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Prostate cancer (PCa) currently ranks second in male tumor mortality. Targeting immune checkpoint in tumor as immunotherapy is a new direction for tumor treatment. However, targeting PD-1/PD-L1 and CTLA4 to treat PCa has poor immunotherapeutic efficacy because PCa is known as a cold tumor. Understanding the mechanism of immunosuppression in PCa can promote the use of immunotherapy to treat PCa. ELAVL1 is highly expressed in many tumors, participates in almost all tumor biological activities and is an oncogene. ELAVL1 is also involved in the development and differentiation of T and B lymphocytes. However, the relationship between ELAVL1 and tumor immunity has not yet been reported. In recent years, ELAVL1 has been shown to regulate downstream targets in an m6A -dependent manner. PD-L1 has been shown to have m6A sites in multiple tumors that are regulated by m6A. In this study, ELAVL1 was highly expressed in PCa, and PCa with high ELAVL1 expression is immunosuppressive. Knocking down ELAVL1 reduced PD-L1 expression in PCa. Moreover, PD-L1 was shown to have an m6A site, and its m6A level was upregulated in PCa. ELAVL1 interacts with PD-L1 mRNA and promotes PD-L1 RNA stability via m6A, ultimately inhibiting the infiltration of CD4-positive T cells. In addition, androgen receptor (AR) was shown to be regulated with ELAVL1, and knocking down AR could also affect the expression of PD-L1. Therefore, ELAVL1 can directly or indirectly regulate the expression of PD-L1, thereby affecting the infiltration of CD4-positive T cells in PCa and ultimately leading to immune suppression. [ABSTRACT FROM AUTHOR]

The purpose of this study was to develop an erectile dysfunction (ED) risk assessment tool suitable for the general population. Based on an ED network survey of the general adult male population in China from October to November 2019, a total of 612 cases with a mean age of 31 years (interquartile range: 28–37) with valid data were collected: 357 cases were assigned to the training set and 255 to the validation set. The ED risk prediction model was established by multifactor logistic regression analysis, and nomograms were constructed for visualisation. In the validation set, a receiver operating characteristic curve, calibration curve analysis and decision curve analysis were used to evaluate the discrimination, calibration and clinical usefulness of the ED risk prediction model. Based on multivariate logistic regression, education, smoking, chronic diseases, feelings about one's spouse, frequency of sexual intercourse, masturbation and self‐reported sexual satisfaction were selected as predictors to develop the ED prediction model. The model had good discrimination, calibration and clinical applicability. The ED risk prediction model developed in this study can effectively predict ED risk in the general population. [ABSTRACT FROM AUTHOR]

Purpose. To determine the role of history of prostatitis (HP) as an independent risk factor for erectile dysfunction (ED) in Chinese adult males. Methods. We conducted an online survey using a crowd-sourced questionnaire in Chinese adult males. The participants were separated into two groups as adult participants with HP and with no history of prostatitis (NHP) according to the medical history record. As diagnosis criteria of ED, we used the 5 questions of the International Index for Erectile Function (IIEF-5). The general data including height, weight, monthly income, academic background, smoking history, alcohol drinking, marital status, conjugal affection, and other disease history was asked and recorded. The relationship between HP and ED using the chi-square test and logistic regression analyses was investigated and analyzed. Results. In total, 1873 participants answered the questionnaire. 95 participants in the HP group and 1778 participants in the NHP group were included in this study. The rate of participants with HP was 5.343%. ED was found in 68.4% of the HP group and 43% of the NHP group (p < 0.001). Regression analysis showed that participants in HP were more likely to have ED (OR 2.135, 95% CI 1.266–3.60) after adjusting for the participant's age, body mass index (BMI), monthly income, academic background, smoking history, alcohol drinking, marital status, conjugal affection, BPH, hypertension, and diabetes mellitus, when compared with NHP. Conclusions. The present study indicated a high prevalence of ED in Chinese adult males with history of prostatitis, and HP is an independent risk factor for erectile dysfunction. [ABSTRACT FROM AUTHOR]

