Wen-Wei Sung

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Background/Objectives: Although α-blockers are commonly used to treat lower urinary tract symptoms in men with benign prostatic hyperplasia (BPH), their differential neuropsychiatric safety profiles remain underexplored. Some studies have suggested an increased risk of cognitive decline, mood disorders, and falls, but the results remain inconclusive. Methods: We conducted a large retrospective cohort study using the TriNetX global network, identifying over 264,000 men treated with a single α-blocker between 2005 and 2023. Patients were grouped by α-blocker type—tamsulosin, doxazosin, terazosin, alfuzosin, silodosin, or prazosin—and matched 1:1 using propensity scores to adjust for demographic, clinical, and psychosocial variables. The primary outcomes were new-onset dementia, depression, and unintentional injuries, assessed at 1-, 3-, and 10-year intervals. The median follow-up duration was approximately 5.5 years, ranging from 1824 to 2200 days across cohorts, indicating balanced observation periods among the six α-blocker groups. Results: Among the included patients, tamsulosin (n = 213,690) and prazosin (n = 1184) were associated with significantly higher risks of neurodegenerative, psychiatric, and injury-related outcomes. Alfuzosin (n = 10,138) exhibited the most favorable safety profile across all endpoints. The findings remained robust in sensitivity analyses, excluding patients with prior malignancy or other α-blocker exposure. Conclusions: Substantial differences in long-term neuropsychiatric safety exist among α-blockers. Given its favorable profile, alfuzosin may be the preferred agent in patients at elevated risk of cognitive or psychiatric disorders. These findings highlight the need for individualized α-blocker selection and long-term pharmacovigilance in BPH management.

Background: Partial nephrectomy (PN) and radical nephrectomy (RN) are surgical options for localized renal cell carcinoma; however, PN is p referred for preserving renal function in patients with chronic kidney disease (CKD). This study compares the risks of end-stage renal disease (ESRD), hemodialysis, and cardiovascular complications between PN and RN in patients with stable stage 4 CKD, with a further focus on postoperative electrolyte imbalances as outcome predictors. Methods: This retrospective cohort study used TriNetX data (between 2005 and 2023). Patients with stable stage 4 CKD undergoing nephron-sparing procedures or RN were included. Propensity-score matching ensured balanced baseline characteristics. The analyzed outcomes included renal function, hemodialysis, electrolyte imbalances, and cardiovascular events. Statistical analyses were hazard ratios (HRs) and risk ratios (RRs) with 95% confidence intervals (CIs). Results: The PN and RN groups showed no statistically significant differences in their progression to ESRD or need for long-term hemodialysis. Patients undergoing RN had a higher risk of pulmonary embolism (HR: 2.60; 95% CI: 1.12–6.02). Electrolyte imbalances, particularly abnormal calcium and phosphate levels, were more common in the RN cohort in the early postoperative period, but they stabilized over time. Notably, these electrolyte imbalances were associated with an increased risk of cardiovascular complications. The study limitations include the absence of tumor grade, tumor staging, and pathological information. Conclusions: Nephron-sparing PN did not reduce ESRD risk compared with RN, but provided a lower incidence of certain postoperative complications, such as pulmonary embolism and early electrolyte disturbances. Early postoperative electrolyte imbalances, especially abnormal calcium and phosphate levels, may predict adverse renal and cardiovascular outcomes.

Advanced renal cell carcinoma (RCC) has a poor prognosis; this drives the exploration of alternative systemic therapies to identify more effective treatment options. Recent research has revealed that crebanine, an alkaloid derivative of the Stephania genus, induces apoptotic effects in various cancers; however, a thorough investigation of the role of crebanine in RCC has not been conducted thus far. For this study, we evaluated tumor cell viability, clonogenicity, cell-cycle distributions, morphological changes, and cell mortality with the aim of exploring the antitumor effects of crebanine in RCC. Furthermore, we compared gene and protein expressions using RNA sequencing analysis and Western blotting. The findings indicated that crebanine significantly inhibited RCC colonies and caused G1-phase cell-cycle arrest with sub-G1-phase accumulation, thus leading to suppressed cell proliferation and cell death. In addition, Hoechst 33342 staining was used to observe apoptotic cells, which revealed chromatin condensation and a reduction in the nuclear volume associated with apoptosis. Further, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that differentially expressed genes are involved in the initiation of DNA replication, centrosome duplication, chromosome congression, and mitotic processes in the cell cycle along with signaling pathways, such as I-kappaB kinase/NF-kappaB signaling, Hippo signaling, and intrinsic apoptotic pathways. Consistent with GO and KEGG analyses, increased levels of cleaved caspase-3, cleaved caspase-7, and cleaved PARP, and decreased levels of cIAP1, BCL2, survivin, and claspin were observed. Finally, the expressions of G1/S phase transition cyclin D1, cyclin E/CDK2, and cyclin A2/CDK2 complexes were downregulated. Overall, these findings supported the potential of crebanine as an adjuvant therapy in RCC.

