During meiosis, ZMM proteins play essential roles in stabilizing the recombination intermediates and promoting crossover (CO) formation. In mice, shortage in chiasmata 1 (SHOC1) forms a trimeric complex with the other two ZMM proteins, SPO16 and TEX11, to bind recombination intermediates after strand invasion. Although genetic variants of SHOC1 are clinically associated with male infertility, their conserved functions in human gametogenesis remain enigmatic. Here, we delineated species-specific divergences between human and mouse SHOC1 complex and identified a missense variant within the XPF-like domain in SHOC1 (p.Q590R). This variant impaired DNA double-strand breaks repair by compromising its ability to bind branched DNA structures and the recruitment of crucial proteins to recombination intermediates, ultimately abolishing CO formation. Furthermore, the variant disrupted dynamic chromatin structure in pachytene spermatocytes and induced synapsis defects. Importantly, the XPF-like domain in SHOC1 was revealed to prevent autosome intrusion into the sex body compartment, thereby protecting critical autosomal loci from meiotic silencing of unsynapsed chromatin (MSUC). Overall, our study underscores the critical role of the XPF-like domain in human SHOC1 in CO formation and in protecting autosomes from MSUC.

During meiosis, a group of evolutionarily conserved ZMM proteins plays essential roles in stabilizing the recombination intermediates and promoting crossover (CO) formation. In mice, SHOC1 forms a trimeric complex with the other two ZMM proteins, SPO16 and TEX11, to bind recombination intermediates after strand invasion. Although genetic variants of SHOC1 are clinically associated with meiotic arrest and male infertility, their precise molecular mechanisms and evolutionarily conserved functions in human gametogenesis remain enigmatic. Here, we delineated species-specific divergences between human and mouse SHOC1 complex, and identified a missense variant within the XPF-like domain in SHOC1 (c.A1769G:p.Q590R) that was associated with meiotic arrest and non-obstructive azoospermia (NOA). The disorder of the XPF-like domain in SHOC1 impaired DNA double-strand breaks repair by compromising its ability to bind branched DNA structures and the recruitment of M1AP, REDIC1, and ZMM factors to recombination intermediates, ultimately abolishing CO formation. Furthermore, the variant disrupted dynamic 3D chromatin structure in pachytene spermatocytes and induced defects in homologous chromosome synapsis. More importantly, the XPF-like domain in SHOC1 was revealed to prevent autosome intrusion into the sex body compartment, thereby safeguarding critical autosomal loci from meiotic silencing of unsynapsed chromatin (MSUC). Overall, our study demonstrated that the XPF-like domain in SHOC1 is required for homologous recombination and safeguarding autosome from MSUC in meiosis. ### Competing Interest Statement The authors have declared no competing interest. National Key Research and Development Program of China, 2022YFC2702701, 2022YFC2703000 National Natural Science Foundation of China, 82401869, 82371616, 82371607, 82171590, 82401868 Inner Mongolia Academy of Medical Sciences Public Hospital Joint Science and Technology Project, 2023GLLH0045 Scientific Research Startup Funding for High-Level Talents of Taizhou School of Clinical Medicine Fujian Provincial Natural Science Foundation of China, 2023J05271 Scientific Research Startup Funding for High-Level Talents of Taizhou School of Clinical Medicine, TZKY2023RC01

Biochemical recurrence (BCR) of prostate cancer (PCa) negatively impacts patients’ post-surgery quality of life, and the traditional predictive models have shown limited accuracy. This study develops an AI-based prognostic model using deep learning that incorporates androgen receptor (AR) regional features from whole-slide images (WSIs). Data from 545 patients across two centres are used for training and validation. The model showed strong performances, with high accuracy in identifying regions with high AR expression and BCR prediction. This AI model may help identify high-risk patients, aiding in better treatment strategies, particularly in underdeveloped areas.

