[Correlation of environment temperature with the incidence of testicular torsion].

Objective： To explore the influence of environment temperature on the incidence of testicular torsion. METHODS: We collected the clinical data on 172 cases of testicular torsion diagnosed in the Second Hospital of Hebei Medical University from December 2013 to December 2020. According to the local environment temperature on the day of onset, we divided the patients into groups A (below 0℃), B (0－10℃), C (10－20℃) and D (above 20℃), and compared the incidence rates of testicular torsion among the four groups, followed by correlation analysis. RESULTS: The incidence rate of testicular torsion was 12.8% (n = 22) in group A, 35.5% (n = 61) in B, 34.9% (n = 60) in C and 16.9% (n = 29) in D, the highest at 0－10℃ in group B, with statistically significant difference among the four groups (χ2 = 29.07, P <0.001). Spearman correlation analysis indicated that the incidence of testicular torsion was negatively correlated with the environment temperature (r = －0.261, P <0.01), with no statistically significant difference among different seasons (χ2 = 5.349, P >0.05), but higher in autumn and winter than in the other two seasons. CONCLUSION: The incidence of testicular torsion is negatively correlated with the environment temperature, elevated when the temperature decreases, but has no statistically significant difference among different seasons, though relatively higher in autumn and winter.

[A comparative study of transcolonic and paracolic laparoscopic pyeloplasty in children with UPJO].

OBJECTIVE: Comparing the laparoscopic pyeloplasty via the mesocolon and para-colonic gutter approach for the treatment of pediatric pelvi-ureteric junction obstruction (UPJO) induced simple hydronephrosis, and analyzing the potential factors influencing surgical outcomes. METHODS: Clinical data of 71 children with UPJO who underwent laparoscopic pyeloplasty at the Department of Urology of the Second Hospital of Hebei Medical University from January 2020 to January 2023 were analyzed. The patients, aged 0.25 to 18 years, were divided into two groups: 30 cases underwent the transcolonic route (mesangial group) and 41 cases underwent the transcolonic paragutter route (paragrow group). RESULTS: showed that both surgical approaches had similar outcomes in terms of operation completion, smooth process, absence of laparotomy, operation time, intraoperative blood loss, postoperative feeding time, and postoperative drainage tube indwelling time, total hospitalization cost, surgical effect, and satisfaction. Common complications such as postoperative fever and abdominal pain were managed with drug treatment or observation, with no need for secondary surgery or fatal complications. Factors such as age, body mass index, preoperative symptoms, severity of hydronephrosis, and ABO blood group classification did not impact the surgical outcome. CONCLUSIONS: There was no statistically significant difference between laparoscopic pyeloplasty and another surgical method in terms of various surgical outcomes for children with ureteropelvic junction obstruction. Factors such as age, body mass index, preoperative symptoms, severity of hydronephrosis, and ABO blood group classification did not have a significant impact on the surgical outcome.

[Advantage analysis of modified day surgery procedure for concealed penis].

OBJECTIVE: The modified day surgery procedure was compared with traditional inpatient procedure and standard day surgery procedure of concealed penile surgery to investigate its advantages, as well as the feasibility of promoting it in our country. METHODS: Retrospective analyzing the clinical data between 135 cases of the concealed penis in children who underwent modified day surgery (day group) and 101 cases who underwent hospitalization surgery (hospitalization group) at the Second Hospital of Hebei Medical University and the results of follow-up.The modified day surgery procedure involves the establishment of dedicated day wards in each surgical department, where the patient's condition is monitored until 8 o'clock the following morning to assess their discharge eligibility.The children's clinical data was divided into two groups to compare clinical parameters, including age at surgery, bleeding volume, operation time, hospitalization expenses, day of hospitalization, and the occurrence of short-term complications before the initial dressing change after surgery.The satisfaction survey of the children was conducted among three distinct groups: the modified day group, the standard day group, and the hospitalization group enabling a comparison of satisfaction levels among these groups. RESULTS: The mean ages of the inpatient and day surgery groups were 8.92±4.42 years old and 11.85±4.43 years old, respectively. No significant differences were observed between these two groups regarding operation time, bleeding volume, and postoperative complications (P>0.05). Compared to the inpatient group, the mean inpatient time and the hospitalization cost of the day group decreased by 69% and 27%, respectively (P<0.05). The patients in the modified procedure group reported the highest satisfaction among the three groups. CONCLUSION: Modified day surgery procedure offers advantages over the standard day surgery procedure and traditional inpatient surgical procedures for the operative treatment of the concealed penis, which makes it suitable for large-scale popularization in China.

