Urinary exosomes: Potential diagnostic markers and application in bladder cancer.

Background: The exosome is a critical component of the intercellular communication., playing a vital role in regulating cell function. These small vesicles contain proteins, mRNAs, miRNAs, and lncRNAs, surrounded by lipid bilayer substances. Most cells in the human body can produce exosomes, released into various body fluids such as urine, blood, and cerebrospinal fluid. Bladder cancer is the most common tumor in the urinary system, with high recurrence and metastasis rates. Early diagnosis and treatment are crucial for improving patient outcomes. Methods: This study employed the PubMed search engine to retrieve publicly accessible data pertaining to urinary exosomes. Results: We summarize the origins and intricate biological characteristics of urinary exosomes, the introduction of research methodologies used in basic experiments to isolate and analyze these exosomes, the discussion of their applications and progress in the diagnosis and treatment of bladder cancer, and the exploration of the current limitations associated with using urinary exosomes as molecular biomarkers for diagnosing bladder cancer. Conclusion: Exosomes isolated from urine may be used as molecular biomarkers for early detection of bladder cancer.

Machine learning identifies the role of SMAD6 in the prognosis and drug susceptibility in bladder cancer.

BACKGROUND: Bladder cancer (BCa) is among the most prevalent malignant tumors affecting the urinary system. Due to its highly recurrent nature, standard treatments such as surgery often fail to significantly improve patient prognosis. Our research aims to predict prognosis and identify precise therapeutic targets for novel treatment interventions. METHODS: We collected and screened genes related to the TGF-ß signaling pathway and performed unsupervised clustering analysis on TCGA-BLCA samples based on these genes. Our analysis revealed two novel subtypes of bladder cancer with completely different biological characteristics, including immune microenvironment, drug sensitivity, and more. Using machine learning classifiers, we identified SMAD6 as a hub gene contributing to these differences and further investigated the role of SMAD6 in bladder cancer in the single-cell transcriptome data. Additionally, we analyzed the relationship between SMAD6 and immune checkpoint genes. Finally, we performed a series of in vitro assays to verify the function of SMAD6 in bladder cancer cell lines. RESULTS: We have revealed two novel subtypes of bladder cancer, among which C1 exhibits a worse prognosis, lower drug sensitivity, a more complex tumor microenvironment, and a 'colder' immune microenvironment compared to C2. We identified SMAD6 as a key gene responsible for the differences and further explored its impact on the molecular characteristics of bladder cancer. Through in vitro experiments, we found that SMAD6 promoted the prognosis of BCa patients by inhibiting the proliferation and migration of BCa cells. CONCLUSION: Our study reveals two novel subtypes of BCa and identifies SMAD6 as a highly promising therapeutic target.

Cellular-level analyses of SCN5A mutations in left ventricular noncompaction cardiomyopathy suggest electrophysiological mechanisms for ventricular tachycardia.

Left ventricular noncompaction cardiomyopathy (LVNC) is a cardiovascular disease characterized by arrhythmia and heart failure. In this study, LVNC myocardial samples were collected from patients who underwent heart transplantation and were analyzed using exome sequencing. Approximately half of the LVNC patients carried SCN5A variants, which are associated with clinical symptoms of ventricular tachycardia. To investigate the electrophysiological functions of these SCN5A variants and the underlying mechanism by which they increase arrhythmia susceptibility in LVNC patients, functional evaluations were conducted in CHO-K1 cells and human embryonic stem cell-derived cardiomyocytes (hESC-CMs) using patch-clamp or microelectrode array (MEA) techniques. These findings demonstrated that these SCN5A mutants exhibited gain-of-function properties, leading to increased channel activation and enhanced fast inactivation in CHO-K1 cells. Additionally, these mutants enhanced the excitability and contractility of the cardiomyocyte population in hESC-CMs models. All SCN5A variants induced fibrillation-like arrhythmia and increased the heart rate in cardiomyocytes. However, the administration of Lidocaine, an antiarrhythmic drug that acts on sodium ion channels, was able to rescue or alleviate fibrillation-like arrhythmias and secondary beat phenomenon. Based on these findings, it is speculated that SCN5A variants may contribute to susceptibility to arrhythmia in LVNC patients. Furthermore, the construction of cardiomyocyte models with SCN5A variants and their application in drug screening may facilitate the development of precise therapies for arrhythmia in the future.

