AAT resistance-related AC007405.2 and AL354989.1 as novel diagnostic and prognostic markers in prostate cancer.

OBJECTIVE: Prostate cancer (PCa) is the second disease threatening men's health, and anti-androgen therapy (AAT) is a primary approach for treating this condition. Increasing evidence suggests that long non-coding RNAs (lncRNAs) play crucial roles in the development of PCa and the process of AAT resistance. The objective of this study is to utilize bioinformatics methods to excavate lncRNAs association with AAT resistance and investigate their biological functions. METHODS: AAT resistance-related risk score model (ARR-RSM) was established by multivariate Cox analysis. Paired clinical tissue samples of 36 PCa patients and 42 blood samples from patients with PSA over 4 ng/ml were collected to verify the ARR-RSM. In vitro, RT-qPCR, CCK-8 and clone formation assays were displayed to verify the expression and function of AL354989.1 and AC007405.2. RESULTS: Pearson correlation analysis identified 996 lncRNAs were associated with AAT resistance (ARR-LncRs). ARR-RSM was established using multivariate Cox regression analysis, and PCa patients were divided into high-risk and low-risk groups. High-risk patients showed increased expression of AL354989.1 and AC007405.2 had poorer prognoses. The high-risk score correlated with advanced T-stage and N-stage. The AUC of ARR-RSM outperformed tPSA in diagnosing PCa. Silencing of AC007405.2 and AL354989.1 inhibited PCa cells proliferation and AAT resistance. CONCLUSIONS: In this study, we have discovered the clinical significance of AC007405.2 and AL354989.1 in predicting the prognosis and diagnosing PCa patients. Furthermore, we have confirmed their correlation with various clinical features. These findings provide potential targets for PCa treatment and a novel diagnostic and predictive indicator for precise PCa diagnosis.

MiR-15b-3p weakens bicalutamide sensitivity in prostate cancer via targeting KLF2 to suppress ferroptosis.

Bicalutamide (BIC) resistance impedes the treatment of prostate cancer (PCa) and seems to involve ferroptosis; however, the underlying mechanism remains unclear. Our study aimed to explore how miR-15b-3p modulates ferroptosis in response to BIC resistance and determine whether the miRNA is suitable for early screening of PCa. Here, we found that PCa tissues had significantly higher miR-15b-3p expression than adjacent normal tissues. Analysis of blood samples in patients who underwent prostate-specific antigen (PSA) screening revealed that miR-15b-3p was a more accurate diagnostic than PSA (miR-15b-3p area under the curve [AUC] = 0.941, PSA AUC = 0.815). In vitro experiments then demonstrated that miR-15b-3p expression was markedly higher in LNCaP, PC-3, and DU145 cells than in RWPE-1 cells. Treatment with BIC decreased miR-15b-3p expression and progressive ferroptosis. Mechanistically, we identified KLF2 as the downstream target of miR-15b-3p. Overexpressing KLF2 facilitated ferroptosis via augmenting MDA and iron concentrations, in turn inhibiting the SLC7A11/GPX4 axis and decreasing GSH concentration. Through modulating ferroptosis, miR-15b-3p mimic and inhibitor weakened and enhanced BIC sensitivity, respectively. Furthermore, BIC treatment limited xenograft tumor volume in vivo, whereas agomir-15b-3p promoted tumor growth, indicating that miR-15b-3p attenuated the tumor-suppressive effects of BIC. Taken together, our results suggested that miR-15b-3p is crucial to BIC resistance, specifically via targeting KLF2 and thereby suppressing ferroptosis. High miR-15b-3p expression in early PCa screening should reflect a higher probability of cancer. In conclusion, miR-15b-3p has strong potential as a screening and diagnostic biomarker with reliable prospects for clinical application. Furthermore, because patients with high miR-15b-3p and low KLF2 expression have a greater risk of BIC resistance and malignant progression, targeting the miRNA and its downstream protein may be a new treatment strategy.

Evaluation of risk factors, treatment options, and prognostic-related factors in patients with benign ureteral strictures: An 8-year single-center experience.

