Prostate cancer (PCa) remains a major clinical challenge, particularly because of its progression to more aggressive disease states, and the molecular mechanisms driving its progression are still incompletely understood. KH-type splicing regulatory protein (KHSRP) is a multifunctional RNA-binding protein involved in post-transcriptional gene regulation, but its role and downstream regulatory mechanisms in PCa remain unclear. The clinical relevance of KHSRP in PCa was assessed using public datasets and patient specimens. We assessed the biological functions of KHSRP in vitro and in vivo, identified DUSP6 by integrative RNA-seq and RIP-seq analyses, and further validated the associated signaling and phenotypic changes using Western blotting and functional assays. KHSRP was significantly upregulated in PCa and was associated with aggressive clinicopathological features and poor prognosis. Functional experiments showed that KHSRP overexpression promoted proliferation, migration, and invasion while suppressing apoptosis in PCa cells, whereas KHSRP knockdown produced the opposite effects. Mechanistically, integrative RNA-seq and RIP-seq analyses identified DUSP6 as a candidate downstream target of KHSRP. Further validation using RNA immunoprecipitation assays and RNA decay assays demonstrated that KHSRP accelerated DUSP6 mRNA decay and repressed DUSP6 expression at the post-transcriptional level. Reduced DUSP6 expression was accompanied by enhanced ERK phosphorylation and coordinated activation of PI3K/AKT/mTOR signaling. Restoration of DUSP6 attenuated the pro-tumorigenic effects of KHSRP and weakened the associated signaling activation. Xenograft assays further confirmed the tumor-promoting role of KHSRP in vivo. KHSRP drives PCa progression through a DUSP6-dependent signaling axis by repressing DUSP6 at the post-transcriptional level and facilitating coordinated activation of ERK and PI3K/AKT/mTOR signaling. These findings identify a previously unrecognized KHSRP–DUSP6 regulatory axis in PCa and suggest that KHSRP may serve as a potential therapeutic target.
Robot-assisted radical prostatectomy (RARP) has become an increasingly discussed surgical option for patients with high-risk or locally advanced prostate cancer. Nevertheless, how publications, knowledge structures, and research priorities have developed in this area remains insufficiently clarified. This study aimed to characterize the bibliometric profile and clinically oriented evidence domains of RARP for this patient population, with emphasis on oncologic safety, functional outcomes, lymph-node management, and multimodal treatment. Publications were retrieved from the Web of Science Core Collection. Eligible records included English-language original articles and reviews with official publication years up to 2025. After database filtering and manual screening, 643 records were retained, including 596 original articles and 47 review articles. Bibliometric assessment, data processing, and graphical visualization were performed using R, Bibliometrix, VOSviewer, CiteSpace, and Scimago Graphica. We analyzed publication trajectories, geographic and institutional contributions, author activity, journal distribution, citation links, reference co-citation patterns, keyword networks, thematic clusters, burst keywords, and longitudinal topic changes. Scientific output increased progressively from 2003 to 2025, with publication activity becoming more pronounced in the most recent period. In terms of national contribution, the United States showed the strongest overall performance in both publication output and citation impact, whereas Italy, the Netherlands, Japan, China, and several other countries also made substantial contributions. At the institutional level, the Netherlands Cancer Institute, Vita-Salute San Raffaele University, and the University of Verona represented major contributors. BJU International, European Urology, World Journal of Urology, Journal of Endourology, and Journal of Robotic Surgery were identified as key journals for disseminating research in this area. Keyword and co-citation findings indicated a gradual transition from early surgical experience, learning-curve assessment, and technical feasibility toward research on oncologic outcomes, lymph-node management, functional recovery, and multimodal treatment, alongside increasing attention to magnetic resonance imaging, pathological grading, and predictive factors. Research activity concerning robot-assisted radical prostatectomy for high-risk and locally advanced prostate cancer has expanded consistently over the past 20 years and has progressively shifted toward an integrated clinical research framework centered on oncologic safety, functional outcomes, lymph-node management, and multimodal treatment. Diagnostic and risk-assessment themes have increasingly supported patient selection, staging, and treatment planning within this framework. Future investigations incorporating harmonized definitions, longer follow-up, prospective multicenter designs, and consistent reporting of oncologic, functional, nodal, and treatment-sequencing outcomes are needed to define more precisely the clinical role of RARP in this patient population.
