Prostate cancer (PCa) ranks among the most prevalent malignancies affecting the male population worldwide, and metastatic PCa (mPCa) carries a poor prognosis. Circular RNAs (circRNAs), a distinct class of RNAs, have been implicated in the progression of various tumors. However, their specific biological functions and underlying mechanisms in PCa, particularly in mPCa, remain largely undefined. In this study, we identified a novel circRNA derived from the back-splicing of exons 20-21 of the Dopey Family Member 2 (DOPEY2) gene. This circRNA, which we named circDOPEY2, was highly expressed in PCa. The circDOPEY2 expression was significantly correlated with multiple clinicopathological indicators associated with PCa severity and prognosis, including Gleason score, clinical M stage, and D'Amico risk classification. Functional assays demonstrated that circDOPEY2 significantly promoted PCa cell metastasis both in vitro and in vivo. Mechanistically, circDOPEY2 directly bound to heterogeneous nuclear ribonucleoprotein M and inhibited its degradation via the ubiquitin-proteasome pathway. The resulting stabilization of heterogeneous nuclear ribonucleoprotein M upregulated the intercellular adhesion molecule 2 expression by enhancing the stability of its mRNA, ultimately promoting PCa metastasis. Moreover, serine/arginine-rich splicing factor 1 mediates circDOPEY2 biogenesis through specific interactions with AluSx1 and AluSx elements. In summary, our findings identify circDOPEY2 as a key promoter of PCa metastasis, highlighting its potential as both a clinical biomarker and therapeutic target for mPCa. SIGNIFICANCE STATEMENT: This study identifies circDOPEY2 as a driver of prostate cancer (PCa) metastasis. Mechanistically, circDOPEY2 inhibits heterogeneous nuclear ribonucleoprotein M ubiquitin-proteasome degradation, stabilizing it to upregulate intercellular adhesion molecule 2 and promote PCa metastasis. This study also provides the first evidence that serine/arginine-rich splicing factor 1 interacts with Alu sequences to regulate circDOPEY2 biogenesis. These findings highlight circDOPEY2 as a novel clinical biomarker and therapeutic target for metastatic PCa.

OBJECTIVES:Current surgical interventions for pelvic fracture urethral injury (PFUI) are constrained by multiple limitations. This study aimed to introduce the prior exposure maneuvers urethroplasty (PEM-U) in complex posterior anastomotic urethroplasty for PFUI. METHODS:From February 2018 to March 2023 at Shanghai Ninth People's Hospital, 78 patients with complex PFUI underwent transperineal anastomotic urethroplasty, 39 patients of whom underwent classic Webster urethral urethroplasty in which bodies splitting or an inferior pubectomy after transection of bulbar urethra (Group A), and the other 39 patients underwent improved urethral urethroplasty (Group B), in which using PEM-U (corporeal bodies splitting or an inferior pubectomy before transection of bulbar urethra). Postoperative evaluations were performed at 1, 3, 6, and 12 months after catheter removal. Success was defined as a urine flow rate ≥15 mL/s, no difficulty in urination, and no further intervention was required. RESULTS:There was no statistical difference in the length of urethral defect between 39 patients (mean age 43.7 years) in Group A and 39 patients (mean age 41.3 years) in Group B. The average operation time of Group A was 115 min (range, 90-150 min), and that of Group B was 93 min (range, 85-115 min) (p = 0.012). The blood loss was 265 mL (range, 100-650 mL) in Group A and 214 mL (range, 90-350 mL) in Group B (p = 0.015). The success rate was 89.7% in the classical group and 92.3% in the improved group. CONCLUSION:The PEM-U was effective for treating complex PFUI cases, improving surgical efficacy, reducing the operation time, and the amount of blood loss.