Background and Objective. Knowledge on the clinical features of timely ovulatory intercourse failure (TOIF) is limited. The current study is aimed at investigating the psychological status, infertility-associated factors, and erectile function in males with TOIF. Material and Methods. Between June 2018 and December 2018, all qualified patients of infertile couples were continuously enrolled from the andrologic clinic of Peking Union Medical College Hospital. Semen analyses and demographic data were collected, and the International Index of Erectile Function 15 (IIEF-15) questionnaire was used to evaluate the erectile function in the participants with or without TOIF. In addition, the Mental Health Inventory-5 and State-Trait Anxiety Inventory-Short Form questionnaires were used to evaluate the psychological status. Results. A total of 1128 patients were enrolled, and 264 of them (23.40%) suffered from TOIF. TOIF was positively associated with smoking, drinking, hypertension, diabetes, anxiety, unknown cause of infertility, lower semen concentration, lower frequency of intercourse, and decreased erectile function. The total IIEF-15 scores, erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction were significantly decreased in patients with TOIF. Conclusion. TOIF is associated with lower semen concentration, anxiety, and other comorbidities such as hypertension and diabetes. Clinicians are required to focus on these associated factors in addition to improve the erectile function. [ABSTRACT FROM AUTHOR]

Bladder cancer (BC) is the most common urinary system malignancy and is a serious threat to human health. Circular RNAs (circRNAs) are members of a newly defined class of noncoding RNAs (ncRNAs) that can regulate gene expression at the transcriptional or posttranscriptional level. Studies have shown that circRNAs are related to the clinicopathological characteristics, prognosis, and chemosensitivity of BC, and basic research has further confirmed that changes in the expression of circRNAs in BC are closely related to various tumor biological functions. CircRNAs promote tumor development by interacting with miRNAs to regulate transcription factors and both classical and nonclassical tumor signaling pathways. The nonclassical signaling pathways are related to cell cycle progression, epithelial–mesenchymal transition (EMT), extracellular matrix maintenance, and tumor stem cell maintenance. In this article, the relationships between circRNAs and the clinical characteristics of BC are reviewed, and the molecular mechanisms by which circRNAs promote tumor development are explored. [ABSTRACT FROM AUTHOR]

Introduction. Several studies have explored the association between outdoor air pollution and semen quality. However, the results were inconsistent. We performed the current meta-analysis to evaluate the role of outdoor air pollution in semen quality. Material and Methods. Databases including PubMed, Web of Science, and Embase were searched to identify relevant studies. Relative data in participants under higher exposure and lower exposure to air pollution were extracted. Pooled weighted mean differences (WMDs) with corresponding 95% confidence intervals (CIs) were utilized to assess the effects of outdoor air pollution on semen quality. In addition, trial sequential analyses (TSAs) were performed to obtain a more comprehensive assessment of analyses. Results. A total of 11 studies with 4562 males were enrolled in the current meta-analysis. Higher air pollution levels were associated with significant decreases in semen volume (WMD: -0.16, 95% CI: -0.27 to -0.05), sperm concentration (WMD: -5.52, 95% CI: -9.88 to -1.16), progressive motility (WMD: -6.23, 95% CI: -11.64 to -0.81), total motility (WMD: -7.65, 95% CI: -14.09 to -1.20), and normal sperm morphology rate (WMD: -3.71, 95% CI: -5.59 to -1.82). In addition, the DNA fragmentation index significantly increased (WMD: 4.11, 95% CI: 1.94 to 6.29). Conclusions. Air pollution is associated with decreased semen volume, sperm concentration, motility, and normal morphology rate. [ABSTRACT FROM AUTHOR]