A low-frequency normal conducting cavity with higher-order mode damping for fourth-generation synchrotron radiation sources.

The utilization of a low-frequency (<200 MHz) RF system in storage facilitates the attainment of ultra-low emittances in synchrotron light sources through on-axis injection. This paper focuses on the development of a low-frequency normal conducting (NC) cavity with higher-order mode (HOM) damping for fourth-generation synchrotron light sources. We propose a novel approach to achieve efficient HOM damping in a NC cavity by optimizing the lowest frequency HOM and implementing a beam-line absorber. Notably, unlike conventional NC cavities, the presence of a large beam tube for the beam-line absorber does not compromise the accelerating performance in a coaxial resonant cavity, enabling effective HOM damping while maintaining a high shunt impedance. Through simulations, the prototype design of a 166.6 MHz HOM-damped cavity demonstrates a fundamental mode impedance of ∼8 MΩ, with longitudinal and transverse HOM impedances below 2.0 and 50 kΩ/m, respectively.

Efficacy of atorvastatin administration after surgery in patients with chronic subdural hematoma.

To explore the clinical efficacy of atorvastatin administration after surgery in patients with chronic subdural hematoma. We conducted a retrospective study to analyze the clinical data of patients with chronic subdural hematoma. Patients receiving atorvastatin treatment after surgery were divided into the study group while others were divided into the control group. As the primary outcome, we compared the hematoma recurrence rate. The secondary outcomes were the remaining volume of hematoma and the activities of daily living (Barthel index) score at 3 months after discharge. A total of 53 patients were included in the study: 30 patients in the study group (n = 30) and 23 patients in the control group (n = 23). The baseline clinical data were similar in the 2 groups (P > .05). Four patients had recurrence of hematoma in the study group, while 5 patients had recurrence of hematoma in the control group [4/30 (13.3%) versus 5/23 (21.7%), P = .661] at 3 months after discharge. The mean remaining volume of hematoma was 12.10 ±â€…8.80 mL in the study group and 17.30 ±â€…9.50 mL in the control group at 3 months after discharge, respectively. The remaining volume of hematoma in the study group was less than that in the control group (P = .045).The activities of daily living score in the study group were higher than those in the control group (97.83 ±â€…4.48 vs 94.78 ±â€…5.73, P = .034) at 3 months after discharge. Atorvastatin administration after surgery barely reduce the recurrence rate of chronic subdural hematoma, however, reduced the remaining volume of hematoma and improved neurological function.

Methionine orchestrates the metabolism vulnerability in cisplatin resistant bladder cancer microenvironment.

Metabolism vulnerability of cisplatin resistance in BCa cells remains to be discovered, which we applied integrated multi-omics analysis to elucidate the metabolism related regulation mechanism in bladder cancer (BCa) microenvironment. Integrated multi-omics analysis of metabolomics and proteomics revealed that MAT2A regulated methionine metabolism contributes to cisplatin resistance in BCa cells. We further validated MAT2A and cancer stem cell markers were up-regulated and circARHGAP10 was down-regulated through the regulation of MAT2A protein stability in cisplatin resistant BCa cells. circARHGAP10 formed a complex with MAT2A and TRIM25 to accelerate the degradation of MAT2A through ubiquitin-proteasome pathway. Knockdown of MAT2A through overexpression of circARHGAP10 and restriction of methionine up-take was sufficient to overcome cisplatin resistance in vivo in immuno-deficiency model but not in immuno-competent model. Tumor-infiltrating CD8+ T cells characterized an exhausted phenotype in tumors with low methionine. High expression of SLC7A6 in BCa negatively correlated with expression of CD8. Synergistic inhibition of MAT2A and SLC7A6 could overcome cisplatin resistance in immuno-competent model in vivo. Cisplatin resistant BCa cells rely on methionine for survival and stem cell renewal. circARHGAP10/TRIM25/MAT2A regulation pathway plays an important role in cisplatin resistant BCa cells while circARHGAP10 and SLC7A6 should be evaluated as one of the therapeutic target of cisplatin resistant BCa.

Knock-down of PGM1 inhibits cell viability, glycolysis, and oxidative phosphorylation in glioma under low glucose condition via the Myc signaling pathway.