OBJECTIVES: To investigate the etiology, therapeutic effect, and prognosis-related factors of benign ureteral strictures. METHODS: We analyzed the date of 142 patients with benign ureteral strictures from 2013 to 2021. Ninety-five patients received endourological treatment and 47 patients underwent reconstruction. Preoperative, intraoperative, and postoperative information were compared and analyzed. Symptomatic improvement and radiographic blockage alleviation defined therapeutic success. RESULTS: Stone-related factors caused 85.2% of cases. The overall success rate of endourological treatment was 51.6% versus 95.7% of reconstruction (p < 0.01). However, endourological treatment was better in terms of postoperative hospital stay time, operation time, and intraoperative blood loss (p < 0.001). In endourological group, patients with stricture length ≤2 cm, mild-to-moderate hydronephrosis, proximal or distal stricture had a higher success rate. Multivariate regression analysis showed that the surgical method was the only independent risk factor affecting success and recurrence. Reconstruction success rate was higher than endourological treatment (p = 0.001, OR 0.057, 95% CI (0.011-0.291)), and recurrence rate was also lower (p = 0.001, HR 0.074, 95% CI (0.016-0.338)). No obvious recurrence was seen in reconstruction, and the median recurrence time in endourological treatment was 51 months. CONCLUSIONS: Stone-related factors are an important cause of benign ureteral strictures. Reconstruction is the gold standard treatment due to its high success rate and low recurrence rate. Endourological therapy is also preferred as the initial treatment in proximal or distal ureter with length ≤2 cm and mild-to-moderate hydronephrosis. Further close follow-up is required after treatment.

Starvation-induced long non-coding RNAs are significant for prognosis evaluation of bladder cancer.

BACKGROUND: Starving intratumoral microenvironment prominently alters genic profiles including long non-coding RNAs (lncRNAs), which further regulate bladder cancer (BCa) malignant biological properties, such as invasion and migration. METHODS: Transcriptome RNA-sequencing data of 414 BCa tumor tissues and 19 normal tissues were obtained from TCGA database and paired samples of 132 BCa patients. A chain of in vitro validations such as qPCR, migration and invasion assays were performed to reveal the clinical relevance of AC011472.4 and AL157895.1. RESULTS: A total of 11 lncRNAs were identified as starvation-related lncRNAs, of which AC011472.4 and AL157895.1 were relevant to overall survival of BCa patients. Besides, a starvation-related risk score model was established based on the levels of AC011472.4 and AL157895.1. BCa patients with higher levels of AL157895.1 were divided into the high-risk group and usually obtained higher mortality rate, but AC011472.4 was contrary. AL157895.1 expressed highly in BCa cell lines and tumour tissues, especially in patients with the advanced grade, stage and T-stage, while AC011472.4 showed the reversed result. Moreover, increased level of AL157895.1 was remarkably correlated to T-stage, muscle invasion status and distant metastasis. SiRNAs-mediated silence of AC011472.4 and AL157895.1 respectively increased and diminished invasion and migration properties of BCa cells. CONCLUSIONS: In this study, we highlight the significant roles of AC011472.4 and AL157895.1 on evaluating prognoses of BCa patients and validate their correlation with various clinical parameters. These findings provide an appropriate risk score model for BCa clinical decision making.

Age-related changes in eggshell physical properties, ultrastructure, calcium metabolism-related serum indices, and gene expression in eggshell gland during eggshell formation in commercial laying ducks.

This study evaluated the changes in eggshell mechanical properties, ultrastructure, calcium metabolism-related serum indices, and gene expression in eggshell gland during eggshell formation between laying ducks in the peak (young duck) and late phase (aged duck) of production. A total of 84 healthy young (31 wk of age) and 84 healthy aged (65 wk of age) Longyan laying ducks were each divided into 6 replicates of 14 birds, and caged individually. All the ducks were fed in one house with the same corn-soybean meal-based diet for 5 wk. The eggshell mechanical properties (shell proportion, thickness, breaking strength, and fracture toughness) and chemical components (matrix proteins, calcium, phosphorus, and magnesium) decreased in aged laying ducks (P < 0.05). Shell structural indices: total thickness, effective thickness and its proportion decreased, whereas mammillary knob width and its proportion increased (P < 0.05). The regulation values of early fusion, cuffing, caps, and total score of mammillary knobs were higher in aged laying ducks relative to the young ducks (P < 0.05). During the initial, growth and terminal stages of eggshell formation, shell thickness and breaking strength (terminal), shell weight, and its proportion (terminal) decreased in aged laying ducks (P < 0.05). Ultrastructural changes during shell formation indicated that the mammillary-knob density and effective thickness decreased (P < 0.05). Decreases occurred in serum content of phosphorus (growth), and estradiol and calcium contents (terminal) (P < 0.05). Relative expression of Ca2+ transporter and HCO3- exchanger, and matrix proteins genes decreased in aged laying ducks (P < 0.05) at all stages of eggshell formation. Collectively, the decreased incidence of early fusion and caps, increased thickness and width of mammillary knobs, and decreased effective thickness are the crucial differences leading to the compromised mechanical properties of eggshell in the late laying period. A disturbed regulation of calcium metabolism and uterine expression of ion transporters, especially for HCO3- exchange of aged laying ducks likely contribute to age-induced ultrastructural deterioration of the eggshell.

