Stromal vascular fraction (SVF), an uncultured adipose-derived cell population, exerts regenerative effects primarily through paracrine mechanisms. While local intratesticular injection of SVF alleviates busulfan-induced testicular injury, the intravenous route remains unexplored. This study investigated whether intravenous SVF administration could mitigate busulfan-induced spermatogenic impairment. Adult male Sprague-Dawley rats received busulfan (15 mg/kg, intraperitoneal) or vehicle; the busulfan + SVF group received 2 × 106 allogeneic SVF cells intravenously immediately after busulfan injection. Two weeks later, we evaluated sperm parameters, testicular histopathology (Johnsen’s score, seminiferous tubule diameter, germinal epithelial thickness), and immunohistochemical expression of SOX9 (Sertoli cells), CYP11A1 (Leydig cells), and DDX4 (germ cells). Busulfan alone induced severe spermatogenic defects, including reduced sperm count and motility, increased abnormal morphology, marked histopathological damage, and decreased expression of SOX9, CYP11A1, and DDX4. In contrast, intravenous SVF treatment significantly improved sperm count, motility, and testicular architecture, and restored the expression of SOX9, CYP11A1, and DDX4 within two weeks. This is the first demonstration that intravenous SVF attenuates early busulfan-induced testicular injury, providing preliminary evidence for a rapid, culture-free approach as a less invasive alternative to local injection. However, longer follow-up and fertility studies are needed to confirm sustained spermatogenic restoration.

Lactate accumulates in large amounts in tumor cells due to the Warburg effect. However, the role of lactate-mediated lactylation, a post-translational modification, in regulating tumor immunity remains unclear. Here, we report that lactate-driven lactylation of STAT1 K193 inhibits interferon (IFN)-γ signaling pathway-mediated tumor immunity. Mechanistically, AARS1 lactylates STAT1 K193 and inhibits its binding to JAK2 and phosphorylation, thereby disrupting tumor responsiveness to IFN-γ, which leads to a reduction in the expression of downstream chemokines, including CXCL9, CXCL10, and CXCL11, ultimately facilitating immune escape of the tumor. Furthermore, we developed a cell-penetrating peptide, K193-pe, that can competitively inhibit STAT1 K193 lactylation and re-sensitize tumor cells to IFN-γ signaling, thus enhancing CD8+ T cell recruitment and improving the efficacy of immune checkpoint blockade therapy. Collectively, this study elucidates the functional significance of STAT1 K193 lactylation in tumor immunity and suggests that targeted inhibition of this modification, when paired with immunotherapy, may offer a viable treatment strategy.

INTRODUCTION:Premature ejaculation (PE) is one of the most prevalent male sexual disorders, with lifelong PE (LPE) affecting ~cx3%-5% of men. While peripheral, psychological, and relational factors are well-known contributing factors, accumulating neuroimaging and electrophysiological evidence suggests central neural mechanisms, including serotonergic, dopaminergic, and other neuromodulatory pathways play a role. OBJECTIVES:To synthesize findings from neuroimaging and electrophysiological (electroencephalography) studies, providing an integrative perspective on the neural substrates of LPE and identifying gaps for future research. METHODS:A narrative review was conducted based on 43 original studies reporting structural-, functional-, and network-level neural correlates of LPE. The literature search and selection were performed in accordance with the Scale for the Assessment of Narrative Review Articles guidelines to ensure transparency and methodological rigor. Studies were categorized by modality, and findings were qualitatively synthesized to identify convergent patterns, regional alterations, and clinical correlations. RESULTS:Structural neuroimaging in LPE patients consistently demonstrates altered gray matter volume, cortical thickness, and white matter microstructure in prefrontal, orbitofrontal, striatal, thalamic, limbic, and temporal regions. Functional analyses reveal reduced top-down inhibitory control from prefrontal regions, hyperconnectivity within limbic-temporal sensory circuits, and dysregulated network dynamics across cortico-striato-thalamic pathways. Electroencephalography studies indicate abnormal cortical excitability and high-beta responses in frontal and temporal regions during sexual arousal. Multimodal studies show these neural alterations correlate with clinical severity, and machine learning models achieve high accuracy in differentiating LPE patients from healthy controls. CONCLUSIONS:LPE is associated with distributed neural network dysfunction, characterized by impaired inhibitory control, exaggerated sensory processing, and dysregulation of serotonergic, dopaminergic, and other neuromodulatory systems. Although central changes may be both a cause and a consequence of LPE, these findings primarily advance mechanistic understanding and should be considered research-level indicators rather than diagnostic biomarkers.