[Feasibility low cryptorchidism surgery following modified day surgical procedures].

OBJECTIVE: To explore the feasibility and safety of cryptorchidism surgery in the day surgery center. METHODS: This retrospective study included 122 cases of unilateral low cryptorchidism (ULC) and 27 cases of bilateral low cryptorchidism (BLC) treated by orchidopexy from July 2018 to July 2022 in the Second Hospital of Hebei Medical University. We divided the patients with ULC into an Ad (day surgery following modified day surgical procedures) and an Ac (conventional surgery) group, and those with BLC into a Bd and a Bc group. We analyzed the clinical data and compared the surgical parameters and patients' satisfaction between different groups. RESULTS: There were no statistically significant differences in the operation age, operation time, intraoperative blood loss, or postoperative complications between the Ad and Ac groups (P > 0.05), but the hospital stay and total cost were markedly reduced in the Ad group by 69% and 10%, respectively, compared with those in the Ac group (P < 0.05). No statistically significant differences were observed between the Bd and Bc groups in the operation age or intraoperative blood loss (P > 0.05), but the Bd group showed significant decreases in the operation time, hospital stay (62%) and total cost (14%) in comparison with the Bc group (P < 0.05). The satisfaction of the patients was remarkably higher in the former than in the latter group. CONCLUSION: Low cryptorchidism surgery following the modified day surgical procedures in the day surgery center is safe and feasible, with the advantages of lower cost and shorter hospital stay.

Myc-associated zinc-finger protein promotes clear cell renal cell carcinoma progression through transcriptional activation of the MAP2K2-dependent ERK pathway.

BACKGROUND: The dysfunction of myc-related zinc finger protein (MAZ) has been proven to contribute to tumorigenesis and development of multiple cancer types. However, the biological roles and clinical significance of MAZ in clear cell renal carcinoma (ccRCC) remain unclear. METHODS: MAZ expression was examined in ccRCC and normal kidney tissue by quantitative real-time PCR and Western blot. Statistical analysis was used to evaluate the clinical correlation between MAZ expression and clinicopathological characteristics to determine the relationship between MAZ expression and the survival of ccRCC patients. The biological roles of MAZ in cells were investigated in vitro using MTT and colony assays. Luciferase reporter assays and chromatin immunoprecipitation (ChIP) were used to investigate the relationship between MAZ and its potential downstream signaling molecules. RESULTS: MAZ expression is elevated in ccRCC tissues, and higher levels of MAZ were correlated with poor survival of patients with ccRCC. MAZ upregulation elevates the proliferation ability of ccRCC cells in vitro, whereas silencing MAZ represses this ability. Our results further reveal that MAZ promotes cell growth, which is dependent on ERK signaling. Importantly, we found that MAZ positively regulates MAP2K2 expression in ccRCC cells. Mechanistically, MAZ binds to the MAP2K2 promoter and increases MAP2K2 transcription. Furthermore, MAP2K2 levels were shown to be increased in ccRCC tissues and to be associated with a poor prognosis of ccRCC patients. MAP2K2 upregulation activates the ERK signaling pathway and promotes ccRCC progression. CONCLUSION: These results reveal that the MAZ/MAP2K2/ERK signaling axis plays a crucial role in promoting ccRCC progression, which suggests the potential therapeutic utility of MAZ in ccRCC.

The reasons and countermeasures of Bladder Rupture caused by Transurethral Clot Evacuation.

