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Hai Cai,1,* Shao-Ming Chen,2,* Zhi-Bin Ke,1,* Hang Chen,1,* Jun-Ming Zhu,1 Ting-Ting Lin,1 Fei Huang,3,4 Yong Wei,1 Qing-Shui Zheng,1 Xue-Yi Xue,1 Xiong-Lin Sun,1 Ning Xu1,3 1Department of Urology, Urology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, People’s Republic of China; 2Department of Nuclear Medicine, First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, People’s Republic of China; 3Fujian Key Laboratory of Precision Medicine for Cancer, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, People’s Republic of China; 4Central Lab, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ning Xu; Xiong-Lin Sun Tel +86-059187981687Email drxun@fjmu.edu.cn; sunxionglin@fjmu.edu.cnObjective: To develop and validate hub genes involving in the development and progression of primary aldosteronism (PA) and adrenal aldosterone-producing adenoma (APA).Materials and Methods: A total of four datasets of gene expression profiles related to APA were downloaded from GEO datasets. GSE60042 and GSE8514 were used to identify DEGs. Weighted gene co-expression network analysis (WGCNA) and protein–protein interaction (PPI) network module analysis were conducted. GO and KEGG enrichment analysis was performed. GSE10927 and GSE33371 were used for further external validation.Results: We identified a total of 892 DEGs from GSE60042 and 1167 DEGs from GSE8514. WGCNA analysis demonstrated that the blue module (255 genes) and turquoise module (303 genes) were significantly correlated with APA. PPI networks were then constructed. GO term enrichment analysis suggested that cellular divalent inorganic cation homeostasis, calcium ion homeostasis, collagen-containing extracellular matrix, transport vesicle and metal ion transmembrane transporter activity were the vital annotations. KEGG pathway analysis found that these genes were significantly enriched in neuroactive ligand−receptor interaction, calcium signaling pathway. Finally, we identified a total of 11 candidate genes involving in the development and progression of APA and PA. Besides, two independent datasets (GSE10927 and GSE33371) were used for external validation, and there were seven hub genes successfully verified, including C3, GRM3, AVPR1A, WFS1, PTGFR, NTSR2, and JUN.Conclusion: These newly identified genes could contribute to the understanding of potential mechanism in APA and PA and might be promising targets for the treatment of APA and PA.Keywords: aldosterone-producing adenoma, bioinformatics, primary aldosteronism, gene expression omnibus datasets

Hao Li,1,2 Lu Chen,1,2 Zhi-Bin Ke,3 Shao-Hao Chen,3 Xue-Yi Xue,3 Qing-Shui Zheng,3 Yong Wei,3 Kai Zeng,1,2 Ning Xu3,4 1Department of Anesthesiology, Anesthesiology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, People’s Republic of China; 2Department of Surgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, People’s Republic of China; 3Department of Urology, Urology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, People’s Republic of China; 4Fujian Key Laboratory of Precision Medicine for Cancer, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, People’s Republic of ChinaCorrespondence: Ning XuDepartment of Urology, Urology Research Institute, The First Affiliated Hospital, Fujian Medical University, 20 Chazhong Road, Fuzhou, 350005, People’s Republic of ChinaTel +86-59187981687Email drxun@fjmu.edu.cnKai ZengDepartment of Anesthesiology, Anesthesiology Research Institute, The First Affiliated Hospital, Fujian Medical University, 20 Chazhong Road, Fuzhou, 350005, People’s Republic of ChinaEmail zengkai6822@163.comBackground: This study aimed to develop and validate a novel angiogenesis-related gene (ARG) signature and molecular subtypes by bioinformatics analysis.Materials and Methods: The transcriptome data and clinical data were obtained from TCGA and ICGC database. We performed consensus clustering analysis to identify angiogenesis molecular subtypes for ccRCC. Univariate and multivariate Cox regression analyses were used to develop a novel ARG-related signature as a prognostic biomarker for ccRCC. Internal and external validation were then performed in TCGA and ICGC cohort, respectively.Results: We identified a total of two angiogenesis molecular subtypes of ccRCC. The overall survival (OS) of subtype 1 ccRCC was significantly decreased compared with that of subtype 2 ccRCC (P=0.001). These two molecular subtypes have significantly different tumor microenvironment and immune checkpoint inhibitor sensitivities (P< 0.05). Besides, we developed a novel signature based on three ARGs (including MSX1, TIMP1 and JAG2) for subtype 1 ccRCC. The difference in OS between high- and low-risk group was statistically significant in training cohort (P=0.009), test cohort (P=0.024), the whole type 1 cohort (P< 0.001), and validation cohort (P=0.041). The AUC for one-year OS prediction was 0.732, 0.710, 0.725, and 0.645 in training cohort, test cohort, the whole type 1 cohort, and validation cohort, respectively. Independent prognostic analysis showed that this signature was an independent predictor for OS of subtype 1 ccRCC (P=0.028914). The power of this prognostic signature was superior to other signatures reported in previous studies.Conclusion: We developed and successfully validated a novel ARG signature for predicting prognosis of subtype 1 ccRCC, which was superior to several previous signatures.Keywords: clear cell renal cell carcinoma, angiogenesis, molecular subtypes, signature, prognosis

Ye-Hui Chen,1,&ast; Ru-Nan Dong,1,&ast; Jian Hou,1,&ast; Ting-Ting Lin,1,&ast; Shao-Hao Chen,1 Hang Chen,1 Jun-Ming Zhu,1 Jia-Yin Chen,1 Zhi-Bin Ke,1 Fei Lin,1 Xue-Yi Xue,1 Yong Wei,1 Ning Xu1,2 1Department of Urology, Urology Research Institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, People’s Republic of China; 2Fujian Key Laboratory of Precision Medicine for Cancer, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ning Xu; Yong WeiDepartment of Urology, Urology Research Institute, the First Affiliated Hospital, Fujian Medical University, 20 Chazhong Road, Fuzhou, 350005, People’s Republic of ChinaTel +86-059187981687Email drxun@fjmu.edu.cn; weiyong2017@fjmu.edu.cnBackground: Urethral stricture is a clinical challenge for both patients and clinicians. Post-traumatic urethral stricture is associated with formation of scar tissue caused by excessive inflammation. The aim of this study is exploring potential therapeutic strategies for this condition.Methods: In vivo experiments on New Zealand rabbits and in vitro experiments on THP-1 monocytes and urethral fibroblasts were performed to investigate the effects on post-traumatic urethral stricture of exosomes isolated from IL-1β-treated mesenchymal stem cells (Exo-MSCsIL− 1β) and the role of macrophage M2 polarization in this process. Additionally, related signaling and mechanism behind were explored.Results: In a New Zealand rabbit model of post-traumatic urethral stricture, injection of Exo-MSCsIL− 1β significantly reduced urethral stricture and collagen fiber accumulation compared with Exo-MSCs. Addition of Exo-MSCsIL− 1β to THP-1 monocytes in vitro induced M2 macrophage polarization, which, in turn, inhibited activation of urethral fibroblasts and synthesis of collagen. Mechanistically, Exo-MSCsIL− 1β were found to contain high levels of the microRNA let-7c, and luciferase reporter assays showed that let-7c interacted with the 3′UTR of PAK1 mRNA. Transfection of THP-1 cells with a let-7c mimic downregulated PAK1 expression and inhibited activation of the NF-κB signaling pathway.Conclusion: These results support a role for let-7c-containing Exo-MSCsIL− 1β in reducing urethral stricture via inhibition of PAK1–NF-κB signaling, M2 macrophage polarization, and differentiation of urethral myofibroblasts.Keywords: urethral stricture, mesenchymal stem cells, polarization of macrophages, exosomes, let-7c

Shao-Hao Chen,1,* Zhi-Bin Ke,1,* Yu-Peng Wu,1,* Dong-Ning Chen,1,* Xiang Yu,1 Yu Chen,2,3 Yong Wei,1 Qing-Shui Zheng,1 Xue-Yi Xue,1 Ning Xu1 1Department of Urology, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, People’s Republic of China; 2Cancer Bio-Immunotherapy Center, Fujian Medical University Cancer Hospital and Fujian Cancer Hospital, Fuzhou, People’s Republic of China; 3Department of Medical Oncology, Fujian Medical University Cancer Hospital and Fujian Cancer Hospital, Fuzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ning Xu; Xue-Yi XueDepartment of Urology, The First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou 350005, People’s Republic of ChinaTel +86-59187981687Email drxun@fjmu.edu.cn; xuexueyi@fjmu.edu.cnPurpose: To identify the relevant factors, and create and validate a predictive scoring system for the duration of laparoscopic radical prostatectomy (LRP).Patients and Methods: We retrospectively analyzed clinicopathological data from 436 patients who underwent LRP between January 2014 and January 2019, of whom 304 cases were used as a model creation group and 132 were used as a validation group. Uni/multivariate linear regression analysis was performed to determine the predictors of the duration of the procedure and a novel scoring system was created using these predictors. External validation of the scoring system was performed. The Hosmer–Lemeshow test was used to determine the goodness-of-fit of the model and calibration plots were created for visual assessment.Results: “Prolonged duration” was defined as a duration of the procedure that was longer than the mean (> 150 min) duration. Multivariate analysis showed that body mass index (BMI), prostate volume, intravesicular protrusion of the prostate (IPP), the ratio of the cross-sectional areas of the prostate and the Retzius space (P/R), pelvic lymph node dissection, and neurovascular bundle (NVB) preservation were significant predictors of prolonged duration. A scoring system that included these six parameters was created and the area under the curve achieved during receiver operating characteristic analysis using this scoring system was 0.874 (95% confidence interval [CI]: 0.836– 0.913). The Hosmer–Lemeshow test showed that the scoring system was well calibrated (X2=5.339, P=0.376). The external validation showed that the model had high predictive accuracy (AUC=0.835, 95% CI: 0.764– 0.906) and goodness-of-fit (X2=4.401, P=0.493).Conclusion: The following factors were significantly associated with prolonged duration of laparoscopic radical prostatectomy: BMI, prostate volume, IPP, P/R, pelvic lymph node dissection, and NVB preservation. The novel scoring system created can be used to accurately predict the duration of the procedure, assess the difficulty of surgery, and improve perioperative efficiency.Keywords: prostate volume, intravesical protrusion of prostate, predictive factor, pelvic lymph node dissection, neurovascular bundle preservation, prostate cancer

