World Journal of Mens Health最新文献

Purpose: In recent decades, the incidence of male infertility has been increasing annually. In clinical practice, the question of whether to supplement folic acid is common among patients. Given the limited guidelines and research on the impact of folic acid on male infertility, this study aims to assess the effect of folic acid on male infertility using Mendelian randomization (MR) analysis.

Materials and methods: We conducted a two-sample bidirectional MR study using IEU database data for folate levels and supplementation. Male infertility genome-wide association study (GWAS) data were obtained from the FinnGen Consortium R8 dataset. To evaluate the causal relationship between folate, folate supplementation, and the risk of male infertility, we employed various MR methods, including inverse-variance weighted (IVW), MR-Egger, and Maximum Likelihood. The analysis results were assessed using MR-PRESSO, MR-Egger, and leave-one-out analysis. Genes related to folate metabolism were sourced from the MSigDB database, and the Expression Quantitative Trait Loci (eQTL) information of related genes was obtained from the IEU database. Single nucleotide polymorphism data for other male infertility risk factors, such as diabetes and obesity, were also analyzed.

Results: According to the MR analysis, there is no causal relationship between serum folate levels and male infertility in the general population. However, reverse Mendelian analysis indicated that male infertility may promote elevated serum folate levels. Folate supplementation appears to act as a protective factor against male infertility, while reverse MR analysis shows no causal relationship between male infertility and folate supplementation. Furthermore, we identified SERPINE1 and LDLR as potential causal genes in the folate metabolism pathway related to male infertility. Hypertension and hyperlipidemia also showed causal relationships with these two genes.

Conclusions: This study used MR to discover that folate supplementation is a protective factor against male infertility, and that SERPINE1 and LDLR may be influential genes in folate metabolism affecting male infertility.

Purpose: Nocturia is increasingly recognized as a significant factor influencing sleep quality and potentially linked to increased mortality risk. This meta-analysis aimed to systematically review and synthesize existing research investigating the relationship between nocturia, sleep quality, and mortality, in a single framework.

Materials and methods: A comprehensive systematic search across PubMed, Embase, and the Cochrane Library was conducted from the inception of each database until April 2, 2024, yielding studies investigating the methodological qualities and the relationship between nocturia and its impact on mortality and sleep quality. Risk of Bias was assessed using ROBINSE tool and RevMan 5.4 was used to analyze the results.

Results: Of the 1,450 studies subjected to screening, 33 were selected for analysis. Fourteen studies examined the association between nocturia and mortality, and 19 studies investigated impact of nocturia on sleep quality. Significant associations were found between nocturia and both mortality (pooled risk ratio: 1.78, 95% confidence interval [CI]: 1.50-2.10) and poor sleep quality (pooled odds ratio: 3.05, 95% CI: 1.89-4.93). Patients with nocturia demonstrated significantly poorer sleep quality scores compared with controls (pooled standardized mean difference: 1.01, 95% CI: 0.55-1.47).

Conclusions: This meta-analysis underscores the significance of addressing nocturia as a public health concern owing to its association with poor sleep quality and increased mortality risk. It advocates for comprehensive patient care strategies for addressing nocturia, sleep quality, and mortality.

Purpose: Prostate cancer is a prevalent malignancy among males, necessitating precise diagnosis for effective treatment and prognosis. However, there is a lack of accurate, reliable, and cost-effective methods for precise diagnosis of prostate cancer.

Materials and methods: The bisulfite-treated DNA was amplified by a blocker strand-assisted methylation-specific PCR method, and the signal was amplified by a guiding strand-assisted enzyme/probe detection system. On this basis, an Optimized DNA Methylation Detection Assay was developed. Fifty-five prostate cancer patients and 24 healthy patients were selected for blood/urine sample testing to evaluate the clinical value of the assay.

Results: The experimental results showed that the detection limit of the Tri-Component Liquid Biopsy Assay reached 0.002%. Assays for six prostate cancer methylation variants were constructed and finally three sites, GSTP1, ADCY4, and HOXA7, were selected for the design of prostate cancer diagnostic panel. The differences in methylation were statistically significant. Additionally, evaluating this approach on liquid biopsies from prostate cancer patients, we obtained a sensitivity and specificity of 89% and 76% respectively. Meanwhile, the cost of a single test on this platform is about $7.5, and the testing time is only about 5 hours.

