Development and validation of a nomogram to predict lymph node metastasis in patients with progressive muscle-invasive bladder cancer.

Purpose: To develop and validate a nomogram for preoperative prediction of lymph node metastasis in patients with progressive muscle-invasive bladder cancer. Materials and methods: We retrospectively recruited patients, divided them into training and validation cohorts, and gathered patient demographics, pathology data of transurethral bladder tumor resection specimens, imaging findings, and laboratory information. We performed logistic regression analyses, both single-variable and multi-variable, to investigate independent preoperative risk variables and develop a nomogram. Both internal and external validations were conducted to evaluate the predictive performance of this nomogram. Results: The training cohort consisted of 144 patients with advanced muscle-invasive bladder cancer, while the validation cohort included 62 individuals. The independent preoperative risk factors identified were tumor pathology grade, platelet count, tumor size on imaging, and lymph node size, which were utilized to develop the nomogram. The model demonstrated high predictive accuracy, as evidenced by the area under the receiver operating characteristic curve values of 0.898 and 0.843 for the primary and external validation cohorts, respectively. Calibration curves and decision curve analysis showed a good performance of the nomogram in both cohorts, indicating its high clinical applicability. Conclusion: A nomogram for preoperative prediction of lymph node metastasis in patients with advanced muscle-invasive bladder cancer was successfully developed; its accuracy, reliability, and clinical value were demonstrated. This new tool would facilitate better clinical decisions regarding whether to perform complete lymph node dissection in cases of radical cystectomy.

Predictive model of positive surgical margins after radical prostatectomy based on Bayesian network analysis.

Objective: This study aimed to analyze the independent risk factors for marginal positivity after radical prostatectomy and to evaluate the clinical value of the predictive model based on Bayesian network analysis. Methods: We retrospectively analyzed the clinical data from 238 patients who had undergone radical prostatectomy, between June 2018 and May 2022. The general clinical data, prostate specific antigen (PSA)-derived indicators, puncture factors, and magnetic resonance imaging (MRI) characteristics were included as predictive variables, and univariate and multivariate analyses were conducted. We established a nomogram model based on the independent predictors and adopted BayesiaLab software to generate tree-augmented naive (TAN) and naive Bayesian models based on 15 predictor variables. Results: Of the 238 patients included in the study, 103 exhibited positive surgical margins. Univariate analysis revealed that PSA density (PSAD) (P = 0.02), Gleason scores for biopsied tissue (P = 0.002) and the ratio of positive biopsy cores (P < 0.001), preoperative T staging (P < 0.001), and location of abnormal signals (P = 0.002) and the side of the abnormal signal (P = 0.009) were all statistically significant. The area under curve (AUC) of the established nomogram model based on independent predictors was 73.80%, the AUC of the naive Bayesian model based on 15 predictors was 82.71%, and the AUC of the TAN Bayesian model was 80.80%. Conclusion: The predictive model of positive resection margin after radical prostatectomy based on Bayesian network demonstrated high accuracy and usefulness.

Prediction model of gleason score upgrading after radical prostatectomy based on a bayesian network.

OBJECTIVE: To explore the clinical value of the Gleason score upgrading (GSU) prediction model after radical prostatectomy (RP) based on a Bayesian network. METHODS: The data of 356 patients who underwent prostate biopsy and RP in our hospital from January 2018 to May 2021 were retrospectively analysed. Fourteen risk factors, including age, body mass index (BMI), total prostate-specific antigen (tPSA), prostate volume, total prostate-specific antigen density (PSAD), the number and proportion of positive biopsy cores, PI-RADS score, clinical stage and postoperative pathological characteristics, were included in the analysis. Data were used to establish a prediction model for Gleason score elevation based on the tree augmented naive (TAN) Bayesian algorithm. Moreover, the Bayesia Lab validation function was used to calculate the importance of polymorphic Birnbaum according to the results of the posterior analysis and to obtain the importance of each risk factor. RESULTS: In the overall cohort, 110 patients (30.89%) had GSU. Based on all of the risk factors that were included in this study, the AUC of the model was 81.06%, and the accuracy was 76.64%. The importance ranking results showed that lymphatic metastasis, the number of positive biopsy cores, ISUP stage and PI-RADS score were the top four influencing factors for GSU after RP. CONCLUSIONS: The prediction model of GSU after RP based on a Bayesian network has high accuracy and can more accurately evaluate the Gleason score of prostate biopsy specimens and guide treatment decisions.