OBJECTIVE: Bladder rupture caused by transurethral clot evacuation is rare in clinic, but an emergency operation is indeed needed in the patient with bladder rupture. We analyzed the reasons of bladder rupture caused by transurethral clot evacuation and provided the countermeasures to guide clinical surgeon to prevent the iatrogenic damage of bladder. METHOD: We retrospectively reviewed the records of 287 patients in our hospital, who had bladder tamponade resulting from clots of blood for various reasons and underwent transurethral clot evacuation from January 2007 to January 2019. Six male cases, aged from 28 to 76 years (mean 56.67±17.76) had bladder rupture. Four patients whose bladder ruptured intraperitoneally were changed to open surgery to repair bladder and clear the remanent blood clots. Two patients with extraperitoneal bladder rupture and a small bladder crevasse underwent a conservative therapy. RESULTS: We observed that the incidence rate of bladder rupture was not associated with bladder tamponade and the age, but may be associated with gender, bladder paracentesis preoperative and urinary retention preoperative. All six cases were male.. They had different period of urinary retention before operation. No supra-pubis bladder paracentesis was made before operation. The bladder crevasses located in the triangle zone and posterior wall of bladder entirely, and the length of the bladder crevasses ranged from 3 to 7cm (mean 4.83cm). The bladder crevasses were all lengthways, and four cases were of' bladders ruptured intraperitoneally while another two presented an extraperitoneal bladder rupture. CONCLUSIONS: The reasons of bladder rupture caused by transurethral clot evacuation may be related to gender, bladder paracentesis preoperative and urinary retention preoperative. We should decide to use expectant treatment or open surgery immediately according to the extent of the rupture when bladder rupture occurs.

A comparative study on the Efficacy of Retroperitoneoscopic Pyeloplasty and Open Surgery for Ureteropelvic Junction Obstruction in Children.

OBJECTIVES: To compare the therapeutic effect of retroperitoneoscopic dismembered pyeloplasty and open ureteropelvic junction plasty on the ureteropelvic junction obstruction (UPJO) in children. METHODS: After the retrospective analysis of clinical data, 78 children with ureteropelvic junction stenosis treated from January, 2012 to June, 2018 were divided into two groups: OP (open pyeloplasty) group (38 cases) and LP (laparoscopic dismembered pyeloplasty) group (40 cases) according to the surgical methods. The operation time, intraoperative bleeding volume, postoperative length of stay (LOS), postoperative complication rate, postoperative hydronephrosis improvement and other indicators were compared between the two groups. RESULTS: All patients underwent surgery successfully, without conversion to open surgery in LP group. The incidence of postoperative urine leakage and the recovery of hydronephrosis between LP group and OP group 12 months after operation showed no statistically significant difference (P>0.05). The intraoperative bleeding volume, the incidence of postoperative retroperitoneal hematoma, and the postoperative LOS in LP group were lower than those in OP group, while the operation time was longer than that in the OP group, with statistically significant difference (P<0.05). CONCLUSION: Retroperitoneoscopic dismembered pyeloplasty had similar effect with open dismembered pyeloplasty, but faster recovery and fewer complications, so it has become the preferred treatment method for UPJO in children.

Effect of tadalafil combined with atorvastatin on hemodynamics and sexual function in middle-aged and elderly patients with hyperlipidemia complicated with erectile dysfunction.

OBJECTIVE: To evaluate the effect and clinical significance of tadalafil combined with atorvastatin on hemodynamics and sexual function in middle-aged and elderly patients with hyperlipidemia complicated with Erectile dysfunction (ED). METHODS: Eighty patients with hyperlipidemia complicated with ED who were treated at The Second Hospital of Hebei Medical University from January 2019 to June 2020 were selected. Using a completely randomized design experimental method, these 80 patients were randomly divided into two groups: the experimental group and the control group, with 40 cases in each group. The control group was treated with a single drug, atorvastatin calcium, while the experimental group was given tadalafil orally on the basis of the control group for 3 months. Changes in the levels of inflammatory factors such as IL-6, TNF and CRP, adverse drug reactions, changes in hemodynamic indicators such as HSV, LSV, PSV, HCT and ESR before and after treatment, as well as changes in sexual function after treatment were compared and analyzed between the two groups. RESULTS: TNF-a, CRP and IL-6 in the experimental group were significantly lower than those in the control group after treatment, with statistically significant differences (p<0.05). There was no significant difference in the incidence of adverse drug reactions between the two groups (p=0.18). After treatment, hemodynamic indexes and sexual function indexes of the experimental group were significantly improved compared with those in the control group, with statistically significant differences (p<0.05). CONCLUSION: A significant improvement effect can be achieved by tadalafil combined with atorvastatin on hemodynamics and sexual function in middle-aged and elderly patients with hyperlipidemia complicated with ED. At the same time, the combination of the two has synergism on inflammatory factors and blood rheology, and the incidence of adverse reactions is not significantly increased.

