Percutaneous nephrolithotomy guided by 5G-powered robot-assisted teleultrasound diagnosis system: first clinical experience with a novel tele-assistance approach (IDEAL stage 1).

BACKGROUND: To demonstrate the technical feasibility of percutaneous nephrolithotomy (PCNL) guided by 5G-powered robot-assisted teleultrasound diagnosis system (RTDS) in a complex kidney-stone (CKS) cohort and present our preliminary outcomes. PCNL is highly skill-required, which hinders it popularization in primary medical units of remote regions. We designed an innovative tele-assistance approach to make PCNL easy to be operated by inexperienced surgeons. METHODS: This was a prospective proof-of-concept study (IDEAL phase 1) on intraoperative tele-assistance provided by online urological experts via a 5G-powered RTDS. Total 15 CKS patients accepted this technology. Online experts manipulated a simulated probe to assist unskilled local operators by driving a patient-side robot-probe to guide and monitor the steps of access establishment and finding residual stones. RESULTS: Median total delay was 177ms despite one-way network-connecting distance > 5,800 km. No perceptible delay of audio-visual communication, driving robot-arm or dynamic ultrasound images was fed back. Successful tele-assistance was obtained in all cases. The first-puncture access-success rate was 78.6% with a one-session SF rate of 71.3% and without complications of grade III-V. CONCLUSIONS: The current technology based on 5G-powered RTDS can provide high-quality intraoperative tele-assistance, which has preliminarily shown satisfactory outcomes and reliable safety. It will break down a personal competence-based barrier to endow PCNL with more popular utilization. TRIAL REGISTRATION: The study was approved by ethics committee of the Xinjiang Kezhou People's Hospital and ethics committee of the First Affiliated Hospital of Nanjing Medical University and was registered on http://www.chictr.org.cn (ChiCTR2200065849, 16/11/2022).

A novel splicing mutation in helicase for meiosis 1 leads to non-obstructive azoospermia.

PURPOSE: Non-obstructive azoospermia (NOA) is an essential cause of male infertility for which treatment options are limited. The pathogenic mechanism of NOA, especially idiopathic NOA, remains unclear. Gene variations are associated with the occurrence of NOA. Our study was performed to investigate the genetic causes of NOA. METHODS: Whole exome sequencing (WES) was performed in two probands diagnosed with NOA from a Chinese family. Sanger sequencing was applied to verify the pathogenic variants. A minigene assay was carried out to identify the effect of the splicing variants. RESULTS: We detected a novel homozygous variant (c.2681-3 T > A) in the HFM1 gene in the two siblings diagnosed with NOA, and their parents carried heterozygous mutations in the same gene. The results of the minigene assay revealed this splicing variant results in exon25 of HFM1 being skipped, leading to a protein truncation (p.Trp894Cysfs*44). CONCLUSION: Our results showed that a deleterious splicing variant in HFM1 was related to NOA in these two patients. This novel variant of HFM1 may serve as a potential genetic biomarker for NOA patients.

Analysis of influenza trend and impact of COVID-19 in Kezhou, Xinjiang for 8 consecutive years.

To study the trend of influenza and the impact of coronavirus disease 2019 (COVID-19) in Kezhou, Xinjiang from 2013 to 2020. The data of influenza in Kezhou, Xinjiang from January 1, 2013, to December 31, 2020, were collected by the China Influenza Surveillance Information System to study the trend of ILI proportion, the distribution of influenza-like cases in different age groups, the positive cases and positive rate of influenza, and the trend of different influenza subtypes, and to analyze the impact of COVID-19 epidemic on influenza. The proportion of ILI in the Xinjiang Kezhou area was mainly children under 15 years old, and children under 5 years old accounted for the largest proportion. The proportion of ILI, the number of influenza-positive cases, and the influenza-positive proportion were mainly in winter and spring, especially in December and January each year. At the same time, this study found that the overall trend of H3N2 influenza in this region was on the rise, and the outbreaks in 2018 and 2019 were dominated by novel H1N1 and H3N2, respectively. The trend of influenza in Kezhou, Xinjiang is on the rise, and the prevention and control measures of COVID-19 have significantly reduced the data of influenza. It is necessary to strengthen the vaccination work and maintain the basic prevention and control measures of respiratory infectious diseases to prevent and control influenza more effectively.

