Background: The coronavirus disease 2019 (COVID‐19) has been spreading all over the world since December 2019. However, medical information regarding the urogenital involvement in recovered COVID‐19 patients is limited or unknown.Objectives: To comprehensively evaluate urogenital involvement in recovered COVID‐19 patients.Materials and methods: Men aged between 20 years and 50 years who were diagnosed with SARS‐CoV‐2 infection and recovered when the study was conducted were enrolled in our study. Demographic and clinical characteristics, and history of hospitalization were collected and analyzed. Urine, expressed prostatic secretions (EPSs), and semen samples were collected for SARS‐CoV‐2 RNA detection. Semen quality and hormonal profiles were analyzed.Results: Among 74 male recovered COVID‐19 patients, 11 (14.9%) were asymptomatic, classified into mild type, and 31 (41.9%) were classified into moderate type. The remaining patients (32/74, 43.2%) had severe pneumonia. No critically ill recovered COVID‐19 patient was recruited in our cohort. The median interval between last positive pharyngeal swab RT‐PCR test and semen samples collection was 80 days (IQR, 64‐93). The median age was 31 years (IQR, 27‐36; range, 21‐49), and the median body mass index (BMI) was 24.40 (IQR, 22.55‐27.30). Forty‐five (61.6%) men were married, and 28 (38.4%) were unmarried. Fifty‐three (72.6%) patients denied cigarette smoking, 18 (24.7%) were active smokers, and 2 of them were past smokers. The majority of our participants (53/74, 72.6%) did not consume alcohol. Fever occurred in most of the patients (75.3%), and 63 of them had abnormal chest CT images. Only one patient complained of scrotal discomfort during the course of COVID‐19, which was ruled out orchitis by MRI (data not shown). A total of 205 samples were collected for SARS‐CoV‐2 detection (74 urine samples, 70 semen samples, and 61 EPS samples). However, viral nucleic acid was not detected in body fluids from the urogenital system. In terms of hormonal profiles, the levels of FSH, LH, testosterone, and estradiol were 5.20 [4.23] mIU/mL, 3.95 [1.63] mIU/mL, 3.65 [1.19] ng/mL, and 39.48 [12.51] pg/mL, respectively. And these values were within the normal limits. The overall semen quality of recovered COVID‐19 patients was above the lower reference limit released by the WHO. While compared with healthy control, sperm concentration, total sperm count, and total motility were significantly declined. In addition, different clinical types of COVID‐19 have no significant difference in semen parameters, but total sperm count showed a descending trend. Interestingly, subjects with a longer recovery time showed worse data for sperm quality. Small sample size and lacking semen parameters before the infection are the major limitations of our study.Discussion and conclusions: To the best of our knowledge, it is the largest cohort study with longest follow‐up for urogenital evaluation comprehensively so far. Direct urogenital involvement was not found in the recovered COVID‐19 male patients. SARS‐CoV‐2 RNA was undetectable in the urogenital secretions, and semen quality declined slightly, while hormonal profiles remained normal. Moreover, patients with a long time (≥90 days) since recovery had lower total sperm count. Great attention and further study should be conducted and follow‐up on the reproductive function in the following months.

We performed this meta-analysis to evaluate the predictive value of different parameters in the sperm retrieval rate (SRR) of microdissection testicular sperm extraction (TESE) in patients with nonobstructive azoospermia (NOA). All relevant studies were searched in PubMed, Web of Science, EMBASE, Cochrane Library, and EBSCO. We chose three parameters to perform the meta-analysis: follicle-stimulating hormone (FSH), testicular volume, and testicular histopathological findings which included three patterns: hypospermatogenesis (HS), maturation arrest (MA), and Sertoli-cell-only syndrome (SCOS). If there was a threshold effect, only the area under the summary receiver operating characteristic curve (AUSROC) was calculated. Otherwise, the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and the diagnostic odds ratio (DOR) were also calculated. Twenty-one articles were included in our study finally. There was a threshold effect among studies investigating FSH and SCOS. The AUSROCs of FSH, testicular volume, HS, MA, and SCOS were 0.6119, 0.6389, 0.6758, 0.5535, and 0.2763, respectively. The DORs of testicular volume, HS, and MA were 1.98, 16.49, and 1.26, respectively. The sensitivities of them were 0.80, 0.30, and 0.27, while the specificities of them were 0.35, 0.98, and 0.76, respectively. The PLRs of them were 1.49, 10.63, and 1.15, respectively. And NLRs were 0.73, 0.72, and 0.95, respectively. All the investigated factors in our study had limited predictive value. However, the histopathological findings were helpful to some extent. Most patients with HS could get sperm by microdissection TESE.