Dietary zinc supplementation affects eggshell quality and ultrastructure in commercial laying ducks by influencing calcium metabolism.

This study evaluated dietary Zn supplementation on productive performance, eggshell quality and ultrastructure, and calcium metabolism during eggshell formation in laying ducks. A total of 360 Longyan laying ducks (45-wk) were randomly divided into 5 treatment groups with 6 replicates of 12 birds each and fed for 20 wk. The 6 treatments fed the basal diet supplemented with 0 (control), 20, 40, 80, or 160 mg Zn/kg (ZnSO4·H2O). Dietary supplemental level at 80 mg/kg increased egg production (4.3%) and mass (5.7%), and decreased FCR (2.9%) compared to the basal diet, and these indices increased quadratically with increasing Zn supplemental levels (P < 0.05). The shell breaking strength (15.8%) and fracture toughness (10.6%) were higher with the supplementation of Zn at 80 mg/kg than the basal diet, and increased quadratically with Zn supplementation (P < 0.05). Dietary supplementation of Zn at 80 mg/kg improved shell ultrastructure by increasing total (9.0%) and effective thickness (14.2%) and decreasing mammillary thickness (12.0%), and their responses were quadratic with increasing Zn levels (P < 0.05). The supplementation of Zn affected the calcium contents in plasma, tibias and ulna, ulna phosphorus content, and linear and quadratic effects were observed, and higher values were observed with 160 mg/kg Zn supplementation than control (P < 0.05). The supplemental Zn level at 80 mg/kg increased shell effective thickness in growth stage (P < 0.05), and shell calcium and phosphorus content in initial and growth stages (P < 0.05). Dietary Zn supplementation did not affect the gene expression of Ca2+ transporters in the eggshell gland, but affected the expression of HCO3- exchanger in initial and growth stage (P < 0.05). Overall, dietary Zn supplementation could improve productive performance and shell quality in laying ducks at late phase of production, and calcium metabolism and deposition were modulated by Zn influencing HCO3- secretion and thus affecting shell ultrastructure and quality. A supplemental level of 80 mg/kg Zn in the diet with a basal content of 34.0 mg/kg was optimal, and higher level (160 mg/kg) decreased shell calcium deposition by depressing its metabolism.

Post ureteroscopic stone surgery ureteral strictures management: a retrospective study.

PURPOSE: To share experience in managing ureteral strictures following ureteroscopic lithotripsy. METHODS: Ninety five patients diagnosed as ureteral strictures after ureteroscopic lithotripsy between January 2013 and January 2018 were included. 53 received endourological treatment, 34 underwent reconstruction, 6 underwent nephrectomy for severe renal impairment, and 2 chose routine ureteral stent replacement. Therapeutic success was defined as absence of clinical symptoms and radiologic relief of obstruction. RESULTS: The follow-up time ranged from 13 to 57 months, with a median time of 24. It lasted more than 13 months in all patients, exception for 2 nephrectomies. Two patient groups including 69 endourological procedures and 37 reconstructions were used to compare therapeutic effects and complications. The overall success rate was 60.9% (42/69) in endourological intervention vs. 97.3% (36/37) in reconstruction (p < 0.001), while 74.4% (29/39) patients with stricture less than 1 cm and 68.8% (33/48) patients with mild-to-moderate hydronephrosis achieved success in endourological group. All except 1 failure appeared within the first year postoperatively. Subgroup analyses for endourological procedures revealed significant differences in the success rate of different stricture lengths and hydronephrosis (p = 0.004 and p = 0.043). Multivariate Cox regression analysis indicated that reconstruction was significantly related to a more successful outcome, compared with endourological procedures (HR 0.052, 95% CI 0.007-0.394, p = 0.004). CONCLUSION: Reconstruction performs better than endourological procedures in surgical outcome. Endourological procedure provides an acceptable success rate in patients with stricture shorter than 1 cm and slight hydronephrosis. Most stricture recurrence appeared within the first year postoperatively.

