Bladder cancer is characterized by high recurrence rates and limited long-term benefit from current intravesical therapies, highlighting the need for alternative localized treatment strategies. Among tumor suppressors altered in bladder cancer, CDKN1A, which encodes the cyclin-dependent kinase inhibitor p21, is recurrently inactivated and downregulated, supporting its potential as a target for tumor suppressor replacement. Here, we developed a non-viral therapeutic strategy based on chemically modified p21 mRNA encapsulated in lipid nanoparticles (p21-LNP) for intravesical delivery. Public dataset analysis, tissue microarray staining, and cell line validation showed that p21 expression decreases during bladder cancer progression and that endogenous p21 protein levels are very low in bladder cancer cells. In vitro, synthetic p21 mRNA achieved robust nuclear p21 expression and markedly suppressed bladder cancer cell proliferation, viability, and clonogenicity. Mechanistically, p21 restoration reduced retinoblastoma protein (Rb) phosphorylation, decreased Cyclin E, Cyclin B, and proliferating cell nuclear antigen (PCNA) expression, increased γ-H2A.X accumulation, and promoted apoptosis. The resulting p21-LNP showed favorable physicochemical properties for intravesical administration. In vivo, reporter mRNA-LNP mediated strong bladder-localized protein expression with limited and transient systemic distribution. In an orthotopic bladder cancer mouse model, repeated intravesical administration of p21-LNP significantly suppressed tumor growth, restored p21 expression in bladder tissues, and preserved urothelial architecture without obvious adverse effects. Together, these findings establish intravesical delivery of p21 mRNA-LNP as a clinically compatible strategy for localized tumor suppressor replacement therapy in bladder cancer.

Bladder cancer (BC) remains a prevalent malignancy worldwide, with rising incidence rates each year. Despite progress in therapeutic strategies, many patients suffer recurrence or progression, emphasizing the urgent need for novel prognostic biomarkers and therapeutic targets. This research evaluated the prognostic relevance and functional role of Cleavage and Polyadenylation Specificity Factor 3 (CPSF3) in BC. We analyzed CPSF3 expression using The Cancer Genome Atlas data and immunohistochemistry on a cohort of 203 BC patients. A nomogram incorporating CPSF3 expression was developed based on CPSF3 expression for prediction of overall survival and disease-free survival. Immune infiltration analyses and transcriptome sequencing were performed to explore underlying biological mechanisms. In vitro and in vivo experiments were utilized to examine the results of CPSF3 silencing on bladder cancer cell growth, colony-forming ability and cell cycle transitions. Elevated CPSF3 expression was significantly linked to unfavorable overall survival and disease-free survival both in TCGA datasets and our cohort. The CPSF3-based nomogram outperformed conventional prognostic models. CPSF3 expression was associated with tumor-infiltrating immune cells and immune checkpoint markers. Enrichment analysis revealed CPSF3 enrichment in cell cycle-related pathways. Suppression of CPSF3 expression led to marked reductions in cell proliferation, colony formation, tumor growth in animal models and inhibited G1 to S phase progression. CPSF3 is a promising prognostic biomarker for BC and may play a crucial role in BC progression. Incorporating CPSF3 into clinical prognostic models may enhance prediction of patient outcomes. CPSF3 may represent a promising therapeutic target for BC management.

