Bladder cancer (BLCA) exists a profound molecular diversity, with basal and luminal subtypes having different prognostic and therapeutic outcomes. Traditional methods for molecular subtyping are often time-consuming and resource-intensive. This study aims to develop machine learning models using deep learning features from hematoxylin and eosin (H E)-stained whole-slide images (WSIs) to predict basal and luminal subtypes in BLCA. RNA sequencing data and clinical outcomes were downloaded from seven public BLCA databases, including TCGA, GEO datasets, and the IMvigor210C cohort, to assess the prognostic value of BLCA molecular subtypes. WSIs from TCGA were used to construct and validate the machine learning models, while WSIs from Shanghai Tenth People’s Hospital (STPH) and The Affiliated Guangdong Second Provincial General Hospital of Jinan University (GD2H) were used as external validations. Deep learning models were trained to obtained tumor patches within WSIs. WSI level deep learning features were extracted from tumor patches based on the RetCCL model. Support vector machine (SVM), random forest (RF), and logistic regression (LR) were developed using these features to classify basal and luminal subtypes. Kaplan-Meier survival and prognostic meta-analyses showed that basal BLCA patients had significantly worse overall survival compared to luminal BLCA patients (hazard ratio = 1.47, 95
Background:Clear cell renal cell carcinoma (ccRCC) represents the most aggressive form of renal cell carcinoma (RCC), distinguished by pronounced intratumoral heterogeneity, extensive metabolic reprogramming, and marked resistance to conventional therapeutic approaches. This study aimed to comprehensively characterize the cellular heterogeneity, epigenetic regulation, and transcription factor (TF) networks in ccRCC by integrating multi-omics data, and to identify functional key genes with prognostic and therapeutic significance. Methods:Single-cell RNA sequencing (scRNA-seq), single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq), and spatial transcriptomics (ST) were integrated to comprehensively explore cellular heterogeneity, epigenetic regulation, and TF networks in ccRCC. To uncover dynamic alterations in gene expression during cellular differentiation, single-cell pseudotime analysis and gene set enrichment analysis (GSEA) were performed. Furthermore, the functional significance of Y-box binding protein 3 (YBX3) in ccRCC cells was experimentally validated. Results:Single-cell transcriptomic profiling revealed 16 distinct cell populations within the ccRCC tumor microenvironment (TME), including ccRCC tumor cells, exhausted CD8+ T cells (Exhau CD8+ T cells), and macrophages. The scATAC-seq analysis demonstrated cell type-specific chromatin accessibility in immune cells, whereas ccRCC tumor cells exhibited reduced accessibility at immune-related genes, such as cluster of differentiation 2 (CD2). Epigenetic profiling further indicated that differentially accessible chromatin peaks in ccRCC cells were primarily enriched within intronic and exonic regions, implicating key TFs, including hepatocyte nuclear factor 1-beta (HNF1B) and the FOS-JUNB complex. An integrated analysis of scRNA-seq and scATAC-seq datasets identified five critical genes, YBX3, cubilin (CUBN), small nucleolar RNA host gene 8 (SNHG8), acetyl-CoA acyltransferase 2 (ACAA2), and protein kinase AMP-activated catalytic subunit α2 (PRKAA2), that were significantly associated with ccRCC prognosis. Pathway enrichment analysis revealed their involvement in metabolic reprogramming and tumor progression. Functional assays further confirmed that YBX3 knockdown inhibited ccRCC cell proliferation and migration. Conclusions:This study elucidates cellular heterogeneity, the epigenetic regulatory landscape, and the key genes driving ccRCC progression. The integration of multi-omics data offers novel insights into precise diagnostic strategies and therapeutic interventions, highlighting the pivotal role of genes such as YBX3.
