Translational andrology and urology最新文献

Background and objective: Recent investigations have highlighted mitochondrial dysfunction as a major component in reduced sperm function and male infertility. The creation of energy, control of reactive oxygen species (ROS), apoptosis, and sperm motility are all critically dependent on mitochondria. The health of the male reproductive system may be significantly impacted by any alteration of mitochondrial structure, function, or integrity. This review intends to open the door to better diagnostic methods, novel therapy strategies, and improved reproductive outcomes for infertile couples by clarifying the crucial function of mitochondria.

Methods: We searched PubMed, Google Scholar, and others for articles related to male infertility and mitochondrial dysfunction from 2014 to 2023. The articles related to the theme were preliminarily screened by abstract, and then the selected literature was read and summarized. In this essay, we examine the research on male infertility and mitochondrial malfunction. We investigate the intricate connection between sperm quality, deoxyribonucleic acid damage, oxidative stress (OS), and mitochondrial bioenergetics. We discuss about how spermatogenesis and sperm function are affected by mitochondrial mutations, deletions, and single nucleotide polymorphisms. We also explore the impact of age-related changes, lifestyle choices, and environmental factors on mitochondrial function and male fertility. This review also clarifies the mechanisms by which mitochondrial dysfunction impacts the viability, morphology, and capacitation of sperm, among other aspects of male reproductive health. Furthermore, we go over the recently developed field of mitochondrial treatments and possible therapeutic approaches that target mitochondrial malfunction to enhance male fertility.

Key content and findings: Mitochondria are important for sperm: The control of sperm motility, capacitation, and general quality is largely dependent on mitochondria. Deterioration of sperm motility and male infertility may result from disruption of the structure, function, or integrity of the mitochondria. Future studies should focus on figuring out the processes underlying mitochondrial dysfunction as fertility and reproductive health are significantly impacted by it.

Conclusions: We discuss the evaluation of infertile men mitochondrial function defects and difficulties, and make recommendations for further study in this area. This article provides a thorough resource for clinicians, researchers, and reproductive biologists to understand the underlying mechanisms of male infertility and explore potential therapeutic interventions.

Background: Stress urinary incontinence (SUI) remains a prevalent complication after Holmium Laser Enucleation of the Prostate (HoLEP). This retrospective analysis aims to delineate perioperative and anatomical determinants of SUI as observed on preoperative multiparametric magnetic resonance imaging (mpMRI) in patients subjected to HoLEP.

Methods: We reviewed 216 benign prostatic hyperplasia (BPH) cases managed via HoLEP by a singular urologist at Sun Yat-sen Memorial Hospital from January 2021 to September 2022. Comprehensive medical documentation, including age, body mass index (BMI), prostate volume (PV), total prostate-specific antigen (tPSA), and perioperative variables: operative time (OT), enucleated prostate volume (EPV), were assessed. Detailed analyses of preoperative prostate mpMRI scans were conducted to measure factors such as thickness of the posterior wall of the membranous urethral sphincter (TPWMUS), membranous urethral length (MUL), membranous urethral volume (MUV), and prostatic apex morphology.

Results: The cohort encompassed 216 participants, among whom 45 (20.83%) experienced SUI subsequent to one month of HoLEP therapy. At three months, 23 individuals exhibited recovery, reducing the prevalence of SUI to 10.19%. By the six-month milestone, the incidence further declined to 1.38%, with 19 patients reporting normalization of continence. Binary logistic regression analysis identified OT, TPWMUS, and prostatic apex and membranous urethral overlap (PAOMU) emerged as independent risk factors for SUI, while MUV was identified as a protective factor.

Conclusions: The risk of SUI post-HoLEP is significantly associated with OT, TPWMUS, and PAOMU, while MUV imparting a protective effect.

