Jianguang Qiu

Urothelial bladder cancer (UBC) poses a considerable threat to public health, and its clinical management is limited by high recurrence rates and a tendency for progression. While dysregulation of the ubiquitin‒proteasome system (UPS) is a hallmark of tumorigenesis, the specific landscape of deubiquitinating enzymes (DUBs) in UBC remains largely underexplored. Multiple transcriptomic datasets were used for a comprehensive screening of ubiquitination-related genes in UBC, and ZRANB1 was identified as a potential oncogenic DUB, whose expression was validated using immunohistochemistry. High ZRANB1 expression was correlated with advanced pathological T stage, lymph node metastasis, and poor overall survival. The oncogenic role of ZRANB1 was assessed by proliferation, migration, and invasion assays in vitro, as well as in subcutaneous xenograft and lymph node metastasis models in vivo. Using immunoprecipitation coupled with mass spectrometry, we revealed that ZRNAB1 acted as a DUB to prevent the UPS-dependent degradation of SF3B3. The ZRANB1-SF3B3 axis subsequently modulates the alternative splicing of the cell cycle checkpoint kinase CHEK2, specifically inhibiting the production of the exon 4-skipped isoform (CHEK2-e4-). We demonstrated that while full-length CHEK2 is permissive for growth, the CHEK2-e4- isoform exerts a potent tumour-suppressive effect. This study reveals a novel post-translational mechanism linking the UPS to the RNA splicing machinery in UBC. ZRANB1 promotes tumorigenesis by stabilizing SF3B3 to prevent the generation of the tumour-suppressive CHEK2-e4- isoform, suggesting that ZRANB1 is a promising prognostic biomarker and therapeutic target.

Chemotherapy-associated gonadotoxicity compromises Leydig cell steroidogenesis and leads to testosterone deficiency, yet repair is hindered by the testicular barrier-immune niche and by limited manufacturability of biologics. Inspired by the tubular architecture of seminiferous tubules, we develop a coaxial bioprinting-enabled encapsulation culture that generates continuous core-shell hydrogel microfibers for high-density 3D culture of human umbilical cord MSCs (hUMSCs) and continuous conditioned-medium harvesting, producing seminiferous tubule-inspired coaxial bioprinting-derived extracellular vesicles (STi-EVs). We directly benchmark STi-EVs against conventional 2D culture-derived EVs (2D-EVs) in a 4-hydroperoxycyclophosphamide (4-HC)-injured TM3 model and a cyclophosphamide-induced mouse model. Across cellular fitness, re-engagement of steroidogenic programs, and testosterone output, STi-EVs consistently outperform 2D-EVs, while more effectively alleviating testicular histopathology and restoring serum testosterone in vivo. Transcriptomics prioritize Wnt signaling and nominate Wnt4; orthogonal validation and Wnt4 gain- and loss-of-function perturbations, and β-catenin stabilization experiments support that modulation of Wnt4/β-catenin signaling functionally contributes to STi-EV-mediated steroidogenic restoration. Collectively, this work couples a scalable extracellular vesicles (EV) manufacturing paradigm with a mechanism-informed repair strategy for endocrine sequelae after alkylating chemotherapy.

Urothelial bladder cancer (UBC) poses a considerable threat to public health, and its clinical management is challenged by high recurrence rates and tendency to progression. While dysregulation of the ubiquitin-proteasome system (UPS) is a hallmark of tumourigenesis, the specific landscape of deubiquitinating enzymes (DUBs) in UBC remains largely underexplored. Multiple transcriptomic datasets were applied for a comprehensive screening of ubiquitination-related genes in UBC. And ZRANB1 was identified as a potential oncogenic DUB molecule, whose expression was validated using immunohistochemistry. High ZRANB1 expression was correlated with advanced pathological T stages, lymph node metastasis, and poor overall survival. The oncogenic role of ZRANB1 was assessed by proliferation, migration, and invasion assays in vitro, as well as subcutaneous xenograft and lymph node metastasis models in vivo. By conducting immunoprecipitation coupled with mass spectrometry, we revealed that ZRNAB1 acted as a DUB to prevent the UPS-dependent degradation of SF3B3. The ZRANB1-SF3B3 axis subsequently modulates the alternative splicing of the cell cycle checkpoint kinase CHEK2, specifically inhibiting the production of the exon 4-skipped isoform (CHEK2-e4-). We demonstrated that while full-length CHEK2 is permissive for growth, the CHEK2-e4- isoform exerts a potent tumour-suppressive effect. This study uncovers a novel post-translational mechanism linking the UPS to RNA splicing machinery in UBC. ZRANB1 promotes tumourigenesis by stabilizing SF3B3 to prevent the generation of the tumour-suppressive CHEK2-e4- isoform, suggesting ZRANB1 is a promising prognostic biomarker and therapeutic target.