Renal clear cell carcinoma (ccRCC) is a highly aggressive and common form of kidney cancer, with limited treatment options for advanced stages. Recent studies have highlighted the importance of the ubiquitin-proteasome system in tumor progression, particularly the role of ubiquitin-conjugating enzyme E2 (UBE2) family members. However, the prognostic significance of UBE2-related genes (UBE2RGs) in ccRCC remains unclear. In this study, bulk RNA-sequencing and single-cell RNA-sequencing data from ccRCC patients were retrieved from the Cancer Genome Atlas and Gene Expression Omnibus databases. Differential expression analysis was performed to identify UBE2RGs associated with ccRCC. A combination of 10 machine learning methods was applied to develop an optimal prognostic model, and its predictive performance was evaluated using area under the curve (AUC) values for 1-, 3-, and 5-year overall survival (OS) in both training and validation cohorts. Functional enrichment analyses of gene ontology and Kyoto Encyclopedia of Genes and Genomes were conducted to explore the biological pathways involved. Correlation analysis was conducted to investigate the association between the risk score and tumor mutational burden (TMB) and immune cell infiltration. Immunotherapy and chemotherapy sensitivity were assessed by immunophenoscore and tumor immune, dysfunction, and exclusion scores to identify potential predictive significance. In vitro, knockdown of the key gene UBE2C in 786-O cells by specific small interfering RNA to validate its impact on apoptosis, migration, cell cycle, migration, invasion of tumor cells, and induction of regulatory T cells (Tregs). Analysis of sc-RNA revealed that UBE2 activity was significantly upregulated in malignant cells, suggesting its role in tumor progression. A three-gene prognostic model comprising UBE2C, UBE2D3, and UBE2T was constructed by Lasoo Cox regression and demonstrated robust predictive accuracy, with AUC values of 0.745, 0.766, and 0.771 for 1-, 3-, and 5-year survival, respectively. The model was validated as an independent prognostic factor in ccRCC. Patients in the high-risk group had a worse prognosis, higher TMB scores, and low responsiveness to immunotherapy. Additionally, immune infiltration and chemotherapy sensitivity analyses revealed that UBE2RGs are associated with various immune cells and drugs, suggesting that UBE2RGs could be a potential therapeutic target for ccRCC. In vitro experiments confirmed that the reduction of UBE2C led to an increase in apoptosis rate, as well as a decrease in tumor cell invasion and metastasis abilities. Additionally, si-UBE2C cells reduced the release of the cytokine Transforming Growth Factor-beta 1 (TGF-β1), leading to a decreased ratio of Tregs in the co-culture system. This study presents a novel three-gene prognostic model based on UBE2RGs that demonstrates significant predictive value for OS, immunotherapy, and chemotherapy in ccRCC patients. The findings underscore the potential of UBE2 family members as biomarkers and therapeutic targets in ccRCC, warranting further investigation in prospective clinical trials.
Influenza is an acute viral respiratory infection that causes mild to severe illness in humans and animals. Current studies show that glucose-regulated protein 78 (GRP78) can exert crucial functions during viral infection; however, the mechanism by which GRP78 regulates influenza A virus (IAV) infection remains unclear. In the present study, we found that IAV infection increased GRP78 expression. Overexpression of GRP78 significantly inhibited IAV replication, as indicated by reduced viral mRNA levels, protein levels, and viral titers. Mechanistically, Type I interferon (IFN) response signaling is upregulated during IAV infection by GRP78. Further study showed that GRP78 interacts with tyrosine kinase 2 (TYK2) and enhances its phosphorylation, thereby activating downstream STAT1/2 and antiviral IFN-stimulated gene (ISG) expression. Collectively, these results demonstrate an important mechanism by which GRP78 exerts in innate antiviral effect in IAV infection. This mechanism could be used as a therapeutic target for anti-influenza treatment.
Clear cell renal cell carcinoma (ccRCC) presents challenges in early diagnosis and effective treatment. In this study, we aimed to establish a prognostic model based on G2M checkpoint-related genes and identify associated clusters in ccRCC through clinical bioinformatic analysis and experimental validation. Utilizing a single-cell RNA dataset (GSE159115) and bulk-sequencing data from The Cancer Genome Atlas (TCGA) database, we analyzed the G2M checkpoint pathway in ccRCC. Differential expression analysis identified 45 genes associated with the G2M checkpoint, leading to the construction of a predictive model with four key genes (E2F2, GTSE1, RAD54L, and UBE2C). The model demonstrated reliable predictive ability for 1-, 3-, and 5-year overall survival, with AUC values of 0.794, 0.790, and 0.794, respectively. Patients in the high-risk group exhibited a worse prognosis, accompanied by significant differences in immune cell infiltration, immune function, TIDE and IPS scores, and drug sensitivities. Two clusters of ccRCC were identified using the "ConsensusClusterPlus" package, cluster 1 exhibited a worse survival rate and was resistant to chemotherapeutic drugs of Axitinib, Erlotinib, Pazopanib, Sunitinib, and Temsirolimus, but not Sorafenib. Targeted experiments on RAD54L, a gene involved in DNA repair processes, revealed its crucial role in inhibiting proliferation, invasion, and migration in 786-O cells. In conclusion, our study offers valuable insights into the molecular mechanisms underlying ccRCC, identifying potential prognostic genes and molecular subtypes associated with the G2M checkpoint. These findings hold promise for guiding personalized treatment strategies in the management of ccRCC.