Background: Infection remains a significant concern following penile prosthesis (PP) implantation surgery. Published guidelines have indicated the use of pre-operative intravenous (IV) antibiotics but have not provided specific recommendations regarding intra-operative irrigation. For long in our practice, we have been using a combination of antibiotics for irrigation (rifampin 600 mg/L of sterile water, gentamicin 80 mg/L of sterile water). Recently, 0.05% chlorhexidine gluconate (CHG) (Irrisept^®) (Irrimax Corp, Lawrenceville, GA, USA), has shown promise as an alternative irrigant, with potential advantages in terms of cost, ease of administration and reduced antibiotic resistance risk. The study aims to assess the non-inferiority of CHG antiseptic irrigation compared to conventional combined antibiotic irrigation in preventing postoperative infections for men undergoing de-novo PP implantation.

Methods: This is a two-center Institutional Review Board (IRB) approved prospective randomized controlled non inferiority trial, involving men undergoing de-novo PP implantation with a predetermined non-inferiority margin of 4%. Patients were randomly assigned into one of two groups: the CHG irrigation or the group receiving conventional antibiotic irrigation. All patients received IV antibiotics preoperatively and were sent home on oral antibiotics for 2 weeks post-operatively. The primary endpoint of this trial was to evaluate the incidence of PP infections. Secondary objectives encompassed the assessment of simplicity of use and cost-effectiveness.

Results: A hundred patients were enrolled in our study so far (50 in each arm). Only one case of PP infection necessitating explanation was reported in each arm. Moreover, the use of CHG irrigation offered the potential advantages of ease of administration and less cost as compared to antibiotic irrigation solutions.

Conclusions: Preliminary data from this non-inferiority study demonstrate that CHG irrigation is non-inferior to conventional antibiotic irrigation in preventing postoperative infection following PP implantation. These findings support the consideration of CHG irrigation as a viable alternative during PP implantation, offering both clinical effectiveness and potential cost savings as well as reducing the risk of antibiotic resistance.

Trial registration: ClinicalTrials.gov NCT06489431.

Background: Incidences of rectal infiltration by prostate cancer (PCa) are reported to affect up to 12% of patients studied. PCa invading the rectum is prone to cause difficulty in defecation, bloody stool and pain, leading to a decline in patients' quality of life. Unfortunately, the prognosis for these patients is poor and the survival period is short. Total pelvic exenteration (TPE) has been demonstrated to mitigate pain and improve symptoms such as defecation difficulty, dysuria, and hematuria. However, most patients still harbor residual tumor and fail to exhibit any improvement in long-term survival.

Case description: Here, we present a case of PCa invading the rectum with focal neuroendocrine differentiation, characterized by clinical presentations of defecation difficulties and rectal bleeding. A TPE procedure was performed, with a whole exome sequencing (WES) assay indicating that the patient exhibited a high tumor mutation burden (TMB) and high microsatellite instability (MSI-H). Subsequently, the patient received androgen deprivation therapy (ADT) combined with adjuvant immunotherapy following the procedure. At the subsequent six-year follow-up, no local or systemic recurrence was observed, and the prostate-specific antigen (PSA) level remained undetectable.

Conclusions: This disease entity remains relatively rare in the literature. Accurate differential diagnosis is important. TPE combined with immunotherapy may improve the prognosis. It is of utmost importance to achieve an accurate differential diagnosis, which necessitates the collaboration of multiple disciplines and the performance of requisite tests, including immunohistochemistry and genetic testing.

Background: Renal function deterioration during systemic therapy in patients with metastatic renal cell carcinoma (mRCC) is a long-term concern in treatment planning. Although hypertension (HTN) and diabetes mellitus (DM) are the most common factors that affect chronic kidney disease (CKD) development and progression, their impact on renal function during targeted therapy is unclear. This study investigated whether DM and HTN were associated with a decline in renal function during first-line targeted therapy for mRCC.

Methods: This retrospective multicenter study analyzed patients receiving first-line targeted therapy for mRCC. They were classified as follows: group 1: HTN-, DM-; group 2: HTN+, DM-; group 3: HTN-, DM+; and group 4: HTN+, DM+. Changes in renal function and factors affecting progression to stage 4 CKD after targeted therapy were analyzed.