To report our single-center experience of laparoscopic pyeloplasty for the treatment of ureteropelvic junction obstruction (UPJO) in infants managed with t

Objective To evaluate the feasibility and effectiveness of robot-assisted laparoendoscopic single-port surgery (R-LESS) in infant urology and to report our early single-center experience. Methods Clinical data were retrospectively collected from 20 infants (≤ 12 months) who underwent R-LESS using the Da Vinci Xi system between February 2024 and April 2025. Information included demographic characteristics, perioperative parameters, and postoperative outcomes. The median age at surgery was 2.5 (IQR: 2, 4) months. Sixteen patients underwent pyeloplasty, two underwent ureteral reimplantation, and two underwent nephrectomy. Results All procedures were completed successfully without conversion to open surgery or intraoperative complications. The median docking time, console time, and total operative time were 7 (IQR: 6, 8) min, 181 (IQR: 156, 207) min, and 212 (IQR: 189, 238) min, respectively. Median estimated blood loss was 5 (IQR: 5, 9) mL. Median total hospital stay was 6 (IQR: 6, 10) days, with a median postoperative stay of 2 (IQR: 1, 4) days. The median follow-up duration was 9.1 (IQR: 5.4, 11.2) months. Postoperative complications were observed in three cases (15%): two patients (10%) developed febrile urinary tract infections (Clavien–Dindo Grade II), which resolved with antibiotic treatment; one patient (5%) required hospital readmission for wound debridement due to poor healing (Clavien–Dindo Grade III), with favorable postoperative recovery. Conclusion R-LESS is a safe and effective minimally invasive surgical approach in infant urology.

Tumors have a unique niche system that plays an important role in their occurrence and development. At present, there is increasing interest in the biomechanical properties of niches. The increased stemness of cancer cells is closely related to bladder cancer progression and recurrence. However, how biomechanical properties in the niche regulate bladder cancer stemness remains unclear. Here, we show that as bladder cancer progresses, matrix stiffness increases, and tumor stemness increases. Mechanistically, high matrix stiffness mediates β-catenin nuclear translocation by increasing the nuclear pore size. On the other hand, it promotes the expression of the nuclear cytoskeletal protein Lamin A/C, inhibits the nuclear export of β-catenin, and finally, it upregulates the Wnt pathway to increase the stemness of cancer cells. These findings reveal a role for matrix stiffness in the regulation of stemness in bladder cancer cells and suggest that targeting matrix stiffness may be an effective strategy to delay bladder cancer progression.