829 Background: Bladder cancer (BC) is a global health issue, with a significant number of new cases diagnosed annually. Despite advances in treatment, many patients experience recurrence or progression, emphasizing the need for novel prognostic biomarkers and therapeutic targets. This study aimed to investigate the prognostic significance and biological function of Cleavage and Polyadenylation Specificity Factor 3 (CPSF3) in BC. Methods: We analyzed CPSF3 expression using The Cancer Genome Atlas (TCGA) data and immunohistochemistry (IHC) on a cohort of 203 BC patients. A nomogram incorporating CPSF3 expression was constructed to predict overall survival (OS) and disease-free survival (DFS). In vitro experiments were conducted to assess the effect of CPSF3 knockdown on BC cell proliferation, colony formation and cell cycle distribution. Bioinformatics analyses, including Gene Set Enrichment Analysis (GSEA) and immune infiltration analysis, were performed to explore potential mechanisms. Results: High CPSF3 expression was significantly associated with poor OS and DFS in TCGA and our cohort. The nomogram incorporating CPSF3 showed superior predictive performance compared to traditional models. Downregulation of CPSF3 inhibited BC cell proliferation, colony formation and transition from G1 phase to S phase. GSEA revealed enrichment of oncogentic pathways in CPSF3 high-expression phenotype. CPSF3 expression was correlated with immune cell infiltration and expression of immune checkpoints in the tumor microenvironment. Conclusions: Our study demonstrates that CPSF3 is a promising prognostic biomarker for BC and may play a crucial role in BC progression. The nomogram incorporating CPSF3 expression provides an improved tool for predicting BC patient outcomes. These findings suggest that CPSF3 could be a potential therapeutic target for BC treatment.

This study aimed to explore the exact roles of lysine acetyltransferase 5 (KAT5) in prostate cancer (PCa). PCa tumour tissue samples and paired adjacent normal prostate tissues as well as three PCa cell lines were used. Gene expression was determined utilizing real-time PCR, western blotting and immunohistochemical staining. Cell viability, migration, and invasion was determined utilizing CCK-8, Transwell and Scratch assays, respectively. Levels of glucose, lactate, and ATP were measured utilizing corresponding assay kits. Extracellular acidification rate (ECAR) and oxygen consumption rates (OCR) were measured using Seahorse method. Xenografted tumor mice model was established to detect the roles of KAT5 in vivo. KAT5 expression was elevated in PCa tissue and cell lines, particularly in castration-resistant PCa tissue and DU145 cells. Overexpression of KAT5 promoted proliferation, migration, invasion, and expression of phosphorylated p38 and JNK of DU145 cells, whereas such effects was reversed after transfecting si-KAT5 or inhibiting p38 and JNK. KAT5 expression positively correlated with PKM and GLUT1, and its overexpression elevated PKM2 and GLUT1 levels. KAT5 overexpression promoted glucose uptake, lactate production, ATP levels in DU145 cells, and these were reversed after si-KAT5 treatment or inhibiting p38 and JNK. ECAR and OCR assays further confirmed that KAT5 facilitating aerobic glycolysis. After inhibiting glycolysis using 2-DG, KAT5 mediated cells proliferation was partly suppressed. Inhibition KAT5 expression suppressed tumor growth in vivo. KAT5 may involve in PCa tumor progression via p38-mediated aerobic glycolysis, which might be a promising anti-tumor strategy in PCa.

Paraganglioma (PGL) is rare, and PGL that arises from the urogenital system is even rarer. Here we report a case of PGL in spermatic cord and review the relevant literatures. We encountered a 15-year-old boy with a history of hypertension for almost 2 years, accompanied with headache and palpitations. His serum and urine catecholamines were elevated, but no adrenal lesions were detected, suggesting the existence of PGL. Upon physical examination, a painless nodule adherent to the spermatic cord in the right scrotum was found. A systemic Ga68 DOTATATE PET-CT was then performed, and it revealed a mass with high DOTATATE uptake in the right scrotum. The CT, MRI, and ultrasound images showed the abundant blood supply to the tumor. Based on the above-mentioned imaging and biochemical information, a diagnosis of PGL was made prior to surgery. After 2 weeks of preparation with Cardura, an open surgery was performed to remove the tumor together with the right testis and right epididymis. The blood pressure increased to 180/100 mmHg when the tumor was touched intraoperatively and decreased to 90/55 mmHg after the tumor was removed. Post-operative pathology confirmed our diagnosis of PGL originating from the spermatic cord. Immunohistochemical (IHC) staining showed SDHB (+), CgA (+), synaptophysin (+), GATA3 (+), CD56 (+), sertoli cells S-100 (+), and Ki67 (5%). Genetic testing revealed a missense mutation in the SDHA gene. Only 16 cases of spermatic cord PGL have been reported to date. Although it is easy to diagnose by histology and IHC examinations, preoperative diagnosis is quite important as it can actually reduce intraoperative complications.

