Enzalutamide is a potent androgen receptor (AR) inhibitor widely used for the treatment of castration-resistant prostate cancer (CRPC). However, the development of drug resistance severely limits its therapeutic efficacy, and the underlying mechanisms remain poorly understood. We have demonstrated that decorin (DCN), a suppressor of prostate cancer (PCa) progression, is significantly down-regulated in enzalutamide-resistant PCa cells. Therefore, we hypothesized that diminished expression of DCN contributes to enzalutamide resistance in PCa. In this study, we found that DCN was decreased in enzalutamide-resistant LNCaP cells (LNCaP-ER), which exhibited resistance to ferroptosis. Consistently, DCN was significantly reduced in high-grade PCa and CRPC tissues, as well as in those with poor clinical survival outcomes through integrative analysis. Moreover, DCN overexpression re-sensitized LNCaP-ER cells to enzalutamide by activating ferroptosis. What's more, DCN overexpression significantly inhibited tumor growth and metastasis of LNCaP-ER cells in vivo under enzalutamide-treated conditions, in a ferroptosis-dependent manner. Mechanistically, DCN activated calcium-dependent Protein Kinase C Beta II (PKCβII), thereby enhancing phosphorylation of long-chain acyl-CoA synthetase 4 (ACSL4) to regulate lipid remodeling and promote ferroptosis. In addition, enzalutamide-mediated AR nuclear translocation negatively regulates DCN transcription. In conclusion, promoting DCN-mediated ferroptosis might be a potential strategy for enhancing the sensitivity of enzalutamide in PCa cells. This study delineates a novel mechanism by which DCN downregulation suppresses ferroptosis and drives enzalutamide resistance in CRPC.

ABSTRACT Background Immune cells have been linked to the initiation and progression of tumors, and their presence is often used to predict disease prognosis. However, when it comes to bladder urothelial carcinoma (BLCA), there has not been a comprehensive investigation into the function and prognostic value of different immune cell types. Methods We integrated data from more than 2300 BLCA patients across 14 public datasets. Then we analyzed the quantity of 170 different immune cell signatures using the ssGSEA algorithm. Through meta‐analysis and univariable Cox analysis, we identified prognosis‐associated immune cells and established an immune cell related prognostic signature (IRPS). We then conducted survival analyses to observe the differences in survival across different IRPS‐risk groups. Furthermore, based on the DEGs associated with IRPS, we screened for potential targeted therapeutic agents. Finally, we integrated IRPS with clinical features to establish a comprehensive prognostic index (ICPI). Results Our analysis identified 90 immune cell types that were particularly relevant to BLCA. Then we constructed and validated the IRPS, with high IRPS significantly associated with longer overall survival (HR = 0.73, 95% CI, 0.71–0.76, p < 0.001). In two independent immunotherapy cohorts (IMvigor210 and GSE78220), patients with high IRPS demonstrated significantly prolonged survival following immune checkpoint inhibitor treatment (p = 0.035, p = 0.019). Several candidate drugs targeting IRPS were identified. The ICPI, developed by integrating IRPS with clinical features, also demonstrated enhanced accuracy in prognostic analysis. Conclusions This study successfully developed and validated a prognostic signature (IRPS) based on comprehensive immune cell infiltration analysis, along with its integrated index (ICPI). IRPS/ICPI serves as an effective tool for predicting BLCA patient prognosis and guiding immunotherapy strategies, while also aiding in the identification of patient populations likely to benefit from immunotherapy.

RNA-binding proteins (RBPs) are pivotal mediators of the alternative splicing (AS) machinery of pre-mRNA. Research has demonstrated that the AS process is significantly dysregulated and plays a crucial role in bladder cancer (BLCA). We conducted comprehensive screening and analysis of the TCGA-BLCA cohort, specifically focusing on genes with significant differences in expression levels between carcinoma and adjacent non-cancerous tissues. Among the 500 differentially expressed genes, 5 RNA-binding proteins were identified. Only the RNA-binding protein with multiple splicing (RBPMS) demonstrated a consistent downregulation in BLCA and was correlated with an unfavorable prognosis for affected patients. Subsequent experiments revealed that RBPMS exerted inhibitory effects on the epithelial-mesenchymal transition (EMT) pathway and the migratory potential of BLCA cells. RNA-Seq analysis identified ANKRD10 as a key target mRNA regulated by RBPMS in BLCA. RBPMS depletion in BLCA cells resulted in AS of ANKRD10 and increased ANKRD10-2 expression. ANKRD10-2 functioned as a transcriptional co-activator of MYC proteins, thereby augmenting their transcriptional activity. Furthermore, ANKRD10-2 knockdown significantly rescued the migration enhancement induced by RBPMS depletion in BLCA cells. Taken together, this study revealed a mechanism whereby RBPMS suppresses the migration and invasion of BLCA cells by attenuating MYC pathway activity via the AS of ANKRD10.

