Trends in death and life lost due to bladder cancer in Suzhou Cityfrom 2003 to 2022 / 预防医学

Objective @#To analyze the trends in mortality and life lost due to bladder cancer in Suzhou City, Jiangsu Province from 2003 to 2022, so as to provide the reference for prevention and treatment strategy of bladder cancer.@*Methods@# The data of bladder cancer death in Suzhou City from 2003 to 2022 were collected through Suzhou Residents' Death Registration System, including age, gender, date of death and underlying cause of death. The crude mortality, standardized mortality, years of potential life lost (PYLL), standardized years of potential life lost (SPYLL), years of potential life lost rate (PYLLR), standardized years of potential life lost rate (SPYLLR) and average years of life lost (AYLL) were calculated. The average annual percent change (AAPC) was used to analyze the trends in bladder cancer death and life lost. @*Results@#Totally 2 978 deaths occurred due to bladder cancer in Suzhou City from 2003 to 2022. The crude mortality was 2.22/105, which appeared a tendency towards a rise (AAPC=4.271%, P<0.05). The standardized mortality was 0.91/105, which appeared no significant changing trend (P>0.05). The standardized mortality was 1.58/105 in males and 0.37/105 in females, which appeared no significant tendency in males (P>0.05) and appeared a tendency towards a decline in females (AAPC=-2.331%, P<0.05). The age-specific crude mortality was low among people who aged under 45 years, began to rise among people aged over 45 years and peaked among people aged 60 years and older. The crude mortality of bladder cancer in males aged 60 years and older showed an increasing trend (AAPC=2.864%, P<0.05), but there was no significant tendency in females aged 60 years and older (P>0.05). The PYLL, SPYLL, PYLLR, SPYLLR and AYLL of bladder cancer were 5 020.00 person-years, 2 945.14 person-years, 0.04‰, 0.03‰ and 9.07 years per person. SPYLL, SPYLLR and AYLL showed an decreasing trend (AAPC=-2.867%, -3.321%, -3.738%, P<0.05). @*Conclusions@#The mortality of bladder cancer in Suzhou City appeared a tendency towards a rise from 2003 to 2022. The PYLL appeared a downward trend. Males aged 60 years and older are the key groups for the prevention and control of bladder cancer.

Expression and Clinical Significance of MIS18BP1 in Bladder Cancer Tissues / 肿瘤防治研究

Objective To explore the expression, correlation with clinicopathologic parameters, and clinical significance of MIS18 binding protein 1 (MIS18BP1) in bladder cancer. Methods TCGA and GEO databases were used to analyze the mRNA expression of MIS18BP1 in tumors and controls, and the results were verified via qRT-PCR. UALCAN online database was utilized in the analysis of the expression of MIS18BP1 and its correlation with clinicopathological parameters and the degree of immune cell infiltration. Immunohistochemistry was employed to analyze the expression of MIS18BP1 in bladder cancer and its relationship with clinicopathological features. The ROC curve was applied to evaluate the diagnostic value of MIS18BP1 mRNA in bladder cancer. Results Bioinformatics analysis and qRT-PCR results revealed the increased expression of MIS18BP1 mRNA in bladder cancer compared with that in the control group (P<0.05). Immunohistochemistry unveiled the significantly high positive rate of MIS18BP1 protein in bladder cancer (P<0.05) and its correlation with the clinical stage of tumors, depth of invasion, and lymph node metastasis (P<0.05). The immune infiltration analysis showed the association of MIS18BP1 with immune cell infiltration in bladder cancer. Conclusion The increased expression level of MIS18BP1 gene and protein in bladder cancer may regulate the development of bladder cancer by influencing immune cell infiltration.

Potential Mechanism of Taraxaci Herba Against Bladder Cancer： A Review / 中国实验方剂学杂志

Bladder cancer （BCa） is the most common malignant tumor of the urinary system， and its incidence is increasing year by year. At present， for all patients with resectable non-metastatic muscle-invasive BCa， radical cystectomy + bilateral pelvic lymph node dissection is strongly recommended， but they still face the risk of recurrence， metastasis and death. In recent years， the proportion of patients with advanced and metastatic BCa is increasing among patients with newly diagnosed BCa. Although current treatment models are diverse， they often struggle to achieve significant efficacy due to their low effectiveness and adverse effects， resulting in low survival rates for patients with advanced and metastatic BCa. Therefore， the treatment of BCa still faces great challenges， and there is an urgent need to discover an effective new antitumor drug. With the improvement of medical standards， traditional Chinese medicine has shown great advantages in the treatment of BCa. Traditional Chinese medicine is mild and easy to accept， and can inhibit tumor progression through a multi-pathway， multi-way and multi-target manner， so as to exert its anticancer effect. Taraxaci Herba is a medicinal and food homologous plant， which has many biological activities， such as antibacterial， anti-inflammatory， anti-oxidation， anti-tumor， protecting liver and gallbladder， reducing blood sugar and enhancing immunity， and it has shown a clear anticancer effect in breast cancer， liver cancer， gastric cancer， tongue cancer and lung cancer. By reviewing previous studies worldwide， this article summarizes the mechanism of Taraxaci Herba extract in inducing autophagy and apoptosis， inhibiting cell migration and invasion， regulating cell cycle and proliferation， regulating cell metabolism， inhibiting tumor angiogenesis， combining the effects of chemotherapeutic drugs， and regulating the transduction of related signal pathways. On this basis， this study systematically elaborates on the potential mechanism of Taraxaci Herba against BCa， in order to provide a theoretical basis for the research and treatment of BCa.

