Molecular and spatial signatures of human and rat corpus cavernosum physiopathological processes at single-cell resolution.

The composition and cellular heterogeneity of the corpus cavernosum (CC) microenvironment have been characterized, but the spatial heterogeneity at the molecular level remains unexplored. In this study, we integrate single-cell RNA sequencing (scRNA-seq) and spatial transcriptome sequencing to comprehensively chart the spatial cellular landscape of the human and rat CC under normal and disease conditions. We observe differences in the proportions of cell subtypes and marker genes between humans and rats.

HSF5 Deficiency Causes Male Infertility Involving Spermatogenic Arrest at Meiotic Prophase I in Humans and Mice.

Meiosis is a specialized cell division process that generates gametes for sexual reproduction. However, the factors and underlying mechanisms involving meiotic progression remain largely unknown, especially in humans. Here, it is first showed that HSF5 is associated with human spermatogenesis.

The tRNA Gm18 methyltransferase TARBP1 promotes hepatocellular carcinoma progression via metabolic reprogramming of glutamine.

Cancer cells rely on metabolic reprogramming to sustain the prodigious energetic requirements for rapid growth and proliferation. Glutamine metabolism is frequently dysregulated in cancers and is being exploited as a potential therapeutic target. Using CRISPR/Cas9 interference (CRISPRi) screening, we identified TARBP1 (TAR (HIV-1) RNA Binding Protein 1) as a critical regulator involved in glutamine reliance of cancer cell.

Primate-Specific DAZ Regulates Translation of Cell Proliferation-Related mRNAs and is Essential for Maintenance of Spermatogonia.

Primate-specific DAZ (deleted in azoospermia) has evolved in the azoospermia factor c (AZFc) locus on the Y chromosome. Loss of DAZ is associated with azoospermia in patients with deletion of the AZFc region (AZFc_del). However, the molecular mechanisms of DAZ in spermatogenesis remain uncertain.

scRNA-seq reveals that origin recognition complex subunit 6 regulates mouse spermatogonial cell proliferation and apoptosis via activation of Wnt/β-catenin signaling.

The regulation of spermatogonial proliferation and apoptosis is of great significance for maintaining spermatogenesis. The single-cell RNA sequencing (scRNA-seq) analysis of the testis was performed to identify genes upregulated in spermatogonia. Using scRNA-seq analysis, we identified the spermatogonia upregulated gene origin recognition complex subunit 6 ( Orc6 ), which is involved in DNA replication and cell cycle regulation; its protein expression in the human and mouse testis was detected by western blot and immunofluorescence.

Identification of a missense variant of MND1 in meiotic arrest and non-obstructive azoospermia.

Meiotic arrest is a common pathologic phenotype of non-obstructive azoospermia (NOA), yet its genetic causes require further investigation. Meiotic nuclear divisions 1 (MND1) has been proved to be indispensable for meiotic recombination in many species. To date, only one variant of MND1 has been reported associated with primary ovarian insufficiency (POI), yet there has been no report of variants in MND1 associated with NOA.

A homozygous frameshift variant in SYCP2 caused meiotic arrest and non-obstructive azoospermia.

Genetic causation for the majority of non-obstructive azoospermia (NOA) remains unclear. Mutations in synaptonemal complex (SC)-associated genes could cause meiotic arrest and NOA. Previous studies showed that heterozygous truncating variants in SYCP2 encoding a protein essential for SC formation, are associated with non-obstructive azoospermia and severe oligozoospermia.

Bi-allelic MEI1 variants cause meiosis arrest and non-obstructive azoospermia.

Non-obstructive azoospermia (NOA) is characterized by the failure of sperm production due to testicular disorders and represents the most severe form of male infertility. Growing evidences have indicated that gene defects could be the potential cause of NOA via genome-wide sequencing approaches. Here, bi-allelic deleterious variants in meiosis inhibitor protein 1 (MEI1) were identified by whole-exome sequencing in four Chinese patients with NOA.

Bi-allelic SPATA22 variants cause premature ovarian insufficiency and nonobstructive azoospermia due to meiotic arrest.