Purpose: To determine the feasibility and safety of a new domestic single-port surgical robot in urologic partial nephrectomy and radical prostatectomy, as measured by the primary metric outcome (surgical success rate). In addition, this study measured important perioperative surgical outcomes, such as operative time, blood loss, postoperative length of stay, docking time, and thermal ischemia time, and reported pathologic data using the surgical robot. Materials and Methods: This prospective, single-center, single-group clinical study was conducted between August 2023 and October 2023. One surgeon used a new domestic single-port surgical robot (EDGE SP1000) to perform six urologic procedures, including three partial nephrectomies and three extraperitoneal radical prostatectomies. Perioperative data were prospectively recorded, early oncologic outcomes were assessed based on the surgical margin status, and equipment ergonomic comfort was assessed using the National Aeronautics and Space Administration Task Load Index (NASA-TLX). Results: All six procedures were effectively completed without conversion to open surgery, laparoscopy, or use of multiport robots. The average total operation time was 207.92 ± 32.42 minutes, estimated blood loss was 100 mL (10-900 mL), and postoperative hospital stay was 8.67 ± 1.33 days. The average docking time was 16.25 ± 5.68 minutes, and warm ischemia time was 17.00 ± 2.65 minutes. None of the patients required perioperative blood transfusion. All pathologic examination margins were negative. No serious perioperative complications occurred (Clavien-Dindo grade 3). The surgeon reported that the device was comfortable to use, with a NASA-TLX score of 35.67 ± 4.23. Conclusions: It is safe and feasible to perform urologic procedure using the EDGE single-port endoscopic surgical robot (EDGE SP1000) control system.

BACKGROUND:Many studies have evaluated the performance of fluorescence in situ hybridization (FISH) in detecting urothelial carcinoma, while few of them compared it in detecting bladder cancer (BC) vs. upper tract urothelial carcinoma (UTUC). This study aimed to determine and compare the FISH performance in detecting BC and UTUC. METHODS:Data of patients with suspected urothelial carcinoma (UC) who accepted FISH from January 2021 to April 2023 were retrieved. The sensitivity and specificity of FISH in detecting BC and UTUC were determined and compared. RESULTS:A total of 145 BC, 62 UTUC, and 170 non-UC patients were included. No significant differences existed between BC and UTUC cohorts in FISH sensitivity (46.2% vs. 51.6%, p = 0.476) and specificity (100% vs. 95.8%, p = 0.271). FISH sensitivity was significantly higher in high-grade vs. low-grade BC and increased gradually from Ta to ≥T2 group. It was also higher in patients with multiple or large tumors or older age. Similar tendencies were observed in UTUC. FISH sensitivity was higher in BC vs. UTUC in detecting T1 or ≥T2 tumors (p < 0.05). Multivariate analysis confirmed the tumor stage and the patient's age as predictors of FISH results in BC. CONCLUSIONS:FISH demonstrated overall similar sensitivity and specificity in detecting BC vs. UTUC, while the sensitivity was higher in BC for T1 or ≥T2 tumors. FISH was more sensitive in detecting more invasive or advanced tumors. The tumor stage and the patient's age were predictors of the FISH result in BC.

