Translational andrology and urology最新文献

Background: Previous studies have investigated the association between immune inflammation, metabolism and erectile dysfunction (ED). However, these studies are limited by biases, confounding factors, and reverse causality, failing to establish causality. We conducted a two-sample Mendelian randomization (MR) study to elucidate the causal relationships between immune cells, inflammatory cytokines, plasma metabolites, and the risk of ED.

Methods: Data on 91 inflammatory cytokines (n=14,736), 731 immune phenotypes (n=3,757) and 1,400 circulating metabolites (n=8,000) were obtained from genome-wide association studies (GWAS) as exposures, while ED data were sourced from the Integrative Epidemiology Unit (IEU) Open GWAS database (n=223,805) as outcomes. A two-sample MR analysis was performed to determine the relationships between exposures and outcomes. The inverse variance weighted (IVW) method was used as the primary MR analysis approach, supplemented by additional methods. Sensitivity analyses, including Cochran's Q test for heterogeneity and MR-Egger intercept for horizontal pleiotropy, were conducted to assess the robustness of the MR results.

Results: At a significance level of P<0.01, we identified 12 factors associated with ED: five immune cells, one inflammatory cytokine, two metabolites, and four metabolite ratios. Specifically, CD19 on immunoglobulin D- (IgD-) CD38+ B cells [odds ratio (OR) =1.17; 95% confidence interval (CI): 1.06-1.30], CD4 on terminally differentiated CD4+ T cells (OR =1.07; 95% CI: 1.02-1.12), CD25 on IgD+ CD38dim B cells (OR =1.05; 95% CI: 1.01-1.09), CD25 on IgD+ CD24- B cells (OR =1.04; 95% CI: 1.01-1.07), and IgD on IgD+ B cells (OR =0.88; 95% CI: 0.79-0.97) were associated with ED. Among inflammatory cytokines, only elevated levels of urokinase-type plasminogen activator (uPA) significantly reduced the risk of ED (OR =0.83; 95% CI: 0.73-0.95). Six metabolites, including glycerol levels (OR =1.30; 95% CI: 1.08-1.56), aspartate to N-acetylglucosamine to N-acetylgalactosamine ratio (OR =1.21; 95% CI: 1.07-1.37), cholesterol to taurocholate ratio (OR =1.23; 95% CI: 1.07-1.42), 4-methyl-2-oxopentanoate to 3-methyl-2-oxobutyrate ratio (OR =1.26; 95% CI: 1.07-1.48), alpha-ketoglutarate to kynurenine ratio (OR =0.86; 95% CI: 0.76-0.96), and X-16964 levels (OR =1.24; 95% CI: 1.06-1.45) were significantly associated with ED. Sensitivity analyses did not reveal any heterogeneity or pleiotropy.

Conclusions: Our MR analysis indicates that immune inflammation and metabolism have both inducing and protective effects on ED risk. These findings provide new insights for clinicians regarding the treatment and prevention of ED. Additionally, our study offers novel insights into the pathogenesis of ED.

Background: Epididymitis, a common disease of the male reproductive system, is often caused by nonspecific infections. Antibiotics alone cannot reverse histopathological changes or prevent long-term reproductive issues. Lycopene (LYC), a potent antioxidant, has shown potential in alleviating epididymitis, yet its specific mechanisms remain unclear. This study used network pharmacology and in vivo experiments to explore LYC's mechanisms in treating epididymitis.

Methods: Epididymitis- and LYC-related target proteins were identified from multiple databases and analyzed using the Venny platform. Protein interactions were examined with the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and key targets were identified via topological analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using the Database for Annotation, Visualization and Integrated Discovery (DAVID) database. Target-pathway networks were visualized in Cytoscape, molecular docking was performed with AutoDock Vina, and LYC's effects were validated in a lipopolysaccharide (LPS)-induced epididymitis mouse model.

Results: Network pharmacology results indicated that LYC's effects involve the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, which plays a crucial role in regulating inflammation and apoptosis. In vivo, LYC improved epididymal pathology, reduced inflammatory cell infiltration, and decreased key inflammatory cytokines, including interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). By inhibiting PI3K/AKT activation, LYC modulated inflammation and reduced apoptosis. Additionally, LYC enhanced antioxidant enzyme activity and elevated the B-cell lymphoma-extra large (Bcl-xL) ratio, reducing oxidative stress and apoptosis. Molecular docking supported these findings, showing strong binding affinities with PI3K/AKT pathway targets.

