We conducted a meta-analysis to evaluate the efficacy of low-intensity extracorporeal shock wave therapy (LI-ESWT) in the treatment of erectile dysfunction (ED). From July 2011 to June 2021, we finally selected 16 randomized controlled trials (RCTs) including 1,064 participants to evaluate the efficacy of LI-ESWT in the treatment of ED from PubMed, EMBASE, and Cochrane databases. The data are analyzed by Review Manager Version 5.4. Fifteen articles mentioned International Index of Erectile Function (IIEF), in the follow-up of 1 month (mean difference [MD] = 3.18, 95% confidence interval [CI] = [1.38, 4.98], p = .0005), 3 months (MD = 3.01, 95% CI = [2.04, 3.98], p < .00001), and 6 months (MD = 3.20, 95% CI = [2.49, 3.92], p < .00001). After treatment, the improvement of IIEF in the LI-ESWT group was better than that in the control group. Besides, eight of the 16 trials provided data on the proportion of patients with baseline Erectile Hardness Score (EHS) ≤ 2 improved to EHS ≥ 3. The LI-ESWT group was also significantly better than the placebo group (odds ratio [OR] = 5.07, 95% CI = [1.78, 14.44], p = .002). The positive response rate of Questions 2 and 3 of the Sexual Encounter Profile (SEP) was not statistically significant (SEP2: OR = 1.27, 95% CI = [0.70, 2.30], p = .43; SEP3: OR = 4.24, 95% CI = [0.67, 26.83], p = .13). The results of this meta-analysis suggest that treatment plans with an energy density of 0.09 mJ/mm² and pulses number of 1,500 to 2,000 are more beneficial to IIEF in ED patients. In addition, IIEF improvement was more pronounced in patients with moderate ED after extracorporeal shockwave therapy.

Background: Lactylation, a recently identified post-translational modification derived from lactate, has emerged as a regulator of tumor metabolism. However, its functional relevance and molecular targets in bladder cancer (BLCA) remain unclear. Methods: We performed immunohistochemistry on patient tissues, global lactylation proteomics using LC–MS/MS, and in vitro and in vivo functional assays. Gene editing via CRISPR/Cas9, overexpression systems, and pharmacological interventions were employed to study P300-mediated HNRNPA1-K350 lactylation in driving BLCA cell aggression. Metabolomics and glycolytic flux assays were used to assess the metabolic consequences of HNRNPA1 lactylation. Molecular characterization was validated through gene expression and splicing analyses. Small-molecule drug screening was conducted via molecular docking to identify potential inhibitors targeting HNRNPA1. Results: Protein lactylation levels were significantly elevated in BLCA tissues, correlating with poor prognosis. HNRNPA1 was identified as a central lactylation target. Glycolysis-induced lactate production promoted P300-mediated lactylation of HNRNPA1 at lysine 350, which facilitated PKM pre-mRNA splicing toward the PKM2 isoform, enhancing glycolytic flux and supporting tumor growth. Inhibition of glycolysis or LDHA knockdown reduced HNRNPA1 lactylation, suppressed PKM2 expression, and impaired BLCA cell proliferation, migration, and invasion. Metabolomic profiling linked HNRNPA1-K350 lactylation with increased aerobic glycolysis in BLCA cells. A small-molecule inhibitor, identified through molecular docking, attenuated cell proliferation by binding to HNRNPA1 and suppressing PKM2 expression. Conclusions: This study reveals a lactate-driven mechanism coupling alternative splicing to metabolic reprogramming via HNRNPA1 lactylation, identifying HNRNPA1-K350 lactylation as a key driver of glycolysis-dependent tumor progression. A therapeutic approach targeting HNRNPA1 in BLCA is proposed.

Bladder cancer (BC) is among the top ten most common cancer types worldwide and is a serious threat to human health. Circular RNAs (circRNAs) are a new class of non-coding RNAs generated by covalently closed loops through back-splicing. As an emerging research hotspot, circRNAs have attracted considerable attention due to their high conservation, stability, abundance, and specificity of tissue development. Accumulating evidence has revealed different form of circRNAs are closely related to the malignant phenotype, prognosis and chemotherapy resistance of BC, suggesting that different circRNAs may be promising biomarkers and have therapeutic significance in BC. The intention of this review is to summarize the mechanisms of circRNA-mediated BC progression and their diagnostic and prognostic value as biomarkers, as well as to further explore their roles in chemotherapy resistance.

Introduction: The abnormal expression of the Wiskott-Aldrich syndrome protein (WASP) encoded by the Wiskott-Aldrich syndrome (WAS) gene has been implicated in tumor invasion and immune regulation. However, prognostic implications of WAS and its correlation tumor infiltrating in renal clear cell carcinoma (ccRCC) is not clear cut.Methods: The correlation between WAS expression, clinicopathological variables and clinical outcomes were evaluated using The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Tumor Immune Estimation Resource (TIMER), UALCAN, Gene Expression Profiling Interaction Analysis (GEPIA), Kaplan-Meier (KM) plotter and other databases. Furthermore, we assessed the transcription expression of WAS in renal cancer tissues, various renal carcinoma cell lines and human renal tubular cells (HK2) using quantitative polymerase chain reaction (qPCR). A comprehensive analysis of multiple databases including TIMER, GEPIA, TISIDB, ESTIMATE algorithm, and CIBERSORT algorithm were performed to determine the correlation between WAS and tumor infiltrating immune cells in ccRCC.Results: The results displayed an increase in WAS mRNA level in ccRCC compared to normal tissue. WAS protein level was found highly expressed in cancer tissues, particularly within renal tumor cells via the human protein atlas (HPA). Interestingly, we found that elevated WAS expression was significantly positively correlated with the infiltration of CD8+ T cells, B cells, Monocytes, Neutrophils, Macrophages, T cell regulation, NK cells, and Dendritic cells in ccRCC. Bioinformatics demonstrated a strong correlation between WAS expression and 42 immune checkpoints, including the T cell exhaustion gene PD-1, which is critical for exploring immunotherapy for ccRCC. We revealed that patients with high WAS expression were less sensitive to immunotherapy medications.Conclusion: In conclusion, our study identified that WAS was a prognostic biomarker and correlated with immune infiltrates in ccRCC.

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A meta-analysis of efficacy and safety of PDE5 inhibitors in the treatment of ureteral stent-related symptoms Dongxu Zhang, Kai Sun, Tianqi Wang, Gang Wu, Jipeng Wang, Jitao Wu, Jian Ma, Yuanshan Cui