Long Tian

Male infertility remains a major unmet medical challenge, with poorly defined molecular mechanisms and no effective therapies. Here, we identify a stress granule-mediated necroptotic pathway as a key driver of non-obstructive azoospermia, a severe form of male infertility marked by the loss of spermatogenesis. Environmental or physiological stress activates eIF2α kinases, inducing stress granule formation and the recruitment of ZBP1 and RIPK3 into a cytoplasmic complex. This assembly triggers RIPK3 activation, MLKL phosphorylation, and necroptotic death of spermatogonia and Sertoli cells. Genetic ablation of Zbp1 or Ripk3 protects mice from heat-induced testicular degeneration, establishing their essential role in stress-induced testicular damage. Importantly, activation of this pathway is also observed in aged human testes, linking stress-responsive necroptosis to both pathological infertility and the broader process of reproductive aging. These findings reveal an unrecognized mechanism that couples cellular stress responses to regulated cell death in the male reproductive system.

Background: Erectile dysfunction (ED) is the most common type of sexual dysfunction, which seriously affects male reproductive health. Recently, stem cell therapy and low‐intensity pulsed ultrasound (LIPUS) have been applied in the treatment of ED, but the specific mechanism is still unclear. Objectives: The study aims to investigate the effect and underlying mechanism of further LIPUS treatment on the basis of bone marrow mesenchymal stem cells (BMSCs) transplantation in the treatment of ED rats. Materials and methods: We established a cavernosa injury‐induced ED rat model and injected BMSCs into the penile corpus cavernosum with or without LIPUS treatment every other day for three times. The survival rate of BMSCs, value of ICP/MAP, blood flow, the endothelial content, and expression of CD31 and ɑ‐SMA in the rat penis were investigated. Transcriptome analyses and in vitro assays of cell proliferation, migration, and tube formation were also performed. Results: The results showed that LIPUS treatment significantly promoted the survival rate of BMSCs in the rat penis after 1, 7, and 14 days of final treatment. The values of ICP/MAP and blood flow in rats treated with BMSCs were significantly increased compared to the control group, and the values were further enhanced in rats treated with BMSCs plus LIPUS. The endothelial content and CD31 and ɑ‐SMA mRNA and protein expression in the BMSCs plus LIPUS group were remarkably higher than in other groups, indicating improved endothelial vascular function. Transcriptome analyses found that insulin‐like growth factor binding protein‐3 (IGFBP3) was remarkably downregulated in the BMSCs plus LIPUS group compared to the other two groups. In in vitro assays, LIPUS intervention significantly increased BMSCs proliferation and HUVECs migration, and HUVECs angiogenesis was improved after IGFBP3 siRNA transfection. Conclusions: BMSCs transplantation combined with LIPUS treatment could improve erectile function in ED rats via downregulation of IGFBP3, which might be a proposed optimized strategy for the ED treatment.

Background: There are few studies on cryptorchidism in adults, and its treatment is still controversial. Methods: To summarize the surgical strategy and clinical efficacy of laparoscopic orchidopexy for the treatment of cryptorchidism in adults, 37 adult cryptorchidism patients were retrospectively analyzed between September 2017 and February 2022. All 37 patients underwent laparoscopic orchidopexy, of whom 33 underwent inguinal hernia repair without tension. The intraoperative procedures and surgical techniques were recorded in detail. Preoperative examination and regular postoperative review of color Doppler ultrasound, and reproductive hormone, alpha-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase levels were performed. Results: All testes descended successfully into the scrotum, including 25 through the inguinal route and 12 through Hesselbach’s triangle route. No intraoperative or postoperative complications were observed. The follow-up time was 38.6 (± 19.4) months, and no evidence of testicular malignancy was found during the follow-up period. After analyzing the reproductive hormone levels at 1 year postoperatively in 28 patients with more than 1 year of follow-up, it was found that the patients had a significant increase in testosterone levels and a decrease in follicle-stimulating hormone levels after surgery. None of the patients showed any significant improvement in semen quality after surgery. Conclusion: Our study suggests that laparoscopic orchidopexy is a safe and feasible surgical procedure for the treatment of cryptorchidism in adults, especially high cryptorchidism, which is difficult to treat. After comprehensive consideration, preserving the testis should be preferred for treating cryptorchidism in adults to maximize the protection of the patient’s reproductive hormone secretion function.