Conclusions: This study highlights LYC's potential as an adjunctive treatment for epididymitis, targeting inflammation and oxidative stress via the PI3K/AKT pathway. These findings suggest that LYC could enhance current therapies and provide new options for the clinical management of epididymitis.

Background: Recently, some observational studies have suggested potential associations between erectile dysfunction (ED) and respiratory function. However, the underlying biological mechanisms and causal relationships between ED and lung function require further investigation. This study aimed to explore the causalities between ED and lung function traits.

Methods: Single-nucleotide polymorphisms (SNPs) for ED were extracted from the Finngen_r7 (1,154 cases and 94,024 controls), and the summary statistics of respiratory function were extracted from the UK Biobank (UKB) (n=321,047). We utilized several Mendelian randomization (MR) methods to mitigate the impact of weak instrument bias and pleiotropy. To address potential confounding effects, multivariable MR (MVMR) analyses were also conducted, adjusting for demographic factors and respiratory conditions. Moreover, recently developed latent causal variable (LCV) modeling was also performed to enhance the robustness of the findings.

Results: Totally 15 SNPs robustly associated with ED were included. We found that higher risk of ED was associated with decreased of forced expiratory volume in the first second (FEV1) [odds ratio (OR) 0.992, 95% confidence interval (CI): 0.986, 0.997, P=0.003], as was the case for forced vital capacity (FVC) (OR 0.994, 95% CI: 0.989, 1.000, P=0.04), peak expiratory flow (PEF) (OR 0.990, 95% CI: 0.990, 0.990, P=0.01) and FEV1/FVC ratio (OR 0.991, 95% CI: 0.985, 0.997, P=0.002). After adjusting for confounding factors, ED only demonstrated causal effects on FEV1/FVC ratio. Notably, the LCV analysis provided additional support for the positive causal impact of ED on FEV1 and FVC. Conversely, reverse MR analysis did not reveal compelling evidence for a causal effect of lung function on ED.

Conclusions: Our study suggests a potential causal relationship between higher ED susceptibility and reduced respiratory function, as indicated by decreased FEV1, FVC, PEF, and the FEV1/FVC ratio. The results enhanced understanding of the intricate interrelationships between ED and lung function.

Background: Diabetic nephropathy (DN), a severe complication of diabetes, is characterized by glomerular and tubular damage, which often leads to end-stage renal disease (ESRD). The role of renal macrophages (Mφs), particularly their phenotypic plasticity and function in DN, remains poorly understood. This study investigated the key factors influencing Mφ polarization and their impact on podocyte (PODO) injury in DN.

Methods: Single-nuclear RNA sequencing (snRNA-seq) data from DN and control (CON) kidney samples were analyzed for cell clustering, differential expression, and cell communication. Mφs were identified and categorized based on their gene expression profiles. The proportions and functions of different Mφ phenotypes were compared between DN and CON samples, with a focus on their interaction with PODOs.

Results: A subset of Mφs, characterized by high expression of CD163, MRC1, PTH2R, PDE4D, and CUBN, was significantly depleted in DN as compared to in CON samples. This depletion was associated with the overexpression of AHR and underexpression of IGF1R, inhibiting the differentiation of these protective Mφs. The remaining Mφs in the DN samples exhibited altered functions, particularly in regulating oxidative stress and tight junctions. Their interaction with PODOs through ligands including NRG3 and THBS1 suggested a role in promoting PODO dysfunction and apoptosis and their contribution to the progression of DN.

Conclusions: The depletion of Mφs with a moderate-to-high expression of CD163, MRC1, PTH2R, PDE4D, and CUBN in patients with DN leads to enhanced PODO injury and apoptosis, highlighting a potential therapeutic target for mitigating DN progression. Further research into the mechanisms governing Mφ-PODO interactions could provide insights into novel treatment strategies for DN.

Background: Standard postoperative care following laparoscopic radical nephrectomy (LRN) typically includes routine blood tests. Recent studies have assessed the safety of omitting routine postoperative labs in minimally invasive surgeries to reduce hospital costs. Our primary objective was to evaluate if routine postoperative day 1 (POD1) labs were necessary following LRN.

Methods: We evaluated 650 consecutive LRN performed by a single surgeon. Patients on dialysis or that previously had a renal transplant were excluded from the study. Our final analysis included 478 LRN. We examined POD1 labs of potassium (K), sodium (Na), and hemoglobin (Hgb) and their associations to preoperative and postoperative outcomes. Abnormal K at POD1 was defined as less than 3.5 mEq/L or greater than 5.0 mEq/L. Abnormal Na at POD1 was defined as less than 135 mEq/L or more than 145 mEq/L. Abnormal Hgb at POD1 was defined as POD1 Hgb less than 8 g/dL or POD1 Hgb 3.0 g/dL or more decrease from preoperative Hgb.