Background:Pheochromocytoma and paraganglioma, collectively known as PPGL, are categorized as neuroendocrine tumors with the potential for malignancy. Plasminogen activator, tissue type (PLAT) is a protein encoding gene that encodes tissue-type plasminogen activator, which converts plasminogen to plasmin. There is limited research on the association between PLAT and PPGL. Previous studies have only found that the expression level of PLAT protein is significantly increased in PPGL with deficient blood supply, and its role in the occurrence and progression of PPGL remains unclear and needs further clarification. The purpose of this study is to provide some new clues to elucidate the role of PLAT in PPGL, in order to better guide future research directions. Methods:The PC-12 cell line was selected for this study, and lentivirus transfection technology was used to construct control and PLAT overexpression cell models. Transcriptomic information of PLAT regulation in PC-12 cells was obtained through RNA sequencing, and differentially expressed genes (DEGs) were screened using bioinformatics methods. The physiological functions and related signaling pathways of these genes were analyzed. Results:After validating the overexpression cell model and performing quality control analysis on the transcriptome sequencing data, DEGs were identified. The Gene Ontology (GO) functional enrichment analysis of DEGs revealed significant enrichment in 46 GO functions, while the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed significant enrichment in seven pathways. It was found that these genes were significantly enriched in functional pathways associated with mitochondrial respiratory chain and energy metabolism. Conclusions:This study provides some insights into the role of PLAT in pheochromocytoma and suggests directions for further research on its involvement in tumor development and angiogenesis. However, the specific regulatory mechanisms still require further validation.

BACKGROUND:Pheochromocytoma (PCC) is a rare neuroendocrine tumor. Angiogenesis is primary contributing factor for tumorigenesis. Cytochrome c oxidase 4I2 (COX4I2) has been confirmed to take part in the progression of cancer. Hypoxia-inducible factor 1A (HIF1A) is the main regulatory factor for the steady-state response of hypoxia, involved in metabolism and angiogenesis. In this study, we intended to explore the functions of COX4I2 in PCC and the effect mechanism between HIF1A and COX4I2. MATERIALS AND METHODS:The RNA-sequencing and immunohistochemistry tested COX4I2 expression in highly vascular PCC. Small interfering RNA (siRNA) was used to reduce the mRNA expression of COX4I2, and a small molecule inhibitor was utilized to reduce the protein expression of HIF1A. Culturing cells in 1% O2environment was performed to activate HIF1A. Western blot was applied to quantify the expression of target genes at the protein levels. The supernatant from PCC cells and fibroblasts acted as the conditioned medium. We conducted the tube formation and transwell assays in human vascular endothelial cells (HUVECs) to determine angiogenesis, the binding of COX4I2 promoter and HIF1A was evaluated by the dual luciferase reporter assay. RESULTS:COX4I2 had been rigorously shown to be overexpressed in highly vascular PCC. Knockdown of COX4I2 in PCC cells (MPC) did not significantly impact angiogenesis, while knockdown of COX4I2 in fibroblast (3T3) notably inhibited angiogenesis. RNA sequencing suggested that the expression of 11 vascular markers, such as CD34 and angiogenesis associated pathways in 3T3, decreased with knockdown of COX4I2. HIF1A had been shown to enhance the mRNA expression of COX4I2 through transcriptional regulation. Activation and inhibition of HIF1A resulted in upregulation and downregulation of COX4I2, respectively. The HIF1A inhibitor demonstrated a reduction in angiogenesis. CONCLUSION:COX4I2 is overexpressed in highly vascular PCC and contributes to angiogenesis in fibroblasts. Mechanistically, HIF1A transcriptional regulation enhances COX4I2 and its effects on angiogenesis in PCC. COX4I2 might serve as a vascular marker and represent a potential target for vascular therapy.

