Altered regional brain activity and functional connectivity in primary intravaginal anejaculation patients revealed by resting-state fMRI.

ABSTRACT: Ejaculation is regulated by the central nervous system. However, the central pathophysiology of primary intravaginal anejaculation (PIAJ) is unclear. The present study aimed to examine the changes in regional brain activity and functional connectivity underlying PIAJ. A total of 20 PIAJ patients and 16 healthy controls (HCs) were enrolled from September 2020 to September 2022 in the Department of Andrology, Nanjing Drum Tower Hospital (Nanjing, China). Magnetic resonance imaging data were acquired from all participants and then were preprocessed. The measures of fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), and functional connectivity (FC) were calculated and compared between the groups. PIAJ patients showed increased fALFF values in the left precuneus compared with HCs. Additionally, PIAJ patients showed increased ReHo values in the left precuneus, left postcentral gyrus, left superior occipital gyrus, left calcarine fissure, right precuneus, and right middle temporal gyrus, and decreased ReHo values in the left inferior parietal gyrus, compared with HCs. Finally, brain regions with altered fALFF and ReHo values in PIAJ patients showed increased FC with widespread cortical regions, which included the frontal, parietal, temporal, and occipital regions, compared with HCs. In conclusion, increased regional brain activity in the parietal, temporal, and occipital regions, and increased FC between these brain regions, may be associated with PIAJ occurrence.

Application of the sexual therapy combined with vacuum negative pressure hydropneumatic/pneumatic bubble massage in primary intravaginal anejaculation.

INTRODUCTION: Primary intravaginal anejaculation (PIAJ) is a relatively uncommon male sexual dysfunction characterized by an inability to achieve intravaginal ejaculation during all sexual intercourse. Effective treatment options for this condition are lacking. We aimed to explore the clinical effect of the sexual therapy combined with vacuum negative pressure hydropneumatic/pneumatic bubble massage (VNPHP/PBM) on primary intravaginal anejaculation, and its possible mechanism. METHODS: A total of 95 PIAJ patients were randomly divided into three groups, including group A with 32 patients treated with the sexual therapy combined with VNPHP/PBM, group B with 32 patients treated with the sexual therapy and group C with 31 patients treated with VNPHP/PBM. The efficacy of therapeutic regimes, latency of the somatosensory evoked potentials of dorsal nerve (DNSEP), glans penis (GPSEP) and penile shaft sensory threshold (PSST), measures of sexual behavior of patients, as well as the self-rating anxiety scale (SAS) sores of patients and their partners, were compared before and after treatment among three groups. RESULTS: The total effective rate of group A (84.38%) was higher than those of groups B and C (53.13% and 41.94%), however, no differences were found between groups B and C. The ratios of patients and their partners with anxiety, frequency of observing erotic films of patients, ratios of patients with special self-masturbation and frequency of masturbation decreased significantly in the three groups after the treatment. The decrease in the ratios of patients and their partners with anxiety, frequency of observing erotic films of patients in groups A and B were higher than those of group C, however, no differences were identified between groups A and B. The decrease in the ratios of patients with special self-masturbation and frequency of masturbation in group A were higher than those of group B, however, no differences were found between groups A and C, B and C. There were no differences in the latency of DNSEP, GPSEP, and PSST among the three groups before and after treatment. CONCLUSION: The sexual therapy combined with VNPHP/PBM has good therapeutic effects on PIAJ, which might be achieved by reducing the anxiety level of patients and their partners, improving sexual behavioral patterns, rather than increasing the sensitivity of penis including dorsal nerve and glans penis.

ADSCs labeled with SPIONs tracked in corpus cavernosum of rat and miniature pig by MR imaging and histological examination.

