World Journal of Mens Health最新文献

Purpose: To investigate the correlation between male high-normal fasting blood glucose (FBG) and semen quality, embryonic development, and pregnancy outcomes of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI).

Materials and methods: This retrospective cohort study included 921 couples undergoing their first single blastocyst frozen-thawed embryo transfer cycles. Participants were divided into 4 groups depending on quartiles of male FBG (3.90-6.10 mmol/L): from the lowest Quartile 1 (Q1) to the highest Q4. Firstly, semen quality and reproductive outcomes were compared across groups. Next, based on male FBG quartiles, logistic regression models were performed to explore associations between FBG with semen quality and IVF/ICSI outcomes. Finally, with male FBG considered as continuous variables, generalized additive models (GAMs) were conducted to visualize the non-linear relationship of FBG with the outcomes. Primary outcome: live birth rate (LBR). Secondary outcomes: semen quality, embryonic development parameters, biochemical pregnancy rate (BPR), clinical pregnancy rate, miscarriage rate, and other pregnancy outcomes.

Results: Higher FBG quartiles exhibited significantly reduced sperm total motility, progressive motility, and progressive sperm count, alongside increased asthenozoospermia prevalence (p<0.05). BPRs rose from Q1 (4.4%) to Q4 (11.0%) (p=0.033), while LBR showed a declining trend from Q1 (46.7%) to Q4 (36.0%) (p=0.102). Regression analysis indicated that males in Q4 had a higher biochemical pregnancy risk and lower live birth likelihood (p-trend<0.05). GAMs revealed a dose-dependent increase in both asthenozoospermia and biochemical pregnancy risks with rising FBG levels.

Conclusions: High-normal male FBG is significantly associated with both impaired semen quality (particularly asthenozoospermia) and adverse IVF/ICSI outcomes, including increased biochemical pregnancy risk and reduced LBRs. These findings highlight the significance of assessing paternal metabolic health and suggest that FBG screening may serve as a valuable tool for optimizing IVF/ICSI strategies and improving reproductive success.

Purpose: This study aimed to estimate genetic susceptibility to prostate cancer (PCa) by constructing a polygenic risk score (PRS) using single nucleotide polymorphisms (SNPs) identified from genome-wide association studies.

Materials and methods: The study included 1,015 PCa patients from our institutions and 1,015 age-matched controls from the Taiwan Biobank (TWB). An independent external validation cohort of 188 PCa patients and 188 TWB controls (excluding those from the primary cohort) was assembled. DNA was extracted from blood samples, with approximately 690,000 SNPs genotyped (minor allele frequency ≥0.05) and 15 million additional SNPs imputed using the 1000 Genomes Project. After quality control, 958 PCa patients and 999 controls were included in the analysis. The PRS was developed using PRSice2 by dividing samples into a base dataset and a model-testing set. Model performance was assessed using receiver operating characteristic analysis and cross-validation (CV).

Results: Of the 87,092 SNPs initially considered, 24 were used to construct the PRS, located in intronic regions of genes such as KCNH7, HLA-DQA1, and PRNCR1. The PRS significantly improved PCa prediction, achieving an area under the curve (AUC) of 0.824 (p=1.23×10⁻⁵⁰). Patients in the top 25th percentile of PRS had a 34-fold higher risk compared to those in the bottom 25th percentile (odds ratio=34.37, 95% confidence interval=22.93-51.68, p=1.96×10⁻⁵². The model showed stable performance with mean accuracies of 0.75 (3-fold CV) and 0.76 (10-fold CV) and achieved an AUC of 0.757 in the independent validation cohort.

Conclusions: The developed PRS showed robust predictive ability for PCa in the Taiwanese population and may inform future risk stratification and personalized interventions.

Purpose: Metachronous cancer following the cure of the primary cancer could be related with the tumor microenvironment. Recently it has been known that nuclear factor erythroid 2-related factor 2 (NRF2), a key transcription factor regulates immune checkpoint expression, including programmed cell death-ligand 1 (PD-L1), a well-known checkpoint molecule. The aim of this study was to investigate the roles of NRF2 and PD-1 in the tumor microenvironment using the normal colon tissue, with a focus on sex-specific differences.

