This study examined the inhibitory effects of pluviatolide, a lignan derived from Podophyllum hexandrum, on mast cell activation and IgE-mediated type I hypersensitivity, focusing on FcεRI-dependent and calcium-mediated pathways. Using bone marrowderived mast cells (BMMCs) and rat basophilic leukemia (RBL)-2H3 cells, we found that pluviatolide significantly decreased β-hexosaminidase release and suppressed the expression and secretion of TNF-α and IL-6 in a concentration-dependent manner, without causing cytotoxicity. While we initially hypothesized that it would selectively modulate antigen-specific FcεRI signaling, pluviatolide also inhibited degranulation induced by calcium ionophore and thapsigargin, indicating its effects extend to receptorindependent, Ca2+-dependent activation mechanisms. Immunoblot analyses revealed decreased phosphorylation of proximal kinases (Lyn, Syk), adaptor proteins (LAT, PLCγ1), MAPKs (ERK1/2, JNK, p38), and NF-κB p65. In a passive cutaneous anaphylaxis (PCA) mouse model, oral administration of pluviatolide significantly reduced Evans blue extravasation and mast cell degranulation in ear tissues. These findings demonstrate that pluviatolide suppresses both early and late-phase mast cell responses through multi-nodal inhibition of activation pathways, highlighting its potential as a therapeutic candidate for both IgE-mediated and non-IgE-mediated allergic disorders.

Background: Phase angle (PA) has been proposed as a prognostic factor for evaluating postoperative outcomes across various types of surgery. In this study, we investigated whether preoperative PA measured in living liver donors is associated with postoperative recovery. Methods: Donors aged over 19 years, scheduled for elective purely laparoscopic donor hepatectomy, were included. Each donor underwent bioimpedance analysis(BIA), including PA, on the day before surgery (PA pre ) and the third postoperative day (PAPOD3 ) using the InBody S10 (InBody Co., Ltd, Seoul, Korea). Postoperativerecovery quality was assessed using the Korean version of the quality of recovery (QoR-15K). All donors completed the QoR-15K on POD3 and POD21 to evaluate their recovery following surgery and anesthesia. Results: The mean age of the participants was 38.7±13.2 years, and 24 maledonors (59%) were included. PAPOD3 significantly decreased compared to PA pre(5.42±0.97 vs. 5.99±0.76; mean difference: —0.57, p=0.004). The extracellular water ratio (ECWR) on POD3 increased compared to preoperative levels (0.391±0.011 vs.0.378±0.007; mean difference: 0.013, p<0.001). However, skeletal muscle massindex (SMI) did not significantly change over time (SMI pre : 7.5±1.1; SMI POD3 : 8.0±1.2;p=0.67). Neither PA pre nor ECWR pre was associated with QoR-15K scores on POD3.However, SMI pre was significantly associated with QoR-15K on POD3, but not onPOD21. In the logistic regression model, preoperative BIA variables were not associated with in-hospital complications. Conclusion While PA pre was not associated with postoperative recovery or com-plications, a higher SMI was identified as a significant predictor of better recovery, suggesting its potential use as a screening tool in living liver donors.

Purpose: Although bladder cancer occurs three to 4 times more frequently in men than in women, the relative number of deaths compared to incidence is higher in women, suggesting that women have a worse prognosis than men. Emerging evidence indicates that the activity of the sex steroid hormone pathway may play a role in bladder cancer development, with demonstrations that both androgens and estrogens have biological effects on bladder cancer in vitro and in vivo. This study investigates the influence of sex and menopausal status on recurrence and cancer-specific death (CSD) in bladder cancer patients undergoing radical cystectomy (RC). Materials and Methods: This retrospective analysis included 3,913 patients from the Korean Bladder Cancer Study Group Database who underwent RC between 2010 and 2019. Patients were categorized based on gender and menopausal status (≤50 years: premenopausal; >50 years: postmenopausal). Pathological factors, neoadjuvant chemotherapy, recurrence, and CSD rates were analyzed using chi-square and Fisher exact tests. Results: Among the 3,913 patients, 400 (10.2%) were female. Premenopausal females exhibited significantly lower recurrence rates (28.6%) compared to postmenopausal females (45.7%). CSD rates were similarly reduced in premenopausal females (12.0% vs. 22.2% in postmenopausal females). No significant sex differences in recurrence or CSD were observed among premenopausal patients. Pathological T stage, nodal status, and lymphovascular invasion were significantly associated with recurrence in males, while nodal status alone was significant in females. Neoadjuvant chemotherapy was significantly more frequently administered to male patients under the age of 50, while no difference was observed in the administration of neoadjuvant chemotherapy among female patients based on menopausal status. Conclusion Hormonal changes associated with menopause significantly influence bladder cancer outcomes in women. Premenopausal hormonal environments seem protective, underscoring the need for further research into hormone-driven mechanisms in bladder cancer.

