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.

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.

[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.

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.

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.

[Contrast-enhanced ultrasonography in the diagnosis of venous erectile dysfunction].

OBJECTIVE: To investigate the effect and safety of contrast-enhanced ultrasonography (CEUS) in the diagnosis of venous erectile dysfunction (VED). METHODS: From June 2015 to March 2016, 43 ED patients underwent corpus cavernography, of whom 23 were diagnosed with and the other 20 without corpus cavernosal venous leakage (CCVL). All the patients received intracorporal injection of a vasoactive drug and CEUS. RESULTS: Of the 23 patients with CCVL, 21 were confirmed by CEUS, including 12 cases of double venous leakage, 2 cases of single venous leakage, 5 cases of crural venous leakage, and 2 cases of the mixed type, while the other 2 showed no CCVL on CEUS. Of the 20 patients with CCVL, 2 presented CCVL on CEUS. CONCLUSIONS: CEUS has the advantages of accuracy, safety, and less invasiveness in the diagnosis of VED.

[Microscopic spermatic vein ligation for nutcracker phenomenon complicated with left varicocele].

OBJECTIVE: To investigate the clinical effect of microscopic spermatic vein ligation in the treatment of nutcracker phenomenon (NCP) complicated with left varicocele (VC). METHODS: This retrospective study included 31 cases of NCP complicated with left VC treated in our hospital by subinguinal microscopic ligation of the left spermatic vein (group A, n = 11), open retroperitoneal high ligation of the left spermatic vein (group B, n = 11), or conservative therapy (group C, n = 9). The patients were followed up for 6－24 (15.3 ± 5.4) months. We compared the semen parameters, spermatic vein diameter, left testis volume, and recurrence rate among the three groups of patients before and after treatment. RESULTS: Compared with the baseline, the semen quality parameters were significantly improved in both groups A and B at 6 months after treatment (P<0.05) but reduced in group C (P<0.05); the spermatic vein diameter at rest and that at Valsalva maneuver were markedly decreased in groups A (ï¼»2.53 ± 0.27ï¼½ vs ï¼»1.84 ± 0.22ï¼½ and ï¼»3.53 ± 0.19ï¼½ vs ï¼»2.16 ± 0.25ï¼½ mm, P<0.05) and B (ï¼»2.62 ± 0.33ï¼½ vs ï¼»2.15 ± 0.43ï¼½ and ï¼»3.36 ± 0.25ï¼½ vs ï¼»2.44 ± 0.27ï¼½ mm, P<0.05) but increased in group C (ï¼»2.56 ± 0.28ï¼½ vs ï¼»2.94 ± 0.24ï¼½ and ï¼»3.33 ± 0.21ï¼½ vs ï¼»3.77 ± 0.26ï¼½ mm, P<0.05). No statistically significant differences were found in the left testis volume at 6 months after treatment in group A (ï¼»9.85 ± 1.86ï¼½ vs ï¼»10.27 ± 1.18ï¼½ ml, P>0.05), B (ï¼»9.77 ± 2.03ï¼½ vs ï¼»9.96 ± 1.72ï¼½ ml, P>0.05), or C (ï¼»9.83 ± 1.59ï¼½ vs ï¼»10.48 ± 2.05ï¼½ ml, P>0.05), nor in the recurrence rate between groups A and B (P>0.05). CONCLUSIONS: Hematuria, proteinuria and other mild symptoms of nutcracker phenomenon complicated with left VC can be treated palliatively by microscopic ligation of the spermatic vein, which can relieve the clinical symptoms, improve the semen quality, and protect the testicular function of the patient.

[Laparoscopic extraperitoneal high ligation of the spermatic vein for the treatment of varicocele].

OBJECTIVE: To investigate the effect of laparoscopic extraperitoneal (LSEP) high ligation of the spermatic vein in the treatment of varicocele. METHODS: We retrospectively analyzed the clinical data about 80 cases of varieocele, 48 treated by LSEP and the other 32 by laparoscopic transabdominal retroperitoneal (LSTR) high ligation of the spermatic vein. We recorded the semen parameters before and at 1, 3 and 6 months after surgery, intraoperative blood loss, operation time, postoperative complications, time of gastrointestinal function recovery and rate of pregnancy, followed by comparison of the data obtained between the two groups of patients. RESULTS: Semen parameters were remarkably improved in both the LSEP and LSTR groups of patients postoperatively as compared with the baseline (P <0.05), but with no statistically significant difference at different postoperative months (P >0.05). The intraoperative blood loss was less in the LSEP than in the LSTR group (ï¼»8.3 ± 5.2ï¼½ vs ï¼»9.1 ± 6.1ï¼½ ml, P >0.05), the operation time was shorter in the former than in the latter (ï¼»38.27 ± 9.23ï¼½ vs ï¼»43.46 ± 11.72ï¼½ min, P >0.05), and so was the time of gastrointestinal function recovery (ï¼»1.27 ± 0.26ï¼½ vs ï¼»2.43 ± 0.41ï¼½ d, P <0.05). No statistically significant differences were observed between the two groups during the 6- to 18-month follow-up in the rates of postoperative subcutaneous hematoma, scrotal and subcutaneous emphysema, recurrence, or pregnancy (P >0.05). CONCLUSIONS: Laparoscopic extraperitoneal high ligation of the spermatic vein is safe and effective and has the advantage of quick recovery in the treatment of varicocele.