Xiao-Dong Li,* Yu-Peng Wu,* Zhi-Bin Ke,* Ting-Ting Lin,* Shao-Hao Chen, Xue-Yi Xue, Ning Xu, Yong Wei Departments of Urology, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yong Wei; Ning XuDepartment of Urology, The First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou 350005, People’s Republic of ChinaTel +86 0591 8798 1687Email weiyong2017@fjmu.edu.cn; drxun@fjmu.edu.cnObjective: To explore the factors associated with improvement of lower urinary tract symptoms (LUTS) after transurethral plasmakinetic enucleation of the prostate (PKEP) and transurethral resection of the prostate (TURP) in patients with a small-volume prostate and bladder outlet obstruction (BOO).Methods: The clinicopathologic data of 257 patients with BOO and a small-volume prostate from January 2013 to January 2018 were retrospectively collected preoperatively, 3 months postoperatively, and 12 months postoperatively. Patients were divided into postoperative success and failure groups based on the IPSS, IPSS-v, and IPSS-s. The relationship between each parameter and the improvement of postoperative LUTS was analyzed. Subgroup analysis was performed to compare the differences between the TURP and PKEP groups.Results: Among patients followed up for 3 months postoperatively, multivariate analysis demonstrated that IPP, PUA, and post-PCB were significant predictors of postoperative IPSS improvement; TZI, IPP, and PUA were significant predictors of postoperative IPSS-v improvement; post-PCB and the surgical procedure were significant predictors of IPSS-s improvement; and IPP and PUA were significant predictors of postoperative Qmax improvement. Among patients followed up for 12 months postoperatively, multivariate analysis revealed that IPP, PUA, and post-PCB were significant predictors of postoperative IPSS improvement; PUA was a significant predictor of postoperative IPSS-v improvement; post-PCB was a significant predictor of IPSS-s improvement; and IPP and PUA were significant predictors of postoperative Qmax improvement. The post-PCB was significantly lower in the PKEP than the TURP group and the prostatic calculi removal rate was significantly higher in the PKEP than the TURP group.Conclusion: Patients with a greater preoperative IPP and PUA and smaller post-PCB showed greater improvement of postoperative LUTS. PKEP might help to remove calculi from between the transitional and peripheral zones of prostate. Compared with conventional TURP, PKEP may improve the early postoperative storage symptoms of LUTS in patients with a small-volume prostate and BOO.Keywords: small-volume prostate, lower urinary tract symptoms, International Prostate Symptom Score

Ye-Hui Chen*, Ting-Ting Lin*, Yu-Peng Wu*, Xiao-Dong Li, Shao-Hao Chen, Xue-Yi Xue, Yong Wei, Qing-Shui Zheng, Jin-Bei Huang, Ning XuDepartments of Urology, the First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, People’s Republic of China *These authors contributed equally to this work Background: Seminoma accounts for the most part of cases of testicular germ cell tumor, which is the most common malignancy among males between ages 15 and 44 years. Understanding the molecular mechanism of tumorigenesis is important for better clinical diagnosis and treatment.Purpose: We performed bioinformatics analysis to better understand seminoma at the genetic level and to explore potential candidate genes or molecules for diagnosis, treatment, and prognosis.Methods: A gene expression profile (GSE8607), containing 40 seminoma samples and three healthy testes samples, was analyzed to identify differentially expressed genes (DEGs) associated with the occurrence of seminoma. Functional annotation was then performed using gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Cytoscape with Search Tool for the Retrieval of Interacting Genes was used to construct a protein–protein interaction (PPI) network of the DEGs and select hub genes. Moreover, validation of expression level and Kaplan–Meier analysis for overall survival were conducted to those hub genes.Results: A total of 1,636 DEGs were identified between seminoma and healthy samples, including 701 up-regulated in seminoma that were enriched in the regulation of immune responses, defense responses, receptor activity, and signal transducer activity; 935 were down-regulated in seminoma and were associated with reproductive processes, kinase activity, and carbohydrate derivative binding. Five hub genes were selected from the PPI network according to the degree of connectivity: IL6, VEGFA, IL10, CCR5, and CXCR4. Among them, high expression levels of CCR5 and CXCR4 were associated with poor prognosis for seminoma patients. Four modules selected from the PPI network revealed that seminoma was connected with the Janus kinase-signal transducers and activators of transcription signaling pathway, chemokine signaling pathway, endocytosis, and cytokine–cytokine receptor interaction.Conclusion: These identified DEGs and hub genes facilitate our knowledge of the underlying molecular mechanism of seminoma and have the potential to be used as diagnostic biomarkers or therapeutic targets for seminoma.Keywords: seminoma, bioinformatics analysis, DEGs, key genes, pathways

Xiao-Dong Li,* Yu-Peng Wu,* Shao-Hao Chen,* Ying-Chun Liang, Ting-Ting Lin, Tian Lin, Yong Wei, Xue-Yi Xue, Qing-Shui Zheng, Ning Xu Departments of Urology, First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China *These authors contributed equally to this work Purpose: To examine the effects and mechanism of action of fasudil on cytoskeletal polymerization, collagen synthesis, and apoptosis in fibroblasts derived from human urethral scar tissue. Materials and methods: Fibroblasts treated with or without transforming growth factor β1 (TGF-β1, 10 ng/mL) were incubated with fasudil (12.5, 25, 50 µmol/L) for 24 hours. Quantitative real-time polymerase chain reaction and Western blotting were used to determine the expression of Arp2, Arp3, WASP, and WAVE2. Collagen I and III protein levels were also evaluated by Western blotting. The filamentous actin cytoskeleton was examined by immunofluorescence and epifluorescence microscopy. An Annexin V-FITC/PI staining assay was used to investigate apoptosis. Results: TGF-β1-dependent induction of actin polymerization and collagen synthesis and promotion of apoptosis were dose dependent. When compared with untreated controls, fasudil significantly decreased the expression of Arp2, Arp3, WASP, WAVE2, Collagen I, and Collagen III in cells treated with or without TGF-β1. Fasudil also promoted apoptosis in cells, irrespective of TGF-β1 treatment. Conclusion: Irrespective of TGF-β1 activation status, fasudil suppressed actin polymerization and collagen synthesis and induced apoptosis in human urethral scar fibroblasts via the Rho/ROCK signaling pathway. Keywords: fasudil, polymerization, cytoskeleton, Rho/ROCK

Yu-Peng Wu,* Xiao-Dong Li,* Zhi-Bin Ke,* Shao-Hao Chen, Ping-Zhou Chen, Yong Wei, Jin-Bei Huang, Xiong-Lin Sun, Xue-Yi Xue, Qing-Shui Zheng, Ning Xu Department of Urology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China *These authors contributed equally to this work Objective: To explore risk factors of infectious complications following transrectal ultrasound-guided prostate biopsy (TRUSPB).Methods: We retrospectively analyzed 1,203 patients with suspected prostate cancer who underwent TRUSPB at our center between December 2012 and December 2016. Demographics, clinical characteristics, and data regarding complications were collected, and then univariate and multivariate logistic regression analyses were used to identify independent risk factors for infectious complications after prostate biopsy.Results: Multivariate logistic analysis demonstrated that body mass index (BMI) (OR=2.339, 95% CI 2.029–2.697, P28.196 kg/m2, history of diabetes, and preoperative catheterization are independent risk factors for infection after prostate biopsy. Keywords: body mass index, diabetes mellitus, preoperative catheterization, infectious complications, transrectal ultrasound-guided prostate biopsy

Ning Xu,* Gen-Yi Qu,* Yu-Peng Wu,* Xiao-Dong Li, Min-Yi Lin, Shao-Hao Chen, Xue-Yi Xue, Yong Wei Department of Urology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China *These authors contributed equally to this work Objective: Upregulation of actin-related protein 2/3 complex subunit 2 (Arp2) is observed in various tumors, but its expression pattern has not been revealed in bladder urothelial carcinoma (BUC). The purpose of this study was to investigate the role of Arp2 expression in the pathological features and the prognosis as well as lymph node metastasis of BUC. Methods: A total of 228 tissue specimens from BUC patients who underwent a radical cystectomy were collected. In addition, 40 lymph node specimens and 40 normal bladder tissue specimens as controls were used. All of the specimens were used to construct a tissue microarray and were subsequently subjected to immunohistochemical staining for Arp2 expression. Logistic and Cox regression analyses and Kaplan–Meier curve analysis were applied to analyze the relation between Arp2 expression and multiple clinical features of patients with BUC. Results: Immunohistochemical staining observation showed that Arp2 was mainly expressed in the cytoplasm and nucleus of positive cells and that Arp2 expression in BUC was significantly higher than that in normal bladder tissues. Arp2 expression in BUC tissues was associated with tumor size, tumor multiplicity, tumor stage, tumor grade, and lymph node metastasis (P