Pelvic lymph-node dissection (PLND) during robot-assisted radical prostatectomy (RARP) is important for nodal staging, but its optimal extent, morbidity profile, and integration with precision-guided techniques remain unsettled. This study mapped the knowledge structure and thematic evolution of RARP-associated PLND research. A single-database search of the Web of Science Core Collection was performed for English-language articles and reviews formally published through 2025. Two reviewers independently screened records directly evaluating PLND, nodal staging, lymphatic morbidity, or related preventive and guidance strategies during RARP according to predefined eligibility criteria. Bibliometrix, VOSviewer, CiteSpace, and Scimago Graphica were used to assess publication trends, collaboration patterns, citation structure, and keyword evolution. The final dataset comprised 225 eligible records, including 208 original research articles and 17 review articles published during 2006–2025. Output increased markedly after 2019 and peaked at 27 publications in 2024. The United States received the most citations, whereas the Netherlands Cancer Institute was the most productive institution. van der Poel H.G. was the most productive author. The knowledge base initially focused on PLND templates, anatomical extent, and lymph-node yield, then expanded toward risk-adapted nodal staging, oncologic implications, lymphatic morbidity, and precision-guided nodal assessment. Keyword analysis identified eight thematic clusters and showed recent attention to peritoneal flap and fixation strategies, node-positive disease, and image- or radioguided nodal approaches. This bibliometric analysis characterizes a shift in RARP-associated PLND research from surgical extent and staging yield toward individualized selection, morbidity reduction, and precision-guided nodal strategies. Further prospective studies are needed to clarify how preventive reconstruction and targeted nodal techniques should be integrated with anatomically defined extended PLND.
Bladder cancer (BC) is a prevalent malignancy of the urinary system worldwide, with a rising global incidence, posing a significant threat to public health. The treatment of advanced and metastatic disease remains particularly challenging. Chimeric antigen receptor T-cell (CAR-T) immunotherapy has demonstrated remarkable efficacy in hematologic malignancies and is increasingly being explored in solid tumors. This review summarizes recent advances in CAR-T cell therapy for BC, focusing on major therapeutic targets, mechanisms of action, and potential combination strategies. Furthermore, we discuss findings from preclinical studies and early-phase clinical trials. Current evidence indicates that CAR-T therapy exhibits promising antitumor activity in BC. However, several critical challenges remain, including optimal target selection, the immunosuppressive tumor microenvironment (TME), and insufficient clinical validation. These findings may guide future translational and clinical investigations in this field.
This review aims to synthesize the current progress, challenges, and future directions of Natural Killer (NK) and Chimeric Antigen Receptor-NK (CAR-NK) cell therapies for urological cancers, including renal cell carcinoma, bladder cancer, and prostate cancer. We detail the unique biology of NK cells, such as 'missing-self' recognition and intrinsic antibody-dependent cellular cytotoxicity (ADCC), which offer potential safety and efficacy advantages over CAR-T cells, including a lower risk of severe cytokine release syndrome and graft-versus-host disease. The analysis covers conventional NK-based strategies, the engineering and 'armouring' of CAR-NK platforms to overcome the immunosuppressive tumour microenvironment, and preclinical and early clinical advances with target antigens like CAIX, CD70, PSMA, and nectin-4 across different urological malignancies. We conclude that while CAR-NK therapy represents a promising 'off-the-shelf' modality for these cancers, its success in solid tumours hinges on next-generation designs that solve critical challenges of in vivo persistence, efficient tumour homing, and resistance to local metabolic and immunosuppressive pressures.
