BACKGROUND:Premature ejaculation is a prevalent sexual dysfunction, yet the variable patient response to first-line dapoxetine treatment poses a major clinical challenge, highlighting the unmet need for biomarkers to guide diagnosis and therapy. AIM:This study aimed to investigate the distinct plasma metabolic profile of primary premature ejaculation (PPE) patients, and to develop machine learning-based diagnostic and therapeutic response prediction models. METHODS:A multicenter cohort comprising 69 patients with PPE and 51 healthy control (HC) subjects was enrolled. Plasma samples underwent untargeted metabolomic analysis. Differentially expressed metabolites were identified, and pathway enrichment analyses were conducted using Small Molecule Pathway Database and Kyoto Encyclopedia of Genes and Genomes. Three machine learning algorithms-Support Vector Machine, Random Forest, and Least Absolute Shrinkage and Selection Operator regression-were employed to screen biomarkers. Subsequently, targeted metabolomics analysis was used to quantify neurotransmitter levels. OUTCOMES:The primary outcomes included the Premature Ejaculation Diagnostic Tool, the intravaginal ejaculation latency time, and the Clinical Global Impression of Change scale score after a 4-week observation period of on-demand dapoxetine treatment. RESULTS:Multivariate analysis revealed clear separations in metabolic profiles between the PPE and HC groups, and between dapoxetine treatment (DT)-Response and DT-No response groups. Pathway analysis indicated significant enrichment in amino acid metabolism pathways for PPE-related differentially expressed metabolites (DEMs). Additionally, DT-Response-related DEMs were associated with D-Amino acid metabolism and Arginine biosynthesis. Machine learning identified a panel of 4 consensus metabolites for diagnosing PPE, achieving an area under the curve (AUC) of 0.995 in the train cohort and 0.917 in the test cohort. For predicting DT response, three metabolites were selected, forming a model with an AUC of 0.905 (train) and 0.811 (test). It is important to note that these promising initial results require further validation in larger, independent cohorts to confirm their generalizability. Furthermore, targeted metabolomics analysis confirmed significant dysregulation of multiple neurotransmitters in the PPE group. CLINICAL IMPLICATIONS:The machine learning-based models we established show robust performance in diagnostic and dapoxetine treatment response prediction. STRENGTHS & LIMITATIONS:The establishment of the machine learning-based diagnostic and predictive models represents a key strength, though their clinical translation requires further validation in larger cohorts. CONCLUSION:This study delineates distinct metabolic profiles in PPE, establishes robust machine learning-based models for diagnosis and DT-Response prediction, and reveals the involvement of neurotransmitter dysregulation in its pathophysiology.

BACKGROUND:Simenafil, a new potent selective phosphodiesterase-5 inhibitor (PDE5i), has been developed for erectile dysfunction (ED) treatment. AIMS:To evaluate the efficacy and safety of simenafil therapy in patients with ED. METHODS:A randomized, double-blind, placebo-controlled, multicenter, parallel-group, phase 2 trial was conducted in men aged ≥22 years with a history of ED of 3 months or more. The subjects were randomized in a ratio of 1:1:1:1 to on-demand receive either placebo or simenafil at fixed doses of 5, 10, and 20 mg for 8 weeks. OUTCOMES:Primary efficacy endpoints were the least square mean (LSM) changes from baseline to week 8 in the erectile function (EF) domain of the International Index of Erectile Function (IIEF), percentages of "yes" responses to Sexual Encounter Profile (SEP) diary Question 2 (SEP Q2: Were you able to insert your penis into your partner's vagina?) and Question 3 (SEP Q3: Did your erection last long enough for you to have successful intercourse?). RESULTS:A total of 255 patients were randomized. After 8 weeks of treatment, doses of 5, 10, and 20 mg of simenafil exhibited substantial increases than placebo in IIEF-EF score (9.7, 9.2, 9.5 vs. 5.5, P < .001), the percentages of "yes" responses to SEP Q2 (36.11%, 30.79%, 33.12% vs. 19.56%, P < .01), and SEP Q3 (55.96%, 51.14%, 51.05% vs. 31.02%, P < .001). The incidence of adverse drug reactions was 36.5%, 44.3%, 45.9%, and 61.7% for the placebo, 5 mg, 10 mg, and 20 mg simenafil groups, respectively. Overall, the adverse events were generally mild or moderate. CLINICAL IMPLICATIONS:Simenafil could effectively improve erectile function and the adverse reaction profile of simenafil was consistent with its pharmacological mechanism, with most adverse reactions being mild to moderate. The results provide a rationale for further evaluation in larger and longer-term phase 3 clinical trials. STRENGTHS & LIMITATIONS:We did not conduct a head-to-head study comparing the efficacy and safety of simenafil with other PDE5 inhibitors. Meanwhile, we did not further analyze the efficacy and safety of simenafil in specific populations, such as ED patients with diabetes. CONCLUSION:Simenafil is an effective and well-tolerated treatment for men with ED.