Background: Bladder cancer ranks ninth among the most commonly diagnosed cancers, with urothelial carcinoma (UC) accounting for more than 90% of all cases. Given the high recurrence rate and progression risk of bladder cancer, investigating alternative adjunct therapies is imperative. One potential candidate is isoliensinine, which has shown antitumor potential in various cancers; however, the effectiveness of isoliensinine on UC is largely unknown. Methods: In the present study, the effects of isoliensinine on UC cells were examined in a variety of in vitro experiments, including MTT assays, colony formation assays, flow cytometry assays, RNA sequencing analysis, and Western blotting. Results: The isoliensinine-treated T24 and UMUC3 UC cell lines showed cell growth inhibition and proliferation in the MTT and colony formation assays and an apoptotic effect in the flow cytometry assays. RNA sequencing analysis, performed to explain the underlying mechanisms, revealed a significant regulation of cell functions, including apoptosis, the cell cycle, hypoxia-inducible factor 1 (HIF-1) signaling, tumor necrosis factor (TNF) signaling, and ferroptosis. Subsequent Western blotting results verified all these findings. Conclusions: Overall, our data indicate that isoliensinine inhibits UC cell growth and proliferation by inducing apoptosis through alterations in the TNF and HIF1 pathways and ferroptosis. Overall, isoliensinine shows potential for use in new or combined adjunct therapies for the treatment of bladder cancer.

Background: Chat Generative Pre-Trained Transformer (ChatGPT), launched by OpenAI in November 2022, features advanced large language models optimized for dialog. However, the performance differences between GPT-3.5, GPT-4, and GPT-4o in medical contexts remain unclear. Objective: This study evaluates the accuracy of GPT-3.5, GPT-4, and GPT-4o across various medical subjects. GPT-4o’s performances in Chinese and English were also analyzed. Methods: We retrospectively compared GPT-3.5, GPT-4, and GPT-4o in Stage 1 of the Taiwanese Senior Professional and Technical Examinations for Medical Doctors (SPTEMD) from July 2021 to February 2024, excluding image-based questions. Results: The overall accuracy rates of GPT-3.5, GPT-4, and GPT-4o were 65.74% (781/1188), 95.71% (1137/1188), and 96.72% (1149/1188), respectively. GPT-4 and GPT-4o outperformed GPT-3.5 across all subjects. Statistical analysis revealed a significant difference between GPT-3.5 and the other models (p < 0.05) but no significant difference between GPT-4 and GPT-4o. Among subjects, physiology had a significantly higher error rate (p < 0.05) than the overall average across all three models. GPT-4o’s accuracy rates in Chinese (98.14%) and English (98.48%) did not differ significantly. Conclusions: GPT-4 and GPT-4o exceed the accuracy threshold for Taiwanese SPTEMD, demonstrating advancements in contextual comprehension and reasoning. Future research should focus on responsible integration into medical training and assessment.

Prostate cancer (PCa), especially metastatic castration-resistant prostate cancer (mCRPC), is a significant cancer characterized by its poor prognosis and limited treatment options. Prostate-specific membrane antigen (PSMA) has emerged as a diagnostic and therapeutic target for PCa due to its restricted expression in malignant prostate tissues. In this case, several PSMA-targeting molecules were developed for radiotherapy and immunotherapy. Antibody–drug conjugates (ADCs) are a novel therapeutic approach for various carcinomas that can selectively target PSMA-positive tumor cells and minimize off-target toxicity. ADCs have made great progress in the treatment of breast and bladder cancers, and some have received FDA approval for target therapy. However, studies on PSMA ADCs are limited, and most clinical trials are at stage I or II. Therefore, this study reviewed trials about PSMA-targeting ADCs for the treatment of PCa. Clinical trials have reported a favorable pharmacokinetic profile and antitumor activity. Toxicity studies have revealed manageable adverse effects, with no significant off-target toxicity in PSMA-negative tissues. This study highlights the therapeutic potential of PSMA ADCs for the treatment of mCRPC. However, it also emphasizes the necessity of further clinical investigation to optimize efficacy, safety, and patient outcomes.

Background: Gleason scores of 8 or higher indicate a poorer prognosis in metastatic castration-sensitive prostate cancer (mCSPC). This study aims to perform a systematic review and network meta-analysis (NMA) to compare overall survival (OS) and progression-free survival (PFS) among combination therapies with androgen receptor signaling inhibitors (ARSIs) in mCSPC patients, stratified by Gleason score ≥8 and <8. Methods: A literature search was conducted across PubMed, Embase, and Web of Science, using a PRISMA-guided systematic search strategy, covering January 2013 to June 2024. Results: Twelve studies including 12,652 patients were included in the NMAs. In the overall population, most ARSI combination therapies improved survival outcomes, except for orteronel + androgen deprivation therapy (ADT). In the Gleason score ≥8 subgroup, all ARSI combination therapies improved OS, with rezvilutamide showing the highest probability of being the best treatment for OS (HR 0.48, 95% CI 0.31–0.76, P-scores 0.88). In the Gleason score <8 subgroup, only darolutamide + docetaxel + ADT (HR 0.49, 95% CI 0.29–0.81) and apalutamide + ADT (HR 0.67, 95% CI 0.46–0.98) improved OS. Conclusions: ARSI combination therapy is effective for mCSPC patients with Gleason score ≥8, but further investigation is needed to confirm its efficacy in patients with Gleason score <8.