The present research provides a comprehensive systematic review of the safety and effectiveness of robotic-assisted artificial urinary sphincter (AUS) implantation in treating urodynamic stress incontinence. In line with the PRISMA framework and a protocol registered in PROSPERO, we conducted a comprehensive search of PubMed, Web of Science, and the Cochrane Library for relevant studies published from inception to August 2025. Key perioperative parameters—operative time, estimated blood loss, hospital stay, continence rate, and complication rate—were extracted. Data analysis was carried out using STATA software, with heterogeneity assessed by the I² statistic and sensitivity by leave-one-out analysis. Eight studies involving 328 patients were included. Among three comparative cohorts (n = 224), operative time did not differ between robotic and open AUS (WMD = 7.62, 95
With advances in robotic technology, robot-assisted prostatectomy (RAP) has become a key surgical approach for the management of prostate diseases. Compared with conventional open or laparoscopic procedures, RAP provides superior surgical precision, intraoperative stability, and postoperative functional recovery. To comprehensively characterize the global research landscape and trends in RAP, we conducted a bibliometric analysis of English-language publications indexed in the Web of Science Core Collection from its inception to May 2025. Data were analyzed using Bibliometrix, VOSviewer, and CiteSpace to evaluate publication trends, country and institutional distribution, author collaboration networks, leading journals, and keyword clusters. A total of 2753 publications were included in the analysis. Results showed a significant increase in publications since 2009, with a sharp rise after 2020. The United States led in both publication volume and academic influence, followed by Italy, South Korea, and Germany. Leading institutions included Yonsei University, the University of California, Vita-Salute San Raffaele University, and the Cleveland Clinic Foundation. Major studies were published in core journals such as Journal of Endourology, BJU International, European Urology, The Journal of Urology, and Journal of Robotic Surgery. Keyword analysis indicated that current research mainly focuses on robot-assisted surgery for prostate diseases, particularly robot-assisted radical prostatectomy (RARP), covering aspects such as surgical optimization, functional recovery, and biochemical recurrence. Robotic techniques have also expanded to benign prostatic hyperplasia, giving rise to robot-assisted simple prostatectomy (RASP). In recent years, research has increasingly focused on refining robotic surgical techniques and evaluating multimodal outcomes. Meanwhile, studies exploring artificial intelligence (AI) have emerged, but their overall representation in the field remains limited. In conclusion, global RAP research has increasingly shifted toward precision and intelligence-driven robotic techniques, with RARP remaining the central focus. Future studies should further advance technical innovation, expand applications to benign prostatic diseases, and prioritize long-term functional and quality-of-life outcomes, providing guidance for future research directions and clinical practice improvements.
Prostate cancer (PCa) is the tumor with the highest incidence rate among men worldwide. There is still a lack of effective treatment options for metastatic PCa and castration-resistant prostate cancer (CRPC). Protein phosphatase 1 regulatory subunit 14B (PPP1R14B) has been found to be associated with the occurrence and development of various cancers. However, the role and mechanism of PPP1R14B in PCa have not yet been deeply explored. Here, we found that PPP1R14B was highly expressed in PCa tissues and was significantly associated with a higher Gleason score and clinical T stage. Knockdown of PPP1R14B significantly inhibited the proliferation, migration and invasion abilities of PCa cells, while overexpression of PPP1R14B produced the opposite effect. Mechanistic investigations revealed that PPP1R14B mainly regulates the expression of AR through the JAK2/STAT3 pathway and forms a positive feedback loop with STAT3 to promote the progression of PCa, reduce the sensitivity of tumors to enzalutamide, and accelerate the formation of drug resistance. In addition, genistein, a drug screened through virtual drug prediction and molecular alignment, mainly inhibits the expression of STAT3 by targeting PPP1R14B. Moreover, when combined with STAT3-IN-13, it can more effectively curb the malignant ability of PCa and enhance the sensitivity of tumor cells to enzalutamide. In conclusion, these findings reveal the function and mechanism of PPP1R14B in the progression of PCa and the resistance of enzalutamide, indicating that PPP1R14B is a potential target for the treatment of PCa and the prospect of genistein as a therapeutic drug.