Materials and methods: A total of 280 participants were enrolled including 66 healthy controls (HC), 109 patients with colorectal adenoma (AD), and 105 patients with colorectal cancer (CRC). Quantitative real-time polymerase chain reaction (PCR) for NRF2 and PD-1 and methylation-specific PCR for NRF2 were performed with normal mucosal tissue above the 20 cm from anal verge.

Results: NRF2 methylation levels were significantly lower in the AD and CRC groups compared to the HC in both sexes. PD-1 mRNA expression was significantly reduced in the AD and CRC groups compared to the HC group. In terms of sex males showed significantly lower PD-1 mRNA levels in the AD and CRC groups, whereas females displayed significantly higher PD-1 expression in the AD group but significantly lower levels in the CRC group. In conclusion there were significant differences in NRF2 methylation and PD-1 expression in the normal mucosal tissue among CRC, AD, and HC groups, suggesting that metachronous lesions might arise from this underlying tumor microenvironment.

Conclusions: Our results suggest that mRNA expressions of NRF2 and PD-L1 in the normal colon tissue may serve as early molecular markers in colorectal carcinogenesis with distinct sex-specific patterns.

Cadmium telluride (CdTe) quantum dots (QDs) are widely utilized in biomedical applications because of their unique optical properties. However, concerns regarding their potential reproductive toxicity have emerged, necessitating comprehensive toxicological evaluations. Evidence suggests that Cd-based QDs can traverse the blood-testis barrier, accumulate in testicular tissue, and impair male fertility. Studies have reported detrimental effects, including reduced sperm quality, endocrine disruption, and oxidative stress-induced cellular damage. Moreover, multigenerational toxicity has been observed, with adverse effects on offspring, such as developmental delays, lower body weights, and biochemical markers of hepatic and renal dysfunction. To mitigate these toxic effects, various protective strategies have been investigated. Antioxidants, including astaxanthin nanoparticles and N-acetylcysteine, have demonstrated efficacy in reducing oxidative stress by neutralizing reactive oxygen species and restoring the cellular balance. Additionally, surface modifications, particularly zinc sulfide coatings, have shown promise in limiting cadmium ion release, thereby decreasing cytotoxicity and reproductive harm. The potential reproductive toxicity of CdTe QDs underscores the importance of developing safer nanomaterials. Future research should prioritize optimizing nanoparticle design, refining exposure parameters, and elucidating the molecular mechanisms underlying their toxicity to increase biocompatibility while minimizing reproductive risk.

Purpose: Diabetic erectile dysfunction (DMED) is a prevalent condition with limited treatment options. The role of RNA N6-methyladenosine (m⁶A) modification in the pathogenesis of DMED remains elusive. This study aimed to investigate the underlying m⁶A modification patterns and identify potential therapeutic targets for DMED.

Materials and methods: A rat model of DMED was established using streptozotocin injection and confirmed by apomorphine-induced penile erection. Erectile function was assessed via cavernous nerve electrostimulation. Fibrosis in the corpus cavernosum was evaluated using Masson's trichrome staining. RNA m⁶A modification levels and the expression of associated methyltransferases were examined by dot blot and quantitative real-time PCR. MeRIP-seq and RNA-seq were employed to identify differentially methylated and expressed genes. Conjoint analysis was performed to explore associated biological processes and identify key genes, which were subsequently validated.

Results: Elevated levels of RNA m⁶A modification were observed in DMED, accompanied by altered expression of METTL14 and METTL3. A total of 2,789 genes associated with 3574 m⁶A peaks were identified (p<0.05). Differentially methylated m⁶A genes were implicated in muscle cell differentiation, cell junction organization, and Wnt signaling pathways. Combined analysis of MeRIP-seq and RNA-seq identified and validated POSTN and LOX as key genes. These genes were associated with fibrosis, cell-matrix adhesion, and regulated Notch signaling pathway, and were predominantly enriched in corpus cavernosum fibroblasts of DMED.

Conclusions: This exploratory study provides the first exploration of RNA m⁶A modification in DMED, and offers novel insights into the pathogenesis of DMED and potential therapeutic targets.

Purpose: The role of varicocele repair (VR) in infertile men with non-obstructive azoospermia (NOA) and varicocele is controversial in the current guidelines, despite available studies. This study aims to assess the impact of VR on testicular sperm retrieval, sperm recovery from the ejaculate, and clinical pregnancy rates in infertile men with NOA and clinical varicocele through a systematic review and meta-analysis (SRMA) of controlled studies.