Adipose tissue-derived stem cells (ADSCs) have been shown to improve erectile function in animal models of erectile dysfunction. However, few studies have been carried out using a reliable in vivo imaging method to trace transplanted cells in real time, which is necessary for systematic investigation of cell therapy. The study aims to explore the feasibility of non-invasively monitoring intracavernous injection of ADSCs in rat and miniature pig corpus cavernosum using in vivo magnetic resonance (MR) imaging. Thirty-six male Sprague Dawley rats (10 weeks old) and six healthy, sexually mature male miniature pigs (20 kg weight) were obtained. ADSCs were isolated from paratesticular fat of donor rats and cultured. Then ADSCs were labeled with superparamagnetic iron oxide nanoparticles (SPIONs), a type of MR imaging contrast agent, before transplantation into rats and pigs. After intracavernous injection, all rats and pigs underwent and were analyzed by MR imaging at the day of ADSC transplantation and follow-up at 1, 2 and 4 weeks after transplantation. In addition, penile histological examination was performed on all rats and pigs before (n = 6) and at 1 day (n = 6), 1 week (n = 6), 2 weeks (n = 6) or 4 weeks (n = 12) after ADSC transplantation. SPION-labeled ADSCs demonstrated a strong decreased signal intensity compared with distilled water, unlabeled ADSCs or agarose gel. SPION-labeled ADSCs showed a hypointense signal at all concentrations, and the greatest hypointense signal was observed at the concentration of 1 × 106. MR images of the corpus cavernosum showed a hypointense signal located at the injection site. T2*-weighted signal intensity increased over the course of 1 week after ADSCs transplantation, and demonstrated a similar MR signal with that before ADSCs transplantation. After SPION-labeled ADSC injection, T2*-weighted MR imaging clearly demonstrated a marked hypointense signal in pig corpus cavernosum. The T2*-weighted signal faded over time, similar to the MR imaging results in rats. Obvious acute inflammatory exudation was induced by intracavernous injection, and the T2*-weighted signal intensity of these exudation was higher than that of the injection site. The presence of iron was detected by Prussian blue staining, which demonstrated ADSC retention in rat corpus cavernosum. Lack of cellular infiltrations were demonstrated by H&E staining before and 4 weeks after transplantation, which indicated no negative immune response by rats. Prussian blue staining was positive for iron oxide nanoparticles at 2 weeks after transplantation. SPION-labeled ADSCs showed a clear hypointense signal on T2-weight MRI in vitro and in vivo. The MR signal intensity in the corpus cavernosum of the rats and miniature pigs faded and disappeared over time after ADSC transplantation. These findings suggested that MR imaging could trace transplanted ADSCs in the short term in the corpus cavernosum of animals.

Abnormal cortical surface-based spontaneous and functional connectivity in the whole brain in lifelong premature ejaculation patients.

Recent research has highlighted structural and functional abnormalities in the cerebral cortex of patients with premature ejaculation (PE). These anomalies could play a pivotal role in the physiological mechanisms underlying PE. This study leveraged functional magnetic resonance imaging (fMRI), a noninvasive technique, to explore these neural mechanisms. We conducted resting-state fMRI scans on 36 PE patients and 22 healthy controls (HC), and collected data on Premature Ejaculation Diagnostic Tool (PEDT) scores and intravaginal ejaculation latency time (IELT). Employing a surface-based regional homogeneity (ReHo) approach, we analyzed local neural synchronous spontaneous activity, diverging from previous studies that utilized a volume-based ReHo method. Areas with significant ReHo differences between PE and HC groups underwent surface-based functional connectivity (FC) analysis. Significant discrepancies in ReHo and FC across the cortical surface were observed in the PE cohort. Notably, PE patients exhibited decreased ReHo in the left triangular inferior frontal gyrus and enhanced ReHo in the right middle frontal gyrus. The latter showed heightened connectivity with the left lingual gyrus and the right orbital superior frontal gyrus. Furthermore, a correlation between ReHo and FC values with PEDT scores and IELT was found in the PE group. Our findings, derived from surface-based fMRI data, underscore specific brain regions linked to the neurobiological underpinnings of PE.