RATIONALE:Immunoglobulin G4-related disease (IgG4-RD) is a chronic immune-mediated fibroinflammatory condition that can mimic infection or malignancy. Renal involvement may present as a perirenal mass suggestive of an abscess. This case highlights a diagnostic pitfall and a favorable response to therapy. PATIENT CONCERNS:A 48-year-old man had a persistent fever for over 20 days. Imaging revealed a left renal mass. Empirical antibiotics were initiated without improvement, and he was transferred for further evaluation. DIAGNOSES:Laboratory tests showed elevated inflammatory markers, including C-reactive protein and interleukin-6, positive proteinase 3 antineutrophil cytoplasmic antibody, and markedly increased serum immunoglobulin G4 (IgG4). Computed tomography and magnetic resonance imaging demonstrated renal and pulmonary abnormalities. Renal biopsy confirmed dense infiltration of IgG4-positive plasma cells. The final diagnosis was IgG4-RD involving the kidneys and lungs, initially misdiagnosed as a perirenal abscess. INTERVENTIONS:Systemic corticosteroid therapy was started. OUTCOMES:The patient experienced rapid resolution of fever and clinical improvement, with reductions in serum IgG4 and interleukin-6 levels. LESSONS:IgG4-RD should be considered in patients with unexplained fever and space-occupying renal lesions unresponsive to antibiotics. Timely recognition and immunosuppressive therapy can lead to favorable outcomes and help prevent irreversible organ damage.
This study is aimed at exploring the potential mechanisms of melatonin (MT) in treating chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) using network pharmacology and experimental study. The target genes of MT were acquired from the Swiss Target Prediction, SuperPred, SEA, and PharmMapper databases, and the CP/CPPS targets were collected based on OMIM, DisGeNET, and GeneCards databases. The intersection of MT and CP/CPPS target genes was analyzed. A PPI network was constructed using Cytoscape to identify core targets. The shared targets underwent GO and KEGG enrichment analyses by Using R software. Molecular docking of MT with core targets was performed using AutoDock and PyMOL. GROMACS software was used for molecular dynamics simulation. And using cell experiments to verify the potential effect of MT in CP/CPPS. Network pharmacology analysis reveals 284 shared targets between MT and CP/CPPS, with AKT1, SRC, HSP90AA1, PTGS2, BCL2L1, ALB, CASP3, NFKB1, HIF1A, and ESR1 identified as key targets. Enrichment analysis indicates that MT affects CP/CPPS through various biological processes, and pathway analysis emphasizes the significance of PI3K-Akt, MAPK, Ras, FoxO, HIF-1, EGFR, and apoptosis pathways. Molecular docking confirms strong binding between MT and core targets. It is worth noting that the molecular dynamics simulation showed that the average binding free energy of AKT1, PTGS2, ALB, HSP90AA1 proteins, and MT was − 26.15, − 29.48, − 18.59, and − 20.09 kcal/mol, respectively. These results indicated that AKT1, PTGS2, ALB, and HSP90AA1 proteins were strongly bound to MT. Cell experiments demonstrate that MT can inhibit the secretion of IL-1β, IL-6, and TNF-α in LPS-induced RWPE-1 cells, alleviate inflammation, and suppress cell apoptosis and oxidative stress. Network pharmacology, molecular docking, molecular dynamics simulation, and cell experiments showed that MT could play a role in CP/CPPS by regulating multiple targets and pathways. These findings provide an important scientific basis for further exploration of the molecular mechanism and clinical application of MT in CP/CPPS treatment and are expected to provide new ideas and directions for the development of novel therapeutic strategies.