Background: Erectile dysfunction (ED), as one of the most prevalent consequences in male diabetic patients, has a serious impact on men's physical and mental health, and the treatment effect of diabetic mellitus erectile dysfunction (DMED) is often worse. Therefore, the development of a novel therapeutic approach is urgent. As stem cells with high differentiation potential, human umbilical cord mesenchymal stem cells (HUCMSCs) have been widely used in the treatment of diseases in other systems, and are expected to be a promising strategy for the treatment of DMED. In this study, we investigated the role of HUCMSCs in managing erectile function in rat models of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) and compared the effects of two different injection methods. Methods: T1DM and T2DM ED rats were given labelled HUCMSCs by corpus cavernosum injection and tail vein injection, respectively. ICP and MAP were monitored simultaneously by electrical stimulation four weeks after injection to indicate the erectile function of rats. To track the development and colonisation capabilities of stem cells, we performed EdU assay with penile tissue. The histological changes of the penis were observed by hematoxylin–eosin staining, and Masson’s trichrome staining was conducted to evaluate the smooth muscle content and the degree of fibrosis in the rat penis. Then, we employed specific kits to measure the level of NO, cGMP, MDA, SOD and Fe in penis. Electron transmission microscopy was implemented to observe morphology of mitochondria. Besides, western blot and immunofluorescence staining were performed to demonstrate the expression of ferroptosis-related genes. Results: We found that HUCMSCs improved erectile function in T1DM and T2DM ED rats, with no difference in efficacy between corpus cavernosum injection and tail vein injection. The EdU assay revealed that only a tiny percentage of HUCMSCs colonised the corpus cavernosum, while smooth muscle in the penis expanded and collagen decreased following HUCMSC injection. Moreover, the levels of oxidative stress in the penis of the rats given HUCMSCs were dramatically reduced, as was the tissue iron content. HUCMSCs normalised mitochondrial morphology within corpus cavernosum smooth muscle cells (CCSMCs), which were characteristically altered by high glucose. Furthermore, the expression of ferroptosis inhibitory genes SLC7A11 and GPX4 was obviously elevated in CCSMCs after stem cell management, but the abundances of ACSL4, LPCAT3 and ALOX15 showed the polar opposite tendency. Conclusions: HUCMSCs can effectively and safely alleviate erectile dysfunction in T1DM and T2DM ED rats, while restoring erectile function by attenuating diabetes-induced ferroptosis in CCSMCs. Additionally, this study provides significant evidence for the development of HUCMSCs as a viable therapeutic strategy for DMED.

Summary: Excessive production of reactive oxygen species (ROS) by an overactive nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system in penile tissue is an important mechanism of erectile dysfunction (ED). S‐allyl cysteine (SAC), a bioactive component derived from garlic, was recently reported to exert versatile antioxidant properties. We hypothesized that SAC would be able to resolve diabetes‐related ED by reducing ROS generation, and designed this study to investigate this possibility as well as to determine the related underlying mechanisms. A streptozotocin‐induced diabetes rat model was established and used for comparative analysis of 4‐week treatment regimens with insulin or SAC. The ratio of maximal intracavernous pressure (ICP) to mean arterial blood pressure (MAP) was measured to determine erectile function. Differential levels of ROS, NADPH oxidase subunits, nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signalling pathway, and apoptosis were evaluated in cavernous tissues. Max ICP/MAP was found to be markedly decreased in untreated diabetic rats; SAC, but not insulin, treatment restored the ratio to baseline (in non‐diabetic untreated controls). The corpus cavernosum of untreated diabetic rats showed increased p47^phox and p67^phox expression, ROS production and penile apoptotic index, and decreased phospho‐endothelial nitric oxide synthase (phospho‐eNOS, Ser1177) expression, cGMP concentration, B‐cell lymphoma 2 (Bcl‐2)/Bcl‐2‐associated X protein (Bax) ratio and smooth muscle cell number. SAC treatment normalized all the diabetes‐induced effects, whereas insulin treatment partially normalized the alterations, but produced no effects on P47^phox expression, penile ROS level, apoptotic index, Bcl‐2/Bax ratio and smooth muscle cell number. Collectively, these data indicate that SAC treatment can restore erectile function in diabetic rats by preventing ROS formation through modulation of NADPH oxidase subunit expression. Furthermore, the poor efficacy of conventional insulin treatment for diabetic ED may be associated with an elevated level of ROS in penile tissue.

The morbidity of prostate cancer (PCa) is rising year by year, and it has become the primary cause of tumor-related mortality in males. It is widely accepted that macrophages account for 50% of the tumor mass in solid tumors and have emerged as a crucial participator in multiple stages of PCa, with the huge potential for further treatment. Oftentimes, tumor-associated macrophages (TAMs) in the tumor microenvironment (TME) behave like M2-like phenotypes that modulate malignant hallmarks of tumor lesions, ranging from tumorigenesis to metastasis. Several clinical studies indicated that mean TAM density was higher in human PCa cores versus benign prostatic hyperplasia (BPH), and increased biopsy TAM density potentially predicts worse clinicopathological characteristics as well. Therefore, TAM represents a promising target for therapeutic intervention either alone or in combination with other strategies to halt the “vicious cycle,” thus improving oncological outcomes. Herein, we mainly focus on the fundamental aspects of TAMs in prostate adenocarcinoma, while reviewing the mechanisms responsible for macrophage recruitment and polarization, which has clinical translational implications for the exploitation of potentially effective therapies against TAMs.

Background: The coronavirus disease 2019 (COVID-19) has spread worldwide with alarming levels of spread and severity. The distribution of angiotensin converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) from bioinformatics evidence, the autopsy report for COVID-19 and the published study on sperm quality indicated COVID-19 could have a negative impact on male fertility. However, whether the negative impact of COVID-19 on male fertility is persistent remains unknown, which requires long-term follow-up investigation. Methods: Semen samples were collected from 36 male COVID-19 patients with a median recovery time of 177.5 days and 45 control subjects. Then, analysis of sperm quality and alterations of total sperm number with recovery time were performed. Results: There was no significant difference in semen parameters between male recovered patients and control subjects. And the comparisons of semen parameters between first follow-up and second follow-up revealed no significant difference. In addition, we explored the alterations of sperm count with recovery time. It showed that the group with recovery time of ≥120 and <150 days had a significantly lower total sperm number than controls while the other two groups with recovery time of ≥150 days displayed no significance with controls, and total sperm number showed a significant decline after a recovery time of 90 days and an improving trend after a recovery time of about 150 days. Conclusions: The sperm quality of COVID-19 recovered patients improved after a recovery time of nearly half a year, while the total sperm number showed an improvement after a recovery time of about 150 days. COVID-19 patients should pay close attention to the quality of semen, and might be considered to be given medical interventions if necessary within about two months after recovery, in order to improve the fertility of male patients as soon as possible.