Identification of endocrine-disrupting chemicals targeting the genes and pathways of genital anomalies in males.

Hypospadias and cryptorchidism are the most common congenital malformations in male neonates, both of which are also the important clinical manifestations of testicular dysgenesis syndrome and share a same origin. Many studies have suggested that prenatal exposure to endocrine-disrupting chemicals (EDCs) is associated with hypospadias and cryptorchidism development. However, the consistent mechanisms remain unclear. To identify the key EDCs, genes and biological networks related to the development of hypospadias and cryptorchidism respectively and commonly, we conduct the present study and found a new method for predicting the correlation between the interactive genes of hypospadias/cryptorchidism and chemicals. Transcriptome profiles were obtained from the Comparative Toxicogenomics Database (CTD). Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analyses and protein-protein interaction (PPI) network were applied for integrative analyses. The rat model and molecular docking were applied to furtherly verifying the findings of the integrative analyses. Besides the highly related genes, most enriched pathways and chemicals for hypospadias and cryptorchidism respectively, we found hypospadias and cryptorchidism share many same highly associated EDCs (e.g., dibutyl phthalate) and genes (e.g., androgen receptor and estrogen receptor 1) through comparing highly related chemicals or genes of hypospadias and cryptorchidism respectively. GO and KEGG analysis showed that these same interactive genes were mainly enriched in steroidogenesis, response to steroid hormone and nuclear receptor activity. PPI network analysis identified 15 biological hub genes. Furtherly, hypospadias and cryptorchidism were induced by prenatal dibutyl phthalate exposure. Decreased serum testosterone level, downregulation of nuclear androgen-dependent and upregulation of cytoplasmic estrogen-dependent pathways may lead to hypospadias and cryptorchidism. This study proposed a new method for predicting the correlation between the interactive genes of hypospadias/cryptorchidism and chemicals and found that hypospadias and cryptorchidism share many same highly associated EDCs and genes.

[Ultra-remote robot-assisted laparoscopic surgery for varicocele through 5G network: Report of two cases and review of the literature].

OBJECTIVE: At present, the longest network transmission distance (NTD) for 5G remote endoscopic surgery is reportedly only about 229 km, and the NTD longer than 5 000 km has not yet been reported in clinical application. In this study, we attempted the clinical application of 5G ultra-remote robot-assisted laparoscopic surgery in spermatic vein ligation. METHODS: This retrospective study included two cases of 5G ultra-remote robot-assisted laparoscopic spermatic vein ligation using the home-made Tumai Surgical Robot System. The operation table was located in Xinjiang Kezhou People's Hospital, with an NTD of about 5 800 km (a linear distance of about 3 800 km) from the surgeon's console in the Telemedical Center of the First Affiliated Hospital of Nanjing Medical University, the apparatuses connected through the public 5G network. We observed the network connection delay, network fluctuation, and data packet loss rate of the devices at both ends of the loop through the feedback value of the Ping command by real-time monitoring. RESULTS: The total operation time of the two cases was 45 and 40 minutes respectively, with a mean blood loss of < 5 ml. The patients resumed a liquid diet and out-of-bed activity on the first day, the abdominal drainage tubes removed on the second, and both discharged from the hospital on the third day. The intraoperative average two-way network delay was 130 ms, and the average continuous data packet loss rate was 1.4%. No adverse network events, such as network interruption, occurred during the operation. CONCLUSION: Through the public 5G network and home-made Tumai Surgical Robot System, ultra-remote robot-assisted laparoscopic surgery was performed safely and successfully.

Potential of testis-derived circular RNAs in seminal plasma to predict the outcome of microdissection testicular sperm extraction in patients with idiopathic non-obstructive azoospermia.