Prostate cancer (PCa) is one of the most prevalent malignant tumors affecting men. Metastatic PCa is generally considered incurable. Circular RNA (circRNA) is a distinct class of RNA implicated in the tumorigenesis and development of various cancers, including PCa. However, the specific role and underlying molecular mechanisms of circRNA in PCa remain poorly understood. This study identifies hsa_circ_0007444, generated from the back-splicing of exons 6-7 of the Rho Related BTB Domain Containing 3 (RHOBTB3) gene and named as circRHOBTB3, as being downregulated in PCa. Low expression of circRHOBTB3 correlates with elevated pathological T stage, clinical M stage, and D'Amico grade. Functionally, circRHOBTB3 inhibits PCa cell proliferation and metastasis both in vitro and in vivo. Mechanistically, circRHOBTB3 binds to the non-POU domain-containing octamer-binding protein (NONO), a transcription factor for monoamine oxidase A (MAOA), sequestering NONO in the cytoplasm and preventing it from upregulating MAOA transcription. This results in decreased MAOA expression, ultimately suppressing PCa cell proliferation and metastasis. Furthermore, the RNA binding protein serine/arginine-rich splicing factor 9 specifically interacts with AluSx and AluJb, inhibiting circRHOBTB3 circularization. In conclusion, this study identifies circRHOBTB3 as a tumor suppressor with potential to be a promising clinical biomarker and therapeutic target for metastatic PCa.

The nasty urine microenvironment (UME) impedes neourethral regeneration by inhibiting angiogenesis and inducing an excessive inflammatory response. Cellular adaptation to hypoxia improves regeneration in numerous tissues. In this study, heterogeneous porous hypoxia-mimicking scaffolds were fabricated for urethral reconstruction via promoting angiogenesis and modulating the inflammatory response based on sustained release of dimethyloxalylglycine (DMOG) to promote HIF-1α stabilization. Such scaffolds exhibit a two-layered structure: a dense layer composed of electrospun poly (l-lactic acid) (PLLA) nanofibrous mats and a loose layer composed of a porous gelatin matrix incorporated with DMOG-loaded mesoporous silica nanoparticles (DMSNs) and coated with poly(glycerol sebacate) (PGS). The modification of PGS could significantly increase rupture elongation, making the composite scaffolds more suitable for urethral tissue regeneration. Additionally, sustained release of DMOG from the scaffold facilitates proliferation, migration, tube formation, and angiogenetic gene expression in human umbilical vein endothelial cells (HUVECs), as well as stimulates M2 macrophage polarization and its regulation of HUVECs migration and smooth muscle cell (SMCs) contractile phenotype. These effects were downstream of the stabilization of HIF-1α in HUVECs and macrophages under hypoxia-mimicking conditions. Furthermore, the scaffold achieved better urethral reconstruction in a rabbit urethral stricture model, including an unobstructed urethra with a larger urethral diameter, increased regeneration of urothelial cells, SMCs, and neovascularization. Our results indicate that heterogeneous porous hypoxia-mimicking scaffolds could promote urethral reconstruction via facilitating angiogenesis and modulating inflammatory response.

[This corrects the article on p. 697 in vol. 12, PMID: 32194916.].

目的 探讨前列腺癌改良术式腹腔镜下顺行双保根治性前列腺切除术(LabNSRP)在术后患者控尿和勃起功能恢复的效果和安全性.方法 回顾性分析本院于2017年7月-2020年1月由同一术者行LabNSRP的50例患者的临床资料.术前均行Rigiscan检测,记录手术时间、术中出血量、住院时间,术后随访患者的排尿控制、勃起功能恢复及相关并发症.结果 50例患者均手术顺利.手术时间(86.3±6.4)min,出血量(90.2±26.6)mL.术后病理无切缘阳性.术后1周内1例(2％)发生漏尿,经牵拉尿管并延长尿管留置时间后恢复正常.术后随访(12.4±6.7)个月.拔除尿管后即刻控尿率26％(13/50),1月控尿率62％(31/50),1年控尿率为98％(49/50).术后3月和12月勃起功能恢复率分别为56％(28/50)和80％(40/50).结论 腹腔镜下顺行双保根治性前列腺切除术简化了手术步骤,缩短了手术时间,减少了并发症,瘤控效果好,可较大程度保护和恢复控尿、勃起功能.