The downregulated expression of forkhead box F1 (FOXF1) has been found in many malignant tumors but no research was done in bladder cancer (BC). The present study aimed to investigate the prognostic value and antitumor effects of FOXF1 in patients with BC. Herein, a retrospectively recruited BC cohort and public datasets were utilized to identify the predictive ability of FOXF1 and determine its association with the clinical characteristics of BC patients. It was found that the expression level of FOXF1 was notably lower in BC tissues than in para-cancerous mucosae. Low FOXF1 expression was associated with unfavorable clinicopathological features and poor prognosis. Furthermore, in BC cells, the mRNA and protein expression levels of FOXF1 were examined using reverse transcription-quantitative PCR and western blot analysis. Cell viability was examined using Cell Counting Kit-8, EdU and clonogenic capacity assays. Cell apoptosis was detected using flow cytometry. The results revealed that the activation of FOXF1 impaired cell viability and induced apoptosis in BC. The antitumor effects of FOXF1 were also validated using animal models. Subsequently, caspase-3 was spotted as a downstream gene of FOXF1 by using RNA sequencing and protein-protein interaction analyses. FOXF1 inhibited proliferation and induced apoptosis of BC cells via caspase signaling pathway. The present study demonstrates the expression patterns, prognostic predictive ability and antitumor effects of FOXF1 in BC. FOXF1 is a favorable biomarker for predicting clinical outcomes in patients with BC and represents a potential therapeutic target.

BACKGROUND:MicroRNAs (miRNAs) play a critical role in cancer development and progression, the dis-regulation of miR-30c-5p has been observed in various malignant tumors but no research was done in bladder cancer (BCa). This study aims to investigate the downregulation of miR-30c-5p in BCa, and examine its mechanism and prognostic significance.METHODS:Bioinformatics analyses and clinical specimens were employed to investigate the relationship between miR-30c-5p and clinical information in BCa patients. The expression levels of miR-30c-5p and its target gene were assessed by real-time PCR and western blot. Cell viability was evaluated through clonogenic capacity, CCK-8, and EdU assays. Cell cycle distribution and cell apoptosis were determined by flow cytometry. The anti-tumor effect of miR-30c-5p was also validated in animal models.RESULTS:The expression levels of miR-30c-5p were significantly decreased in both bladder tumor tissue and BCa cell lines. Low miR-30c-5p expression was found to be correlated with unfavorable TNM stages and poor prognosis. Over-expressing miR-30c-5p was observed to hinder BCa cell growth, migration, and invasion abilities and causing cell cycle arrest. Mechanistically, miR-30c-5p directly binds and suppresses PRC1, thereby blocking the CDK1/Cyclin B1 axis in BCa, thus impairing BCa cell viability and inducing cell cycle arrest at G2/M phase.CONCLUSION:Down-regulated miR-30c-5p promotes BCa through its target gene PRC1, miR-30c-5p is a favorable biomarker for predicting clinical outcomes in BCa patients and has the potential to be a therapeutic target.

Background: The depth of response to platinum in urothelial neoplasm tissues varies greatly. Biomarkers that have practical value in prognosis stratification are increa-singly needed. Our study aimed to select a set of BC (bladder cancer)-related genes involved in both platinum resistance and survival, then use these genes to establish the prognostic model. Materials and Methods: Platinum resistance-related DEGs (differentially expressed ge-nes) and tumorigenesis-related DEGs were identified. Ten most predictive co-DEGs were acquired followed by building a risk score model. Survival analysis and ROC (receiver operating characteristic) plot were used to evaluate the predictive accuracy. Combined with age and tumor stages, a nomogram was generated to create a graphical representation of survival rates at 1-, 3-, 5-, and 8-year in BC patients. The prognostic performance was validated in three independent BC datasets with platinum-based che-motherapy. The potential mechanism was explored by enrichment analysis. Results: PPP2R2B, TSPAN7, ATAD3C, SYT15, SAPCD1, AKR1B1, TCHH, AKAP12, AGLN3, and IGF2 were selected for our prognostic model. Patients in high-and low--riskgroups exhibited a significant survival difference with HR (hazard ratio) = 2.7 (p < 0.0001). The prognostic nomogram of predicting 3-year OS (overall survival) for BC patients could yield an AUC (area under the curve) of 0.819. In the external validation dataset, the risk score also has a robust predictive ability. Conclusion: A prognostic model derived from platinum resistance-related genes was constructed, we confirmed its value in predicting platinum-based chemotherapy be-nefits and overall survival for BC patients. The model might assist in therapeutic deci-sions for bladder malignancy.