BACKGROUND:The burden of common urologic diseases, including benign prostatic hyperplasia (BPH), urinary tract infections (UTI), urolithiasis, bladder cancer, kidney cancer, and prostate cancer, varies both geographically and within specific regions. It is essential to conduct a comprehensive and precise assessment of the global burden of urologic diseases. METHODS:We obtained data on incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) for the aforementioned urologic diseases by age, sex, location, and year from the Global Burden of Disease (GBD) 2021. We analyzed the burden associated with urologic diseases based on socio-demographic index (SDI) and attributable risk factors. The trends in burden over time were assessed using estimated annual percentage changes (EAPC) along with a 95% confidence interval (CI). RESULTS:In 2021, BPH and UTI were the leading causes of age-standardized incidence rate (ASIR) and age-standardized prevalence rate (ASPR), with rates of 5531.88 and 2782.59 per 100,000 persons, respectively. Prostate cancer was the leading cause of both age-standardized mortality rate (ASMR) and age-standardized DALYs rate (ASDR), with rates of 12.63 and 217.83 per 100,000 persons, respectively. From 1990 to 2021, there was an upward trend in ASIR, ASPR, ASMR, and ASDR for UTI, while urolithiasis showed a downward trend. The middle and low-middle SDI quintile levels exhibited higher incidence, prevalence, mortality, and DALYs related to UTI, urolithiasis, and BPH, while the high and high-middle SDI quintile levels showed higher rates for the three cancers. The burden of these six urologic diseases displayed diverse age and sex distribution patterns. In 2021, a high body mass index (BMI) contributed to 20.07% of kidney cancer deaths worldwide, while smoking accounted for 26.48% of bladder cancer deaths and 3.00% of prostate cancer deaths. CONCLUSIONS:The global burden of 6 urologic diseases presents a significant public health challenge. Urgent international collaboration is essential to advance the improvement of urologic disease management, encompassing the development of effective diagnostic screening tools and the implementation of high-quality prevention and treatment strategies.

Background Hepatoid adenocarcinoma (HAC) is rare in the urinary system, with only 7 reported cases in upper urinary tract. This report aimed to explore the genetic characteristics of ureteral HAC for first time, and to describe the treatment prognosis of ureteral HAC. Case presentation We present a rare case of ureteral HAC in a 53-year-old female, showing elevated serum levels of AFP and CEA, prolonged chronic irritation may be an important cause of her ureteral HAC. Radical nephroureterectomy was performed, the serum levels of AFP and CEA decreased significantly, and metastasis in lymph nodes was found at 9 months after surgery, she had no related symptoms after 18 months postoperatively without adjuvant chemotherapy. Three driver somatic mutations in cancer were identified by NGS testing, including: TP53 D281H , KMT2D L1211Ifs*2 , KMT2D T1843Nfs*5 , demonstrating that ureteral HAC has the similar mutational features to upper tract urothelial carcinoma. Homologous-recombination deficiency (HRD) was positive in this tumor with no mutations in HRD-related genes, which was possibly induced by the copy number deletion of SETD2 gene. Conclusions We report a rare case of ureteral HAC with elevated serum levels of AFP and CEA. NGS testing demonstrated that ureteral HAC has the similar mutational features to upper tract urothelial carcinoma, which is an important guide for the diagnosis and treatment of ureteral HAC.

Cell-free DNA (cfDNA), a burgeoning class of molecular biomarkers, has been extensively studied across a variety of biomedical fields. As a key component of liquid biopsy, cfDNA testing is gaining prominence in disease detection and management due to the convenience of sample collection and the abundant wealth of genetic information it provides. However, the broader clinical application of cfDNA is currently impeded by a lack of standardization in the preanalytical procedures for cfDNA analysis. A number of fundamental challenges, including the selection of appropriate preanalytical procedures, prevention of short cfDNA fragment loss, and the validation of various cfDNA measurement methods, remain unaddressed. These existing hurdles lead to difficulties in comparing results and ensuring repeatability, thereby undermining the reliability of cfDNA analysis in clinical settings. This review discusses the crucial preanalytical factors that influence cfDNA analysis outcomes, including sample collection, transportation, temporary storage, processing, extraction, quality control, and long-term storage. The review provides clarification on achievable consensus and offers an analysis of the current issues with the goal of standardizing preanalytical procedures for cfDNA analysis.

Abstract Objectives This study aims to describe a novel dorsal venous complex (DVC) ligation‐free and parietal endopelvic fascia preserving technique for laparoscopic radical prostatectomy and to evaluate its post‐operative outcomes. Methods From April 2020 to May 2021, a total of 125 patients with localized prostate cancer received laparoscopic radical prostatectomy by a single surgeon. In the procedure, a novel technique of DVC ligation‐free and parietal endopelvic fascia preserving was used. Preoperative characteristics of patients and perioperative results were recorded. In this study, continence was defined as zero to one pad per day. Oncological outcomes were evaluated based on positive surgical margin. Results Five patients required a blood transfusion. Mean post‐operative hospital stay was 3.9 days (2–5), and the catheter could be removed on post‐operative day 7 to 9. Final pathologic evaluations were 87 stage pT2, 22 stage pT3a, and 7 pT3b, 9 stage pT4, respectively. The positive surgical margin rate was 10.4% in total. Ninety‐three patients (74.4%) returned to urinary continence 2 months post‐operatively, and 11 patients (11/125) developed biochemical recurrence 6 months post‐operatively. Conclusions The DVC ligation‐free and parietal endopelvic fascia preserving technique provides early recovery from incontinence without adversely affecting the oncological outcome.