Yong Wei,* Yu-Peng Wu,* Ning Xu,* Xiao-Dong Li, Shao-Hao Chen, Hai Cai, Qing-Shui Zheng, Xue-Yi Xue Department of Urology, First Affiliated Hospital of Fujian Medical University, Fuzhou, China *These authors contributed equally to this work Purpose: To analyze the Surveillance, Epidemiology, and End Results (SEER) database to determine the effects of sex and prognostic factors on the survival of patients with primary urethral carcinoma (PUC). Materials and methods: We selected 453 patients diagnosed with PUC from 2004 to 2013 from the SEER database. Statistical analysis was used to identify sex-specific differences associated with tumor characteristics and cancer-specific survival (CSS) and overall survival (OS). Results: Compared with men, there was a higher proportion of black women, more negative lymph-node status, higher American Joint Committee on Cancer (AJCC) stage, more advanced T3 stage, more with adenocarcinoma (Ac), and fewer with squamous cell carcinoma (SCC) or transitional cell carcinoma (TCC). Among women, black race and M1 stage were associated with shorter CSS and OS, respectively. In addition, surgery was associated with longer OS in women. Among men, AJCC III and IV and M1 stages were associated with shorter CSS and OS. In addition, age >75 years associated with shorter OS in men. Conclusion: Black race was associated with shorter OS and CSS of women, and surgery was associated with longer OS of women. Among men, AJCC stage III and IV were associated with shorter OS and CSS. Age >75 years was associated with shorter OS in men only. Women with Ac experienced poor CSS compared with men. Men with TCC experienced worse CSS compared with those with Ac or SCC. Keywords: sex, prognostic, survival, transitional cell carcinoma, adenocarcinoma, squamous cell carcinoma

Objective: This study aimed to explore the Liquid-liquid phase separation (LLPS)-related genes associated with the prognosis of bladder cancer (BCa) and assess the potential application of LLPS-related prognostic signature for predicting prognosis in BCa patients., Methods: Clinical information and transcriptome data of BCa patients were extracted from the Cancer Genome Atlas-BLCA (TCGA-BLCA) database and the GSE13507 database. Furthermore, 108 BCa patients who received treatment at our institution were subjected to a retrospective analysis. The least absolute shrinkage and selection operator (LASSO) analysis was performed to develop an LLPS-related prognostic signature for BCa. The CCK8, wound healing and Transwell assays were performed., Results: Based on 62 differentially expressed LLPS-related genes (DELRGs), three DELRGs were screened by LASSO analysis including kallikrein-related peptidase 5 (KLK5), monoacylglycerol O-acyltransferase 2 (MOGAT2) and S100 calcium-binding protein A7 (S100A7). Based on three DELRGs, a novel LLPS-related prognostic signature was constructed for individualized prognosis assessment. Kaplan-Meier curve analyses showed that LLPS-related prognostic signature was significantly correlated with overall survival (OS) of BCa. ROC analyses demonstrated the LLPS-related prognostic signature performed well in predicting the prognosis of BCa patients in the training group (the area under the curve (AUC) = 0.733), which was externally verified in the validation cohort 1 (AUC = 0.794) and validation cohort 2 (AUC = 0.766). Further experiments demonstrated that inhibiting KLK5 could affect the proliferation, migration, and invasion of BCa cells., Conclusions: In this study, a novel LLPS-related prognostic signature was successfully developed and validated, demonstrating strong performance in predicting the prognosis of BCa patients., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Objective: Bladder cancer (BCa) is a highly lethal urological malignancy characterized by its notable histological heterogeneity. Autophagy has swiftly emerged as a diagnostic and prognostic biomarker in diverse cancer types. Nonetheless, the currently accessible autophagy-related signature specific to BCa remains limited., Methods: A refined autophagy-related signature was developed through a 10-fold cross-validation framework, incorporating 101 combinations of machine learning algorithms. The performance of this signature in predicting prognosis and response to immunotherapy was thoroughly evaluated, along with an exploration of potential drug targets and compounds. In vitro and in vivo experiments were conducted to verify the regulatory mechanism of hub gene., Results: The autophagy-related prognostic signature (ARPS) has exhibited superior performance in predicting the prognosis of BCa compared to the majority of clinical features and other developed markers. Higher ARPS is associated with poorer prognosis and reduced sensitivity to immunotherapy. Four potential targets and five therapeutic agents were screened for patients in the high-ARPS group. In vitro and vivo experiments have confirmed that FKBP9 promotes the proliferation, invasion, and metastasis of BCa., Conclusions: Overall, our study developed a valuable tool to optimize risk stratification and decision-making for BCa patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: This study was designed to develop an innovative classification and guidance system for renal hilar tumors and to assess the safety and effectiveness of robot-assisted partial nephrectomy (RAPN) for managing such tumors., Methods: A total of 179 patients undergoing RAPN for renal hilar tumors were retrospectively reviewed. A novel classification system with surgical techniques was introduced and the perioperative features, tumor characteristics, and the efficacy and safety of RAPN were compared within subgroups., Results: We classified the tumors according to our novel system as follows: 131 Type I, 35 Type II, and 13 Type III. However, Type III had higher median R.E.N.A.L., PADUA, and ROADS scores compared with the others (all p < 0.001), indicating increased operative complexity and higher estimated blood loss [180.00 (115.00-215.00) ml]. Operative outcomes revealed significant disparities between Type III and the others, with longer operative times [165.00 (145.00-200.50) min], warm ischemia times [24.00 (21.50-30.50) min], tumor resection times [13.00 (12.00-15.50) min], and incision closure times [22.00 (20.00-23.50) min] (all p < 0.005). Postoperative outcomes also showed significant differences, with longer durations of drain removal (77.08 ± 18.16 h) and hospitalization for Type III [5.00 (5.00-6.00) d] (all p < 0.05). Additionally, Type I had a larger tumor diameter than the others (p = 0.009) and pT stage differed significantly between the subtypes (p = 0.020)., Conclusions: The novel renal hilar tumor classification system is capable of differentiating the surgical difficulty of RAPN and further offers personalized surgical steps tailored to each specific classification. It provides a meaningful tool for clinical practice., (© 2024. Society of Surgical Oncology.)

