Introduction: Ureteral stricture caused by iatrogenic ureteral injury induced ureteral injury is more common and challenging to recover quickly. The effective prevention of ureteral stricture due to iatrogenic ureteral injury-induced ureteral damage is a current challenge for urologists. The purpose of this study was to evaluate the effectiveness of nanoparticle/pirfenidone complex-coated ureteral stents with slow-release pirfenidone for the prevention of ureteral stricture in rabbits. In this study, we developed a nanoparticle/pirfenidone complex-coated ureteral stent to deliver pirfenidone into the injured ureter to inhibit ureteral stricture. Methods: Twelve New Zealand rabbits were divided into four groups: Sham, US, US+ Unmodified ureteral stent, and US+NP/PFD ureteral stent; we constructed an irreversible electroporation model of ureteral injury in rabbits and placed unmodified ureteral stents and nanoparticle/pirfenidone complex-coated ureteral stents into the ureter. Two weeks later, we euthanized the rabbits and removed their bilateral kidneys and ureters. We evaluated the effect of ureteral stent prophylaxis by gross specimen observation, section staining, and Western Blot. Results: We found that the nanoparticle/pirfenidone complexes could adhere uniformly to the surface of the ureteral stent. After placement into the ureter, the nanoparticle/pirfenidone complexes were able to remain on the surface of the ureteral stent. We found nanoparticle/pirfenidone complexes could diffuse in the ureteral epithelial tissue two weeks after the order. The study showed that nanoparticle/pirfenidone complex-coated ureteral stents placed into the ureter showed significantly less stenosis due to fibrosis than in US control rabbits and rabbits treated with unmodified ureteral stents. Conclusion: We used a novel platform based on nanoparticle/pirfenidone complex-coated ureteral stents for local and sustained delivery of pirfenidone, which can effectively deliver pirfenidone to the tissue and can slowly control the release of pirfenidone. Therefore, combining ureteral stents with nanoparticle/pirfenidone complexes was an effective measure to prevent ureteral stricture.

Background: Cancer is a common cause of death around the world. Immunotherapy plays a significant role in cancer treatment but still has limitations. The ankyrin-3 (ANK3) gene has been shown to have a variety of biological roles and has also been shown to be closely linked to individual cancers. Methods: We systematically investigated the role of ANK3 in pan-cancer, particularly in relation to immunity. We collected data from a number of databases, including the The University of ALabama at Birmingham CANcer data analysis Portal (UALCAN), tumor-immune system interactions (TISIDB), cBioPortal, Tumor Immune Estimation Resource (TIMER), Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), BioGRID, and SangerBox databases. R (version 3.6.3) was used for the statistical analysis and data visualization. The expression of ANK3 in tumors and its effects on patient prognosis, immune infiltration, neoantigens, the microenvironment, immune checkpoints (ICs), the tumor mutation burden, microsatellite instability (MSI), methylation, mismatch repair (MMR) genes, and cancer-associated fibroblasts were investigated. A gene set enrichment analysis (GSEA) was also conducted. Results: The ANK3 gene was differentially expressed at the messenger RNA (mRNA) and protein levels in various human tumors. The prognosis of patients with different types of malignancies was correlated with the level of ANK3 expression. The immunological microenvironment was also linked to ANK3 expression, especially in colon adenocarcinoma (COAD), kidney renal clear cell carcinoma (KIRC), and liver hepatocellular carcinoma (LIHC). ANK3 was also associated with ICs, immune neoantigens, MSI, the tumor mutation load, MMR genes, and DNA methylation. Finally, we found the key pathway related to the ANK3 gene through the enrichment analysis. Conclusions: ANK3 could serve as a new biomarker specific to prognosis and immunotherapy in various cancers. Our findings could contribute to the development of novel strategies for treating malignancies.