STUDY QUESTION: Do testis-derived circular RNAs (circRNAs) in seminal plasma have potential as biomarkers to predict the outcome of microdissection testicular sperm extraction (micro-TESE) in patients with idiopathic non-obstructive azoospermia (NOA)? SUMMARY ANSWER: Testis-derived circRNAs in the seminal plasma can indeed be used for predicting the outcome of micro-TESE in patients with idiopathic NOA. WHAT IS KNOWN ALREADY: Micro-TESE is an effective method to obtain sperm samples from patients with idiopathic NOA. However, its success rate is only 40-50% in such patients. STUDY DESIGN, SIZE, DURATION: Six idiopathic NOA patients with different micro-TESE results were included as the discovery cohort. Their testicular tissues were used for extracting and sequencing circRNAs. Five circRNAs with the most significantly different expression levels were selected for further verification. PARTICIPANTS/MATERIALS, SETTING, METHODS: Fifty-two patients with idiopathic NOA were included as the validation cohort. Preoperative seminal plasma samples of 52 patients with idiopathic NOA and 25 intraoperative testicular tissues were collected and divided into 'success' and 'failure' groups according to the results of micro-TESE. Quantitative real-time polymerase chain reaction was performed to verify differences in the expression levels of the selected circRNAs between the two groups in the testicular tissues and seminal plasma. MAIN RESULTS AND THE ROLE OF CHANCE: Whether at the seminal plasma or testicular tissue level, the differences in the expression levels of the three circRNAs (hsa_circ_0000277, hsa_circ_0060394 and hsa_circ_0007773) between the success and failure groups were consistent with the sequencing results. A diagnostic receiver operating curve (ROC) analysis of the AUC indicated excellent diagnostic performance of these circRNAs in seminal plasma in predicting the outcome of micro-TESE (AUC values: 0.920, 0.928 and 0.891, respectively). On the basis of least absolute shrinkage and selection operator (LASSO) logistic regression, the three circRNAs were combined to construct a new prediction model. The diagnostic ROC curve analysis of the model showed an AUC value of 0.958. The expression levels of these circRNAs in seminal plasma using three normospermic volunteer samples remained stable after 48 h at room temperature. LARGE SCALE DATA: NA. LIMITATIONS, REASONS FOR CAUTION: This was a single-center retrospective study with relatively few cases. The functions of these circRNAs, as well as their relationship with spermatogenesis, have not yet been established. WIDER IMPLICATIONS OF THE FINDINGS: Testis-derived circRNAs in seminal plasma can reflect the microenvironment of the testis and can be used as reliable biomarkers to screen patients with idiopathic NOA who might be suitable for micro-TESE. STUDY FUNDING/COMPETING INTEREST(S): This article was funded by the National Natural Science Foundation of China (Grant no. 81871151). There were no competing interests.

A novel signature constructed by ferroptosis-associated genes (FAGs) for the prediction of prognosis in bladder urothelial carcinoma (BLCA) and associated with immune infiltration.

BACKGROUND: Ferroptosis, a novel form of regulated cell death, has been implicated in the pathogenesis of cancers. Nevertheless, the potential function and prognostic values of ferroptosis in bladder urothelial carcinoma (BLCA) are complex and remain to be clarified. Therefore, we proposed to systematically examine the roles of ferroptosis-associated genes (FAGs) in BLCA. METHODS: According to The Cancer Genome Atlas (TCGA) database, differently expressed FAGs (DEFAGs) and differently expressed transcription factors (DETFs) were identified in BLCA. Next, the network between DEFAGs and DETFs, GO annotations and KEGG pathway analyses were performed. Then, through univariate, LASSO and multivariate regression analyses, a novel signature based on FAGs was constructed. Moreover, survival analysis, PCA analysis, t-SNE analysis, ROC analysis, independent prognostic analysis, clinicopathological and immune correlation analysis, and experimental validation were utilized to evaluate the signature. RESULTS: Twenty-eight DEFAGs were identified, and four FAGs (CRYAB, TFRC, SQLE and G6PD) were finally utilized to establish the FAGs based signature in the TCGA cohort, which was subsequently validated in the GEO database. Moreover, we found that immune cell infiltration, immunotherapy-related biomarkers and immune-related pathways were significantly different between two risk groups. Besides, nine molecule drugs with the potential to treat bladder cancer were identified by the connectivity map database analysis. Finally, the expression levels of crucial FAGs were verified by the experiment, which were consistent with our bioinformatics analysis, and knockdown of TFRC could inhibit cell proliferation and colony formation in BLCA cell lines in vitro. CONCLUSIONS: Our study identified prognostic ferroptosis-associated genes and established a novel FAGs signature, which could accurately predict prognosis in BLCA patients.

