Background: Observational studies have investigated the association between lipid-lowering drugs and breast cancer (BC) and endometrial cancer (EC), but some controversy remains. Objective: This paper aims to explore the causal relationship between genetic proxies for lipid-lowering drugs and breast and endometrial cancers using drug-target Mendelian randomization (MR). Methods: Analyses were mainly performed using inverse variance weighted (IVW), heterogeneity and horizontal pleiotropy tests, and sensitivity analysis to assess the robustness of the results and causal relationship. Results: HMGCR, APOB, and NPC1L1 increased the risk of breast cancer, LPL increased the risk of endometrial cancer, and APOC3 decreased the risk of breast and endometrial cancer. No heterogeneity or horizontal pleiotropy was detected, and nor was there any evidence of an association between other lipid-lowering drugs and breast and endometrial cancer. Conclusion: Our study demonstrated genetically that HMGCR inhibition, APOB inhibition, and NPC1L1 inhibition decrease the risk of breast cancer, LPL agonist increases the risk of endometrial cancer, and APOC3 inhibition decreases the risk of breast cancer and endometrial cancer, and these findings provide genetic insights into the potential risks of lipid-lowering drug therapy.

Background: Due to the complex pathogenesis of sequelae of pelvic inflammatory disease (SPID), targeted therapeutic agents are still lacking. Here, we investigated the interactions between neutrophils and uterine fibroblasts (FBs) in developing tissue fibrosis in SPID. Methods: A rat model of SPID was constructed to assess the roles of autophagy and neutrophil extracellular traps (NETs) in SPID rats. Single‐cell sequencing data from the public database GSE223639 were utilized to identify the specific cell cluster FBs where NETs act. A DMSO‐induced HL‐60‐driven neutrophil‐like (dHL‐60) cell model was established, and neutrophil‐like cells were treated with rapamycin and MHY1485 to activate and inhibit autophagy, respectively, to observe the differences in the production of NETs. NETs were cocultured with FBs to observe the effects on FB proliferation, migration, apoptosis, and phenotypic transformation. Results: In vivo experiments revealed that there was a consistency in the expression of autophagy and NETs in the adherent tissues of rats with the SPID model and that autophagy promotes the generation of NETs, which are collectively involved in the fibrosis of pelvic tissues in SPID. Single‐cell sequencing identified FBs, the cells in which NETs play a major role in aseptic inflammation. Further in vitro studies confirmed that NETs inhibit FB apoptosis while promoting horizontal and longitudinal migration, phenotypic transformation, and hyperproliferation of FBs, thereby exacerbating tissue fibrosis. Conclusions: Autophagy promotes the generation of NETs, which facilitates FB transformation and hyperproliferation and exacerbates the degree of adhesion and fibrosis in the pelvic tissue of SPID.