We report a case of a 72-year-old female who presented with fever, abdominal pain, and diarrhea accompanied by leukopenia, anemia, and thrombocytopenia. The diagnosis of acute aplastic anemia was confirmed through bone marrow aspiration. Treatment included glucocorticoids, immunoglobulin therapy, and plasma exchange. Subsequently, the patient developed gastrointestinal bleeding and abdominal Computed Tomography (CT) revealed perforation of the transverse colon. Pathological examination of surgically removed diseased tissue confirmed mucor infection. Despite receiving antifungal therapy with amphotericin B, the patient's condition deteriorated due to the sepsis progression. Mucor infection in immunocompromised patients should be vigilant, and early diagnosis may help improve prognosis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Purpose: The aim of this study was to assess the potential application of a radiomics features-based nomogram for predicting therapeutic responses to neoadjuvant chemohormonal therapy (NCHT) in patients with high-risk non-metastatic prostate cancer (PCa)., Methods: Clinicopathologic information was retrospectively collected from 162 patients with high-risk non-metastatic PCa receiving NCHT and radical prostatectomy at our center. The postoperative pathological findings were used as the gold standard for evaluating the efficacy of NCHT. The least absolute shrinkage and selection operator (LASSO) was conducted to develop radiomics signature. Multivariate logistic regression analyses were conducted to identify the predictors of a positive pathological response to NCHT, and a nomogram was constructed based on these predictors., Results: Sixty-three patients (38.89%) experienced positive pathological response to NCHT. Receiver operating characteristic analyses showed that the area under the curve (AUC) of periprostatic fat (PPF) radiomics signature was 0.835 (95% CI, 0.754-0.898), while the AUC of intratumoral radiomics signature was 0.822 (95% CI, 0.739-0.888). Multivariate logistic regression analysis revealed that PSA level, PPF radiomics signature and intratumoral radiomics signature were independent predictors of positive pathological response. A nomogram based on these three predictors was constructed. The AUC was 0.908 (95% CI, 0.839-0.954). The Hosmer-Lemeshow goodness-of-fit test showed that the nomogram was well calibrated. Decision curve analysis revealed the favorable clinical practicability of the nomogram. The nomogram was successfully validated in the validation cohort. Kaplan-Meier analyses showed that nomogram and positive pathological response were significantly related with survival of PCa., Conclusion: The radiomics-clinical nomogram based on mpMRI radiomics features exhibited superior predictive ability for positive pathological response to NCHT in high-risk non-metastatic PCa., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: Polychlorinated biphenyls (PCBs) have caused great environmental concerns. The study aims to investigate underlying molecular mechanisms between PCBs exposure and prostate cancer (PCa)., Methods: To investigate the association between PCBs exposure and prostate cancer by using CTD, TCGA, and GEO datasets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to explore pathways associated with PCBs-related genes (PRGs). Using Lasso regression analysis, a novel PCBs-related prognostic model was developed. Both internal and external validations were conducted to assess the model's validity. Molecular docking was utilized to assess the binding capacity of PCBs to crucial genes. At last, preliminary experimental validations were conducted to confirm the biological roles of Aroclor 1254 in PCa cells., Results: The GO enrichment analysis of PRGs revealed that the biological processes were most enriched in the regulation of transcription from the RNA polymerase II promoter and signal transduction. The KEGG enrichment analysis showed that of the pathways in cancer is the most significantly enriched. Next, a PCBs-related model was constructed. In the training, test, GSE70770, and GSE116918 cohorts, the biochemical recurrences free survival of the patients with high-risk scores was considerably lower. The AUCs at 5 years were 0.691, 0.718, 0.714, and 0.672 in the four cohorts, demonstrating the modest predictive ability. A nomogram that incorporated clinical characteristics was constructed. The results of the anti-cancer drug sensitivity analysis show chemotherapy might be more beneficial for patients at low risk. The molecular docking analysis demonstrated PCBs' ability to bind to crucial genes. PCa cells exposed to Aroclor 1254 at a concentration of 1 μM showed increased proliferation and invasion capabilities., Conclusions: This study provides new insights into the function of PCBs in PCa and accentuates the need for deeper exploration into the mechanistic links between PCBs exposure and PCa progression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The incidence of metabolic diseases has progressively increased, which has a negative impact on human health and life safety globally. Due to the good efficacy and limited side effects, there is growing interest in developing effective drugs to treat metabolic diseases from natural compounds. Kaempferol (KMP), an important flavonoid, exists in many vegetables, fruits, and traditional medicinal plants. Recently, KMP has received widespread attention worldwide due to its good potential in the treatment of metabolic diseases. To promote the basic research and clinical application of KMP, this review provides a timely and comprehensive summary of the pharmacological advances of KMP in the treatment of four metabolic diseases and its potential molecular mechanisms of action, including diabetes mellitus, obesity, non-alcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH), and atherosclerosis. According to the research, KMP shows remarkable therapeutic effects on metabolic diseases by regulating multiple signaling transduction pathways such as NF-κB, Nrf2, AMPK, PI3K/AKT, TLR4, and ER stress. In addition, the most recent literature on KMP's natural source, pharmacokinetics studies, as well as toxicity and safety are also discussed in this review, thus providing a foundation and evidence for further studies to develop novel and effective drugs from natural compounds. Collectively, our manuscript strongly suggested that KMP could be a promising candidate for the treatment of metabolic diseases., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Aberrant activation of the epithelial-mesenchymal transition (EMT) pathway drives the development of solid tumors, which is precisely regulated by core EMT-related transcription factors, including Twist1. However, the expression pattern and regulatory mechanism of Twist1 in the progression of bladder cancer is still unclear. In this study, we explore the role of Twist1 in the progression of bladder cancer. We discovered that the EMT regulon Twist1 protein, but not Twist1 mRNA, is overexpressed in bladder cancer samples using RT-qPCR, western blot and immunohistochemistry (IHC). Mechanistically, co-immunoprecipitation (Co-IP) coupled with liquid chromatography and tandem mass spectrometry identified USP5 as a binding partner of Twist1, and the binding of Twist1 to ubiquitin-specific protease 5 (USP5) stabilizes Twist through its deubiquitinase activity to activate the EMT. Further studies found that USP5 depletion reduces cell proliferation, invasion and the EMT in bladder cancer cells, and ectopic expression of Twist1 rescues the adverse effects of USP5 loss on cell invasion and the EMT. A xenograft tumor model was used to reconfirmed the inhibitor effect of silencing USP5 expression on tumorigenesis in vivo. In addition, USP5 protein levels are significantly elevated and positively associated with Twist1 levels in clinical bladder cancer samples. Collectively, our study revealed that USP5-Twist1 axis is a novel regulatory mechanism driving bladder cancer progression and that approaches targeting USP5 may become a promising cancer treatment strategy., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The tumor microenvironment (TME) encompasses a variety of cells that influence immune responses and tumor growth, with tumor-associated macrophages (TAM) being a crucial component of the TME. TAM can guide prostate cancer in different directions in response to various external stimuli., Methods: First, we downloaded prostate cancer single-cell sequencing data and second-generation sequencing data from multiple public databases. From these data, we identified characteristic genes associated with TAM clusters. We then employed machine learning techniques to select the most accurate TAM gene set and developed a TAM-related risk label for prostate cancer. We analyzed the tumor-relatedness of the TAM-related risk label and different risk groups within the population. Finally, we validated the accuracy of the prognostic label using single-cell sequencing data, qPCR, and WB assays, among other methods., Results: In this study, the TAM&#95;2 cell cluster has been identified as promoting the progression of prostate cancer, possibly representing M2 macrophages. The 9 TAM feature genes selected through ten machine learning methods and demonstrated their effectiveness in predicting the progression of prostate cancer patients. Additionally, we have linked these TAM feature genes to clinical pathological characteristics, allowing us to construct a nomogram. This nomogram provides clinical practitioners with a quantitative tool for assessing the prognosis of prostate cancer patients., Conclusion: This study has analyzed the potential relationship between TAM and PCa and established a TAM-related prognostic model. It holds promise as a valuable tool for the management and treatment of PCa patients., (© 2024. The Author(s).)

Introduction: Neonatal stress disrupts brain development and increases the risk of neurological disorders later in life. However, the impact of neonatal stress on the development of the glymphatic system and susceptibility to Parkinson's disease (PD) remains largely unknown., Methods: Neonatal maternal deprivation (NMD) was performed on mice for 14 consecutive days to model chronic neonatal stress. Adeno-associated virus expressing A53T-α-synuclein (α-syn) was injected into the substantia nigra to establish PD model mice. Glymphatic activity was determined using in vivo magnetic resonance imaging, ex vivo fluorescence imaging and microplate assay. The transcription and expression of aquaporin-4 (AQP4) and other molecules were evaluated by qPCR, western blotting, and immunofluorescence. Animal's responses to NMD and α-syn overexpression were observed using behavioral tests., Results: Glymphatic activity was impaired in adult NMD mice. AQP4 polarization and platelet-derived growth factor B (PDGF-B) signaling were reduced in the frontal cortex and hippocampus of both young and adult NMD mice. Furthermore, exogenous α-syn accumulation was increased and PD-like symptoms were aggravated in adult NMD mice., Conclusion: The results demonstrated that NMD could disrupt the development of the glymphatic system through PDGF-B signaling and increase the risk of PD later in life, indicating that alleviating neonatal stress could be beneficial in protecting the glymphatic system and reducing susceptibility to neurodegeneration., (© 2024 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC., Patients and Methods: Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib [50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle)]. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety., Results: A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028]. The median PFS was 18.0 months in the toripalimab-axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab-axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab-axitinib group and 58.6% of patients in the sunitinib group., Conclusion: In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile TRIAL REGISTRATION: ClinicalTrials.gov NCT04394975., (Copyright © 2023 X. Yan, M. Ye, Q. Zou, P. Chen, Z. He, B. Wu, D. He, C. He, X. Xue, Z. Ji, H. Chen, S. Zhang, Y. Liu, X. Zhang, C. Fu, D. Xu, M. Qiu, J. Lv, J. Huang, X. Ren, Y. Cheng, W. Qin, X. Zhang, F. Zhou, L. Ma, J. Guo, D. Ding, S. Wei, Y. He, H. Guo, B. Shi, L. Liu, F. Liu, Z. Hu, X. Jin, L. Yang, S. Zhu, J. Liu, Y. Huang, T. Xu, B. Liu, T. Sun, Z. Wang, H. Jiang, D. Yu, A. Zhou, J. Jiang, G. Luan, C. Jin, J. Xu, J. Hu, Y. H, Jun, W. Zhai, X. Sheng, Shanghai Junshi Biosciences Co. LTD, Shanghai Junshi Biosciences Co. LTD., a. Published by Elsevier Ltd.. All rights reserved.)

Background: Many imaging scoring models have been developed for tumor surgery to provide critical guidance for the selection of surgical methods. However, little research has been aimed at developing scoring models for adrenal tumors and retroperitoneal laparoscopic adrenal surgery (RLAS), which has become the primary technique for treating adrenal tumors. The study set out to establish a computed tomography (CT)-based adrenal tumor scoring model for predicting perioperative outcomes in patients with adrenal tumors who have undergone RLAS., Methods: The retrospective analysis included 306 patients with adrenal tumors diagnosed by preoperative unenhanced or enhanced CT from January 2014 to August 2018 in the First Affiliated Hospital of Fujian Medical University. CT images were used to quantify the tumor location and size; the relationships of the tumors with the surrounding organs and tissues, the large abdominal blood vessels, and the upper poles of the kidneys and renal hila; the adhesion of periadrenal fat (PF); and the tumor CT enhancement value. We conducted multivariate ordinal logistic regression analysis to screen variables and performed principal component analysis to construct a novel scoring model for RLAS. The perioperative outcomes of RLAS were evaluated according to postoperative length of stay, operative time (OT), intraoperative blood loss (IBL), and postoperative complications., Results: The final scoring model included tumor size; the relationships of the tumors with the surrounding organs and tissues, the large abdominal blood vessels, and the upper poles of the kidneys and renal hila; the tumor CT enhancement value; the adhesion of the PF; and the functional status of adrenal tumors. The total score had positive correlations with the OT (r s =0.431), IBL (r s =0.446), and postoperative length (r s =0.180) (all P values <0.001). Compared to any single metric, the total score provided better prediction of OT and IBL. The grading system for RLAS based on the scoring model also performed well in predicting the complexity and difficulty of RLAS. The coincidence rate for these factors was good (all P values <0.001)., Conclusions: The developed model is feasible and repeatable in the prediction of the perioperative outcomes, complexity, and difficulty of RLAS., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-764/coif). The authors have no conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