Purpose: To evaluate whether extended pelvic lymph node dissection (PLND) improves survival outcomes compared with standard PLND in patients with bladder cancer (BCa) undergoing radical cystectomy (RC), and to assess its potential benefits in patients with prior or concurrent radical nephroureterectomy (p/cRNU). Materials and Methods: A multicenter analysis included 2202 patients with BCa undergoing RC with standard or extended PLND at 11 tertiary centers from 2003 to 2023. Following propensity score matching, 659 pairs (n=1,318), including 128 patients with p/cRNU, were analyzed. Recurrence-free survival (RFS) was the primary outcome, while overall survival (OS), cancer-specific survival (CSS), and readmission rates were secondary outcomes. Survival analyses performed using Kaplan-Meier methods and clustered Cox models. Results: Extended PLND yielded significantly more lymph nodes than standard PLND (median: 27.0 vs. 17.0, p<0.001) but did not improve RFS, CSS, or OS in the overall cohort (all p>0.05). Extended PLND increased readmission rates (28.4% vs. 20.2%, p=0.001) and readmission risk (odds ratio, 1.57; 95% confidence interval [CI], 1.15–2.16, p=0.005). However, subgroup analysis revealed extended PLND significantly improved RFS in patients with p/cRNU (hazard ratio, 0.54; 95% CI, 0.38–0.77; p<0.001). Conclusion Extended PLND does not provide survival benefits for overall patient population and increases readmission risk but significantly improves RFS in patients with p/cRNU. Tailoring PLND extent based on upper tract disease status is recommended.

BACKGROUND/OBJECTIVES: Recently, herbal medicines have gained attention for the treatment of benign prostatic hyperplasia (BPH), a common disease in elderly men. In this study, we aimed to determine the effect of ethanol extract of Asparagi radix (EAR), which is traditionally used to treat various diseases, on BPH development using a testosteroneinduced BPH model.MATERIALS/METHODS: Testosterone propionate (TP)-treated Sprague–Dawley rats were used to establish a BPH model in vivo. EAR was orally administered along with TP, and finasteride was used as a positive control. All rats were sacrificed at the end of the experiment, and pathological changes in the prostate tissue and levels of key biomarkers associated with BPH pathogenesis were assessed. RESULTS: Oral administration of EAR significantly inhibited TP-induced BPH by reducing the prostate weight, lumen size, and epithelial thickness in a concentration-dependent manner. EAR also significantly abrogated the expression of 5α-reductase type 2 (SRD5A2), proliferating cell nuclear antigen, and prostate-specific antigen (PSA) induced by TP.Additionally, serum levels of testosterone, dihydrotestosterone, and PSA were elevated in the TP-induced group but decreased in the EAR-treated group. EAR also decreased the expression levels of the androgen receptor (AR) and its coactivators in TP-induced BPH model rats. CONCLUSION Our findings revealed that EAR protected against BPH by inhibiting 5α-reductase activity and AR signaling pathway, suggesting its potential for BPH treatment.

BACKGROUND/OBJECTIVES: Recently, herbal medicines have gained attention for the treatment of benign prostatic hyperplasia (BPH), a common disease in elderly men. In this study, we aimed to determine the effect of ethanol extract of Asparagi radix (EAR), which is traditionally used to treat various diseases, on BPH development using a testosteroneinduced BPH model.MATERIALS/METHODS: Testosterone propionate (TP)-treated Sprague–Dawley rats were used to establish a BPH model in vivo. EAR was orally administered along with TP, and finasteride was used as a positive control. All rats were sacrificed at the end of the experiment, and pathological changes in the prostate tissue and levels of key biomarkers associated with BPH pathogenesis were assessed. RESULTS: Oral administration of EAR significantly inhibited TP-induced BPH by reducing the prostate weight, lumen size, and epithelial thickness in a concentration-dependent manner. EAR also significantly abrogated the expression of 5α-reductase type 2 (SRD5A2), proliferating cell nuclear antigen, and prostate-specific antigen (PSA) induced by TP.Additionally, serum levels of testosterone, dihydrotestosterone, and PSA were elevated in the TP-induced group but decreased in the EAR-treated group. EAR also decreased the expression levels of the androgen receptor (AR) and its coactivators in TP-induced BPH model rats. CONCLUSION Our findings revealed that EAR protected against BPH by inhibiting 5α-reductase activity and AR signaling pathway, suggesting its potential for BPH treatment.

Purpose: A widely distributed cell cycle inhibitor, p27, regulates cyclin-dependent kinase-cyclin complexes. Although the prognostic value of p27 has been established for various types of carcinomas, its role in luminal breast cancer remains poorly understood. This study aimed to explore the functional enrichment of p27 and identify potential drug targets in patients with luminal-type breast cancer. Methods: Clinicopathological data were collected from 868 patients with luminal-type breast cancer. Additionally, publicly available data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset (1,500 patients) and the Gene Expression Omnibus database (855 patients) were included in the analysis. Immunohistochemical staining for p27, differential gene expression analysis, disease ontology analysis, survival prediction modeling using machine learning (ML), and in vitro drug screening were also performed. Results: Low p27 expression correlated with younger age, advanced tumor stage, estrogen receptor/progesterone receptor negativity, decreased cluster of differentiation 8+ T cell count, and poorer survival outcomes in luminal-type breast cancer. The METABRIC data revealed that reduced cyclin-dependent kinase inhibitor 1B (CDKN1B) expression (encoding p27) was associated with cell proliferation-related pathways and epigenetic polycomb repressive complex 2. Using ML, p27 emerged as the second most significant survival factor after N stage, thereby enhancing survival model performance. Additionally, luminal-type breast cancer cell lines with low CDKN1B expression demonstrated increased sensitivity to specific anticancer drugs such as voxtalisib and serdemetan, implying a potential therapeutic synergy between CDKN1B-targeted approaches and these drugs. Conclusion The integration of ML and bioinformatic analyses of p27 has the potential to enhance risk stratification and facilitate personalized treatment strategies for patients with breast cancer.