Objective:To investigate the safety and efficacy of 3D laparoscopy combined with ureteroscopy in the treatment of ureteropelvic junction obstruction complicated with calyx calculi.Methods:The clinical data of 14 patients with renal pelvic ureteral junction obstruction and renal calyx stones who were admitted and operated in Guangdong Second Provincial General Hosptial from December 2019 to January 2022 were analyzed retrospectively. The size of kidney stones, number of stones, operation time, intraoperative blood loss, and one-stage stone removal rate and surgical effect were collected and analyzed. Results:All patients underwent transabdominal 3D laparoscopic nephroplasty. The ureteroscope was placed in the renal pelvis and calyces through the laparoscopic channel to find and remove calyx stone. The mean stone size was (0.89±0.32) cm, the number of stones was 2-6, the operation time was (138±18) min, the intraoperative blood loss was (12±5) ml, the primary stone clearance rate was 100%, The ureteral stent was removed 6-8 weeks after operation, and CT scan revealed hydronephrosis significant reduced or disappeared 3 month after operation, and there was no recurrence of renal calculus or aggravation of hydronephrosis.Conclusion:3D laparoscopy combined with rigid ureteroscopy is safe, effective, minimal invasive and has a high stone removal rate in the treatment of renal pelvic ureteral junction obstruction with calyx calculus, which is a good alternative therapy for partial UPJO with calyx calculi patients.
Objective:To evaluate the safety and efficacy of resectoscope and ureteroscope in the treatment of middle-lower ureteral calculi accompanied with difficulty in entering ureteral opening.Methods:Forty cases of middle-lower ureteral calculi with difficulty in entering ureteral opening patients were admitted in General Hospital of Southern Theatre Command of China People's Liberation Army from March 2008 to December 2019. All patients underwent transurethral resection of the ureter opening, under the guidance of the guide wire, the ureteroscope entered the ureter, and then holmium laser lithotripsy under ureteroscope was performed.Results:All patients were completed the operations successfully. The average operative time was (27±6) min, intraoperative blood loss was (7.0±1.4) ml, the duration of hospitalization postoperative was (3.6±0.9) d. The abdominal plain film was examined and D-J stent was in good position one week after operation, the stone clearance rate was 97.5%. All patients were followed up (4.3±1.0) months after the operations, and intravenous urography and cystourethrography examination showed no ureteral stenosis and reflux.Conclusions:Resectoscope and ureteroscope is safe and effective in the treatment of middle- lower ureteral calculi accompanied with difficulty in entering ureteral opening, it can increase the success rate of endoscopic surgeries and worthy of promotion.
Objective:To investigate the effect of high mobility group protein A2 (HMGA2) gene regulating microRNA (miR)-497-5p in the bladder cancer cells.Methods:Real-time reverse transcription-polymerase chain reaction (RT-qPCR) and Western blot were used to determine HMGA2 expression. Different HMGA2 expression plasmids were transfected into EJ cells, and to detect miR-497-5p and p65 and p-p65 expression in EJ cells of each group. The abilities of proliferation and invasion were detected by colony formation and Transwell assay. The difference between two groups were analyzed by independent- t test. Results:The expression of HMGA2 in 5 bladder cancer cell lines (10.31±0.86, 138.38±19.32, 34.55±3.95, 10.88±0.56, 220.55±15.32) was higher than SV-HUC-1 (2.02±0.32, t=15.648, 12.223, 14.218, 23.793, 24.701, P<0.01). The number of clones and invasive cells in the HMGA2 group (254.33±7.64, 380.67±7.10) were higher than blank group (170.67±14.79, 267±11.37, t=9.768, 17.168, P<0.01). The miR-497-5p mimic group (174.00±1.73, 109.00±3.46) were lower than miR-NC group (189.00±7.55, 219.00±16.64, t=3.354, 11.207, P<0.01). The si-HMGA2+ miR-497-5p inhibitor group (203.00±13.08, 305.00±3.46) were higher than si-HMGA2 group (138.67±19.04, 170.33±24.99, t=4.825, 9.247, P<0.01). The ratio of p-p65/p65 in the HMGA2-transfected group (254.33±7.64) was higher than control group (254.33±7.64, t=18.557, P<0.01). Conclusion:HMGA2 gene negatively regulates miR-497-5p to promote the progression of bladder cancer cells.