Background:Previous studies on penile color Doppler ultrasound (CDU) examination after intracavernosal injection (ICI) have included a small number of patients and rarely focused on the effects of intracavernous communicating branches and persistent rigid erection. This study aimed to explore these issues using a large institutional database of erectile dysfunction (ED) patients. Methods:We conducted a retrospective study of 9,109 ED patients who underwent CDU examination after ICI with prostaglandin E1 (PGE1) at our Department of Andrology. Results:Obvious communicating branches between the bilateral cavernous arteries were observed in 200 patients, and the blood flow of the main trunk of the cavernous artery was significantly better than that of the main branch. Another 19 patients remained in a phase of persistent rigid erection and showed no obvious blood flow in at least one cavernous artery. Based on the peak systolic velocity (PSV) and end diastolic velocity (EDV), the remaining 8,890 patients were allocated to non-vascular, arterial, and venous ED groups. Based on the erection duration, the patients in the non-vascular ED group were allocated to persistent erection and non-persistent erection subgroups. The data of each group were standardized and statistically analyzed according to the age gradient. The PSV of the persistent erection, arterial ED, and venous ED groups showed a negative correlation with age, while the EDV of the arterial ED and venous ED groups showed a positive correlation with age. Conclusions:The CDU parameters were found to be correlated with age. Additionally, the communicating branches between bilateral cavernous arteries and persistent rigid erection significantly affected the CDU results.

BACKGROUND:Premature ejaculation (PE) is a highly prevalent male sexual dysfunction with undefined etiopathogenesis and a lack of validated objective biomarkers. Lifelong premature ejaculation (LPE) represents a more severe and persistent form of the disorder. Noninvasive plasma protein biomarkers for LPE diagnosis and their association with dapoxetine treatment outcomes remain insufficiently investigated. OBJECTIVES:This study aims to identify and validate novel plasma protein biomarkers for LPE via data-independent acquisition (DIA) proteomics, construct a diagnosis model and clinical nomogram, and explore the association between these biomarkers and clinical outcomes after dapoxetine treatment. METHODS:The study comprised a discovery phase and a validation phase from three centers. Initially, DIA proteomic analysis was performed on plasma samples from 5 LPE patients and 5 matched healthy controls. Differentially expressed proteins (DEPs) were identified and subsequently subjected to functional enrichment analyses, including GO, KEGG, and Reactome pathway analyses. Then, five core proteins were selected and validated using enzyme-linked immunosorbent assay (ELISA) in a larger cohort of 115 LPE patients and 60 healthy controls. LPE patients received 4-week on-demand dapoxetine treatment, with efficacy assessed by intravaginal ejaculatory latency time (IELT) and premature ejaculation diagnostic tool (PEDT) scores. The diagnostic model and the nomogram were constructed based on logistic regression, and the correlations between hub biomarkers and treatment efficacy were analyzed via the Spearman correlation analysis. RESULTS:Proteomic analysis identified 519 DEPs between groups, functionally enriched in neurotransmitter-related processes and metabolic pathways. ELISA validation confirmed significant differential expression of the five candidate proteins (PC, DDX39B, PPP2R2A, SLC8A2, HYI). The combined diagnostic model demonstrated excellent performance, with an area under the curve (AUC) of 0.902, superior to any single marker, and the derived nomogram showed excellent calibration and clinical net benefit. Furthermore, posttreatment levels of PC, DDX39B, PPP2R2A, and SLC8A2 were negatively correlated with IELT and positively correlated with PEDT scores, whereas HYI exhibited the opposite correlation pattern, suggesting that these biomarkers were associated with clinical outcomes after dapoxetine treatment. CONCLUSION:This study successfully identifies a panel of five plasma protein biomarkers for LPE, which not only facilitate accurate noninvasive diagnosis but also may be associated with clinical outcomes after dapoxetine treatment.