PGM1 is an essential enzyme for glucose metabolism and is involved in cell viability, proliferation, and metabolism. However, the regulatory role of PGMI in glioma progression and the relation between gliomas and PGM1 expression are still unclear. This study aimed to explore the role of PGM1 in glycolysis and oxidative phosphorylation in glioma. Correlation and enrichment analyses of PGM1 in glioma cells were explored in TCGA database and two hospital cohorts. The cell viability, glycolysis, and oxidative phosphorylation were investigated in PGM1 knock-down and overexpression situations. Higher PGM1 expression in glioma patients was associated with a poor survival rate. However, knock-down of PGM1 reduced glioma cell viability, glycolysis, and oxidative phosphorylation under low glucose condition. Moreover, it suppressed tumor growth in vivo. On the other hand, PGM1 overexpression promoted glioma cell viability, glycolysis, and oxidative phosphorylation under low glucose condition by a Myc positive feedback loop. Glioma patients with higher PGM1 expression were associated with poor survival rates. Additionally, PGM1 could promote glioma cell viability, glycolysis, and oxidative phosphorylation under low glucose condition via a myc-positive feedback loop, suggesting PGM1 could be a potential therapeutic target for gliomas.

Development of a Molecular-Subtype-Associated Immune Prognostic Signature That Can Be Recognized by MRI Radiomics Features in Bladder Cancer.

Background: Bladder cancer (BLCA) is highly heterogeneous with distinct molecular subtypes. This research aimed to investigate the heterogeneity of different molecular subtypes from a tumor microenvironment perspective and develop a molecular-subtype-associated immune prognostic signature that can be recognized by MRI radiomics features. Methods: Individuals with BLCA in The Cancer Genome Atlas (TCGA) and IMvigor210 were classified into luminal and basal subtypes according to the UNC classification. The proportions of tumor-infiltrating immune cells (TIICs) were examined using The Cell Type Identification by Estimating Relative Subsets of RNA Transcripts algorithm. Immune-linked genes that were expressed differentially between luminal and basal subtypes and associated with prognosis were selected to develop the immune prognostic signature (IPS) and utilized for the classification of the selected individuals into low- and high-risk groups. Functional enrichment analysis (GSEA) was performed on the IPS. The data from RNA-sequencing and MRI images of 111 BLCA samples in our center were utilized to construct a least absolute shrinkage and selection operator (LASSO) model for the prediction of patients' IPSs. Results: Half of the TIICs showed differential distributions between the luminal and basal subtypes. IPS was highly associated with molecular subtypes, critical immune checkpoint gene expression, prognoses, and immunotherapy response. The prognostic value of the IPS was further verified through several validation data sets (GSE32894, GSE31684, GSE13507, and GSE48277) and meta-analysis. GSEA revealed that some oncogenic pathways were co-enriched in the group at high risk. A novel performance of a LASSO model developed as per ten radiomics features was achieved in terms of IPS prediction in both the validation (area under the curve (AUC): 0.810) and the training (AUC: 0.839) sets. Conclusions: Dysregulation of TIICs contributed to the heterogeneity between the luminal and basal subtypes. The IPS can facilitate molecular subtyping, prognostic evaluation, and personalized immunotherapy. A LASSO model developed as per the MRI radiomics features can predict the IPSs of affected individuals.

Bladder cancer-associated microbiota: Recent advances and future perspectives.

Recent evidence suggests that the human genitourinary microbiome plays a significant role in mediating the development and progression of urological tumors, including bladder cancer (BC). Clinicians widely recognize the role of Bacille Calmette Guérin (BCG), an attenuated Mycobacterium tuberculosis vaccine, in the management of intermediate- and high-risk NMIBC. However, compared to the large body of evidence on the gut microbiota and gastrointestinal tumors, limited information is available about the interaction between BC and the genitourinary microbiome. This is an expanding field that merits further investigation. Urologists will need to consider the potential impact of the microbiome in BC diagnosis, prevention of recurrence and progression, and treatment prospects in the future. This review highlights the approaches adopted for microbiome research and the findings and inadequacies of current research on BC.

Metabolic-associated signature and hub genes associated with immune microenvironment and prognosis in bladder cancer.