Results: Among the 424 enrolled patients, 303 (71.5%) and 121 (28.5%) were treated with sunitinib and pazopanib, respectively [median duration: 10.3 months, interquartile range (IQR), 3.1-37.0 months]. Although all groups showed a decreased mean estimated glomerular filtration rate (eGFR) after treatment (P<0.001 for group 1, group 2, and group 4, P=0.02 for group 3, respectively), there were no significant differences in changes in eGFR (∆eGFR) between groups (P=0.10). However, actual renal function change calculated using percent ∆eGFR (%∆eGFR) showed differences between groups (P=0.02); the %∆eGFR of group 4 was significantly lower compared with group 1 (P=0.008). The mean progression time to stage 4 CKD in group 4 (38.6 months) was significantly shorter compared to the other groups (P<0.001). Multivariate analysis identified increased age (P=0.008), increased number of metastatic sites (P=0.047), and DM and HTN coexistence (P<0.001) as predictors of progression to stage 4 CKD.

Conclusions: Patients with DM and HTN experienced further decline in renal function and had a higher risk of progression to stage 4 CKD after targeted therapy compared to patients without these risk factors. Recognition and proactive management of DM and HTN are necessary to facilitate the proper administration of life-prolonging oncological treatments.

Background: As the Omicron variant became the dominant coronavirus disease 2019 (COVID-19) strain and the threat to human health decreased, the impact of COVID-19 on male reproductive health and semen quality may have changed. In this prospective observational study, we aimed to investigate the changes in semen quality and sexual function before and after the Omicron variant infection by self-controlled study and to explore the influence of Omicron variant infection on male reproductive health.

Methods: We recruited 373 participants who provided semen samples before their first COVID-19 infection. During the subsequent follow-up, only 154 participants provided the second semen samples, 11 of whom were not infected with COVID-19. Sperm quality was assessed approximately 45 and 90 days after COVID-19, as well as before infection.

Results: Semen parameters, including total sperm count, total forward sperm, progressive motility, and sperm concentration, significantly declined 45 days after COVID-19 infection. At 90 days after infection, the total sperm count, total forward sperm, and sperm concentration gradually increased to pre-infection levels. Participants who experienced fever showed worse semen quality in terms of total forward sperm, sperm concentration, and sperm progressive rate. However, this phenomenon was not observed in the other group infected with COVID-19 without fever or not infected. In addition, 49 (34.3%) of 143 persons confirmed that the COVID-19 infection resulted in changes in sexual function, with an increase in premature ejaculation diagnostic tool (PEDT) scores.

Conclusions: The results of our self-controlled study indicate that COVID-19 is associated with impaired semen quality early after disease onset. After 1-2 spermatogenesis cycles, the semen quality gradually recovers from the infection. These findings are beneficial for better understanding the COVID-19-associated sequelae, which are fundamental for semen collection during assisted reproduction.

Background: Bladder cancer carries a large societal burden, with over 570,000 newly diagnosed cases and 210,000 deaths globally each year. Platelets play vital functions in tumor progression and therapy benefits. We aimed to construct a platelet-related signature (PRS) for the clinical outcome of bladder cancer cases.

Methods: Ten machine learning techniques were used in the integrative operations to build PRS using the datasets from The Cancer Genome Atlas (TCGA), gene series expression (GSE)13507, GSE31684, GSE32894 and GSE48276. A number of immunotherapy datasets and prediction scores, including GSE91061, GSE78220, and IMvigor210, were utilized to assess how well the PRS predicted the benefit of immunotherapy. Vitro experiment was performed to verify the role of α1C-tubulin (TUBA1C) in bladder cancer.

Results: Enet (alpha =0.4) algorithm-based PRS had the highest average C-index of 0.73 and it was suggested as the optimal PRS. PRS acted as an independent risk factor for bladder cancer and patients with high PRS score portended a worse overall survival rate, with the area under the curve of 1-, 3- and 5-year operating characteristic curve being 0.754, 0.779 and 0.806 in TCGA dataset. A higher level of immune-activated cells, cytolytic function and T cell co-stimulation was found in the low PRS score group. Low PRS score demonstrated a higher tumor mutation burden score and programmed cell death protein 1 & cytotoxic T-lymphocyte associated protein 4 immunophenoscore, lower tumor immune dysfunction and exclusion score, intratumor heterogeneity score and immune escape score in bladder cancer, suggesting the PRS as an indicator for predicting immunotherapy benefits. Vitro experiment showed that TUBA1C was upregulated in bladder cancer and knockdown of TUBA1C obviously suppressed tumor cell proliferation.

