Organoids are novel in vitro models that can effectively simulate the complexities of tumor microenvironments.Compared to tra-ditional preclinical models,organoids retain most of the histological and molecular properties of the primary tumor;therefore,they are more useful for studying tumor heterogeneity,underlying functional pathways,and immune microenvironments as well as for research on biomarker discovery,drug screening,and individual chemotherapy.Furthermore,current limitations,challenges such as low modeling suc-cess rates,high costs,and lack of standardization are expected to be overcome by continued innovations in bioengineering technologies and interdisciplinary integration.This article reviews the advantages,establishment processes,and prospects and challenges associated with the clinical application of organoids in bladder cancer.

[Objective] To explore the clinical application of cutaneous ureterostomy-flap embedding in radical cystectomy plus urinary diversion. [Methods] The clinical data of 10 patients with bladder cancer treated with this method in our hospital during Feb.and May 2023 were involved.Cutaneous ureterostomy-flap embedding was used in urinary diversion.The stoma-free rate and stenosis rate of stomas within 1 year postoperatively, differences in renal function indicators 1 day before operation and 1 year after operation, urinary diversion-related complications within 6 months postoperatively, including hydronephrosis, urinary tract infections, renal stones were analyzed. [Results] All surgeries were successfully completed.At 1 year postoperatively, renal function indicators showed no significant difference compared to preoperative levels (P>0.05). At 6 months postoperatively, 1 patient developed renal stones, successfully treated with surgery; 2 had urinary tract infection, recovered after antibiotic treatment; 2 had mild unilateral hydronephrosis, alleviated with conservative management.At 1 year postoperatively, the catheter-free rate was 80%(8/10), with no worsening of hydronephrosis or occurrence of ureteral obstruction, and the stent placement duration ranged from 97 to 211 days, average (151.63±42.47) days.The ureteral stent was not removed in 2 patients within 1 year, so the stoma stenosis rate was 20%(2/10). [Conclusion] The application of flap embedding in urinary diversion following radical cystectomy is a simple and safe procedure, with few postoperative complications, high success rate of stent removal, and overall favorable outcomes.

Objective:To investigate the molecular mechanisms of chronic rhinosinusitis (CRS), to identify key cell subgroups and genes, to construct effective diagnostic models, and to screen for potential therapeutic drugs.Methods:Key cell subgroups in CRS were identified through single-cell transcriptomic sequencing data. Essential genes associated with CRS were selected and diagnostic models were constructed by hdWGCNA (high dimensional weighted gene co-expression network analysis) and various machine learning algorithms. Causal inference analysis was performed using Mendelian randomization and colocalization analysis. Potential therapeutic drugs were identified using molecular docking technology, and the results of bioinformatics analysis were validated by immunofluorescence staining. Graphpad Prism, R, Python, and Adobe Illustrator software were used for data and image processing.Results:An increased proportion of basal and suprabasal cells was observed in CRS, especially in eosinophilic CRS with nasal polyps (ECRSwNP), with P=0.001. hdWGCNA revealed that the "yellow module" was closely related to basal and suprabasal cells in CRS. Univariate logistic regression and LASSO algorithm selected 13 key genes ( CTSC, LAMB3, CYP2S1, TRPV4, ARHGAP21, PTHLH, CDH26, MRPS6, TENM4, FAM110C, NCKAP5, SAMD3, and PTCHD4). Based on these 13 genes, an effective CRS diagnostic model was developed using various machine learning algorithms (AUC=0.958). Mendelian randomization analysis indicated a causal relationship between CTSC and CRS (inverse variance weighted: OR=1.06, P=0.006), and colocalization analysis confirmed shared genetic variants between CTSC and CRS (PPH4/PPH3>2). Molecular docking results showed that acetaminophen binded well with CTSC (binding energy:-5.638 kcal/mol). Immunofluorescence staining experiments indicated an increase in CTSC +cells in CRS. Conclusion:This study integrates various bioinformatics methods to identify key cell types and genes in CRS, constructs an effective diagnostic model, underscores the critical role of the CTSC gene in CRS pathogenesis, and provides new targets for the treatment of CRS.

Objective To explore the efficacy and technical points of complete preservation of female reproductive organ in radical cystectomy.Methods In 2020 and 2021,two female patients with bladder cancer undergoing radical cystectomy in The First Affiliated Hospital of Naval Medical University were selected.The clinical conditions of the patients were evaluated before surgery,and the reproductive organs were completely preserved according to the patients'wishes during the operation.The patients were regularly followed up after surgery.The efficacy and prognosis of patients were evaluated.Results The operation was successful and the two patients recovered well without surgery-related complications.The follow-up time for two patients were 22 months and 36 months.During the follow-up period,no tumor recurrence was found,and the scores of sexual function and quality of life were good.One patient was successfully pregnant at 17 months after surgery,and routine prenatal examination and non-invasive fetal DNA testing showed no abnormalities.Conclusions Under the premise of strictly grasping the surgical indications,the complete preservation of female reproductive organs in radical cystectomy can improve patients'quality of life after surgery,especially protect the reproductive function of women of childbearing age.