Objective:To explore the application value of enhanced recovery after surgery (ERAS) in laparoscopic radical resection of bladder cancer and ileal bladder surgery under modular operation procedures.Methods:A retrospective selection of 42 cases of laparoscopic radical radical resection of bladder cancer and ileal bladder surgery performed by the Department of Urology, General Hospital of Southern Theater Command from January 2017 to December 2019 were divided into two groups according to the different management methods adopted during the perioperative period: ERAS management group and conventional management group, each with 21 cases. Among them, patients in the ERAS management group were managed by ERAS during the perioperative period, and patients in the conventional management group were managed by conventional management during the perioperative period. The postoperative hospital stay, first exhaust time, first defecation time, first time to get out of bed, first liquid food time, postoperative visual analogue scale (VAS) score, as well as transferrin, upper arm circumference, body mass index, plasma albumin, total protein, and total protein were compared between the two groups of patients after surgery. The measurement data conforming to the normal distribution were expressed as mean±standard deviation ( Mean± SD), and the in dependent t-test was used for comparison between groups; the measurement data of non-normal distribution were expressed as the median (interquartile range) [ M( P25, P75)], the independent sample Mann-Whitney U test was used for comparison between groups; the Chi-square test was used for comparison of enumeration data between groups. Results:The postoperative hospital stay in the ERAS group was (8.9±1.8) d, the first exhaust time was (33.4±3.2) h, the first defecation time was (60.3±7.8) h, the first time to get out of bed was (23.1±6.7) h, the first liquid food time was (82.7±18.5) h and postoperative VAS was (1.3±0.6), that were significantly reduced compared with the conventional treatment group [(12.3±2.3) d, (51.4±5.2) h, (73.0±8.1) h, (34.7±8.2) h, (109.7±21.6) h, (3.6±0.8)], the difference were statistically significant ( P<0.05). In the ERAS group, the decreased value of transferrin was [0.8 (-0.4, 2.2) g/L], the decreased value of body mass index was[1.61±0.73], the decreased value of plasma albumin was [3.5±1.5 g/L], the decrease value of total protein was[10.1±5.6 g/L] and the decrease value of prealbumin was [90.5±11.3 mg/L] were significantly lower than those of the conventional management group[(1.9(0.9, 3.6) g/L, (2.32±1.05) kg/m 2, (9.6±2.0) g/L, (16.3±4.9) g/L, (131.3±7.4) g/L], and the difference were statistically significant ( P<0.05). Conclusion:Modular laparoscopic precision resection of bladder cancer and ERAS concept after ileal bladder surgery is beneficial to shorten the hospital stay, reduce postoperative pain, have less impact on the patient′s body loss and immune function, and can speed up the patient′s postoperative recovery.
Background Octamer-binding transcription factor 4 pseudogene 5 (OCT4-pg5) contributes to tumor progression in many cancer types, but contributions to bladder cancer (BC) have not been investigated. Methods Real-time quantity PCR ( RT-qPCR) was performed to measure OCT4-pg5 and OCT4B expressions in different bladder cell lines and different grades of cancer. The effects of OCT4-pg5, OCT4B and miR-145 on proliferation and metastasis were determined by in vitro and in vivo experiments. Luciferase reporter assay was carried out to reveal the interaction among OCT4-pg5, OCT4B and miR-145. Flow cytometry was performed to explore the effects of OCT4-pg5 and OCT4B expression on the cell cycle stage distribution of T24 cells. Results OCT4-pg5 expression was significantly increased in BC cell lines, which was correlated with OCT4B expression and advanced tumor grade. Overexpression of OCT4-pg5 and OCT4B promoted the proliferation and invasion of BC cells, while miR-145 suppressed these activities. Mechanically, OCT4-pg5 3’ untranslated region (3’UTR) competed for miR-145, thereby increasing OCT4B expression. In addition, OCT4-pg5 promoted EMT by activating the Wnt/β-catenin pathway and upregulating the expression levels of matrix metalloproteinases (MMPs) 2 and 9 as well as transcription factors zinc finger E-box binding homeobox (ZEB) 1 and 2. Furthermore, elevated expression of OCT4-pg5 and OCT4B reduced the sensitivity of BC cells to cisplatin by reducing apoptosis and increasing the proportion of cells in G1. Conclusions These findings indicate that OCT4-pg5/miR-145/OCT4B axis promotes the progression of BC by inducing EMT via Wnt/β-catenin pathway and enhances the cisplatin resistance. It could be prospect for the therapeutic approaches for BC.
