USP15 facilitates the progression of bladder cancer by amplifying the activation of the NF-κB signaling pathway.

USP15, a pivotal member of the deubiquitinase family, plays a crucial role in orchestrating numerous vital biological processes, including the regulation of NF-κB signaling pathway and deubiquitination of proto-oncogenes. In various cancers, USP15 has been validated to exhibit up-regulated expression, impacting the initiation and progression of cancer. However, its precise mechanism in bladder cancer remains elusive. Our study shed light on the significant overexpression of USP15 in bladder cancer cells compared to normal bladder cells, correlating with a poorer prognosis for bladder cancer patients. Strikingly, attenuation of USP15 expression greatly attenuated the proliferation, migration, and invasion of bladder cancer cells. Moreover, upregulation of USP15 was found to drive cancer progression through the activation of the NF-κB signaling pathway. Notably, USP15 directly deubiquitinates BRCC3, heightening its expression level, and subsequent overexpression of BRCC3 counteracted the antitumoral efficacy of USP15 downregulation. Overall, our findings elucidated the carcinogenic effects of USP15 in bladder cancer, primarily mediated by the excessive activation of the NF-κB signaling pathway, thereby promoting tumor development. These results underscore the potential of USP15 as a promising therapeutic target for bladder cancer in the future.

Risk prediction of the progression of chronic kidney disease stage 1 based on peripheral blood samples: construction and internal validation of a nomogram.

Patients with chronic kidney disease (CKD) have high morbidity and mortality, and the disease progression has a significant impact on their survival and living standards. This research aims to analyze risk factors for CKD stage 1 and provide a reference for clinical decision making. The clinical data and peripheral blood samples of 300 patients with CKD stage 1 were collected retrospectively. Patients were randomly assigned into a training set (n = 210) and a validation set (n = 90). Patients' baseline characteristic levels were subjected to statistical tests for difference. Univariate and multivariate Cox regression analyses were utilized to identify risk factors influencing disease progression. Subsequently, a prediction model for disease progression was developed using a nomogram, and the model's accuracy was assessed using the C-index and calibration curve. The results revealed that hypertension, diabetes, and urinary albumin were essential factors in the progression of CKD stage 1. The nomogram was constructed and then the C-index was calculated. The calibration curve was utilized to assess the risk model. The C-index of the training set was 0.75, and the C-index of the validation set was 0.73, suggesting a good predictive ability of the model. The risk model accurately predicted the progression of CKD stage 1, which is of great significance to developing personalized treatment for patients in clinical practice.

Effects of Varicocele Surgical Repair on Serum Hormone and Inhibin B Levels for Patients With Varicocele: A Systematic Review and Meta-Analysis.

Varicocele surgical repair can improve the function of the testis for patients with varicocele. We carried out a systematic review and meta-analysis to assess the effects of varicocele surgical repair on serum hormones and inhibin B levels in patients with varicocele. A literature search was performed in August 2022, and no language or geographic region restrictions were applied. The search included the following databases: PubMed, Embase, and Medline. A literature review was performed to identify all published clinical trials assessing serum hormone and inhibin B levels before and after varicocele surgical repair. The reference lists of retrieved studies were also investigated. A systematic review and meta-analysis were conducted. Eight articles were selected from 162 articles, including 452 patients. The combined analysis showed that after surgical treatment, mean serum testosterone, inhibin B, and sperm concentration levels increased compared with preoperative levels (p < .05). After surgical treatment, mean serum follicle-stimulating hormon (FSH), and Luteinizing hormone (LH) levels decreased compared with preoperative levels (p < .05). This meta-analysis demonstrates that varicocele surgical repair can improve testicular function, increase serum testosterone, and inhibin B levels and decrease serum FSH and LH levels in patients with varicocele. This might be related to the improvement of infertility. A large-scale multicenter randomized controlled study is needed for further confirmation.

Effect of Varicocelectomy on Serum FSH and LH Levels for Patients with Varicocele: a Systematic Review and Meta-analysis.

Varicocelectomy can improve the function of testicular Leydig cell for patients with varicocele. We carried out a systematic review and meta-analysis to assess effect of varicocelectomy on serum FSH and LH levels for patients with varicocele. A literature review was performed to identify all published randomized preoperation-postoperation clinical trials of assessing serum FSH and LH levels before and after varicocelectomy. The search included the following databases: PUBMED and EMBASE. The reference lists of retrieved studies were also investigated. A systematic review and meta-analysis were conducted. Five studies were selected from 149 studies, including 312 patients. The meta-analysis showed that serum FSH level (95% confidence interval 0.19-0.77, P = 0.001) and serum LH level (95% confidence interval 0.25-0.91, P = 0.0005) were higher preoperation than postoperation. Serum FSH level decreased by 0.48 ng/dL after varicocelectomy. The mean decrease of the serum FSH was from 0.1 to 4.8 ng/dL. And serum LH decreased by 0.58 ng/dL. The mean decrease of the serum LH was from 0.2 to 2.1 ng/dL. This meta-analysis proves that varicocelectomy perhaps can decrease serum FSH and LH levels in patients with varicocele. And it might be related to the improvement of the function of Leydig cell. But it remains to need a large-scale multicenter randomized controlled study to be further confirmed.