Background:Previous studies have indicated that corporal venous occlusive dysfunction (CVOD) may be misdiagnosed in some patients with psychogenic erectile dysfunction (ED), as the observed venous leakage could actually reflect cavernous smooth muscle (CSM) relaxation failure due to sympathetic overactivity. Misdiagnosed CVOD can lead to inappropriate treatment decisions, such as unnecessary penile venous surgery or reliance solely on phosphodiesterase type 5 inhibitors (PDE5i), overlooking the need for psychogenic interventions. Therefore, it is important to identify the misdiagnosis of CVOD. Corpus cavernosum electromyography (CC-EMG) offers unique insights into the autonomic and myogenic integrity of CSM. This retrospective analysis aimed to evaluate the clinical value of spontaneous cavernous activity (SCA) assessment in identifying misdiagnosed CVOD in psychogenic ED. Methods:The study enrolled 168 ED patients who underwent comprehensive evaluation using color duplex Doppler ultrasound (CDDU) and CC-EMG-based SCA assessment (amplitude and duration). Psychogenic ED was confirmed through nocturnal penile tumescence and rigidity (NPTR) monitoring. CVOD patients identified by CDDU were stratified into two subgroups based on NPTR results: psychogenic ED group (misdiagnosed CVOD) and organic ED group (actual CVOD). Results:The cohort comprised 69 cases (41.1%) of non-vascular ED (NVED), 67 cases (39.9%) of CVOD, 15 cases (8.9%) of arterial ED (AED), and 17 cases (10.1%) of mixed ED (MED). Among CVOD patients, 30 cases were classified as misdiagnosed CVOD and 37 as actual CVOD. Comparative analysis demonstrated that the SCA parameters were significantly higher in the misdiagnosed CVOD group compared to those of the actual CVOD group, with notable differences in amplitude (305.65±196.79 vs. 172.07±86.36 µV, P=0.002) and duration (3.31±1.94 vs. 2.36±1.26 s, P=0.046). Receiver operating characteristic (ROC) curve analysis demonstrated an area under the curve (AUC) of 0.666 [P=0.02, 95% confidence interval (CI): 0.503-0.830] for SCA amplitude, with an optimal cutoff of 357.50 µV yielding 94.7% specificity and 55.0% sensitivity, indicating its potential predictive value for identifying misdiagnosed CVOD in psychogenic ED. Conclusions:The findings suggested that elevated SCA may contribute to CVOD development in psychogenic ED through impaired CSM relaxation due to sympathetic overactivity. SCA assessment might be a useful diagnostic tool for identifying misdiagnosed CVOD in psychogenic ED. However, given the modest AUC, along with high specificity but low sensitivity of SCA parameters for diagnosing misdiagnosed CVOD, further research is needed to identify additional clinical parameters with better predictive performance.

Background This study aims to investigate the changing trends in the penile prothesis implantation(PPI) of male with refractory erectile dysfunction(ED) in China. Method We retrospectively reviewed medical records from January 2019 to October 2023 to identify men who had undergone PPI in China. We also retrospectively reviewed medical records of PPI we had undergone during that time at Shanghai General Hospital. Results The overall trajectory of PPI surgeries exhibits an upward trend in China. Concurrently, the expertise in this surgical technique is currently limited to a minority of surgeons. A total of 112 patients were included in the study. Median age was 39[27–63] years, median International Index of Erectile Function-5 score (IIEF-5) significantly improved from 10.23 ± 1.26 to 22.6 ± 2.73. The causes of severe ED were: vasculogenic tower (n = 58, 51.8%), diabetes (n = 21,18.8%) and pelvic/spinal cord injury (n = 14, 12.5%). Overall satisfaction rate for the PPI surgery was 93.0% for men and 90.4% for their partners. The 3-year PPI survival rate was 87%. Conclusion The prevalence of PPI has witnessed a steady increase since 2019 in China, indicating a growing acceptance and endorsement of this surgical intervention among both patients and andrological practitioners for the treatment of severe ED. PPI is a safe and effective treatment option for Chinese patients with refractory ED and experienced surgeon perform PPI according to standard PPI procedure could reduce the complications and improve sexual satisfaction of patients and sexual partners .

BACKGROUND:Pediatric inguinal hernia repair (IHR) is a common cause of obstructive azoospermia (OA). Yet, the surgical treatment for this kind of OA remains difficult with poor fertility outcome. OBJECTIVES:To evaluate the safety and effectiveness of totally extraperitoneal laparoscopy-assisted microsurgical vasovasostomy (VV) in the treatment of OA caused by pediatric bilateral IHR. MATERIALS AND METHODS:Totally, 37 patients with OA caused by pediatric bilateral IHR were enrolled in this study from March 2015 to December 2020 in Shanghai General Hospital. The clinical data and fertility outcomes were collected and analyzed. RESULTS:All patients enrolled had a history of bilateral IHR at the age of 1-10 years old. The mean age of patients was 27 ± 4.31 (range: 18-35) years. Totally extraperitoneal laparoscopy (TEP) was applied in 31 patients for the exploration and retrieval of pelvic vas deferens end, and 30 of them underwent microsurgical VV successfully. Among the six cases where TEP was not applied, five cases underwent microsurgical anastomosis. Intraoperative exploration revealed that the location of vas deferens injuries included scrotum (2.70%, 1/37), inguinal canal (5.41%, 2/37), pelvic cavity (78.37%, 29/37), and multiple sites (13.51%, 5/37). The mean operation time was 339 ± 96.73 min (range: 130-510 min). There were no surgical complications. Thirty-three cases were followed up for 5-48 months with four cases lost to follow-up. The overall patency rate, pregnancy rate, and natural pregnancy rate were 75.86% (22/29), 46.67% (14/30), and 36.84% (7/19, 3 patients without family planning), respectively. And seven couples conceived through the assisted reproductive technique, two of which using fresh sperm in the ejaculate. CONCLUSION:TEP laparoscopy-assisted microscopic VV is an effective treatment for patients with OA caused by pediatric bilateral IHR.