The genetic causes of idiopathic premature ovarian insufficiency (POI) and nonobstructive azoospermia (NOA) remain unclear. We performed whole-exome sequencing (WES) in members of a consanguineous family with two POI and two NOA patients to screen for potential pathogenic variants for familial POI and NOA. And a homozygous variant in SPATA22 (c.

Novel Bi-Allelic Variants of Cause Sertoli Cell-Only Syndrome and Non-Obstructive Azoospermia.

Non-obstructive azoospermia (NOA) is the most severe disease in male infertility, but the genetic causes for the majority of NOA remain unknown. FANCM is a member of Fanconi Anemia (FA) core complex, whose defects are associated with cell hypersensitivity to DNA interstrand crosslink (ICL)-inducing agents. It was reported that variants in (MIM: 609644) might cause azoospermia or oligospermia.

Identification of new biomarkers in immune microenvironment of testicular germ cell tumour.

To seek novel prognostic biomarkers for testicular germ cell tumour (TGCT) and investigate the tumour immune microenvironment, we identified critical differentially expressed genes (DEGs) by overlapping GSE1818 dataset from Gene Expression Omnibus (GEO). Protein-protein interaction (PPI) network was used to investigate key modules and hub genes. Functional enrichment analysis was performed to investigate the underlying molecular functions of the DEGs in TGCT development and progression.

Development and Validation of a Nomogram to Predict Lymph Node Metastasis in Patients With T1 High-Grade Urothelial Carcinoma of the Bladder.

Purpose: This study aims to develop and validate a nomogram to predict lymph node (LN) metastasis preoperatively in patients with T1 high-grade urothelial carcinoma.

Methods: We retrospectively evaluated the data of 2,689 patients with urothelial carcinoma of the bladder (UCB) treated with radical cystectomy (RC) and bilateral lymphadenectomy in two medical centers. Eventually, 412 patients with T1 high-grade urothelial carcinoma were enrolled in the primary cohort to develop a prognostic nomogram designed to predict LN status.

Identification and verification of hub microRNAs in varicocele rats through high-throughput sequencing and bioinformatics analysis.

Varicocele (VC) is the most common treatable cause of infertility, but it is difficult to distinguish fertile from infertile VC populations because the pathogenesis is unclear. In order to study the related mechanism of VC causing male sterility, we made VC rats model by surgery, analyzed the rat epididymal sperm, and use the transcriptome sequencing compared all the miRNA expression differences in testicular tissue between VC rats, surgical treatment rats and control rats. The differentially expressed miRNAs (DEMs) of testicular tissue were also screened by the edgeR package in R software.

Relationship between aryl hydrocarbon receptor and spermatogenic dysfunction in male patients with varicocele.

The main purpose of this project is to verify whether there is a difference in the expression of aryl hydrocarbon receptor (AhR) between varicocele (VC) and normal male semen, and determine whether there is a connection with the parameters of semen analysis. The risk factors of infertility in patients with VC were also studied. Semen samples were collected for semen analysis and Western blot.

Can the combination of biparametric magnetic resonance imaging and PSA-related indicators predict the prostate biopsy outcome?

To assess the value of biparametric magnetic resonance imaging (bpMRI) for detecting and ruling out prostate cancer in patients with elevated prostate-specific antigen (PSA). The basic information and bpMRI images of enrolled patients who took transperineal template saturate biopsy were retrospectively collected for analysis. Based on our results, we found that free/total PSA, and PI-RADS score were independent risk factors of PCa (p < .

Identification and verification of key genes in varicocele rats through high-throughput sequencing and bioinformatics analysis.

Varicocele (VC) is the most common treatable cause of infertility, but it is difficult to distinguish fertile from infertile VC populations because the pathogenesis is unclear. In order to study the related mechanism of VC causing male sterility, we made VC rat model by surgery, analysed the rat epididymal spermatozoa and used the transcriptome sequencing to compare all the mRNA expression differences in testicular tissue between VC rats and control rats. The differentially expressed genes (DEGs) of testicular tissue were also screened by the limma package in R software (version 3.

Do testosterone supplements enhance response to phosphodiesterase 5 inhibitors in men with erectile dysfunction and hypogonadism: a systematic review and meta-analysis.