Bladder cancer(BC) is one of the most prevalent cancers in the urinary tract, with high recurrence and fatality rates. Research indicates that go-ichi-ni-san complex subunit 1 (GINS1) crucially influences cancer progression by regulating DNA replication through cell cycle modulation. Thus, suppressing the active proliferation of cells in tumor tissues may require silencing GINS1. However, the consequences of GINS1 in bladder cancer aren’t to be determined. In this paper, we examine the role and mechanism of GINS1 in the development of bladder cancer. GINS1 expression levels and prognostic relevance in bladder cancer were validated using Western blotting, immunohistochemistry, and Kaplan-Meier survival analysis. The influence of GINS1 on bladder cancer was investigated using a variety of approaches, including cell transfection, cell counts, transwell migrations, colony formation, and flow cytometry. Immunohistochemistry studies demonstrate that GINS1 expression is increased in bladder cancer tissues. GINS1 silencing resulted in an arrest of the cell cycle at the phase of G0/G1, which inhibited BC cell growth both in vitro and in vivo. GINS1 knockdown also hindered the AKT/mTOR pathway. Furthermore, increased GINS1 expression affects the cell cycle and stimulates the AKT/mTOR pathway, allowing BC to develop more quickly. Consequently, GINS1 occurs as a latent therapeutic target, particularly for individuals with BC.

Background Transrectal (TR) ultrasound guided prostate biopsy and transperineal (TP) ultrasound guided prostate biopsy are the two most commonly used methods to detect prostate cancer, the detection rate of the two biopsy approaches may differ in patients with different clinical characteristics. Here we aimed to compare the prostate cancer detection rate and positive rate of biopsy cores between TR and TP prostate biopsy in patients with different clinical characteristics. Methods We retrospectively analyzed and compared the clinical data of 452 patients underwent TR or TP prostate biopsy in our hospital from June 2017 to September 2021. And patients were stratified according to several clinical characteristic (serum PSA level, prostate volume, PSA density, T stage and ISUP grade), cancer detection rate and positive rate of biopsy cores were compared in different stratified groups. Results There was no significant difference in age, PSA level, prostate volume, and PSA density between the TR and TP groups. TR group had a higher overall cancer detection rate and positive rate of biopsy cores than TP group. Further subgroup analysis showed that TR group had a higher cancer detection rate in patients with prostate volumes 30–80 mL, and that the TR group had a higher positive rate of biopsy cores among the patients with T3–T4 stages, while TP group had a higher positive rates of biopsy cores among the patients with T1–T2 stages. There were no significant differences between the TR and TP groups for each subgroup when stratified by PSA level, PSA density and ISUP grade. Conclusions TR approach may have advantage in patients with prostate volumes 30–80 mL and T3–T4 stages, while TP approach may have advantage in patients with T1–T2 stages.

Lymphorrhea following retroperitoneal surgery is a challenging complication. This study aimed at exploring the efficiency, mechanisms of immunotherapeutic agent OK-432 in urological cancer-associated lymphorrhea. Intracavitary administration of OK-432 suppressed lymphorrhea after urological tumorectomy. In malignancy-related lymphorrhea, researches on OK-432 was in high-profile. Expressions of VEGFC increased in infiltrating urothelial cancer compared to superficial tumor and was correlated to immune cell infiltration. OK-432 impaired T24 cells viability and anchorage-independent growth by inhibiting Akt/NFκB-mediated VEGFC expression, while facilitated migration and tube formation of lymphatic endothelial cells by enhancing Akt/NFκB-mediated VEGFR-3 expression. OK-432 is an alternative for the lymphorrhea after urological tumorectomy by promoting VEGFR-3 mediated-lymphatic endothelial cells migration and impairing viability of cancer cells through down-regulating expression of VEGFC, and both of which were Akt/NFκB signaling dependent.