Abstract Background Surgical penile prosthesis implantation (PPI) procedures have only recently been introduced to mainland China, with the overall number of such procedures having been conducted to date remaining relatively low. Accordingly, relatively little remains known with respect to the annual trends in PPI. Accordingly, this study was developed with the goal of clarifying these trends across different hospitals in mainland China, while also providing a single-center overview of post-PPI patient outcomes. Results To identify males in mainland China who had undergone PPI, a retrospective review of data from January 2019 – October 2023 was conducted. This approach revealed an increase in the total PPI caseload from 120 in 2019 to 413 within the first 10 months of 2023. Over this same interval, the number of surgeons performing PPI rose from 33 to 74. A retrospective review of the 112 patients who had undergone PPI at Shanghai General Hospital from 2019–2023 revealed that these patients had a median age of 39 [27–63] years, and PPI treatment led to a significant increase in median International Index of Erectile Function-5 (IIEF-5) scores from a baseline value of 10.23 ± 1.26 to a post-treatment value of 22.6 ± 2.73. The underlying causes of erectile dysfunction for these patients included vasculogenic factors (58/112; 51.8%), diabetes mellitus (21/112; 18.8%), and injuries to the spinal cord or pelvis (14/112; 12.5%). The overall rates of satisfaction with the PPI reported by patients and their partners were 93.0% and 90.4%, respectively, and the 3-year PPI survival rate for this cohort was 87%. Conclusion These data highlight a rising trend in the number of PPI being performed in China, with these steadily increasing rates since 2019 emphasizing the increasingly high levels of acceptance of this procedure by patients and clinicians as a means of treating erectile dysfunction. However, the expertise is restricted to a small number of surgeons. Even so, it is a safe and efficacious approach to managing severe erectile dysfunction for patients in China, and when performed by experienced surgeons based on standardized protocols, low complication rates can be achieved while providing patients and their sexual partners with high levels of satisfaction.

OBJECTIVE:To explore the effect of a novel transurethral thulium laser vapoenucleation of the prostate with low-power conventional pulse mode (LP-ThuVEP) on sexual function in patients with benign prostatic hyperplasia (BPH). METHODS:89 BPH patients admitted to Department of Urology, Jintan People's Hospital, Affiliated to Jiangsu University, from January 2022 to June 2023 were selected and randomly divided into the LP-ThuLEP group (45 cases) and the transurethral plasma kinetic resection of the prostate (TUPKRP) group (44 cases). Perioperative indicators were recorded, and the IPSS, Qmax, Qavg, PVR, and QoL of the two groups of patients before surgery and 3 months and 6 months after surgery were comparatively analyzed. The effect of surgery on male sexual function was evaluated through the International Index of Erectile Function-5 (IIEF-5) score and the Male Sexual Health Questionnaire-Ejaculatory Dysfunction (MSHQ-EjD) score. RESULTS:Compared with the TUPKRP group, the LP-ThuVEP group had no statistically significant difference in operation time (P>0.05), but there were statistical differences in bladder irrigation time and indwelling urinary catheter time (P<0.05) and significant statistical differences in the decrease in hemoglobin on the day of surgery and the disappearance time of gross hematuria induced by defecation after surgery (P<0.001). The perioperative complications of the two groups were comparable. Among the urinary tract symptom indicators, the LP-ThuVEP group had statistically significant differences in IPSS score, QoL score, and PVR compared with the TUPKRP group 3 months after surgery (P<0.05). In terms of male sexual function, there was a statistical difference in IIEF-5 scores between the two groups at 3 months and 6 months after surgery (P<0.05); Except that there was no statistical difference in the ejaculation-related satisfaction scores between the two groups at 3 months after surgery (P>0.05), there had all significant statistical differences in ejaculation function and satisfaction scores between and within the groups at 3 months and 6 months after surgery (P<0.001). CONCLUSION:Compared with TUPKRP, the LP-ThuVEP can also effectively relieve urinary tract obstruction caused by BPH and has the advantages of less damage and faster recovery of erectile function and ejaculatory function of patients.

