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

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.

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 ± 3.59) and drug therapy (23.31 ± 0.75) was higher than that before psychotherapy (15.30 ± 2.72, t=-4.31, P < 0.01) and drug therapy (16.62 ± 1.50, t=-19.13, P < 0.01). IIEF-5 scores of mild VED (18.25 ± 2.60) and moderate VED group (14.83 ± 4.17) after treatment was improved significantly by intervention embolism of corpus cavernosum when compared with those before treatment (mild: 15.50 ± 2.14, t= -2.31, P < 0.05;moderate: 11.83 ± 2.86, 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 ± 0.71) compared with that before treatment (8.00 ± 0.39, 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.

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.

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.

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(FOX03a)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.

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.