Background Globally, despite prostate cancer (PCa) representing second most prevalent malignancy in male, the precise molecular mechanisms implicated in its pathogenesis remain unclear. Consequently, elucidating the key molecular regulators that govern disease progression could substantially contribute to the establishment of novel therapeutic strategies, ultimately advancing the management of PCa. Methods A total of 49 PCa tissues and 43 adjacent normal tissues were collected from January 2017 to December 2021 at Zhongnan Hospital of Wuhan University. The advanced transcriptomic methodologies were employed to identify differentially expressed mRNAs in PCa. The expression of aspartoacylase (ASPA) in PCa was thoroughly evaluated using quantitative real-time PCR and Western blotting techniques. To elucidate the inhibitory role of ASPA in PCa cell proliferation and metastasis, a comprehensive set of in vitro and in vivo assays were conducted, including orthotopic and tumor-bearing mouse models ( n = 8 for each group). A combination of experimental approaches, such as Western blotting, luciferase assays, immunoprecipitation assays, mass spectrometry, glutathione S-transferase pull-down experiments, and rescue studies, were employed to investigate the underlying molecular mechanisms of ASPA’s action in PCa. The Student’s t -test was employed to assess the statistical significance between two distinct groups, while one-way analysis of variance was utilized for comparisons involving more than two groups. A two-sided P value of less than 0.05 was deemed to indicate statistical significance. Results ASPA was identified as a novel inhibitor of PCa progression. The expression of ASPA was found to be significantly down-regulated in PCa tissue samples, and its decreased expression was independently associated with patients’ prognosis ( HR = 0.60, 95% CI 0.40–0.92, P = 0.018). Our experiments demonstrated that modulation of ASPA activity, either through gain- or loss-of-function, led to the suppression or enhancement of PCa cell proliferation, migration, and invasion, respectively. The inhibitory role of ASPA in PCa was further confirmed using orthotopic and tumor-bearing mouse models. Mechanistically, ASPA was shown to directly interact with the LYN and inhibit the phosphorylation of LYN as well as its downstream targets, JNK1/2 and C-Jun, in both PCa cells and mouse models, in an enzyme-independent manner. Importantly, the inhibition of LYN activation by bafetinib abrogated the promoting effect of ASPA knockdown on PCa progression in both in vitro and in vivo models. Moreover, we observed an inverse relationship between ASPA expression and LYN activity in clinical PCa samples, suggesting a potential regulatory role of ASPA in modulating LYN signaling. Conclusion Our findings provide novel insights into the tumor-suppressive function of ASPA in PCa and highlight its potential as a prognostic biomarker and therapeutic target for the management of this malignancy.

Bladder cancer is the tenth most frequently diagnosed cancer in the world, and is more common among men. Transurethral resection of bladder tumor is not only an important diagnostic method for bladder tumors, but also a major treatment for non-muscle invasive bladder cancer. Com-pared with traditional unipolar electrotomy, plasma bipolar electrotomy has the advantages of good surgical results and fewer complications, and its clinical application is becoming more and more exten-sive. In order to standardize the diagnosis and treatment of common diseases, the National Health Commission continues to issue relevant clinical pathways; however, the content of a clinical pathway is limited, and its interpretation can help it be better disseminated and used. This interpretation is based on the latest "clinical pathway for transurethral plasma resection of bladder tumor (2019 edition)". It uses the method of evidence-based medicine to make a detailed and necessary supplementary descrip-tion of the pathway, and gives a detailed interpretation of the drug delivery scheme involved, so as to provide reference for medical staff and managers to better understand, grasp and correctly use it.

To compare a novel vacuum suction ureteroscopic laser lithotripsy (VS-URS) with traditional ureteroscopic laser lithotripsy (T-URS) for impacted upper ureteral stones and to better define the potential benefits of VS-URS. Between May 2019 and March 2021, 158 patients with impacted upper ureteral stones underwent ureteroscopic holmium-YAG laser lithotripsy. Of these, 76 underwent VS-URS and 82 underwent T-URS. In VS-URS procedures, the vacuum suction device is composed of a 5F ureteral catheter and a tee joint. The ureteral catheter is linked to the vacuum aspirator by the sidearm of the tee joint, and a 200 μm fiber is inserted through the tee joint and the ureteral catheter into the stone site for lithotripsy. When compared to the T-URS group, the VS-URS group had a shorter mean operation time (38.18 ± 6.37 min vs. 46.65 ± 5.66 min; P = 0.000), lower fever rate (3.9% vs. 14.6%; P < 0.022), less stone retropulsion (5.3% vs. 18.3%; P = 0.012), lower extra management rate (6.58% vs. 21.95%; P = 0.006), and a higher stone-free rate of the first postoperative day (88.2% vs. 72.0%; P = 0.011). There were no significant differences in stone-free rates 1 month after surgery between groups (94.7% vs. 92.7%; P = 0.748). VS-URS is an effective modality for impacted upper ureteral stones, and has a shorter operating time, lower fever rate, less stone retropulsion, and a higher primary stone-free rate compared with T-URS.