Results: One or more abnormal POD1 labs were observed in 32.4% (155/478) patients. Sixty-five patients had abnormal Hgb, 57 had abnormal Na, and 53 had abnormal K. Preoperative patient factors associated with abnormal labs included older age [odds ratio (OR) 0.461; 95% confidence interval (CI): 0.26-0.809], higher Charlson comorbidity index (CCI) (OR 1.671; 95% CI: 1.036-2.7), and increased intraoperative blood loss (OR 1.213; 95% CI: 1.069-1.39; all P<0.05). Intraoperative variables such as longer operative time and complications were not significantly associated with abnormal labs (P>0.05).

Conclusions: Abnormal labs on POD1 following LRN were found in 32.4% of patients. POD1 lab tests appear to be needed following LRN in older patients with more comorbidities.

Background: Nephrogenic adenoma (NA) is a rare benign tumor that can develop at any site of the urinary system, with the bladder being the most common, followed by the urethra, ureters, renal pelvises, etc. Currently, it is unclear what the pathogenesis of NA is. This study discussed a rare case of malignant transformation from NA to mesonephric adenocarcinoma of the bladder.

Case description: A 66-year-old man with a bladder mass was admitted to the hospital. A cystoscopic electro biopsy and transurethral resection of bladder tumor (TUR-BT) pathologically indicated that the patient had an NA of the bladder. Furthermore, immunohistochemistry analysis revealed: Pax-8 (+), Pax-2 (-), CK7 (+), EMA (+), p63 (a small proportion+), Ki-67 (1%+). The patient underwent a robot-assisted laparoscopic partial cystectomy, and the pathology of the resected tumor revealed mesonephric adenocarcinoma of the bladder. Moreover, the immunohistochemistry investigation results showed: AE1/AE3 (+), CK7 (+), CK20 (-), PAX-8 (+), P63 (partial+), GATA-3 (weak+), P53 (a small amount+), and Ki-67 (+, 30% of hot spots). And there were no signs of recurrence found during the 1-year follow-up.

Conclusions: It is rare for NAs of the bladder to develop to mesonephric adenocarcinomas of the bladder, and pathological immunohistochemistry staining is used to make the definitive diagnosis. The high proliferation activity of carcinoembryonic antigen (CEA) (+), P53(+), and Ki-67 are important molecular markers for identifying the malignant transformation of NA, as well as the elevation in the Ki-67 proliferation index.

Background: Despite the availability of advanced imaging technologies, it remains difficult to achieve sufficient staging accuracy to ensure a tailored treatment strategy for patients with upper tract urothelial carcinoma (UTUC). The aim of the study was to identify preoperative risk factors for tumor upstaging in patients with UTUC initially staged as clinical T2 or lower and to analyze these factors separately for renal pelvic cancer and ureteral cancer.

Methods: This retrospective study included data from patients with UTUC who underwent nephroureterectomy. Among them, patients who underwent a staging evaluation using computed tomography urography within 90 days before surgery were selected. Various preoperative factors were evaluated, and multivariate logistic regression analyses were conducted to identify predictors of pathological tumor upstaging.

Results: The study included 496 patients, of whom 392 were diagnosed with clinical T2 stage or lower. Among these, 125 patients (31.9%) were upstaged to pathological T3 or T4 disease. Multivariate analysis identified positive voided urine cytology [hazard ratio (HR) =2.94, P<0.001] and tumor size ≥30 mm (HR =1.90, P=0.008) as independent predictors of upstaging. Subgroup analysis showed that positive voided urine cytology (HR =2.71, P=0.004) and tumor size ≥30 mm (HR =3.39, P=0.001) were significant risk factors for renal pelvic cancer. In contrast, significant predictors for ureteral cancer included positive voided urine cytology (HR =3.11, P=0.003) and hydronephrosis (HR =2.69, P=0.03).

Conclusions: Positive voided urine cytology and larger tumor size were significant predictors of pathological upstaging in patients with UTUC. Differences in the risk factors between renal pelvic and ureteral cancers highlight the need for tailored preoperative evaluations and management strategies. Further studies are required to refine these predictive models and improve clinical decision-making.