目的:分析不同病因的非梗阻性无精子症(non-obstructive azoospermia,NOA)患者经显微镜下睾丸取精术(microdis-section testicular sperm extraction,micro-TESE)的治疗结局.方法:回顾性分析上海市第一人民医院2015年3月—2022年1月1 355例接受micro-TESE的患者,病因/危险因素包括克氏综合征(Klinefelter syndrome,KS)、Y染色体AZFc缺失、隐睾、腮腺炎性睾丸炎、放化疗、精索静脉曲张以及特发性NOA,研究分析各组患者精子获取率(sperm retrieval rate,SRR),并比较各组取精成功的妊娠结局.结果:NOA患者的总体SRR为26.2％(355/1 355),其中腮腺炎性睾丸炎SRR最高(75.9％,22/29),其次分别为隐睾(70.5％,43/61)、Y染色体AZFc缺失(55.6％,30/54)、KS(47.6％,71/149)、特发性NOA(18.6％,167/897)、放化疗(15.4％,2/13),精索静脉曲张SRR最低(13.2％,20/152).根据手术结局,将NOA患者分为取精成功组及取精失败组.特发性NOA及放化疗类型中,取精成功组卵泡刺激素(follicle-stimulating hormone,FSH)和黄体生成素(luteinizing hormone,LH)水平显著高于取精失败组;Y染色体AZFc缺失类型中,取精成功组FSH、LH水平显著低于取精失败组;腮腺炎性睾丸炎类型中,取精成功组睾丸体积高于取精失败组.回归分析发现年龄可作为预测特发性NOA患者取精结局的因素,年龄较高者拥有较好的取精结局.卵胞浆内单精子注射治疗的妊娠率为51.4％(200/389),活产率为73.5％(147/200).结论:不同病因/危险因素NOA患者的SRR具有显著差异,是影响micro-TESE取精结局的重要指标.

Patients with congenital unilateral absence of the vas deferens (CUAVD) manifest diverse symptoms from normospermia to azoospermia. Treatment for CUAVD patients with obstructive azoospermia (OA) is complicated, and there is a lack of relevant reports. In this study, we describe the clinical features and evaluate the treatments and outcomes of CUAVD patients with OA. From December 2015 to December 2020, 33 patients were diagnosed as CUAVD with OA in Shanghai General Hospital (Shanghai, China). Patient information, ultrasound findings, semen analysis, hormone profiles, and treatment information were collected, and the clinical outcomes were evaluated. Of 33 patients, 29 patients were retrospectively analyzed. Vasoepididymostomy (VE) or cross VE was performed in 12 patients, the patency rate was 41.7% (5/12), and natural pregnancy was achieved in one of the patients. The other 17 patients underwent testicular sperm extraction as the distal vas deferens (contralateral side) was obstructed. These findings showed that VE or cross VE remains an alternative treatment for CUAVD patients with OA, even with a relatively low rate of patency and natural pregnancy.

OBJECTIVE:Analyze the application effect of multidimensional nursing intervention in postoperative patients with benign prostatic hyperplasia in urology, and explore targeted nursing measures.METHODS:A total of 118 patients who underwent benign prostatic hyperplasia surgery at the Urology Department of Jintan First People's Hospital in Changzhou City from December 2022 to June 2023 were selected and divided into an experimental group of 59 and an intervention group of 59 according to different nursing measures. Collect IPSS, QoL, SDS, and SAS scores from patients to evaluate their quality of life and psychological changes during hospitalization.RESULTS:The postoperative SAS score of the experimental group patients (54.44 ±2.93) was lower than that of the control group (56.05±2.22), and the predischarge SAS score (46.19 ± 5.56) was lower than that of the control group (51.32 ± 1.48), with statistical significance (P<0.05). The SDS preoperative score (61.53 ± 6.40), postoperative score (54.75 ± 5.13),and pre discharge score (46.71 ± 4.32) of the experimental group patients were lower than preoperative score (67.76 ± 3.44), postoperative score (58.34 ± 3.03), and predischarge score (50.59 ± 2.58) of the control group with statistical significance (P<0.05). The preoperative IPSS score of the experimental group patients (27.97 ± 3.82) was lower than that of the control group (25.49 ± 4.00), and the difference was statistically significant (P<0.05), but there was no significant difference between the two groups after surgery and before discharge. The preoperative QoL score of the experimental group patients (91.90 ± 6.19) was lower than that of the control group (95.17 ± 5.56), and before discharge (105.15 ± 4.66) was higher than that of the control group (101.63 ± 5.66), with a statistically significant difference (P<0.05).CONCLUSION:Multidimensional nursing measures for postoperative patients with benign prostatic hyperplasia can improve their quality of life, reduce psychological pressure, and benefit patients significantly, which is worth further promotion.