Materials and methods: A systematic literature search was conducted using the Scopus and PubMed databases up to November 2023. Among the 1,847 articles retrieved, five observational controlled studies comparing reproductive outcomes between infertile men with NOA and clinical varicocele who underwent VR, and a control group that received no treatment, met the inclusion criteria for this SRMA.

Results: The selected studies included 269 men with NOA who underwent VR before the testicular sperm extraction (TESE) procedure and 364 men who did not undergo VR. The pooled estimate demonstrated a significantly higher odds ratio (OR) of 2.17 (95% confidence interval [95% CI]: 1.17-4.01, p=0.01) for surgical sperm retrieval in the VR group. VR significantly increased the likelihood of sperm appearance in the ejaculate, with an OR of 7.8 (95% CI: 3.59-16.94, p<0.001). Besides, VR provided a significantly greater clinical pregnancy rate with intracytoplasmic sperm injection (ICSI) compared to non-operated men (OR: 2.18, 95% CI: 1.03-4.60; p=0.04).

Conclusions: This is the first SRMA, consisting of only controlled studies, to demonstrate that VR performed prior to TESE in men with NOA significantly improves sperm production as reflected in the spontaneous appearance of sperm in the semen and higher odds of surgical sperm retrieval and clinical pregnancy compared with non-operated men. Thus, these findings highlight the potentially beneficial impact of VR in men with NOA and clinical varicocele.

Purpose: To assess the relationship between perirectal hydrogel spacer placement and the clinical outcomes in men undergoing radiotherapy (RT) for prostate cancer.

Materials and methods: An extensive literature review was conducted using the PubMed/Medline, Embase, Cochrane Library, and Web of Science databases, encompassing studies published through June 2024. Group comparisons were performed using the weighted mean difference for continuous variables and the risk ratio for dichotomous measures. The primary endpoint was to compare rectal radiation doses with or without a perirectal spacer. Secondary outcomes included gastrointestinal (GI) and genitourinary (GU) toxicities (acute/late and any/grade ≥2, with subgroup analyses for hypofractionated RT.

Results: We reviewed 35 studies comprising 4,664 males. Rectal spacers effectively reduced the mean and maximum rectal radiation exposure, with reductions of 51.8% in V50 (mL) and 56.8% in V70 (mL). Furthermore, the percentage-based analysis showed reductions of 54.5% in V50 (%) and 62.2% in V70 (%). Acute GU toxicities (any grade and grade ≥2) showed no significant difference between the spacer and no-spacer groups, with no subgroup differences by fractionation. Late GU toxicities (any grade) were lower in the spacer group, while grade ≥2 toxicities showed no difference. Acute GI toxicities (any grade) were significantly reduced with spacers, particularly in hypofractionated RT, while grade ≥2 toxicities showed no difference. Late GI toxicities (any grade) were lower in the spacer group, with a stronger protective effect in hypofractionated RT. No significant difference was observed in grade ≥2 late GI toxicities.

Conclusions: Hydrogel spacers significantly reduced rectal radiation exposure and overall GI toxicity. However, their limited impact on severe toxicity highlights the need for further research on high-risk treatments and advanced RT techniques.

Purpose: A variety of treatment options are now available for men with localized prostate cancer (PC); however, there is still debate in determining how and when to intervene for Grade Group (GG) 2 disease. Our study aims to formulate strategies to identify men at risk of upgrading and having adverse pathological outcomes.

Materials and methods: This retrospective study includes 243 patients with GG2 PC that were treated with radical prostatectomy between 2015 and 2021. Patients on active surveillance, previous history of prostate biopsy, hormonal and/or radiation therapy prior to surgery were excluded from this study. A retrospective analysis was conducted using clinicopathological data obtained from medical records.

Results: Prostate-specific antigen (PSA) and Prostate Imaging Reporting and Data System (PI-RADS) score were statistically significant variables for risk of upgrading. In men who had presence of composite poor outcomes, PSA, PI-RADS score, presence of extraprostatic extension and seminal vesical invasion on MRI, number of positive cores, percentage of high grade (pattern 4/5) on prostate biopsy and Gleason pattern 4 volume on biopsy were all statistically significant variables. Strategy 8 (PI-RADS 5 lesion or percentage high grade [Gleason pattern 4] on prostate biopsy grade >10% or >3 cores positive on prostate biopsy) had significant association to identifying the highest number of men with upgrading and composite poor outcomes.

