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.

[Objective] To study the molecular biological mechanism for a case of ABO blood group B subtype, and perform three-dimensional modeling of the mutant enzyme. [Methods] The ABO phenotype was identified by the tube method and microcolumn gel method; the ABO gene of the proband was detected by sequence-specific primer polymerase chain reaction (PCR-SSP), and the exon 6 and 7 of the ABO gene were sequenced and analyzed. Homologous modeling of Bw.03 glycosyltransferase (GT) was carried out by Modeller and analyzed by PyMOL2.5.0 software. [Results] The weakening B antigen was detected in the proband sample by forward typing, and anti-B antibody was detected by reverse typing. PCR-SSP detection showed B, O gene, and the sequencing results showed c.721 C>T mutation in exon 7 of the B gene, resulting in p. Arg 241 Trp. Compared with the wild type, the structure of Bw.03GT was partially changed, and the intermolecular force analysis showed that the original three hydrogen bonds at 241 position disappeared. [Conclusion] Blood group molecular biology examination is helpful for the accurate identification of ambiguous blood group. Homologous modeling more intuitively shows the key site for the weakening of Bw.03 GT activity. The intermolecular force analysis can explain the root cause of enzyme activity weakening.