This cross-sectional study aimed to validate the male version of the Orgasmometer in Mandarin and to examine whether Chinese men with premature ejaculation (PE) experience reduced orgasmic intensity. From September 2020 to January 2023, a group of 230 men with PE (mean age=28.2 ± 4.8) and 107 men without sexual dysfunction (mean age= 35.1 ± 6.7), who were seeking help from the Department of Infertility and Sexual Medicine, underwent a detailed assessment from the andrologist and completed a questionnaire that included the Mandarin Orgasmometer (Orgasmometer-m), the Premature Ejaculation Diagnostic Tool (PEDT), and the erectile function domain of the International Index of Erectile Function (IIEF-6). Orgasmometer-m scores were 5.0 (4.0) in the PE group and 8.0 (3.0) in the non-PE group; PEDT scores were 14.8 ± 2.5 and 3.3 ± 2.4, and IIEF-6 scores were 27.9 ± 1.6 and 29.1 ± 1.2, respectively (p < 0.001). The Orgasmometer demonstrated good discriminative validity, with an area under the curve (AUC) of 0.8296 (95% CI: 0.7873–0.8719, p < 0.0001). A score of ≤6 was identified as the optimal cutoff for distinguishing low from high orgasm intensity, yielding 66.1% sensitivity and 86.9% specificity. These findings support the reliability of the Orgasmometer-m and suggest that men with PE report diminished orgasmic experiences.

Introduction:Peyronie's disease (PD) and erectile dysfunction (ED) are prevalent and frequently coexisting male sexual disorders that share endothelial dysfunction, oxidative stress, and tunical fibrosis as common pathophysiologic pathways. Recognizing their interconnected nature has reframed both conditions within a unified model of penile vascular-fibrotic disease. Objectives:To synthesize recent advances in the mechanistic, diagnostic, and therapeutic understanding of PD and ED, and to propose an integrated framework for comprehensive sexual medicine care. Methods:A integrative narrative review of contemporary clinical studies, translational studies, molecular studies and guideline recommendations was conducted to evaluate epidemiologic trends, shared molecular mechanisms, and evolving therapeutic modalities addressing both PD and ED. Results:Up to 60% of PD patients experience concomitant ED. Both disorders are linked by endothelial nitric oxide synthase dysregulation, oxidative stress, and transforming growth factor-β1-mediated fibrosis. Diagnostic evaluation now integrates penile duplex Doppler ultrasonography, elastography, and psychometric tools to assess vascular, structural, and psychosexual domains. Therapeutic strategies increasingly adopt multimodal approaches: phosphodiesterase-5 inhibitors improve hemodynamics and may attenuate early fibrotic activity; intralesional therapy remains central to nonsurgical management, with collagenase Clostridium histolyticum as the established standard for plaque remodeling and adjunct injectables such as verapamil, interferon-α2b, and hyaluronic acid providing additional anti-inflammatory or antifibrotic benefits, particularly in the active phase; and low-intensity shockwave therapy promotes angiogenesis and tissue recovery. Regenerative therapies-including stem cell, exosome, and gene-targeted interventions-offer promising disease-modifying potential. Surgery (plication, grafting, or prosthesis implantation) remains definitive for refractory cases, complemented by psychosexual rehabilitation. Conclusions:PD and ED represent a shared vascular-fibrotic spectrum requiring integrated, mechanism-driven management. Emerging regenerative and molecular therapies, supported by artificial intelligence-assisted diagnostics and digital health tools, signal a paradigm shift toward personalized, holistic restoration of structure, function, and intimacy.