Objective:To explore the safety and feasibility of the robot-assisted retroperitoneal partial nephrectomy(RARPN).Methods:Twenty cases underwent RARPN since March 2016 in our department, and the perioperative data were compared with 52 cases of robot-assisted transperitoneal partial nephrectomy (RATPN) retrospectively. In RARPN group and RATPN group, the mean age was (53±8) vs (47±6) years. The median of tumor size was 2.8 cm vs 3 cm, and the median of R.E.N.A.L score was 6 vs 6.Results:RARPN was equivalent with RATPN in operating time (OT), estimated blood loss (EBL), docking time (DT) and hospital stay (HS), but was superior to RATPN as early resumption of food intake was concerned (18 h vs 27 h).Conclusion:RARPN is a safe and feasible modality for the treatment of renal tumor which offers earlier food oral intake, especially for those with previous abdominal surgery.

Background: Adrenocortical carcinoma (ACC) is an extremely rare malignant tumor with poor prognosis. Existing treatment options have limited effects, and new therapeutic targets urgently need to be discovered. TNFSF13B has been reported to be associated with the prognosis of clear cell renal cell carcinoma, but it has not been studied in ACC. Methods: TNFSF13B expression was analyzed and compared between ACC tumors and normal tissues by using public datasets from TCGA and GTEx. Kaplan-Meier analysis was employed to evaluate survival, and Cox regression was employed to evaluate clinicopathologic features. The upstream and downstream regulatory mechanisms of TNFSF13B were also analyzed. GSEA was performed to explore the mechanisms of TNFSF13B in ACC. Finally, 14 ACC clinical samples were used to verify the relationships between TNFSF13B expression and disease-free survival (DFS) and overall survival (OS). Results: TNFSF13B expression was significantly higher in ACC tissues than in normal tissues. The prognosis of ACC patients with high TNFSF13B expression was worse than that of patients with low TNFSF13B expression. High TNFSF13B expression was strongly correlated with poor prognosis, and TNFSF13B was a prognostic factor. TNFSF13B expression is modified by upstream mi RNAs, methylation and ubiquitination, and downstream, it interacts with other proteins. GSEA showed that regulation of cholesterol biosynthesis by SREBP and SREBF, downstream signaling events of the B cell receptor (BCR) and activation of gene expression by SREBF and SREBP were significantly enriched in the TNFSF13B high-expression phenotype. Clinical samples confirmed that TNFSF13B expression was significantly associated with DFS but not with OS. Conclusions: TNFSF13B may be a potential prognostic molecular marker of poor survival in ACC patients, offering a new therapeutic target.

目的 评价基于经尿道手术模拟器培训是否有助于提高新手泌尿外科膀胱镜临床操作水平.方法 选择在上海交通大学医学院附属瑞金医院外科类专业住院医师规范化培训基地接受培训的住院医师(简称外科类基地组)15人、泌尿外科医学硕士专业学位研究生(简称专硕组)6人、低年资泌尿外科医师(简称低年资组)6人为研究对象,采用系统教学方法进行培训.培训完成后在模拟器上进行操作考核,通过模拟器考核者在上级医师指导下完成真实病例临床膀胱镜考核.收集操作时长、考官评分、损伤和出血情况相关数据,采用配对t检验(正态分布)或Wilcoxon符号秩和检验(非正态分布)进行统计学分析.结果 培训后所有人都一次性通过模拟器考核,观察完整性均为100％.培训前后临床膀胱镜操作考核结果分析表明,专硕组经过系统培训后,操作时长缩短(t=10.0074,P=0.0002)、损伤出血次数降低(t=2.7116,P=0.0422)、考官评分提高(t=-3.285,P=0.0218),差异有统计学意义.低年资组虽然培训前后操作时长和损伤出血次数的差异无统计学意义,但考官评分提高(t=-3.9967,P=0.0104),差异有统计学意义.外科类基地组经过培训后均能在上级医师指导下完成临床膀胱镜操作,操作时长(792.00±65.92)s,考官评分(83.87±5.18)分,损伤出血次数(0.93±0.80)次.结论 基于模拟器的系统膀胱镜教学对于零基础的初学者以及具有一定基础的医师都有较好的学习效果,在教学活动中具备有效性和可操作性.

