Toll-like receptors (TLRs) are transmembrane components that sense danger signals, like damage- and pathogen-associated molecular pattern molecules, as receptors, and maintain homeostasis in tissues. They are mainly involved in immune system activation through a variety of mediators, which either carry out (1) elimination of pathogenic threats and redressing homeostatic imbalances or (2) contribution to the initiation and worsening of pathological conditions, including cancers. Under physiological conditions, TLRs coordinate the innate and adaptive immunity, and inhibit autoimmune disorders. In pathological conditions, such as cancer, they can present both tumor and receptor-specific roles. Although the roles of individual TLRs in various cancers have been described, the effects of targeting TLRs to treat cancer and prevent metastasis are still controversial. A growing body of literature has suggested contribution of both activators and inhibitors of TLR signaling pathway for cancer treatment, dependent on several context-specific factors. In short, TLRs can play dual roles with contradictory outcomes in neoplastic conditions. This hampers the development of TLR-based therapeutic interventions. A better understanding of the interwoven TLR pathways in cancerous microenvironment is necessary to design TLR-based therapies. In this review, we consider the molecular mechanisms of TLRs signaling and their involvement in tumor progression. Therapeutic modalities targeting TLRs for cancer treatment are discussed as well.

Objective Surgery simulators have gained popularity in medical education during recent decades especially following COVID-19 pandemics. This study was designed to find the most effective and applicable model for development of total knee arthroplasty surgery simulator. Method The protocol of this study is evaluated and confirmed by Tehran university of Medical Sciences research committee (No: 52841-101-1-1400) in March 2021. This is a qualitative study using focus group discussion (FGD) for data gathering. Three FGDs were performed through online platform. Eligible five orthopedics residents, four fellowship trainees, and seven university professors from 3 different university hospitals were interviewed. Results The main domains of discussion were the necessity of a TKA simulator, virtual vs. physical model, bone and soft tissue characteristics, and the feedback system. 12% of participants (2 senior residents) said a virtual model has more advantages than a physical one while the other two thought physical model is more applicable. 12% of them (One senior resident and a fellowship trainee) suggested a mixed model would be more useful. The essential parts of the TKA simulator were mainly addressed by fellowship trainees focusing on presence of foot, ankle and hip in the model and inclusion of vital soft tissue elements and ligaments and tendons (especially collateral ligaments). Gap balancing was noticed as a crucial part by 40% of participants (senior residents and fellowships). To improve the simulator, participants suggested that it should have a modular design with sensors to alarm any damage to vital elements and feedbacks given during the procedures. Conclusion Through this study, the participants highlighted the most important parts of hard and soft tissues in the model, as well as the fundamental points in designing the TKA simulator.