The relationship between metabolism and immune microenvironment remains to be studied in bladder cancer (BCa). We aimed to construct a metabolic-associated signature for prognostic prediction and investigate its relationship with the immune microenvironment in BCa. The RNA expression of metabolism associated genes was obtained from a combined data set including The Cancer Genome Atlas, GSE48075, and GSE13507 to divide BCa patients into different clusters. A metabolic-associated signature was constructed using the differentially expressed genes between clusters in the combined data set and validated in the IMvigor210 trial and our center. The composition of tumor-infiltrating immune cells (TIICs) was evaluated using the single-sample Gene Set Variation Analysis. BCa patients in Cluster A or high-risk level were associated with advanced clinicopathological features and poor survival outcomes. The percentage of high-risk patients was significantly lower in patients responding to anti-PD-L1 treatment. Compared with low-risk patients, the IC50 values of cisplatin and gemcitabine were significantly lower in high-risk patients. Thiosulfate transferase (TST) and S100A16 were significantly associated with clinicopathological features and prognosis. Downregulation of TST promoted BCa cell invasion, migration, and epithelial-to-mesenchymal transition, which are inhibited by downregulation of S100A16. CD8 + T cells, neutrophils, and dendritic cells had higher infiltration in the TST low-level and the S100A16 high-level. Furthermore, loss of function TST and S100A16 significantly affected the expression of PD-L1 and CD47. The metabolic-associated signature can stratify BCa patients into distinct risk levels with different immunotherapeutic susceptibility and survival outcomes. Metabolism disorder promoted the dysregulation of immune microenvironment, thus contributing to immunosuppression.

A Minimum Cost Consensus-Based Failure Mode and Effect Analysis Framework Considering Experts' Limited Compromise and Tolerance Behaviors.

This study proposes a minimum cost consensus-based failure mode and effect analysis (MCC-FMEA) framework considering experts' limited compromise and tolerance behaviors, where the first behavior indicates that a failure mode and effect analysis (FMEA) expert might not tolerate modifying his/her risk assessment without limitations, and the second behavior indicates that an FMEA expert will accept risk assessment suggestions without being paid for any cost if the suggested risk assessments fall within his/her tolerance threshold. First, an MCC-FMEA with limited compromise behaviors is presented. Second, experts' tolerance behaviors are added to the MCC-FMEA with limited compromise behaviors. Theoretical results indicate that in some cases, this MCC-FMEA with limited compromise and tolerance behaviors has no solution. Thus, a minimum compromise adjustment consensus model and a maximum consensus model with limited compromise behaviors are developed and analyzed, and an interactive MCC-FMEA framework, resulting in an FMEA problem consensual collective solution, is designed. A case study, regarding the assessment of COVID-19-related risk in radiation oncology, and a detailed sensitivity and comparative analysis with the existing FMEA approaches are provided to verify the effectiveness of the proposed approach to FMEA consensus-reaching.

CD8A as a Prognostic and Immunotherapy Predictive Biomarker Can Be Evaluated by MRI Radiomics Features in Bladder Cancer.

As an important member of T cytotoxic pathway-related genes, CD8a molecule (CD8A) may be a useful biomarker of immunotherapeutic response and immune cell infiltration. We aimed to investigate the clinical predictive value of CD8A in prognosis and tumor microenvironment (TME) and preoperatively predict the expression of CD8A using radiogenomics in bladder cancer (BCa). Among 12 T cytotoxic pathway-related genes, CD8A was a novel protective gene and had the highest correlations with T cells and Macrophages M1 in BCa. In advanced cancer patients treated with immunotherapy, low CD8A expression was associated with immunotherapeutic failure and poor survival outcomes. CD8A expression was highly related to tumor mutation burden, critical immune checkpoint genes and several types of tumor-infiltrating immune cells, predicting effective response to immunotherapy. The preoperative MRI radiomics features and RNA-sequence data of 111 BCa samples were used to develop a radiomics signature that achieved good performance in the prediction of CD8A expression in both the training (area under curve (AUC): 0.857) and validation sets (AUC: 0.844). CD8A is a novel indicator for predicting the prognosis and immunotherapeutic response in BCa. A radiomics signature has the potential to preoperatively predict the expression of CD8A in BCa patients.

PHGDH Inhibits Ferroptosis and Promotes Malignant Progression by Upregulating SLC7A11 in Bladder Cancer.