目的 探讨新型高尔基相关蛋白高尔基膜蛋白1(golgi membrane protein 1,GOLM1)在前列腺癌组织中的表达特点及在诊断中的临床价值.方法 获取正常前列腺、良性前列腺增生和前列腺癌等不同前列腺组织芯片,采用免疫组化法检测GOLM1蛋白的表达,并分析其表达差异.在人前列腺癌细胞(human prostate cancer cell,PC-3)、DU145和22Rv1三种不同前列腺癌细胞系中,分别采用定量PCR技术和Western blot方法,同时检测GOLM1在mRNA水平和蛋白水平的表达情况.在DU145中,使用免疫荧光技术观察GOLM1在前列腺癌细胞中的定位情况.结果 GOLM1在正常前列腺、良性前列腺增生和前列腺癌组织中表达程度不同,其中阳性表达率分别为40.0％(4/10)、50.0％(10/20)和92.0％(46/50),前列腺癌组织中阳性表达率显著高于其他两组,差异有统计学意义(P＜0.05).但病理结果显示,GOLM1的高表达状态与肿瘤Gleason分级和病理分期则差异无统计学意义(P＞0.05).PC-3、DU145和22Rv1三种不同前列腺癌细胞中均见GOLM1表达,激素依赖型前列腺癌细胞22Rv1显著低于激素非依赖型前列腺癌细胞(PC-3和DU145),差异有统计学意义(P＜0.05).GOLM1定位于前列腺癌细胞DU145高尔基体顺面网络结构.结论 与正常前列腺和良性前列腺增生相比,GOLM1在前列腺癌中表达明显升高,是一种潜在的肿瘤标志物,进一步研究其在前列腺癌中的作用机制具有重要意义.

高尔基磷酸化蛋白3(golgi phosphoprotein 3,GOLPH3)具有典型的高尔基体结构,发挥着维持高尔基体正常形态结构和生理功能的重要作用.在多种肿瘤的研究中,GOLPH3均被证明呈高表达状态,与肿瘤的发生和转移密切相关.近年来随着研究的不断深入,成为肿瘤诊治的重要靶点,因此文章对高尔基磷酸化蛋白3在肿瘤中的研究进展进行综述.

Background Extramammary Paget's disease (EMPD) is a rare malignant intraepidermal adenocarcinoma that is poorly understood. Regulatory long noncoding RNAs (lncRNAs) are characterized in many species and shown to be involved in processes such as development and pathologies, revealing a new layer of regulation in different diseases, especially in cancer studies. In the present study, we used high-throughput sequencing to reveal the lncRNA-mRNA interaction network in extramammary Paget's disease. Methods High-throughput sequencing was used to identify differentially expressed lncRNA and mRNA profiles between EMPD patients and healthy controls. Then, a series of bioinformatics analyses were conducted to construct the lncRNA-mRNA interaction network, which was finally confirmed in vitro. Results Six pairs of EMPD tumor and normal skin samples were collected and sequenced to identify the differentially expressed lncRNA and mRNA profiles between EMPD and healthy controls. A total of 997 differentially expressed mRNAs and 785 differentially expressed lncRNAs were identified. The GO and KEGG analyses show that epidermal development and cell adhesion play important roles in EMPD. The results of the lncRNA-mRNA interaction network analysis suggested that NEAT1, PGAP1, FKBP5 and CDON were the pivotal nodes of the network and that lncRNA NEAT1 might regulate mRNA PGAP1, FKBP5 and CDON. The results of the quantitative real-time RT-PCR performed in ten other patients for NEAT1, PGAP1, FKBP5 and CDON were consistent with those of the sequencing analysis. Moreover, an in vitro experiment confirmed the interactions between NEAT1 and PGAP1, FKBP5 and CDON in human immortalized keratinocytes. Conclusion These findings suggest that the lncRNA-mRNA interaction network based on four pivotal nodes, NEAT1, PGAP1 FKBP5 and CDON, may play an important role in EMPD, which will contribute to a deeper understanding of the pathogenesis of EMPD.