Background: Combining testosterone and phosphodiesterase 5 inhibitors (PDE5-Is) has become increasingly common in the treatment of men with erectile dysfunction (ED) and low testosterone levels, but combination therapy involving PDE5-Is and testosterone is highly debated, with strong reasons for and against argued by the various opinion leaders. PDE5-Is can be given prior to, alongside or after the commencement of any testosterone replacement therapy. Meanwhile, combination of PDE5-Is and testosterone is reported to better increase testosterone levels and thus improve International Index of Erectile Function (IIEF) score in hypogonadal men.

The prevalence and prognostic and clinicopathological value of PD-L1 and PD-L2 in renal cell carcinoma patients: a systematic review and meta-analysis involving 3,389 patients.

Background: The research of the prognostic and clinicopathologic values of programmed cell death ligand 1/2 (PD-L1/2) in renal cell carcinoma (RCC) patients has been mired by a dearth of studies and considerable controversy. We thus conducted a systematic review and meta-analysis to report the prevalence and prognostic and clinicopathological value of programmed cell death ligand 1 (PD-L1) and programmed cell death-legend 2 (PD-L2) in RCC patients.

Methods: The PubMed, Cochrane Library, EMBASE databases were searched to find human studies limited to English language literature published through October 1, 2019.

Relationship Between the (rs7975232), (rs1544410), (rs2228570), and (rs731236) Variants in the Vitamin D Receptor Gene and Urolithiasis Susceptibility: An Updated Meta-Analysis and Trial Sequential Analysis.

The relationship between urolithiasis and vitamin D receptor (VDR) gene variants is still under debate according to the available published literature. To assess correlations between gene variants (rs7975232), (rs1544410), (rs2228570), and (rs731236) and urolithiasis susceptibility, we performed the present study through meta-analysis. The PubMed, Cochrane Library, China National Knowledge Infrastructure, EMBASE, Web of Science, and Wanfang databases were searched to retrieve qualified case-control studies.

Gene Expression Profiles Identified Novel Urine Biomarkers for Diagnosis and Prognosis of High-Grade Bladder Urothelial Carcinoma.

Bladder urothelial carcinoma (BC) has been identified as one of the most common malignant neoplasm worldwide. High-grade bladder urothelial carcinoma (HGBC) is aggressive with a high risk of recurrence, progression, metastasis, and poor prognosis. Therefore, HGBC clinical management is still a challenge.

Predictive value of haematologic parameters in diagnosis of testicular torsion: Evidence from a systematic review and meta-analysis.

To compare the difference of mean platelet volume (MPV), platelet lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), platelet (PLT) and leucocyte between testicular torsion (TT), epididymo-orchitis and healthy controls and further evaluate predictive values of these haematologic parameters in diagnosis and the differential diagnosis of TT. Databases were systematically retrieved, and reference search was also conducted manually. We applied Stata software 12.

Is androgen deprivation therapy for prostate cancer associated with cardiovascular disease? A meta-analysis and systematic review.

Background: Androgen deprivation therapy (ADT) is widely being applied in men who suffered from prostate cancer. Whether androgen deprivation therapy (ADT) is associated with an increased risk of developing cardiovascular-related disease is poorly defined.

Objectives: The aim of the present meta-analysis is to explore the relationship between ADT and the risk of cardiac events.

Seminal plasma miR-210-3p induces spermatogenic cell apoptosis by activating caspase-3 in patients with varicocele.

The aim of this study was to investigate the role of seminal plasma miR-210-3p in the impairment of semen quality caused by varicocele. This study included 102 patients whose semen quality was normal when they were diagnosed with varicocele. A 2-year follow-up for included patients was performed, and they were divided into Group A (semen quality became abnormal) and Group B (semen quality remained normal) according to the results of semen analysis during the follow-up.

Bilateral is superior to unilateral varicocelectomy in infertile men with bilateral varicocele: Systematic review and meta-analysis.

To investigate whether bilateral surgery can bring more benefits to infertile patients with bilateral varicocele than unilateral surgery. A search of PubMed, Web of Science, EMBASE and the Cochrane Library on 13 January 2019 was conducted to identify studies published in English that used varicocelectomy. The protocol of the present meta-analysis was pre-published on PROSPERO (registration number CRD42019093894).