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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]

Congenital bilateral absence of the vas deferens (CBAVD) is clinically characterized by the absence of the bilateral vas deferens; the main clinical manifestation is infertility, accounting for 1–2% of male infertility cases. CBAVD may be accompanied by congenital abnormalities in the urogenital system and cystic fibrosis (CF)-related clinical manifestations. CBAVD can develop as a mild manifestation of CF or can be isolated. The main pathogenic mechanism of CBAVD is gene mutation, and CBAVD and CF have a common genetic mutation background. CFTR mutation is the main pathogenic cause of CBAVD and CF, and ADGRG2 mutation is the second most common cause. Although lack of the vas deferens in CBAVD patients causes infertility due to the inability to release sperm, the testes of CBAVD patients have spermatogenic function. Therefore, CBAVD patients can achieve fertility through sperm retrieval surgery and assisted reproductive technology (ART). However, gene mutations in CBAVD patients can have an impact on the ART outcome, and there is a risk of passing on gene mutations to offspring. For CBAVD patients and their spouses, performing genetic counseling (which currently refers mainly to CFTR mutation screening) helps to reduce the risks of genetic mutations being passed on to offspring and of offspring having CF with concomitant CBAVD. [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]

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]

Androgens are some of the most important sex hormones in men, and they maintain important physiological activities in the human body. Cognitive impairment is one of the most common manifestations of aging in the elderly population and an important factor affecting the quality of life of elderly individuals. The levels of sex hormones in elderly people decrease with age, and low levels of androgens in older male individuals have been closely linked to the development of cognitive impairment. Basic studies have shown that androgens have neuroprotective effects and that androgen deficiency impairs cognitive function by increasing oxidative stress and decreasing synaptic plasticity, among other effects. Additionally, clinical studies have also shown that androgen deficiency is closely related to cognitive impairment. This article reviews the relationship between low androgen levels and cognitive impairment, their potential mechanisms, and the effects of testosterone supplementation in improving cognition. [ABSTRACT FROM AUTHOR]

There is a lack of objective tools to comprehensively evaluate premature ejaculation (PE) treatment results clinically. We aimed to describe the development of a novel scoring system for PE treatment results as an example of using the Delphi method and an analytical hierarchy process for complex decision-making in the field of sexual medicine. A Delphi question survey was adopted to collect expert opinions from 47 Chinese specialists in andrology/urology on the assessment of PE treatment outcomes based on four primary properties, that is, the improvement in intravaginal ejaculation latency time, a couple's mental status, the ability to control ejaculation, and sexual intercourse satisfaction. Different weights on those primary properties were assigned to create a mathematical hierarchy matrix and then perform an analysis. The scores were assigned according to the calculated weights. The ratio among the combined weights of the four primary properties was 1:3:2:3. The total numerical score was 36. Scores above 27, between 26 and 18, and below 17 indicated significant improvement, moderate improvement, and no improvement in PE, respectively, with selected treatments. The scoring system with 36 points can be used by physicians, patients, and their sexual partners to comprehensively and objectively assess quantitative PE treatment results. [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]

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]

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]

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]

This study aimed to report a rare case of intermittent azoospermia and ring-like small supernumerary marker chromosomes (sSMCs). An infertile man was diagnosed with azoospermia presenting a normal male phenotype with complete masculinization. Karyotyping and polymerase chain reaction (PCR) were used to detect 16 sequence-tagged sites on the AZF subregions of the Y chromosome, and 115 candidate genes were screened for mutations. Mutations included single nucleotide variations, insertions, and deletions. Metaphase chromosomes were studied by standard trypsin-Giemsa banding; fluorescent in situ hybridization and PCR were performed to analyze specific Y chromosome regions; gene mutations were detected. Chromosomal analysis detected 117 metaphase cells; a mosaicism with marker 1 and marker 2 sSMCs in 2 metaphase cells (47, X, +mar1x2 karyotype), a mosaicism with marker 2 sSMCs in 14 metaphase cells (46, X, +mar2 karyotype), and a mosaicism with marker 1 sSMCs in 76 metaphase cells (46, X, +mar1 karyotype), coexisting with a 45,X cell line in the remaining 25 metaphase cells. PCR analysis showed the sY160 heterochromosome on the AZFc subregion was absent. Next-generation sequencing identified an asthenozoospermia-specific mutation in GAPDHS (rs2293681), and Sanger sequencing verified this mutation. This gene encodes a protein belonging to the glyceraldehyde-3-phosphate dehydrogenase family of enzymes that play an important role in carbohydrate metabolism. Like its somatic cell counterpart, this sperm-specific enzyme functions in a nicotinamide adenine dinucleotide-dependent manner to remove hydrogen and add phosphate to glyceraldehyde 3-phosphate to form 1,3-diphosphoglycerate. During spermiogenesis, this enzyme may play an important role in regulating the switch between different energy-producing pathways, and it is required for sperm motility and male fertility. A mosaic 46, X, +mar1[76]/45, X[25]/46, X, +mar2[14]/47, X, +mar1x2[2] karyotype could be the main explanation for the azoospermia/severe oligospermia, while the likely pathogenic GAPDHS intron mutation may contribute to the symptom of immotile sperms detected in the semen analysis. [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]

