Background: Resolvin D1 (RvD1), a member of the specialized pro-resolving lipid mediators family, has a potent anti-inflammatory effect and alleviates tissue damage. The purpose of the current research was to study the effect of RvD1 on CP/CPPS and the underlying mechanisms using a mouse model of experimental autoimmune prostatitis (EAP) mice. Materials and Methods: The EAP mouse model was successfully established, and was used to test the therapeutic effect of RvD1. Hematoxylin-eosin staining and dihydroethidium staining were used to evaluate the histological changes and oxidative stress levels of prostate tissues. Chronic pelvic pain was assessed by applying von Frey filaments to the lower abdomen. The superoxide dismutase enzyme and malondialdehyde levels were detected using enzyme-linked immunosorbent assay (ELISA). The levels of inflammation-related cytokines, including IL-1β, IL-6, and TNF-α were detected by ELISA. Results: RvD1 treatment ameliorated prostatic inflammation and the pelvic pain of EAP mice. RvD1 treatment could inhibit activation of the NLRP3 inflammasome and oxidative stress. RvD1 treatment could activate Nrf2/HO-1 signaling in mice with EAP. Blockade of Nrf2/HO-1 signaling abolished the RvD1-mediated inhibition of oxidative stress, NLRP3 inflammasome activation and the anti-inflammatory effect of RvD1 in EAP. Conclusion: RvD1 treatment can reduce inflammatory cell infiltration in prostate tissue and attenuate pelvic pain associated with EAP by inhibiting oxidative stress and NLRP3 inflammasome activation via the Nrf2/HO-1 pathway. These results provide new insights that RvD1 has the potential as an effective agent in the treatment of EAP.
We evaluated outcomes and donor site complications in male patients with complex urethral strictures who underwent urethroplasty using with long strip oral mucosal grafts. We also analyzed whether a lingual mucosa graft is a good substitute for repairing long segment urethral strictures. This retrospective study was done in 81 male patients with complex urethral strictures who underwent oral mucosal graft urethroplasty. Patients with long segment (8 cm or greater) anterior urethral strictures who were considered candidates for long strip lingual mucosa graft urethroplasty were included in study. Oral mucosal graft urethroplasty was performed in 81 patients with complex urethral strictures between August 2006 and December 2014. Mean urethral stricture length was 12.1 cm (range 8 to 20). A single 9 to 12 cm long strip lingual mucosa graft was used in 52 patients, a lingual mucosa graft greater than 12 cm was placed in 17 and a lingual mucosa graft combined with a buccal mucosal graft was used in 12. Mean followup was 41 months (range 15 to 86) postoperatively. The overall urethroplasty success rate was 82.7%. Urethral complications developed in 14 patients (17.3%), including urethral strictures in 10 and urethrocutaneous fistulas in 4. At 12 months 5 patients (6.2%) reported minimal difficulty with fine motor movement of the tongue. Lingual mucosa harvested from the ventrolateral surface of the tongue can provide a wide and long graft that is an excellent urethral substitute. Donor site complications are primarily limited to postoperative year 1. Our study confirms that the lingual mucosa graft is a good substitute for urethral reconstruction and lingual mucosa graft urethroplasty is a valuable procedure to treat long anterior urethral strictures.
Costimulatory molecules have been proven to enhance antitumor immune responses, but their roles in clear cell renal cell carcinoma (ccRCC) remain unexplored. In this study, we aimed to explore the gene expression profiles of costimulatory molecule genes in ccRCC and construct a prognostic signature to improve treatment decision-making and clinical outcomes. We performed the first comprehensive analysis of costimulatory molecules in patients with ccRCC and identified 13 costimulatory molecule genes with prognostic values and diagnostic values. Consensus clustering analysis based on these 13 costimulatory molecular genes showed different distribution patterns and prognostic differences for the two clusters identified. Then, a costimulatory molecule-related signature was constructed based on these 13 costimulatory molecular genes, and validated in an external dataset, showing good performance for predicting a patient’s prognosis. The signature was an independent risk factor for ccRCC patients and was significantly correlated with patients’ clinical factors, which could be used as a complement for clinical factors. In addition, the signature was associated with the tumor immune microenvironment and the response to immunotherapy. Patients identified as high-risk based on our signature exhibited a high mutation frequency, a high level of immune cell infiltration, and an immunosuppressive microenvironment. High-risk patients tended to have high cytolytic activity scores and immunophenoscore of CTLA4 and PD1/PD-L1/PD-L2 blocker than low-risk patients, suggesting these patients may be more suitable for immunotherapy. Therefore, our signature could provide clinicians with prognosis predictions and help guide treatment for ccRCC patients.
Purpose: To investigate the etiology and management of male iatrogenic urethral stricture in China. Methods: The data of 172 patients with iatrogenic urethral stricture who underwent treatment at a high volume reference center in China from January 2008 to February 2014 were analyzed retrospectively. Databases were analyzed to understand the impact of different types of iatrogenic injury on stricture location, length and treatment of urethral strictures, as well as success rates. Results: The most common type of iatrogenic stricture was urethral instrumentations in 80 patients (46.51%). Mean stricture length was 3.3 ± 2.54 cm and the longest strictures were those caused by intravesical instillation. Substitution urethroplasty was the most common intervention and was performed in 60.47% (104/172) of patients. The overall success rate was 85.00% (136/160). Univariable analyses revealed that the type of iatrogenic injury was significantly related to restenosis (p = 0.036), and it is more apt to postoperative restenosis in the type of intravesical instillation than others. Conclusion: Our results showed that urethral instrumentation is the most common etiology of iatrogenic urethral stricture, and most iatrogenic urethral strictures involve the anterior urethra. The different etiologies are closely associated with stricture location, length and the overall prognosis of urethral strictures.
6 July 2023 in Journal of the American Chemical Society