Classification of bladder cancer based on immune cell infiltration and construction of a risk prediction model for prognosis / 浙江大学学报·医学版

OBJECTIVES@#To classify bladder cancer based on immune cell infiltration score and to construct a risk assessment model for prognosis of patients.@*METHODS@#The transcriptome data and data of breast cancer patients were obtained from the TCGA database. The single sample gene set enrichment analysis was used to calculate the infiltration scores of 16 immune cells. The classification of breast cancer patients was realized by unsupervised clustering, and the sensitivity of patients with different types to immunotherapy and chemotherapy was analyzed. The key modules significantly related to the infiltration of key immune cells were identified by weighted correlation network analysis (WGCNA), and the key genes in the modules were extracted. A risk scoring model and a nomogram for risk assessment of prognosis for bladder cancer patients were constructed and verified.@*RESULTS@#The immune cell infiltration scores of normal tissues and tumor tissues were calculated, and B cells, mast cells, neutrophils, T helper cells and tumor infiltrating lymphocytes were determined to be the key immune cells of bladder cancer. Breast cancer patients were clustered into two groups (Cluster 1 and Custer 2) based on immune cell infiltration scores. Compared with patients with Cluster 1, patients with Cluster 2 were more likely to benefit from immunotherapy (P<0.05), and patients with Cluster 2 were more sensitive to Enbeaten, Docetaxel, Cyclopamine, and Akadixin (P<0.05). WGCNA screened out 35 genes related to key immune cells, and 4 genes (GPR171, HOXB3, HOXB5 and HOXB6) related to the prognosis of bladder cancer were further screened by LASSO Cox regression. The areas under the ROC curve (AUC) of the bladder cancer prognosis risk scoring model based on these 4 genes to predict the 1-, 3- and 5-year survival of patients were 0.735, 0.765 and 0.799, respectively. The nomogram constructed by combining risk score and clinical parameters has high accuracy in predicting the 1-, 3-, and 5-year overall survival of bladder cancer patients.@*CONCLUSIONS@#According to the immune cell infiltration score, bladder cancer patients can be classified. And the bladder cancer prognosis risk scoring model and nomogram based on key immune cell-related genes have high accuracy in predicting the prognosis of bladder cancer patients.

The prognostic effect of immunohistochemical staining rates in patients with non–muscle-invasive bladder cancer

Context: Despite the follow-up protocols developed in non–muscle-invasive bladder cancer patients, progression and recurrence could not be prevented. Aims: We aimed to investigate whether proteins such as OCT-4, CD47, p53, Ki-67, and Survivin, which increase in bladder cancer cells, can be used as prognostic markers for patients with non–muscle-invasive bladder cancer. Settings and Design: The study included a total of 89 patients with newly diagnosed non–muscle-invasive bladder cancer between January 2015 and December 2020. Materials and Methods: Levels of OCT-4, CD47, p53, K?-67, and Survivin proteins in cancer cells were determined with a semi-quantitative immunohistochemical experiment. Pathological data and survival rates were compared according to the staining rates. Statistical Analysis Used: Data obtained in the study were analyzed statistically with SPSS 22.0 (SPSS, Chicago, IL, USA). Results: The mean age of the patients was 64.25 ± 9.91 years, and the median follow-up period was 55 months. Recurrence rate was determined to be 36% (n = 32), and the rate of progression at 40.4% (n = 36). The staining rates were stronger for each marker in the progression group and advanced-stage tumors (p < 0.001). The findings of the multivariate analysis carried out as part of the study showed that older age and higher tumor stage were independent risk factors for recurrence-free survival (HR = 1.048 and 7.074, respectively; P = 0.02). Also, higher tumor stages, diameters, and grades were associated with reduced progression-free survival (HR = 0.105, 0.395, 0.225, respectively; P < 0.05). Conclusions: Although immunohistochemical staining rates are promising, it is more appropriate to use tumor characteristics when assessing survival rate in patients with non–muscle-invasive bladder cancer.

