Design, synthesis, and biological evaluation of piperazine derivatives as pan-PPARs agonists for the treatment of liver fibrosis.

Liver fibrosis is commonly occurred in chronic liver diseases, but there is no approved drug for clinical use. The nuclear receptor peroxisome proliferator-activated receptors (PPARs) could not only regulate metabolic homeostasis but also possess anti-inflammatory and antifibrotic effects, and pan-PPARs agonist was considered as a potential anti-liver fibrosis agent. In this study, a series of novel piperazine pan-PPARs agonists were developed, and the preferred compound 12 displayed potent and well-balanced pan-PPARs agonistic activity. Moreover, compound 12 could dose-dependently stimulate the PPARs target genes expression and showed high selectivity over other related nuclear receptors. Importantly, compound 12 exhibited excellent pharmacokinetic profiles and good anti-liver fibrosis effects in vivo. Collectively, compound 12 holds promise for developing an anti-liver fibrosis agent.

Hill-based musculoskeletal model for a fracture reduction robot.

BACKGROUND: The introduction of fracture reduction robot can solve the problem of large reduction forces during fracture reduction surgeries and the need to collect multiple medical images. However, because its safety has not been certified, there are few academic achievements on this type of robot. To calculate the safety factor during its operation, a musculoskeletal model needs to be established to study the constraints of muscles on the robot. The existing academic achievements of musculoskeletal modelling are mainly for application such as rehabilitation treatment and collision in car accidents. METHODS: A musculoskeletal model applied to the fracture reduction robot is proposed in this paper. First, by comparing the characteristics of mainstream muscle models and combining the biological characteristics of the anesthetised muscles, the Hill model was selected as the muscle model for this study. Second, based on the motion composition of six spatial degrees of freedom, five basic fractural malposition situations are proposed. Then, a 170-cm tall male musculoskeletal model was built in Opensim. Based on this model, the muscle force curves of the above malposition situations are calculated. Finally, a similar musculoskeletal model was established in Adams, and the accuracy of its muscle force data was tested. The study is approved by the ethics committee of the Rehabilitation Hospital, National Research Center for Rehabilitation Technical Aids, Beijing, China. RESULTS: The muscle force curve of Opensim and Adams model under situations of five basic malposition are compared. Most of the correlation coefficients are in the range of 0.98-0.99. The overall correlation coefficient is greater than 0.95. CONCLUSIONS: The simulation results prove that this model can be used for the safety assessment of the fracture reduction robots. This model will be served as an environmental constraint to study the control of fracture reduction robot.

Indirect visual guided fracture reduction robot based on external markers.

BACKGROUND: Traditional fracture reduction surgery cannot ensure the accuracy of the reduction while consuming the physical strength of the surgeon. Although monitoring the fracture reduction process through radiography can improve the accuracy of the reduction, it will bring radiation harm to both patients and surgeons. METHODS: We proposed a novel fracture reduction solution that parallel robot is used for fracture reduction surgery. The binocular camera indirectly obtains the position and posture of the fragment wrapped by the tissue by measuring the posture of the external markers. According to the clinical experience of fracture reduction, a path is designed for fracture reduction. Then using position-based visual serving control the robot to fracture reduction surgery. The study is approved by the ethics committee of the Rehabilitation Hospital, National Research Center for Rehabilitation Technical Aids, Beijing, China. RESULTS: Ten virtual cases of fracture were used for fracture reduction experiments. The simulation and model bone experiments are designed respectively. In model bone experiments, the fragments are reduced without collision. The angulation error after the reduction of this method is 3.3° ± 1.8°, and the axial rotation error is 0.8° ± 0.3°, the transverse stagger error and the axial direction error after reduction is 2 ± 0.5 mm and 2.5 ± 1 mm. After the reduction surgery, the external fixator is used to assist the fixing, and the deformity will be completely corrected. CONCLUSIONS: The solution can perform fracture reduction surgery with certain accuracy and effectively reduce the number of radiographic uses during surgery, and the collision between fragments is avoided during surgery.

Indirect visual guided fracture reduction robot based on external markers.

BACKGROUND: Traditional fracture reduction surgery cannot ensure the accuracy of the reduction while consuming the physical strength of the surgeon. Although monitoring the fracture reduction process through radiography can improve the accuracy of the reduction, it will bring radiation harm to both patients and surgeons. METHODS: We proposed a novel fracture reduction solution that parallel robot is used for fracture reduction surgery. The binocular camera indirectly obtains the position and posture of the fragment wrapped by the tissue by measuring the posture of the external markers. According to the clinical experience of fracture reduction, a path is designed for fracture reduction. Then using position-based visual serving control the robot to fracture reduction surgery. The study is approved by the Rehabilitation Hospital, National Research Center for Rehabilitation Technical Aids, Beijing , China. RESULTS: 10 virtual cases of fracture were used for fracture reduction experiments. The simulation and model bone experiments are designed respectively. In model bone experiments, the fragments are reduction without collision. The angulation error after the reduction of this method is:3.3°±1.8°, and the axial rotation error is 0.8°±0.3°, the transverse stagger error and the axial direction error after reduction is 2mm±0.5mm and 2.5mm±1mm. After the reduction surgery, the external fixator is used to assist the fixing, and the deformity will be completely corrected. CONCLUSIONS: The solution can perform fracture reduction surgery with certain accuracy and effectively reduce the number of radiographic uses during surgery, and the collision between fragments is avoided during surgery. This article is protected by copyright. All rights reserved.