prevented such a motion at the outer articulating interface. In addition, the contact area and the sliding distance at the outer articulating surface were markedly greater than those at the inner cup-head interface, potentially leading to extensive wear at the outer surface of the liner. [ABSTRACT FROM AUTHOR]

The surgical installation accuracy of the components in unicompartmental knee arthroplasty (UKA) is an important factor affecting the joint function and the implant life. Taking the ratio of the medial-lateral position of the femoral component relative to the tibial insert (a/A) as a parameter, and considering nine installation conditions of the femoral component, this study established the musculoskeletal multibody dynamics models of UKA to simulate the patients' walking gait, and investigated the influences of the medial-lateral installation positions of the femoral component in UKA on the contact force, joint motion and ligament force of the knee joint. The results showed that, with the increase of a/A ratio, the medial contact force of the UKA implant was decreased and the lateral contact force of the cartilage was increased; the varus rotation, external rotation and posterior translation of the knee joint were increased; and the anterior cruciate ligament force, posterior cruciate ligament force and medial collateral ligament force were decreased. The medial-lateral installation positions of the femoral component in UKA had little effect on knee flexion-extension movement and lateral collateral ligament force. When the a/A ratio was less than or equalled to 0.375, the femoral component collided with the tibia. In order to prevent the overload on the medial implant and lateral cartilage, the excessive ligament force, and the collision between the femoral component and the tibia, it is suggested that the a/A ratio should be controlled within the range of 0.427-0.688 when the femoral component is installed in UKA. This study provides a reference for the accurate installation of the femoral component in UKA.

Posterior-stabilized total knee prostheses have been widely used in orthopedic clinical treatment of knee osteoarthritis, but the patients and surgeons are still troubled by the complications, for example severe wear and fracture of the post, as well as prosthetic loosening. Understanding the in vivo biomechanics of knee prostheses will aid in the decrease of postoperative prosthetic revision and patient dissatisfaction. Therefore, six different designs of posterior-stabilized total knee prostheses were used to establish the musculoskeletal multibody dynamics models of total knee arthroplasty respectively, and the biomechanical differences of six posterior-stabilized total knee prostheses were investigated under three simulated physiological activities: walking, right turn and squatting. The results showed that the post contact forces of PFC Sigma and Scorpio NGR prostheses were larger during walking, turning right, and squatting, which may increase the risk of the fracture and wear as well as the early loosening. The post design of Gemini SL prosthesis was more conductive to the knee internal-external rotation and avoided the edge contact and wear. The lower conformity design in sagittal plane and the later post-cam engagement resulted in the larger anterior-posterior translation. This study provides a theoretical support for guiding surgeon selection, improving posterior-stabilized prosthetic design and reducing the prosthetic failure.

Backgrounds : To evaluate the predictive power of 18 F-Fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) derived radiomics in molecular subtype classification of breast cancer (BC). Methods : A total of 273 primary BC patients who underwent a 18 F-FDG PET/CT imaging prior to any treatment were included in this retrospective study, and the values of five conventional PET parameters were calculated, including the maximum standardized uptake value (SUVmax), SUVmean, SUVpeak, metabolic tumor volume (MTV), and total lesion glycolysis (TLG). The ImageJ 1.50i software and METLAB package were used to delineate the contour of BC lesions and extract PET/CT derived radiomic features reflecting heterogeneity. Then, the least absolute shrinkage and selection operator (LASSO) algorithm was used to select optimal subsets of radiomic features and establish several corresponding radiomic signature models. The predictive powers of individual PET parameters and developed PET/CT derived radiomic signature models in molecular subtype classification of BC were evaluated by using receiver operating curves (ROCs) analyses with areas under the curve (AUCs) as the main outcomes. Results : All of the three SUV parameters but not MTV nor TLG were found to be significantly underrepresented in luminal and non-triple (TN) subgroups in comparison with corresponding non-luminal and TN subgroups. Whereas, no significant differences existed in all the five conventional PET parameters between human epidermal growth factor receptor 2+ (HER2+) and HER2- subgroups. Furthermore, all of the developed radiomic signature models correspondingly exhibited much more better performances than all the individual PET parameters in molecular subtype classification of BC, including luminal vs. non-luminal, HER2+ vs. HER2-, and TN vs. non-TN classification, with a mean value of 0.856, 0.818, and 0.888 for AUC. Conclusions : PET/CT derived radiomic signature models outperformed individual significant PET parameters in molecular subtype classification of BC., (© 2021 The Author(s). Published by BRI.)