Immunohistochemical appraisal of epithelial mesenchymal transition type III in gall bladder cancer

Background: Epithelial-mesenchymal transition (EMT) is the heart of invasion. EMT associated with cancer progression and metastasis is known as type III EMT. Beta-catenin, E-cadherin, and MMP9 markers of EMT are routinely employed for diagnostic purposes. Aims: We employed these markers to study EMT by immunohistochemistry (IHC) in gall bladder cancer (GBC) with respect to depth of tumor invasion, clinical outcome, and disease-free survival. Settings and Design: This was a prospective case-control study. Material and Methods: Seventy gall bladders were included (50 GBC and 20 CC). After detailed histology, immunoexpression was studied in terms of percentage and strength of expression. Statistics Analysis Used: Expression was compared between CC and GBC by Student t test and analysis of variance. Kaplan–Meier was used for survival analysis, and the extent of agreement (“Kappa”) was calculated. Results and Conclusions: The age of incidence of GBC was 49.40 (+11.6) years with female predominance (F:M = 4:1). In 88% (44/50) of GBC, the fundus was involved. Moderately differentiated adenocarcinoma was most frequent [54%; 27/50]. Significant downregulation of E-cadherin (P = 0.022) and beta-catenin (P < 0.001) and upregulation in MMP9 (P < 0.001) were seen in GBC with respect to CC with significant association among them. MMP9 expression was significantly associated with higher tumor stage but with chemotherapeutic response. Our results display that epithelial-mesenchymal transition type III plays a role in GBC invasion. MMP9 overexpression and loss of membranous beta-catenin may be considered a marker for poor clinical outcomes and advanced disease.

La esquistosomiasis como factor de riesgo del cáncer de vejiga. Hospital Central de Nampula, Mozambique

Introducción: la esquistosomiasis es la infección por trematodos más importante a nivel global. El carcinoma de células escamosas constituye el 2 % de todos los tipos histológicos de cáncer vesical; sin embargo, la incidencia de esta variedad en países endémicos de esquistosomiasis es mayor. Objetivo: evaluar la relación entre la esquistosomiasis y el cáncer de vejiga en pacientes del Hospital Central de Nampula. Materiales y métodos: se realizó un estudio observacional, descriptivo y transversal en el período comprendido entre enero de 2014 y diciembre de 2020. Los pacientes se dividieron en grupos etarios, por intervalos de 10 años. Se tomaron muestras de biopsias de tumores de vejiga, clasificándose por tipo histológico, además de los hallazgos relacionados con infestación por esquistosomiasis y formas de presentación del cáncer de vejiga. El universo estuvo constituido por 184 pacientes, y la muestra se conformó por 135 casos. Resultados: se comprobó que el mayor número de pacientes con cáncer de vejiga es del sexo masculino; el tipo histológico más frecuente fue el carcinoma de células escamosas, representando un 84,3 % del total. La cistitis, la presencia de esquistosomas, y sus huevos estuvieron presentes en casi todas las biopsias realizadas. Sus formas de presentación más frecuente fueron la cistitis, la hematúrica y la dolorosa. Conclusiones: el cáncer de vejiga mostró una mayor incidencia en las edades comprendidas entre 30 y 69 años. El carcinoma de células escamosas fue el más frecuente, y su relación con la cistitis y la infección por esquistosomas estuvo presente en más del 90 % de las biopsias.

Introduction: schistosomiasis is the most important trematode infection globally. Squamous cell carcinoma constitutes 2% of all the histological types of bladder cancer; however, the incidence of this variety of cancer in squistosomiasis-endemic countries is higher. Objective: to evaluate the relationship between squistosomiasis and bladder cancer in patients from the Central Hospital of Nampula. Materials and methods: a cross-sectional descriptive observational study was carried in the period between January 2014 and December 2020. Patients were divided into age-groups, by 10-year intervals. Biopsy samples of bladder tumors were taken, classified by histological type, in addition to findings related to squistosomiasis infestations and bladder cancer presentation forms. The universe consisted of 184 patients and the sample of 135 cases. Results: it was found that the largest number of patients with bladder cancer is male; squamous cell carcinoma is the most frequent histological type, representing 84.3% of the total. Cystitis, schistosome and their eggs were present in almost all the biopsies performed. Its most frequent presentation forms were hematuric and painful cystitis. Conclusions: bladder cancer showed higher incidence at the ages between 30 and 69 years. The squamous cell carcinoma was the most frequent, and its relationship with cystitis and schistosome infection was present in more than 90% of biopsies.