Background. Previously published predictive models for microdissection testicular sperm extraction (micro-TESE) were generally assumed patients with nonobstructive azoospermia (NOA) a homogenous population, i.e., the laboratory predictors were associated with sperm retrieval rate (SRR) in a similar way among different subpopulations. In addition, previous studies primarily regarded the success of sperm retrieval as the sole endpoint, although live birth is the ultimate goal for the couples. Objectives. The main objective is to develop and evaluate the clinical benefit of a model predicting the clinical outcome of micro-TESE in heterogeneous population with NOA. The outcome of pregnancy was taken into account via assessing the association between the predicted outcome of micro-TESE and pregnancy. Materials and Methods. A development cohort of 1,292 patients with NOA and an external validation cohort of 530 patients were included. Sperm retrieval was performed using micro-TESE. Clinical outcomes, including sperm retrieval, clinical pregnancy, and live birth, were collected. We developed a model using the machine learning method random forest and provided a web-based calculator. Results. The SRR was 38.1% (492/1,292) in the development cohort and 48.5% (257/530) in the validation cohort. The final model includes etiology, AMH, sperm retrieval surgical history, testicular volume, FSH, LH, and age as predictors (ordered by variable importance). The area under the curve of our model was 0.76 (0.74–0.79) in the development cohort and 0.75 (0.71–0.79) in the external validation cohort. The decision curve analysis showed that personalized model-based surgical decision provides additional clinical benefit. The clinical pregnancy rate (CPR) and cumulative live birth rate (CLBR) were 45.3% (405/895) and 57.6% (338/587), respectively, in the overall population. For patients of different SRR, the CPR and CLBR of whom had successful sperm retrieval were similar. Discussion and Conclusion. Our model predicting the SRR of micro-TESE was generalizable and easy to use. Predicted pregnancy outcomes like CPR and CLBR could also be derived from predicted SRR. A model-based surgical decision after personalized consultation would be beneficial to patients with NOA.

BACKGROUND:A recent sham-controlled clinical study has shown that low-intensity pulsed ultrasound twice per week can safely and effectively treat patients with mild-to-moderate erectile dysfunction (ED). However, large-scale clinical trials are needed to verify its efficacy and safety and determine a reasonable treatment interval. AIM:To study whether low-intensity pulsed ultrasound therapy thrice per week is non-inferior to twice per week in patients with mild-to-moderate ED. METHODS:A randomized, open-label, parallel-group, non-inferiority clinical trial was conducted in 7 hospitals in China. A total of 323 patients with mild-to-moderate ED were randomized (1:1) into thrice per week (3/W) and twice per week (2/W) groups. Low-intensity pulsed ultrasound was applied on each side of the penis for 16 sessions. OUTCOMES:The primary outcome was response rate using the minimal clinically important difference in the International Index of Erectile Function (IIEF-EF) score at week 12. Secondary outcomes included Erection Hardness Score (EHS), Sexual Encounter Profile, Global Assessment Question, and Self Esteem and Relationship Questionnaire. RESULTS:Response rates in 3/W and 2/W groups were 62.0% and 62.5%, respectively. Treatment effect in the 3/W group was noninferior to that of the 2/W group, with rate difference lower bound of -0.01% [95% confidence interval -0.11 to 0.10%] within the acceptable margin (-14.0%). No significant difference was found among secondary outcomes. IIEF-EF score showed a significant increase from baseline in the 3/W group (16.8 to 20.7) and 2/W group (17.8 to 21.7), and the percentage of patients with EHS ≥3 increased in the 3/W (54.9% to 84.0%) and 2/W (59.5% to 83.5%) groups. There was no significant difference in response rate between the 2 groups after controlling for strata factors and homogeneous tests. No treatment-related adverse events were reported. CLINICAL IMPLICATIONS:Low-intensity pulsed ultrasound therapy displays similar efficacy and safety for mild-to-moderate ED when administered thrice or twice per week for 16 sessions. This study provides two options to suit patients' needs. STRENGTHS & LIMITATIONS:This is a large-sample, randomized, controlled, noninferiority trial study. Short-term follow-up and mostly younger patients are the main limitations. CONCLUSION:Low-intensity pulsed ultrasound therapy thrice and twice per week showed equivalent therapeutic effects and safety for mild-to-moderate ED in a young and generally healthy population. This therapy warrants further investigation of its potential value in rehabilitation of ED. Chen, H., Li Z., Li X., et al. The Efficacy and Safety of Thrice vs Twice per Week Low-Intensity Pulsed Ultrasound Therapy for Erectile Dysfunction: A Randomized Clinical Trial. J Sex Med 2022;19:1536-1545.

