Translational andrology and urology最新文献

Background: Patients with end-stage erectile dysfunction (ED) who fail to respond to phosphodiesterase-5 inhibitors lack well-defined molecular targets for new pharmacologic therapies. To identify common expression patterns of key biomarkers in corpora cavernosa tissue from men undergoing penile prosthesis placement, thereby informing future drug development for treatment-resistant ED.

Methods: Formalin-fixed corpora cavernosa specimens were collected intraoperatively from 14 men receiving penile prostheses for ED. Sections were immunohistochemically stained for Rho-associated protein kinase (ROCK1/ROCK2), CD31 (endothelial marker), smooth muscle actin (SMA), and lysyl oxidase (LOX1). Staining intensity was graded under light microscopy on a 0 to +4 scale: 0 (negative), +1 (weak/mild), +2 (moderate), +3 (strong), and +4 (intense). Baseline demographics and comorbidities were recorded.

Results: Older age, longer ED duration, hypertension, hyperlipidemia, and coronary artery disease were associated with higher ROCK1/2 expression. SMA staining was elevated in hypertensive patients and those with prolonged ED. Both current and former smokers showed increased CD31 expression, while LOX1 levels were highest in subjects with coronary artery disease. Across all samples, mean scores for ROCK1/2 and SMA exceeded those for CD31 and LOX1.

Conclusions: This preliminary analysis reveals differential expression of four biomarkers in treatment-resistant ED associated with specific comorbidities. ROCK1/2- and SMA-driven pathways may represent promising targets for new ED therapies.

Background: Asthenozoospermia is a leading cause of male infertility with limited treatment options. Emerging evidence implicates epigenetic alterations, particularly DNA methylation, in its pathogenesis. The Qixiong Formula (QXF) has shown clinical efficacy in improving sperm motility, yet its underlying epigenetic mechanism remains unclear. This study therefore aimed to investigate the therapeutic effects of QXF and its regulation of genome-wide sperm DNA methylation in a rat model of asthenozoospermia.

Methods: Asthenozoospermia was induced in male Sprague-Dawley rats via oral administration of ornidazole (400 mg/kg/day) for 28 days. Rats were treated with low, medium, or high doses of QXF. Semen parameters, testicular and epididymal histology, organ coefficients, and liver and kidney function were assessed. Reduced representation bisulfite sequencing (RRBS) was used to profile genome-wide DNA methylation in sperm and identify differentially methylated regions (DMRs), followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses.

Results: QXF significantly improved sperm motility without affecting sperm concentration or systemic toxicity. Histological analysis showed partial recovery of epididymal architecture in QXF-treated rats. RRBS revealed that QXF induced a shift toward global hypomethylation in sperm DNA, reversing the hypermethylation pattern observed in the model group. Enrichment analyses implicated several key signalling pathways in QXF's action, particularly cAMP, cGMP-PKG, and PI3K/Akt pathways, which are known to regulate sperm motility and survival.

Conclusions: QXF improves sperm motility and reverses aberrant methylation patterns in a rat model of asthenozoospermia. These findings suggest that QXF exerts its therapeutic effect through dual regulation of DNA methylation and activation of sperm-related signalling pathways, offering new insights into the epigenetic basis of its action.

Background: Sepsis is a leading cause of mortality following ureteroscopic lithotripsy (URSL). Current diagnostic criteria, such as the Sequential Organ Failure Assessment (SOFA) score, are effective for identifying established sepsis but often fail to provide early warning before clinical deterioration. This creates a critical need for readily available predictive biomarkers. Given that a rise in neutrophils and a fall in platelets are central to sepsis pathophysiology, neutrophil-to-platelet ratio (NPR) represents a promising candidate for early risk stratification. This study aimed to evaluate the NPR for the early prediction of postoperative sepsis following URSL.

Methods: We retrospectively analyzed data from 674 patients undergoing URSL (January-December 2024). After screening, 385 patients were included and classified into sepsis (n=40) and control (n=345) groups based on postoperative urine culture and SOFA score. Biomarkers measured 3-hour postoperatively were analyzed using logistic regression. Diagnostic performance was assessed by receiver operating characteristic (ROC) curves.