Conclusions: Here we have successfully developed a highly sensitive methylation assay for prostate cancer diagnosis that features both accuracy, efficiency, and low cost. Combined with the established detection panel, this method can realize accurate and non-invasive early diagnosis of prostate cancer, which substantially augments the pragmatic utility of liquid biopsy.

Purpose: Minimally invasive surgical treatments (MIST) provide emerging alternatives to transurethral resection of the prostate (TURP) for benign prostatic hyperplasia (BPH). This network meta-analysis provides a comparative analysis of clinical efficacy and tolerability for individual MIST versus TURP in BPH.

Materials and methods: A PRISMA-compliant systematic review was performed by searching the PubMed, EMBASE, and Cochrane Library databases from inception to 31 August 2023. Eligible studies compared post-treatment change scores or relative risks between ≥2 distinct BPH interventions for International Prostate Symptom Score (IPSS), peak urinary flow rate (Qmax), post-void residual urine, Sexual Health Inventory in Men (SHIM) and Men's Sexual Health Questionnaire (MSHQ) scores, and re-intervention rate. Pairwise comparisons were synthesized through a random-effects frequentist model to determine aggregate estimates for treatment-outcome associations.

Results: Of 4,416 screened articles, 59 studies were included for quantitative analysis, comprising 21,078 patients across 47 unique cohorts. Prostatic arterial embolization (PAE) and Aquablation appeared to induce similar reductions in IPSS to TURP; however, there was insufficient data to evaluate the tolerability of PAE or Aquablation. Water vapor thermal therapy (WVTT) and prostatic urethral lift (PUL) were less efficacious at reducing IPSS than TURP but exhibited greater preservation of SHIM and MSHQ scores. TURP demonstrated the lowest relative risk of re-intervention.

Conclusions: PAE and Aquablation appear to be efficacious approaches to BPH management, with PAE also producing a comparable increase in Qmax to TURP. WVTT and PUL appear less effective than TURP but are associated with lower risk of male sexual dysfunction.

Purpose: Prostate cancer is the second most common male cancer, with incidence increasing with age. When prostate cancer extends beyond the prostatic capsule, treatment options and prognosis change significantly. This study aims to investigate prognostic genes related to capsular invasion in prostate cancer by integrating single-cell data with Mendelian randomization (MR) analysis.

Materials and methods: Single-cell sequencing data from six prostate cancer cases were obtained from the Gene Expression Omnibus (GEO) database. Cell clustering and annotation were performed using R, and high-dimensional weighted gene co-expression network analysis (hdWGCNA) identified differentially expressed genes in advanced-stage cancer. Single nucleotide polymorphism loci corresponding to these genes were retrieved from the UK Biobank (UKB), and MR exposure data were acquired from the ukb-b-13348 dataset. MR analysis assessed the impact of hdWGCNA-identified genes. Clinical and gene expression data from TCGA and GEO were analyzed using univariate Cox regression to evaluate gene effects on prognosis. Cellular functional experiments and immunohistochemistry assessed gene expression and function in prostate cancer.

Results: We employed the Seurat package for quality control and integration of single-cell data from four patients. hdWGCNA identified three modules, from which 200 genes were selected. The combined analysis of eQTL and MR revealed that TMEM59, JUNB, NECTIN2, OSBPL10, ATF3, and WLS may have relevant associations with prostate cancer. Further investigation using TCGA and GEO data suggested that TMEM59 might act as a protective factor in prostate cancer. Cellular experiments confirmed that TMEM59 knockdown enhanced the proliferation and invasion capabilities of prostate cancer cells. Immunohistochemistry demonstrated a significant decrease in TMEM59 expression in both normal and tumor tissues, particularly in the tumor group.

Conclusions: These findings suggest that TMEM59 may play a crucial role in the progression of prostate cancer and could serve as a prognostic predictor and therapeutic target for the disease.

Purpose: This study evaluated the trends in medical travel for radical prostatectomy (RP) in Korea during the robotic surgery era over a 10-year period. Regional self-sufficiency rates (SSR) for RP were analyzed, and factors associated with medical travel were identified.

Materials and methods: We retrospectively analyzed nationwide claims data from 2009 to 2019. Among 161,385 men newly diagnosed with prostate cancer, 57,096 (35.4%) underwent RP, including 6,482 laparoscopic RP (LRP), 16,092 open RP (ORP), and 34,522 robot-assisted RP (RARP). The regional SSR was defined as the proportion of patients undergoing RP within the same region of diagnosis, whereas medical travel was defined as RP performed outside the region of diagnosis. Logistic regression analysis was used to identify the factors associated with medical travel, and SSR trends were assessed using chi-square trend analysis.

