Objective: To identify metabolic predictors of urolithiasis recurrence and investigate whether the predictive value of urinary citrate differs across metabolic subgroups, with the aim of developing a subgroup-specific prediction model. Methods: We retrospectively analyzed patients who experienced a first episode of urolithiasis between 2013 and 2015 and subsequently underwent metabolic evaluation at the Department of Urology of our institution. Baseline assessment included demographic characteristics, blood biochemical parameters, and 24-h urinary metabolic indices. Follow-up data on stone recurrence were collected through standardized telephone interviews conducted between 2023 and 2025. Multivariable logistic regression and subgroup analyses were performed to identify predictors of recurrence. A prediction model for patients with hyperuricemia was developed using stepwise logistic regression and internally validated by tenfold cross-validation. Results: A total of 184 patients were included. Multivariable logistic regression identified 24-h urinary citrate as the only metabolic parameter independently associated with stone recurrence ( P = 0.04). Correlation analysis demonstrated significant associations between urinary citrate and serum uric acid, urinary calcium, urinary oxalate, and age. Subgroup analysis showed that the inverse association between urinary citrate and recurrence remained significant only among patients with hyperuricemia ( P = 0.03), whereas similar trends in other metabolic subgroups did not reach statistical significance. The interaction between serum uric acid and urinary citrate was not statistically significant ( P = 0.40). A preliminary prediction model incorporating urinary citrate, age, BMI, triglycerides, and parathyroid hormone demonstrated moderate discriminative performance, with a mean cross-validated AUC of 0.747. Conclusion: Urinary citrate was independently associated with urolithiasis recurrence, with this association being particularly evident among patients with hyperuricemia. These findings suggest that the predictive value of urinary citrate may vary across different metabolic backgrounds and support further investigation of metabolically stratified approaches to recurrence risk assessment. External validation in larger prospective cohorts is warranted.

Background: Bladder cancer (BCa) is a prevalent and aggressive malignancy characterized by high recurrence and metastasis rates. Despite advances in treatment, the prognosis for patients with advanced BCa remains poor. This study aimed to investigate the role of SAPCD2 in BCa progression and its potential as a therapeutic target. Methods: We performed a series of in vitro and in vivo experiments to assess the expression and function of SAPCD2 in BCa. The correlation between SAPCD2 expression and clinicopathological features was analyzed using tissue samples from BCa patients. Functional assays, including cell proliferation, migration, invasion, and metastasis tests, were conducted to evaluate the biological impact of SAPCD2. Mechanistic studies focused on the MAPK signaling pathway, TANK stabilization, and the interaction between SAPCD2 and the PLAGL2–CREB feedback loop. Results: Our results showed that SAPCD2 was significantly upregulated in BCa tissues and correlated with advanced clinicopathological features and poor prognosis. Overexpression of SAPCD2 promoted cell proliferation, migration, invasion, and metastasis, while its silencing led to the opposite effects. Mechanistically, SAPCD2 activated the MAPK signaling pathway by stabilizing TANK and preventing its degradation by SYVN1. Furthermore, we identified a positive feedback loop in which SAPCD2 enhanced PLAGL2 expression through CREB phosphorylation, further amplifying SAPCD2 expression and MAPK signaling. Conclusions: This study indicated that SAPCD2 could serve as a critical driver of BCa malignancy, emphasizing its role in sustaining oncogenic signaling through the SAPCD2–TANK–MAPK axis and the PLAGL2–SAPCD2–CREB feedback loop. Targeting this pathway may offer novel therapeutic strategies for treating aggressive BCa.