Summary: The human embryonic lethal abnormal visual protein, HuR, belongs to the Hu family of RNA-binding proteins. Over the past two decades, HuR has been extensively associated with multiple biological characteristics of tumors, including tumor development and progression, angiogenesis, invasion, migration and prognosis, since this protein regulates the stability of cancer-associated target mRNAs due to its posttranscriptional regulatory mechanisms. A recent investigation of the multiple functions of HuR has provided emerging evidence of its role in drug resistance in various tumors. Herein, we demonstrate the roles of HuR proteins in the development of drug resistance, examine their involvement in various mechanisms, including apoptosis, the ABC transporter family, the cell cycle and the DNA damage response, and provide insight into ongoing studies for developing therapeutic strategies aimed at targeting this molecule in tumor cells. [ABSTRACT FROM AUTHOR]

Selenium is an essential trace element in the human body and plays an important role in the body via selenoprotein, which contains selenium. Selenoproteins (glutathione peroxidase, thioredoxin reductase, methionine sulfoxide reductase1 and endoplasmic reticulum-selenoproteins, etc.) have antioxidant effects and are involved in regulating antioxidant activities. Aging is an inevitable process and is always accompanied by aging-related diseases. Reactive oxygen species are important initial factors in aging and aging-related diseases. Selenium contributes to the alleviation of reduced reactive oxygen species-mediated inflammation, reduced DNA damage and prolonged telomere length and thereby plays roles in fighting aging and preventing aging-related diseases. In the elderly, aging-related diseases include neuropsychiatric diseases, tumors, cardiovascular diseases, and skin aging, among others. Selenium supplementation is an important strategy for anti-aging and the prevention of aging-related diseases and is of great significance for the elderly. However, with the accumulation of related research, selenium supplementation does not necessarily contribute to the prevention of aging and aging-related diseases. It is believed that a low level of selenium is beneficial to the human body. Thus, the effect of selenium on human aging and aging-related diseases is still controversial. This paper reviews the research progress and objective role of selenium in aging and aging-related diseases. [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]

Androgen deprivation therapy is an important therapy for prostate cancer (PCa) in aging men. Under the background of castration, it is inevitable that prostate cancer will develop into castration-resistant prostate cancer (CRPC), which has a high mortality rate, after 2-3 years. Androgen receptor (AR) plays a key role in PCa development and is essential to CRPC. More recent research studies have reported that the development of CRPC is largely due to altered mechanisms related to AR, so it is important for us to understand the roles of AR and detailed AR-related mechanisms in CRPC. The multiple AR-related mechanisms promoting the development of CRPC are as follows: (1) enhanced transformation and increased synthesis of intratumoral androgen; (2) AR overexpression, which enables CRPC to be hypersensitive to low levels of androgen; (3) AR cofactors, which enhanced AR transactivation; (4) AR-spliced variants, which mediated downstream gene expression without androgen; (5) the interaction between the AR pathway and classic tumor-related pathways; and» (6) AR mutations, which reduced AR specificity and enhanced AR transcription. [ABSTRACT FROM AUTHOR]

Langitudinally sliced embryonic axes from pea and lentil mature seeds cocultivated with A. tumefaciens carrying a gus reporter gene in its T-DNA provided a convenient means to evaluate the efficiency of gene transfer to tissues in different cultivars and cocultivation conditions. Use of this technique demonstrated wide variation in susceptibility to Agrobacterium among several pea and lentil commercial genotypes. [ABSTRACT FROM AUTHOR]

The objective of the current study was to explore the role of body mass index (BMI) in sperm quality and erectile function in Chinese males of infertile couples. A total of 28 fertility centers in different regions of China were enrolled. Patient data were collected from June 1, 2017, through October 31, 2017. Semen analyses and demographic data were collected and the five-item International Index of Erectile Function (IIEF-5) questionnaire was used to evaluate the erectile function in participants with different BMIs. In total, 3,174 Chinese men of infertile couples with an average age of 33.11 ± 6.08 years were enrolled. The occurrence of obesity, overweight, normal weight, and underweight were 5.4%, 36.6%, 56.8%, and 1.2%, respectively. In addition to hypertension and diabetes, primary infertility, a longer course of infertility, and chronic prostatitis were risk factors for obesity. Compared with men of normal weight, adjusted odds ratios (ORs) for men with obesity, overweight, and underweight for semen volume <2 ml were 2.53 (95% CI [1.61, 3.97]), 1.33 (95% CI [1.09, 1.62]), and 0.84 (95% CI [0.29, 2.43]); for sperm progressive motility (A + B) (%) <32, the ORs were 1.60 (95% CI [1.16, 2.22]), 1.30 (95% CI [1.12, 1.51]), and 1.03 (95% CI [0.54, 1.98]); and for IIEF-5 ≤ 21, the ORs were 1.52 (95% CI [1.10, 2.10]), 1.11 (95% CI [0.96, 1.30]), and 0.62 (95% CI [0.31, 1.26]), respectively. Obesity was associated with lower semen volume, lower sperm motility, and erectile dysfunction in Chinese males of infertile couples. [ABSTRACT FROM AUTHOR]