BACKGROUND:The brain plays a critical role in premature ejaculation (PE), but the specific regions involved remain unclear. This study aimed to identify functional brain network alterations in PE-like rats and investigate the modulatory effects of electroacupuncture (EA) at SP6. METHODS:Sixteen male Sprague-Dawley rats were divided into PE-like (n = 8) and control (n = 8) groups based on ejaculation frequency (EF). Copulatory behavior (EF, ejaculation latency [EL]), resting-state fMRI, and plasma norepinephrine (NE) were assessed at baseline and after 4 weeks of daily EA at SP6. Functional brain networks were constructed using graph theory, and nodal measures were compared between groups. RESULTS:PE-like rats exhibited significantly shortened EL and elevated plasma NE. Global network measures did not differ between groups. However, PE-like rats showed: (1) decreased nodal strength and betweenness centrality in hypothalamus; (2) decreased betweenness centrality in retrosplenial granular cortex zone a/postsubiculum; (3) increased clustering coefficient and global efficiency in RSD/RSGa; (4) decreased local efficiency in primary somatosensory and dorsal thalamic nucleus. EF and NE were negatively associated with dorsal thalamic nucleus local efficiency, while EL was negatively associated with hypothalamus strength and betweenness centrality. EA treatment significantly reduced EF and NE, prolonged EL, and normalized most nodal abnormalities; the improvement in dorsal thalamic nucleus local efficiency survived FDR correction. CONCLUSION:PE-like behavior in rats is associated with specific nodal alterations in hypothalamus, thalamus, and somatosensory cortex, alongside elevated NE. EA at SP6 was associated with partial normalization of these abnormalities, suggesting potential neuromodulatory mechanisms for PE, though causal relationships require further investigation.

This study evaluated the clinical value of penile sympathetic skin response (PSSR) in patients with non-organic erectile dysfunction (ED) and its correlation with psychological status. Based on the results of the nocturnal penile tumescence and rigidity (NPTR) test, the study included 68 patients with non-organic ED, 30 patients with organic ED, and 120 matched control subjects with normal erectile function. All subjects underwent PSSR testing to measure PSSR latency, International Index of Erectile Function-5 (IIEF-5) scores, and self-rating anxiety scale (SAS) scores. The results showed that the PSSR latency in patients with non-organic ED was significantly shorter than that in patients with organic ED and normal controls (NCs) (1179.12 ± 145.38 vs. 1420.00 ± 145.97 vs. 1382.00 ± 179.68 ms, p < 0.001). Furthermore, PSSR latency in patients with non-organic ED was negatively correlated with the SAS anxiety score (p < 0.001, r = −0.681) and positively correlated with the IIEF-5 score (p < 0.001, r = 0.493). Our study results suggest that patients with non-organic ED have excessive sympathetic excitation, and PSSR can be used as an objective electrophysiological indicator to assess autonomic nerve dysfunction, providing a rapid, non-invasive auxiliary tool for clinical differential diagnosis. This study is the first to reveal a significant association between PSSR latency and psychological anxiety, suggesting that enhanced sympathetic nerve activity may be an important pathological mechanism of non-organic ED.

Leydig cell (LCs) apoptosis is responsible for decreased serum testosterone levels during late-onset hypogonadism (LOH). Our study was designed to illustrate the regulatory effect of lncRNA XIST on LCs and to clarify its molecular mechanism of action in LOH. The Leydig cells (TM3) was treated by 300 μM H 2 O 2 for 8 h to establish Leydig cell oxidative stress model in vitro. The expression levels of lncRNA XIST in the testicular tissues of patients with LOH were measured using fluorescence in situ hybridization (FISH). The interaction between lncRNA XIST/SIRT1 and miR-145a-5p was assessed using starBase and dual-luciferase reporter gene assays. Apoptotic cells and Caspase3 activity were determined by flow cytometry (FCM) assay. Testosterone concentration was determined by ELISA. Moreover, histological assessment of testicles in mice was performed by using HE staining and the TUNEL assay was used to determine apoptosis. We found that the lncRNA XIST was downregulated in the testicular tissues of LOH patients and mice and in H 2 O 2 -induced TM3 cells. XIST siRNA significantly promoted apoptosis, enhanced Caspase3 activity and reduced testosterone levels in H 2 O 2 -stimulated TM3 cells. Further studies showed that the miR-145a-5p inhibitor reversed the effect of XIST-siRNA on H 2 O 2 -induced Leydig cell apoptosis. MiR-145a-5p negatively regulated SIRT1 expression, and SIRT1-siRNA reversed the effects of the miR-145a-5p inhibitor on H 2 O 2 stimulated TM3 cells. The in vivo experiments indicated that silencing of the lncRNA XIST aggravated LOH symptoms in mice. Inhibition of lncRNA XIST induces Leydig cell apoptosis through the miR-145a-5p/SIRT1 axis in the progression of LOH.