Objective To investigate octamer-binding transcription factor 4 pseudogene 5 (OCT4-pg5) expression in bladder cancer cell lines and its effect on T24 migration and invasion and the potential mechanism.Methods The real-time quantitative reverse transeriptase-polymerase chain reaction (RT-qPCR) was conducted to detect OCT4-pg5 expression in 5 kinds of bladder cancer cell lines (5637,EJ,BIU-87,T24,TCCSUP) and one normal Bladder epithelial cell line SV-HUC-1.Si-OCT4-pg5 vector and its control vector were transfected into T24 cells by Lipofectamine 2000,and OCT4-pg5 expression was detected by RT-qPCR.Next,wound healing assay and Transwell assay were used to examine the effects of OCT4-pg5 on T24 cell migration and invasion.Moreover,the possible mechanism by which OCT4-pg5 mediated T24 migration and invasion was explored using Western blotting and RT-qPCR.Results In comparison to SV-HUC-1,OCT4-pg5 levels were up-regulated in bladder cancer cell lines,especially in T24 cell (P <0.01).RT-qPCR results showed that OCT4-pg5 espression was obviously down-regulated after being translated with si-OCT4-pg5 vector.OCT4-pg5 down-expression in T24 cell could inhibit cell migration [(28.50 ± 4.08) % and (43.26 5.49) %,P < 0.01] and invasion [(104.50 ± 6.95) and (140.50 ± 8.90) cells,P < 0.01].In addition,down-regulation of OCT4-pg5 significantly reduced Vimentin (0.60 ± 0.06) and β-catenin (0.70 ± 0.08)mRNA expression,and improved E-cadherin mRNA expression (1.50 ± 0.10) when compared with their contral groups (1.00 ± 0.02,1.00 ± 0.04 and 1.00 ± 0.05,respectively,P < 0.01).Moreover,the same results were also obtained by western blotting.Conclusion OCT4-pg5 is overexpression in bladder cancer cells.And OCT4-pg5 down-expression in T24 cell could inhibit cell migration and invasion.OCT4-pg5 mediated T24 migration and invasion probably induced by regulating E-cadherin,Vimentin,β-catenin expression.
目的:探究阿昔替尼(axitinib)对人肾上腺皮质癌SW-13细胞生物学行为的影响.方法:CCK-8法检测不同浓度axitinib对SW-13细胞活力的影响;流式细胞术检测细胞周期分布;Annexin V/PI双染法检测细胞凋亡率;划痕愈合实验及Transwell侵袭实验观察细胞迁移及侵袭的情况;Western blot实验检测细胞中血管内皮生长因子受体2(VEGFR2)、细胞外信号调节蛋白激酶1/2(ERK1/2)和p-ERK1/2的蛋白水平.结果:Axitinib能抑制SW-13细胞活力,阻滞细胞于G2/M期,促进细胞凋亡,并抑制SW-13细胞的迁移及侵袭能力(P<0.05);axitinib可以下调SW-13细胞VEGFR2和p-ERK1/2的蛋白水平(P<0.05).结论:Axitinib可以抑制SW-13细胞生长、阻滞细胞周期、促进细胞凋亡并抑制其迁移和侵袭,其作用机制可能与抑制VEGFR2的表达和减少ERK1/2的磷酸化有关.
Objective To observe the expression of microRNA-497 (miR-497) in bladder cancer cells and investigate its possible functions in epithelial-mesenchymal transition (EMT) of bladder cancer.Methods The expression of miR-497 in bladder cells and human normal bladder tissue were measured by real-time quantitative polymerase chain reaction (RT-qPCR).MiR-497 mimics and miR-497 inhibitor were transfected into bladder cancer EJ cells and RT-qPCR was used to analyze the effect of transfection.Then,morphological changes of cells were observed under the inverted microscope and the wound healing assay,transwell invasion assay were used to detect the cell migration and invasion of bladder cancer EJ cells transfected by miR-497 mimics and miR-497 inhibitor.cytometry.Finally,Western blotting was applied to detect the levels of EMT-related proteins.Results MiR-497 levels were obviously down-regulated in bladder cancer cells (5637,EJ,BIU-87,TCCSUP and T24) in comparison to human bladder pillon biochemical cell (SV-HUC-1),the difference was statistically significant (P =0.000).Compared with negative control,overexpression of miR-497 significantly suppressed EJ cells migration [(74.00 ± 3.61) % vs.(25.33 ± 6.11) %] and invasion [(219 ± 17) cells vs.(109 ± 3) cells],and EJ ceils turned into epithelioid cells morphology,when compared with the control group.Moreover,opposite results were obtained when miR-497 inhibitor was transfected into EJ cells.Compared with mimics NC,the protein expression of E-cadherin was upregulated (P =0.000),while N-cadherin and vimentin downregulated (P =0.001,P =0.000) in miR-497 mimics transfection group.Conclusion MiR-497 may play an important role of EMT in bladder cancer.