Background and objective: Despite the growing popularity of acupuncture for sexual dysfunction (SD) in the Western world, many clinicians struggle to understand the exact therapeutic mechanism of acupuncture which is based on traditional Chinese medicine (TCM). This study aims to describe the fundamentals of acupuncture theory from TCM perspectives and its relevance to SD; evaluate the current state of acupuncture research within literature evidence; and critically analyze its therapeutic effects in premature ejaculation (PE), erectile dysfunction (ED), and female SD.

Methods: All published English-language SD clinical studies treated by acupuncture were searched in PubMed from database inception to 1 April 2024. Articles in non-English languages, case reports, letters, comments and review articles were excluded. Data accrued from the related studies were extracted by sample, disease, study type, age, acupoints, interventions and clinical outcomes.

Key content and findings: Out of the 64 articles identified in the database, 15 studies were included in this final review. Acupuncture is effective in improving SD. Of the 114 acupoints identified, the ren meridian had the highest number of occurrences, followed by the liver meridian of foot-jueyin, the kidney meridian of foot-shaoyin, the stomach meridian of foot-yangming and the spleen meridian of foot-taiyin.

Conclusions: While acupuncture therapy has its characteristics in treating PE, ED, and female SD, the specific mechanisms should be further explored and validated in larger multicenter clinical trials.

Background: Understanding the molecular mechanisms and identifying prognostic markers across various subtypes and stages of prostate cancer (PCa) are crucial for improving therapeutic strategies against the disease. This study focuses on discovering novel immune-related biomarkers that could aid in the evaluation and prognosis of PCa at different stages and serve as promising therapeutic targets.

Methods: Transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were analyzed to identify differentially expressed genes (DEGs) linked to PCa progression. The relationship between immune cell infiltration in the tumor microenvironment (TME) and the expression levels of baculoviral inhibitor of apoptosis protein repeat containing 5 (BIRC5) and hyaluronan-mediated motility receptor (HMMR) were examined using xCELL and quanTIseq algorithms.

Results: The analysis identified ten key hub genes, with survival analysis indicating that higher expressions of BIRC5 and HMMR were associated with poor outcomes and may contribute to tumor progression. Notably, the expressions of BIRC5 and HMMR showed a significant correlation with tumor-infiltrating lymphocytes (TILs) in various PCa subgroups. Immunohistochemistry (IHC) evaluations further corroborated the bioinformatics findings.

Conclusions: This study confirms BIRC5 and HMMR as potential biomarkers for predicting the prognosis of PCa, providing important evidence for the development of future therapeutic strategies. Through further research, these biomarkers may be utilized in clinical practice to improve patient management and treatment outcomes.

Background: Immunotherapy is an emerging treatment modality for clear cell renal cell carcinoma (CCRCC). As a molecule involved in the prognosis of CCRCC, the effect of complement C3a expression levels on immunotherapy is unclear. This study aims to investigate the correlation between C3a and clinicopathological features in early CCRCC, as well as the alterations in complement C3a during immunotherapy for advanced CCRCC and its influence on therapeutic outcomes.

Methods: Immunohistochemistry was used to detect the expression of complement C3a in newly diagnosed CCRCC tissues and paracancerous tissues. The peripheral serum of advanced CCRCC patients who underwent programmed cell death protein 1 (PD-1) antibody immunotherapy was collected before treatment and after four cycles of treatment, and detected by enzyme-linked immunosorbent assay. For the concentration of complement C3a, the Response Evaluation Criteria in Solid Tumors version 1.1 was used to evaluate the therapeutic effect.

Results: Of the 110 CCRCC cases, 76 (69.09%) were positive for C3a expression, showing brown staining in the cytoplasm and membrane of the tumor cells. No difference was observed in the expression of complement C3a in the tumor tissues in terms of gender, age, location, and histological grade. The expression of complement C3a in tumors with a maximum transverse diameter >3.5 cm was higher than that in tumors with a maximum transverse diameter ≤3.5 cm (P=0.02), and the expression of complement C3a in the tissues of the tumor node metastasis classification (TNM) stage II patients was higher than that of the TNM stage I patients (P=0.005). Among the 30 patients with advanced CCRCC who underwent immunotherapy, 12 had a complete response (CR) or a partial response (PR), 7 had stable disease (SD), and 11 had progressive disease (PD). The C3a concentration decreased in the CR + PR + SD group after treatment, while it increased in the PD group and the difference was statistically significant. The survival analysis indicated that the progression-free survival of patients with decreased complement C3a after treatment was longer than that of patients with increased C3a (P<0.001).

Conclusions: Complement C3a is highly expressed in CCRCC, and the high expression of complement C3a is related to the stage and tumor size. During immunotherapy for CCRCC, changes in complement C3a can reflect the curative effect to a certain extent.