Chemotherapy is an important cancer treatment method. Tumor chemotherapy resistance is one of the main factors leading to tumor progression. Like other malignancies, bladder cancer, especially muscle-invasive bladder cancer, is prone to chemotherapy resistance. Additionally, only approximately 50% of muscle-invasive bladder cancer responds to cisplatin-based chemotherapy. miRNAs are a class of small, endogenous, noncoding RNAs that regulate gene expression at the posttranscriptional level, which results in the inhibition of translation or the degradation of mRNA. In the study of miRNAs and cancer, including gastric cancer, prostate cancer, liver cancer, and colorectal cancer, it has been found that miRNAs can regulate the expression of genes related to tumor resistance, thereby promoting the progression of tumors. In bladder cancer, miRNAs are also closely related to chemotherapy resistance, suggesting that miRNAs can be a new therapeutic target for the chemotherapy resistance of bladder cancer. Therefore, understanding the mechanisms of miRNAs in the chemotherapy resistance of bladder cancer is an important foundation for restoring the chemotherapy sensitivity of bladder cancer and improving the efficacy of chemotherapy and patient survival. In this article, we review the role of miRNAs in the development of chemotherapy-resistant bladder cancer and the various resistance mechanisms that involve apoptosis, the cell cycle, epithelial-mesenchymal transition (EMT), and cancer stem cells (CSCs). [ABSTRACT FROM AUTHOR]

Purpose: Human embryonic lethal abnormal visual-like protein, HuR, belongs to a member of the Hu family of RNA-binding protein and plays a critical role in urinary tumors. The purpose of this review is to summarize the current literature to demonstrate the importance of HuR in urinary tract tumors' biology and explore the potential role in therapeutic strategies aimed at targeting this molecule in cancer cells.Methods: The relevant literature from PubMed and Medline databases is reviewed in this article.Results: Increasing evidence supports that HuR plays a critical role in urinary tumors' biology because it regulates the expression of many urinary tumors-associated molecules through post-transcriptional regulatory mechanisms (including mRNA trafficking, mRNA decay and protein translation). Recent studies have demonstrated that HuR is associated with chemoresistance of urinary tumors, suggesting that HuR might be a novel therapeutic target and a marker for therapeutic response and prognosis assessment.Conclusion: HuR is associated with various urinary tumors biological characteristics. Targeted therapy of HuR may become an attractive treatment strategy. What's more, more preclinical and clinical trials of this targeted strategy are necessary for the treatment of urinary tumors. [ABSTRACT FROM AUTHOR]

Aspirin has been widely used as an antipyretic analgesic drug. More and more evidences have shown that aspirin may be play some role on anti-tumor. In this article, we reviewed the research history of aspirin in the treatment and prevention of cancer. Many epidemiological and clinical studies have shown that aspirin can reduce the risk of a variety of malignant tumors and reduce cancer mortality. In addition, we discuss the specific mechanisms of aspirin in the anti-tumor effects. It has been found that aspirin mainly depends on the COX pathway and non-COX pathway to inhibit tumor cell growth and to curb tumor development. In this article, clinical studies and anti-tumor mechanism studies published in recent years are reviewed. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer is a highly heterogeneous disease, presenting a major obstacle to personalized treatment. Effective markers of the immune checkpoint blockade response are needed for precise patient classification. We, therefore, divided patients with gastric cancer according to collagen gene expression to indicate their prognosis and treatment response. Methods: We collected data for 1250 patients with gastric cancer from four cohorts. For the TCGA‐STAD cohort, we used consensus clustering to stratify patients based on expression levels of 44 collagen genes and compared the prognosis and clinical characteristics between collagen subtypes. We then identified distinct transcriptomic and genetic alteration signatures for the subtypes. We analyzed the associations of collagen subtypes with the responses to chemotherapy, immunotherapy, and targeted therapy. We also established a platform‐independent collagen‐subtype predictor. We verified the findings in three validation cohorts (GSE84433, GSE62254, and GSE15459) and compared the collagen subtyping method with other molecular subtyping methods. Results: We identified two subtypes of gastric adenocarcinoma: a high‐expression collagen subtype (CS‐H) and a low‐expression collagen subtype (CS‐L). Collagen subtype was an independent prognostic factor, with better overall survival in the CS‐L subgroup. The inflammatory response, angiogenesis, and phosphoinositide 3‐kinase (PI3K)/Akt pathways were transcriptionally active in the CS‐H subtype, while DNA repair activity was significantly greater in the CS‐L subtype. PIK3CA was frequently amplified in the CS‐H subtype, while PIK3C2A, PIK3C2G, and PIK3R1 were frequently deleted in the CS‐L subtype. CS‐H subtype tumors were more sensitive to fluorouracil, while CS‐L subtype tumors were more sensitive to immune checkpoint blockade. CS‐L subtype was predicted to be more sensitive to HER2‐targeted drugs, and CS‐H subtype was predicted to be more sensitive to vascular endothelial growth factor and PI3K pathway‐targeting drugs. Collagen subtyping also has the potential to be combined with existing molecular subtyping methods for better patient classification. Conclusions: We classified gastric cancers into two subtypes based on collagen gene expression and validated these subtypes in three validation cohorts. The collagen subgroups differed in terms of prognosis, clinical characteristics, transcriptome, and genetic alterations. The subtypes were closely related to patient responses to chemotherapy, immunotherapy, and targeted therapy. [ABSTRACT FROM AUTHOR]