Identification of an independent immune-genes prognostic index for renal cell carcinoma.

BACKGROUND: Considerable evidence has indicated an association between the immune microenvironment and clinical outcome in ccRCC. The purpose of this study is to extensively figure out the influence of immune-related genes of tumors on the prognosis of patients with ccRCC. METHODS: Files containing 2498 immune-related genes were obtained from the Immunology Database and Analysis Portal (ImmPort), and the transcriptome data and clinical information relevant to patients with ccRCC were identified and downloaded from the TCGA data-base. Univariate and multivariate Cox regression analyses were used to screen out prognostic immune genes. The immune risk score model was established in light of the regression coefficient between survival and hub immune-related genes. We eventually set up a nomogram for the prediction of the overall survival for ccRCC. Kaplan-Meier (K-M) and ROC curve was used in evaluating the value of the predictive risk model. A P value of < 0.05 indicated statistically significant differences throughout data analysis. RESULTS: Via differential analysis, we found that 556 immune-related genes were expressed differentially between tumor and normal tissues (p < 0. 05). The analysis of univariate Cox regression exhibited that there was a statistical correlation between 43 immune genes and survival risk in patients with ccRCC (p < 0.05). Through Lasso-Cox regression analysis, we established an immune genetic risk scoring model based on 18 immune-related genes. The high-risk group showed a bad prognosis in K-M analysis. (p < 0.001). ROC curve showed that it was reliable of the immune risk score model to predict survival risk (5 year over survival, AUC = 0.802). The model indicated satisfactory AUC and survival correlation in the validation data set (5 year OS, Area Under Curve = 0.705, p < 0.05). From Multivariate regression analysis, the immune-risk score model plays an isolated role in the prediction of the prognosis of ccRCC. Under multivariate-Cox regression analysis, we set up a nomogram for comprehensive prediction of ccRCC patients' survival rate. At last, it was identified that 18 immune-related genes and risk scores were not only tremendously related to clinical prognosis but also contained in a variety of carcinogenic pathways. CONCLUSION: In general, tumor immune-related genes play essential roles in ccRCC development and progression. Our research established an unequal 18-immune gene risk index to predict the prognosis of ccRCC visually. This index was found to be an independent predictive factor for ccRCC.

Abnormal Thalamic Metabolism in Patients With Lifelong Premature Ejaculation.

BACKGROUND: Although some recent neuroimaging studies have indicated the abnormal brain structure or function in patients with lifelong premature ejaculation (LPE), whether and how the abnormal thalamic function participates in processing sexual behavioral information are still unclear in patients with LPE. AIM: The aim of this study was to assess the changes in the thalamus metabolism and structural integrity in patients with LPE. METHODS: We performed a multimodal magnetic resonance approach in a 3.0 T system, including proton magnetic resonance spectroscopy (1H-MRS), diffusion tensor imaging, and volumetric analysis to detect the differences in thalamic metabolism and structure between 20 patients with LPE and 15 healthy controls. OUTCOMES: We analyzed and correlated the clinical symptoms of the subjects with significant 1H-MRS-based features. Peak areas of N-acetylaspartate, choline, creatine (Cr), and glutamate/glutamine (Glu) were calculated with the LCModel software. RESULTS: Diffusion tensor imaging and volumetric analysis of thalami showed no differences between the 2 groups. On the contrary, 1H-MRS study disclosed that both Glu concentrations and Glu/Cr ratio values in the thalami of patients with LPE were remarkably increased when compared with healthy controls (P < .01 for both variables). In addition, both the intravaginal ejaculatory latency time score and Chinese Index of Sexual Function for Premature Ejaculation-5 score were negatively related to increased Glu concentrations and Glu/Cr ratio values. CLINICAL IMPLICATIONS: Glutamatergic activity changes of thalamus may be an underlying indicator for evaluating sensory conduction efficiency in patients with LPE. STRENGTHS & LIMITATIONS: The present study first found the abnormal thalamic metabolism in patients with LPE and contributed to a better understanding of the LPE etiology. Limitations include a cross-sectional study design with small samples and no examination of other brain areas. CONCLUSION: Our findings show that the increase in glutamatergic activity of thalamus is related to LPE, suggesting that the increased Glu neurotransmission in the thalamus may contribute to the development of premature ejaculation. Xia J-D, Chen F, Zhang Q-J, et al. Abnormal Thalamic Metabolism in Patients With Lifelong Premature Ejaculation. J Sex Med 2021;18:275-283.

m6A RNA methylation regulators correlate with malignant progression and have potential predictive values in clear cell renal cell carcinoma.