Classification and minimally invasive management of ureteroileal bladder anastomotic stricture after radical cystectomy / 中华泌尿外科杂志

Objective:To discuss the classification and treatment of ureteroileal anastomotic stricture (UAS) after radical cystectomy.Methods:The clinical data of 34 patients with UAS after radical cystectomy in the Department of Urology of Tongji Hospital from January 2017 to January 2022 were reviewed and analyzed. There were 25 males and 9 females. The average age was (66.3±7.7)years, including 2 cases of bilateral hydronephrosis and 32 cases of unilateral hydronephrosis. The average time of UAS was detected (14.7±6.5)months after radical cystectomy. There were 32 patients of unilateral hydronephrosis and 2 patients of bilateral hydronephrosis. Two patients had undergone nephrostomy in an external hospital. Three patients had elevated leukocytes in blood routine. Among them, two patients had fever. First, nephrostomy on the hydronephrosis side and anti-infection treatment were performed. After routine blood tests showed that the white blood cells were normal and antibiotics were stopped for 24 hours without fever, the operation was performed. 34 patients had preoperative hydronephrosis of (2.7±0.6) cm. Of the 34 cases in this group, 5 cases were injected with methylene blue through a preoperative nephrostomy tube, and 29 were injected with methylene blue through the renal pelvis using an 18G puncture needle under ultrasound guidance. Using a ureteroscope to observe in the ileal bladder, methylene blue was seen in 4 cases. Methylene blue was used to guide the search for the stenosis and a super smooth guide wire was inserted. Among them, 3 cases were dilated with a 5 mm ureteral dilation balloon catheter, 1 case was dilated with a F14 ureteral access sheath, and then a F6 single J stent was inserted. Methylene blue was not seen in the ileal conduit in 30 cases, of which 16 cases were treated with a flexible ureteroscope through the nephrostomy to locate the stenosis, incised with a 30 W holmium laser. 9 cases were treated with 5 mm ureteral dilation balloon catheter, and 7 cases were treated with a F14 ureteral access sheath, and then an F6 single J stent was inserted. 14 cases were unable to find the stenosis by antegrade method. According to the operation time and patient's condition, it was decided to perform immediate or second stage dual endoscope surgery. Through the nephrostomy, a flexible ureteroscope was used to enter the stenosis along the super slide guide wire. A rigid ureteroscope was used to observe the stenosis through the ileal conduit, and the stenosis was found. The stenosis was found in 10 cases and incised with a 30 W holmium laser. 8 cases were treated with 5 mm ureteral dilation balloon catheter, and 2 cases were treated with a F14 ureteral access sheath, and then an F6 single J stent was inserted. 4 cases were still unable to accurately locate the stenosis using the dual endoscope surgery(one case was bilateral stenosis, and one side was relieved), and continued indwelling nephrostomy. The definition of successful removal of stricture in this study is that an F6 single J stent can be inserted into the ureter.Results:UAS were classified into four types based on the severity of the intraoperative findings: Type Ⅰ, the narrow ureteral lumen is more than 50% narrower than the normal ureteral lumen, but methylene blue can pass through in strands; Type Ⅱ, needle like stricture of the ureteral lumen, allowing only methylene blue filaments to pass through; Type Ⅲ, membranous atresia of the ureter, with a narrow segment of 1 to 3 mm in length, and methylene blue cannot pass through; Type Ⅳ, long segment stenosis. Of the 34 cases in this group, 4 cases were type Ⅰ, and the stenosis was dredged by retrograde method; 16 cases were type Ⅱ, and the stenotic segments were dredged by antegrade method; 10 cases were type Ⅲ, and the stenosis was dredged by the dual endoscope surgery; Four cases were of type Ⅳ (one case was of bilateral UAS, one side was of type Ⅲ, and the other side was of type Ⅳ, which was classified as type Ⅳ). The stenotic segment could not be solved through the above methods. Among the 34 patients, 30 patients were successfully relieved of anastomotic obstruction, and 1 patient with bilateral obstruction was unilaterally relieved of anastomotic obstruction. In the other 3 cases, because the stenosis segment was too long, 2 cases were changed to nephrostomy, and 1 case was changed to open surgery, with a success rate of 88.2%. UAS was classified into 4 types based on the severity of UAS seen during surgery. No serious complications occurred during and after the operation. During the follow-up of 6-24 months, the imaging evaluation of 4 patients showed that hydronephrosis was aggravated, with an average increase in creatinine of (32.5±10.9)μmol/L, requiring replacement of a single J tube. The imaging evaluation of the remaining 26 patients showed that the postoperative hydronephrosis was 0.9 ± 0.6 cm less than the preoperative hydronephrosis 2.6 ± 0.6 cm, with a statistically significant difference ( P<0.01). The quality of life score at 3 months after surgery was (1.9±0.6), which was significantly improved compared to the preoperative indwelling nephrostomy period (5.2±0.7), with a statistically significant difference ( P<0.01) Conclusions:The treatment of UAS after radical cystectomy with retrograde, antegrade, and dual endoscope surgery has a high success rate, which can help some patients avoid the inconvenience of indwelling external drainage tubes and the risk of open surgery. Choosing an appropriate surgical method can achieve the goal of treating UAS with minimal trauma.