目的:本研究拟对促肾上腺皮质激素(adrenocorticotropic hormone,ACTH)非依赖性肾上腺大结节增生(ACTH-independent macronodular adrenal hyperplasia,AIMAH)患者行单侧肾上腺切除术后的临床价值进行评估,以探讨该方法作为治疗AIMAH首选方法的可行性.方法:回顾性分析2008-2019年46例行单侧肾上腺切除术后的AIMAH患者的临床资料.男20例,女26例;年龄31～72岁,平均(55.13±8.89)岁;亚临床型6例,临床型33例,危重型7例.患者在术前均有不同程度的临床表现,高血压41例,超重或肥胖27例,上午8点血皮质醇浓度升高20例,24 h尿游离皮质醇升高42例.2 mg地塞米松抑制试验在41例中进行,均报告不被抑制;8 mg地塞米松抑制试验在40例中进行,均报告不被抑制.CT影像上显示双侧肾上腺明显增大伴多个大小不等结节.46例患者行单侧肾上腺全切术.术后患者康复出院,嘱患者术后第1、3、6、9和12个月之后每半年随访.应用SPSS 23.0软件进行统计分析,使用GraphPad Prism 8进行绘图.结果:经手术切除的标本可见多个大小不等的结节,切面呈金黄色.共42例随访,平均随访26.93个月,4例失访.随访期内,未复发29例,复发13例.未复发患者库欣综合征症状好转,血压较术前下降,平均收缩压下降22.30 mmHg(P=0.001),平均舒张压下降16.05 mmHg(P=0.003).平均8点血皮质醇浓度下降8.23 μg/dL(P＜0.000 1),平均24 h尿游离皮质醇下降273.21 μg/24 h(P＜0.000 1),平均ACTH浓度升高6.40 pg/mL(P=0.006 2).CT检查发现,未复发患者的对侧肾上腺在随访期内无显著变化.6例亚临床AIMAH患者均未复发,血压较术前降低或恢复正常.13例患者在术后有过一定时间的缓解,但5～63个月后复发,平均27.38个月,中位复发时间18个月.复发患者行对侧肾上腺全切或部分切术,46例患者手术累计59例次.结论:AIMAH患者应诊断分型.单侧肾上腺切除应被推荐作为AIMAH患者的首选治疗方式,这可以避免双侧同时切除后肾上腺皮质激素分泌不足导致的各种并发症,且对于3种亚型的患者术后均可获益.在术后,患者应定期随访,对侧肾上腺的异常增大应警惕复发可能.一旦复发,对侧肾上腺需要被处理.长期来看,单侧肾上腺切除可能使患者终身受益,患者有一定的概率无需处理对侧肾上腺.

Renal cell carcinoma (RCC) is a malignant tumor that can metastasize easily. Hence, many patients have already developed metastasis when they are diagnosed. It is also one of the most common tumors that metastasize to the head and neck through extranodal disease. Herein, we reported a case of a 53-year-old man with cervical metastasis from bilateral RCC. Interestingly, whole exome sequencing (WES) and clonal evolution analysis revealed that bilateral renal tumor lesions and neck metastases (squamous cell carcinoma) share the same subclones and a large number of gene variants, while the pathological morphology is different (left nephrotic foci, a mixed pattern of mucinous tubular and spindle cell carcinoma (MTSCC) with papillary adenoma; right renal foci, papillary renal cell carcinoma (PRCC)). This was first reported in RCCs to the best of our knowledge. This case suggests that genotype analysis can be a powerful supplementary examination for clinical histopathological diagnosis. Gene detection has great significance for the accurate diagnosis and treatment of RCC metastasis or multiple lesions.