目的 比较腹腔镜先天性胆总管囊肿根治术中2种胆肠吻合方式的优劣,为临床选择不同术式提供理论依据.方法 回顾性分析兰州大学第二医院2016年7月-2022年4月收治的117例先天性胆总管囊肿患者,按手术方式分为Roux-en-Y吻合组(63例)与改良Warren吻合组(54例).2组患者均行腹腔镜下胆总管囊肿根治性切除术,肠-肠吻合方式有Roux-en-Y式肠-肠吻合及改良Warren式肠-肠吻合.比较2组患者手术效果、术后效果及术后并发症等指标.结果 2组患者手术时间、吻合时间、术后恢复排气排便时间、术后并发肠梗阻及反流性胆管炎方面差异均有统计学意义(P<0.05),而其余指标没有显示明显差异(P>0.05).结论 改良Warren吻合术较Roux-en-Y吻合术,具有手术时间短、吻合快、术后肠功能恢复快、防反流效果好等优点,且操作简便,不切断肠管,保证肠管电生理活动的连续性,适合在基层医院推广.
The primary objective of the current study is to undertake a comparative analysis of the effectiveness and safety of minimally-invasive partial nephrectomy (MIPN; including laparoscopic and robotic approaches) and open partial nephrectomy (OPN) for the treatment of highly complex renal tumors (defined as PADUA or RENAL score ≥ 10). A comprehensive search was conducted in four electronic databases (PubMed, Web of Science, Embase, and Cochrane Library) to identify relevant studies published in the English language up to April 2023. The current study employed Review Manager 5.4 and encompassed controlled trials of both MIPN and OPN for the treatment of highly complex renal tumors. This study comprised a total of eight comparative trials involving 1161 patients. MIPN demonstrated a significant reduction in length of hospital stay (weighted mean difference [WMD] − 2.08 days, 95
Abstract Background: Boys with cryptorchidism are susceptible to infertility. However, there are few known molecular markers of cryptorchidism-related infertility. Potential genes and molecular pathways to drive cryptorchidism-related infertility were investigated in this study via bioinformatics methods.Methods: Gene Expression Omnibus (GEO) database was utilized to download raw GSE25518 (training set) and GSE16191 (validation set) datasets. GSE25518 was used for differentially expressed genes (DEGs) identification and weighted gene co-expression network analysis (WGCNA). Hub genes were identified from the intersection of key genes from DEGs and the key module in WGCNA. Hub genes’ expression differences and diagnostic value were subsequently verified via GSE16191. Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and Gene set enrichment analysis (GSEA) were deployed for functional annotation.Results: 761 definitive DEGs were identified while 12 hub genes (CHRM4, CCR4, LMNB1, MTNR1B, TAC3, TRHR, RAD54L, CCNA1, SMC1B, GPRC6A, SYCE2, TAS2R19) were identified finally. The hub genes were also differentially expressed and showed excellent diagnostic value to distinguish cryptorchidism from normal testes in GSE16191. Additionally, they were well correlated with genes from the hallmark_spermatogenesis gene set. And they might be involved in oxidative phosphorylation, MYC targets V1, cholesterol homeostasis, KRAS activation, etc. Hallmark_spermatogenesis gene set was significantly enriched by five hub genes (RAD54L, CCNA1, SMC1B, TAC3, MTNR1B).Conclusion: We have identified 12 genes that might become new biomarkers for cryptorchidism-related infertility while five genes (RAD54L, CCNA1, SMC1B, TAC3, MTNR1B) deserve more attention.