This study aims to develop fatty acid metabolism-related molecular subtypes and construct a fatty acid metabolism-related novel model for bladder cancer (BCa) by bioinformatic profiling. Genome RNA-seq expression data of BCa samples from the TCGA database and GEO database were downloaded. We then conducted consensus clustering analysis to identify fatty acid metabolism-related molecular subtypes for BCa. Univariate and multivariate Cox regression analysis were performed to identify a novel prognostic fatty acid metabolism-related prognostic model for BCa. Finally, we identified a total of three fatty acid metabolismrelated molecular subtypes for BCa. These three molecular subtypes have significantly different clinical characteristics, PD-L1 expression levels, and tumor microenvironments. Also, we developed a novel fatty acid metabolism-related prognostic model. Patients with low-risk score have significantly preferable overall survival compared with those with high-risk score in the training, testing, and validating cohorts. The area under the ROC curve (AUC) for overall survival prediction was 0.746, 0.681, and 0.680 in the training, testing and validating cohorts, respectively. This model was mainly suitable for male, older, high-grade, cluster 2-3, any TCGA stage, any N-stage, and any T-stage patients. Besides, we selected FASN as a hub gene for BCa and further qRT-PCR validation was successfully conducted. In conclusion, we developed and successfully validated a novel fatty acid metabolism-related prognostic model for predicting outcome for BCa patients.

Objective: Genomic instability can drive clonal evolution, continuous modification of tumor genomes, and tumor genomic heterogeneity. The molecular mechanism of genomic instability still needs further investigation. This study aims to identify novel genome instabilityassociated lncRNAs (GI-lncRNAs) and investigate the role of genome instability in pan-Renal cell carcinoma (RCC)., Materials and Methods: A mutator hypothesis was employed, combining the TCGA database of somatic mutation (SM) information, to identify GI-lncRNAs. Subsequently, a training cohort (n = 442) and a testing cohort (n = 439) were formed by randomly dividing all RCC patients. Based on the training cohort dataset, a multivariate Cox regression analysis lncRNAs risk model was created. Further validations were performed in the testing cohort, TCGA cohort, and different RCC subtypes. To confirm the relative expression levels of lncRNAs in HK-2, 786-O, and 769-P cells, qPCR was carried out. Functional pathway enrichment analyses were performed for further investigation., Results: A total of 170 novel GI-lncRNAs were identified. The lncRNA prognostic risk model was constructed based on LINC00460, AC073218.1, AC010789.1, and COLCA1. This risk model successfully differentiated patients into distinct risk groups with significantly different clinical outcomes. The model was further validated in multiple independent patient cohorts. Additionally, functional and pathway enrichment analyses revealed that GI-lncRNAs play a crucial role in GI. Furthermore, the assessments of immune response, drug sensitivity, and cancer stemness revealed a significant relationship between GI-lncRNAs and tumor microenvironment infiltration, mutational burden, microsatellite instability, and drug resistance., Conclusions: In this study, we discovered four novel GI-lncRNAs and developed a novel signature that effectively predicted clinical outcomes in pan-RCC. The findings provide valuable insights for pan-RCC immunotherapy and shed light on potential underlying mechanisms., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Bladder cancer represents a significant public health concern with diverse genetic alterations influencing disease onset, progression, and therapy response. In this study, we explore the multifaceted role of Solute Carrier Family 31 Member 1 (SLC31A1) in bladder cancer, a pivotal gene involved in copper homeostasis. Methods: Our research involved analyzing the SLC31A1 gene expression via RT-qPCR, promoter methylation via targeted bisulfite sequencing, and mutational status via Next Generation Sequencing (NGS) using the clinical samples sourced by the local bladder cancer patients. Later on, The Cancer Genome Atlas (TCGA) datasets were utilized for validation purposes. Moreover, prognostic significance, gene enrichment terms, and therapeutic drugs of SLC31A1 were also explored using KM Plotter, DAVID, and DrugBank databases. Results: We observed that SLC31A1 was significantly up-regulated at both the mRNA and protein levels in bladder cancer tissue samples, suggesting its potential involvement in bladder cancer development and progression. Furthermore, our investigation into the methylation status revealed that SLC31A1 was significantly hypomethylated in bladder cancer tissues, which may contribute to its overexpression. The ROC analysis of the SLC31A1 gene indicated promising diagnostic potential, emphasizing its relevance in distinguishing bladder cancer patients from normal individuals. However, it is crucial to consider other factors such as cancer stage, metastasis, and recurrence for a more accurate evaluation in the clinical context. Interestingly, mutational analysis of SLC31A1 demonstrated only benign mutations, indicating their unknown role in the SLC31A1 disruption. In addition to its diagnostic value, high SLC31A1 expression was associated with poorer overall survival (OS) in bladder cancer patients, shedding light on its prognostic relevance. Gene enrichment analysis indicated that SLC31A1 could influence metabolic and copper-related processes, further underscoring its role in bladder cancer. Lastly, we explored the DrugBank database to identify potential therapeutic agents capable of reducing SLC31A1 expression. Our findings unveiled six important drugs with the potential to target SLC31A1 as a treatment strategy. Conclusion: Our comprehensive investigation highlights SLC31A1 as a promising biomarker for bladder cancer development, progression, and therapy., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: ND630 is believed to be a new therapy pharmacologic molecule in targeting the expression of ACACA and regulating the lipid metabolism. However, the function of ND630 in prostate cancer remains unknown. KIF18B, as an oncogene, plays a vital role in prostate cancer progression. circKIF18B&#95;003 was derived from oncogene KIF18B and was markedly overexpressed in prostate cancer tissues. We speculated that oncoprotein KIF18B-derived circRNA circKIF18B&#95;003 might have roles in prostate cancer promotion. The aim of this study was to validate whether ND630 could control ACACA and lipid reprogramming in prostate cancer by regulating the expression of circKIF18B&#95;003., Methods: RT-qPCR was used to analyze the expression of circKIF18B&#95;003 in prostate cancer cell lines and prostate cancer samples. circKIF18B&#95;003 expression was modulated in prostate cancer cells using circKIF18B&#95;003 interference or overexpression plasmid. We examined the function and effects of circKIF18B&#95;003 in prostate cancer cells using CCK-8, colony formation, wound healing, and Transwell invasion assays and xenograft models. Fluorescence in situ hybridization (FISH) was performed to evaluate the localization of circKIF18B&#95;003. RNA immunoprecipitation (RIP), RNA pull down, and luciferase reporter assay were performed to explore the potential mechanism of circKIF18B&#95;003., Results: The function of ND630 was determined in this study. circKIF18B&#95;003 was overexpressed in prostate cancer tissues, and overexpression of circKIF18B&#95;003 was associated with poor survival outcome of prostate cancer patients. The proliferation, migration, and invasion of prostate cancer cells were enhanced after up-regulation of circKIF18B&#95;003. circKIF18B&#95;003 is mainly located in the cytoplasm of prostate cancer cells, and the RIP and RNA pull down assays confirmed that circKIF18B&#95;003 could act as a sponge for miR-370-3p. Further study demonstrated that up-regulation of circKIF18B&#95;003 increased the expression of ACACA by sponging miR-370-3p. The malignant ability of prostate cancer cells enhanced by overexpression of circKIF18B&#95;003 was reversed by the down-regulation of ACACA. We found that overexpression of circKIF18B&#95;003 was associated with lipid metabolism, and a combination of ND-630 and docetaxel markedly attenuated tumor growth., Conclusion: ND630 could control ACACA and lipid reprogramming in prostate cancer by regulating the expression of circKIF18B&#95;003. ND630 and circKIF18B&#95;003 may represent a novel target for prostate cancer., (© 2023. The Author(s).)