Results: Multivariable analysis identified NPR, monocyte-to-lymphocyte ratio (MLR), and female gender as independent predictors of sepsis. Among these, NPR demonstrated the strongest association. The sepsis group exhibited a significantly higher NPR (0.081±0.051 vs. 0.020±0.013, P<0.01). NPR showed robust diagnostic efficacy with an area under the curve (AUC) of 0.89 [95% confidence interval (CI): 0.838-0.955], sensitivity of 80.0%, and specificity of 88.4% at an optimal threshold of >2.77×10^-2.

Conclusions: The NPR, obtained from a routine blood count 3-hour after URSL, is a strong independent predictor of subsequent sepsis, showing high diagnostic accuracy. These findings highlight its potential clinical utility for early risk stratification, pending validation in prospective multicenter cohorts.

Background: Prostate cancer (PC), a common male urogenital malignancy, and coronary heart disease (CHD), a cardiovascular disease from coronary lesions causing myocardial ischemia, interact in comorbidity. This study integrated their transcriptome data to reveal comorbid mechanisms and develop cross-disease targets.

Methods: In this research, candidate genes were derived from differential analysis and intersection analysis. Subsequently, machine learning algorithms were integrated with receiver operating characteristic (ROC) curve assessment and expression confirmation to identify key genes. Nomograms were further constructed, and analyses were carried out on the subcellular and chromosomal localization, enrichment pathways, molecular regulatory networks, and immune infiltration of these key genes. Potential drugs were predicted and molecular docking was performed. Ultimately, to confirm whether the expression patterns of key genes in clinical samples aligned with the bioinformatics analysis results, reverse transcription quantitative polymerase chain reaction (RT-qPCR) was conducted.

Results: A total of 84 candidate genes were identified using bioinformatics approaches in this study. Through machine learning and validation with multiple datasets, ADD3 and ATP2B4 were identified as key genes, with good predictive performance. ADD3 is located on chromosome 10, and ATP2B4 is on chromosome 1. Both are distributed in the cell nucleus and are mainly enriched in ribosomes, ubiquitin-mediated protein degradation, and cancer-related pathways. ADD3 is associated with 21 micro RNAs (miRNAs) and 4 transcription factors (TFs), while ATP2B4 is associated with 11 miRNAs and 6 TFs. They are also involved in immune cell regulation. The study predicted 22 drugs, and molecular docking confirmed that they stably bound with potential drugs (e.g., DL-175) (docking score ≤-5 kcal/moL). RT-qPCR results were consistent with bioinformatics analyses (P<0.05).

Conclusions: This study determined the key genes related to PC and CHD, providing new bases and targets for diagnosis, treatment, and drug development.

Background: C-reactive protein (CRP) is one of the most important markers reflecting systemic inflammatory response. The objective of this study was to evaluate the prognostic value of CRP in patients undergoing treatment with immune checkpoint inhibitor (ICI) for renal cell carcinoma.

Methods: We performed a systematic search of PubMed, Cochrane Library, and Web of Science databases in July 2024, following the PRISMA statement. A pooled meta-analysis was conducted to assess the prognostic value of CRP. We also evaluated the prognostic values of CRP kinetics.

Results: The search identified 12 non-randomized controlled trials (NRCTs), of which 7 assessed the prognostic value of CRP and 5 evaluated CRP kinetics. Higher CRP level before treatment with ICI was a predictor of overall survival (OS) [hazard ratio (HR): 3.97, 95% confidence interval (CI): 2.27-6.94]. In a subgroup of patients treated with nivolumab alone, the pooled HR of OS and progression-free survival (PFS) was HR: 5.67, 95% CI: 2.12-15.12 and HR: 1.62, 95% CI: 1.01-2.61, respectively. "CRP flare-responders" defined as having CRP elevation of at least double the baseline during the first month after ICI-initiation followed by a decrease below the baseline within 2 months and "CRP-responders" defined as having a decrease in CRP levels of at least 30% from baseline within 3 months, did not show significantly better prognosis regarding PFS.