Background:Premature ejaculation (PE) is a common male sexual dysfunction with treatment limitations including side effects and partner dependency. Aim:To evaluate vacuum negative pressure hydropneumatic/pneumatic bubble massage (VNPHP/PBM) efficacy in primary PE (PPE) patients stratified by sexual frequency, focusing on subjective low-frequency (avoidance due to PE) vs objective low-frequency subgroups. Methods:Retrospective analysis of 42 PPE patients: 22 low-frequency (LF; <4 intercourse/month) including 13 subjective (sub-LF) and 9 objective (ob-LF) vs 20 non-low-frequency (NLF; ≥4/month). Outcomes:Primary: intravaginal ejaculation latency time (IELT); secondary: Premature Ejaculation Diagnostic Tool (PEDT), Self-Rating Anxiety Scale (SAS) scores, and sexual frequency changes at 4 weeks. Results:Both groups showed significant improvements in IELT, PEDT, and SAS scores (P < .05). Low-frequency group showed greater improvements than NLF in PEDT reduction (6.36 ± 2.38 vs 7.90 ± 2.02, P = .03), SAS reduction (30.95 ± 9.57 vs 38.45 ± 8.85, P = .01), and sexual frequency increase (0.50 [0.00, 4.00] vs 1.00 [1.00, 2.00], P = .02). Crucially, sub-LF patients exhibited dramatic sexual frequency normalization (6.00 [4.00, 7.50] vs 2.00 [1.00, 2.00], P < .001), while ob-LF unchanged (P = .56). No adverse events. Clinical implications:Vacuum negative pressure hydropneumatic/pneumatic bubble massage is a partner-independent therapy that not only improves ejaculatory control but also restores sexual activity in patients avoiding intercourse due to PE-related anxiety. Strengths and limitations:Strengths: First study analyzing subjective vs objective low-frequency PE, standardized protocols. Limitations: Retrospective design, self-reported IELT data, lack of a control group, and the non-blinded nature of the study. Conclusion:Vacuum negative pressure hydropneumatic/pneumatic bubble massage significantly improves PE symptoms with amplified benefits in low-frequency patients, particularly those with PE-driven sexual avoidance.

Background:Situational delayed ejaculation (SD-DE, intravaginal anejaculation phenotype) is a clinically significant disorder marked by preserved masturbatory function but persistent coital anejaculation. This condition substantially impairs quality of life and causes significant distress. The underlying neurophysiology, particularly autonomic mechanisms, remains unclear. This study aimed to investigate sympathetic function in SD-DE using penile sympathetic skin response (PSSR) and assess its clinical correlates. Methods:Sixty-seven SD-DE patients and 65 normal controls (NCs) were enrolled. PSSR latency and amplitude, penile sensory threshold (PST), and clinical characteristics (including psychological evaluations via the Self-Rating Anxiety Scale, SAS) were systematically analyzed to evaluate sympathetic nervous system function. Results:SD-DE patients exhibited significantly shorter PSSR latency compared to NCs (P<0.001), indicating sympathetic hyperactivity. A significant negative correlation was observed between PSSR latency and anxiety scores (P<0.001), suggesting stress-mediated sympathetic overactivation. SD-DE patients also demonstrated higher PST (P=0.03), increased masturbation frequency (>2 times/week: 38.81% vs. 20.00%, P=0.02), and a higher prevalence of atypical masturbation (28.36% vs. 3.08%, P<0.001), reflecting compensatory sensorimotor adaptations. Conclusions:These findings establish sympathetic dysfunction as a core feature of SD-DE [Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) 302.74], with PSSR serving as an objective biomarker. The intravaginal anejaculation phenotype represents a distinct clinical entity within DSM-5 302.74, informing targeted therapeutic strategies. In the future, it is necessary to further verify its pathological circuit mechanism by combining multimodal neuroimaging techniques.