Cough Test during Tension-Free Vaginal Tape Procedure in Preventing Postoperative Urinary Retention.

Objective. To discuss the practical value of the cough test during the tension-free vaginal tape (TVT) procedure. Methods. In the first group, 41 patients of female stress incontinence received TVT operations which were performed according to the Ulmsten's method strictly, only that the stress of tape was adjusted in light of the cough test. In the second group, 44 patients of female stress incontinence received TVT operations in which the tape was put under the urethral tract without stress, not adjusted by cough test. Results. The cure rate was 38/41 (92.6%) in the cough test group and 41/44 (93.1%) in the noncough test group; detrusor pressure-uroflow study indicated that there were 11 cases in the obstruction zone in the cough test group while only 3 cases were in the obstruction zone in the noncough test group; 4 cases of urinary retention and 5 cases of voiding dysfunction were found in the cough test group, while difficulties of urination were not found in the non-cough test group. Conclusion. Adjusting the tape stress in accordance with the cough test during the TVT can increase the opportunity of urinary retention or difficulty of urination after operation. So there is no benefit of the cough test during tension-free vaginal tape procedure in preventing post-operative urinary retention.

Laparoscopic radical cystectomy for bladder cancer with prostatic and neurovascular sparing: initial experience.

PURPOSE: This study presents our initial experience with laparoscopic radical cystectomy with preservation of the neurovascular bundles and partial prostate for the treatment of bladder cancer. METHODS: Thirty-seven patients with bladder cancer were selected for the study between June 2007 and December 2009. The criteria for patient selection included prostate-specific antigen level below 4.0 ng/mL; negative involvement of the trigone and/or prostatic urethra; and no self-reported erectile dysfunction. The surgical procedure included laparoscopic prostate- and neurovascular bundles-sparing cystectomy with an ileal neobladder construction. Mean follow-up was 18 months. RESULTS: All patients underwent laparoscopic resection without requiring a traditional open procedure. The mean operation time was 215 min with a mean volume of intraoperative hemorrhage of 190 mL. After removal of the urinary catheter, all patients had a daytime urinary continence; six had a short period of nighttime urinary incontinence. Most patients reported a strong desire for sexual activity and were able to complete sexual intercourse without auxiliary measures at 3 months postoperatively. Grade-3 complications developed in 2 patients graded by the classification of Clavien system. One patient was diagnosed with pelvic recurrence 16 months postoperatively. CONCLUSION: The laparoscopic radical cystectomy with a partial prostate preservation offers the advantages of a high continence, minimal impairment of erectile function, and low recurrence rate.

Transplantation of endothelial progenitor cells transfected with VEGF165 to restore erectile function in diabetic rats.

The present study investigated the effect of transplanting endothelial progenitor cells (EPCs) transfected with the vascular endothelial growth factor gene (VEGF165) into the corpora cavernosa of rats with diabetic erectile dysfunction (ED). A rat model of diabetic ED was constructed via intraperitoneal injection of streptozotocin. After streptozotocin treatment, pre-treated EPCs from each of three groups of rats were transplanted into their corpora cavernosa. Our results, following intracavernosal pressure (ICP) monitoring, showed that ICP increased significantly among rats in the trial group when compared to the results from rats in the blank-plasmid and control groups during basal conditions and electrical stimulation (P<0.01 for both comparisons). Histological examination revealed extensive neovascularisation in the corpora cavernosa of rats in the trial group. Fluorescence microscopy indicated that many of the transplanted EPCs in the trial group survived, differentiated into endothelial cells and integrated into the sites of neovascularisation. Based on the results of this study, we conclude that transplantation of VEGF165-transfected EPCs into the corpora cavernosa of rats with diabetic ED restores erectile function.