Objective:To compare the features and advantages of the standardized residency training of urology in America and China, and to provide a reference for the improvement of the Chinese standardized residency training system.Methods:By studying the latest standardized training documents in China and the America, referring to the specific training rules of standardized training pilots (Shanghai and other cities), and the latest related researches, this article compares the differences between the Chinese and American standardized residency training systems from such five aspects as the source of urology training students, training objectives, training content, quality control and external environment, and tries to figure out the reasons for their formation.Results:There are many places in American standardized residency training system that can be referred, such as unifying the period of training system, strengthening the assessment of clinical capabilities of residents, focusing on the combination of clinical and scientific research, and improving the remuneration and practice environment of residents. At present, the quality and effectiveness of Chinese urology standardized residency training needs to be improved, especially the ability of independent diagnosis and surgical skills.Conclusion:By analyzing the differences of standardized residency training system between China and the United States, this article puts forward the following suggestions: a) to unify the educational system and establish a unified admission standard for urologists; b) to formulate a clear training goal and establish a national standardized assessment system; c) to improve the income level of urology residents, willing to establish a standardized residency training system that truly suits China's national conditions.

Purpose: To compare the efficacy and safety of plasma kinetic enucleation of the prostate (PKEP) with holmium laser enucleation of the prostate (HoLEP) for treatment of benign prostatic hyperplasia (BPH). Methods: A total of 160 patients with indications for the surgical treatment of BPH were randomly assigned to receive either PKEP or HoLEP prospectively. Baseline characteristics, perioperative data, and postoperative outcomes of the patients were recorded. One hundred twenty-six (78.75%) patients (PKEP 64 vs HoLEP 62) completed the 3-year follow-up assessment. Results: Patients in both groups had similar baseline characteristics. Compared with PKEP, HoLEP was associated with shorter operative time as well as take-out time, lower perioperative hemoglobin decrease, and shorter bladder irrigation time, catheterization time, and hospital stay time. PKEP was superior to HoLEP in terms of the noise of the machine and hospitalization expenses. There were no significant differences in enucleating time, resected weight, and serum sodium levels. Both groups achieved satisfactory results and maintained improvement from baseline in terms of maximum urinary flow rate (Qmax), International Prostatic Symptomatic Score, quality of life, and postvoid residual at 3-year follow-up, with no significant differences between the two procedures. Except for re-catheterization rate, postoperative data such as transrectal ultrasound volume, International Index of Erectile Function-5, and follow-up scores of the flexible cystourethroscopy results, as well as the acute and mid-to long-term complications after surgery, were statistically similar. Conclusion: The 3-year follow-up data of this randomized trial confirmed that both PKEP and HoLEP were effective and safe surgical procedures for the transurethral management of BPH. HoLEP presented certain advantages compared to PKEP, such as reduced operative duration, decreased risk of blood loss, and less bladder irrigation, hospital stay time, and re-catheterization rate, whereas PKEP had lower noise and no additional laser cost. Chinese Clinical Trial Registry (ChiCTR-TRC-13004468).

Subject: Collagen And Calcium Binding EGF Domains 1 (CCBE1) is a coding protein which plays a significant role in extracellular matrix remodeling and migration and is involved in the development of Hennekam syndrome and lymphangiogenesis. Here, we investigate its prognostic value in prostate cancer based on TCGA database and its antioncogenic role in prostate cancer.Methods: Wilcoxon rank sum test, Pearson χ2 test, and logistic regression analysis were utilized to evaluate the correlation between CCBE1 and clinicopathological variables. Kaplan-Meier and Cox regression analysis were used to reveal the relation between CCBE1 and survival rates. The role of CCBE1 in prostate cancer was investigated using CCK-8 assay, EdU assay, and transwell experiments, respectively.Results: Here, we found that CCBE1 expression is down-regulated in prostate cancer tissue dramatically in TCGA database. Furthermore, high CCBE1 expression predicted a good prognosis in patients with prostate cancer. High expression level of CCBE1 in PRAD cohort was prominently correlated with T classification (OR =0.49 for T3&T4 vs T2, P<0.001), Gleason score (OR = 0.42 for8&9&10 vs. 6&7, P<0.001). Kaplan-Meier and Cox regression analysis showed that prostate cancer patients with high CCBE1 expression had a better progression-free interval (hazard ratio [HR]:0.50; 95% confidence interval [CI]: 0.33-0.77; P = 0.002) and overall survival (hazard ratio [HR]:0.38; 95% confidence interval [CI]: 0.15-0.92; P = 0.032). In vitro experiments indicated that overexpressed CCBE1 inhibited prostate cancer cell proliferation, migration, and invasion.Conclusion: CCBE1 plays a pivotal role in the progression of prostate cancer and up-regulated CCBE1 expression inhibits prostate cancer tumorgenicity.

