Identification of molecular subtypes and diagnostic model in clear cell renal cell carcinoma based on collagen-related genes may predict the response of immunotherapy.

Background: Collagen represents a prominent constituent of the tumor's extracellular matrix (ECM). Nonetheless, its correlation with the molecular subtype attributes of clear cell renal cell carcinoma (ccRCC) remains elusive. Our objective is to delineate collagen-associated molecular subtypes and further construct diagnostic model, offering insights conducive to the precise selection of ccRCC patients for immunotherapeutic interventions. Methods: We performed unsupervised non-negative matrix factorization (NMF) analysis on TCGA-KIRC samples, utilizing a set of 33 collagen-related differentially expressed genes (33CRDs) for clustering. Our analysis encompassed evaluations of subtype-associated differences in pathways, immune profiles, and somatic mutations. Through weighted gene co-expression network analysis (WGCNA) and four machine learning algorithms, two core genes were found and a diagnostic model was constructed. This was subsequently validated in a clinical immunotherapy cohort. Single cell sequencing analysis and experiments demonstrated the role of core genes in ccRCC. Finally, we also analyzed the roles of MMP9 and SCGN in pan-cancer. Results: We described two novel collagen related molecular subtypes in ccRCC, designated subtype 1 and subtype 2. Compared with subtype 1, subtype 2 showed more infiltration of immune components, but had a higher TIDE (tumor immunedysfunctionandexclusion) score and increased levels of immune checkpoint molecules. Furthermore, reduced prognosis for subtype 2 was a consistent finding in both high and low mutation load subgroups. MMP9 and SCGN were identified as key genes for distinguishing subtype 1 and subtype 2. The diagnostic model based on them could better distinguish the subtype of patients, and the differentiated patients had different progression free survival (PFS) in the clinical immunotherapy cohort. MMP9 was predominantly expressed in macrophages and has been extensively documented in the literature. Meanwhile, SCGN, which was overexpressed in tumor cells, underwent experimental validation, emphasizing its role in ccRCC. In various cancers, MMP9 and SCGN were associated with immune-related molecules and immune cells. Conclusion: Our study identifies two collagen-related molecular subtypes of ccRCC and constructs a diagnostic model to help select appropriate patients for immunotherapy.

Evaluation of transrectal ultrasound-based dosimetry for brachytherapy of prostate cancer: a single-center experience.

PURPOSE: To explore the possibility of intraoperative transrectal ultrasound (TRUS)-based dose verification in transperineal brachytherapy (BT) with iodine-125 (125I) seeds for prostate cancer. MATERIAL AND METHODS: Fifteen patients with prostate cancer were treated using BT with 125I seeds. Post-implant TRUS and computed tomography (CT) images were imported into treatment planning system (TPS) for dosimetry. Dosimetry parameters, including minimum dose received by 90% of the volume (D90), percentage of the volume receiving 100% of prescribed dose (V100), and percentage of the volume receiving 200% of prescribed dose (V200) were calculated based on TRUS and CT images, separately. The D90 value of TRUS-based dosimetry was transformed to its expected value. Comparisons of the dosimetric parameters between post-operative verification and preoperative plans were made by paired t-test. One-way ANOVA model was used to assess the differences in preoperative plans. Agreements were evaluated between the preoperative planning and post-operative actual dose parameters using Bland-Altman analysis. RESULTS: In total, 825 of 125I seeds were implanted successfully in 15 patients. In TRUS-based dosimetry, 674 seeds (81%) were identified clearly in TRUS-based images, and the expected value of D90 parameter showed no significant differences compared with the preoperative planning and CT post-operation results (p > 0.05). In CT-based dosimetry, 810 seeds (98%) were identified clearly in CT-based images, and there was good consistency of D90, V100, and V200 values (p > 0.05). Post-implant CT-based dosimetry indicated that 125I seed implantation had fulfilled the expected plan. CONCLUSIONS: Intraoperative TRUS can be used for dosimetric verification of BT for prostate cancer.

Silencing of miR-152 contributes to DNMT1-mediated CpG methylation of the PTEN promoter in bladder cancer.

AIM: Bladder cancer (BCa) is one of the most commonly occurring urological malignancy. DNA methylation mediated by DNA methyltransferase 1 (DNMT1) plays a crucial role in the physiological and pathological processes of cancer. However, the role of upstream regulatory factors and downstream target genes of DNA methylation mediated by DNMT1 needs further study in BCa. We aim to discover the upstream regulatory factor and downstream target gene of DNMT1, which form a signaling pathway to regulate the progression of BCa. MAIN METHODS: DNMT1 expression in BCa tissues and cells was detected by qPCR and Western Blot. Balbc/nu/nu mice were used to determine the relationship between DNMT1 expression and tumor growth. CCK8, EdU, and transwell assays were employed to measure cell viability, proliferation, and migration respectively. RNA immunoprecipitation (RIP) assays and dual luciferase reporter assays were applied to determine the relationships among DNMT1, miR-152-3p and PTEN. KEY FINDINGS: A significant up-regulation of DNMT1 in BCa tissues and cells, and silencing of DNMT1 expression inhibited the tumor growth in vivo. Knockdown of DNMT1 inhibited the cell growth and migration of BCa cells. miR-152-3p inhibited the DNMT1 and over-expression of DNMT1 restored the cellular function of miR-152-3p in BCa cells. DNMT1 regulated the phosphatase and tensin homolog (PTEN) expression via modulating the status of DNA methylation in the promoter of PTEN. SIGNIFICANCE: This study confirmed the role and underlying mechanism of DNMT1-mediated DNA methylation and displayed a novel regulatory pathway miR-152/DNMT1/PTEN in BCa, thus, providing a potential diagnostic and therapeutic targets for BCa.