Down-regulated RBM5 inhibits bladder cancer cell apoptosis by initiating an miR-432-5p/ß-catenin feedback loop.

RNA-binding motif protein 5 (RBM5) acts as a tumor suppressor in various human cancers and presents with several important characteristics, such as the potentiation of apoptosis, inhibition of the cell cycle, and alternative splicing of Fas and caspase-2 precursor mRNA. However, its role in bladder urothelial carcinoma (BUC) remains unknown. In this study, we found that RBM5 expression was significantly down-regulated in BUC tissues when compared with the adjacent nontumor tissues. The down-regulation of RBM5 activates ß-catenin, which binds to the T-cell factor/lymphocyte enhancer factor element of the miR-432-5p promoter and elevates the expression of miR-432-5p in bladder cancer cells. The up-regulated miR-432-5p directly targets 3'-UTR and depresses RBM5 expression. Thus, RBM5-miR-432-5p-ß-catenin forms a feedback loop in regulating bladder cancer cell apoptosis. Our findings provide evidence that the regulatory feedback loop among RBM5, miR-432-5p, and Wnt-ß-catenin is responsible for the progress of bladder cancer cells.-Zhang, Y.-P., Liu, K.-L., Wang, Y.-X., Yang, Z., Han, Z.-W., Lu, B.-S., Qi, J.-C., Yin, Y.-W., Teng, Z.-H., Chang, X.-L., Li, J.-D., Xin, H., Li, W. Down-regulated RBM5 inhibits bladder cancer cell apoptosis by initiating an miR-432-5p/ß-catenin feedback loop.

Enhanced recovery after surgery for radical cystectomy with ileal urinary diversion: a multi-institutional, randomized, controlled trial from the Chinese bladder cancer consortium.

PURPOSE: Enhanced recovery after surgery (ERAS) has played an important role in recovery management for radical cystectomy with ileal urinary diversion (RC-IUD). This study is to evaluate ERAS compared with the conventional recovery after surgery (CRAS) for RC-IUD. METHODS: From October 2014 and July 2016, bladder cancer patients scheduled for curative treatment from 25 centers of Chinese Bladder Cancer Consortium were randomly assigned to either ERAS or CRAS group. Primary endpoint was the 30-day complication rate. Secondary endpoints included recovery of fluid and regular diet, flatus, bowel movement, ambulation, and length of stay (LOS) postoperatively. Follow-up period was 30-day postoperatively. RESULTS: There were 144 ERAS and 145 CRAS patients. Postoperative complications occurred in 25.7 and 30.3% of the ERAS and CRAS patients with 55 complications in each group, respectively (p = 0.40). There was no significant difference between groups in major complications (p = 0.82), or type of complications (p = 0.99). The ERAS group had faster recovery of bowel movements (median 88 versus 100 h, p = 0.01), fluid diet tolerance (68 versus 96 h, p < 0.001), regular diet tolerance (125 versus 168 h, p = 0.004), and ambulation (64 versus 72 h, p = 0.047) than the CRAS group, but similar time to flatus and LOS. CONCLUSIONS: ERAS did not increase 30-day complications compared with CRAS after RC. ERAS may be better than CRAS in terms of bowel movement, tolerance of fluid and regular diet, and ambulation.

[Transumbilical single-port laparoscopy combined with improved double hernia needles for pediatric hydrocele].