Efficacy and safety of short- and long-term, regular and on-demand regimens of phosphodiesterase type 5 inhibitors in treating erectile dysfunction after nerve-sparing radical prostatectomy: a systematic review and meta-analysis.

BACKGROUND: We performed a meta-analysis to evaluate the efficacy and safety of short-term (≤6 months) and long-term (>6 months), regular (OaD) and on-demand (PRN) regimens of phosphodiesterase type 5 inhibitors (PDE5-Is) in treating erectile dysfunction (ED) after nerve-sparing radical prostatectomy (NSRP). METHODS: We conducted a literature search in August 2016. Sources included PubMed, EMBASE, and MEDLINE databases. The main outcome was International Index of Erectile Function-Erectile Function (IIEF-EF) domain score, and the secondary outcome was treatment-emergent adverse events (TEAEs). RESULTS: Eight articles involving 13 randomized controlled trials (RCTs) were used in this analysis: they suggested that PDE5-Is can improve the IIEF-EF distinctly in comparison with placebo in short and long term (mean difference [MD]: 2.26, 95% confidence interval [CI]: 1.45-3.08, P<0.00001, and MD: 4.5, 95% CI: 3.6-5.4, P<0.00001), and long-term use of PDE5-Is (>6 months) can improve the IIEF-EF distinctly in comparison with short-term use of PDE5-Is (≤6 months) (MD: 3.9, 95% CI: 3.01-4.8, P<0.00001). OaD of PDE5-Is significantly improved the IIEF-EF compared to placebo in short and long term (MD: 4.08, 95% CI: 3.2-4.97, P<0.00001, and MD: 4.74, 95% CI: 3.79-5.69, P<0.00001). No significant differences were found in IIEF-EF changes between PRN and placebo (≤6 months) (MD: 2.64, 95% CI: -0.87 to 6.14, P=0.14), and between PRN and OaD group (>6 months) (MD: -0.58, 95% CI: -9.86 to 8.74, P=0.91). There were more TEAEs in PDE5-Is group in comparison with placebo (odds ratio [OR]: 1.55, 95% CI: 1.26-1.91, P<0.0001), and TEAEs in OaD group were not significantly different from those seen in PRN group (OR: 1.05, 95% CI: 0.78-1.4, P=0.77). CONCLUSION: Our meta-analysis suggests that PDE5-Is are efficient and safe for treatment of ED after NSRP, and we should choose the regular regimen for short term and regular or on-demand regimen for long term. Further high-quality RCTs are needed to validate this result.

The efficacy and safety of adrenergic alpha-antagonists in treatment of distal ureteral stones in pediatric patients: A systematic review and meta-analysis.

OBJECTIVE: We carried out a systematic review and meta-analysis to evaluate the efficacy and safety of adrenergic alpha-antagonists as a medical expulsive therapy for ureteral stones in pediatric patients. METHODS: The PubMed, EMBASE and Cochrane Controlled Trials Register databases were searched up to January 2016. All randomized controlled trials and all cohort studies in which patients were randomized to receive either adrenergic alpha-antagonists or placebo for ureteral stones were identified. The outcome measures assessed were overall stone expulsion rate (primary), expulsion time (secondary), and treatment-emergent adverse events. RESULTS: Five trials with a total of 406 pediatric patients met the inclusion criteria. According to the doses of adrenergic alpha-antagonists, the pooling effects of adrenergic alpha-antagonists were analyzed, with a higher expulsion rate obtained than in controls, the stone expulsion rate (OR=2.70, 95% CI 1.49 to 4.91, P=0.001). Adrenergic alpha-antagonists statistically did not significantly decrease the number of the stone expulsion time with the placebo, the stone expulsion time (SMD=-4.65, 95% CI -9.76 to 0.45, P=0.07). Safety assessments included common treatment-emergent adverse events (TEAEs) (OR=2.01, 95% CI 0.74 to 5.48, P=0.17). Compared with placebos, there was a higher stone expulsion rate with the adrenergic alpha-antagonists; in addition, fewer adverse effects were observed. CONCLUSIONS: This meta-analysis may suggest that adrenergic alpha-antagonists are a safe and effective medical expulsive therapy choice for ureteral stones in pediatric patients. As the level of classification of evidence-based medicine, the level of evidence of our article is Ia. But it remains to need a large-scale multicenter randomized controlled study to be further confirmed. LEVEL OF EVIDENCE: The level of evidence of our study is V.