Abstract Background State‐of‐art non‐invasive diagnosis processes for bladder cancer (BLCA) harbour shortcomings such as low sensitivity and specificity, unable to distinguish between high‐ (HG) and low‐grade (LG) tumours, as well as inability to differentiate muscle‐invasive bladder cancer (MIBC) and non‐muscle‐invasive bladder cancer (NMIBC). This study investigates a comprehensive characterization of the entire DNA methylation (DNAm) landscape of BLCA to determine the relevant biomarkers for the non‐invasive diagnosis of BLCA. Methods A total of 304 samples from 224 donors were enrolled in this multi‐centre, prospective cohort study. BLCA‐specific DNAm signature discovery was carried out with genome‐wide bisulfite sequencing in 32 tumour tissues and 12 normal urine samples. A targeted sequencing assay for BLCA‐specific DNAm signatures was developed to categorize tumour tissue against normal urine, or MIBC against NMIBC. Independent validation was performed with targeted sequencing of 259 urine samples in a double‐blinded manner to determine the clinical diagnosis and prognosis value of DNAm‐based classification models. Functions of genomic region harbouring BLCA‐specific DNAm signature were validated with biological assays. Concordances of pathology to urine tumour DNA (circulating tumour DNA [ctDNA]) methylation, genomic mutations or other state‐of‐the‐art diagnosis methods were measured. Results Genome‐wide DNAm profile could accurately classify LG tumour from HG tumour (LG NMIBC vs. HG NMIBC: p = .038; LG NMIBC vs. HG MIBC, p = .00032; HG NMIBC vs. HG MIBC: p = .82; Student's t‐test). Overall, the DNAm profile distinguishes MIBC from NMIBC and normal urine. Targeted‐sequencing‐based DNAm signature classifiers accurately classify LG NMIBC tissues from HG MIBC and could detect tumours in urine at a limit of detection of less than .5%. In tumour tissues, DNAm accurately classifies pathology, thus outperforming genomic mutation or RNA expression profiles. In the independent validation cohort, pre‐surgery urine ctDNA methylation outperforms fluorescence in situ hybridization (FISH) assay to detect HG BLCA (n = 54) with 100% sensitivity (95% CI: 82.5%–100%) and LG BLCA (n = 26) with 62% sensitivity (95% CI: 51.3%–72.7%), both at 100% specificity (non‐BLCA: n = 72; 95% CI: 84.1%–100%). Pre‐surgery urine ctDNA methylation signature correlates with pathology and predicts recurrence and metastasis. Post‐surgery urine ctDNA methylation (n = 61) accurately predicts recurrence‐free survival within 180 days, with 100% accuracy. Conclusion With the discovery of BLCA‐specific DNAm signatures, targeted sequencing of ctDNA methylation outperforms FISH and DNA mutation to detect tumours, predict recurrence and make prognoses.

目的 评价1990-2019年中国归因于吸烟的前列腺癌、膀胱癌和肾癌的疾病负担.方法 基于2019年全球疾病负担研究,采用人群归因分值(PAF)、死亡和伤残调整寿命年(DALY)为指标分析中国归因于吸烟的前列腺癌、膀胱癌和肾癌的疾病负担现状,并采用joinpoint回归模型计算年度百分比变化率(APC)和平均年度百分比变化率(AAPC),描述1990-2019年3种癌症归因于吸烟的疾病负担变化趋势.结果 2019年因吸烟导致的膀胱癌死亡人数和DALY分别为18 800例和393 106人年,标化死亡率和DALY率分别每年平均下降0.41％和0.39％.2019年归因于吸烟的前列腺癌死亡人数和DALY分别为5 016例和98 276人年,标化死亡率和DALY率每年平均下降0.28％和0.25％.2019年吸烟所致肾癌死亡人数和DALY分别为4 935例和120 620人年,标化死亡率和DALY率每年平均上升3.03％和2.98％.2019年男性归因于吸烟的疾病负担远高于女性,吸烟所致的疾病负担随年龄增长呈上升趋势,中老年人群的疾病负担最大.结论 中国归因于吸烟的泌尿系统癌症疾病负担形势较为严峻,且存在人群差异.男性和中老年人群为高危人群.3种癌症中,膀胱癌的吸烟归因疾病负担最高,肾癌的吸烟归因疾病负担在1990-2019年间上升幅度最大.