Objective?To evaluate the application of two kinds of retroperitoneal laparoscopic nephroureterectomy in upper urinary tract urothelial carcinoma and select the best operative approaches.?Methods?The clinical data of 40 cases of retroperitoneal laparoscopic surgery in patients with upper urinary tract tumor were analyzed. Among the 40 patients, 21 cases (14 males and 7 females) underwent modified retroperitoneal laparoscopic nephroureterectomy combined with transurethral incision of the ureteral orifice (group A), and 19 cases (13 males and 6 females) underwent retroperitoneal laparoscopic nephroureterectomy combined with hypogastrium minor incision and transurethral incision of the ureteral orifice (group B). The operative time, the blood loss, the retention time of drainage tube, the first exhaust time of postoperative and the hospital stay were compared between the two groups.?Results?The operation was successfully completed in all the 40 cases without conversion to open surgery. The operative time in group A was significantly shorter than that in group B (P < 0.01), and the hospital stay was significantly shorter than that in group B (P < 0.05). There were no statistical differences in blood loss, the retention time of drainage tube, and the first exhaust time of postoperative between the two groups (P > 0.05).?Conclusions?Compared with the retroperitoneal laparoscopic nephroureterectomy combined with hypogastrium minor incision, the modified retroperitoneal laparoscopic nephroureterectomy is safe and effective, which can shorten the operative time and reduce hospital saty. Tumor located in renal pelvis and the proximal &middle part of ureter, modified retroperitoneal laparoscopic nephroureterectomy combined with transurethral incision of the ureteral orifice is the most effective method.
Objective To evaluate the feasibility and safety of retroperitoneal laparoscopic "T-Q"three-step procedure for dismembered pyeloplasty in the treatment of ureteropelvic junction obstruction ( UPJO ) . Methods Between January 2015 and January 2016, 5 patients with UPJO were selected . The "T-Q"three-step pyeloplasty was performed through retroperitoneal laparoscopy under general anesthesia .The first step was to cut a "T"incision at 0.5 cm of the distal of the obstruction of ureter , and then to cut a "Q"incision at renal pelvis of the proximal of the obstruction .The obstructed segment half was kept dismembered and under traction , and the lower edge of the dismembered section was interrupted sutured to apply combined traction .And a double-J tube was placed .The second step was to suture the dorsal of the margin of "T"and"Q"with 5-0 absorbable sutures .The posterior wall of renal pelvis and ureter was anastomosed along the point , and the obstructed tissues were still left isolated and semi-transected .The third step was to close the anterior wall of renal pelvis and ureter , and the hemisected obstruction tissue was removed . Results All the surgeries of the 5 patients were completed successfully , and none was converted to open surgery .The operation time was 60-100 min (mean, 70 min).The estimated blood loss was 10-50 ml (mean, 30 ml).After surgery, the recovery time of intestinal function were 1-2 days (mean, 1.6 days), the drainage tube was removed at 2-4 days (mean, 2.6 days), and the postoperative inpatient time was 4-8 days (mean, 6 days).All the patients were followed up for 6-10 months, and symptoms disappeared in 4 cases. Ultrasound examination showed that 3 patients with hydronephrosis from grade Ⅲto grade Ⅰ, 1 case from grade Ⅳto grade Ⅲ, and disappeared in 1 case.No complications such as anastomotic stenosis or leakages were found . Conclusions The treatment of UPJO by retroperitoneal laparoscopic "T-Q"three-step procedure for dismembered pyeloplasty is safe and effective .The improved operation process is easy to master and is worthy of promoting .