The interpretation of urothelial carcinoma at the 2023 ASCO-GU / 中华泌尿外科杂志

The 2023 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO-GU) reported several advancements in the field of urothelial carcinoma. Multiple new treatment options for non-muscle invasive bladder cancer (NMIBC) were introduced, providing more choices for bladder preservation in BCG-resistant/failed NMIBC cases. In muscle invasive bladder cancer (MIBC) perioperative treatment, the updated 3-year follow-up data from the CheckMate 274 study demonstrated a clear advantage in disease-free survival for the nivolumab monotherapy adjuvant treatment group. For metastatic urothelial carcinoma (mUC), the final overall survival (OS) report from the IMvigor130 study was published, prompting further considerations for future first-line treatment options in mUC. Additionally, the conference highlighted research progress in upper tract urothelial carcinoma (UTUC).

Prediction of myometrial invasion of bladder cancer based on texture analysis of the bladder wall at tumor base / 中华超声影像学杂志

Objective:To identify the value of ultrasound radiomic features extracted from the bladder wall at tumor base in predicting myometrial invasion of bladder cancer.Methods:A total of 175 cases with bladder cancer confirmed by pathology from January 2017 to February 2022 in the First Affiliated Hospital of Guangxi Medical University were retrospectively analyzed. They were divided into training set and testing set in a ratio of 7∶3. The MaZda texture analysis software was used to draw the region of interest (ROI) of the bladder wall and the tumor region for extracting texture features. The minimum absolute reduction and variable selection operator (LASSO) regression and 10-fold cross-validation were used to screen the features of training set for establishing the models. And the ROC curve was used to evaluate the efficiency of the models.Results:A total of 279 texture features were extracted from the ROI of the bladder wall and the tumor region, and 5 texture features were screened out for constructing omics scoring models by LASSO regression and 10-fold cross-test. The area under ROC curve (AUC)s used in training set and testing set of the bladder wall were 0.921 and 0.856, while the AUCs applied in training set and testing set of the tumor region were 0.849 and 0.704. Both in the training set and test set, the AUCs of the model of the bladder wall were higher than those of the model of the tumor region (all P<0.05). Conclusions:The omics scoring model based on the texture features of the bladder wall at tumor base can effectively identify muscle-invasive bladder cancer(MIBC) and non-muscle-invasive bladder cancer(NMIBC), and has better performance than the model based on the texture feature of the tumor region.

Effect of CYFIP2 overexpression on biological function and Wnt/β-catenin signaling pathway of bladder cancer cell line T24 / 国际生物医学工程杂志

Objective:To investigate the effects of cytoplasmic fragile X mental retardation protein 1 binding protein 2 (CYFIP2) overexpression on the biological functions and Wnt/β-catenin signaling pathways of bladder cancer T24 cells.Methods:The control group was T24 cells transfected with the empty pcDNA3 vector, and the overexpression group was T24 cells transfected with the CYFIP2 overexpression vector. The expression of CYFIP2 mRNA and protein was detected by reverse transcriptase, quantitative polymerase chain reaction, and Western Blot. The effect of CYFIP2 overexpression on T24 cell proliferation was detected by CCK-8. The effect of CYFIP2 overexpression on T24 cell migration and invasion was detected by Transwell. The effects of CYFIP2 overexpression on Wnt/β-catenin signaling pathway in T24 cells were detected by Western Blot.Results:Compared with the control group, the expression levels of CYFIP2 mRNA and protein were increased in the overexpression group (all P < 0.001), and the cell proliferation, migration, and invasion abilities were reduced (all P < 0.01). β-catenin, c-Myc, and Cyclin D1 protein expression were down-regulated in CYFIP2 overexpressed T24 cells (all P < 0.05), while the protein levels of p-β-catenin were increased ( P < 0.05). Conclusions:CYFIP2 overexpression can inhibit T24 cell proliferation, migration, and invasion, and its possible molecular mechanism is related to the inhibition of Wnt/β-catenin signaling pathway.

Efficacy and safety of PD-1/PD-L1 inhibitors for neoadjuvant treatment of bladder cancer：meta-analysis of single-group rates / 中国药房