Intravaginal ejaculation latency time (IELT) is traditionally considered a stable parameter in premature ejaculation (PE), although recent findings suggest that physiological, behavioural and contextual factors may influence it. This cross-sectional study assessed intraindividual variations in self-reported IELT among 119 men with PE, examining the effects of time of day, sexual position, alcohol consumption, condom use and foreplay duration. Participants completed validated questionnaires and provided IELT estimates across multiple conditions. Masturbation latency (MELT) was significantly longer than vaginal IELT (Z = 7.53, p = 3.0 × 10⁻¹⁴). Daily longest and morning IELT were significantly higher than the "average" IELT (Z = 4.06, p = 4 × 10⁻⁵; Z = 3.95, p = 8 × 10⁻⁵), whereas the shortest IELT did not differ significantly (Z = -1.26, p = 0.206). No sexual position emerged as significantly more likely to be associated with the longest or shortest IELT, although position-related IELT differences were reported (longest IELT: Z = 4.97, p = 6.7 × 10⁻⁷; shortest IELT: Z = -6.00, p = 2.0 × 10⁻⁹). IELT increased significantly after alcohol consumption (Z = 4.84, p = 1.3 × 10⁻⁶) and condom use (Z = 4.56, p = 5.1 × 10⁻⁶), while foreplay duration showed minimal impact (p = 9.3 × 10⁻⁸). These findings challenge the assumption of IELT as a fixed diagnostic parameter and highlight the influence of contextual and behavioural factors.

INTRODUCTION:Disorders of ejaculation and orgasm (DEO) in men are poorly understood and can pose a substantial burden to men and their sexual partners. OBJECTIVES:Under the aegis of the International Consultation on Sexual Medicine, a multinational, multidisciplinary panel of experts was convened to review the world literature and generate a consensus on management of DEO in men. This document represents a summary of the panel's report on physiology of ejaculation and orgasm, mental health conditions, and specific DEO that are not related to the timing of climax (ie, premature and delayed ejaculation). METHODS:Narrative review of existing literature and consensus recommendations from the expert panel. RESULTS:The processes of ejaculation and orgasm are complex and include neuronal and hormonal factors as well as psychological and interpersonal dynamics. Care of the patient presenting with a potential DEO centers on sensitive history taking and selective testing. Declines in semen volume may occur naturally with age and can be seen in the context of medical or surgical therapies. Pain with ejaculation/orgasm has a myriad of potential etiologies and may be part of a complex chronic pelvic pain syndrome; assessment for related diagnoses that may be contributory is warranted. Hematospermia can be distressing but is often benign; management when indicated is geared toward detecting potentially reversible etiologies. Climacturia is a troublesome condition of urine loss common after prostate surgeries; Behavioral and physical therapy and surgical intervention may be of value in these cases. Management strategies for anhedonic orgasm and post-orgasmic illness syndrome are not well established. Dhat is a complex syndrome oftentimes centered around pathological fear of semen loss that is best managed with a sensitive and culturally appropriate focus. CONCLUSIONS:An understanding of the processes of ejaculation and what is known about DEO can aid clinicians and researchers in providing optimal care.

Purpose: To propose a novel surgical approach for managing inflammatory adhesions of the tunica vaginalis (TV) during vasoepididymostomy (VE), and to report surgical outcomes. Materials and Methods: A T-shaped incision of the TV was used to expose the epididymis and vas deferens in cases with adhesions between the TV and the testis. We retrospectively analyzed data from five patients who underwent microsurgical VE for obstructive azoospermia (OA) secondary to epididymal obstruction. Operative time, postoperative patency rate and semen analysis, and natural pregnancy rates were recorded. For comparison, 50 patients who underwent conventional longitudinal TV incision were included to assess operative time, while 46 and 36 of these patients were used to compare patency and pregnancy rates, respectively, with the T-shaped incision group. Results: The T-shaped incision involves a longitudinal incision of the TV at the epididymal-testicular junction followed by an incision (T) in the direction towards the epididymis and vas deferens area. Among the five patients who underwent this approach, four (80.0%) had sperm detected in semen two months postoperatively, and their partners achieved natural pregnancy (4/5, 80.0%) within one year after VE. No postoperative wound infections occurred. No statistically significant differences were observed in mean operative time, patency rates, or pregnancy rates between the T-shaped and longitudinal incision groups. Conclusions: The T-shaped TV incision is a feasible approach for VE in OA patients with inflammatory TV-testis adhesions, providing adequate epididymal access without compromising operative time or surgical outcomes.