Background: Bladder cancer (BCa) is a prevalent urologic malignancy that shows a poor prognosis. Abnormal metabolism and its key genes play a critical role in BCa progression. In this study, the role played by PhosphoGlycerol Dehydrogenase (PHGDH), an important molecule of serine metabolism, was investigated with regard to the regulation of ferroptosis in BCa. Methods: The BCa tissues of 90 patients were analyzed by RNA-sequencing for differential pathways and genes. Western blot, qPCR, and IHC were used to determine PHGDH expression in the cell lines (in vitro) and patient tissues (in vivo). R software was used to analyze PHGDH expression, prognosis, and PHGDH+SLC7A11 score. The biological functions of PHGDH were examined through organoids, and in vitro and in vivo experiments. C11 probes, electron microscopy, and ferroptosis inhibitors/ inducers were used to detect cellular ferroptosis levels. Protein profiling, co-IP, and RIP assays were used to screen proteins that might bind to PHGDH. PHGDH-targeted inhibitor NCT-502 was used to evaluate its effect on BCa cells. Results: PHGDH was highly expressed in patients with BCa. Knock-down of PHGDH promoted ferroptosis, while the decreased proliferation of BCa cells. Additionally, PHGDH knock-down downregulated the expression of SLC7A11. Co-IP and mass spectrometry experiments indicate that PHGDH binds to PCBP2, an RNA-binding protein, and inhibits its ubiquitination degradation. PCBP2 in turn stabilizes SLC7A11 mRNA and increases its expression. NCT-502, a PHGDH inhibitor, promotes ferroptosis and inhibits tumor progression in BCa. The PHGDH+ SLC7A11 score was significantly correlated with patient prognosis. Conclusions: To conclude, the PHGDH, via interaction with PCBP2, upregulates SLC7A11 expression. This inhibits ferroptosis and promotes the malignant progression of BCA. The results of this study indicated that NCT-502 could serve as a therapeutic strategy for BCa.

Alleviation of Diabetic Tendon Injury via Activation of Tendon Fibroblasts Autophagy under Berberine Treatment.

Berberine (BBR) is an isoquinoline alkaloid isolated from Coptis chinensis and possesses valuable pharmacological activities, including anti-inflammatory, anti-tumor, and alleviating several complications of type 2 diabetes mellitus (T2DM). However, the role of BBR in regulating diabetic tendon injury remains poorly understood. In this study, a rat model of T2DM was constructed, and cell apoptosis and autophagy were assessed in tendon tissues after BBR treatment through TdT-Mediated dUTP nick-end labeling (TUNEL) assay and immunohistochemical analysis. Tendon fibroblasts were obtained from the rat Achilles tendon, and the role of BBR in regulating cell apoptosis, the production of inflammatory cytokines, and autophagy activation were assessed using flow cytometry, quantitative real-time PCR (qRT-PCR), and western blot analysis. We demonstrated that BBR treatment significantly increased autophagy activation and decreased cell apoptosis in tendon tissues of T2DM rats. In tendon fibroblasts, BBR repressed High glucose (HG)-induced cell apoptosis and production of proinflammatory cytokines. HG treatment resulted in a decrease of autophagy activation in tendon fibroblasts, whereas BBR restored autophagy activation. More important, pharmacological inhibition of autophagy by 3-MA weakened the protective effects of BBR against HG-induced tendon fibroblasts injury. Taken together, the current results demonstrate that BBR helps relieve diabetic tendon injury by activating autophagy of tendon fibroblasts.

Recent Trends in the Incidence of Clear Cell Adenocarcinoma and Survival Outcomes: A SEER Analysis.

Background: Clear cell adenocarcinoma (CCA) is considered a relatively rare tumor with a glycogen-rich phenotype. The prognosis of CCA patients is unclear. In this study, recent trends in the epidemiological and prognostic factors of CCA were comprehensively investigated. Methods: Patients with CCA from years 2000 to 2016 were identified from the Surveillance, Epidemiological, and End Results (SEER) database. Relevant population data were used to analyze the rates age-adjusted incidence, age-standardized 3-year and 5-year relative survivals, and overall survival (OS). Results: The age-adjusted incidence of CCA increased 2.7-fold from the year 2000 (3.3/100,000) to 2016 (8.8/100,000). This increase occurred across all ages, races, stages, and grades. Of all these subgroups, the increase was largest in the grade IV group. The age-standardized 3-year and 5-year relative survivals increased during this study period, rising by 9.1% and 9.5% from 2000 to 2011, respectively. Among all the stages and grades, the relative survival increase was greatest in the grade IV group. According to multivariate analysis of all CCA patients, predictors of OS were: age, gender, year of diagnosis, marital status, race, grade, stage, and primary tumor site (P < 0.001). The OS of all CCA patients during the period 2008 to 2016 was significantly higher than that from 2000 to 2007 (P < 0.001). Conclusions: The incidence of CCA and survival of these patients improved over time. In particular, the highest increases were reported for grade IV CCA, which may be due to an earlier diagnosis and improved treatment.