Objective: Proliferative nodular formation represents a characteristic pathological feature of benign prostatic hyperplasia (BPH) and serves as the primary cause for prostate volume enlargement and consequent lower urinary tract symptoms (LUTS). Its specific mechanism is largely unknown, although several cellular processes have been reported to be involved in BPH initiation and development and highlighted the crucial role of epithelial cells in proliferative nodular formation. However, the technological limitations hinder the in vivo investigation of BPH patients. Methods: The robust cell type decomposition (RCTD) method was employed to integrate spatial transcriptomics and single cell RNA sequencing profiles, enabling the elucidation of epithelial cell alterations during nodular formation. Immunofluorescent and immunohistochemical staining was performed for verification. Results: The alterations of epithelial cells during the formation of nodules in BPH was observed, and a distinct subgroup of basal epithelial (BE) cells, referred to as BE5, was identified to play a crucial role in driving this progression through the hypoxia-induced epithelial-mesenchymal transition (EMT) signaling pathway. BE5 served as both the initiating cell during nodular formation and the transitional cell during the transformation from luminal epithelial (LE) to BE cells. A distinguishing characteristic of the BE5 cell subgroup in patients with BPH was its heightened hypoxia and upregulated expression of FOS. Histological verification results confirmed a significant association between c-Fos expression and key biological processes such as hypoxia and cell proliferation, as well as the close relationship between hypoxia and EMT in BPH tissues. Furthermore, a strong link between c-Fos expression and the progression of BPH was also been validated. Additionally, notable functional differences were observed in glandular and stromal nodules regarding BE5 cells, with BE5 in glandular nodules exhibiting enhanced capacities for EMT and cell proliferation characterized by club-like cell markers. Conclusions: This study elucidated the comprehensive landscape of epithelial cells during in vivo nodular formation in patients, thereby offering novel insights into the initiation and progression of BPH. [ABSTRACT FROM AUTHOR]

Objective: We performed this meta-analysis to assess serum testosterone changes in adult males with Type 2 diabetes (T2DM).Methods: PubMed, Embase, Web of Science, and Cochrane Library were searched to identify qualified studies. Pooled weighted mean differences (WMDs) with 95% confidence intervals (CIs) were utilized to test the changes of total testosterone (TT), free testosterone (FT) and sex hormone-binding globulin (SHBG) in patients with T2DM. Besides, trial sequential analysis was used to verify the pooled results.Results: A total of 56 studies were enrolled in our meta-analysis. Meta-analyses of the cross-sectional studies showed that patients with T2DM has significant decreases in TT (WMD: -2.98, 95%CI: -3.48 to -2.47), FT (WMD: -32.82, 95%CI: -39.70 to -25.95) and SHBG (WMD: -2.47, 95%CI: -3.93 to -1.02). In terms of the prospective studies, our results showed decreases in TT (WMD: -2.35, 95%CI: -3.24 to -1.46), FT (WMD: -25.96, 95%CI: -83.98 to 32.05), and SHBG (WMD: -10.06, 95%CI: -13.29 to -6.84) in patients with T2DM. By trial sequential analyses, the findings in current meta-analysis were based on reliable evidence.Conclusion: Our results indicate that patients with T2DM have lower serum TT, FT, and SHBG levels. [ABSTRACT FROM AUTHOR]