Objective:To analyze the effectiveness and safety of reoperation for obstructive azoospermia (OA) with initial microsurgical anastomosis failure.Methods:A retrospective case series was performed for OA patients who underwent reoperation after initial microsurgical anastomosis failure, in Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Institute of Urology, Urologic Medical Center from March 2015 to June 2020. Totally, 21 patients were enrolled in the study, and the clinical data, patency and pregnancy outcomes were reviewed.Results:During the initial surgery, 8 cases underwent vasovasostomy and 8 cases underwent vasoepididymostomy, while the other 5 cases underwent crossover anastomosis; 19 cases underwent reoperation because of reproductive needs, and 2 for post-vasectomy chronic testicular pain. During the reoperation, anastomotic stricture was found in 14 cases, and sperm granuloma was found in 6 cases, while spermatogenic dysfunction was confirmed in 1 case. Unilateral or bilateral anastomosis was performed successfully in 19 cases. Testicular sperm extraction was performed for 1 case with non-obstructive azoospermia (NOA) and 1 case with severe adhesion respectively. Totally 19 cases was followed for 3 to 58 months [(30.21±18.43) months], and 2 cases were lost to follow-up. Chronic testicular pain was relieved completely in 1 of the 2 cases suffering from the post-vasectomy testicular pain. Overall, 11 cases achieved patency, and 4 cases concieved naturally. Furthermore, 3 cases underwent in vitro fertilization cycle (1 case with semen sperm, and the other 2 cases with frozen testicular sperm). There were no severe post-operational complications in all cases. Conclusion:Microsurgical reoperation, which allows a favorable patency rate and natural pregnancy rate, is a valid option for the treatment of OA with initial microsurgical anastomosis failure.

Objectives. Erectile dysfunction is a major comorbidity of diabetes. Stem cell transplantation is a promising method to treat diabetic erectile dysfunction. In this study, we evaluated whether low-intensity pulsed ultrasound (LIPUS) could enhance the efficacy of adipose-derived stem cells (ADSCs) and investigated the underlying molecular mechanism. Materials and methods. Sixty 8-week-old male Sprague–Dawley rats were randomly divided into the normal control (NC) cohort or the streptozocin-induced diabetic ED cohort, which was further subdivided into DM, ADSC, LIPUS, and ADSC+LIPUS groups. Rats in the ADSC or ADSC+LIPUS group received ADSC intracavernosal injection. Rats in the LIPUS or ADSC+LIPUS group were treated with LIPUS. The intracavernous pressure (ICP) and mean arterial pressure (MAP) were recorded at Day 28 after injection. The corpus cavernosum tissues were harvested and subjected to histologic analysis and ELISA. The effects of LIPUS on proliferation and cytokine secretion capacity of ADSCs were assessed in vitro. RNA sequencing and bioinformatic analysis were applied to predict the mechanism involved, and western blotting and ELISA were used for verification. Results. Rats in the ADSC+LIPUS group achieved significantly higher ICP and ICP/MAP ratios than those in the DM, ADSC, and LIPUS groups. In addition, the amount of cavernous endothelium and cGMP level also increased significantly in the ADSC+LIPUS group. In vitro experiments demonstrated that LIPUS promoted proliferation and cell cycle progression in ADSCs. The excretion of cytokines such as CXCL12, FGF2, and VEGF was also enhanced by LIPUS. Bioinformatic analysis based on RNA sequencing indicated that LIPUS stimulation might activate the MAPK pathway. We confirmed that LIPUS enhanced ADSC VEGF secretion through the Piezo-ERK pathway. Conclusion. LIPUS enhanced the curative effects of ADSCs on diabetic erectile dysfunction through the activation of the Piezo-ERK-VEGF pathway. ADSC transplantation combined with LIPUS could be applied as a synergistic treatment for diabetic ED.

KASH5 is an essential component of the LINC (linker of the nucleoskeleton and cytoskeleton) complex that regulates chromosome movements and nuclear envelope (NE) remodeling in mouse spermatocytes during meiosis prophase I, but its expression and function in human cells, as well as its association with male infertility are largely unknown. In this study, a novel heterozygous copy number variation (CNV) (seq [GRCh37] del(19) (19q13.33) chr19: g.49894043-49903011del) and a heterozygous loss of function variant (NM_144688: c.979_980del: p.R327Sfs*21) in human KASH5 were identified in a non-obstructive azoospermia (NOA)-affected patient and in his infertile sister by whole-exome sequencing and CNV array. Spermatogenesis in the proband was arrested at zygotene-like stage with a deficiency in homolog pairing and synapsis. KASH5 protein expression in human spermatocytes was evaluated and reported first in this study. Single-cell RNA sequencing demonstrated that the LINC complex and associated genes in human and mouse shared a similar expression pattern, indicating a conserved mechanism in the regulation of chromosome movements and NE remodeling. Kash5 knockout mouse displayed similar phenotypes, including a meiotic arrest at a zygotene-like stage and impaired pairing and synapsis. Collectively, we have identified novel rare variants within human KASH5 in patients with NOA and meiosis arrest. Our study expands the knowledge of KASH5 and associated proteins in regulating human meiosis prophase I progress and provides new insight into the genetic etiology of NOA.