Liver fibrosis is a wound-healing process characterized by excess formation of extracellular matrix (ECM) from activated hepatic stellate cells (HSCs). Previous studies show that both EZH2, an epigenetic regulator that catalyzes lysine 27 trimethylation on histone 3 (H3K27me3), and long non-coding RNA H19 are highly correlated with fibrogenesis. In the current study, we investigated the underlying mechanisms. Various models of liver fibrosis including Mdr2 -/- , bile duct ligation (BDL) and CCl 4 mice were adapted. We found that EZH2 was markedly upregulated and correlated with H19 and fibrotic markers expression in these models. Administration of EZH2 inhibitor 3-DZNeP caused significant protective effects in these models. Furthermore, treatment with 3-DZNeP or GSK126 significantly inhibited primary HSC activation and proliferation in TGF-β-treated HSCs and H19-overexpreesing LX2 cells in vivo. Using RNA-pull down assay combined with RNA immunoprecipitation, we demonstrated that H19 could directly bind to EZH2. Integrated analysis of RNA-sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) further revealed that H19 regulated the reprogramming of EZH2-mediated H3K27me3 profiles, which epigenetically promoted several pathways favoring HSCs activation and proliferation, including epithelial-mesenchymal transition and Wnt/β-catenin signaling. In conclusion, highly expressed H19 in chronic liver diseases promotes fibrogenesis by reprogramming EZH2-mediated epigenetic regulation of HSCs activation. Targeting the H19-EZH2 interaction may serve as a novel therapeutic approach for liver fibrosis., (© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Objective: To explore the influence of postoperative body mass index (BMI) change on postoperative quality of life (QOL) in patients undergoing radical cystectomy (RC) plus modified single stoma cutaneous ureterostomy (MSSCU) or ileal conduit (IC)., Methods: Patients were divided into two groups according to different BMI change patterns: patients experiencing an elevated postoperative BMI level, along with a clinically significant increase in their BMI (an increase of more than 10%) were categorized as Group 1, while patients experiencing a decrease postoperative BMI level, along with a clinically significant reduction in their BMI (a decrease of more than 5%) were categorized as Group 2. Spearman correlation analysis was used to examine the correlations between quality-of-life scores and postoperative clinical parameters., Results: Spearman correlation analysis showed that postoperative BMI, late complications and catheter-free state were significantly associated with postoperative global QoL and symptom scale in MSSCU and postoperative global QoL and physical scale in IC patients. Additionally, postoperative BMI, catheter-free state and the use of adjuvant therapy were associated with bad performance in many scales of QoL like body image, future perspective, social scale, future perspective (MSSCU), and abdominal bloating (IC) (Table 2, p<0.05). Patients in Group 2 with significant weight loss had a better Global QoL, a lower rate of stomal stricture and a higher catheter-free state compared with those in Group 1 in both IC and MSSCU patients. MSSCU patients in Group 2 could achieve a comparable Global QoL as to IC patients in Group 1., Conclusion: Controlling the substantial increase in body weight after surgery contributes to improving QoL, reducing the occurrence of stomal stricture, and ensuring a postoperative catheter-free state in BCa patients undergoing MSSCU., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objectives: Accurate preoperative prediction of adverse pathology is crucial for treatment planning of renal cell carcinoma (RCC). Previous studies have emphasized the potential of prostate-specific membrane antigen positron emission tomography / computed tomography (PSMA PET/CT) in differentiating between benign and malignant localized renal tumors. However, there is a scarcity of case reports elucidating the identification of aggressive pathological features using PET/CT. Our study was designed to prospectively compare the diagnostic value of enhanced CT, 68Ga-PSMA-11 and 18F-fluorodeoxyglucose (18F-FDG) PET/CT in clear-cell renal cell carcinoma (ccRCC) with necrosis or sarcomatoid or rhabdoid differentiation., Materials and Methods: A prospective case series of patients with a newly diagnosed renal mass who underwent enhanced CT, 68Ga-PSMA-11 and 18F-FDG PET/CT within 30 days prior to nephrectomy was included. Complete preoperative and postoperative clinicopathological data were recorded. Patients who received neoadjuvant targeted therapy, declined enhanced CT or PET/CT scanning, refused surgical treatment or had non-ccRCC pathological indications were excluded. Radiological parameters were compared within subgroups of pathological characteristics. Bonferroni corrections were used to adjust for multiple testing and statistical significance was set at a p-value less than 0.017., Results: Seventy-two patients were available for the final analysis. Enhanced CT demonstrated poor performance in identifying necrosis, sarcomatoid or rhabdoid differentiation and adverse pathology (all P > 0.05). The maximum standardized uptake value (SUVmax) of 68Ga-PSMA-11 PET/CT was more effective than 18F-FDG PET/CT in identifying tumor necrosis and adverse pathology, with an area under the curve (AUC) of 0.85 (cutoff value=25.26, p<0.001; Delong test z=2.709, p=0.007) for tumor necrosis and AUC of 0.90 (cutoff value=25.26, p<0.001; Delong test z=3.433, p<0.001) for adverse pathology. However, no significant statistical difference was found between 68Ga-PSMA-11 and 18F-FDG PET/CT in predicting sarcomatoid or rhabdoid feature (AUC of 0.91 vs.0.75, Delong test z=1.998, p=0.046). Subgroup analyses based on age, sex, tumor location, maximal diameter, stage and WHO/ISUP grade demonstrated that 68Ga-PSMA-11 PET/CT SUVmax had a significant predictive value for adverse pathology. Enhanced CT value and SUVmax demonstrated strong reliability [intraclass correlation coefficient (ICC) > 0.80], indicating a robust correlation., Conclusions: 68Ga-PSMA-11 PET/CT demonstrates distinct advantages in identifying aggressive pathological features of primary ccRCC when compared to enhanced CT and 18F-FDG PET/CT. Further research and assessment are warranted to fully establish the clinical utility of 68Ga-PSMA-11 PET/CT in ccRCC., Competing Interests: None declared., (Copyright® by the International Brazilian Journal of Urology.)

Objectives: To examine the characteristics of blood lymphocyte subsets in dermatomyositis-interstitial lung disease (DM-ILD) inflicted patients with positive anti-melanoma differentiation-associated gene 5 (anti-MDA5), as well as its prognosis value in this set of patients., Methods: Data were retrospectively collected from 253 DM-ILD patients from three hospitals in China between January 2016 to January 2021. Patients were grouped into anti-MDA5 antibody positive group (MDA5 + DM-ILD) and anti-MDA5 antibody negative group (MDA5 - DM-ILD) based on myositis-specific autoantibody test results. Demographic characteristics, lymphocyte subsets patterns and other clinical features were compared between the two groups. The association of lymphocyte subsets with 180-day mortality was investigated using survival analysis in MDA5 + DM-ILD., Results: Out of 253 eligible patients with DM-ILD, 59 patients were anti-MDA5 + and 194 were anti-MDA5 - . Peripheral blood lymphocyte count, CD3 + count, percentage of CD3 + , CD3 + CD4 + count, and CD3 + CD8 + count was lower in MDA5 + DM-ILD than in MDA5 - DM-ILD - (all P < 0.001) as well as CD3 - CD19 + count (P = 0.04). In MDA5 + DM-ILD, CD3 + CD8 + count ≤ 49.22 cell/μL (HR = 3.81, 95%CI [1.20,12.14]) and CD3-CD19 + count ≤ 137.64 cell/μL (HR = 3.43, 95%CI [1.15,10.24]) were independent predictors of mortality. CD3 + CD8 + count ≤ 31.38 cell/μL was associated with a higher mortality risk in all DM-ILD patients (HR = 8.6, 95%CI [2.12,31.44]) after adjusting for anti-MDA5 and other clinical characteristics., Conclusion: Significant lymphocytes decrease was observed in MDA5 + DM-ILD patients. CD3 + CD8 + cell count was associated with worse prognosis in both MDA5 + DM-ILD and all DM-ILD patients., (© 2023. The Author(s).)