Results: In 2009, 2,983 RPs (ORP: 1,163, LRP: 358, RARP: 1,462) were performed, increasing to 8,332 (ORP: 1,449, LRP: 670, RARP: 6,213) by 2019. The proportion of patients who underwent RARP increased from 49% to 75%. Nationwide SSR for overall RP showed a significant increasing trend (χ²_trend=73.413, p_trend<0.001). Non-Seoul regions exhibited a significant upward trend (χ²_trend=7.19, p_trend=0.007), whereas Seoul showed no significant trend (χ²_trend=1.905, p_trend=0.168). Non-Seoul SSR for RARP demonstrated the most pronounced growth (χ²_trend=156.085, p_trend<0.001). However, nationwide SSR for RARP showed no significant increasing trend (χ²_trend=1.888, p_trend=0.169). Younger age, lower Charlson comorbidity index score, non-Seoul residence, and preference for robotic surgery were associated with medical travel.

Conclusions: The proportion of RARPs steadily increased with the expansion of robotic surgical systems for prostate cancer in Korea. Despite improvements in the SSR for RARP in non-Seoul regions, disparities remain, with Seoul being the primary location for robotic surgery.

Purpose: While the association between defect of DNA damage repair (DDR) genes and prostate cancer (PCa) risk is well-established, there has been a lack of data in East Asian population. This study reports contemporary prevalence of DDR genes mutations in Korean PCa patients.

Materials and methods: We analysed samples from 1,316 patients with PCa in Korea. Whole genome sequencing and targeted cancer panel sequencing were employed for genetic analysis. A total of 26 DDR genes were analysed based on the previous literature.

Results: Germline mutation profiling was conducted in 1,026 patients, identifying 66 mutations (6.4%) at 14 genes. Somatic mutation profiling in 550 patients revealed 105 mutations (19.1%) at 15 genes. While BRCA2 was most frequent (3.4%) among germline mutations, CDK12 was most frequent (6.5%) among somatic mutations in our study. Patients with metastatic disease showed significantly higher mutation frequency than patient with localized disease in both germline and somatic mutation (both p-value<0.05). There were statistically positive correlation between increase of grade group and higher frequency in both germline and somatic DDR gene mutations (p<0.001). The patients with higher stage showed significantly higher rate of DDR gene mutation in germline analysis (p<0.001) but not in somatic analysis (p=0.888).

Conclusions: BRCA2 was the most prevalent in germline mutations but CDK12 was out-numbered BRCA2 in somatic mutations in the present study. The higher frequency of DDR gene mutation was associated with advanced cancer stage and higher cellular grade group.

Purpose: Managing Prostate Imaging-Reporting and Data System (PI-RADS) 3 lesions on prostate magnetic resonance imaging (MRI) remains challenging due to their intermediate and equivocal nature. The Prostate Health Index (PHI) and its derivative, PHI density (PHID), have shown promise in improving risk stratification beyond prostate-specific antigen (PSA); however, their utility in PI-RADS 3 lesions is not well established. This study aimed to assess the diagnostic performance of PHI and PHID in detecting clinically significant prostate cancer (csPCa), focusing on PI-RADS 3 lesions.

Materials and methods: This study analyzed 1,001 male who underwent multiparametric MRI and prostate biopsy. PHI and PHID were calculated prior to biopsy. Logistic regression, receiver operating characteristic (ROC) analysis, decision curve analysis (DCA), and reclassification metrics (integrated discrimination improvement/net reclassification improvement) were used to evaluate diagnostic performance across PI-RADS categories.

Results: csPCa was diagnosed in 485 patients (48.5%). PHID demonstrated superior risk stratification compared to PHI, particularly in PI-RADS 3 lesions. A PHID≥0.49 identified all csPCa cases (100% sensitivity), allowing 15.8% of PI-RADS 3 patients to avoid biopsy. Models combining PHID+PI-RADS yielded the highest area under the ROC curve and the greatest net benefit in DCA, outperforming models based on PSA or PHI alone.

Conclusions: PHID significantly enhances risk stratification for csPCa, especially in PI-RADS 3 lesions. A PHID threshold of 0.49 may serve as a safe criterion to reduce unnecessary biopsies. Integrating PHID with PI-RADS improves diagnostic accuracy and facilitates more personalized biopsy decisions.