Conclusions: The present study developed an ideal PRS for bladder cancer, which may be used as a predictor of prognosis, a risk classification system, and a therapy guide.

Background: In recent decades, there has been increasing evidence that Go-Ichi-Nii-San (GINS) subunits play an important role in the development and progression of various tumors. However, little research has been conducted on the role of GINS subunits in clear cell renal cell carcinoma (ccRCC). This study sought to explore the differential expression, prognosis, and immunological significance of GINS subunits in ccRCC.

Methods: We used various analysis packages of R (version 3.6.3), the University of ALabama at Birmingham CANcer (UALCAN) data analysis portal, the Cancer Cell Line Encyclopedia (CCLE), the cBio Cancer Genomics Portal (cBioPortal), and the Tumor Immune Estimation Resource (TIMER) to study the gene expression, promoter methylation level, gene mutations, prognostic and diagnostic value, immune infiltration, pathway enrichment, and other aspects of the GINS subunits. Next, the genes related to the GINS subunits were analyzed using the STRING and GeneMANIA platforms, and the correlation between GINS subunits and the functions involved were investigated.

Results: The expression level of GINS1/2/3/4 was significantly higher in ccRCC tumor tissues than normal tissues, and was significantly related to tumor grade and stage. The expression of GINS1/2/4 may be related to the methylation degree of the promoter region. The prognostic and diagnostic analyses showed that the increased expression of GINS1 was associated with various poor prognoses and had diagnostic value. The GINS subunit mutation also significantly affected the clinical prognosis of ccRCC patients. Finally, the correlation analysis of the immune infiltration level, co-expression, and enrichment of related genes indicated that GINS subunit expression was associated with different levels of ccRCC immune infiltration.

Conclusions: The analysis results showed that the differential expression of GINS subunits in ccRCC, which had prognostic and diagnostic value, was correlated with clinicopathological stage, immune infiltration, and other related aspects. GINS1 may serve as a new potential prognostic biomarker for ccRCC patients and be used to guide treatment.

Background: While deficiencies in vitamin B₆, folate, and vitamin B₁₂ are linked to various human diseases, including anemia, depression, peripheral neuropathy, and cardiovascular disease (CVD), literature regarding the association between vitamin B₆, folate, and vitamin B₁₂ and erectile dysfunction (ED) is scarce. We aimed to determine the dietary intake of vitamin B₆, folate, and vitamin B₁₂ and ED in the United States population.

Methods: We extracted data from the 2001-2004 cycles of the National Health and Nutrition Examination Survey (NHANES). Dietary intakes of B vitamins were collected based on one 24-hour dietary recall. The association between dietary intake of vitamin B₆, folate, vitamin B₁₂ and ED was examined using multivariate logistic regression models.

Results: A total of 3,875 participants were included for analysis, with 1,201 reporting ED and 2,894 not experiencing ED. The multivariable odds ratios (ORs) for the highest vs. lowest quartiles of vitamin B₆ was 0.77 [95% confidence interval (CI): 0.60-0.99; P for trend =0.03] for the prevalence of ED. Subgroup analyses demonstrated a significant inverse association between dietary intake of vitamin B₆, folate, vitamin B₁₂ and the prevalence of ED among men aged ≤60 years, individuals of Mexican American and non-Hispanic White ethnicity, and those without a history of CVD, diabetes, hypertension, and high cholesterol.

Conclusions: The consumption of dietary vitamin B₆, folate, and vitamin B₁₂ was significantly linked to decreased risks of ED among younger healthier men, suggesting a potential protective role of these nutrients against ED in United States adults.