SMARCA5 (circSMARCA5) is involved in the occurrence of different cancers, but its role in prostate cancer carcinogenesis and metastatic transformation remains elusive. Thus, we evaluated the circSMARCA5 functional relevance in prostate cancer and its associated molecular mechanism. First, circSMARCA5 expression and function in this cancer were evaluated. To determine the miR-181b-5p/miR-17-3p target and clarify how circSMARCA5 regulates the miR-181b-5p-TIMP3 and miR-17-3p-TIMP3 axis, RNA immunoprecipitation, biotin-coupled microRNA capture, luciferase reporter, Western blot, and quantitative real-time PCR assays were employed. In primary and metastatic prostate cancer tissues, circSMARCA5 was significantly downregulated compared with normal controls. Functionally, circSMARCA5 exhibited a suppressive effect on prostate cancer cells' metastasis and growth. At the molecular level, circSMARCA5 could affect the tissue inhibitor of metalloproteinases 3 (TIMP3) expression through miR-181b-5p or miR-17-3p interactions. Moreover, lysine acetyltransferase 5 (KAT5) induced circSMARCA5 biogenesis and regulated the miR-181b-5p-TIMP3 and miR-17-3p-TIMP3 axis. These results suggested that targeting circSMARCA5-miR-181b-5p-TIMP3 and circSMARCA5-miR-17-3p-TIMP3 axis might be a novel therapeutic strategy for prostate cancer.

目的:检测缺氧诱导因子1α (hypoxia-inducible factor-1α,HIF-1α)在乳头状肾细胞癌(papillary renal cell carcinoma,PRCC)组织中的表达情况,分析其与微血管密度(microvessel density,MVD)间的关系,并探讨HIF-1α与患者预后间的关系.方法:应用免疫组织化学(免疫组化)技术检测PRCC组织和癌旁肾组织(对照)中HIF-1α及MVD表达,分析二者之间的相关性.采用Kaplan-Meier法和Logrank法对患者的生存数据进行分析,对有意义的因素行Cox模型多因素回归分析.结果:PRCC组织中HIF-1α的阳性表达率为42.17％(35/83),其中Ⅰ型、Ⅱ型PRCC组织中HIF-1α阳性表达率分别为32.65％、55.88％,二者间差异有统计学意义(P=0.035).Ⅱ型PRCC组织中的MVD高于Ⅰ型PRCC(40.74个/高倍镜比25.63个/高倍镜),在Ⅰ型和Ⅱ型PRCC中,HIF-1α的表达均与MVD呈正相关(γ=0.65).83例PRCC患者的5年生存率为89.16％(74/83),13例死亡的病例中,10例为Ⅱ型PRCC,采用Kaplan-Meier生存曲线分析显示,Ⅰ型PRCC患者的预后好于Ⅱ型PRCC(5年总体生存率87.8％比76.5％,P＜0.05).单因素分析显示,肾细胞癌Fuhrman核分级Ⅲ～Ⅳ级、肿瘤发生远处转移和HIF-1α阳性表达是PRCC患者预后不良的危险因素;多因素分析显示,Ⅱ型PRCC、Fuhrman核分级Ⅲ～Ⅳ级、肿瘤远处转移及HIF-1α阳性表达是PRCC预后不良的因素.结论:相对于Ⅰ型PRCC,HIF-1α在Ⅱ型PRCC组织中的阳性率更高,其阳性表达是PRCC患者预后不良的因素.