The paper, which entitled ‘Red blood cell distribution width at admission outcome in critically ill patients with kidney failure: a retrospective cohort study based on the MIMIC-IV database’ by Hua et al. [1], is of great interest to us. The retrospective study included 674 kidney failure patients (643 hemodialysis and 31 peritoneal dialysis patients), who were divided into three groups based on tertiles of red blood cell distribution width (RDW) {the low group: <15.4% (n1⁄4 223); the middle group: 15.5%, <17.1% (221); the high group: 1.72%(n1⁄4 230)}. The Kaplan-Meier analysis showed that elevated RDW ( 15.5%) had a lower survival rate. The Cox regression model indicated that middle and high levels of RDW were associated with an increased risk of ICU all-cause mortality (HR: 3.81 and 4.71, p< 0.05, respectively), 30-day all-cause mortality (HR: 2.85 and 6.62, p< 0.05, respectively), 180day all-cause mortality (HR: 2.55 and 4.43, p< 0.05, respectively), and 1-year all-cause mortality (HR: 2.51 and 4.08, p< 0.05, respectively) in critically ill patients with kidney failure after adjusting for potential confounders in model II. Subgroup analysis showed that RDW was a risk factor in all of there interactive stratifications in Table 3. The paper found that the value of RDW could provide useful information for risk classification to clinicians, and elevated levels of RDW were associated with an increased risk of all-cause mortality in critically ill patients with kidney failure. I pay special attention to the laboratory results of this research because it caused me some concerns. RDW has emerged as a novel prognostic marker for serious adverse events in recent decades. Malnutrition is common in patients on dialysis in terms of dialysisinduced nutrient losses and a low protein diet [2] and has been proposed as possible etiology about the underly mechanism between higher RDW levels and elevated allcause mortality of patients with kidney failure. Firstly, a restrospective observational study conducted by Tania et al. [3]. 109,675 adult maintenance HD patients with baseline and time-varying RDW showed that higher RDW ( 15.5%) is associated with incrementally higher mortality risk. Correlation and liner regression analysis showed that every 1 g/dL increase in albumin level, RDW decreased by 0.731% (correlation coefficient, 0.20). Secondly, Soohoo et al. [4]. conducted a large cohort study of 14,323 PD patients with a mean RDW of 15.3 ± 1.6% to show the higher baseline and time-varying RDW ( 15.0%) were associated with a greater risk of mortality, including all-cause and CV, and time to first hospitalization. Subgroup analysis showed that higher RDW ( 15.0%) was not significantly associated with allcause mortality among patients with iron saturation (ISAT) 30%. However, neither nutritional data (e.g., serum levels of folate, vitamin B12, and serial iron profifiles) nor of bone marrow function parameters (e.g., reticulocyte and platelet count) nor blood transfusion data and erythropoietinstimulating agent (ESA) use and dosage were routinely examined in the paper by Hua et al. [1]. Thirdly, a large population-based retrospective cohort study of 3,156,863 adults from the general population by Tonelli et al. [5]. evaluated the association of RDW and standard deviation of red blood cell size (SD-RBC: calculated from the product of RDW and mean corpuscular volume) with the risk of adverse outcome for a median follow-up of 6.8 year. The paper used Cox regression to determine the association between baseline RDW and SDRBC percentiles (<1, 1–5, 5–25, 25–75, 75–95, 95–99, >99) and the first occurrence of each clinical outcomes during follow-up. The association between SD-RBC and mortality was similar to that between RDW and mortality. The values of RDW for the risk of ESRD (initiation of renal replacement therapy) were not associated in the <25th percentiles but higher for participants in the 75th–95th percentiles (HR 1.15, p< 0.05), the 95th–99th percentiles (HR 1.29, p< 0.05) and the 99th percentile (HR 1.05, p> 0.05), the association between RDW and ESRD was progressively attenuated with further adjustment for confounders and was not observed in the fully adjusted model. The lower (<25th percentile) values of SD-RBC were strongly associated with ESRD in Model 3. The higher values of SD-RBC for participants in the 95th–99th percentiles (HR 1.35, p< 0.05) and the 99th percentile (HR 1.38, p< 0.05) were associated with excess risk of ESRD in the fully adjusted model. Finding that SD-RBC is stronger than RDW for all associations, and both lower (<25th percentile) and higher (>95th percentile) values of SD-RBC were independently associated with ESRD. I think SD-RBC may be useful as prognostic marker for serious adverse events. Finally, I found some problems with the sequence of references from 14 to 17 that were inconsistent with the content of the paper [1]. Therefore, the accuracy of the reference has yet to be further verified by the author.
calcification association with (CVE) in 3 (CKD). to an increased risk for CVE test, p