N6-methyladenosine (m6A) has been reported to be involved in several biological processes in tumors. In this study, we found that most of the m6A RNA methylation regulators were not only differentially expressed between clear cell renal cell carcinoma (ccRCC) and normal but also among ccRCC stratified by different clinicopathologic characters. Two ccRCC subgroups, cluster 1 and 2, were identified using consensus clustering based on the expression of m6A methylation regulators. Although no obvious differences were observed between two subgroups regarding clinicopathologic characters, except gender, patients in cluster 1 had a relatively more favorable survival rate than cluster 2. Moreover, we established a risk signature with two m6A methylation regulators, METTL3 and METTL14, which was not only of great value for prognosis prediction but also closely associated with clinicopathological features. In conclusion, m6A RNA methylation regulators play an important role in ccRCC progression and are potentially favorable for prognostic stratification.

Prenatal exposure to di-n-butyl phthalate induces erectile dysfunction in male adult rats.

Di-n-butyl phthalate (DBP) is a widely used plasticizer and an environmental endocrine-disrupting compound. However, whether prenatal exposure to DBP can impair erectile function remains unknown. We conducted this study to investigate the potential effects of prenatal exposure to DBP on erectile function and the underlying mechanisms. A rat model of prenatal DBP exposure (12.5, 100 or 800 mg/kg/day by gavage during gestational days 13-21) was established. Prenatal DBP exposure significantly decreased penis/body weight ratio, myelin sheath thickness of cavernosum nerves and serum testosterone level in male rats at the age of 10 weeks. Furthermore, erectile dysfunction was detected in all DBP exposure groups, which exhibited substantial increases in transforming growth factor-ß1 (TGF-ß1) expression and decreases in the expression of alpha smooth muscle actin (α-SMA), neuronal and endothelial nitric oxide synthase (nNOS and eNOS). Additionally, the phospho-B-cell lymphoma 2 (Bcl-2)-associated death promoter (p-Bad)/Bad and phospho-the protein kinase B (p-AKT)/AKT ratios were remarkably lower, but the Bcl-2-associated X protein (Bax)/Bcl-2 ratio and caspase-3 were higher in DBP exposure groups than in the control group. Notably, prenatal exposure to DBP increase the risk of ED in male adult rats, even taking low dose of DBP (12.5 mg/kg/day). DBP exposure causing penile fibrosis, decreased testosterone level, and endothelial dysfunction may be responsible for ED by activating Akt/Bad/Bax/caspase-3 pathway and suppressing NOS/cGMP pathway in penis.

[Stem cell therapy for erectile dysfunction: An update].

Erectile dysfunction (ED) is a common andrological disorder, and traditional oral drugs often fail to achieve satisfactory therapeutic effects. As a new field of biomedicine, stem cell therapy (SCT) has seen a significantly increasing number of researches on its treatment of ED in recent years. Preclinical animal models for the study of ED mainly include the models of diabetes mellitus-, aging-, cavernous nerve injury-, and Peyronie's disease-related ED. Previous studies indicated that SCT improved erectile function through paracrine and was more effective when combined with other therapies than used alone in restoring ED-induced pathological changes. Although clinical trials on SCT have partially proved its safety and effectiveness for the treatment of ED, they were still in the early stages and with relatively small sample sizes. This article summarizes the latest advances in the treatment of ED by SCT.

The management and composition of symptomatic seminal vesicle calculi: aetiological analysis and current research.

