The proposed DIA workflow yields optimum time efficiency and data reliability and provides a good choice for proteomic analysis in biological and clinical studies, and these dysregulated proteins might be potential biomarkers for ccRCC diagnosis.

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Background Refractory non-malignant ureterostenosis is challenging to treat. The experience to treat the stenosis primarily cause by retroperitoneal fibrosis with the Resonance and Allium metallic stent is still limited. We aim to evaluate the efficacy and safety of these two stents and provide alternative treatment options. Methods A retrospective study was conducted for patients with non-malignant ureterostenosis and treated with the Resonance and Allium stents from March 2011 to September 2020 in our department. The efficacy was evaluated by the change of serum creatinine, glomerular filtration rate (GFR), the proportion of GFR of the affected side and hydronephrosis grade. The safety was evaluated by postoperative presence of moderate or severe overactive bladder (OAB), recurrent urinary infection, pain, stent displacement, encrustation and re-obstruction. Results 33 patients were eligible for the study, including 18 cases treated by the Resonance stents and 15 patients treated by the Allium stents. The patients of two groups had similar age and gender proportion. The cause of ureterostenosis was mainly retroperitoneal fibrosis in both groups but the Resonance group had more idiopathic cases. Follow-up time was significantly longer in the Resonance group than the Allium group (36.2 ± 24.0 vs 9.4 ± 5.0 months, p < 0.001). Both groups showed improvement or maintenance of serum creatinine level, GFR, the GFR proportion of the affected side and hydronephrosis grade after treatment. The Resonance group presented significant higher incidence of moderate or severe OAB, recurrent urinary infection and pain, while the Allium group showed significant more cases of re-obstruction. Conclusion Both the Resonance and Allium stent can relieve the non-malignant refractory ureterostenosis effectively. The Resonance stent may cause more irritable symptoms while the Allium stent may have a higher rate of re-obstruction. The long term efficacy and safety of the Allium stent in treating non-malignant refractory ureterostenosis requires further study.

Background: Intradetrusor botulinum toxin A injection is recommended for the treatment of refractory detrusor overactivity (DO) in patients with neurogenic bladder, however, whether it could inhibit neurogenic bladder fibrosis is uncertain. This study aimed to investigate the effect of botulinum toxin A on neurogenic bladder fibrosis and the underlying mechanism.Methods: Forty eight Female Wistar rats were evenly randomized into 4 groups: Sham, T10 transection, Early and Late groups. The last three groups were subjected to T10 spinal cord transection, while the Sham group was treated with sham surgery. 0.9% saline was injected into the detrusor in the Sham and T10 transection groups simultaneously with the surgery, while 2 U/rat botulinum toxin A was injected into the detrusor simultaneously with the surgery in the Early group and 4 weeks following the surgery in the Late group. Body/bladder weight, cystometric parameters, bladder Hematoxylin-eosin staining were used to evaluate the bladder fibrosis. Western blot and quantitative Real-time PCR were used to evaluate the expression of bladder transforming growth factor β1.Results: Compared with the T10 transection group, the bladder/body weight was decreased significantly in the Early and Late groups (P<0.05), along with the significant inhibition of non-voiding contraction (NVC) frequency and amplitude (P<0.05), and the significant increase of bladder volume (P<0.05). The detrusor connective tissue percentage (P<0.05) and the expression of transforming growth factor β1 (P<0.05) also decreased significantly in the Early and Late groups. Those changes were more obviously in the Early group than in the Late group.Conclusions: Intradetrusor botulinum toxin A injection reduced bladder fibrosis in rats with spinal cord injury (SCI), which was more obviously in the Early group than in the Late group. The mechanisms might be mediated by suppression of transforming growth factor β1 (TGF-β1) expression.

Bladder cancer stem cells (BCSCs) have the abilities of self-renewal, differentiation, and metastasis; confer drug resistance; and exhibit high tumorigenicity. We previously identified that the KMT1A-GATA3-STAT3 axis drives the self-renewal of BCSCs. However, the therapeutic effect of targeting KMT1A in BCSCs remains unknown. In this study, we confirmed that the expression of KMT1A was remarkably higher in BCSCs (3-5-fold) than those in bladder cancer non-stem cells or normal bladder epithelial cells. Among the six KMT1A inhibitors, chaetocin significantly suppressed the cell propagation (inhibition ratio: 65%-88%, IC 50 = 24.4-32.5 nM), induced apoptosis (2-5fold), and caused G1 phase cell cycle arrest (68.9 vs 55.5%) of bladder cancer (BC) cells, without influencing normal bladder epithelial cells. More importantly, chaetocin abrogated the self-renewal of BCSCs (inhibition ratio: 80.1%) via the suppression of the KMT1A-GATA3-STAT3 circuit and other stemness-related pathways. Finally, intravesical instillation of chaetocin remarkably inhibited the growth of xenograft tumors (inhibition ratio: 71-82%) and prolonged the survival of tumor-bearing mice (70 vs 53 days). In sum, chaetocin abrogated the stemness maintenance and tumor growth of BCSCs via the suppression of the KMT1A-GATA3-STAT3 circuit. Chaetocin is an effective inhibitor targeting KMT1A in BCSCs and could be a promising therapeutic strategy for BC.