Background: Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cell carcinoma. The myosin 6 (MYO6) plays an important role in tumorigenesis and progression. However, its prognostic and immunological effects in ccRCC have not been comprehensively and systematically studied. Therefore, this study aimed to investigate the prognostic value and immune-related role of MYO6 in ccRCC. Methods: The expression of MYO6 mRNA and protein in normal and tumor tissues using The Cancer Genome Atlas (TCGA) and other public databases were analyzed. In order to further improve the accuracy of the results, immunohistochemistry (IHC) was performed to verify the results. R software, an integrated repository portal for tumor-immune system interactions (TISIDB) and other online analysis tools were used to investigate the relationship between MYO6 expression and clinicopathological features, diagnostic and prognostic value, and the level of immune infiltration in patients with ccRCC. MYO6 genomic alterations were then investigated using the cBio Cancer Genomics Portal (cBioPortal) database. Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and Gene Set Enrichment Analysis (GSEA) enrichment analysis were used to elucidate the biological processes and signaling pathways. Finally, a protein interaction network was constructed using Biological Universal Repository for Interactive Datasets (BioGRID) and some online analysis tools to investigate the correlation between MYO6 and its co-expressed genes in ccRCC patients. Results: In the present study, MYO6 expression was significantly reduced in ccRCC tumors compared with normal tissues.This was consistent with the results of immunohistochemistry. Lower MYO6 expression levels were significantly associated with higher cancer grade and later TNM stage in ccRCC. Compared with the MYO6 high expression group, ccRCC patients with low MYO6 expression had a poor prognosis of overall survival (OS). MYO6 expression has diagnostic and prognostic potential in ccRCC. MYO6 expression is associated with different tumor-infiltrating immune cells, especially macrophages. Conclusions: The findings suggest that reduced MYO6 expression levels are associated with disease progression, poor prognosis, and immune cell infiltration, and can be considered as a promising prognostic biomarker for ccRCC.

Background: Urethral strictures are common injurious conditions of the urinary system. Reducing and preventing urethral strictures has become a hot and challenging topic for urological surgeons and related researchers. In this study, we developed a catheter loaded with nanoparticle/pirfenidone (NP/PFD) complexes and evaluated its effectiveness at inhibiting urethral stricture in rabbits, providing more references for the clinical prevention and reduction of urethral stenosis.Methods: Twelve adult male New Zealand rabbits were selected and divided into the following four groups in a ratio of 1:1:1:1 using the random number table method: Group A, sham; Group B, urethral stricture (US); Group C, US + unmodified catheter; and Group D, US + NP/PFD catheter. On the 30th day after modelling, retrograde urethrography was performed to evaluate urethral stricture formation, and histopathological examination was performed on the tissues of the corresponding surgical site. Meanwhile, changes in the expression level of Transforming growth factor β1 (TGF-β1) in the tissues were detected by immunohistochemistry.Results: The NP/PFD complexes adhered uniformly to the catheter surface. They remained on the surface of the catheter after insertion into the urethra. In addition, the NP/PFD complexes spread into the urethral epithelium 2 weeks after surgery. Ultimately, urethral strictures were significantly reduced with the placement of the NP/PFD complex catheter.Conclusion: Our catheter loaded with NP/PFD complexes effectively delivered PFD to the urethral epithelium through continuous local delivery, thereby reducing fibrosis and stricture after urethral injury, which may be associated with the inhibition of TGF-β1 expression.

Background: In recent decades, there has been increasing evidence that Go-Ichi-Nii-San (GINS) subunits play an important role in the development and progression of various tumors. However, little research has been conducted on the role of GINS subunits in clear cell renal cell carcinoma (ccRCC). This study sought to explore the differential expression, prognosis, and immunological significance of GINS subunits in ccRCC. Methods: We used various analysis packages of R (version 3.6.3), the University of ALabama at Birmingham CANcer (UALCAN) data analysis portal, the Cancer Cell Line Encyclopedia (CCLE), the cBio Cancer Genomics Portal (cBioPortal), and the Tumor Immune Estimation Resource (TIMER) to study the gene expression, promoter methylation level, gene mutations, prognostic and diagnostic value, immune infiltration, pathway enrichment, and other aspects of the GINS subunits. Next, the genes related to the GINS subunits were analyzed using the STRING and GeneMANIA platforms, and the correlation between GINS subunits and the functions involved were investigated. Results: The expression level of GINS1/2/3/4 was significantly higher in ccRCC tumor tissues than normal tissues, and was significantly related to tumor grade and stage. The expression of GINS1/2/4 may be related to the methylation degree of the promoter region. The prognostic and diagnostic analyses showed that the increased expression of GINS1 was associated with various poor prognoses and had diagnostic value. The GINS subunit mutation also significantly affected the clinical prognosis of ccRCC patients. Finally, the correlation analysis of the immune infiltration level, co-expression, and enrichment of related genes indicated that GINS subunit expression was associated with different levels of ccRCC immune infiltration. Conclusions: The analysis results showed that the differential expression of GINS subunits in ccRCC, which had prognostic and diagnostic value, was correlated with clinicopathological stage, immune infiltration, and other related aspects. GINS1 may serve as a new potential prognostic biomarker for ccRCC patients and be used to guide treatment.