OBJECTIVE: To report our experience in the diagnosis, minimally invasive treatment, and composition of seminal vesicle calculi (SVC). PATIENTS AND METHODS: In the present study, we evaluated 20 patients who were admitted to our hospital from January 2013 to January 2018. All the patients were diagnosed with intractable haematospermia and SVC. The diagnosis was further confirmed by seminal vesiculoscopy. SVC were removed by basket extraction; with larger SVC fragmented by holmium laser before extraction. Scanning electron microscopy, X-ray diffraction, and infrared spectroscopy were used to determine the SVC composition. RESULTS: All operations were completed successfully without surgical complications. SVC were mostly composed of hydroxyapatite and protein, suggesting that they were produced by infections. CONCLUSIONS: Seminal vesiculoscopy is a simple, minimally invasive technique that can be used for diagnostic confirmation and treatment of seminal vesiculitis with SVC. This study improves our understanding of SVC and provides a theoretical basis for the prevention of postoperative recurrence of SVC.

Comprehensive Analysis of lncRNA Expression Pattern and lncRNA-miRNA-mRNA Network in a Rat Model With Cavernous Nerve Injury Erectile Dysfunction.

BACKGROUND: Long noncoding RNAs (lncRNAs) are differentially expressed in erectile dysfunction (ED) associated with aging and diabetes mellitus; however, the lncRNA expression profile in cavernous nerve (CN) injury-related ED (CNI-ED) is unknown. AIM: To investigate the dysregulated lncRNAs, microRNAs (miRNAs), and mRNA expression in CNI-ED and construct a potential lncRNA-miRNA-mRNA network. METHODS: 22 male Sprague-Dawley (SD) rats were divided into bilateral CN crush (BCNC) and Sham groups. Using second-generation high-throughput sequencing technology, we analyzed the expression profiles of lncRNA, miRNA, and mRNA of the 2 groups. 17 differentially expressed lncRNAs were selected and further validated by quantitative real-time polymerase chain reaction (RT-qPCR). The lncRNA-miRNA-mRNA network, Gene Ontology (GO) term enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using Cytoscape. OUTCOMES: Intra-cavernosal pressure, mean arterial pressure, smooth muscle content, and the expression of miRNA, mRNA, and lncRNA were measured. RESULTS: The BCNC group showed decreased intra-cavernosal/mean arterial pressure as well as decreased smooth muscle/collagen ratios compared with the Sham group. The RNA sequencing results revealed dysregulated expressions of 65 lncRNA, 14 miRNA, and 750 mRNA in the BCNC group based on the following criteria: fold change >2 and P < .05. Among the 17 lncRNAs further selected based on mean count number >4 in both groups, 3 lncRNAs (TCONS_00028173, TCONS_00049985, and TCONS_00058429) were further validated for differential expression by RT-qPCR. GO analysis suggests that these 3 lncRNAs could regulate various processes such as myotube differentiation and muscle cell differentiation. Furthermore, the KEGG pathway analysis showed that the mRNAs in the competing endogenous RNA (ceRNA) network are involved in pathways, including axon guidance and vascular endothelial growth factor signaling pathway. CLINICAL TRANSLATION: Our findings may provide new information on molecular pathophysiology of CNI-ED and suggest further research to find a more effective therapy for CNI-ED. STRENGTHS & LIMITATIONS: This study is the first to identify the lncRNA expression pattern and propose a ceRNA network in a rat model with cavernous nerve injury-related erectile dysfunction. However, analogous studies are needed to confirm these findings in humans. In addition, we constructed the network by only confirming the lncRNA. CONCLUSION: Our study reveals differential expression profiles of lncRNAs, miRNAs, and mRNAs between the BCNC and Sham groups and suggests that these differentially expressed lncRNAs may play critical roles in CNI-ED by regulating apoptosis and fibrosis in the corpus cavernosum via targeting mRNAs or miRNAs. Cong R, Wang Y, Wang Y. Comprehensive Analysis of lncRNA Expression Pattern and lncRNA-miRNA-mRNA Network in a Rat Model With Cavernous Nerve Injury Erectile Dysfunction. J Sex Med 2020;17:1603-1617.

Inhibitory Role of Gamma-Aminobutyric Receptors in Paraventricular Nucleus on Ejaculatory Responses in Rats.