目的:可膨胀性人工海绵体植入术常规将储水囊放置于耻骨后膀胱前间隙,而对于盆腔外伤或手术的重度勃起功能障碍患者,储水囊放置存在风险与困难.本研究旨在改良可膨胀性人工海绵体植入术的储水囊放置方法,评估其安全性与有效性.方法:回顾性分析2017年6月-2021年12月在上海市第一人民医院泌尿男科实施可膨胀性人工海绵体植入术患者的临床资料.其中对照组为常规将储水囊置于耻骨后膀胱前间隙的患者,试验组为因盆腔外伤手术实施改良储水囊植入的患者.通过门诊或电话交流对患者进行术后回访,分析改良方案的安全性、有效性.结果:30例可膨胀性人工海绵体植入术中采用改良储水囊放置的试验组患者有8例,其中放置于右侧腹壁下腹膜前间隙的有5例(16.67％),放置于左侧腹壁下腹膜前间隙的有3例(10.00％),均通过隧道法连接储水囊和泵阀.其余22例(73.33％)为对照组患者.30例手术的二次手术率为3.33％(1/30),为对照组中的1例术后泵阀故障的患者.试验组二次手术率为0(0/8),对照组为4.55％(1/22).试验组性生活满意度为100％(8/8),对照组为90.91％(20/22).试验组不良反应发生率为12.50％(1/8),对照组为13.64％(3/22).结论:可膨胀性人工海绵体植入术是治疗难治性勃起功能障碍的推荐治疗方法,然而对于曾行骨盆骨折或尿道断裂相关手术的严重外伤性勃起功能障碍患者实施常规放置储水囊于耻骨后膀胱前间隙的操作存在一定风险和困难.对这类患者实施储水囊放置于左右腹壁下腹膜前间隙并通过隧道法连接储水囊与泵阀的改良方案可以简化手术操作,降低手术风险,且与常规放置方案之间在二次手术率、性生活满意度和不良反应发生率等方面没有统计学差异,显示出良好的安全性及有效性.

BACKGROUND:Non-obstructive azoospermia (NOA) is one of the most severe type in male infertility, and the genetic causes of NOA with meiotic arrest remain elusive.METHODS:Four Chinese families with NOA participated in the study. We performed whole-exome sequencing (WES) for the four NOA-affected patients in four pedigrees. The candidate causative gene was further verified by Sanger sequencing. Hematoxylin and eosin staining (H&E) and immunohistochemistry (IHC) were carried out to evaluate the stage of spermatogenesis arrested in the patients with NOA.RESULTS:We identified two novel homozygous frameshift mutations of MSH4 and two novel compound heterozygous variants in MSH4 in four pedigrees with NOA. Homozygous loss of function (LoF) variants in MSH4 was identified in the NOA-affected patient (P9359) in a consanguineous Chinese family (NM_002440.4: c.805_812del: p.V269Qfs*15) and one patient with NOA (P21504) in another Chinese family (NM_002440.4: c.2220_2223del:p.K741Rfs*2). Also, compound heterozygous variants in MSH4 were identified in two NOA-affected siblings (P9517 and P9517B) (NM_002440.4: c.G1950A: p.W650X and c.2179delG: p.D727Mfs*11), and the patient with NOA (P9540) (NM_002440.4: c.G244A: p.G82S and c.670delT: p.L224Cfs*3). Histological analysis demonstrated lack of spermatozoa in seminiferous tubules of all patients and IHC showed the spermatogenesis arrested at the meiotic prophase I stage. Consistent with the autosomal recessive mode of inheritance, all of these mutations were inherited from heterozygous parental carriers.CONCLUSIONS:We identified that six novel mutations in MSH4 responsible for meiotic arrest and NOA. And these results provide researchers with a new insight to understand the genetic etiology of NOA and to identify new loci for genetic counselling of NOA.