Magnetic resonance imaging-based radiomics signature for preoperative prediction of Ki67 expression in bladder cancer.

PURPOSE: The Ki67 expression is associated with the advanced clinicopathological features and poor prognosis in bladder cancer (BCa). We aimed to develop and validate magnetic resonance imaging (MRI)-based radiomics signatures to preoperatively predict the Ki67 expression status in BCa. METHODS AND MATERIALS: We retrospectively collected 179 BCa patients with Ki67 expression and preoperative MRI. Radiomics features were extracted from T2-weighted (T2WI) and dynamic contrast-enhancement (DCE) images. The synthetic minority over-sampling technique (SMOTE) was used to balance the minority group (low Ki67 expression group) in the training set. Minimum redundancy maximum relevance was used to identify the best features associated with Ki67 expression. Support vector machine and Least Absolute Shrinkage and Selection Operator algorithms (LASSO) were used to construct radiomics signatures in training and SMOTE-training sets, and diagnostic performance was assessed by the area under the curve (AUC) and accuracy. The decision curve analyses (DCA) and calibration curve and were used to investigate the clinical usefulness and calibration of radiomics signatures, respectively. The Kaplan-Meier test was performed to investigate the prognostic value of radiomics-predicted Ki67 expression status. RESULTS: 1218 radiomics features were extracted from T2WI and DCE images, respectively. The SMOTE-LASSO model based on nine features achieved the best predictive performance in the SMOTE-training (AUC, 0.859; accuracy, 80.3%) and validation sets (AUC, 0.819; accuracy, 81.5%) with a good calibration performance and clinical usefulness. Immunohistochemistry-based high Ki67 expression and radiomics-predicted high Ki67 expression based on the SMOTE-LASSO model were significantly associated with poor disease-free survival in training and validation sets (all P < 0.05). CONCLUSIONS: The SMOTE-LASSO model could predict the Ki67 expression status and was associated with survival outcomes of the BCa patients, thereby may aid in clinical decision-making.

CALD1 promotes the expression of PD-L1 in bladder cancer via the JAK/STAT signaling pathway.

BACKGROUND: Bladder cancer (BC) is a common malignant neoplasm with a high rate of recurrence and progression, despite optimal treatment. There is a pressing need to identify new effective biomarkers for the targeted treatment of BC. METHODS: The key gene CALD1 was screened via weighed gene co-expression network analysis (WGCNA) from encoding protein genes of BC. Clinical and prognostic significance was explored in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Cell Counting Kit-8 (CCK-8), flow cytometry, transwell chamber experiment and nude mouse xenograft assay were performed to test cell growth, apoptosis, migration, invasion and tumorigenesis capacities. Immune correlation was analyzed in The Tumor Immune Estimation Resource (TIMER) database. Relevant signaling pathways were explored using gene set enrichment analysis (GSEA). RESULTS: Increased expression of CALD1 was significantly correlated with histological grade, clinical stage, T stage, and lymphatic metastasis. Kaplan-Meier survival curves showed that high CALD1 expression was associated with poor overall survival (OS) and disease-free survival (DFS) in TCGA database, and with poor OS in the four GEO databases. CALD1 promotes growth, migration, invasion, and cell cycle of tumor cell, and inhibits tumor cell apoptosis in vitro and in vivo. CADL1 expression was positively correlated with increased CD274 levels (r=0.357, P=9.71e-14). JAK/STAT signaling pathway was significantly enriched in the high CALD1 expression group. CALD1-mediated PD-L1 overexpression (OE) was via the activation of the JAK/STAT signaling pathway; this effect was blocked by the specific JAK inhibitor Ruxolitinib. CONCLUSIONS: CALD1 is a potential molecular marker associated with prognosis. It promotes the malignant progression of BC and upregulates the PD-L1 expression via the JAK/STAT signaling pathway.

