Cervical squamous cell carcinoma (CSCC) is a type of female cancer that affects millions of families worldwide. Human papillomavirus (HPV) infection is the main reason for CSCC formation, and squamous intraepithelial lesions (SILs) induced by high-risk HPV (HR-HPV) infection are considered precancerous lesions. A previous study reported that HPV-infected cancer cells were able to counteract lipid peroxidation for survival. Recent research has reported that ferroptosis acts in an iron-dependent lipid peroxidation manner to kill cancer cells, and it is proposed as a new approach for female cancer therapy. Here, we investigated the role of ferroptosis throughout SIL development into CSCC. We found that ferroptosis occurred in SIL, but anti-ferroptosis emerged in CSCC. Our data further indicated that an antiferroptotic effect was formed in response to persistent ferroptosis and then promoted oncogenesis. Altogether, we provide novel insight into ferroptosis in cervical SIL development and suggest a potential therapeutic target for the treatment of CSCC.

Background: As a novel prognostic and inflammatory marker, the systemic immune-inflammation index (SII) has come to the foreground in recent years. SII may be used as an indicator reflecting the progressive inflammatory process in patients with polycystic ovary syndrome (PCOS). This study aimed to evaluate the correlation between SII and assisted reproductive outcomes in PCOS patients. Results: A total of 966 women undergoing in vitro fertilization (IVF) procedure with PCOS were included in the study. The SII was calculated as platelet count (/L) × neutrophil count (/L)/lymphocyte count (/L). Participants were divided into four groups according to SII quartiles calculated at baseline, and the differences of clinical and laboratory outcomes between these four groups were compared. Moreover, a univariate linear regression model was used to evaluate the associations between SII and the outcomes. Patients in the highest SII quartile (Q4) had lower antral follicle count (AFC), estradiol (E2), and progesterone (P) levels on the day of human chorionic gonadotropin (HCG) start compared with the lower three SII quartiles (Q1-Q3). Moreover, our analysis demonstrated that women in the lower SII quartiles had a higher rate of available embryos and blastocyst formation compared with those in the highest SII quartile. Logarithm of SII correlated negatively with available embryo rate, but not with number of available embryos. Additionally, the results of our multivariate logistic regression analyses indicated that the highest SII quartile was negatively associated with biochemical pregnancy rate (BPR), clinical pregnancy rate (CPR), live birth rate (LBR), and implantation rate (IR). A non-linear relationship between the SII and number of available embryos, with a negative relationship seen to the right of the inflection point was also found. Conclusions: The interplay among thrombocytosis, inflammation, and immunity could influence assisted reproductive outcomes in PCOS patients. In this regard, SII may serve as a valuable marker for exploring potential correlations.

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