Transposons are the most prevalent elements in human genomes, which plays a vital role in gene expression regulation and evolutionary processes. They also jeopardize genome integrity with the characteristics of jumping and insertions. A delicate balance is maintained between the benefits and deleterious aspects of transposons, mediated by the epigenetic regulatory system. Once the balance is broken, it will give rise to genomic instability, leading to neoplasia. A lot of studies have shown that the transcriptional activation, expression products and methylation of transposons are closely related with urological malignancies, holding tremendous potential as biomarkers for risk and effect prediction, noninvasive diagnosis and targeted therapies of urological malignancies. In this article, the molecular mechanisms of transposons underlying the initiation, promotion and progression of urological malignancies as well as advances in diagnosis and treatment are reviewed.

Objective:To explore the effect of different HER2 expression levels and gene amplification on the efficacy of immunotherapy in metastatic urothelial carcinoma (UC).Methods:The clinical data of 77 patients with metastatic UC who received immunotherapy from June 2017 to April 2021 after failure to the previous chemotherapy were analyzed retrospectively, including 49 males and 28 females with the median age of 62 years. The primary tumors located in bladder in 28 cases (36.4%), renal pelvis in 25 cases (32.5%) and ureter in 24 cases (31.2%). The common metastatic sites included: lymph nodes (n = 45, 58.4%), lung (n = 40, 51.9%), bone (n = 20, 26.0%) and liver (n = 16, 20.8%). 27 patients with bladder UC received surgery on the primary tumors including radical cystectomy (n = 18), partial cystectomy (n = 4) and transurethral resection (n = 5). 43 patients with renal pelvis or ureteral UC received surgery on the primary tumors including radical nephroureterectomy (n = 38), local resection (n = 3) and palliative resection (n = 2). Postoperative intravesical chemotherapy was performed in 15 cases, adjuvant radiotherapy was performed in 6 cases. 3 patients who emerged postoperative bladder recurrence received local radiotherapy. 7 patients received radiotherapy and 1 case received microwave ablation to their metastatic sites. All patients had received first-line chemotherapy and 30 patients (40.0%) had received at least second-line treatment including 70 cases (90.9%) with platinum containing chemotherapy. All 77 patients received anti-PD-1 treatment. 38 patients received sequential regimen after failed to the anti-PD-1 therapy, including antibody-drug conjugate (n = 17), chemotherapy (n = 18) and chemotherapy combined with anti-angiogenesis drugs (n = 12). Immunohistochemical (IHC) staining was used to detect the expression level of HER2 protein in the tumor tissues (74 cases from primary tumors and 3 cases from metastatic tumors) obtained from the initial diagnosis. For patients with HER2 IHC (+ + ), the copy number (CN) of HER2 gene was detected by next-generation sequencing (NGS). HER2 copy number amplification [CN (+ )] was defined as CN ≥ 4, and HER2 copy number non-amplification [CN(-)] was defined as CN < 4. HER2 IHC (0) was defined as HER2 negative, IHC (+ ) or IHC (+ + ) / CN (-)was defined as HER2 low expression, while IHC (+ + ) / CN(+ ) and IHC (+ + + ) were defined as HER2 high expression. Chi-square test or Fisher exact test were used to evaluate the correlation between HER2 expression and objective response rate (ORR) after anti-PD-1 treatment. Kaplan-Meier method and log-rank test were used to compare the differences of median progression free survival (PFS) and overall survival (OS) under different HER2 expression status.Results:All the 77 patients received a median of 11 (range: 2 - 45) doses of anti-PD-1 treatment with a median duration of treatment of 6.4 (range: 1.5 - 47.8) months and the ORR was 33.8% (26/77). The median follow-up time was 30.9 months. The overall median PFS time was 5.8 (95% CI: 3.0 - 8.6) months and the median OS time was 23.6 (95% CI: 8.5 - 38.7) months. HER2 IHC tests were performed in 77 patients. HER2 IHC levels of (0), (+ ), (+ + ) and (+ + + ) were found in 33 (42.9%), 19 (24.7%), 20 (26.0%) and 5 (6.5%) patients, respectively. HER2 copy number was detected in 20 patients with IHC (+ + ), while 1 CN(+ ) and 19 CN(-) were found. The ORR of HER2 negative, low expression and high expression patients were 42.4% (14/33) vs. 31.6% (12/38) vs. 0 (0/6) ( P = 0.08), respectively. The median PFS of the three groups were 11.0 months, 3.7 months and 1.8 months, respectively, with significant differences in overall and pairwise comparison( P=0.001). The median OS of patients with HER2 negative and low expression after anti-PD-1 treatment were 23.6 months and 22.7 months, respectively, while the median OS of patients with HER2 high expression had not been reached, with no significant difference in the overall comparison ( P=0.623). Conclusions:For patients with metastatic UC received anti-PD-1 treatment, the PFS of patients with high HER2 expression was significantly worse than that of patients with low or negative HER2 expression. HER2 expression may have potential value in predicting the efficacy of immunotherapy for metastatic UC who failed the previous chemotherapy, which needs further research.