Background Currently, no recognized evidence is known about the bacterial communities found within seminal vesicles (SV) of men presenting with refractory hematospermia. Methods and results Fifteen male patients with refractory hematospermia or anejaculation were enrolled, and 15 SV-Infection (SV-In) samples from SV with hemorrhage and/or stones, 11 SV-Control (SV-C) samples from SV with non-infection, and 14 Urine (Urine) samples from posterior urethra were obtained via transurethral seminal vesiculoscopy. Then the high-throughput 16 S rRNA gene sequencing method was performed to characterize the microbiota profile. Finally, a total of 1535 operational taxonomic units (OTUs) were found, 1295 OTUs were shared across three groups, 7 OTUs, 45 OTUs, and 48 OTUs were unique to SV-C group, SV-In group, and Urine group, respectively. The 5 top bacterial phyla (mean relative abundance) in all samples were Firmicutes (52.08%), Bacteroidetes (21.69%), Proteobacteria (12.72%), Actinobacteria (9.64%), and Fusobacteria (1.62%), the 5 top bacterial genera in all samples were Bacteroides (9.13%), Lactobacillus (5.38%), Bifidobacterium (5.35%), Faecalibacterium (5.10%), and Allobaculum (3.34%), of which Bifidobacterium had the highest level in SV-C samples and had a significant difference (P < 0.05) across all groups. Differential analysis showed genera Leuconostoc and LachnospiraceaeFCS020group were identified as biomarkers in the SV-In microbiota. Conclusion Altered microbiota composition in seminal vesicles is related to refractory hematospermia in men, and the distribution of genus Leuconostoc or LachnospiraceaeFCS020group within seminal vesicles may interact with hematospermia. This study provides clues for the diagnosis and treatment of this urologic disorder.

Paratesticular liposarcoma is a sporadic urological tumor. We report the clinical presentation, treatment course, and prognosis of 2 cases of primary paratesticular liposarcoma with different pathological types, with the aim of further understanding the diagnosis and treatment of this rare disease. Case 1 was a 53-years-old male patient who presented with left scrotal enlargement with swelling 3 years ago and was considered to have a testicular malignancy on preoperative CT scan and enhanced MRI. The patient underwent resection of the left scrotal mass and left orchiectomy under general anaesthesia. Histopathological study confirmed the diagnosis of dedifferentiated liposarcoma. At the 4-months follow-up, no local recurrence or distant metastasis was observed. Case 2 is a 42-years-old male patient with a left scrotal mass which was discovered six months ago. Preoperatively, he underwent CT plain and enhanced MRI examinations suggesting an intra-scrotal occupancy. The patient underwent scrotoscopic excision of the left scrotal mass under general anesthesia. Histopathological studies confirmed the diagnosis of highly differentiated liposarcoma. At the 10-months follow-up, no local recurrence or distant metastasis was observed. Preoperative differential diagnosis of paratesticular liposarcoma should be noted with testicular tumor and extra-abdominal hernia. Extensive local excision and, if necessary, concomitant radical testicular resection is the treatment of choice. If the tumor in the scrotum spreads to the inguinal region, surgical removal with the aid of a scrotoscope may be attempted. This procedure avoids the formation of a large incision in the inguinal region compared to traditional open surgery. Patients commonly experience local recurrence and less distant metastases after surgery, so long-term follow-up is recommended.

Background: To evaluate the efficacy and safety of aildenafil citrate in the treatment of erectile dysfunction (ED) in Chinese population. Methods: A multicenter, randomized, double-blind, placebo-controlled, double-cycle crossover trial was conducted in three medical centers. Male patients with mild to moderate ED were randomized into two groups and received either aildenafil citrate or placebos, followed by a crossover administration after a 7-day washout. The primary outcome was the duration of penile rigidity over 60% measured by RigiScan^® Plus. Main secondary outcomes were the duration of penile rigidity over 80% and erectile hardness score (EHS). Results: A total of 60 patients with mild to moderate ED were enrolled in the study and 57 of them completed the trial (30 in the aildenafil group and 27 in the placebo group). The median duration of penile tip rigidity over 60% was 4.25 (0.00, 19.00) min in the aildenafil group, as compared with 0.50 (0.00, 2.75) min in the placebo group (PConclusions: These results suggested that aildenafil citrate was efficient and well-tolerated in the treatment of Chinese men with mild to moderate ED. Trial Registration: Chinese Clinical Trial Registry ChiCTR1900026025.

Cavernosa injury is a common cause of organic erectile dysfunction (ED), which requires safe and effective treatments. In the present study, the therapeutic efficiency of muscle-derived stem cells (MDSCs) modified with microRNA-126 (miR-126) was determined in rats with cavernosa injury. MDSCs were transfected with miR-126 and then were transplanted into rats with cavernosa injury. Erectile function, vascular function (western blot and immunofluorescence), extraction, and detection of exosomes were then undertaken. On the 28th day after transplantation, the highest value of intra-cavernous pressure (ICP)/mean arterial pressure (MAP) in rats of miRNA-126 group (0.84 ± 0.14) was observed (Control: 0.38 ± 0.07; MDSC: 0.54 ± 0.11, Vector: 0.60 ± 0.02; respectively). Treatment of miRNA-126-modified-MDSCs remarkably strengthened vascular structure, supported by hematoxylin-eosin staining. The expression of CD31, von Willebrand Factor and vascular endothelial factors were higher than those in other groups, indicating improved vascular function. In vitro mechanism studies showed that exosomes containing miR-126 isolated from MDSCs promoted angiogenesis and attenuated apoptosis of human umbilical venous endothelial cells. Finally, insulin receptor substrate 1 and Krüppel-like factor 10 were determined as the direct target genes of miR-126. MiR-126 engineered MDSCs notably repaired cavernosa injury in rats via vascular reconstruction by directly targeting IRS1 and KLF10, in which the exosomes secreted by MDSCs played a critical role.