Hard-flaccid syndrome (HFS) is a rare condition characterised by a semi-rigid penis in the flaccid state, often accompanied by perineal and urinary symptoms. It may also induce psychological distress, which can exacerbate physical symptoms, creating a vicious cycle. There is currently no standardised treatment for HFS, and management typically focuses on addressing both the underlying causes and presenting symptoms. A systematic review of the literature identified 8 eligible studies. Although the exact aetiopathogenesis remains unclear, it is hypothesised that an initial penile trauma may trigger a cascade of neurovascular and inflammatory events. The associated psychological impact may further perpetuate symptoms, reinforcing the cycle of dysfunction. Common symptoms include perineal pain, urinary disturbances, and erectile and ejaculatory dysfunction. Evaluation involves a comprehensive clinical history, relevant blood and radiological investigations to exclude other pathologies, and the use of symptom questionnaires. Reported treatments include phosphodiesterase-5 inhibitors, anxiolytics, low-intensity shockwave therapy, pelvic floor physical therapy, spinal surgery, and biopsychosocial therapy. Management should be individualised, with a focus on relieving symptoms and breaking the self-perpetuating cycle of HFS. Further evidence-based studies are needed to better understand the pathophysiology of HFS, as well as to develop clear diagnostic criteria and management guidelines.

Background:Men who have not engaged in vaginal intercourse in the past 6 months or have never engaged in it often seek help for sexual dysfunction, identifying factors influencing patients' self-assessment of sexual function and the value of masturbation-related parameters in diagnosing sexual dysfunction is of great importance. Aim:This study aims to understand the reason why patients self-report sexual dysfunction and evaluate the role of masturbation parameters in diagnosing sexual dysfunction in self-reported sexual dysfunction (SRSD) and self-reported no sexual dysfunction (SRNSD) groups. Methods:Our study was conducted mainly by filling out a questionnaire, which collected demographic information, sexual history as well as sexual parameters. The questionnaire summarized the basis of patients' self-reported sexual dysfunction and also included the Erection Hardness Score (EHS), Masturbation Erection Index (MEI), Masturbatory Premature Ejaculation Diagnostic Tool (MPEDT), and masturbatory ejaculation latency time (MELT). Outcomes:The main outcomes were reasons for SRSD individuals to judge their sexual dysfunction, the EHS, MEI, MPEDT, and MELT scores. Results:The most common complaints included insufficient erection hardness and short ejaculation latency time during masturbation, with 84.85% of self-reported erectile dysfunction and 91.80% of self-reported premature ejaculation patients reporting these issues. No significant difference was found between past vaginal sexual experiences (6 months ago) and current self-reported sexual dysfunction. Significant differences were found in EHS, MEI, MPEDT, and MELT scores between the SRSD and SRNSD groups. The MEI showed a sensitivity of 89.29% and a specificity of 81.82%. The MPEDT demonstrated a sensitivity of 98.04% and a specificity of 72.73%. Clinical Implications:We proposed that other than vaginal intercourse, sexual dysfunction should also be assessed from noncoital sex and verified the scientific validity of the masturbation parameters in people without recent vaginal intercourse. Strengths & Limitations:We firstly explored the patients self-perceived basis for sexual dysfunction. However, the objective instruments were not employed in diagnosing sexual dysfunction. Conclusion:The findings emphasize the importance of a comprehensive clinical assessment that includes evaluating masturbation, noncoital sex (between men and women), morning erections, and past vaginal sexual experiences (6 months ago), moreover, masturbatory scales provide valuable insights in diagnosing sexual dysfunction.