Compared with normal tissue, interstitial extracellular pH of tumor cells is acidic. The reverse transmembrane pH gradient around tumor cells is closely related to its uncontrolled progression, angiogenesis and metastasis. Changes in urinary pH have an impact on the occurrence, progression and treatment of bladder cancer by regulating the microenvironment of bladder cancer cells. Relevant studies have shown that urinary pH value is an important factor in predicting the final clinical efficacy of bladder cancer patients combined with alkalization agents, which helps to reflect the acid-base balance and immune defense system in the body. Continuous monitoring of urinary pH can provide guidance and decision-making for the prognosis of bladder cancer patients.

With the development of new drugs, advances in medical technology and progressions in tumor molecular biology, organ preservation surgery has become the new trend for tumor treatment. Here, we discussed how to select right muscle-invasive bladder cancer patient with strict criteria for multimodality bladder-sparing treatment, and we reviewed the new treatment options, outcomes and trend of development for bladder-sparing treatments.

Objective:To evaluate the safety and efficacy of Toumai ? endoscopic robotic system in radical prostatectomy. Methods:This study was a single-center phase Ⅲ randomized controlled study. From June 2020 to January 2021, patients with prostate cancer who met the inclusion criteria in Changhai Hospital Affiliated to Naval Military Medical University were divided into the experimental group and the control group by random table method. Inclusion criteria included aged 18 to 80 years, pathologically diagnosed as prostate cancer, clinical stage ≤T 2N 0M 0. Exclusion criteria included patients requiring emergency surgery, having serious cardiovascular diseases and cannot tolerate surgery, having participated in other investigational drug or device clinical trials within the last 3 months. The experimental group used Toumai ? laparoscopic robotic system, and the continence group used the Da Vinci robotic system. The patients in both groups underwent radical prostatectomy via a transabdominal approach, which was performed by two surgeons. The clinical characteristics between the two groups were compared, related adverse events were recorded, and PSA and urinary continence were followed up one month after the operation. Results:A total of 44 patients were enrolled in this study, including 22 cases in the experimental group and 22 cases in the control group. The mean age of patients in the trial group and the control group was (67.7±7.5) years and (66.4±6.3) years, respectively. The median PSA at diagnosis was 10.5 (7.7, 23.7) ng/ ml and 13.5 (8.9, 24.7) ng/ ml, respectively. Biopsy Gleason score of 6, 7, 8 and 9 in experimental group were 13.6% (3/22), 68.2% (15/22), 4.5% (1/22) and 13.6% (3/22), respectively, and in the control group were 4.5% (1/22), 59.1% (13/22), 22.7% (5/22) and 13.6% (3/22) respectively. The middle risk and high risk group in the experimental group was 50.0% (11/22), 50.0% (11/22), and the control group was 36.4% (8/22), 63.6% (14/22). There was no statistical difference between the two groups.The operations in both groups were successfully performed. There were no conversions to open or laparoscopic surgeries, and no Clavien-Dindo grade Ⅲcomplications. There was no significant difference in the estimated blood loss during the operation [(109.1±51.6)ml vs.(94.5±51.6)ml] and the blood transfusion rate [9.1%(2/22)vs. 4.5%(1/22)] in both groups. The operation time was significantly higher in the experimental group than that in the control group [164.5(130.5, 214.3) min vs. 88.0(65.3, 110.5)min, P<0.001]. The positive rate of surgical margin was 13.6% (3/22) in the experimental group and 36.4% (8/22) in the control group, respectively, showing no significant difference. The pathologic stages of pT 2, pT 3a and pT 3bin experimental group were 63.6% (14/22), 13.6% (3/22) and 22.7% (5/22), respectively, while those in control group were 36.3% (8/22), 40.9% (9/22) and 22.7% (5/22), respectively, showing no significant difference. The recovery rates of urine control in the experimental group and the control group were 22.7% (5/22) and 22.7% (5/22), respectively. The median PSA in the experimental group and the control group were 0.055 (0.021, 0.103) ng/ ml and 0.032 (0.010, 0.089) ng/ ml, respectively, with no statistical difference. Conclusions:The Toumai ? endoscopic robotic system can successfully perform radical prostatectomy, based on insignificant difference from Da Vinci robotic system in safety and efficacy. The short-term follow-up showed that tumor control and urinary continence have recovered well in the test group. The long-term effect of the new system on tumor control and functional recovery after radical prostatectomy needs further multi-center studies.

Bladder cancer is a malignant tumor of the urinary system with the highest and still increasing incidence rate in China in recent years. While most patients with a diagnosis of non-muscle invasive bladder cancer (NMIBC) have a good prognosis, NMIBC is prone to relapse and progress to muscular invasive cancer (MIBC) after treatment, leading to a poor prognosis. At present, diagnosis and postoperative follow-up of bladder cancer still rely on invasive cystoscopy, and there is a lack of effective treatment for advanced tumors. The results show that methylation, as a chemical modification of DNA, is related to the occurrence and development of bladder cancers. This article reviews the research progress of bladder cancer DNA methylation in diagnosis, monitoring and treatment in recent years.