Cell-cycle-associated and expression-elevated protein in tumor (CREPT) functions as a cell cycle modulator that enhances the transcription of cyclin D1 by interacting with RNA polymerase II. CREPT has been identified to be overexpressed in various human cancer types; however, the expression and significance of CREPT in renal cell carcinoma (RCC) has remained largely elusive. In the present study, increased expression of CREPT was identified in 46.7% RCC tissues compared with adjacent normal tissue (31.1%; P=0.032) using immunohistochemistry. Furthermore, overexpression of CREPT was significantly associated with the Tumor-Node-Metastasis stage (χ 2 =11.967, P=0.001) and Fuhrman grade (χ 2 =15.453, P<0.001). In addition, increased expression of CREPT was associated with poor overall survival (P=0.021) and disease-free survival (P=0.015) of patients according to Kaplan-Meier analysis. Cellular function assays demonstrated that knockdown of CREPT in the 786-O and 769P RCC cell lines suppressed their proliferative, colony formation, migratory and invasive capacity and led to cell cycle arrest in the G1 phase. In addition, the western blotting analysis demonstrated that CREPT may control the cell cycle through downregulation of cyclin D1 and c-myc. Collectively, the overexpression of CREPT was indicated to be a negative prognostic factor for RCC, and CREPT may serve as a novel therapeutic target for the treatment of RCC.
Purpose To compare the effects of two different methods of laparoscopic pyeloplasty for the treatment of crossing vessels. Methods From January 2016 to August 2019, 33 patients with ureteropelvic junction obstruction (UPJO) underwent laparoscopic pyeloplasty at our center, including 21 men and 12 women, ranging from 14 to 66 years of age. There were 20 and 13 cases on the left and right sides, respectively. Patients underwent laparoscopic pyeloplasty (Anderson-Hynes operation). During the operation, either a Hem-o-lok clip suspension or transposition was used to treat the crossing vessels. The double-J stent was removed 8 weeks after the operation. The clinical data of patients were collected and follow-ups were regularly performed after the operation. Results All the crossing vessels were successfully preserved, and none of them were severed during the operation. The average operation time was 210.6 ± 58.9 min in this group and the average time to manage the crossing vessel was 8.0 ± 3.5 min, 5.9 ± 1.4 min in the suspension group, and 11.7 ± 3.0 min in the transposition group. The dilation of the affected side was 4.8 ± 1.5 cm before operation and 1.2 ± 1.3 cm 3 months after operation. The difference was statistically significant (P < 0.05). Follow-up to February 2020 showed no significant changes in the kidney size in all patients and hydronephrosis was relieved. Conclusion For UPJO patients with crossing vessel compression, the method of Hem-o-lok suspension or vascular transposition can be used to relieve crossing vascular compression and improve the success of pyeloplasty.
Background: Bladder urothelial carcinoma (BLCA) is one of the most common urinary tract malignant tumors. Immune checkpoint blockade (ICB) therapy has significantly progressed the treatment of BLCA.This study aimed to investigate the role of specific genetic mutations that may serve as immune biomarkers for ICB therapy in BLCA.Methods: Mutation information and expression profiles were acquired from The Cancer Genome Atlas (TCGA) database. Integrated bioinformatics analysis was carried out to explore the subtypes with poor prognosis of BLCA. Functional enrichment analysis was also conducted. The infiltrating immune cells and the prediction of ICB response between different subtypes were explored using the immuCellAI algorithm.Cell Counting Kit-8 (CCK-8) and flow cytometry assays were conducted to explore the effect of filaggrin (FLG) knockdown in BLCA 5637 and T24 cell lines.Results: An overview of mutation information in BLCA patients was shown. FLG was identified to be strongly associated with the prognosis of BLCA patients and FLG wild-type was associated with poorer outcome. Prognostic FLG wild-type was divided into 2 subtypes (Sub1 and Sub2). Following an investigation of the subtypes, Sub2 of FLG wild-type was found to be associated with poorer outcome in BLCA. The differentially expressed genes (DEGs) between Sub1 and Sub2 were screened out and the DEGs were enriched in malignant tumor proliferation, DNA damage repair, and immune-related pathways.Furthermore, Sub2 of FLG wild-type was associated with infiltrated immune cells, and responded worse to ICB. Sub2 of FLG wild-type may be used as a biomarker to predict the prognosis of BLCA patients receiving ICB. The cellular experiments revealed that knockdown of FLG could suppress BLCA cell proliferation and promote apoptosis.Conclusions: FLG is an oncogene that may affect the prognosis of BLCA patients through mutation. Sub2 of FLG wild-type is associated with poor prognosis and can be used to predict ICB response for BLCA treatment. This research provides a new basis and ideas for guiding the clinical application of BLCA immunotherapy.
Objectives Obesity and metabolic status are both modifiable risk factors of lower urinary tract symptoms secondary to benign prostatic hyperplasia (LUTS/BPH). However, the association between metabolically healthy obesity (MHO) and LUTS/BPH is largely unexplored. This study aimed to investigate the risk of LUTS/BPH among different metabolic syndrome‐body mass index (MetS‐BMI) phenotypes in a cohort of Chinese males. Methods A total of 3321 males from the China Health and Retirement Longitudinal Study (CHARLS) without history of LUTS/BPH at baseline were included into the analyses. Participants were categorized into six mutually exclusive groups according to presence or absence of MetS combined with BMI status: metabolically healthy normal weight/overweight/obesity (MHN/MHOW/MHO) and metabolically unhealthy normal weight/overweight/obesity (MUN/MUOW/MUO). Adjusted odds ratios (OR) and 95% CI of LUTS/BPH across MetS‐BMI categories were estimated with multivariable logistic regression models. Results A total of 394 (11.86%) participants developed LUTS/BPH during the follow‐up. After adjusting for age, educational level, smoking status, drinking status, and BMI change, the multivariable‐adjusted OR (95% CI) for incident LUTS/BPH comparing MUO, MHO, MUOW, MHOW, and MUN with MHN were 1.99 (1.23‐3.22), 2.04 (1.14‐3.66), 1.61 (1.11‐2.34), 1.45 (1.02‐2.05), and 0.91 (0.54‐1.56), respectively. Conclusions MHO and MHOW were risk populations of LUTS/BPH, suggesting that overweight and obesity can independently contribute to LUTS/BPH, even among metabolically healthy individuals. These findings emphasize metabolically healthy individuals may still benefit from maintaining normal body weight to prevent LUTS/BPH. Our findings also support that those recommendations for LUTS/BPH should highlight the importance of maintaining metabolic health across all BMI groups among Chinese males.
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