Objective: To investigate the effects of modified three-step procedure for anatrophic nephrolithotomy in the treatment of complex staghorn renal calculi. Methods: A total of 22 patients with complex staghorn renal calculi between June 2013 and June 2016 at Department of Urology in Guangzhou General Hospital of Guangzhou Military Command were retrospective analyzed. There were 13 males and 9 females, ranging from 35 to 62 years old with mean age of 47 years. There were 17 patients with dull pain, and 5 patients who were found through physical examinations. Kidney calculi located in left kidney in 15 patients, right kidney in 7 patients. All patients were treated with modified three-step procedure for anatrophic nephrolithotomy. The operation time, blood loss, time of intraoperative renal ischemia, and postoperative complications were recorded. Serum creatinine (Scr), blood urea nitrogen(BUN), β(2)-microglobulin(β(2)-MG), diseased side glomerular filtration rate(GFR) , and renal cortical thickness of the diseased kidney in preoperative and postoperative were compared. The clinical data were compared by paired sample t test between pre-operation and post-operation. Results: The calculi were completely removed in 22 patients, the mean operation time was 84 minutes (50 to 126 minutes), the mean time of intraoperative renal ischemia was 31 minutes (20 to 56 minutes), the mean blood loss was 246 ml (150 to 360 ml). There were no secondary bleeding or urinary fistula happened, the perinephric drainage tub was removed in 3 to 7 days postoperative, the mean hospitalization time was 7 days.Compared with the preoperative, the Scr ((172.7±21.3)μmol/L vs. (146.4±22.8)μmol/L, t=7.197, P=0.000), BUN ((9.2±1.8)mmol/L vs. (8.0±0.5)mmol/L, t=3.798, P=0.001) and β(2)-MG ((203.0±32.0)μg/L vs. (175.6±23.8)μg/L, t=5.009, P=0.000) in postoperative decreased, the diseased side GFR increased ((28.6±4.0) ml/min(31.8±3.3) ml/min, t=-3.521, P=0.002). There were no significant difference of diseased renal cortical thickness between preoperative and postoperative(t=-1.323, P=0.200). There were 12 patients with postoperative pain, 2 patients with vomiting, 3 patients with fever, and 2 patients with wound infection. The follow-up time was 6 months, no residual stones in 22 patients. Conclusion: The modified three-step procedure for anatrophic nephrolithotomy has high stone free rates with less effects on renal function and fewer complications, the method could be widely applied.
The aim of the present study was to explore sunitinib-induced autophagic effects and the specific molecular mechanisms involved, in vitro, using PC-3 and LNCaP human prostate cancer cell lines. Cells were exposed to escalating doses of sunitinib treatment and subsequent cell viability and cell cycle analyses were performed to evaluate the inhibitory effect of sunitinib in vitro. Immunofluorescence staining of microtubule associated protein 1A/1B-light chain 3 (LC3) puncta was employed to assess autophagy levels after sunitinib treatment. Western blot analysis was performed to evaluate variations in the levels of LC3, sequestosome-1, extracellular signal regulated kinase 1/2 (ERK1/2), mammalian target of rapamycin (mTOR), p70 ribosomal protein S6 kinase (p70S6K) and cleaved caspase-3 proteins. The present study revealed that sunitinib treatment inhibited cell growth and triggered autophagy in a dose-dependent manner in both cell lines. In addition, sunitinib activated ERK1/2 and inhibited mTOR/p70S6K signaling. Sunitinib-induced autophagy was notably reversed by ERK1/2 kinase inhibitor, U0126. Furthermore, inhibition of sunitinib-induced autophagy by 3-methyladenine enhanced apoptosis and exhibited improved cell viability, which indicated that sunitinib induces not only apoptosis but also autophagic cell death in prostate cancer cell lines. These results may lead to an improved understanding of the mechanism of sunitinib's cytotoxic action and may provide evidence that combined sunitinib autophagy-regulating treatment may be of benefit to anti-prostate cancer therapy.
Adrenocortical carcinoma (ACC) is a rare, but aggressive endocrine malignancy with a generally poor clinical outcome. There is no effective therapy for advanced and metastatic ACC. In our study, we found that an existing drug (rottlerin) exerted its tumour-suppressive function in ACC. Specifically, rottlerin inhibited cellular proliferation of ACC cell lines (NCI-H295R and SW-13) in a dose- and time-dependent manner. We also found that rottlerin induced cell apoptosis and promoted G0/G1 cell cycle arrest in ACC cell lines. The cellular migration and invasion of ACC cell lines were decreased after treatment with rottlerin. Further, the molecular expression of lipoprotein receptor related protein 6 (LRP6) and β-catenin were down-regulated in rottlerin-treated ACC cells, which indicated that Wnt/β-catenin signaling was involved in the tumour-suppressive function of rottlerin. To further confirm the anti-tumour function of rottlerin, a nude mouse ACC xenograft model was used. The xenograft growth curves and TUNEL assays demonstrated that rottlerin inhibited proliferation and induced apoptosis in the ACC xenograft model. Furthmore, we verified that rottlerin down-regulated the expression of LRP6 and β-catenin in vivo. The ACC cell line and xenograft mouse model data indicated that rottlerin significantly inhibited proliferation and induced apoptosis of ACC cells, likely via suppression of the Wnt/β-catenin signaling pathway. Our study indicated the potential therapeutic utility of rottlerin as a novel and potential chemotherapeutic agent for ACC.