Identification of a novel splice site mutation in the DNAAF4 gene of a Chinese patient with primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) is a rare hereditary orphan condition that results in variable phenotypes, including infertility. About 50 gene variants are reported in the scientific literature to cause PCD, and among them, dynein axonemal assembly factor 4 ( DNAAF4 ) has been recently reported. DNAAF4 has been implicated in the preassembly of a multiunit dynein protein essential for the normal function of locomotory cilia as well as flagella. In the current study, a single patient belonging to a Chinese family was recruited, having been diagnosed with PCD and asthenoteratozoospermia. The affected individual was a 32-year-old male from a nonconsanguineous family. He also had abnormal spine structure and spinal cord bends at angles diagnosed with scoliosis. Medical reports, laboratory results, and imaging data were investigated. Whole-exome sequencing, Sanger sequencing, immunofluorescence analysis, hematoxylin-eosin staining, and in silico functional analysis, including protein modeling and docking studies, were used. The results identified DNAAF4 disease-related variants and confirmed their pathogenicity. Genetic analysis through whole-exome sequencing identified two pathogenic biallelic variants in the affected individual. The identified variants were a hemizygous splice site c.784-1G>A and heterozygous 20.1 Kb deletion at the DNAAF4 locus, resulting in a truncated and functionless DNAAF4 protein. Immunofluorescence analysis indicated that the inner dynein arm was not present in the sperm flagellum, and sperm morphological analysis revealed small sperm with twisted and curved flagella or lacking flagella. The current study found novel biallelic variants causing PCD and asthenoteratozoospermia, extending the range of DNAAF4 pathogenic variants in PCD and associated with the etiology of asthenoteratozoospermia. These findings will improve our understanding of the etiology of PCD.

Modulation of SIRT1 expression improves erectile function in aged rats.

Silent information regulator 2-related enzyme 1 (SIRT1) is an aging-related protein activated with aging. Herein, we evaluated the role of SIRT1 in aging-related erectile dysfunction. The expression of SIRT1 was modulated in aged Sprague-Dawley rats following intragastric administration of resveratrol (Res; 5 mg kg-1), niacinamide (NAM; 500 mg kg-1) or Res (5 mg kg-1) + tadalafil (Tad; phosphodiesterase-5 [PDE5] inhibitor; 5 mg kg-1) for 8 weeks. Then, we determined erectile function by the ratio of intracavernosal pressure (ICP)/mean systemic arterial pressure (MAP). Cavernosal tissues were extracted to evaluate histological changes, cell apoptosis, nitric oxide (NO)/cyclic guanosine monophosphate (cGMP), the superoxide dismutase (SOD)/3,4-methylenedioxyamphetamine (MDA) level, and the expression of SIRT1, p53, and forkhead box O3 (FOXO3a) using immunohistochemistry, terminal deoxynucleotidyl transferase (TdT)-mediated 2'-deoxyuridine 5'-triphosphate (dUTP) nick-end labeling (TUNEL), enzyme-linked immunosorbent assays, and western blot analysis. Compared with the control, Res treatment significantly improved erectile function, reflected by an increased content of smooth muscle and endothelium, NO/cGMP and SOD activity, and reduced cell apoptosis and MDA levels. The effect of Res was improved by adding Tad. In addition, the protein expression of SIRT1 was increased in the Res group, accompanied by decreased p53 and FOXO3a levels. In addition, inhibition of SIRT1 by NAM treatment resulted in adverse results compared with Res treatment. SIRT1 activation ameliorated aging-related erectile dysfunction, supporting the potential of SIRT1 as a target for erectile dysfunction treatment.

Magnetic-activated cell sorting of nonapoptotic spermatozoa with a high DNA fragmentation index improves the live birth rate and decreases transfer cycles of IVF/ICSI.