Diabetes is a detriment to male reproductive health, notably through its capacity to diminish secretion from accessory glands such as the seminal vesicles and prostate, which are crucial for reproductive function. Curcumin, a naturally derived polyphenol renowned for its anti-inflammatory and antioxidative attributes, has demonstrated potential in mitigating tissue damage across various organs in diabetic patients. Despite its established benefits, the specific impact of curcumin on seminal vesicle damage in the context of diabetes remains underexplored. This investigation delves into the therapeutic potential of curcumin in ameliorating seminal vesicle damage in diabetic rats, thereby elucidating its underlying mechanisms. This study focused on twenty male SD rats divided into two distinct groups, a control cohort and a diabetic contingent, and employed a streptozocin (STZ)-induced type 1 diabetic rat model to ascertain seminal vesicle alterations secondary to diabetes. Ultrasonography was used to measure rat seminal vesicle sizes for comparison with postdissection measurements. This study revealed that (1) seminal vesicle volume and seminal fluid secretion were reduced in diabetic rats and (2) ultrasonography can predict seminal vesicle secretory dysfunction in diabetic rats, providing a theoretical basis for selecting animal models of diabetic seminal vesicle dysfunction for subsequent studies. Thirty male SD rats were subsequently divided into three groups: control, diabetic, and curcumin-treated. The curcumin group, which was subjected to a one-month-long intervention after STZ-induced diabetes onset, exhibited significant histological and functional recovery. Haematoxylin‒eosin (HE) staining revealed disordered seminal vesicle tissue structures and decreased epithelial cell height in diabetic rats, which was partially restored after curcumin treatment. Western blot and PCR results demonstrated that the expression levels of androgen receptor (AR) and aquaporin (AQP)8 in the seminal vesicle tissues of diabetic rats were decreased, whereas curcumin treatment led to increases in the expression levels of AR and AQP8. Seminal vesicle cells were cultured in vitro and divided into six groups: control, HG, HG-CUR-5 µM, HG-CUR-10 µM, HG-CUR-20 µM, and HG-CUR-50 µM. After 48 h of intervention, the fructose concentration in the culture medium was measured, and the expression of AR and AQP8 in the control, HG, and HG-CUR-20 µM groups was determined via Western blotting and PCR. The results revealed that the expression of AR and APQ8 in high glucose-treated seminal vesicle cells was decreased and that curcumin treatment upregulated the expression of AR and AQP8. After the addition of bicalutamide (an AR inhibitor), the expression of AQP8 was reduced. These findings suggest that curcumin may alleviate seminal vesicle damage in type 1 diabetic rats by activating the AR-AQP8 pathway.

OBJECTIVE:This study explored the gradient changes in structural similarity based on the cortical structure of patients with lifelong premature ejaculation (LPE) and further analyzed the characteristics of the associations between these changes and clinical phenotypes, gene expression profiles, and neurotransmitter distributions. MATERIALS AND METHODS:This study employed a novel method, morphological inverse divergence (MIND), to construct structural similarity gradients for 62 LPE patients and 53 healthy controls. Between-group comparisons were performed to examine the abnormalities in gradients among LPE patients. Partial least squares regression analysis explored the relationships between gene expression profiles and gradient changes, as well as neurotransmitter expression associations with these alterations. RESULTS:We found that both groups showed a classic unimodal-to-cross-modal transition along the principal gradient. In LPE patients, the principal gradient increased in the left visual cortex and right prefrontal regions but decreased in the right cingulate gyrus. The secondary gradient also decreased in the right somatosensory cortex and bilateral visual cortices. Notably, changes in these gradients in the right somatosensory and visual cortices were significantly negatively correlated with clinical phenotypes. Connectome-transcriptome analysis revealed that abnormal gradient patterns were linked to whole-brain gene expression profiles, with enriched genes in pathways related to hormone activity and other functions. Additionally, there was a spatial correlation between the gradients and neurotransmitter densities. CONCLUSION:We identified the biological pathways enriched in genes associated with the pathological process of LPE and characterized the distribution patterns of neurotransmitter receptors and transporters, thereby providing critical insights into the neuroimaging and neurobiological underpinnings of LPE. RELEVANCE STATEMENT:The MIND-based brain structural similarity gradient exhibits a pattern of segregation and integration. We analyzed the association between this structural gradient and the clinical phenotype of primary premature ejaculation, offering novel insights into the neuroimaging and neurobiological mechanisms underlying the disorder. KEY POINTS:We employed a novel approach, morphometric inverse divergence, to construct the brain structural similarity gradient. We provide evidence for abnormal structural similarity gradients in patients with LPE. We found an association between abnormal changes in gradients and clinical phenotypes, gene enrichment pathways, as well as neurotransmitter density.