Objective To evaluate the efficacy and safety of transurethral thulium-Yag laser(Tm-Yag Laser) resection of bladder tumor in the treatment of non-muscle invasive bladder cancer(NMIBC).Methods The clinical data of 186 patients who underwent transurethral resection with pathologically identified of NMIBC were retrospectively analyzed.76 cases and 110 cases were in the transurethral resection of bladder cancer Tm-Yag Laser group and TURBT group,respectively.The operative time,intraoperative blood loss,incidence of obturator nerve reflex,days for urethral catheterization,duration of hospitalization after surgery,detection rate of muscle layer in postoperative pathologic examination and recurrence between the two groups were compared.All patients were followed up for 24 months.Regularly gemcitabine intravesical instillation chemotherapy and cystoscopy were performed postoperation.Results The operative time [(27.08±5.56) min vs.(25.55±5.37) min,P>0.05]and intraoperative blood loss [(14.23±4.05) mL vs.(15.10±3.24) mL,P>0.05]showed no differences between the two groups.The incidence of obturator nerve reflex in Tm-Yag laser group was lower than that in TURBT group (0.0% vs.5.5 %,x2=4.28,P=0.038).The days for urethral catheterization [(3.48±1.05) d vs.(4.02±1.14) d,t=3.328,P=0.001]and the duration of hospitalization after surgery [(4.47±1.08) d vs.(5.02±1.13) d,t=3.350,P=0.001]in Tm-Yag laser group were significantly shorter than those in TURBT group.In Tm-Yag laser group,the detection rate of muscle layer in postoperative pathologic examination was higher than that in TURBT group(x2=14.96,P=0.001).The total rate of tumor recurrence in Tm-Yag laser group was significantly lower than that in TURBT group(13.2 % vs.25.5%,x2=4.18,P=0.041).Conclusion Transurethral Tm-Yag laser is safe and effective in the treatment of NMIBC.It can avoid the incidence of complications and reduce tumor recurrence rate,which is worthy of promotion.
OBJECTIVE:To investigate the feasibility of establishing a model of allograft penile transplantation in adult beagle dogs and explore the conditions for constructing a stable animal model of penis transplant.METHODS:Following the principles of similarity, repeatability, feasibility, applicability, and controllability in the construction of experimental animal models, we compared the major anatomic features of the penis of 20 adult beagle dogs with those of 10 adult men. Using microsurgical techniques, we performed cross-transplantation of the penis in the 20 (10 pairs) beagle dogs and observed the survival rate of the transplanted penises by FK506+MMF+MP immune induction. We compared the relevant indexes with those of the 10 cases of microsurgical replantation of the amputated penis.RESULTS:High similarities but no statistically significant differences were observed in penile anatomic features between the 20 beagle dogs and 10 men. All the 10 cases of cross-transplantation of the penis were successfully completed in the 20 beagle dogs, of which the transplanted glans survived with normal micturition in 12 but developed necrosis in the other 8; the success rate of one-time venous anastomosis was 95.0% (38/40) and that of one-time arterial anastomosis was 87.5% (35/40), with an average vascular anastomosis time of (71.0±9.0) minutes, a mean operation time of (133.0±10.3) minutes, and a mean blood loss of (135.8±41.4) ml. In the 10 cases of penile replantation, the success rate of one-time venous anastomosis was 100% (20/20) and that of one-time arterial anastomosis was 90.0% (18/20), with an average vascular anastomosis time of (65.0±7.9) minutes, a mean operation time of (117.4±10.0) minutes, and a mean blood loss of (85.0±10.8) ml. In the 12 cases of replantation of the amputated penis, the success rate of one-time venous anastomosis was 100% (24/24) and that of one-time arterial anastomosis was 95.8% (23/24), with an average vascular anastomosis time of (79.0±17.6) minutes, a mean operation time of (125.0±20.6) minutes, and a mean blood loss of (140.0±44.3) ml. No statistically significant differences were found in the relevant indexes among the three groups.CONCLUSIONS:The anatomic structure of the corpus cavernosum penis of beagle dogs is highly similar to that of men, almost the same in cross-section anatomy. Microsurgical replantation and allograft transplantation of the penis were both successfully performed in beagle dogs, which showed similar operative indexes to those of human penile replantation. The construction of the allograft penile transplantation model in adult beagle dogs is feasible clinically, with the advantages of operability and repeatability.