The corpus cavernosum is the most important structure for penile erection, and its dysfunction causes many physiological and psychological problems. However, its cellular heterogeneity and signalling networks at the molecular level are poorly understood because of limited access to samples. Here, we profile 64,993 human cavernosal single-cell transcriptomes from three males with normal erection and five organic erectile dysfunction patients. Cell communication analysis reveals that cavernosal fibroblasts are central to the paracrine signalling network and regulate microenvironmental homeostasis. Combining with immunohistochemical staining, we reveal the cellular heterogeneity and describe a detailed spatial distribution map for each fibroblast, smooth muscle and endothelial subcluster in the corpus cavernosum. Furthermore, comparative analysis and related functional experiments identify candidate regulatory signalling pathways in the pathological process. Our study provides an insight into the human corpus cavernosum microenvironment and a reference for potential erectile dysfunction therapies.

to cryptozoospermia. After discussion with the couple, the patient elected to pursue conservative treatment to improve his sperm quality. As antioxidant supplements have emerged as a potential therapeutic approach in an attempt to treat male infertility, L-carnitine and vitamin E supplements were prescribed.3 However, his semen quality did not improve after 3 months of treatment, so he returned for surgical treatment by mVE. Surgery was performed under a Zeiss surgical microscope (Vario 700; Carl Zeiss AG, Oberkochen, Germany). During the surgery, testicular tissue was obtained and delivered immediately to the experienced laboratory experts. Many immotile spermatozoa were found under phase-contrast microscopy (Nikon Corporation, Tokyo, Japan) at 200× magnification. Dilated epididymal tubules in the caudae were identified easily, and many immotile spermatozoa were found in the aspirated fluid. The abdominal vas deferens were unobstructed, as confirmed by dilute methylene blue injection. A single-armed suture longitudinal intussusception vasoepididymostomy technique sparing the deferential vessels was adopted, and anastomosis was performed on both caudae. During the postoperative follow-ups, semen analyses indicated cryptozoospermia for the first 2 months, but the sperm recovered. The total progressively motile sperm count fluctuated but kept at a relative high level in most tests (Table 1). This indicated the success of the operation. Thirteen months after the operation, his wife conceived naturally, and a baby boy was born in due course. ICSI has now become an established therapy for cryptozoospermia.2 However, for cryptozoospermia caused by obstructive factors – as in this case – seminal duct reconstructive surgery is recommended. This enables spermatozoa to reappear in ejaculates, making natural conception possible. Compared with ICSI, it avoids oocyte retrieval and reduces medical expenses. In general, we recommend testicular sperm extraction (TESE) during surgery for the following reasons. First, TESE can be used to confirm normal spermatogenesis. Although uncommon, spermatogenic failure may be mistakenly considered normal spermatogenesis. Second, testicular sperm cryopreservation can be carried out for ICSI if the seminal duct reconstruction fails, avoiding reoperation for sperm extraction. In this case, the patient preferred to tolerate his epididymal obstruction. After all the treatment options were informed, the patient only accepted the surgical reconstruction surgery and refused TESE for sperm cryopreservation. The longitudinal intussusception vasoepididymostomy technique has been recognized as the gold standard to achieve a superior patency Dear Editor, Cryptozoospermia is defined as the apparent absence of spermatozoa from fresh semen samples, but they can be found in centrifuged pellets.1 It is usually caused by a spermatogenic disorder, while cryptozoospermia associated with seminal duct obstruction is less common.2 Because of the extremely low sperm counts in semen samples, men with cryptozoospermia are often reliant on intracytoplasmic sperm injection (ICSI) for paternity.2 However, for men with cryptozoospermia caused by seminal duct obstruction, reconstructive surgery might be an option. To our knowledge, there is no report of cryptozoospermia caused by epididymal obstruction. Here, we report a man with this condition who impregnated his wife successfully after undergoing microsurgical vasoepididymostomy (mVE). This study was approved by the Ethics Committee of Shanghai General Hospital (approval number: 2021KY084). Informed consent for this study was obtained from the patient. A 29-year-old man with a 2-year history of infertility presented for treatment in Shanghai General Hospital (Shanghai, China). He was diagnosed with azoospermia by repeated semen analyses but had been confirmed to have active spermatogenesis by fine-needle aspiration in another institution. He had impregnated a previous partner 4 years ago and had a history of epididymitis 3 years ago. He did not have other potential causes of infertility. The patient had well-developed testes. The bilateral epididymides were plump by palpation. The patient had no evidence of other abnormalities of the genitourinary system. Furthermore, no spermatozoa were found in ejaculates. The seminal fructose test was positive. The level of neutral α-glycosidase was 5.78 U l−1 (reference ≥10.12 U l−1). Endocrine evaluations showed a luteinizing hormone (LH) level of 9.98 mIU ml−1, follicle-stimulating hormone (FSH) level of 3.06 mIU ml−1, and total testosterone (T) level of 3.50 ng ml−1. Scrotal ultrasonography showed tubular ectasia in the bilateral corpus and caudae epididymides (Supplementary Figure 1). He was initially diagnosed with obstructive azoospermia (obstruction of epididymides) and was recommended to undergo mVE. Unexpectedly, the day before scheduled surgery, a semen analysis showed several immotile spermatozoa after centrifugation. Therefore, we revised his diagnosis LETTER TO THE EDITOR