Lifelong premature ejaculation (LPE) is associated with abnormal brain function, as evidenced by functional MRI (fMRI) studies. This study investigates the stability of brain network architectures in resting-state conditions following perturbation by erotic tasks in individuals with LPE. We assessed the resting-state fMRI in the task-free and task-modulated dataset in the 28 right-hand LPE and 17 age-matched normal controls (NCs). The dynamic functional connectome based on the phase-locking algorithm and ROI-wise gradient mapping was compared. The stability of dynamic functional gradient mapping was measure by linear mixed effects across the two datasets in the LPE and NCs. In both groups, the brain functional gradient exhibited a clear transition from unimodal to transmodal in the principal gradient. Additionally, there was a segregation of primary networks observed in the secondary gradient, either before or after the task. In LPE patients, we observed increased stability in the bilateral dorsal prefrontal cortex (p < 0.05, Bonferroni corrected) and right temporo-occipital-parietal cortex (p < 0.05, Bonferroni corrected) between the pre- and post-task fMRI datasets. The changes of the gradient stability were significantly correlated with the sexual behavior. Our findings suggest that dysfunction in the salience and default mode networks may contribute to delayed recovery from erotic task stimulation in LPE patients.

To compare brain activation in the dopaminergic reward system between 26 LPE patients and 16 normal controls (NCs) via glans penis electric stimulation task-fMRI and resting-state fMRI (rs-fMRI). The beta value, degree centrality (DC), and functional connectivity (FC) were calculated. The Pearson correlation was used to analyze the correlation between the fMRI measurements and disease severity. After task-fMRI, PE patients had significantly higher beta values in the dopaminergic reward system, including the bilateral thalamus and inferior frontal gyrus than NCs. In the rs-fMRI, higher DC values in the bilateral supplementary motor area (SMA) and lower DC values in the bilateral precuneus were found. Furthermore, our results showed enhanced FC between the right inferior frontal gyrus and the bilateral SMA and decreased FC between the bilateral precuneus and bilateral thalamus after electrical stimulation. The sensitivity was 80.77%, the specificity was 81.25%, and the AUC was 0.83 (p < 0.001) when differentiating the PE and NC using the FC between the inferior frontal gyrus and SMA. The sensitivity was 73.08%, the specificity was 75.00%, and the AUC was 0.82 (P = 0.002) when differentiating the two groups using the FC between the precuneus and thalamus.

OBJECTIVE:To explore the clinical effect of sexual therapy combined with physical methods in the treatment of primary intravaginal anejaculation (PIAE) and its possible action mechanism. METHODS:Ninety PIAE patients with anxiety symptoms were equally randomized into three groups and treated by sexual therapy combined with vacuum negative pressure hydro pneumatic / pneumatic bubble massage (group A), sexual therapy (group B) or (vacuum negative pressure hydro pneumatic / pneumatic bubble massage (group C). After 15 cycles of treatment, the therapeutic effects were compared among the three groups of patients. RESULTS:The effectiveness rates in groups A, B and C were 86.67%, 46.67% and 30.00%, respectively, with statistically significant differences in the total effectiveness rate, the effective rate of the treatment of anxiety symptoms of the patients and their partners, and the effectiveness rate of the treatment of idiosyncratic masturbation (P<0.05). Pairwise comparison showed that the total effectiveness rate was dramatically higher in group A than in groups B and C (P<0.01), with no statistically significant difference between the latter two groups (P>0.05), that the effectiveness rate of the treatment of anxiety symptoms of the patients and sexual partners was remarkably higher in groups A and B than in C (P<0.01), with no statistically significant difference between the former two groups (P>0.05), and that the effectiveness rate of the treatment of idiosyncratic masturbation was significantly higher in group A than in B and C (P< 0.01), with no statistically significant difference between the latter two (P>0.05). CONCLUSION:PIAE is often accompanied by negative psychological state of the patients and their partners and idiosyncratic masturbation, which responds well to sexual therapy combined with vacuum negative pressure hydro pneumatic / pneumatic bubble massage.