AbstractImmune checkpoint inhibitors (ICIs) are novel treatments that significantly improve the survival time of MIBC patients, but immunotherapeutic responses are different among MIBC patients. Therefore, it is urgent to find predictive biomarkers that can accurately identify MIBC patients who are sensitive to ICIs. In this study, we computed the relative abundances of 24 immune cells based on the expression profiles of MIBC patients using single‐sample gene set enrichment analysis (ssGSEA). Unsupervised clustering analysis of the 24 immune cells was performed to classify MIBC patients into different immune‐infiltrating groups. Genome (gene mutation and copy number variation), transcriptome (mRNA, lncRNA, and miRNA), and functional enrichment were found to be heterogeneous among different immune‐infiltrating groups. We identified 282 differentially expressed genes (DEGs) associated with immune infiltration by comparing the expression profiles of patients with different immune infiltration profiles, and 20 core prognostic DEGs were identified by univariate Cox regression analysis. An immune‐relevant gene signature (TIM signature) consisting of nine key prognostic DEGs (CCDC80, CD3D, CIITA, FN1, GBP4, GNLY, SPINK1, UBD, and VIM) was constructed using least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Receiver operating characteristic (ROC) curves and subgroup analysis confirmed that the TIM signature was an ideal biomarker for predicting the prognosis of MIBC patients. Its value in predicting immunotherapeutic responses was also validated in The Cancer Genome Atlas (TCGA) cohort (AUC = 0.69, 95% CI = 0.63‐0.74) and the IMvigor210 cohort (AUC = 0.64, 95% = 0.55‐0.74). The TIM signature demonstrates a powerful ability to distinguish MIBC patients with different prognoses and immunotherapeutic responses, but more prospective studies are needed to assess its reliability in the future.

Objective To discuss the clinical manifestation and pathology of papillary renal cell carcinoma (PRCC).Methods From January 2007 to January 2012,the clinical and pathologic data of 25 patients (17 males and 8 females with average age of 54 years ranging from 24-76 years) with PRCC were retrospectively analyzed in combination with review of literature.The clinical stages of the tumor were as follows,Ⅰ in 16 cases,Ⅱ in 5 cases,Ⅲ in 4 cases.And the radiographic inspections of PRCC were compared with that of 100 randomly selected clear renal cell carcinoma (CRCC).Results All the PRCC cases had different imaging presentations compared with CRCC.CT attenuation of CRCC was higher than that of PRCC in corticomedullary,nephrographic and excretory phase (P＜0.05).Heterogeneous enhancement was most commonly seen in CRCC than PRCC (P＜0.05).There were 21 patients underwent radical nephrectomy,and 4 patients underwent laparoscopic nephron sparing surgery.The pTNM stages of the tumor were as follows,pT1N0M0 in 16 cases,pT2N0M0 in 5 cases,pT3aN0M0 in 2 cases,pT1N1M0 in 1 case,,pT2N1M0 in 1 case.Of these 25 patients,8 (32％) and 17 (68％) were diagnosed as type Ⅰ and type Ⅱ PRCC,respectively.All the 25 cases of patients were followed up from 6 to 60 months.One case died of metastasis,1 case died of cerebrovascular disease and the other 23 patients survived with tumor-free.Conclusions PRCC is a special type of RCC with low morbidity.Radiological examination can be used in the differential diagnosis of CRCC and PRCC before surgery.The prognosis after surgical treatment is good,but the adjuvant systemic treatment is to be study.

Background: Robotic adrenalectomy for pheochromocytoma is increasingly popular because of the advantage that have been proved by some researchers recently. However, prospective randomized clinical trials comparing robotic assisted laparoscopic adrenalectomy (RA) with traditional laparoscopic adrenalectomy (LA) for pheochromocytoma are rare. The aim of this study is to compare perioperative outcomes of RA versus LA for pheochromocytoma prospectively. Methods: From March 2016 to April 2019, all patients with pheochromocytoma suitable for laparoscopic adrenalectomy were assigned randomly to RA or LA. The primary endpoint was the operative (exclude docking time) time. Secondary endpoints were estimated blood loss and postoperative recovery. Demographics and perioperative data were prospectively collected. Results: A total of 140 (RA 70, LA 70) patients were enrolled in this prospective research. The following significant differences were identified in favor of RA: shorter median operative (exclude docking time) time (92.5 vs 122.5 min, P = 0.007), however, RA group has higher total hospitalization cost (8869.9 vs 4721.8 $, P < 0.001). Demographics and other perioperative outcomes were similar in both groups. The RA group showed a significant lower blood loss and operative (exclude docking time) time compared with LA group (P < 0.05) for patients with high Nor-Metanephrine (NMN). Conclusions: Both RA and LA for pheochromocytoma are safe and effective. Patients with high NMN can benefit from less blood loss and operative time when a robotic surgery system was used, but RA has a significant higher cost. (C) 2020 Published by Elsevier Ltd.