BACKGROUND:Grading premature ejaculation (PE) may hold significant value. However, although previous studies have attempted to achieve a uniform severity scale for PE, this has not been widely accepted since design and methodological limitations. OBJECTIVES:In patients with lifelong PE (LPE), we re-evaluated the items suitable for severity grading and established the appropriate severity classification reference through reasonable statistical methods and logic. MATERIALS AND METHODS:Patient perceived intravaginal ejaculatory latency time (PIELT) and premature ejaculation diagnostic tool (PEDT) scores from 264 men (149 with LPE and 115 without PE) were used to analyze surrogate item suitable for classification. Classification and Regression Trees were used to determine the optimal score interval for different severity levels in patients with LPE. RESULTS:For the LPE population with PIELT < 3.5 min, PIELT had no value in the classification of severity of LPE patients. PEDT items 1 and 4, showing high correlation (0.84 and 0.89, respectively) with PEDT total score, reflect the physical and mental effects of LPE patients in terms of ejaculatory control and interpersonal relationship. These items may serve as proxy for the severity scale of LPE patients. Hence, patients diagnosed with LPE can be classified into the following grades based on PEDT scores: mild (11-14), moderate (15-17), severe (18-20). Substantial agreement was shown between these predicted and "true" classes (weighted kappa 0.71). DISCUSSION:Assessing LPE according to three dimensions is a widely accepted definition. While PIELT showed no statistically significant differences in the classification (p > 0.05), the two subjective dimensions of ejaculation control and negative psychological influence did predict the severity grading of LPE. Not only can grading the subjective feelings of patients with LPE help them to self-assess the extent of the disease, but also provide a valuable reference for further treatment. CONCLUSION:Within the PIELT of 3.5 min, the severity of LPE can be classified into severe, moderate, and mild categories based on the PEDT score.

Background: Microsurgical 2-layer vasovasostomy is a commonly used technique to treat vasal obstruction in male infertility, and optimizing the surgical approach has important clinical implications. Objective: To compare the differences between stent-assisted vasovasostomy and the conventional technique in terms of operative time, vasal patency rate, and reproductive function. Materials and Methods: This experimental study included 54 male Sprague-Dawley rats (8–9 wk, 300 ± 15 gr) and 12 female rats (7–8 wk, 250 ± 13 gr, used for co-housing experiments). The male rats were randomly assigned to 3 groups (n = 18/each): control groups, conventional groups, and stent groups. Postoperative assessments were performed at 2, 5, and 8 wk, including operative time, vasal patency rate, morphological changes (such as epithelial integrity and granuloma formation), immune response (serum immunoglobulin G and anti-sperm antibodies), and reproductive function (semen quality, pregnancy rate, and reproductive hormone levels). Results: The average operative time in the stent group was significantly shorter than in the conventional group (28.8 ± 5.2 min vs. 70.4 ± 4.0 min, p < 0.001). The vasal patency rates were 100% and 91.7%, and the pregnancy rates were 83.3% and 75.0% in the stent-assisted and conventional groups, respectively. No statistically significant differences were observed between the 2 groups in terms of immune response (serum immunoglobulin G, anti-sperm antibodies), semen parameters, or reproductive hormone levels. Histological examination showed that most anastomotic sites exhibited good structural integrity without marked inflammation, with only one rat showing mild granuloma formation. Conclusion: The absorbable protein stent shortens the operative time of vasovasostomy while maintaining favorable patency and reproductive outcomes. It shows promising potential for optimizing microsurgical vasovasostomy in clinical practice.