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.

Peyronie’s disease (PD) is a disorder characterized by fibrous plaque formation in the penile tissue that leads to curvature and complications in advanced stages. In this study, we aimed to compare four injectable induction agents for the establishment of a robust rat model of PD: transforming growth factor-β1 (TGF-β1), fibrin, sodium tetradecyl sulfate (STS) combined with TGF-β1, and polidocanol (POL) combined with TGF-β1. The results showed that injection of TGF-β1 or fibrin into the tunica albuginea induced pathological endpoints without causing penile curvature. The STS + TGF-β1 combination resulted in both histological and morphological alterations, but with a high incidence of localized necrosis that led to animal death. The POL + TGF-β1 combination produced pathological changes and curvature comparable to STS + TGF-β1 and led to fewer complications. In conclusion, fibrin, STS + TGF-β1, and POL + TGF-β1 all induced PD with a certain degree of penile curvature and histological fibrosis in rats. The POL + TGF-β1 combination offered comparatively greater safety and clinical relevance and may have the greatest potential for PD research using model rats.

Type 2 diabetes mellitus (T2DM) can trigger cell apoptosis of seminal vesicles (SVs) and impair seminal secretory functions. Complanatuside A (CA) is known for its anti‐inflammatory and antioxidant effects, as well as its ability to repair cellular damage. This study aimed to explore the potential molecular mechanisms through which CA mitigates cell apoptosis in the SVs of type 2 diabetic mice. A streptozotocin‐induced type 2 diabetic mice model was utilized, and a 1‐month intervention using CA (70 mg/kg) was administered. We monitored body weight, blood glucose levels, SV volume, and concentration of SV fluid. Hematoxylin and eosin staining was used to assess tissue damage. RNA sequencing was applied to identify differential gene expression, and the expression of target genes (ARG2, PBK, SerpinB1a, E2F2) was verified by qRT‐PCR. Changes in the apoptosis level of SV tissues in mice were detected with TUNEL staining. Compared to the control group, mice with T2DM exhibited decreased SV volume and SV fluid content, which was improved with CA treatment. Elevated expression of SerpinB1a and reduced apoptosis were observed in the T2DM‐CA group compared to T2DM mice. In summary, CA can inhibit cell apoptosis in the SVs, there by improving tissue damage in type 2 diabetic mice. SerpinB1a may be involved in this process. This study provides a new theoretical foundation for the treatment of seminal vesicle secretory dysfunction in type 2 diabetes mellitus.

The long-term safety and effectiveness of once-daily tadalafil is crucial, but limited data are available in Chinese patients with erectile dysfunction (ED). In this post-marketing, multicenter, randomized, open-label trial with 2-year follow-up, 635 ED cases were randomized to receive daily oral tadalafil 2.5 mg or 5 mg for 3 months, of whom 580 continued once-daily tadalafil 5 mg for 21 months. Treatment-emergent adverse events in the 12-month and 24-month period were similar, with the most common being viral upper respiratory tract infection, upper respiratory tract infection, and headache. Significant improvement from baseline in the International Index of Erectile Function-Erectile Function (IIEF-EF) score was detected at month 12 (least squares mean [LSM] change: 7.9, 95% confidence interval [CI]: 7.5–8.4, P < 0.001) and was maintained to month 24 (LSM change: 8.6, 95% CI: 8.1–9.0, P < 0.001). The proportions of patients regaining normal erectile function (IIEF-EF score ≥26) were 43.7% and 48.0% at months 12 and 24, respectively. Global Assessment Questionnaire results showed improved erection function in 97.5% of patients and improved ability to engage in sexual activity in 95.9% of patients at month 12; these values were 96.1% and 95.0% at month 24, respectively. The quality of sexual life score based on the Sexual Life Quality Questionnaire (SLQQ) was increased by 52.2% at month 12 and by 55.3% at month 24 (both P < 0.001). The treatment satisfaction score determined by SLQQ (mean ± standard deviation) was 62.4 ± 21.0 at month 12 versus 65.9 ± 20.2 at month 24. Two-year daily application of tadalafil 5 mg in Chinese men with ED showed a favorable safety profile and durable improvement in sexual performance and satisfaction.