The present study aimed to evaluate the clinical outcomes of magnetic-activated cell sorting (MACS) in sperm preparation for male subjects with a sperm DNA fragmentation index (DFI) ≥30%. A total of 86 patients who had undergone their first long-term long protocol were selected. The protocol involved in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles, and the patients were divided into the MACS or control groups. The MACS group included sperm samples analyzed with MACS that were combined with density gradient centrifugation (DGC) and the swim-up (SU) technique (n = 39), and the control group included sperm samples prepared using standard techniques (DGC and SU; n = 41). No differences were noted with regard to basic clinical characteristics, number of oocytes retrieved, normal fertilization rate, cleavage rate, or transplantable embryo rate between the two groups in IVF/ICSI. In addition, the clinical pregnancy and implantation rates of the first embryo transfer cycles indicated no significant differences between the two groups. However, there was a tendency to improve the live birth rate (LBR) of the first embryo transfer cycle (63.2% vs 53.9%) and the cumulative LBR (79.5% vs 70.7%) in the MACS group compared with the control group. Moreover, the number of transferred embryos (mean ± standard deviation [s.d.]: 1.7 ± 0.7 vs 2.3 ± 1.6) and the transfer number of each retrieved cycle (mean ± s.d.: 1.2 ± 0.5 vs 1.6 ± 0.8) were significantly lower in the MACS group than those in the control group. Thus, the selection of nonapoptotic spermatozoa by MACS for higher sperm DFI could improve assisted reproductive clinical outcomes.

Mutational landscape of DNAH1 in Chinese patients with multiple morphological abnormalities of the sperm flagella: cohort study and literature review.

PURPOSE: Multiple morphological abnormalities of the sperm flagella (MMAF) are important causes of male infertility. Mutations in DNAH1 are the main causative factors proven so far. We aim to determine the mutational landscape of DNAH1 in Chinese patients with MMAF. METHODS: Forty-one Chinese patients with MMAF were enrolled and underwent a 10-gene next-generation sequencing panel screening. RESULTS: Only the DNAH1 gene was found to have mutations in 12 of these unrelated individuals (29%). Combining published data from two other cohorts of Chinese men with MMAF, we suggest that p.P3909fs*33, p.R868X, p.Q1518X, p.E3284K, and p.R4096L are hotspot mutations. A polymorphism-rs12163565 (G>A)- showed linkage to p.P3909fs*33, suggesting that this involved a founder effect. Four of the 12 patients with DNAH1 mutations were able to use intracytoplasmic sperm injection with their partners and all were successful in obtaining embryos. CONCLUSIONS: Hotspot mutations were identified for Chinese patients with MMAF. MMAF sub-phenotypes might be associated with different combinations of DNAH1 mutations.

[PDE-5i combined with RigiScan-based audiovisual sexual stimulation test versus nocturnal penile tumescence test in evaluation of erectile function].

OBJECTIVE: To explore the clinical value of phosphodiesterase type-5 inhibitors (PDE-5i) combined with RigiScan-based audiovisual sexual stimulation (AVSS) test in comparison with that of nocturnal penile tumescence (NPT) test in evaluation of erectile function. METHODS: A total of 166 ED patients, aged 21－63 (mean 31) years, with a disease course of 3 months to 10 years (mean 14 months), underwent NPT test or PDE-5i + RigiScan-based AVSS test from 2017 to 2018. We compared the results of the diagnostic strategies. Normal NPT patterns were presumed to indicate psychogenic and abnormal ones to indicate organic ED. RESULTS: Compared with the results of NPT test, no statistically significant difference was observed in the accuracy rate between Viagra + AVSS test and Cialis + AVSS test (P > 0.05). PDE-5i + RigiScan-based AVSS test achieved a sensitivity of 78.9% and a specificity of 90.7% in the diagnosis of psychogenic ED and an overall accuracy rate of 81.9%. According to the results of PDE-5i + RigiScan-based AVSS test, the patients fell into a normal and an abnormal erection group, with significant differences between the two groups in age, disease course, IIEF-5 score and maintenance time of penile tip rigidity ≥60% (P < 0.05). ROC curve analysis indicated that PDE-5i + RigiScan-based AVSS test accurately manifested the erectile function of the patients. CONCLUSIONS: Compared with NPT test, PDE -5i combined with RigiScan-based AVSS test is simple, inexpensive, practical and with a high sensitivity and specificity, and therefore can be used as the first-choice strategy for etiological diagnosis of ED.

Protective role of wogonin against cadmium induced testicular toxicity: Involvement of antioxidant, anti-inflammatory and anti-apoptotic pathways.

