Objective: To examine the causal relationship between endometrial cancer and breast cancer using bidirectional two-sample Mendelian randomization (MR) approach. Methods: Genetic association data of endometrial cancer were collected through a meta analysis, including 54 884 participants and 9 464 330 single nucleotide polymorphisms (SNPs), and genetic association data of breast cancer were collected through the Breast Cancer Society Consortium, with 228 951 participants and 10 680 257 SNPs. A forward MR analysis was performed using the inverse variance weighted (IVW) method with 8 endometrial cancer-associated SNPs as instrumental variables and breast cancer as the study outcome, and a reverse MR analysis was performed with 112 breast cancer-associated SNPs as instrumental variables and endometrial cancer as the study outcome. The heterogeneity was assessed using the Cochran's Q test, the horizontal pleiotropy was assessed using the MR-PRESSO test and MR-Egger regression, and the robustness of the results was verified with the leave-one-out. Results: Forward MR analysis results showed that patients with genetically predicted endometrial cancer had an increased risk of breast cancer compared to those without endometrial cancer (OR=1.083, 95%CI: 1.037-1.132). Reverse MR analysis showed that patients with genetically predicted breast cancer had an increased risk of endometrial cancer compared to those without breast cancer (OR=1.070, 95%CI: 1.010-1.134). Cochran's Q test detected no heterogeneity (P>0.05), and neither the MR-PRESSO test nor the MR-Egger regression revealed horizontal pleiotropy of instrumental variables (both P>0.05). Leave-one-out analysis showed robustness of the MR analysis results. Conclusion There are bidirectional causal relationship between endometrial cancer and breast cancer.

Aim To investigate the curative effect of rAAV-PR39-ADM,which co-expressed the gene of an-tibacterial peptide (PR39 ) and adrenomedullin (ADM),in a rat cerebral ischemia/reperfusion (I/R) injury.Methods In vitro,Matrigel angiogenesis as-say was made with human umbilical vein endothelial cells.In vivo,the cerebral I/R model was established by the occlusion of the cerebral artery for 2h and then reperfused for 24 h.SD rats were randomly divided in-to sham group,I/R+normal saline group,I/R+null virus (AAV ) group, and IR +rAAV-PR39-ADM group.rAAV-PR39-ADM,saline and null virus were administered through the femoral vein after 24 h of the reperfusion in I/R group.MRI,neurological deficit score,TTC and HE staining were measured respective-ly 1 ,2,3 and 4 weeks after the injection in order to e-valuate the therapeutic efficacy.Results In vitro, rAAV-PR39-ADM group had significant angiogenic effect compared with sham group and null virus group. In vivo,successful I/R model was verified by the ima-ges of MRI.Compared with sham group,the nerve function defect score and the cerebral infarction size in each time nodes were significantly raised in I/R groups (P<0.01).There was no significant difference in in-farct size and nerve function defect score between I/R+normal saline group and I/R +null virus (AAV ) group,and obviously,the IR +rAAV-PR39-ADM group lowered these indexes compared with the other two groups.HE staining showed that the number of neurons,new capillaries vessels of I/R +PR39-ADM group were significantly more than those in group I/R and group I/R +null virus.Conclusion The treat-ment of rAAV-PR39-ADM promotes vascular forma-tion,neuron protection and reduces the infarct size in the model of cerebral ischemia/reperfusion.