Extreme body mass index is associated with poor survival outcomes after radical cystectomy: a retrospective cohort study in a Chinese population.

BACKGROUND: Body mass index (BMI) has been evidenced to be a significant prognostic factor in multiple cancers. This retrospective study aimed to investigate the association between BMI and survival outcomes after radical cystectomy (RC) in patients with bladder cancer (BCa). METHODS: Clinical and pathological parameters of patients who were diagnosed with BCa and received RC between 2010 and 2018 were collected. The associations between BMI at surgery and clinicopathological features were examined. The prognostic value of BCa for overall survival (OS) and cancer-specific survival (CSS) was examined using the Kaplan-Meier method and Cox regression models. RESULTS: Among the 217 patients enrolled in this study, 13 (6.0%), 121 (55.8%), 60 (27.6%), and 23 (10.6%) had a BMI value of <18.5 kg/m2 (underweight), 18.5-23.9 kg/m2 (normal), 24-27.9 kg/m2 (overweight), and ≥28 kg/m2 (obese), respectively. Underweight and obese patients tended to have poorer survival after RC than normal and overweight patients (P<0.05). Multivariable Cox regression revealed that extreme BMI was an independent predictor of both OS (BMI <18.5 vs. 18.5-27.9 kg/m2, OR =2.675, 95% CI: 1.131-6.327, P=0.025; BMI ≥28 vs. 18.5-27.9 kg/m2, OR =3.693, 95% CI: 1.589-8.583, P=0.002) and CSS (BMI <18.5 vs. 18.5-27.9 kg/m2, OR =3.012, 95% CI: 1.180-7.687, P=0.021; BMI ≥28 vs. 18.5-27.9 kg/m2, OR =3.801, 95% CI: 1.526-9.469, P=0.004), along with tumor stage and urinary diversion type. CONCLUSIONS: Being underweight or obese is associated with a poor prognosis in patients with BCa undergoing RC. For patients who are preparing to undergo RC for BCa, controlling the BMI index through diet or exercise before surgery may contribute to the surgical curative effect and an improved prognosis.

Do Metastatic Kidney Cancer Patients Benefit From Cytoreductive Nephrectomy? A Real-World Retrospective Study From the SEER Database.

Introduction: The benefit of cytoreductive nephrectomy (CN) for metastatic kidney cancer has been challenged recently. The study aimed to evaluate the prognostic roles of surgical resection of primary tumor site for metastatic kidney cancer under a real-world setting. Methods: The Surveillance, Epidemiology, and End Results (SEER) database (2010-2015) and the overall survival (OS) and cancer-specific survival (CSS) were evaluated using the Cox proportional hazards regression model. One-to-one matching using the propensity score was used to estimate and compare the survival rates. Results: The SEER data contain records of 8,932 patients from 2010 to 2015. The data showed that 61.7% of the patients underwent CN while 38.2% did not receive any surgery. The median survival month for a patient without surgery was 4 months and for a patient with surgery was 19 months. The multivariate analysis showed that surgical resection of the primary tumor site was an independent favorable predictor for both OS and CSS (all p < 0.001) in the original and the matching cohort. Conclusions: In the era of target therapy, CN might still be a vital method to treat metastatic kidney cancer.

Cardiac surgery under cardiopulmonary bypass in pregnancy: report of four cases.

BACKGROUND: Open heart surgery during pregnancy is relatively rare at home and abroad, and there is a higher risk and probability of maternal and infant death. How to carry out heart valve replacement under cardiopulmonary bypass (CPB) under the premise of ensuring the safety of mother and child is the focus of attention at home and abroad. CASE INTRODUCTION: We reported four cases of cardiac surgeries under CPB during pregnancy performed in our hospital from March 2020 to March 2021. Two of the patients continued their pregnancy after cardiac surgery under CPB. Three patients had infective endocarditis and the other one had an ascending aortic aneurysm. Three patients underwent heart valve placement with the mechanical mitral valve when the other one underwent Bentall surgery. The operations of four cases were all successful, and further follow-up evaluation of the pregnant women and fetuses showed no abnormalities. The patients' detailed information is shown in the following table. CONCLUSION: Heart disease during pregnancy should be treated actively and proactively when the patient has obvious symptoms. Heart valve replacement under CPB will be the first choice, and this may become the primary surgical treatment for symptomatic heart disease during pregnancy.