The present study was conducted to identify possible health - promoting effects of wogonin (Wog) on testicular dysfunction in rats caused by cadmium. Pre-treatment of cadmium chloride (Cd: 5 mg/kg b.wt.) administered rats with wogonin (10 mg/kg b.wt) resulted in significant improvement in Cd-induced decrease in body and organ (testes and epididymides) weights. Wogonin treatment significantly improved Cd-induced reduction in sperm quality and quantity, steroidogenic gene (SFI, StAR, CYP11A1, 3ß-HSD, CYP17A1 and 17ß-HSD) and protein (SF1, StAR and CYP17A1) expressions and serum testosterone levels. Wogonin treatment provided significant protection to Cd-induced aggression in testicular oxidative (elevated levels of MDA) and anti-oxidative (diminished activities of SOD, CAT and GPx) status. Wog significantly up-regulated mRNA levels of Nrf2, NQO1 and HO-1 and down-regulation of Keap1 in cadmium treated testes. Wogonin administration significantly suppressed Cd-stimulated increase in inflammatory reactions (increase in NF-κB p65 DNA, p-IKKß, TNF-α levels and decrease in IL-10 levels). Wogonin prevented apoptotic damage by enhanced protein distribution of caspase-9, caspase-3, and Bax due to Cd exposure. Furthermore, Wogonin presented significant protection to histo-morphometric changes resulted after Cd administration. Taken together, the findings of this study provided clear evidence of the therapeutic potential of Cd-induced testicular toxicity at least partly due to its antioxidant, anti-inflammatory and anti-apoptotic properties.

Dynamic infusion cavernosometry and cavernosography for classifying venous erectile dysfunction and its significance for individual treatment.

BACKGROUND: The precise pathophysiology of venous erectile dysfunction (VED) was still unclear. Dynamic infusion cavernosometry and cavernosography (DICC) was the gold standard approach for the diagnoses of VED. However, a standard operative procedure of DICC was needed and it was unclear whether DICC could show promise in accurate assessment and treatment of VED. The aim of this study was to establish an optimized operation process of DICC and evaluate the efficacy of DICC in the diagnoses and therapy of VED. METHODS: One hundred and forty-seven VED patients identified by the color doppler duplex ultrasonography (CDDU) were included. Then the method of DICC was adopted to assess the severity of VED and all patients were divided into 4 groups, including (1) non-VED; (2) mild VED; (3) moderate VED and (4) severe VED. All patients received the treatment of psychotherapy. Drug therapy, the intervention embolism of corpus cavernosum and the implantation of penile prosthesis were applied if psychotherapy was ineffective for patients. The international index of erectile function (IIEF-5) scores of patients were collected and compared before and after treatment. RESULTS: IIEF-5 score of non-VED group after psychotherapy (19.35 ±â€Š3.59) and drug therapy (23.31 ±â€Š0.75) was higher than that before psychotherapy (15.30 ±â€Š2.72, t = -4.31, P < 0.01) and drug therapy (16.62 ±â€Š1.50, t = -19.13, P < 0.01). IIEF-5 scores of mild VED (18.25 ±â€Š2.60) and moderate VED group (14.83 ±â€Š4.17) after treatment was improved significantly by intervention embolism of corpus cavernosum when compared with those before treatment (mild: 15.50 ±â€Š2.14, t = -2.31, P < 0.05; moderate: 11.83 ±â€Š2.86, t = -1.45, P < 0.05). However, drug therapy and intervention embolism (IE) of corpus cavernosum showed poor effects on patients with moderate and severe VED patients (P > 0.05). IIEF-5 score of severe VED group was increased under the treatment of implantation of penile prosthesis (23.25 ±â€Š0.71) compared with that before treatment (8.00 ±â€Š0.39, t = -53.25, P < 0.05). CONCLUSION: DICC was a valid diagnostic tool that could identify patients with VED. And DICC had great effect on the diagnosis and individual therapy for patients with VED in varying degrees. Moreover, the manipulation of DICC needed uniform standards.

[Advances in the surgical treatment of premature ejaculation].