By observation of Sprague-Dawley male rats with different ejaculatory behaviors, we have identified distinct behavioral characteristics in rapid ejaculator rats. To validate these differential behaviors, we conducted multifaceted behavioral experiments on rapid ejaculator rats and normal rats. Through mating experiments, 42 male rats were categorized into 5 rapid ejaculator rats, 29 normal ejaculator rats, and 8 sluggish ejaculator rats according to their ejaculation frequency. We selected 5 rats exhibiting rapid ejaculation and 5 rats with normal ejaculation for participation in the Morris water maze, open-field test, and balance beam experiments. The open-field tests revealed that rapid ejaculator rats spent shorter time in the center region (1.23 +/- 1.21 vs. 6.56 +/- 2.40 s, P = 0.0041), less entered the center region (0.80 +/- 0.75 vs. 3.40 +/- 1.50, time, P = 0.0145), traveled shorter distances (17,003.77 +/- 3339.42 vs. 25,037.90 +/- 5499.94 mm, P = 0.0371), and had a lower average speed compared with normal rats (66.09 +/- 62.36 vs. 195.56 +/- 83.41 mm/s, P = 0.0377). However, no significant differences were observed in the Morris water maze and balance beam experiments (0.25 +/- 0.05 vs. 0.26 +/- 0.07, P = 0.7506;16.40 +/- 3.77 vs. 16.25 +/- 2.05, P = 0.9515). These behavioral results indicated that the rapid ejaculator rats were more prone to anxiety. To further substantiate this claim, we examined Brain-derived neurotrophic factor expression levels in the hippocampus of rat brains using immunohistochemistry and western blotting. The results demonstrate lower Brain-derived neurotrophic factor expression in the hippocampus of rapid ejaculator rats compared with that in normal rats (P = 0.0093). Thus, our experiments indicate that rapid ejaculator rats exhibit a higher propensity for anxiety, potentially linked to their abnormal neurophysiologic state. It is concluded that rapid ejaculator rats may be more susceptible to anxiety on a pathophysiological basis.

Purpose: This study aimed to compare the risk of vagal reflex during microsurgical subinguinal varicocelectomy (MSV) under general anesthesia (GA) with or without additional local anesthetic (LA) spermatic cord block (SCB). Method: A single-center randomized controlled trial was conducted between January 2022 and June 2023.300 patients with left-sided grade Ⅲ varicocele were randomly divided into two groups: SCB group (n = 153) and control group (n = 147)（computer-generated random numbers list）. During MSV under GA, the SCB group was given of ropivacaine for SCB before pulling the spermatic cord, while the control group was directly lifted. The primary outcome was the reduction in the lowest heart rate in the SCB group as compared with the control group during spermatic cord traction (SCT). Secondary outcomes included the reduction in the lowest blood pressure in the SCB group as compared with the control group; and the reductions in the lowest heart rate and lowest blood pressure as compared with baseline during SCT. The number of times that surgery and medications were suspended because of symptomatic reflex bradycardia was also recorded. Adverse events were also recorded as secondary outcomes. Result: Five patients in the SCB group and 10 patients in the CG were excluded. The lowest heart rate and systolic blood pressure during SCT in the SCB group and the control group were significantly lower than the baseline values (P < 0.05). However, the decrease in the SCB group (70-73bpm VS 108–115 mmHg) was milder than that of the control group（66–72 bpm VS 105–114 mmHg）(P < 0.05). The number of surgeries and medication pauses due to symptomatic reflex bradycardia during surgery was significantly lower in the SCB group (2 VS 1) than in the control group (9 VS 7) (P < 0.05). Conclusion: SCB can effectively reduce the vagal reflex caused by pulling the spermatic cord during MSV, and reduce the risk of anesthesia and surgery.