Purpose. The purpose of this study was to compare the relative safety and efficacy of different types of phosphodiesterase type 5 inhibitors (PDE5-Is) with tamsulosin for the treatment of lower urinary tract symptoms (LUTS) secondary to benign prostate hyperplasia (BPH) (BPH-LUTS) with or without erectile dysfunction (ED). Methods. We use the Stata version 13.0 to conduct the network meta-analysis (NMA) with a random effects model of the Bayesian framework. The International Prostate Symptom Score (IPSS), Maximum Urinary Flow Fate ( Q max ), International Index of Erectile Function (IIEF), and their credible intervals (CI) were used to compare the efficacy and safety of every medical intervention, including sildenafil plus tamsulosin, tadalafil plus tamsulosin, and vardenafil plus tamsulosin. Results. Seven RCTs including 531 participants with seven interventions were analyzed. The results of NMA SUCRA showed that compared with different doses or types of PDE5-Is combined with tamsulosin (0.4 mg qd), the sildenafil (25 mg qd) combined with tamsulosin (0.4 mg qd) group had the greatest probabilities of being the best in the achievement of improving IIEF. The sildenafil (25 mg 4 days per week) combined with tamsulosin (0.4 mg qd) group had the greatest probabilities of being the best in the achievement of improving Q max , whereas sildenafil (25 mg qd) combined with tamsulosin (0.4 mg qd) ranked the best for the safety outcomes. Conclusions. This meta-analysis indicates that sildenafil combined with tamsulosin is the best effective and tolerated treatment option for BPH-LUTS with or without ED. Further RCTs are strongly required to provide more direct evidence. [ABSTRACT FROM AUTHOR]

Human antigen R (HuR) is a member of the Hu family of RNA-binding proteins. This molecule, which was first described in tumors nearly two decades ago, has recently received much attention in tumor-related research because it regulates the expression of many tumor-associated molecules through posttranscriptional regulatory mechanisms, thereby affecting biological characteristics. It is suggested that HuR might be a novel therapeutic target and a marker for therapeutic response and prognostic assessment. Increasing evidence supports that HuR also plays critical roles in the development, therapy, and prognosis of digestive system tumors. Herein, we review the relationships between HuR and digestive system tumors, demonstrating the importance of HuR in digestive system tumor diagnosis. [ABSTRACT FROM AUTHOR]

• RNA m6A regulators and miRNAs are important parts of molecular regulatory networks during spermatogenesis. • Different germ cell populations have different regulatory networks during spermatogenesis. • RNA m6A regulators, especially METTL3, IGF2BP2 and PRRC2A, may be involved in regulatory almost all germ cells. • miRNAs including hsa-let-7a-2, hsa-let-7f-1, hsa-let-7g, etc. may present important regulatory roles in spermatogenesis. Spermatogenesis is a multistep biological process. In addition to somatic cells, it involves the orderly differentiation of dozens of spermatogenic cells. In this process, the regulatory networks between different spermatogenic cell populations are significantly different. RNA m6A regulators and miRNAs have been found to be closely related to spermatogenesis in recent years, and they are an important part of the above regulatory networks. Understanding gene expression and its rules in different spermatogenic cell populations will help in the in-depth exploration of their detailed roles in spermatogenesis. This study collected a public dataset of nonobstructive azoospermia (NOA). Based on the Johnson score, the testicular samples of NOA were divided into three types, Sertoli-cell only syndrome, meiotic arrest and postmeiotic arrest, which represented the loss of three germ cell populations, including whole spermatogenic cells, postmeiotic spermatogenic cells, and a mixture of late spermatids and spermatozoa, respectively. The aforementioned three types of testis data were compared with normal testis data, and the molecular expression characteristics of the abovementioned three germ cell populations were obtained. Our study showed that different germ cell populations have different active molecules and their pathways. In addition, RNA m6A regulators, including METTL3, IGF2BP2 and PRRC2A, and miRNAs, including hsa-let-7a-2, hsa-let-7f-1, hsa-let-7g, hsa-miR-15a, hsa-miR-197, hsa-miR-21, hsa-miR-30e, hsa-miR-32, hsa-miR-503 and hsa-miR-99a, also presented regulatory roles in almost all germ cells. [ABSTRACT FROM AUTHOR]