OBJECTIVE To evaluate the efficacy and safety of PD-1/PD-L1 inhibitors for neoadjuvant treatment of bladder cancer， and to provide evidence-based reference for clinical treatment. METHODS Retrieved from PubMed， Cochrane Library， Embase， American Society of Clinical Oncology Meeting Library， CNKI， VIP and Wanfang database， etc.， the randomized controlled trials （RCTs）， non-RCT， case-control studies， cohort studies， etc. about PD-1/PD-L1 inhibitors for neoadjuvant treatment of bladder cancer were collected from the inception to Jan 31st， 2023. After literature screening， data extraction and quality evaluation， RevMan 5.3 software was used to perform meta-analysis of single-group rates； sensitivity analysis and publication bias analysis were conducted using Stata12 software. RESULTS A total of 25 studies were included in this discussion， involving 940 patients. The results of meta-analysis showed that the pathologic complete response （pCR） rate was 32% [OR＝0.32， 95%CI （0.22， 0.45）， P＝0.006]， downstaging rate was 52% [OR＝0.52， 95%CI （0.45， 0.60）， P＝0.55]， and the incidence of ≥grade 3 immune-related adverse events （irAEs） was 16% [OR＝0.16， 95%CI （0.11， 0.22）， P＜0.000 01]. Subgroup analysis showed that the patients receiving PD-1/PD-L1 inhibitors alone had a pCR rate of 25% and a incidence of Grade≥3 irAEs of 9%； the patients receiving combined immunotherapy had a pCR rate of 29% and a incidence of Grade≥3 irAEs of 28%； the patients receiving PD-1/PD-L1 inhibitors combined with chemotherapy had a pCR rate of 43% and a incidence of Grade≥3 irAEs of 12%； PD-L1 positive patients had a pCR rate of 44%， and PD-L1 negative patients had a pCR rate of 25%. The results of the sensitivity analysis showed that the study was robust. The results of the publication bias analysis showed that there was no significant publication bias. CONCLUSIONS PD-1/PD-L1 inhibitors are effective and safe for adjuvant treatment of bladder cancer.

Plumbagin Induces Ferroptosis Through Nrf-2/Keap1 Signaling Pathway in Bladder Cancer Cells / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of plumbagin as a novel ferroptosis inducer in bladder cancer inhibition. MethodBladder cancer T24 cells were used in this study. The effect of different concentrations of plumbagin （0.1， 1， 2， 3， 6， 12， 24， 48 μmol·L-1） on the viability of T24 cells was detected by cell counting kit-8 （CCK-8）. The effect of different concentrations of plumbagin （1.5， 3， 6 μmol·L-1） on the apoptosis of T24 cells was detected by annexin V-fluorescein isothiocyanate （Annexin V FITC）/PI apoptosis kit. Different inhibitors （ferroptosis inhibitor Fer-1， apoptosis inhibitor VAD， and necroptosis inhibitor Nec-1） were used in combination with plumbagin （6 μmol·L-1）. Reactive oxygen species （ROS） fluorescent probe （DCFH-DA）， malonaldehyde （MDA）， and glutathione （GSH） kits were used to detect the effects of different concentrations of plumbagin （1.5， 3， 6 μmol·L-1） on the level of ROS and the content of MDA and GSH in T24 cells， respectively. The effect of different concentrations of plumbagin （1.5， 3， 6 μmol·L-1） on peroxide levels in T24 cells was detected by C11-BODIPY fluorescent probe. Western blot was used to detect the effect of different concentrations of plumbagin （1.5， 3， 6 μmol·L-1） on the protein expression of solute carrier family 7 member 11 （SLC7A11）， glutathione peroxidase 4 （GPX4）， nuclear factor E2-related factor-2 （Nrf-2）， and Kelch-like ECH-associated protein 1 （Keap1）. ResultCompared with the blank group， plumbagin could inhibit the activity of T24 cells （P<0.05） with IC50 of 3.52 μmol·L-1. At the concentrations of 1.5， 3， 6 μmol·L-1， plumbagin significantly promoted the apoptosis of T24 cells （P<0.05） as compared with the blank group. Compared with the plumbagin group at 6 μmol·L-1， the ferroptosis inhibitor and apoptosis inhibitor groups could reverse the inhibitory effect of 6 μmol·L-1 plumbagin on the proliferation of T24 cells （P<0.05）. Compared with the blank group， the plumbagin groups at 1.5， 3， 6 μmol·L-1 showed increased content of ROS， MDA， and lipid peroxides in T24 cells， decreased GSH level， and reduced SLC7A11， GPX4， and Nrf-2/Keap1 （P<0.05）. Conclusionplumbagin can induce ferroptosis， and its mechanism is related to the Nrf-2/Keap1 signaling pathway.

Risk modeling based on HER-2 related genes for bladder cancer survival prognosis assessment / 北京大学学报(医学版)