Conclusions: Pre-treatment CRP level may stand as a good prognostic indicator in patients receiving ICI for renal cell carcinoma.

Demand for penile enhancement-driven by cosmetic and psychological goals-is rising, and complications are increasingly encountered in urologic practice. This review offers practical, procedure-focused guidance on diagnosing and managing adverse events after injectable fillers, self-injection of foreign substances, dermal matrices, autologous fat transfer, and the subcutaneous silicone Penuma implant. Hyaluronic acid (HA) is the most commonly used filler and, when applied with standardized, low-volume protocols, generally has lower complication rates than polylactic acid (PLA), polymethylmethacrylate (PMMA), silicone, or nonmedical self-injected materials. Typical HA-related issues include migration, nodules, Tyndall effect, phimosis, and infection; management emphasizes early massage/modeling, warm compresses, judicious hyaluronidase for confirmed HA, antibiotics with drainage for abscess, and selective surgical excision for refractory nodules. Permanent fillers and self-injected substances are associated with granuloma, necrosis, infection, lymphedema, and disfiguring inflammation; these often require wide excision down to Buck's fascia with reconstructive strategies such as split-thickness skin grafts or scrotal/dartos flaps. For dermal matrix and fat transfer, complications include edema, hematoma, infection (commonly Staphylococcus aureus or Escherichia coli), necrosis, contour deformity, and rare fat embolism; treatment ranges from compression and local debridement to staged reconstruction. The Penuma implant presents device-specific problems-seroma, infection, distal flaring with impending erosion, capsular contracture, curvature, and shortening-managed with antibiotics, wound care, traction or vacuum therapy, revision, or explantation with postoperative rehabilitation; salvage in frank infection is not described. Across modalities, prevention hinges on patient selection, informed consent with expectation management, sterile technique, and adherence to standardized injection/implant protocols. Timely recognition of early versus late complications and use of clear algorithms can preserve cosmesis and function. This review distills current data and referral-center experience into actionable steps for clinicians who perform or manage complications of penile enhancement procedures.

Robot-assisted posterior bladder neck (BN) reconstruction is a key technique in complex urological surgery. The posterior BN presents unique challenges due to its narrow anatomical access and lack of surrounding spongiosum. Grafts enhance structural integrity in posterior BN reconstruction, particularly in cases of significant tissue loss, stenosis, or scarring. These challenges require precise graft placement and tissue handling, which we have outlined the best techniques within the existing literature in this review. This article provides a detailed review of robot-assisted posterior BN reconstruction, focusing on graft types, surgical techniques, and outcomes to optimize reconstruction and patient recovery. A literature search was conducted on January 30th, 2025, utilizing PubMed, Medline, Web of Science, and Embase databases. The search focused on terms related to urethral reconstruction, posterior urethral stenosis (PUS), graft types, and grafting techniques in adult populations. Articles were screened for relevance at the title, abstract, and full-text levels, with reference lists of included manuscripts also reviewed. Independent reviewers conducted the selection process. Management of PUS varies based on stenosis length, location, and severity. Robotic-assisted techniques, such as vesicourethral anastomotic reconstruction (VUAR), demonstrate high success rates for complex cases. Grafts provide durable options for substitution urethroplasty, with graft selection tailored to patient-specific factors. Buccal mucosal grafts (BMGs) remain the first choice for many urologists. Robotic systems offer enhanced precision, reduced morbidity, and shorter recovery times, making them a valuable tool in reconstructive urology. Robotic-assisted posterior urethral reconstruction offers a highly effective solution for managing PUS and restoring urinary function. Advancements in surgical techniques and tissue engineering will continue to optimize outcomes and expand treatment options. Future research should focus on long-term studies, patient-centered innovations, and standardized protocols to enhance the quality of care in reconstructive urology.