OBJECTIVE: To compare the clinical effect of transumbilical single-port laparoscopy combined with improved double hernia needles with that of traditional open surgery in the treatment of hydrocele in children. METHODS: We retrospectively analyzed 35 cases (54 sides) of pediatric hydrocele treated by transumbilical single-port laparoscopy combined with improved double hernia needles (laparoscopy group). We recorded the operation time, intraoperative blood loss, hospital stay, scrotal edema, and postoperative complications and compared them with those of another 46 cases (58 sides) treated by traditional open surgery (open surgery group) during the same period. RESULTS: The laparoscopy group showed a significantly shorter operation time, less intraoperative blood loss, milder scrotal edema, and fewer hospital days than the open surgery group (all P<0.05). However, no statistically significant difference was found in the incidence of postoperative complications between the two groups (P>0.05). Subcutaneous emphysema developed in 2 patients in the laparoscopy group, which disappeared after 1－3 days of oxygen inhalation and other symptomatic treatment, while scrotal hematoma occurred in 1 and incision fat liquefaction in 2 patients in the open surgery group 3 days postoperatively, which healed after debridement suture and daily dressing, respectively. The patients were followed up for 3－6 months, which revealed no late complications in the laparoscopy group but 1 case of unilateral recurrence and 2 cases of offside recurrence in the open surgery group, all cured by laparoscopic internal ring ligation. CONCLUSIONS: Transumbilical single-port laparoscopy combined with improved double hernia needles is superior to traditional open surgery for the treatment of pediatric hydrocele and therefore deserves clinical generalization.

Follow-up and histocompatibility observation of urethral reconstruction with different materials.

OBJECTIVE: Our objective is to observe the long-term surgical results of urethral reconstruction using either pedicled penile flaps or lingual mucosa grafts. We also assess the histocompatibility of the reconstructed urethra. MATERIALS AND METHODS: Clinical data of patients with anterior urethral stenosis undergoing urethra reconstruction by applying different materials were collected from 2014 to 2022 in the Second Hospital of Hebei Medical University. We assessed their efficacy and the occurrence of complications. Patients who required reoperation due to complications were selected. Sections of the reconstructed urethra created with various materials were excised during repair procedures. The excised tissues underwent hematoxylin-eosin staining and immunohistochemistry. Comparison with the original histological morphology was conducted to evaluate histocompatibility. RESULTS: 42 of the 55 patients were cured which showed a surgical success rate of 76.36%. The success rate of urethra reconstruction surgery utilizing lingual mucosa is 71.43% and that of surgeries using pedicled penis flaps is 79.41%. The long-term prognosis of the two groups is similar (P > 0.05). Observations show that the histological morphology of the original epithelium gradually disappeared, leading to adaptive changes to the urinary environment with favorable histocompatibility. CONCLUSION: The application of lingual mucosal and pedicled penis flaps for urethral reconstruction both have a high surgical success rate. The long-term follow-up results are positive. Both methods are viable for urethral reconstruction and exhibit favorable histocompatibility.

Associations between oxidative balance score and chronic kidney disease events in US adults: a population-based study.

Oxidative Balance Scores (OBS) are utilized to assess an individual's antioxidant status, encompassing both dietary and lifestyle factors that contribute to oxidative balance. This study investigates the relationship between OBS and chronic kidney disease (CKD) prevalence among U.S. adults, utilizing data from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. The study involved a cross-sectional analysis of 13,373 individuals from NHANES, focusing on adults aged 20 years or older. OBS was calculated using 20 components, including dietary and lifestyle factors. CKD was identified based on albumin-to-creatinine ratio and estimated glomerular filtration rate, with patients stratified into mild, moderate, and high-risk groups. Statistical analysis included logistic regression models and restricted cubic splines to explore the OBS-CKD relationship. Our findings indicate a statistically significant negative correlation between OBS and CKD prevalence, particularly in mild and moderate-risk groups. Higher OBS quartiles were associated with a decreased likelihood of CKD (OR 0.70; 95% CI 0.53-0.92; P = 0.013). Restricted cubic splines indicated a non-linear, inverse association between OBS and CKD odds for the overall population (P for nonlinearity = 0.017). For mild and moderate CKD risk groups, the relationships were less pronounced (P for nonlinearity = 0.053 and 0.184, respectively), suggesting variability in the OBS-CKD link across different risk levels. The study highlights the potential of elevated OBS as a primary prevention measure for CKD, particularly in individuals with mild to moderate risk. These findings underscore the importance of antioxidant status in CKD risk management and encourage further research into the role of dietary and lifestyle factors in CKD prevention.