Background: Prostate cancer (PCa) is a prevalent malignancy and a leading cause of cancer-related death among men. Epithelial-mesenchymal transition (EMT) plays a crucial role in tumor progression, metastasis, and treatment. However, there are limited comprehensive studies on the EMT correlation with prognosis, tumor microenvironment, and therapeutic efficacy in PCa.Methods: We obtained mRNA expression profiles and clinical data of PCa samples, along with 1,011 protein-coding EMT-related genes from public databases. Functional annotation and consensus clustering were performed based on differentially expressed genes. An EMT prognostic signature (EPS) was constructed in the TCGA dataset after a series of bioinformatics analyses and validated in the GSE116918 dataset. The signature was used to explore clinicopathological features, genomic heterogeneity, the immune landscape, and therapy responses. Finally, we examined the expression of key genes in clinical specimens.Results: An EPS was established based on four key genes (MEN1, H2AFZ, UCKL1, and FUS). The patients were classified into low-risk and high-risk groups according to their median EPS risk scores. In both datasets, patients in the high-risk group exhibited significantly lower survival rates compared to those in the low-risk group. Furthermore, the EPS risk score proved to be an independent prognostic factor, and the prognostic nomogram based on the EPS risk score and T stage yielded high accuracy. Subsequent investigations found that the EPS risk score was correlated with both tumor mutation burden and genomic heterogeneity. Notably, the low-risk group displayed a higher proportion of tumor-infiltrating immune cells and exhibited better responses to chemotherapy and immunotherapy. As expected, the validation analysis confirmed substantial overexpression of MEN1, H2AFZ, UCKL1, and FUS in PCa tissues relative to adjacent normal prostate tissues.Conclusion: Our preliminary EPS represents a promising biomarker for predicting PCa prognosis and has great potential for clinical application.

To compare the therapeutic efficacy of conventional laparoscopic pyeloplasty (LP) and robot-assisted single-port laparoscopic pyeloplasty (RSLP) for ureteropelvic junction obstruction (UPJO) in infants and to summarize the preliminary experience and advantage of RSLP. The clinical data of UPJO infants (≤ 12 months) who received LP and RSLP in our center from October 2018 to October 2024 were analyzed retrospectively. A total of 51 patients with UPJO were included, with 11 cases receiving RSLP (8 with left UPJO; 3 with right UPJO) and 40 receiving LP (29 with left UPJO; 11 with right UPJO). In the RSLP group, the median age was 3 months (range: 1–9 months). In the LP group, the median age was 2.5 months (range: 1–11 months). The mean operative time was 217.45 ± 20.77 min for the RSLP group and 258.57 ± 52.56 min for the LP group. The mean time of ureteropelvic anastomosis in the RSLP group was shorter than that in the LP group (79.36 ± 17.74 vs. 99.35 ± 21.03). The mean hospital stay was 6.27 ± 2.53 days for the RSLP group and 6.32 ± 2.71 days for the LP group. The mean postoperative hospital stay was 1.9 ± 0.94 days for the RSLP group and 2.67 ± 2.37 days for the LP group. The mean hospital costs were 57,950.63 ± 1,165.68 yuan for the RSLP group and 30,396.30 ± 5214.06 yuan for the LP group. Significant improvements in the hydronephrosis grading, anterior–posterior renal pelvic diameters, and renal parenchymal thickness were observed in both groups after surgery. RSLP is a safe and effective method for the treatment of UPJO in infants. Compared with LP, RSLP has the advantages of precise suturing, short anastomosis time, and short operation duration, making it an attractive and safe option. However, it faces the disadvantages of higher cost of hospitalization.

To identify independent risk factors for urosepsis in diabetic patients with upper urinary tract stones (UUTS) and develop a prediction model to facilitate early detection and diagnosis, we retrospectively reviewed medical records of patients admitted between January 2020 and June 2023. Patients were divided based on the quick Sequential Organ Failure Assessment (qSOFA) score. The least absolute shrinkage and selection operator (LASSO) regression analysis was used for variable selection to form a preliminary model. The model was optimized and validated using the receiver operating characteristic (ROC) curve, the Hosmer-Lemeshow test and calibration curve, and decision curve analysis (DCA). A nomogram was constructed for visualization. A total of 434 patients were enrolled, with 66 cases and 368 controls. Six optimal predictors were identified: underweight, sarcopenia, poor performance status, midstream urine culture, urinary leukocyte count, and albumin-globulin ratio (AGR). The midstream urine culture was excluded due to its inability to provide rapid results. The final model demonstrated good prediction accuracy and clinical utility, with no significant difference in performance compared to the initial model. The study developed a prediction model for urosepsis risk in diabetic patients with UUTS, presenting a convenient tool for timely diagnosis, particularly in non-operated patients.