Premature ejaculation (PE) is a most common type of ejaculatory dysfunction, which has significant adverse effects on the life quality of the patients and their partners. Medication is currently the first choice for PE and psycho-behavior therapy is sometimes used as an adjuvant means. It is reported in a number of studies that medication alone or combined with psycho-behavior therapy has a great short-term efficacy and a very low risk of side effects. Conservative therapies for PE, however, have some obvious disadvantages such as easy recurrence after drug withdrawal, ineffectiveness in some cases, and so on. Thus, clinicians in China and abroad have developed and tried various surgical methods for the treatment of PE, most of which are reportedly safe and effective. However, International Society for Sexual Medicine guidelines for the diagnosis and treatment of PE recommended against surgical methods because of possible permanent loss of sexual function and insufficient reliable data, though without support from evidence or relevant literature. Although controversial, surgical treatment remains an effective and feasible strategy for refractory PE that does not respond to any conservative therapies. This review summarizes a variety of surgical techniques for PE, along with their basic principles, indications, effects and safety.

Giant intrascrotal embryonal rhabdomyosarcoma in an adult: a case report and review of the literature.

BACKGROUND: Intrascrotal embryonal rhabdomyosarcoma in adults is a rare tumor with high aggression and a poor prognosis. We report our patient's case and review the relevant literature to improve the understanding of this rare disease. CASE PRESENTATION: A 21-year-old Han Chinese man presented to our hospital with a right intrascrotal mass of 1 year's duration. His physical examination revealed an enlarged right scrotum containing a huge tender mass measuring about 10 × 7 cm. Ordinary and contrast-enhanced ultrasonography showed a solid mass in the right scrotum, which was suspected to be a malignant tumor. An abdominopelvic computed tomographic scan revealed metastases in the retroperitoneal lymph nodes. The patient was diagnosed with malignant testicular tumor and underwent a right radical orchiectomy by an inguinal approach. Postoperative pathological examination suggested an intrascrotal embryonal rhabdomyosarcoma. CONCLUSIONS: Intrascrotal embryonal rhabdomyosarcoma is a rare but highly aggressive tumor. Clinical and imaging manifestations of this tumor are nonspecific, so the definitive diagnosis depends on postoperative pathology and immunohistochemistry. Early suspicion, radical orchiectomy, accurate pathologic diagnosis, and adjuvant chemotherapy and/or radiotherapy are the keys to optimal prognosis.

Impaired Prefrontal-Amygdala Pathway, Self-Reported Emotion, and Erection in Psychogenic Erectile Dysfunction Patients With Normal Nocturnal Erection.

Background: Neuroimaging studies have demonstrated that the prefrontal cortex and amygdala play an important role in sexual arousal (SA). However, little is known about the interactions between the prefrontal and cortex amygdala, which mediate the cognitive regulation of emotion and SA. Objective: We seek to determine whether nocturnal erection of psychogenic erectile dysfunction (pED) patients are normal and whether there are changes of topological organization in the prefrontal-amygdala pathway of brain network in pED. In addition, whether there are correlations between network property changes and self-reported emotion and erection. Design, setting, and participants: We used the RigiScan device to evaluate erectile function of patients and employed diffusion MRI and graph theory to construct brain networks of 21 pED patients and 24 healthy controls. Outcome measurements and statistical analysis: We considered four nodal metrics and their asymmetry scores, and nocturnal penile tumescence (NPT) parameters, to evaluate the topological properties of brain networks of pED and their relationships with the impaired self-reported emotion and erection. Results and limitations: All the pED patients showed normal nocturnal penile erection, however impaired self-reported erection and negative emotion. In addition, patients showed lower connectivity degree and strength in the left prefrontal-amygdala pathway. We also found that pED exhibited lower leftward asymmetry in the inferior frontal gyrus. Furthermore, patients showed more hub regions and fewer pivotal connections. Moreover, the degree of the left amygdala of pED showed significantly negative correlation with the self-reported erection and positive correlation with the self-reported negative emotion. Conclusions: Together, these results suggest normal nocturnal erection in pED. However, abnormalities of brain network organization in pED, particularly in the left prefrontal-amygdala pathway, are associated with the impaired self-reported erection and negative emotion.