OBJECTIVE@#To investigate the correlation between the human epidermal growth factor receptor-2-related genes (HRGs) and survival prognosis of bladder cancer and to construct a predictive model for survival prognosis of bladder cancer patients based on HRGs.@*METHODS@#HRGs in bladder cancer were found by downloading bladder tumor tissue mRNA sequencing data and clinical data from the cancer genome atlas (TCGA), downloading HER-2 related genes from the molecular signatures database (MsigDB), and crossing the two databases. Further identifying HRGs associated with bladder cancer survival (P < 0.05) by using single and multi-factor Cox regression analysis and constructing HRGs risk score model (HRSM), the bladder cancer patients were categorized into high-risk and low-risk groups accor-ding to the median risk score. Survival analysis of the patients in high- and low-risk groups was conducted using R language and correlation of HRGs with clinical characteristics. A multi-factor Cox regression analysis was used to verify the independent factors affecting the prognosis of the patients with bladder cancer. The area under the curve (AUC) of the receiver operating characteristic curve (ROC) of HRSM was calculated, and a nomogram was constructed for survival prediction of the bladder cancer patients. Analysis of HRSM and patient immune cell infiltration correlation was made using the TIMER database.@*RESULTS@#A total of 13 HRGs associated with patient survival were identified in this study. Five genes (BTC, CDC37, EGF, PTPRR and EREG) were selected for HRSM by multi-factor Cox regression analysis. The 5-year survival rate of the bladder cancer patients in the high-risk group was significantly lower than that of the patients in the low-risk group. High expression of PTPRR was found to be significantly and negatively correlated with tumor grade and stage by clinical correlation analysis, while EREG was found to be the opposite; Increased expression of EGF was associated with high grade, however, the high expression ofCDC37showed the opposite result. And no significant correlation was found between BTC expression and clinical features. Correlation analysis of HRSM with immune cells revealed a positive correlation between risk score and infiltration of dendritic cells, CD8+T cells, CD4+T cells, neutrophils and macrophages.@*CONCLUSION@#HRGs have an important role in the prognosis of bladder cancer patients and may serve as new predictive biomarkers and potential targets for treatment.

Research progress on the role of urothelial somatic mutations in the occurrence and recurrence of bladder cancer / 现代泌尿外科杂志

Bladder cancer is characterized by high incidence and high recurrence; however, the mechanism of pathogenesis, especially of recurrence is still unclear. This paper reviews the molecular characteristics of bladder cancer, urothelial somatic mutation, driver genes and mutation characteristics, and prospects the future research directions.

Application of blue laser side light in the vaporization and enucleation of bladder cancer: a report of 16 cases / 现代泌尿外科杂志

【Objective】 To observe the efficacy of blue laser side light in the vaporization and enucleation of non-muscle invasive bladder cancer (NMIBC). 【Methods】 A retrospective analysis was performed on the data of NMIBC patients who received transurethral enucleation of bladder tumor (TURBT) using a 50 W blue laser treatment device. The efficacy and safety of surgery were evaluated by observing the application of blue laser in the treatment of bladder cancer in different locations, operation time, presence of bladder perforation and postoperative urine routine indicators. 【Results】 A total of 16 patients completed the surgery, including 5 cases with multiple bladder tumors, 9 with single bladder tumor, and 2 with lichenoid lesions. The postoperative pathological results showed all of them were NMIBC. The operation time was (10.4±4.7) min, postoperative urinalysis was (689.4±316.7)/μL, and no intraoperative bladder perforation occurred. 【Conclusion】 The lateral infusion mode of 50 W blue laser therapy device can be applied to the surgical treatment of NMIBC. The basal vaporization and enucleation of bladder cancer can be performed under direct vision conditions, and the multi-angle enucleation is suitable for bladder cancer in different positions. The tissue penetration depth of blue laser is shallow, which is conducive to the diagnosis and grading of pathological tissues.

Application of semiconductor blue laser in day surgery for 22 cases of bladder cancer / 现代泌尿外科杂志

【Objective】 To investigate the feasibility and safety of semiconductor blue laser in the treatment of non-muscle invasive bladder cancer (NMIBC) in the day surgery model. 【Methods】 The clinical data of 22 NMIBC patients (average age 55.8 years and tumor size 1.4 cm) who underwent outpatient screening and accepted blue laser ambulatory surgery in our hospital during Jun.2022 and Sep.2022 were retrospectively analyzed. On the day of admission, transurethral resection of cancer was performed using blue laser en bloc enucleation. On the day of surgery or in the morning of next day, bladder irrigation was stopped, the catheter was removed, and patients were discharged. The baseline data, pre-hospital waiting time, operation time, length of hospital stay, hemoglobin decrease, complications and management, follow-up, medical costs, and patients’ satisfaction rate were recorded. 【Results】 The pre-hospital waiting time was 2 to 7 days, average (4.1±1.3)days. The operation time was 29 to 50 minutes, average (40.8±5.5)minutes. The length of hospital stay was 0.6 to 1.2 days, average (0.9±0.2)days. Hemoglobin decrease was 1 g/L to 8 g/L, average (3.8±1.8)g/L. The catheter was indwelt for 0.5 to 1 day, average (0.7±0.1)day. The medical costs were 13 790 to 16 811 Yuan, average (14 941.5±690.2) Yuan. Patients’ satisfaction rate was 100.0%. Mild intraoperative and postoperative complications occurred in 2 cases. One patient developed symptoms of cystitis which disappeared after 2 days of oral antibiotic cefixime, and another patient developed bladder spasm which was relieved after oral solifenacin succinate tablets. No adverse events such as obturator nerve reflex or bladder perforation occurred. After removal of the catheter, no urinary retention was observed. 【Conclusion】 This study was the first to apply blue laser ambulatory surgery in the treatment of bladder cancer, confirming that it is a safe, feasible, economical and efficient model for selected patients, which can be promoted in suitable hospitals.