No genetic causal relationship between acne and prostate cancer through Mendelian randomization combined with meta-analysis.

Background: Previous observational studies regarding the relationship between acne and prostate cancer have reported inconsistent results. As such studies are prone to biases, we conducted this Mendelian randomization (MR) analysis to better explore the causal association between acne and prostate cancer. Methods: The genetic data for assessing acne were acquired from the largest genome-wide association study (GWAS) of acne by far, and the genetic data for assessing prostate cancer were acquired from the FinnGen consortium, UK Biobank, European Bioinformatics Institute, and IEU OpenGWAS project. We performed two-sample MR analyses using data from these GWASs followed by a meta-analysis to provide an overall evaluation. The primary MR methods used included inverse variance weighted, MR-Egger, and weighted median. Leave-one-out sensitivity tests, Cochran's Q tests, and MR-Egger intercept tests were used to bolster the robustness of the MR results. Results: Through MR combined with meta-analysis, our study found no genetic causal relationship between acne and prostate cancer (p=0.378; odds ratio=0.985; 95% confidence interval, 0.954-1.018). Sensitivity tests ensured the robustness of this result. Conclusion: Acne should not be considered as a morbidity hazard factor for prostate cancer.

SF3B4 promotes Twist1 expression and clear cell renal cell carcinoma progression by facilitating the export of KLF 16 mRNA from the nucleus to the cytoplasm.

Splicing factor 3B subunit 4 (SF3B4) plays important functional roles not only in pre-mRNA splicing, but also in the regulation of transcription, translation, and cell signaling, and its dysregulation contributes to various diseases including Nager syndrome and tumorigenesis. However, the role of SF3B4 and underlying mechanisms in clear cell renal cell carcinoma (ccRCC) remain obscure. In the present study, we found that the expression of SF3B4 was significantly elevated in ccRCC tissues and negatively correlated with the overall survival of ccRCC patients. Upregulation of SF3B4 promotes migration and invasion of ccRCC cells in vitro and in vivo. The promoting effect of SF3B4 on cell migration and invasion is mediated by Twist1, a key transcription factor to mediate EMT. Interestingly, SF3B4, a component of the pre-mRNA spliceosome, is able to promote KLF16 expression by facilitating the transport of KLF16 mRNA into the cytoplasm. Mechanistically, SF3B4 promotes the export of KLF16 mRNA from the nucleus to the cytoplasm and thus enhances KLF16 expression, and in turn elevated KLF16 directly binds to the Twist1 promoter to activate its transcription, leading to EMT and ccRCC progression. Our findings provide evidence that the SF3B4-KLF16-Twist1 axis plays important functional roles in the development and progression of ccRCC, and manipulating this pathway may be a novel therapeutic target for the treatment of ccRCC.

Robotic adrenalectomy versus laparoscopic adrenalectomy for pheochromocytoma: a systematic review and meta-analysis.