Objective: To identify tumor-associated macrophages (TAMs) related molecular subtypes and develop a TAMs related prognostic model for prostate cancer (PCa)., Methods: Consensus clustering analysis was used to identify TAMs related molecular clusters. A TAMs related prognostic model was developed using univariate and multivariate Cox analysis., Results: Three TAMs related molecular clusters were identified and were confirmed to be associated with prognosis, clinicopathological characteristics, PD-L1 expression levels and tumor microenvironment. A TAMs related prognostic model was constructed. Patients in low-risk group all showed a more appreciable biochemical recurrence-free survival (BCRFS) than patients in high-risk group in train cohort, test cohort, entire TCGA cohort and validation cohort. SLC26A3 attenuated progression of PCa and prevented macrophage polarizing to TAMs phenotype, which was initially verified., Conclusions: We successfully identified molecular clusters related to TAMs. Additionally, we developed a prognostic model involving TAMs that exhibits excellent predictive performance for biochemical recurrence-free survival in PCa., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To identify CD8 + T cell-related molecular clusters and establish a novel gene signature for predicting the prognosis and efficacy of immunotherapy in bladder cancer (BCa)., Methods: Transcriptome and clinical data of BCa samples were obtained from the Cancer Genome Atlas (TCGA) and GEO databases. The CD8 + T cell-related genes were screened through the CIBERSORT algorithm and correlation analysis. Consensus clustering analysis was utilized to identified CD8 + T cell-related molecular clusters. A novel CD8 + T cell-related prognostic model was developed using univariate Cox regression analysis and Lasso regression analysis. Internal and external validations were performed and the validity of the model was validated in a real-world cohort. Finally, preliminary experimental verifications were carried out to verify the biological functions of SH2D2A in bladder cancer., Results: A total of 52 CD8 + T cell-related prognostic genes were screened and two molecular clusters with notably diverse immune cell infiltration, prognosis and clinical features were developed. Then, a novel CD8 + T cell-related prognostic model was constructed. The patients with high-risk scores exhibited a significantly worse overall survival in training, test, whole TCGA and validating cohort. The AUC was 0.766, 0.725, 0.739 and 0.658 in the four cohorts sequentially. Subgroup analysis suggested that the novel prognostic model has a robust clinical application for selecting high-risk patients. Finally, we confirmed that patients in the low-risk group might benefit more from immunotherapy or chemotherapy, and validated the prognostic model in a real-world immunotherapy cohort. Preliminary experiment showed that SH2D2A was capable of attenuating proliferation, migration and invasion of BCa cells., Conclusions: CD8 + T cell-related molecular clusters were successfully identified. Besides, a novel CD8 + T cell-related prognostic model with an excellent predictive performance in predicting survival rates and immunotherapy efficacy of BCa was developed., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose: The purpose of this study was to explore the semantic computed tomography (CT) features associated with BRCA1-associated protein 1 (BAP1) and/or tumor protein p53 (TP53) mutation in clear cell renal cell carcinoma (ccRCC)., Methods and Materials: Clinical characteristics and gene mutation information of 336 ccRCC patients were retrieved from The Cancer Genome Atlas-Kidney Renal Clear Cell Carcinoma database (TCGA-KIRC). Kaplan-Meier analysis was performed to examine prognosis by gene mutation. The CT imaging data and gene mutation information of 156 ccRCC patients treated between January 2019 and January 2021 (the training cohort) were retrospectively analyzed. The CT imaging information and gene mutation data of 123 patients with ccRCC were downloaded from The Cancer Imaging Archive and The Cancer Genome Atlas database (the external validation cohort). Univariate Chi-square test and multivariate binary logistic regression analysis were performed to determine predictors of gene mutation; a nomogram was developed using these predictors. Receiver operating characteristic curve analysis and the Hosmer-Lemeshow test were performed to evaluate the performance of the nomogram., Results: Kaplan-Meier analysis showed that BAP1 and/or TP53 mutation was significantly correlated with worse survival outcome. Multivariate binary logistic regression analysis indicated ill-defined margin (P = .001), spiculated margin (P = .018), renal vein invasion (P = .002), and renal pelvis invasion (P = .001) were independent predictors of BAP1 and/or TP53 mutation. A nomogram containing these 4 semantic CT features was constructed; the area under the receiver operating characteristic curves was 0.872 (95% CI, 0.809-0.920). The Hosmer-Lemeshow test showed acceptable goodness-of-fit for the nomogram (X 2  = 1.194, P = .742). The nomogram was validated in the validation cohort; it showed good accuracy (area under the receiving operating characteristic curve = 0.819, 95% CI, 0.740-0.883) and was well calibrated (X 2  = 3.934, P = .559)., Conclusions: Semantic CT features are a potential and promising method for predicting BAP1 and/or TP53 mutation status in ccRCC patients., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To explore whether 68 Ga-PSMA-11 PET/CT-derived parameters could predict biochemical response to abiraterone acetate (AA) treatment and prognosis in metastatic prostate cancer patients developing castration resistance after chemohormonal therapy at hormone-sensitive stage., Methods: The clinicopathologic data of 106 mCRPC cases receiving AA treatment were retrospectively analyzed. Logistic regression analysis was used to determine the independent predictors of biochemical response to AA treatment. Cox analyses were applied to investigate the independent prognostic factors for time to biochemical progression (TTBP) and radiological progression-free survival (rPFS). Survival analysis and ROC curve were also used., Results: Multivariable Logistic analysis demonstrated that prior ADT duration ≥ 12 months, low prostate specific membrane antigen receptor-expressing tumor volume (PSMA-TV), low tumor to liver ratio (TLR) were independent predictors of biochemical response to AA treatment. Multivariate Cox analysis demonstrated that low PSMA-TV and low TLR were independent prognostic factors of longer TTBP and rPFS. The TTBP and rPFS of patients with higher PSMA-TV or TLR were significantly decreased compared with that of patients with lower PSMA-TV and TLR. The area under ROC curve (AUC) of combining ADT duration, PSMA-TV and TLR was 0.82 for predicting biochemical response to AA, which was significantly increased compared with that of other 68 Ga-PSMA-11 PET/CT-derived parameters alone., Conclusions: Low PSMA-TV, low TLR were vital independent predictors of biochemical response to AA treatment and were associated with preferable prognosis in mCRPC patients. Combining ADT duration, PSMA-TV and TLR performed well in distinguishing AA responders from non-responders in mCRPC patients., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Immunotherapy based on immune checkpoint inhibitors (ICIs) has provided revolutionary results in treating various cancers. However, its efficacy in colorectal cancer (CRC), especially in microsatellite stability-CRC, is limited. This study aimed to observe the efficacy of personalized neoantigen vaccine in treating MSS-CRC patients with recurrence or metastasis after surgery and chemotherapy. Candidate neoantigens were analyzed from whole-exome and RNA sequencing of tumor tissues. The safety and immune response were assessed through adverse events and ELISpot. The clinical response was evaluated by progression-free survival (PFS), imaging examination, clinical tumor marker detection, circulating tumor DNA (ctDNA) sequencing. Changes in health-related quality of life were measured by the FACT-C scale. A total of six MSS-CRC patients with recurrence or metastasis after surgery and chemotherapy were administered with personalized neoantigen vaccines. Neoantigen-specific immune response was observed in 66.67% of the vaccinated patients. Four patients remained progression-free up to the completion of clinical trial. They also had a significantly longer progression-free survival time than the other two patients without neoantigen-specific immune response (19 vs. 11 months). Changes in health-related quality of life improved for almost all patients after the vaccine treatment. Our results shown that personalized neoantigen vaccine therapy is likely to be a safe, feasible and effective strategy for MSS-CRC patients with postoperative recurrence or metastasis., (© 2023. The Author(s).)

Objective and Design: Post-traumatic urethral stricture is a clinical challenge for both patients and clinicians. Targeting glutamine metabolism to suppress excessive activation of urethral fibroblasts (UFBs) is assumed to be a potent and attractive strategy for preventing urethral scarring and stricture., Material or Subjects: In cellular experiments, we explored whether glutaminolysis meets the bioenergetic and biosynthetic demands of quiescent UFBs converted into myofibroblasts. At the same time, we examined the specific effects of M2-polarized macrophages on glutaminolysis and activation of UFBs, as well as the mechanism of intercellular signaling. In addition, findings were further verified in vivo in New Zealand rabbits., Results: It revealed that glutamine deprivation or knockdown of glutaminase 1 (GLS1) significantly inhibited UFB activation, proliferation, biosynthesis, and energy metabolism; however, these effects were rescued by cell-permeable dimethyl α-ketoglutarate. Moreover, we found that exosomal miR-381 derived from M2-polarized macrophages could be ingested by UFBs and inhibited GLS1-dependent glutaminolysis, thereby preventing excessive activation of UFBs. Mechanistically, miR-381 directly targets the 3'UTR of Yes-associated protein (YAP) mRNA to reduce its stability at the transcriptional level, ultimately downregulating expression of YAP, and GLS1. In vivo experiments revealed that treatment with either verteporfin or exosomes derived from M2-polarized macrophages significantly reduced urethral stricture in New Zealand rabbits after urethral trauma., Conclusion: Collectively, this study demonstrates that exosomal miR-381 from M2-polarized macrophages reduces myofibroblast formation of UFBs and urethral scarring and stricture by inhibiting YAP/GLS1-dependent glutaminolysis., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Immunogenic cell death (ICD) plays a vital role in tumor progression and immune response. However, the integrative role of ICD-related genes and subtypes in the tumor microenvironment (TME) in prostate cancer (PCa) remains unknown., Materials and Methods: The sample data were obtained from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Memorial Sloan Kettering Cancer Center (MSKCC) prostate cancer-related databases. We first divided the subtypes based on ICD genes from 901 PCa patients and then identified the prognosis- related genes (PRGs) between different ICD subtypes. Subsequently, all the patients were randomly split into the training and test groups. We developed a risk signature in the training set by least absolute shrinkage and selection operator (LASSO)-Cox regression. Following this, we verified this prognostic signature in both the training test and external test sets. The relationships between the different subgroups and clinical pathological characteristics, immune infiltration characteristics, and mutation status of the TME were examined. Finally, the artificial neural network (ANN) and fundamental experiment study were constructed to verify the accuracy of the prognostic signature., Results: We identified two ICD clusters with immunological features and three gene clusters composed of PRGs. Additionally, we demonstrated that the risk signature can be used to evaluate tumor immune cell infiltration, prognostic status, and an immune checkpoint inhibitor. The low-risk group, which has a high overlap with group C of the gene cluster, is characterized by high ICD levels, immunocompetence, and favorable survival probability. Furthermore, the tumor progression genes selected by the ANN also exhibit potential associations with risk signature genes., Conclusion: This study identified individuals with high ICD levels in prostate cancer who may have more abundant immune infiltration and revealed the potential effects of risk signature on the TME, immune checkpoint inhibitor, and prognosis of PCa., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kang, Sun, Lin, Huang, Huang, Chen, Zheng, Xue, Xu and Wei.)

In our study, 49 key genes significantly associated with renal cell carcinoma (RCC) stemness were obtained. Next, we developed a molecular prognostic signature associated with stemness features of pan-RCC. The difference in overall survival (OS) between the high- and low-risk groups was statistically significant ( p  < .05). The area under the receiver operating characteristic curve for 1-year OS, 5-year OS, and 10-year OS was 0.759, 0.712, and 0.918, respectively. The results of validation in The Cancer Genome Atlas cohort and International Cancer Genome Consortium cohort revealed the predictive capability of this signature. Furthermore, we selected three genes and further validation showed that these three hub genes were potential hub biomarkers for pan-RCC stemness features.