BACKGROUND: Although abnormal sympathetic nerve system (SNS) activity has been demonstrated in the pathogenesis of ejaculation disorders, few data are available on its underlying mechanism. AIM: To investigate whether differences in ejaculatory behavior of rats were associated with the state of SNS activity and gamma-aminobutyric (GABA) receptor expressions in the paraventricular nucleus (PVN) of the hypothalamus and the effects of GABA receptors in the PVN on ejaculatory behavior. METHODS: Based on ejaculatory performance, Sprague-Dawley rats were divided into "sluggish," "normal," and "rapid" ejaculators. PVN microinjection was performed to evaluate the role of GABA receptors on sexual behavior. OUTCOMES: The outcomes include differences in expression and distribution of GABA receptors and norepinephrine level among the 3 groups and changes in copulation behavior parameters after PVN microinjection. RESULTS: Compared with "normal" rats, the "rapid" group ejaculated more times with shorter latency (P < .001, P < .001) and had lower expression and distribution of both GABA-A and GABA-B receptors, while the opposed results appeared in the "sluggish" group. The norepinephrine level was successively increased among "sluggish," "normal," and "rapid" rats (P < .001) and correlated with ejaculation frequency (r = 0.896, P < .001) and ejaculation latency (r = -0.835, P < .001). In addition, bilateral microinjection of the GABA-A and GABA-B receptor agonist (isoguvacine and baclofen) into the PVN both significantly prolonged the intromission latency and inhibited ejaculation, which could be blocked by antagonist gabazine and CGP-35348, respectively. Vigabatrin, the GABA-transaminase inhibitor, caused a significantly reduced ejaculation frequency and extended ejaculation latency in rats, which could be offset by simultaneous injections of gabazine and CGP-35348. CLINICAL IMPLICATIONS: Our findings provide new understanding about GABA receptors in the PVN on sexual behavior and enhance the comprehension of neurobiological mechanisms involved in premature ejaculation. STRENGTHS & LIMITATIONS: Our results have indicated that GABA receptors in the PVN may inhibit ejaculation through restraining the activity of SNS. However, our study did not analyze the changes of GABA receptors in other brain areas, which needs further study. CONCLUSION: Ejaculation behaviors in male rats are associated with SNS activity and could be regulated by GABA receptors in the PVN, which may be of assistance in the treatment of ejaculation disorders in the future. Zhang QJ, Yang BB, Yang J, et al. Inhibitory Role of Gamma-Aminobutyric Receptors in Paraventricular Nucleus on Ejaculatory Responses in Rats. J Sex Med 2020;17:614-622.

Higher urinary nitrate was associated with lower prevalence of congestive heart failure: results from NHANES.

BACKGROUND: Some studies have reported that nitrate intake from vegetables was inversely associated with many vascular diseases, but few studies have paid attention to the relationship between urinary nitrate and cardiovascular diseases (CVDs). This cross-sectional study aimed to explore the connections between urinary nitrate and prevalence of CVDs. METHODS: The data of this study was collected from National Health and Nutrition Examination Survey (NHANES). Finally, several years' data of NHANES were merged into 14,894 observations. Logistic regression models were used to examine the associations between urinary nitrate and CVDs by using the "survey" package in R software (version 3.2.3). RESULTS: In the univariable logistic analysis, significant association was discovered between urinary nitrate and congestive heart failure, coronary heart disease, angina pectoris, myocardial infarction (all P < 0.001). By adjusting related covariates, the multivariable logistic analysis showed that the significant association only existed between urinary nitrate and congestive heart failure (OR = 0.651, 95% CI 0.507-0.838, P < 0.001). Compared to Q1 urinary nitrate level as reference, the risk for prevalent heart failure diminished along with increasing levels of urinary nitrates, (OR of Q2 level = 0.633, 95% CI 0.403-0.994), (OR of Q3 level = 0.425, 95% CI 0.230-0.783), (OR of Q4 level = 0.375, 95% CI 0.210-0.661), respectively. Moreover, urinary nitrate levels were associated with congestive heart failure in a dose-dependent manner in both 20-60 years group, 60+ years group and male, female group (P < 0.001, P = 0.011 and P = 0.009, P = 0.004). CONCLUSIONS: Independent of related covariates, higher urinary nitrate was associated with lower prevalent congestive heart failure.

Tumor infiltrating M2 macrophages could predict biochemical recurrence of localized prostate cancer after radical prostatectomy.