INTRODUCTION: The application of robotic adrenalectomy (RA) has been increasing. However, there is still controversy about whether RA is more feasible than laparoscopic adrenalectomy (LA) for pheochromocytoma (PHEO). AIM: To evaluate the efficacy and safety of RA vs. LA for PHEO. MATERIAL AND METHODS: A literature search of the PubMed, Ovid, and Scopus databases was performed to identify eligible studies up to April 2021. All studies comparing RA versus LA for PHEO were included. Data were analysed using the Cochrane Collaboration's Review Manager (RevMan) 5.4 software. RESULTS: Overall, 4 studies including 386 patients (RA 155; LA 231) were included. RA might have larger tumour size (WMD = 0.72 cm, 95% CI: 0.31 to 1.13; p < 0.001). There were no statistically significant differences in operative time (WMD = -12.49 min, 95% CI: -29.50 to 4.52; p = 0.15), estimated blood loss (EBL) (WMD = -28.48 ml, 95% CI: -58.92, 1.95; p = 0.07), transfusion rate (OR = 0.70, 95% CI: 0.07 to 7.07; p = 0.77), or conversion rate (OR = 0.44, 95% CI: 0.07 to 2.88; p = 0.39). There were no significant differences between the 2 groups in terms of postoperative complications (OR = 1.06, 95% CI: 0.62 to 1.82; p = 0.84) and Clavien Dindo score ≥ 3 complications (OR = 1.15, 95% CI: 0.39 to 3.41; p = 0.80). Patients from the RA group could benefit from shorter length of hospital stay (WMD = -0.51 days, 95% CI -0.91 to -0.12; p = 0.01). CONCLUSIONS: RA is a feasible, safe, and comparable treatment option for PHEO.

Identification of a potentially functional circRNA-miRNA-mRNA ceRNA regulatory network in bladder cancer by analysis of microarray data.

BACKGROUND: Circular RNAs (circRNAs) have received increasing attention in cancer development. However, a substantial number of circRNAs still require characterization. The purpose of this study is to uncover novel circRNAs and their molecular mechanism in bladder cancer (BCa). METHODS: A combinative strategy of extensive data mining and computational biology was employed to identify BCa-related circRNAs and explore their potential mechanisms of action. RESULTS: Three differentially expressed circRNAs (has_circ_0023642, has_circ_0047322, has_circ_0041151) were obtained from the microarray dataset (GSE92675). Four miRNAs (miR-616, miR-515-5p, miR-647, miR-1178) with potential binding sites with these three circRNAs were identified. Pathway analysis demonstrated that all four miRNAs were closely associated with some cancer-related pathways. Survival analysis indicated that these miRNAs might potentially play a role in tumor-suppressive functions in BCa. Subsequently, 181 overlapping genes were identified from 472 up-regulated genes in BCa (TCGA database), and 10,017 predicted target genes of the four miRNAs obtained. A circRNA-miRNA-mRNA network was constructed on the identified three circRNAs, four miRNAs, and 181 overlapping genes. Besides, six hub genes (CENPA, HIST1H2BJ, HIST1H2BO, HIST1H3H, HIST1H3B, HIST1H3F) were identified from establishing a protein-protein interaction (PPI) network on the same overlapping genes. Furthermore, a circRNA-miRNA-hub gene sub-network was built to delineate the links among the differential circRNAs, miRNA, and hub genes. CONCLUSIONS: Our study provided significant insights into the molecular mechanisms that regulate the progression of BCa from the circRNA-miRNA-mRNA network view.

RBM24 exacerbates bladder cancer progression by forming a Runx1t1/TCF4/miR-625-5p feedback loop.

RNA-binding motif protein 24 (RBM24) acts as a multifunctional determinant of cell fate, proliferation, apoptosis, and differentiation during development by regulating premRNA splicing and mRNA stability. It is also implicated in carcinogenesis, but the functions of RBM24 in bladder cancer (BC) remain unclear. In the present study, we revealed that RBM24 was upregulated in BC tissues. Importantly, we found that a higher level of RBM24 was correlated with poor prognosis in BC patients. Overexpression of RBM24 promoted BC cell proliferation, while depletion of RBM24 inhibited BC cell proliferation in vivo and in vitro. Mechanistically, RBM24 positively regulated Runx1t1 expression in BC cells by binding to and enhancing Runx1t1 mRNA stability. Furthermore, Runx1t1 in turn promoted RBM24 expression by interacting with the transcription factor TCF4 and suppressing the transcription of miR-625-5p, which directly targets RBM24 and suppresses RBM24 expression. RBM24-regulated BC cell proliferation was moderated via the Runx1t1/TCF4/miR-625-5p feedback loop. These results indicate that the RBM24/Runx1t1/TCF4/miR-625-5p positive feedback loop participates in BC progression. Disruption of this pathway may be a potential therapeutic strategy for BC treatment.