Mesenchymal stem cells-derived exosomal microRNA-139-5p restrains tumorigenesis in bladder cancer by targeting PRC1.

microRNAs (miRNAs) can be delivered to tumor cells where they exert their function via mesenchymal stem cells (MSCs)-derived exosomes. This study investigated exosomal transfer of miR-139-5p to bladder cancer cells and their role in the regulation of tumorigenesis. The dysregulation of polycomb repressor complex 1 (PRC1) in bladder cancer was characterized by RNA quantification, and its functional significance in bladder cancer cells was identified by loss-of-function experiments. We predicted the miR-139-5p that could play a role in regulating PRC1, which was further verified using dual-luciferase reporter gene assay. Next, we altered the expression of miR-139-5p and PRC1 in bladder cancer cells to identify their functions in cancer progression. Bladder cancer cells were co-cultured with exosomes isolated from human umbilical cord mesenchymal stem cells (hUCMSCs) over-expressing miR-139-5p. The intercellular transfer of miR-139-5p along with in vitro and in vivo functions was determined using gain- and loss-of-function approaches. Our results revealed that PRC1 levels were increased in bladder cancer tissues and cells, and silencing PRC1 appeared to impede the cell proliferation, migration, and invasion potentials. In addition, miR-139-5p was observed to be down-regulated in bladder cancer, which targeted PRC1 and reduced its expression, hereby resulting in ameliorated tumorigenic characteristics of bladder cancer cells in vitro. Furthermore, we noted that miR-139-5p from hUCMSCs-derived exosomes could be transferred into bladder cancer cells to down-regulate the PRC1 expression. Moreover, hUCMSCs-derived exosomal miR-139-5p conferred a suppressive role on bladder cancer development in vitro and in vivo. These data together supported the tumor-inhibiting role of MSCs-derived exosomal miR-139-5p in bladder cancer, highlighting a promising therapeutic strategy.

5G ultra-remote robot-assisted laparoscopic surgery in China.

BACKGROUND: 5G communication technology has been applied to several fields in telemedicine, but its effectiveness, safety, and stability in remote laparoscopic telesurgery have not been established. Here, we conducted four ultra-remote laparoscopic surgeries on a swine model under the 5G network. The aim of the study was to investigate the effectiveness, safety, and stability of the 5G network in remote laparoscopic telesurgery. METHODS: Four ultra-remote laparoscopic surgeries (network communication distance of nearly 3000 km), including left nephrectomy, partial hepatectomy, cholecystectomy, and cystectomy, were performed on a swine model with a 5G wireless network connection using a domestically produced "MicroHand" surgical robot. The average network delay, operative time, blood loss, and intraoperative complications were recorded. RESULTS: Four laparoscopic telesurgeries were safely performed through a 5G network, with an average network delay of 264 ms (including a mean round-trip transporting delay of 114 ms and a 1.20% data packet loss ratio). The total operation time was 2 h. The total blood loss was 25 ml, and no complications occurred during the procedures. CONCLUSIONS: Ultra-remote laparoscopic surgery can be performed safely and smoothly with 5G wireless network connection using domestically produced equipment. More importantly, our model can provide insights for promoting the future development of telesurgery, especially in areas where Internet cables are difficult to lay or cannot be laid.

A meta-analysis of the efficacy and safety of PD-1/PD-L1 immune checkpoint inhibitors as treatments for metastatic bladder cancer.

BACKGROUND: This article is a meta-analysis aiming to systematically assess the efficacy and safety profiles of PD-1/PD-L1 inhibitors in patients with advanced or metastatic bladder cancer. METHODS: We extracted and examined data from phase I, II, and III clinical trials from the Medline, Embase, and the Cochrane Library, which included patients with metastatic bladder cancer who were treated with PD-1/PD-L1 inhibitors. We performed a meta-analysis to investigate several indexes of efficacy and safety, including the objective response rate (ORR), 1-year overall survival (OS) rate, 1-year progression-free survival (PFS) rate, and adverse event (AE) rate of immune checkpoint inhibitors. The material data were calculated and pooled using The R Project for Statistical Computing and Review Manager 5.3. RESULTS: After excluding ineligible records, 14 clinical trials were included in our analysis. The pooled frequencies of all-grade AEs and grade ≥3 AEs were 0.63 (95% CI 0.61-0.65, P=0.34) and 0.14 (95% CI 0.11-0.17, P=0.0072), respectively. The summary ORR was 0.21 (95% CI 0.18-0.24 P=0.07), and the 1-year OS and 1-year PFS rates were 0.48 (95% CI 0.42-0.54 P=0.0013) and 0.21 (95% CI 0.16-0.26 P=0.04), respectively. The OR of ORR between the PD-L1-positive and -negative groups was 3.09 (95% CI 2.01-4.75, P=0.08). CONCLUSION: The PD-1/PD-L1 therapy showed appropriate efficacy and acceptable incidence of treatment-related AEs. In addition, the level of discrimination of PD-L1 expression might be related to the effect of the PD-1/PD-L1 inhibitors, and patients displaying positive expression might experience a better curative effect than patients displaying negative expression.