Prostate cancer involving bilateral seminal vesicles along with bone and testicular metastases: a case report.

BACKGROUND: In the past 20 years, the incidence of prostate cancer has risen rapidly. It has been ranked as the third most common malignant tumor of the male genitourinary system. Testicular metastasis is uncommon in prostate cancer. Most cases are incidentally found in the treatment of prostate cancer with orchiectomy. Therefore, we believed it was necessary to report the case of our patient with this disease. CASE PRESENTATION: We present a case of a 69-year-old Han Chinese man with a high total prostate-specific antigen level. A transrectal ultrasound-guided prostate biopsy was performed. A pathology report showed prostate cancer tissue with a Gleason score of 4 + 4 = 8/10. Imaging findings suggested that the prostate cancer tissue involved bilateral seminal vesicles and multiple bones. Next, radioactive seed implantation was carried out, and endocrine therapy was continued after the operation. Then enlargement of the left scrotum was found along with a total prostate-specific antigen level of 19.21 ng/ml. Computed tomography of the middle abdomen and pelvic cavity revealed 2.0 × 1.3-cm lesions of the left testis. The patient underwent a left testicular high resection and right orchiectomy. The postoperative pathology report showed metastatic prostate cancer cells in the left testis. CONCLUSIONS: Testicular metastasis of prostate cancer is rare. Therefore, a testicular physical examination is necessary for patients without relapse to avoid a missed diagnosis. Testicular metastasis should be treated according to the principle of treatment for advanced prostate adenocarcinoma if testicular metastasis of prostate adenocarcinoma is detected.

Brain structural network topological alterations of the left prefrontal and limbic cortex in psychogenic erectile dysfunction.

AIM: Despite increasing understanding of the cerebral functional changes and structural abnormalities in erectile dysfunction, alterations in the topological organization of brain networks underlying psychogenic erectile dysfunction remain unclear. MATERIALS AND METHODS: Here, based on the diffusion tensor image data of 25 patients and 26 healthy controls, we investigated the topological organization of brain structural networks and its correlations with the clinical variables using the graph theoretical analysis. RESULTS: Patients displayed a preserved overall small-world organization and exhibited a less connectivity strength in the left inferior frontal gyrus, amygdale and the right inferior temporal gyrus. Moreover, an abnormal hub pattern was observed in patients, which might disturb the information interactions of the remaining brain network. Additionally, the clustering coefficient of the left hippocampus was positively correlated with the duration of patients and the normalized betweenness centrality of the right anterior cingulate gyrus and the left calcarine fissure were negatively correlated with the sum scores of the 17-item Hamilton Depression Rating Scale. CONCLUSIONS: These findings suggested that the damaged white matter and the abnormal hub distribution of the left prefrontal and limbic cortex might contribute to the pathogenesis of psychogenic erectile dysfunction and provided new insights into the understanding of the pathophysiological mechanisms of psychogenic erectile dysfunction.

Bilateral is superior to unilateral varicocelectomy in infertile males with left clinical and right subclinical varicocele: a prospective randomized controlled study.

PURPOSE: The purpose of this study is to compare the effect of bilateral versus unilateral varicocelectomy on seminal response and spontaneous pregnancy rates in infertile male patients with left clinical and right subclinical varicocele. METHODS: A total of 358 infertile men with left clinical and right subclinical varicocele were randomized to group that underwent bilateral (n = 179) and group that underwent unilateral microsurgical subinguinal varicocelectomy (n = 179). Baseline data regarding male age, female partner age, grade of varicocele body mass index, bilateral testicular volume and serum follicle-stimulating hormone, luteinizing hormone, total testosterone levels and infertility duration and semen parameters were gathered. One year after the surgery, semen parameters including sperm volume, sperm concentration, normal sperm morphology, progressive motility and sperm DNA fragmentation index were recorded and any pregnancy was also documented via telephone calls and hospital visits. RESULTS: We found the baseline characteristics were comparable between the two groups. The seminal parameters had significant improvements 1 year postoperatively in both groups. However, the bilateral group showed significantly greater improvements than the unilateral group in sperm concentration, normal sperm morphology and progressive motility. Besides, the pregnancy rate was statistically higher in the bilateral group after the surgery (42.5 versus 26.0%, bilateral versus unilateral group). CONCLUSION: In conclusion, our study indicated that bilateral is superior to unilateral varicocelectomy in infertile males with left clinical and right subclinical varicocele, which is associated with greater improvements in sperm concentration, normal sperm morphology and progressive motility and spontaneous pregnancy rate after the surgery.