CDK13 upregulation-induced formation of the positive feedback loop among circCDK13, miR-212-5p/miR-449a and E2F5 contributes to prostate carcinogenesis.

BACKGROUND: Both E2F transcription factor and cyclin-dependent kinases (CDKs), which increase or decrease E2F activity by phosphorylating E2F or its partner, are involved in the control of cell proliferation, and some circRNAs and miRNAs regulate the expression of E2F and CDKs. However, little is known about whether dysregulation among E2Fs, CDKs, circRNAs and miRNAs occurs in human PCa. METHODS: The expression levels of CDK13 in PCa tissues and different cell lines were determined by quantitative real-time PCR and Western blot analysis. In vitro and in vivo assays were preformed to explore the biological effects of CDK13 in PCa cells. Co-immunoprecipitation anlysis coupled with mass spectrometry was used to identify E2F5 interaction with CDK13. A CRISPR-Cas9 complex was used to activate endogenous CDK13 and circCDK13 expression. Furthermore, the mechanism of circCDK13 was investigated by using loss-of-function and gain-of-function assays in vitro and in vivo. RESULTS: Here we show that CDK13 is significantly upregulated in human PCa tissues. CDK13 depletion and overexpression in PCa cells decrease and increase, respectively, cell proliferation, and the pro-proliferation effect of CDK13 is strengthened by its interaction with E2F5. Mechanistically, transcriptional activation of endogenous CDK13, but not the forced expression of CDK13 by its expression vector, remarkably promotes E2F5 protein expression by facilitating circCDK13 formation. Further, the upregulation of E2F5 enhances CDK13 transcription and promotes circCDK13 biogenesis, which in turn sponges miR-212-5p/449a and thus relieves their repression of the E2F5 expression, subsequently leading to the upregulation of E2F5 expression and PCa cell proliferation. CONCLUSIONS: These findings suggest that CDK13 upregulation-induced formation of the positive feedback loop among circCDK13, miR-212-5p/miR-449a and E2F5 is responsible for PCa development. Targeting this newly identified regulatory axis may provide therapeutic benefit against PCa progression and drug resistance.

Desloratadine, a Novel Antigrowth Reagent for Bladder Cancer.

Desloratadine, a potent antagonist for human histamine H1 receptor, has been revealed to exhibit antihistaminic activity and anti-inflammatory activity. However, it is not yet known whether desloratadine has any effect on the biological behaviors of tumor cells. In this study, we aimed to investigate the effects of desloratadine on cell growth and invasion in bladder cancer EJ and SW780 cells in vitro. We observed that desloratadine inhibited cell viability of EJ and SW780 cells in a dose- and time-dependent manner. Desloratadine treatment was also revealed to suppress colony-formation ability and induce cell cycle arrest at G1 phase in EJ cells. Desloratadine promoted cell apoptosis via modulating the expression of Bcl-2, Bax, cleaved caspase 3, and cleaved caspase 9 in EJ and SW780 cells. Western blot resulted showed that desloratadine also impaired the expression of autophagy-related proteins, such as Beclin 1, P62, and LC3I/II in EJ and SW780 cells; while autophagy inhibitor LY294002 reversed the effects of desloratadine on these proteins. Moreover, desloratadine remarkably attenuated cell migration and invasion. Furthermore, we illustrated that desloratadine downregulated the expression of N-cadherin, Vimentin, Snail1, and Snail2, while upregulated the expression of E-cadherin in EJ and SW780 cells in vitro. The level of interleukin 6 was reduced in desloratadine-treated cells, while upregulation of interleukin 6 significantly abolished the anticancer activity of desloratadine in cell invasion and Bcl-2, Bax, Beclin1, LC3-I/II, N-cadherin, and E-cadherin expression in EJ cells. Taken together, our data suggest a potential anticancer activity of desloratadine on cell growth and invasion for bladder cancer, which may be mediated by diminishing the epithelial-to-mesenchymal transition and interleukin 6.