我国新型冠状病毒肺炎疫情控制良好,虽然疫苗屏障逐步建立,但各地仍不断出现本土无症状感染者和输入型病例,防控工作不能掉以轻心.泌尿外科急诊患者多为老年人,常伴有机体免疫功能减退等,新型冠状病毒肺炎感染的风险相对增加.本文对《新型冠状病毒肺炎疫情下泌尿外科急症的诊疗意见》进行解读,并结合目前疫情的新形势,进一步提出符合当前情况的防控和诊疗建议,以更好地应对新型冠状病毒肺炎疫情,满足泌尿外科医务工作者和患者的需求.

目的 总结腹腔镜联合输尿管镜治疗输尿管结石术后输尿管狭窄的临床效果.方法 回顾性分析10例采用腹腔镜联合输尿管镜治疗输尿管结石术后输尿管狭窄患者的临床资料.其中,4例有输尿管上段钬激光碎石和球囊扩张手术史,3例有输尿管下段气压弹道碎石史,3例有输尿管结石反复体外冲击波碎石史.术前泌尿系B超、CT和静脉肾盂造影显示患侧肾脏轻、中度积水,输尿管中上段中、重度扩张,中下段严重狭窄.术中取健侧奔跑位(健侧斜卧位30度+截石位),输尿管镜下明确狭窄段,经腹入路腹腔镜行狭窄段切除和端端吻合术.结果 10例患者手术均顺利,双镜联合治疗输尿管狭窄手术时间(120.3±15.6)min,术后住院时间(5.5±1.0)d.术后2个月顺利拔除双J管,拔管时输尿管镜检查吻合口通畅,无感染及尿漏发生.术后随访6～18个月,泌尿系B超提示10例患者上尿路积水显著减轻,静脉肾盂造影或CT尿路造影显示输尿管通畅,血清肌酐值均在正常范围.结论 腹腔镜联合输尿管镜在术中能精确定位输尿管狭窄段,是治疗输尿管结石术后中下段严重狭窄的有效方法.

Background: Long noncoding RNAs (lncRNAs) are implicated in various human cancers. However, the genetic regulation and clinical significance of most lncRNAs in cancers remain unknown.Method: In this study, we performed expression quantitative trait loci (eQTLs) mapping of lncRNA (elncRNA) in 11 cancer types using The Cancer Genome Atlas (TCGA) data and characterized the role of elncRNAs in the setting of genomic location, cancer association and drug sensitivity prediction. Furthermore, we performed instrumental variable (IV) analysis to dissect the downstream biological perturbation by eQTL-elncRNA pairs.Finding: 10.86% cis-eQTLs and 1.67% trans-eQTLs were related to known cancer risk-associated loci. The elncRNAs were significantly enriched in lncRNA predictors of anticancer drug sensitivity. We found that the target genes affected by eQTL-elncRNA associations are enriched in the immune system processes. We also found that eQTL-elncRNA associations can impact the fraction of immune cell types. In ovarian cancer, the rs34631313-AC092580.4 pair was shown to associate with immune-related genes (FASLG/GZMM/PYHIN1TRAT1), and with increased percentages of CD8+ T cells and M1 Macrophage. The rs9546285(13q12.3)-LINC00426 pair was shown to associate with the expression of IFNG/TNIP3/DTHD1/ZBED2 and with a higher fraction of CD8+ T cells and a lower fraction of M2 macrophages in kidney renal clear cell carcinoma.Interpretation: We revealed the genetic regulation of lncRNAs in cancers and explored the role of eQTL-elncRNA in cancer immunology. Our findings provide valuable genetic and lncRNA biomarkers for drug sensitivity and cancer immune therapy.Funding Statement:This study was supported in part by the National Natural Science Foundation of China (Grant No. 31371289 to Qiyuan Li), the Fundamental Research Funds for the Chinese Central Universities (20720190101 to Qiyuan Li), the Young Scientists Fund of the National Natural Science Foundation of China (Grant No. 81802823 to Ying Zhou), the Natural Science Foundation of Fujian Province of China (Grant No. 2018J01054 to Ying Zhou), and the Major Project of Shanghai Science and Technology Commission of China, (Grant No. 18441901700 to Wenzhi Li).Declaration of Interests: The authors declare that they have no competing interests.Ethics Approval Statement: The authors stated: "Not applicable."