Given the critical role of the tumor microenvironment in PCa progression, we aimed to assess the prognostic effect of tumor infiltrating M2 macrophages (TIMMs) on biochemical recurrence (BCR) in patients with localized prostate cancer (PCa) after radical prostatectomy. A total of 127 localized PCa patients from GSE116918, 268 patients from TCGA database and 77 patients from GSE70770 were enrolled in our study. TIMMs were evaluated by the CIBERSORT method. Patients with high TIMMs had a significantly poorer recurrence free survival (RFS) (P = 0.017, P = 0.0063 and P = 0.001) in the three sets. In the multivariate analysis, the presence of high TIMMs (HR = 3.026, P = 0.023; HR = 2.679, P = 0.017; HR = 2.648, P = 0.005) was identified as an independent prognostic factor for RFS in the three sets. Harrell's Concordance index (C-index) increased in all three sets after combining TIMMs with traditional risk factors (PSA, clinical stage(T) and Gleason score). Gene Set Enrichment Analysis showed that T cell receptor signaling pathway, B cell receptor signaling pathway and primary immunodeficiency were significantly enriched in the low TIMMs group. TIMMs could serve as an independent prognostic factor for BCR in localized PCa patients after RP. Incorporation of TIMMs into traditional risk classification might further stratify patients with different prognosis.

[Role of microRNAs in erectile dysfunction: An update].

MicroRNAs (miRNAs) are short non-coding RNAs consisting of approximately 19－23 nucleotides and involved in many pathological and physiological processes by regulating post-transcriptional gene expressions. ED is one of the common male sexual dysfunctions seriously affecting the patient's quality of life, for which there is currently a lack of effective treatments clinically. More and more experiments have demonstrated that miRNAs are involved in the pathological process of different types of ED. This article presents an overview of the progress in the studies of the pathogenic role of miRNAs in ED.

[Management of androgenic diseases during the epidemic of COVID-19 pneumonia].

The novel coronavirus (COVID-19) pneumonia has been classified as a category B and dealt with as a category A infectious disease by the National Health Commission of China, and also as a public health emergency of international concern by the World Health Organization. During the epidemic, unnecessary visits to hospitals may increase the risk of infection among patients and clinicians. Therefore, it is particularly important to provide some scientific medical guidance for patients with male diseases, which is also a current imperative for andrology management. And it also deserves the attention of clinical researchers whether COVID-19 pneumonia and its clinical treatments currently used may affect the male reproductive system.

[Mu-opioid receptors in the paraventricular nucleus regulate ejaculatory behaviors via the sympathetic nerve system in male rats].

OBJECTIVE: To explore the effects of the mu-opioid receptor (MOR) in the paraventricular nucleus (PVN) on the ejaculatory behaviors of male rats and its potential mechanisms. METHODS: Male SD rats with normal ejaculation ability were mated with female ones in hormone-induced estrus. After bilateral PVN microinjection of D-Ala-2-Me-Phe-4-Gly-ol enkephalin (DAGO) or D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) with an inserted catheter, the male animals were observed for mount latency (ML), mount frequency (MF), intromission latency (IL), intromission frequency (IF), ejaculation latency (EL), ejaculation frequency (EF), post-ejaculation interval (PEI), and intromission ratio (IR). The lumbar sympathetic nerve activity (LSNA) of the rats was recorded using the PowerLab data acquisition hardware device, and the levels of norepinephrine (NE) in the peripheral plasma were measured by ELISA following microinjection of saline or different doses of DAGO or CTAP. RESULTS: Neither CTAP nor DGAO significantly affected the ML of the male rats (P > 0.05). DGAO remarkably increased IF (P < 0.01) and MF (P < 0.01), prolonged IL (P < 0.01), EL (P < 0.01) and PEI (P < 0.01), and reduced EF (P <0.01) and IR (P < 0.05). On the contrary, CTAP markedly decreased IF (P < 0.01) and MF (P < 0.01), shortened IL (P < 0.01), EL (P < 0.01) and PFI (P < 0.01), and elevated EF (P < 0.01) and IR (P < 0.01). Additionally, DAGO decreased LSNA in a dose-dependent manner and reduced the NE level in the peripheral plasma. CTAP, however, not only offset the effects of DAGO on LSNA, but also significantly increased LSNA. CONCLUSIONS: MOR in PVN inhibits ejaculatory behaviors in male rats by weakening LSNA, which has provided some theoretical evidence for the use of highly selective opioids in the treatment of premature ejaculation.