Efficacy and safety of periprostatic nerve block combined with perineal subcutaneous anaesthesia and intrarectal lidocaine gel in transrectal ultrasound guided transperineal prostate biopsy: A Prospective Randomised Controlled Trial.

BACKGROUND: To determine the efficacy and safety of a periprostatic nerve block combined with perineum subcutaneous anaesthesia and intrarectal lidocaine gel for transrectal ultrasound-guided transperineal prostate biopsy (TPBx) through a prospective randomised controlled trial. METHODS: In total, 216 patients from May 2018 to November 2018 were randomly assigned to the experimental group and the control group at a ratio of 1:1. The experimental group received a periprostatic nerve block combined with subcutaneous perineal anaesthesia and intrarectal lidocaine gel. The control group received total intravenous anaesthesia. A visual analogue scale (VAS) score (0-10) was used to evaluate pain at different stages. The operative time, duration of hospitalisation, intraoperative vital signs, perioperative complications and clinicopathological features were recorded. RESULTS: The overall detection rate of prostate cancer was 40.74%, and the median Gleason score was 8 for all patients diagnosed with prostate cancer. No significant differences in terms of detection rates, Gleason scores and ISUP/WHO Grade Groups were found between the two groups (P > 0.05). The experimental group had no pain or just met the criteria for mild pain during the biopsy, which was significantly alleviated after the biopsy, and had a shorter operation time compared with that of the control group (P < 0.05). Compared with the control group, the experimental group had more stable haemodynamics and respiratory status and fewer surgical complications (P < 0.05). CONCLUSIONS: In multiple aspects, a periprostatic nerve block combined with subcutaneous perineal anaesthesia and intrarectal lidocaine gel is a safer and more efficient approach to local anaesthesia for TPBx that can almost replace total intravenous anaesthesia and is worthwhile applying in the clinical setting.

Tamsulosin as a Medical Expulsive Therapy for Ureteral Stones: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

PURPOSE: Tamsulosin is widely administered as a medical expulsive therapy to facilitate stone passage in patients with ureteral calculi. Recently several large, multicenter, randomized controlled trials revealed conflicting results, which led to considerable uncertainty about the efficacy of tamsulosin in the management of ureteral stones. The objective of this systematic review and meta-analysis was to evaluate the efficacy and safety of tamsulosin in the management of ureteral stones. MATERIALS AND METHODS: We searched MEDLINE®, Embase®, Web of Knowledge, Google Scholar™ and the Cochrane Central Search Library databases up to June 2018. Two reviewers independently evaluated eligible randomized controlled trials of the efficacy of tamsulosin to treat ureteral stones. Study quality was assessed with the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) system. Subgroup analyses were performed to explore heterogeneity. RESULTS: Included in study were 56 randomized controlled trials in a total of 9,395 patients. The observed treatment effect indicated that tamsulosin was associated with a higher stone expulsion rate (RR 1.44, 95% CI 1.35-1.55, p <0.01), a shorter stone expulsion time (weighted mean difference -0.73, 95% CI -1.00--0.45, p <0.01), a lesser incidence of ureteral colic (weighted mean difference -0.81, 95% CI -1.24--0.39, p <0.01) and fewer incidences of requiring subsequent intervention (RR 0.68, 95% CI 0.50-0.93, p = 0.017). Treatment with tamsulosin did not differ from a control group in the overall incidence of side effects (RR 1.14, 95% CI 0.86-1.51, p = 0.36). On subgroup analysis we observed a significant benefit in the stone expulsion rate for tamsulosin among patients with stones greater than 5 mm (RR 1.44, 95% CI 1.22-1.68, p <0.01) but no effect for stones 5 mm or less (RR 1.08, 95% CI 0.99-1.68, p <0.01). CONCLUSIONS: Our current meta-analysis results indicate that tamsulosin is effective and relatively safe in patients with ureteral stone as a medical expulsive therapy to facilitate stone passage. It is suggested to administer it selectively in patients with 5 to 10 mm ureteral stones.

Mini-percutaneous nephrolithotomy for pediatric complex renal calculus disease: one-stage or two-stage?

OBJECTIVES: To compare two different treatment strategies, one-stage and two-stage multi-tract mini-percutaneous nephrolithotomy (mt-mPCNL), for pediatric complex renal calculus disease. METHODS: Between the period of July 2016 and July 2018, a total of 36 children aged 15 years and younger, with complex renal calculi disease, who underwent total ultrasound-guided mt-mPCNL by a single experienced urologist were enrolled in our study. All patients were assigned either to Group 1 (n = 18) who received one-stage mt-mPCNL or Group 2 (n = 18) who received planned two-stage mt-mPCNL. RESULTS: The demographic data were comparable between the two groups. There were no serious complications (Modified Clavien Grade ≥ III) observed in either group. The stone -free rate (SFR), operation time, postoperative creatinine increase, and perioperative complication rates were similar in both groups (P = 0.603, 0.818, 0.161, and 0.402, respectively). The postoperative hospital stay (5.8 days vs. 7.4 days) and cost (17373.3 CNY vs. 23717.1 CNY) were statistically less in Group 1. Group 2 had significantly less total estimated blood loss (70.6 ml vs. 130.0 ml, P < 0.001). The operation time of two cases in Group 1 with perioperative sepsis or systemic inflammatory response syndrome (SIRS) was more than two hours. CONCLUSIONS: Our preliminary results indicated that both one-stage and two-stage mt-mPCNL were safe and effective for pediatric complex renal calculi. Two-stage mt-mPCNL could significantly reduce blood loss; while one-stage mt-mPCNL could significantly decrease the length and costs of hospitalization. We also suggest that the planned two-stage mt-mPCNL should be applied in children with estimated operation time more than two hours.