Hypoxia contributes to the initiation and progression of glioblastoma by regulating a cohort of genes called hypoxia-regulated genes (HRGs) which form a complex molecular interacting network (HRG-MINW). Transcription factors (TFs) often play central roles for MINW. The key TFs for hypoxia induced reactions were explored using proteomic analysis to identify a set of hypoxia-regulated proteins (HRPs) in GBM cells. Next, systematic TF analysis identified CEBPD as a top TF that regulates the greatest number of HRPs and HRGs. Clinical sample and public database analysis revealed that CEBPD is significantly up-regulated in GBM, high levels of CEBPD predict poor prognosis. In addition, CEBPD is highly expressed in hypoxic condition both in GBM tissue and cell lines. For molecular mechanisms, HIF1α and HIF2α can activate the CEBPD promotor. In vitro and in vivo experiments demonstrated that CEBPD knockdown impaired the invasion and growth capacity of GBM cells, especially in hypoxia condition. Next, proteomic analysis identified that CEBPD target proteins are mainly involved in the EGFR/PI3K pathway and extracellular matrix (ECM) functions. WB assays revealed that CEBPD significantly positively regulated EGFR/PI3K pathway. Chromatin immunoprecipitation (ChIP) qPCR/Seq analysis and Luciferase reporter assay demonstrated that CEBPD binds and activates the promotor of a key ECM protein FN1 (fibronectin). In addition, the interactions of FN1 and its integrin receptors are necessary for CEBPD-induced EGFR/PI3K activation by promoting EGFR phosphorylation. Furthermore, GBM sample analysis in the database corroborated that CEBPD is positively correlated with the pathway activities of EGFR/PI3K and HIF1α, especially in highly hypoxic samples. At last, HRPs are also enriched in ECM proteins, indicating that ECM activities are important components of hypoxia induced responses in GBM. In conclusion, CEPBD plays important regulatory roles in the GBM HRG-MINW as a key TF, which activates the EGFR/PI3K pathway through ECM, especially FN1, mediated EGFR phosphorylation., (© 2023. The Author(s).)

Purpose: To investigate the risk factors for postoperative lymphorrhea or/and lymphocele (PLL) in patients undergoing radical prostatectomy (RP)., Materials and Methods: The clinical data of 606 patients were retrospectively collected. The receiver operating characteristic (ROC) curve was utilized to identify the optimal cutoff value. Multivariable logistic regression analysis was used to screen the independent predictors of PLL., Results: Univariate analysis showed that nine factors differed between the PLL and non-PLL group. Multivariable logistic regression analysis showed that low preoperative fibrinogen level, extraperitoneal surgery, robot-assisted laparoscopic radical prostatectomy (RALRP), and hypoalbuminemia were risk factors and the use of fibrin glue was a protective factor. Correlation analysis showed that the scope of LN dissection (LND) and number of lymph nodes (LNs) dissected were positively correlated with PLL in the extraperitoneal approach, but were not significantly correlated with PLL in the transperitoneal approach. The use of fibrin glue was negatively associated with PLL in the overall procedure and the extraperitoneal approach, but not significantly so in the transperitoneal approach. Comparison of LNs clearance between the two surgical approaches revealed that the extent of LND and number of LNs dissected in the extraperitoneal approach were less than in the transperitoneal approach., Conclusion: During RALRP, more attention should be paid to fully clotting the broken end of lymphatic vessels. The use of fibrin glue could reduce the probability of PLL. The extent of LND or number of LNs dissected were positively correlated with PLL in the extraperitoneal approach., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To investigate the predictive value of body composition parameters for biochemical response to abiraterone acetate (AA) in metastatic castration-resistant prostate cancer (mCRPC) patients with prior chemohormonal therapy., Methods: We retrospectively evaluated the clinicopathologic information of 132 mCRPC cases receiving AA treatment after chemohormonal therapy at hormone-sensitive stage from July 2018 to June 2021. All patients were divided into AA responders and non-responders according to the biochemical response to AA (prostate-specific antigen (PSA) reduction ≥50% than pretreatment). Multivariate Logistic analysis was used to determine the independent predictors and develop predictive model of biochemical response to AA. Cox regression analysis was utilized to investigate the prognostic factors for time to biochemical progression (TTBP), radiological progression-free survival (rPFS), failure-free survival (FFS), and overall survival (OS) after AA treatment., Results: There were 57 AA responders and 75 AA non-responders. Periprostatic fat area/prostate area (PPFA/PA) was decreased and skeletal muscle index (SMI) was increased in AA responders compared with AA non-responders. Multivariable logistic analysis demonstrated that ADT duration ≥12 months, bone metastasis only, high SMI and low PPFA/PA were independent predictors of biochemical response to AA treatment. The FFS, TTBP, rPFS, and OS of patients with lower SMI or higher PPFA/PA was decreased compared with that of patients with higher SMI or lower PPFA/PA, respectively. Combining SMI, PPFA/PA, ADT duration and metastatic sites performed well in differentiating AA responders from non-responders., Conclusions: High SMI and low PPFA/PA could predict biochemical response to AA treatment and preferable prognosis in mCRPC patients with prior chemohormonal therapy at hormone-sensitive stage., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

To identify liquid-liquid phase separation (LLPS)-related molecular clusters, and to develop and validate a novel index based on LLPS for predicting the prognosis of prostate cancer (PCa) patients. We download the clinical and transcriptome data of PCa from TCGA and GEO database. The LLPS-related genes (LRGs) were extracted from PhaSepDB. Consensus clustering analysis was used to develop LLPS-related molecular subtypes for PCa. The LASSO cox regression analysis was performed to establish a novel LLPS-related index for predicting biochemical recurrence (BCR)-free survival (BCRFS). Preliminary experimental verification was performed. We initially identified a total of 102 differentially expressed LRGs for PCa. Three LLPS related molecular subtypes were identified. Moreover, we established a novel LLPS related signature for predicting BCRFS of PCa patients. Compared to low-risk patients in the training cohort, testing cohort and validating cohort, high-risk populations meant a higher risk of BCR and significantly poorer BCRFS. The area under receiver operating characteristic curve were 0.728, 0.762, and 0.741 at 1 year in the training cohort, testing cohort and validating cohort. Additionally, the subgroup analysis indicated that this index was especially suitable for PCa patients with age ≤ 65, T stage III-IV, N0 stage or in cluster 1. The FUS , which was the potential biomarker related to PCa liquid-liquid phase separation, was preliminarily identified and verified. This study successfully developed three LLPS-related molecular subtypes and identified a novel LLPS related molecular signature, which performed well in predicting BCRFS of PCa.

Purpose: The optimal tool to evaluate the tumour therapeutic responses to neoadjuvant chemohormonal therapy (NCHT) in patients with high-risk non-metastatic prostate cancer (PCa) remains uncertain. We compared the role of [ 68 Ga]-labeled prostate-specific membrane antigen (PSMA)-11 positron emission tomography/computerized tomography ([ 68 Ga]Ga-PSMA-11 PET/CT), multiparametric MRI (mpMRI), and prostate-specific antigen (PSA) and assessed the practical value of the recent European Association of Urology and European Association of Nuclear Medicine (EAU/EANM) recommended criteria of PSMA PET/CT to evaluate the therapeutic responses to NCHT in patients with high-risk non-metastatic PCa., Methods: This prospective study included 72 high-risk non-metastatic PCa patients receiving NCHT followed by radical prostatectomy from June 2021 to March 2022. PSA testing, [ 68 Ga]Ga-PSMA-11 PET/CT, and mpMRI scanning were conducted in all patients before and after NCHT. Therapeutic responses to NCHT were evaluated with PSA, RECIST 1.1, PERCIST 1.0, and EAU/EANM recommended criteria. Postoperative pathological results were considered the reference standard. A favourable pathological response was defined as pathologic complete remission (pCR) or minimal residual disease (MRD). Diagnostic accuracy was assessed by sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), positive predictive value (PPV), negative predictive value (NPV), and Cohen's kappa index. Logistic regression analysis was used to determine the independent predictive value of [ 68 Ga]Ga-PSMA-11 PET/CT-derived parameters., Results: All cases experienced a marked decrease in PSA levels after NCHT. Twenty-four (33.33%) cases experienced a favourable pathological response, including five (6.94%) cases of pCR and 19 (26.39%) cases of MRD. According to the results of [ 68 Ga]Ga-PSMA-11 PET/CT, EAU/EANM recommended criteria indicated that 20 (27.78%) cases had a CR, whereas PERCIST 1.0 criteria indicated that 23 (31.94%) cases had a CR. There was a strong association between EAU/EANM recommended criteria and PERCIST 1.0 criteria (Pearson's R=0.857). The sensitivity (75.00%, 79.17% vs. 58.33%, 58.33%), specificity (95.83%, 91.67% vs. 83.33%, 68.75%), PLR (18.00, 9.50 vs. 3.50, 1.87), NLR (0.26, 0.23 vs. 0.50, 0.61), PPV (90.0%, 82.6% vs. 63.6%, 48.3%), and NPV (88.5%, 89.8% vs. 80.0%, 76.7%) of [ 68 Ga]Ga-PSMA-11 PET/CT (including EAU/EANM recommended criteria and PERCIST 1.0 criteria) to predict favourable pathological responses were all superior to those of mpMRI and nadir PSA. The kappa index to predict a favourable pathological response was 0.257 for PSA, 0.426 for RECIST 1.1, 0.716 for PERCIST 1.0, and 0.739 for EAU/EANM recommended criteria. Multivariate logistic analysis revealed that the post-NCHT maximum standardized uptake value (SUVmax) before radical prostatectomy was an independent predictor of a favourable pathological response to NCHT., Conclusions: [ 68 Ga]Ga-PSMA-11 PET/CT had a better concordance with a favourable pathological response to NCHT compared with nadir PSA and mpMRI. EAU/EANM recommended criteria and PERCIST 1.0 criteria performed equally to identify pathological responders when [ 68 Ga]Ga-PSMA-11 PET/CT was used as a therapeutic response assessment tool., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)