Efficacy and safety of blue laser en bloc enucleation in the treatment of non-muscle invasive bladder cancer: report of 50 cases from a single center / 现代泌尿外科杂志

【Objective】 To compare the efficacy and safety of blue laser en bloc enucleation and traditional plasmakinetic electrocautery in the treatment of non-muscle invasive bladder cancer (NMIBC). 【Methods】 A total of 50 NMIBC patients treated in our hospital during Oct.2018 and Dec.2019 were enrolled. A randomized, incomplete blinding, parallel control design and non-inferior test method was adopted. The control group (electrocautery group) used plasmakinetic electrocautery for transurethral resection, and the experimental group (blue laser group) used semiconductor blue laser for transurethral en bloc enucleation. The effective resection rate, operation time, postoperative catheter indwelling time, length of hospital stay, perioperative hemoglobin changes and obturator nerve reflex were compared. 【Results】 There were 24 patients in the blue laser group and 26 in the electrocautery group. The effective dissection rate and hemostasis rate in both groups reached 100%. The blue laser group had slightly longer operation time than the electrocautery group (55 min vs.42 min, P=0.009), but lesser hemoglobin decrease (5.7 g/L vs. 10.4 g/L, P=0.007). There were no significant differences in urinary catheter indwelling time, length of hospital stay and reoperation rate between the two groups. The electrocautery group had 3 cases of obturator nerve reflex, while the blue laser group had none. 【Conclusion】 Compared with the traditional electrocautery, blue laser has good vaporization cutting and coagulation hemostatic effects on bladder tumor tissue, and can completely enucleate tumors in a front-firing model with less bleeding and no obturator nerve reflex, which can be used as a new, efficient, safe and easy-to-learn method for NMIBC surgery. However, its effects on postoperative recurrence rate and progression rate still need further studies.

Effects of histone acetyltransferase KAT7 inhibitor WM-3835 on the proliferation and migration of bladder cancer cells / 现代泌尿外科杂志

【Objective】 To investigate the effects of WM-3835, a histone acetyltransferase KAT7 (KAT7) inhibitor, on the proliferation and migration of bladder cancer cells and to explore the possible mechanism. 【Methods】 Human ureteral epithelial immortalized cell line SV-HUC-1, and bladder cancer cell lines UM-UC-3 and T24 were treated with different concentrations of WM-3835 (0, 10, 20, 30, 40 μmol/L). After 48 hours, the effects of WM-3835 on the proliferation, cell cycle distribution and migration of cells were detected with MTT assay, flow cytometry, scratch and Transwell assay, respectively. The expressions of cyclin D1 (cyclin D1), proliferating nuclear antigen (PCNA), matrix metalloproteinase 9 (MMP9) and neurocadherin (N-cadherin) were detected with Western blotting and real-time quantitative PCR. 【Results】 WM-3835 significantly inhibited the proli-feration of bladder cancer cells in a dose-dependent manner. After treatment with WM-3835, the cycle of UM-UC-3 and T24 cells were blocked in the G0/G1 phase, the proliferation was effectively inhibited, and the migration was significantly wea-kened. The expressions of cyclin-D1, PCNA, MMP9 and N-cadherin were down-regulated. 【Conclusion】 WM-3835 can inhibit the proliferation and migration of bladder cancer cells, and has the potential as a chemotherapeutic agent for bladder cancer.

Application of syringe needle guided transabdominal double-J tube placement in total laparoscopic ileal neobladder surgery / 现代泌尿外科杂志

【Objective】 To explore the application of 1.2 mm×35 mm thin walled, long oblique angle syringe needle guided double-J tube insertion through abdominal wall in total laparoscopic ileal neobladder surgery. 【Methods】 Clinical data of 5 patients undergoing total laparoscopic ileal neobladder surgery in our hospital during Dec.2020 and Jan.2022 were retrospectively analyzed. Under laparoscopy and direct vision, 3 cm above pubic symphysis was taken as the puncture point, and an syringe needle was inserted to establish a channel. After that, a double-J tube was inserted under the guidance of the guide wire through the needle. 【Results】 The double-J tube was successfully implanted in all 5 patients. The time needed was 2-4 min, with an average of 3 min. 【Conclusion】 Under the guidance of a 1.2 mm×35 mm syringe needle, the placement of a double-J tube through the abdominal wall in total laparoscopic ileal neobladder surgery is safe, effective, simple and accurate. It can not only preserve the original operation channel without destroying the pneumoperitoneum, but also shorten the operation time. It is a new auxiliary means in total laparoscopic ileal neobladder surgery.