Bisphenol S Triggers the Migration and Invasion of Pheochromocytoma PC12 Cells via Estrogen-Related Receptor α.

Pheochromocytoma (PCC) is a tumor of the adrenal medulla for which surgical resection is the only therapy approach. Risk factors responsible for the tumorigenesis and progression of PCC are not well illustrated. Our present study revealed that an industrial chemical, bisphenol S (BPS), can promote the migration and invasion of PCC PC12 cells, which was evidenced by the upregulation of fibronectin (FN) and matrix metalloproteinases (MMP-2 and MMP-9). The inhibitor of estrogen-related receptor α (ERRα), while not estrogen receptor α/ß (ERα/ß) or G protein-coupled estrogen receptor (GPER), can attenuate BPS-induced cell migration. Mechanically, BPS can increase the binding between ERRα and promoter of FN1 and then induce the expression of FN in PC12 cells. Further, BPS can induce the expression of miR-10b in PC12 cells via ERRα. The upregulated miR-10b inhibited the expression of KLF4, which can suppress the migration and invasion of cancer cells. BPS can trigger the mRNA and protein expression of ERRα in PC12 cells via a time-dependent manner. Collectively, our study revealed that nanomolar BPS can trigger the migration and invasion of PC12 cells via activation and upregulation of ERRα.

miR-146a down-regulation alleviates H2O2-induced cytotoxicity of PC12 cells by regulating MCL1/JAK/STAT pathway : miR-146a down-regulation relieves H2O2-induced PC12 cells cytotoxicity by MCL1/JAK/STAT.

Oxidative stress and miRNAs have been confirmed to play an important role in neurological diseases. The study aimed to explore the underlying effect and mechanisms of miR-146a in H2O2-induced injury of PC12 cells. Here, PC12 cells were stimulated with 200 µM of H2O2 to construct oxidative injury model. Cell injury was evaluated on the basis of the changes in cell viability, migration, invasion, apoptosis, and DNA damage. Results revealed that miR-146a expression was up-regulated in H2O2-induced PC12 cells. Functional analysis showed that down-regulation of miR-146a alleviated H2O2-induced cytotoxicity in PC12 cells. Dual-luciferase reporter and western blot assay verified that MCL1 was a direct target gene of miR-146a. Moreover, anti-miR-146a-mediated suppression on cell cytotoxicity was abated following MCL1 knockdown in H2O2-induced PC12 cells. Furthermore, MCL1 activated JAK/STAT signaling pathway and MCL1 overexpression attenuated H2O2-induced cytotoxicity in PC12 cells by JAK/STAT signaling pathway. In conclusion, this study suggested that suppression of miR-146a abated H2O2-induced cytotoxicity in PC12 cells via regulating MCL1/JAK/STAT pathway.

Development of biocompatible and VEGF-targeted paclitaxel nanodrugs on albumin and graphene oxide dual-carrier for photothermal-triggered drug delivery in vitro and in vivo.

In this study, we performed the characterization and synthesis of biocompatible and targeted albumin and graphene oxide (GO) dual-carrier paclitaxel (PTX) nanoparticles for photothermal-triggered tumor therapy. PTX absorbed on GO nanosheets as cores were coated with human serum albumin (HSA), following surface conjugation with monoclonal antibodies (mAb) against vascular endothelial growth factor (VEGF; denoted as mAbVEGF) via polyethylene glycol linker to form targeted nanoparticles (PTX-GHP-VEGF). The spherical nanoparticles were 191±5 nm in size with good stability and biocompatibility. GO functioned as the first carrier and a near infrared absorber that can generate photothermal effects under 5-minute 808-nm laser irradiation to thermal trigger the release of PTX from the second carrier HSA nanoparticles. The mechanism of thermal-triggered drug release was also investigated preliminarily, in which the heat generated by GO induced swelling of PTX-GHP-VEGF nanoparticles which released the drugs. In vitro studies found that PTX-GHP-VEGF can efficiently target human SW-13 adrenocortical carcinoma cells as evaluated by confocal fluorescence microscopy as well as transmission electron microscopy, and showed an obvious thermal-triggered antitumor effect, mediated by apoptosis. Moreover, PTX-GHP-VEGF combined with near infrared irradiation showed specific tumor suppression effects with high survival rate after 100 days of treatment. PTX-GHP-VEGF also demonstrated high biosafety with no adverse effects on normal tissues and organs. These results highlight the remarkable potential of PTX-GHP-VEGF in photothermal controllable tumor treatment.