Genetically modified tool animal models are the animal models,which are generated by modifying a defined gene and can be used as a tool to help realize other objective.Genetically modified large animals have wide applications in agriculture and biomedicine.Tool animal models play important role in biological research and development of new drugs in biomedicine,especially,have made tremendous contribution in revealing gene function and pathway of signal transduction.Pigs are not only an economically important agriculture animals,but also an ideal animal model in biomedicine due to its close similarity to human in physiology,as well as organ structure and size.Thanks to the breakthrough of newly emerged gene editing technology,striking progress has made in establishment of genetically modified tool pig models which include the ones used for monitoring pluripotency of cells,tracing cell lineages,replacing genes mediated by Cre recombinase,mimicking immunodeficiency,as well as gene editing in vivo.These tool models have been widely applied in biological research.Here,we will review the progress in generation of genetically modified tool pig models and their applications.

Objective:To analyze locoregional recurrence (LRR) pattern of patients with pT 1-2N 1 breast cancer after modified radical mastectomy, with and without adjuvant radiotherapy (RT). Methods:A total of 5442 eligible patients with breast cancer from 12 Chinese centers were included. The LRR sites and the effect of RT at different sites on recurrence in patients with and without RT were analyzed. The Kaplan-Meier method was used to calculate the cumulative LRR rate, and the difference was compared by the log-rank test.Results:With a median follow-up time of 63.8 months for the entire cohort, 395 patients developed LRR. The chest wall and supraclavicular fossa were the most common LRR sites, regardless of RT or molecular subtypes. The 5-year chest wall recurrence rates for patients with and without chest wall irradiation were 2.5% and 3.8%( P=0.003); the 5-year supraclavicular lymph nodal recurrence rates for patients with and without supraclavicular fossa irradiation were 1.3% and 4.1%( P<0.001); the 5-year axillary recurrence-free rates for patients with and without axillary irradiation were 0.8% and 1.5%( HR=0.31, 95% CI: 0.04-2.23, P=0.219); and the 5-year internal mammary nodal recurrence-free rates for patients with and without internal mammary nodal irradiation were 0.8% and 1.5%( HR=0.45, 95% CI: 0.11-1.90, P=0.268). Conclusions:The chest wall and supraclavicular fossa are the most common LRR sites of patients with pT 1-2N 1 breast cancer after modified radical mastectomy, which is not affected by adjuvant RT or molecular subtypes. The chest wall and supraclavicular fossa irradiation significantly reduce the risk of recurrence in the corresponding area. However, axillary and internal mammary nodal irradiation has no impact on the risk of recurrence in the corresponding area.