In the DESTINY-Breast03 clinical trial, trastuzumab deruxtecan (T-DXd) showed superior progression-free survival and overall survival versus trastuzumab emtansine (T-DM1) and manageable safety in patients with human epidermal growth factor receptor 2 (HER2)-positive (HER2+) metastatic breast cancer. Here, patient-reported outcomes (PROs) are reported along with hospitalization data. Patients in DESTINY-Breast03 were assessed for prespecified PRO measures, including European Organization for Research and Treatment of Cancer quality of life (EORTC-QoL) questionnaires [the oncology-specific EORTC Quality of Life Questionnaire Core 30 (QLQ-C30) and breast cancer-specific EORTC QLQ-BR45] and the generic EuroQol 5-dimension 5-level questionnaire (EQ-5D-5L) visual analogue scale. Analyses included change from baseline, time to definitive deterioration (TDD), and hospitalization-related endpoints. EORTC QLQ-C30 baseline global health status (GHS) scores for T-DXd (n = 253) and T-DM1 (n = 260) were similar, with no clinically meaningful change (<10-point change from baseline) while on either treatment (median treatment duration: T-DXd, 14.3 months; T-DM1, 6.9 months). TDD analyses of QLQ-C30 GHS (primary PRO variable) and all other prespecified PROs (QLQ-C30 subscales, the QLQ-BR45 arm symptoms scale, and the EQ-5D-5L visual analogue scale) suggested T-DXd was numerically favored over T-DM1 based on TDD hazard ratios. Of all randomized patients, 18 (6.9%) receiving T-DXd versus 19 (7.2%) receiving T-DM1 were hospitalized, and the median time to first hospitalization was 219.5 versus 60.0 days, respectively. In DESTINY-Breast03, EORTC GHS/QoL was maintained on both therapies throughout treatment, indicating that despite the longer treatment duration with T-DXd versus T-DM1, health-related QoL did not worsen on T-DXd. Furthermore, TDD hazard ratios numerically favored T-DXd over T-DM1 in all prespecified variables of interest including pain, suggesting T-DXd may delay time until health-related QoL deterioration compared with T-DM1. Median time to first hospitalization was three times longer with T-DXd versus T-DM1. Together with reported improved efficacy and manageable toxicity, these results support the overall benefit of T-DXd for patients with HER2+ metastatic breast cancer.

Among women undergoing IVF, high BMI negatively affects pregnancy outcomes when using the conventional ovary stimulating protocols combined with fresh embryo transfer. Therefore, finding a proper treatment for these high BMI women is more important and urgent when obesity is prevalent. In our study, we reported a retrospective study of 4457 women who were divided into normal BMI group (18.5 kg/m²–24.9 kg/m²) and high BMI group (≥25 kg/m²) undergoing 4611 IVF treatment cycles with frozen embryo transfer (FET). We found the high BMI group originally had the poor oocytes performance, but after FET they got the similar pregnancy outcomes as the normal BMI group. Then under FET we analyzed the IVF outcomes of our new progestin-primed ovary stimulation (PPOS) protocol, indicating that the hMG + MPA (4 or 10 mg/d) groups had the obvious better pregnancy results than the conventional short group in the high BMI group, and binary logistic regression analysis showed the hMG + MPA (10 mg/d) group was associated with better pregnancy outcomes than the hMG + MPA (4 mg/d) group. These results indicate PPOS - hMG + MPA (10 mg/d) combined with FET might be a new potential treatment choice for the high BMI women undergoing IVF treatments.

Gemcitabine is a widely used intravesical chemotherapeutic agent for non-muscle-invasive bladder cancer (NMIBC), yet its efficacy remains suboptimal, with high recurrence rates. While traditionally considered a cytotoxic agent, emerging evidence suggests that certain chemotherapeutics may exert immunomodulatory effects. This study investigated whether gemcitabine induces immunogenic cell death (ICD) and explored the underlying mechanisms involving endoplasmic reticulum (ER) stress. A retrospective analysis was conducted to assess the association between gemcitabine-related complications and NMIBC recurrence. In vitro assays were used to evaluate ICD hallmarks (ATP, HMGB1, CALR) and pro-inflammatory cytokines. RNA sequencing and western blotting were performed to explore ER stress pathways. Functional assays included dendritic cell (DC) maturation, phagocytosis, and CD8⁺T cell proliferation and cytotoxicity. In vivo vaccination and T cell depletion models were used to evaluate antitumor immunity. Clinical data revealed an inverse correlation between gemcitabine-related complications and tumor recurrence. Gemcitabine induced classical ICD markers in bladder cancer cells and elicited CD8⁺T cell-mediated antitumor immunity in vivo. Mechanistically, gemcitabine activated the PERK branch of the ER stress response, promoting CALR translocation and DAMP release. PERK overexpression enhanced DC maturation, phagocytosis, and stimulation of CD8⁺T cell proliferation and cytotoxicity, whereas PERK knockdown impaired these effects. This study demonstrates that short-term, high-dose gemcitabine induces PERK-dependent ICD, which enhances antitumor immune responses via DC and CD8⁺T cell activation. These findings provide a mechanistic rationale for combining gemcitabine with immunotherapy and suggest PERK as a potential biomarker and therapeutic target for ICD enhancement in bladder cancer.

Previous studies have shown that various active components of licorice have anticancer effects. However, few studies have investigated the mechanism of action of licorice in gastric cancer. The effect of active compounds in licorice on the biological activity of gastric cancer cells was investigated in vitro (MKN-45 cells). Network pharmacology and molecular docking were used to predict the potential targets of licorice against gastric cancer and verify the binding stability of target proteins to compounds. In addition, the anticancer effect of licorice was assessed using a mouse model of gastric cancer. The licorice-active component (quercetin) effectively inhibited proliferation, caused cell cycle arrest, and promoted apoptosis in MKN-45 cells, accompanied by increased Cyt-C, decreased BCL-2, and decreased mitochondrial membrane potential and mitochondrial damage. Further research showed that quercetin targeted EGFR, blocked the ERK signaling pathway, and downregulated PTGS2. In the in vivo experiment, quercetin treatment resulted in reduced tumor volume, decreased Ki67 and BCL-2 expression in tumor tissue, increased caspase 3 and BAX levels, and induced mitochondrial damage.

Zearalenone (ZEN), a non-steroidal estrogenic fungal toxin widely present in forage, food, and their ingredients, poses a serious threat to animal and human reproductive health. ZEN also threatens ovine, a major source of human food and breeding stock. However, the mechanisms underlying the impact of ZEN on the in vitro maturation (IVM) of ovine oocytes remain unclear. This study aimed to elucidate these mechanisms using the Smart-seq2 technology. A total of 146 differentially expressed genes were obtained, using Smart-seq2, from sheep oocytes cultured in vitro after ZEN treatment. ZEN treatment inhibited RUNX2 and SPP1 expression in the PI3K signaling pathway, leading to the downregulation of THBS1 and ultimately the downregulation of TNFAIP6; ZEN can also decrease TNFAIP6 by reducing PTPRC and ITGAM. Both inhibit in vitro maturation of ovine oocytes and proliferation of cumulus cells by downregulating TNFAIP6. These findings provide data and a theoretical basis for elucidating ZEN’s toxicity mechanisms, screening therapeutic drugs, and reducing ZEN-related losses in the ovine industry.