Objective To evaluate the efficacy and tolerance of tamoxifen(TAM)in the treatment of idiopathic oligozoospermia.Methods Clinical data of 123 patients diagnosed with idiopathic oligozoospermia in Department of Sterility and Sexual Medicine of the Third Affiliated Hospital of Sun Yat-sen University from February 1,2021 to August 30,2023 were retrospectively analyzed.All patients with a sperm density of＜15×106/mL were treated with 10 mg TAM twice a day for 4 months or longer.The changes of semen(n=123)and serum hormones(n=71)were assessed in patients with idiopathic oligozoospermia treated with TAM.The efficacy of TAM for oligozoospermia was evaluated.Sperm parameters and hormones among different groups were compared by Friedman test,and two-group comparison was performed by Bonferroni's correction.Results After treating 3 and 4 months,the sperm density(Z=7.428,5.101;both P＜0.05)and the total number of sperm(Z=6.280,3.379;both P＜0.05)in patients with idiopathic oligozoospermia were increased compared with those before treatment.Compared with treating for 3 months,the total number of sperm was decreased after treating for 4 months(Z=-2.901,P=0.011).Compared with before treatment,the total sperm motility tended to increase after 3-and 4-month TAM treatment,but the differences were not statistically significant(Z=4.503,P=0.105).Compared with before treatment,the serum testosterone levels(Z=5.203,4.238;both P＜0.05)and the estradiol levels(Z=3.944,3.734;both P＜0.05)were increased after 3-and 4-months TAM treatment.Compared with before treatment,the improvement rate of sperm density was 62.6%(77/123)after 3 months TAM treatment and 49.6%(61/123)after 4 months TAM treatment.Conclusions TAM can enhance the sperm density and total number of sperm in patients with idiopathic oligozoospermia.However,special attention should be paid to the efficacy and tolerance of TAM treatment.

Erectile dysfunction (ED) is a prevalent condition affecting male sexual health, characterized by the inability to achieve or maintain satisfactory erections. ED has a multifactorial pathogenesis in which psychological, hormonal, neurologic, cardiovascular, and lifestyle factors all contribute to a progressive decline of erectile function. A critical underlying mechanism involves oxidative stress (OS), an imbalance between reactive oxygen species (ROS) production and antioxidant defenses, which disrupts endothelial function, reduces nitric oxide (NO) bioavailability, and contributes to vascular dysfunction. This narrative review explores the interplay between OS and ED, focusing on the roles of ROS sources such as NADPH oxidase, xanthine oxidase, uncoupled nitric oxide synthase, and mitochondrial dysfunction. It examines the impact of OS on chronic conditions like hypertension, diabetes mellitus, hyperlipidemia, hypogonadism, and lifestyle factors like smoking and obesity, which exacerbate ED through endothelial and systemic effects. Emerging research underscores the potential of antioxidant therapies and lifestyle interventions to restore redox balance, improve endothelial function, and mitigate ED’s progression. This review also highlights gaps in understanding the molecular pathways linking ROS to ED, emphasizing the need for further research to develop targeted therapeutic strategies.

PURPOSE:To estimate the prevalence of Erectile dysfunction (ED) in a Hong Kong (HK) population, evaluate the understanding and perception of ED and compare results with the European Association of Urology (EAU) and The Urology Foundation Trust (TRTed-TUF) data. METHODS:A survey-based study was conducted between Dec 2023 and Mar 2024. The EAU and TRTed-TUF surveys were used as a template to design the current survey to ensure consistent reporting. Questions on the understanding of ED, healthcare seeking behaviour and awareness of treatment options were included. The survey was distributed via an online link to students and staff from The Hong Kong University (HKU) and to patients attending outpatient clinics at HKU Queen Mary Hospital. RESULTS:616 responses were received from men aged 18-81 years. The prevalence of ED in our population was 51.8%. 53.2% (EAU 33.6%) were incorrect about what ED is, 54.0% (EAU 56.5%) knew that ED could be treated and 26.4% (TRTed-TUF 22%) were aware that ED could be a sign of heart disease. 73.6% (EAU, 26.3%) do not talk with anyone about ED. 88.3% (TRTed-TUF 77%) would be more likely to seek help if they knew ED was a sign of heart disease. Up to 32.6% (EAU 17.2%) have heard of alternative therapies to oral phosphodiesterase-5 inhibitors. CONCLUSIONS:ED awareness is low, and it is important to raise awareness possibly through charity campaigns, social media and education in primary care in order to detect underlying cardiovascular disease and reduce the impact of ED on psychosocial health.