[Effects of the Rho-kinase inhibitor fasudil on the invasion, migration, and apoptosis of human prostate cancer PC3 and DU145 cells].

OBJECTIVE: To investigate the potential role of the RhoA/Rock signaling pathway in the formation of prostate cancer and the effects of the Rock inhibitor fasudil on the invasion, migration and apoptosis of human prostate cancer cells. METHODS: Human prostate cancer cell lines PC3 and DU145 were treated with fasudil at the concentrations of 5, 10, 20, 40, 80, and 160 µmol/L, respectively, and those as negative controls cultured in the Ham's-F12 medium, all for 24 hours. Then, MTT assay was used to measure the cell inhibition rate and half maximal inhibitory concentration (IC50) value of fasudil, with 1/4 of IC50 as the medication dose for further investigation. The expressions of RhoA, RockⅠ, and RockⅡ proteins in the PC3 and DU145 cells were detected by Western blot and immunohistochemistry, and the invasion, migration and apoptosis of the cells were determined using the Transwell chamber, scratch wound healing assay and flow cytometry. RESULTS: Fasudil inhibited the proliferation of the PC3 cells from (9.29±1.23)% at 5 µmol/L to (81.37±3.97)% at 160 µmol/L and that of DU145 from (7.59±1.54)% to (76.53±2.67)%, both in a dose-dependent manner (P<0.05 ). Significantly fewer PC3 and DU145 cells migrated into the lower compartment in the experimental group (39.2±8.4 and 34.2±6.7) than in the negative control (116.8±9.3 and 112.5±10.8) (P<0.05 ). The wound healing rates of the PC3 and DU145 cells were remarkably lower in the former (ï¼»37.26±1.17ï¼½% and ï¼»32.38±2.73ï¼½%) than in the latter (ï¼»78.12±4.16ï¼½% and ï¼»69.47±6.71ï¼½%) (P<0.05 ). Annexin V-FITC/PI double staining showed markedly increased apoptosis rates of PC3 and DU145 cells treated with fasudil (ï¼»31.88±2.49ï¼½% and ï¼»28.65±2.99ï¼½%) as compared with the negative controls (ï¼»7.51±2.28ï¼½% and ï¼»7.13±1.61ï¼½%) (P<0.05 ). The expressions of RockⅠ and RockⅡ were significantly reduced in the fasudil-treated cells in comparison with those of the control group (P<0.05 ) while that of RhoA showed no significant difference between the two groups (P>0.05 ). CONCLUSIONS: The RhoA/Rock signaling pathway may play an important role in the formation of prostate cancer. Fasudil can significantly inhibit the proliferation, migration, and invasion and promote the apoptosis of human prostate cancer PC3 and DU145 cells by reducing RhoA/Rho kinase activity.

[Effects and complications of five surgical approaches to the treatment of varicocele: A comparative study].

OBJECTIVE: To compare the effects and complications of subinguinal microscopic ligation, laparoscopic transperitoneal varicocelectomy, laparoscopic retroperitoneal varicocelectomy, open retroperitoneal high ligation, and interventional embolotherapy in the treatment of varicocele. METHODS: We conducted a retrospective study that included 632 varicocele patients treated by subinguinal microscopic ligation (group A, n = 79), laparoscopic transperitoneal varicocelectomy (group B, n = 120), laparoscopic retroperitoneal varicocelectomy (group C, n =137), open retroperitoneal high ligation (group D, n = 283), and interventional embolotherapy (group E, n = 13). We compared the baseline and 3-month postoperative semen parameters, postoperative complications, and pregnancy rate among the five groups of patients. RESULTS: The operation time was longer in groups A ([2.02 ± 1.25] h) and E ([2.17 ± 1.02] h) than in the other three groups, while the postoperative hospital stay was the shortest in group E ([1.1 ± 0.1] d). Intestinal injury or incision bleeding occurred intraoperatively in 2 cases in group B and 1 case in group E. Postoperative scrotal edema developed in 3.7, 17, 10, and 19% of the patients in groups A, B, C, and D, respectively, but not in group E. The rate of 1-year recurrence was the lowest in group A (1.6%) and highest in group E (22%). Sperm concentration and the percentages of progressively motile sperm and morphologically normal sperm were improved postoperatively in all the patients (P < 0. 05), but there were no statistically significant differences among the five groups either in the above three parameters or in the postoperative pregnancy rate (P > 0. 05). CONCLUSION: In the surgical treatment of varicocele, laparoscopic retroperitoneal approach involves short operation time and few complications, subinguinal microscopic ligation has the advantages of little injury, rapid recovery, and few complications but requires specialized microsurgical techniques, and interventional embolotherapy leaves no incision scar and needs only local anesthesia and 1-day postoperative hospital stay, which is uitable for those with a contraindication to anesthesia.