Conclusions: Our study supports the use of strategy 8 in treatment decision making of men with GG2 PC. Further validation of the use of this strategy is warranted.

Purpose: Benign prostatic hyperplasia (BPH) is a urinary tract disorder that primarily affects geriatric males. Natural materials have been developed to treat and prevent symptoms of BPH. However, a few natural functional foods has been conclusively proven to cure or prevent symptoms of BPH. The study aimed to investigate the anti-proliferative mechanism of Curcumae Radix (CR) and Syzygium aromaticum (SA) extracts using RWPE-1 cells and testosterone propionate (TP)-induced BPH rats.

Materials and methods: In vitro experiments were performed to assess the synergistic anti-proliferative effects of an equal mixture of CR and SA extracts on TP-treated RWPE-1 cells. In animal experiments, TP-induced BPH rats were administrated with saline, CR and SA extracts at 50, 100, and 200 mg/kg or finasteride at 1 mg/kg daily for 6 weeks. Body weight, prostate weight, dihydrotestosterone (DHT), androgen receptor (AR), and prostate-specific antigen (PSA) levels were measured. Additionally, extracellular signal-regulated kinase and NF-κB levels, oxidative stress, and inflammatory stress responses in the prostate were also analyzed.

Results: In this study, the combination of CR and SA extracts synergistically inhibited cell proliferation compared with the effect of each extract in TP-treated RWPE-1 cells. CR and SA extracts inhibited increasing of prostate weight, thickness of prostate epithelium, the level of PSA and DHT in serum. The expression of protein and gene of PSA and AR in prostate of TP-induced BPH rats were also suppressed by the administration of CR and SA extracts. Furthermore, reactive oxygen species and inflammation axis, NOX4-iNOS-COX2 and its associated representative inflammatory cytokine, interleukin-8 were also reduced in the CR and SA extracts-administered BPH rats.

Conclusions: The results suggest that the combination of CR and SA extracts improves BPH through its anti-inflammatory and anti-oxidative effects, demonstrating great potential as an anti-BPH medicine.

Purpose: There is a lack of pooled data exploring the time and rates for human chorionic gonadotropin (hCG) monotherapy vs. combination therapies (hCG+human menopausal gonadotropin or recombinant human follicle-stimulating hormone) to restore spermatogenesis in azoospermic men with congenital hypogonadotropic hypogonadism (CHH). We aimed to investigate the time and rates to recover spermatogenesis among azoospermic CHH men receiving monotherapy vs. combination therapy.

Materials and methods: We conducted a systematic review and meta-analysis following the PRISMA guidelines. The search was performed on PubMed, EMBASE, Web of Science, and Scopus databases up to November 2023. Forrest plots were generated to visually present the pooled effect sizes for time to recover spermatogenesis, specifically employing the standardized mean difference (SMD). Publication bias was assessed utilizing funnel plots. PROSPERO ID: CRD42023473615.

Results: The search identified 720 studies meeting inclusion criteria. Our meta-analysis of 1,240 men with CHH revealed significant differences in the time to recover spermatogenesis between combination therapies and monotherapy. The weighted mean recovery time was significantly shorter for combination therapies (10 months) compared to monotherapy (33 months). The SMD under the common effect model was 8.8 for combination therapies and 24.98 for monotherapy, indicating a more rapid recovery with combination therapies, p<0.01. The rates of sperm recovery were 66.76% for combination therapies and 51.9% for monotherapy, p=0.03. Significant heterogeneity was observed in both groups (I²=86% for combination therapies and I²=68% for monotherapy), suggesting considerable variation in individual responses.

Conclusions: The present meta-analysis reveals that in men with CHH, combination therapies expedite spermatogenesis recovery more than monotherapy. Additionally, combination therapies yield a higher rate of sperm appearing in the ejaculate as compared to hCG monotherapy. The significant heterogeneity observed in both groups underscores the variability in individual responses, warranting further investigation and caution in interpreting these results.