Repeated Micro-Trauma of the Penile Tunica Albuginea: A New Animal Model of Peyronie's Disease.

OBJECTIVES: To compare effects of repairing injured tunica albuginea (PTA) of rat penis by single or repeated local injections of chlorhexidine ethanol (ChE) into the PTA and to establish a new animal model of Peyronie's disease (PD). MATERIALS AND METHODS: Forty-two rats were divided into 7 groups. Rats either served as the normal control group with 1-5 injections of 0.9% saline or they received a single injection, 2, 3, 4, or 5 injections of ChE (0.1% chlorhexidine gluconate plus 15% ethanol dissolved in saline); rats in the positive control group were injected with TGF-ß1. At 60 days after the last injection, the intracavernous pressure, degree of penile curvature, and histology were evaluated. RESULTS: Compared with the single injection of the ChE group, we found the following in the repeat ChE injections groups: an increase in the degree of penile curvature, fibrous plaques in the PTA and/or corpus cavernosum, broken elastic fibers, slightly decreased erectile function, and an increased expression of TGF-ß1 and αSMA. CONCLUSIONS: Repeated ChE injuries of PTA may lead to fibrosis. This represents an excellent model of PD that involves repeated injections of ChE into the local PTA as well as reveals the pathophysiologic mechanism of PD.

Inhibition of penile tunica albuginea myofibroblasts activity by adipose-derived stem cells.

The activation of tunica albuginea myofibroblasts (MFs) serves an essential role in Peyronie's disease (PD). Increasing evidence has reported that adipose tissue-derived stem cells (ADSCs) have been demonstrated to attenuate the symptoms of PD in animal models. However, the mechanisms of the antifibrotic effects of ADSCs in PD remain to be fully elucidated. In the present study, the inhibitory effects and possible mechanism of ADSCs on the activation of MFs derived from rat penile tunica albuginea were investigated. ADSCs were obtained from the paratesticular fat of Sprague Dawley rats. MFs were transformed from rat penile tunica albuginea fibroblasts through stimulation with 5 ng/ml tumor growth factor-ß1. Transwell cell cultures were adopted for co-culture of ADSCs and MFs. Western blot analysis was used to assess changes in the expression levels of α smooth muscle actin (αSMA), collagen I, phosphorylated (p)-SMAD family member 2 (Smad2), Smad2, ras homolog family member A (RhoA), Rho associated coiled-coil containing protein kinase (ROCK)1 and ROCK2, caspase3, caspase9, and matrix metalloproteinases (MMPs). Collagen gel assays were used to assess cell contractility. Additionally, the concentration of hydroxyproline in the culture medium was detected using commercially available kits. It was demonstrated that ADSCs reduced the expression of αSMA and collagen I of MFs. Furthermore, p-Smad2, RhoA, ROCK1 and ROCK2 expression was significantly reduced in the MFs+ADSCs group compared with that in the MFs-only culture, while the expression of MMPs (MMP2, MMP3, MMP9 and MMP13) and caspases (caspase3 and caspase9) was upregulated. In addition, ADSCs were able to downregulate the concentration of hydroxyproline in the culture medium of MFs and reverse the contraction of MFs. Collectively, these results suggested that ADSCs inhibited the activation of MFs, decreased collagen production, and suppressed the contraction of myofibroblasts, via Smad and RhoA/ROCK signaling pathways. Furthermore, ADSCs reduced the deposition of collagen and promoted the apoptosis of MFs via MMPs, and caspases. Accordingly, the application of ADSCs may provide a novel therapeutic strategy for PD.