Objective Limited attention has been paid to abnormal blood and urine test results for patients with bladder cancer. The present study aimed to identify whether blood and urine parameters are associated with bladder cancer. Methods We used a case–control design and matched each patient with bladder cancer with three healthy controls of the same age and sex. Univariate conditional logistic regression was used to calculate the crude and adjusted odds ratio (OR) and its 95% CI. Multivariate conditional logistic regression was performed for confounders adjustment, and Spearman’s correlation coefficient was used to assess the correlation between tumor T stages and urine parameters. Results Patients with bladder cancer (n = 360) and controls (n = 1050) were recruited. In the univariate conditional logistic analysis, higher urine pH was associated with a decreased risk of bladder cancer (OR = 0.67, 95% CI = 0.57–0.78), while higher values of urine protein (OR = 4.55, 95% CI = 3.36–6.15), urine glucose (OR = 1.56, 95% CI = 1.18–2.05), and urine occult blood (OR = 4.27, 95% CI = 3.44–5.29) were associated with an increased risk of bladder cancer. After adjustment for body mass index, fasting blood glucose, hypertension, red blood cells, white blood cells, lymphocytes, neutrophils, and platelets, significance still remained for urine pH (OR = 0.68, 95% CI = 0.53–0.88), urine protein (OR = 1.97, 95% CI = 1.21–3.19), urine glucose (OR = 2.61, 95% CI = 1.39–4.89), and urine occult blood (OR = 3.54, 95% CI = 2.73–4.58). Conclusion This study indicated that lower urine pH and higher values of urine protein, urine glucose, and urine occult blood might be risk factors for bladder cancer.

目的 探讨前列腺组织切除量及切除率与经尿道前列腺等离子双极电切术(TUPKP)短期临床疗效的关系.方法 采用前瞻性、多中心的研究方法,共274例良性前列腺增生(BPH)行TUPKP的患者纳入本研究.比较前列腺组织切除量及切除率与手术时间、血红蛋白(Hb)下降值、膀胱冲洗时间、留置尿管时间、住院时间及术后最大尿流率(Qmax)、残余尿量(PVR)、国际前列腺症状评分(IPSS)和生活质量评分(QoL)等的关系.结果 前列腺组织切除量与手术时间、Hb下降值和膀胱冲洗时间呈正相关.术后3个月Qmax与前列腺组织切除率呈正相关(r=0.1984,P=0.0010).前列腺组织切除率在50％ ～75％ 的患者其术后3个月Qmax明显大于切除率在<25％(P<0.01)及25％ ～50％(P<0.05)的患者,而切除率50％ ～75％ 与>75％ 的患者无显著性差异(P>0.05).而且,术后3个月Qmax>20 mL/s的患者其前列腺组织切除率明显高于术后3个月Qmax≤20 mL/s的患者(60.2％ ±18.0％v s.43.5％ ±19.1％,P<0.0001).根据术前前列腺体积大小将患者分组(≤30 m L、30～ ≤60 m L、60～90 mL和>90 mL),结果显示前列腺体积较大的患者术后倾向于获得更好的Qmax和IPSS.结论 前列腺组织切除量及切除率会影响TUPKP的短期临床疗效,前列腺体积较大的患者可能获得更好的临床效果.

Intratumor heterogeneity (ITH) of bladder cancer (BLCA) facilitates therapy resistance and immune evasion to affect clinical prognosis directly. However, the molecular and cellular mechanism generating ITH in BLCA remains elusive. Here we show that a TM4SF1-positive cancer subpopulation (TPCS) drives ITH diversification in BLCA. By extensive profiling of the epigenome and transcriptome of BLCA from 79 donors across all stages, we elucidated the evolution trajectories of luminal and basal BLCA. TPCS emerges from the basal trajectory and shows extensive transcriptional plasticity with a distinct epigenomic landscape. Clinically, TPCS were enriched in advanced stage patients and associated with poor prognosis. Our results showed how cancer adapts to its environment by adopting a stem cell-like epigenomic landscape.