2013年底住院医师规范化培训(住培)的实质性启动,是我国医学教育的一场深层次、根本性的改革.随着住培制度的基本健全,医改进入攻坚克难期,人民健康需求快速提升,因此住培由制度体系建设向质量内涵建设转变,要求培训质量实现同质化,达到制度化、标准化、国际化,得到世界认可的"三化一认可"目标.世界范围内,美国的住培体系历史悠久,经验相对丰富,形成了一种严格而完善的模式,对年轻的中国模式有一定的借鉴意义.新时代给住培提出的新要求,更应该是适合新时期形势的培训.

人工智能(artificial intelligence,AI)是在计算机科学、控制论、信息论、神经心理学、哲学、语言学等多种学科基础上发展起来的一门综合性交叉学科,是一门集新思想、新观念、新理论、新技术于一体的新兴学科[1].在医学方面,AI在医疗影像、疾病诊断与预测、智能器械、新药研发、基因组学、健康管理、医院管理、病例/文献分析、虚拟助手等医疗细分领域得到关注并逐步应用.2019年上海科技节亮相的健康智能机器人,它借助数据采集仪与AI云分析,每次只需2分15s,就能精准检测、感知并评估个体潜在的风险,帮助用户直观了解自身9大系统41种疾病.泌尿系肿瘤发病率逐年上升,诊疗手段亦不断精进.随着计算机技术和现代医学的迅速发展,辅助医学手术导航系统为癌症患者手术治疗提供了新的机遇,为医生手术操作提供优化参考手段的同时,也减轻了患者手术的痛苦,有效地避免了许多由术中“盲区”带来的风险[2].

目的 克隆小鼠PD-L1(mouse PD-L1,m PD-L1)全长cDNA,构建其真核表达载体,并验证其在小鼠骨髓源性树突状细胞(dendritic cells,DC)中的表达.方法 采用RT-PCR和TA克隆技术,从小鼠CT-26细胞中扩增mPD-L1全长cDNA,克隆到T载体中,再亚克隆至pTracer-CMV2载体中.以改良脂质体法将构建好的重组质粒转染至小鼠DC,通过流式细胞术检测mPD-L1蛋白及GFP表达.结果 测序证实所得的mPD-L1cDNA序列与其在GenBank中的序列完全一致.mPD-L1真核表达载体转染小鼠DC后,能稳定表达mPD-L1蛋白.结论 成功克隆了mPD-L1基因,构建其真核表达载体,并证明能有效表达于DC中.

Many cancer risk loci act as expression quantitative trait loci (eQTLs) of transcripts including non-coding RNA. Long non-coding RNAs (lncRNAs) are implicated in various human cancers. However, the pathological and clinical impacts of the genetic determinants of lncRNAs in cancers remain largely unknown. In this study, we performed eQTL mapping of lncRNA expression (elncRNA) in 11 TCGA cancer types and characterized the biological processes of elncRNAs in the setting of genomic location, cancer treatment responses, and immune microenvironment. As a result, 10.86% of the cis-eQTLs and 1.67% of the trans-eQTLs of lncRNA were related to known genome-wide association studies (GWAS) cancer risk loci. The elncRNAs are significantly enriched for those which are previously annotated as predictive of drug sensitivities in cancer cell lines. We further revealed the downstream transcriptomic effectors of eQTL-elncRNA pairs. Our data specifically suggested that the genes affected by eQTL-elncRNA associations are enriched in the immune system processes and eQTL-elncRNA associations influence the constitution of tumor infiltrating lymphocytes. In ovarian cancer, the “rs34631313-AC092580.4” pair was associated with increased fraction of CD8+ T cells and M1 Macrophage; whereas in KIRC, the “rs9546285-LINC00426” pair was associated with increased fraction of CD8+ T cells and a decreased fraction of M2 macrophages. Our findings provide a systematic view of the transcriptomic impacts of the eQTL landscape of lncRNA in human cancers and suggest its strong potential relevance to cancer immunity and treatment.