A novel anoikis-related gene signature identifies LYPD1 as a novel therapy target for bladder cancer.

Bladder cancer (BLCA) is a malignant tumor associated with unfavorable outcomes. Studies suggest that anoikis plays a crucial role in tumor progression and cancer cell metastasis. However, its specific role in bladder cancer remains poorly understood. Our objective was to identify anoikis-related genes (ARGs) and subsequently construct a risk model to assess their potential for predicting the prognosis of bladder cancer.The transcriptome data and clinical data of BLCA patients were sourced from The Cancer Genome Atlas and GEO database. We then performed the differential expression analysis to screen differentially expressed ARGs. Subsequently, we conducted non-negative matrix factorization (NMF) clustering analysis to establish molecular subtypes based on the differentially expressed ARGs. The CIBERSORT algorithm was used to estimate the quantification of different cell infiltration in BLCA tumor microenviroment. A prognostic risk model containing 7 ARGs was established using Lasso-Cox regression analysis. The nomogram was built for predicting the survival probability of BLCA patients. To determine the drug sensitivity of each sample from the high- and low-risk groups, the R package "pRRophetic" was performed. Finally, the role of LYPD1 was explored in BLCA cell lines.We identified 90 differential expression ARGs and NMF clustering categorizated the BLCA patientss into two distinct groups (cluster A and B). Patients in cluster A had a better prognosis than those in cluster B. Then, we established a ARGs risk model including CALR, FASN, FOSL1, JUN, LYPD1, MST1R, and SATB1, which was validated in the train and test set. The results suggested overall survival rate was much higher in low risk group than high risk group. The cox regression analysis, ROC curve analysis, and nomogram collectively demonstrated that the risk model served as an independent prognostic factor. The high risk group had a higher level TME scores compared to the low risk group. Furthermore, LYPD1 was low expression in BLCA cells and overexpression of LYPD1 inhibits the prolifearation, migration and invasion.In the current study, we have identified differential expression ARGs and constructed a risk model with the promise for guiding prognostic predictions and provided a therapeutic target for patients with BLCA.

YTHDC1 as a tumor progression suppressor through modulating FSP1-dependent ferroptosis suppression in lung cancer.

Ferroptosis is a regulated cell death process initiated by iron-dependent phospholipid peroxidation and is mainly suppressed by GPX4-dependent and FSP1-dependent surveillance mechanisms. However, how the ferroptosis surveillance system is regulated during cancer development remains largely unknown. Here, we report that the YTHDC1-mediated m6A epigenetic regulation of FSP1 alleviates the FSP1-dependent ferroptosis suppression that partially contributes to the tumor suppressive role of YTHDC1 in lung cancer progression. YTHDC1 knockdown promoted the lung tumor progression and upregulated FSP1 protein level that resulted in ferroptosis resistance of lung cancer cells. Silencing FSP1 abrogated YTHDC1 knockdown-induced proliferation increase and ferroptosis resistance. Mechanistically, YTHDC1 binding to the m6A sites in the FSP1 3'-UTR recruited the alternative polyadenylation regulator CSTF3 to generate a less stable shorter 3'-UTR contained FSP1 mRNA, whereas YTHDC1 downregulation generated the longer 3'-UTR contained FSP1 mRNA that is stabilized by RNA binding protein HuR and thus led to the enhanced FSP1 protein level. Therefore, our findings identify YTHDC1 as a tumor progression suppressor in lung cancer and a ferroptosis regulator through modulating the FSP1 mRNA stability and thus suggest a ferroptosis-related therapeutic option for YTHDC1high lung cancer.

Thoracoscopic esophagectomy for thoracic esophageal cancer with right aortic arch and Kommerell diverticulum: a case report and literature review.

Background: Esophageal carcinoma accompanied by a right aortic arch (RAA) is very rare. When combined with Kommerell diverticulum (KD), a right aortic arch forms a vascular ring encircling both the esophagus and trachea. Due to abnormal anatomy of the upper mediastinum, it is very difficult to dissociate the esophagus and its surrounding tissues, especially the left recurrent laryngeal nerve. Herein, we report a case of successful thoracoscopic esophagectomy in an esophageal cancer patient concurrent with a RAA and KD. Case presentation: A 62-year-old male patient was diagnosed with esophageal squamous carcinoma in the middle esophagus at clinical stage I (cT1N0M0) according to UICC-TNM classification 8th edition. Further examinations revealed RAA and KD. Based on the three-dimensional CT (3D-CT) reconstruction, a Mckeown esophagectomy via a left thoracoscopic approach in semi-prone position was performed. During the operation, the left recurrent laryngeal nerve was accurately exposed and well protected. Postoperatively, severe complications, including anastomotic leakage and recurrent laryngeal nerve palsy, were not observed. The patient was discharged 12 days after the surgery. Conclusion: Preoperative 3D-CT reconstruction is useful to clarify the vascular malformation in esophageal cancer patients with RAA, and helpful to formulate a reasonable surgical approach.

RAB14 promotes epithelial-mesenchymal transition in bladder cancer through autophagy­dependent AKT signaling pathway.

Bladder cancer (BLCA) is the 9th most common cancer of mortality. Autophagy and epithelial to mesenchymal transition (EMT) have an essential role in cancer invasion and metastasis. However, the relationship between autophagy and EMT is still poorly understood in BLCA. Functional enrichment and pathway network analysis were carried out. Comprehensive protein-protein interactions (PPI) networks were proposed to prioritize candidate autophagy-related genes. Furthermore, an autophagy-related signature and a nomogram model were established by integrating clinical information and this signature risk score to evaluate candidate autophagy-related genes. RAB14 expression and its association with pathological information and survival were evaluated in samples from TCGA dataset. Knocking down RAB14 in T24 cells was constructed, and immunofluorescence staining, transmission electron microscopy, immunohistochemistry and western blotting and a series of functional assays were performed to evaluate the migration, invasion, EMT and autophagy abilities of BLCA cells. The autophagy-related gene RAB14 was the only candidate gene identified by three kinds of analytic approaches. RAB14 was highly upregulated in BLCA and correlated with clinical outcomes based on TCGA BLCA datasets. Knocking down RAB14 was found to inhibit EMT and autophagy in T24 cells. RAB14 levels were positively related to those of LC3B and Beclin1, two genes with critical roles in the autophagy process, and the correlation was further confirmed in clinical tissue specimens by IHC and western blot analysis. In addition, RAB14-promoted EMT, migration, and invasion in T24 cells could be partially reversed by autophagy activator, rapamycin. The effects of RAB14 on autophagy was associated with level of p-Akt, indicating that they were possibly mediated via PI3K/AKT signaling. These findings indicated that autophagy-related gene RAB14-promoted EMT, migration and invasion of bladder cancer via the Akt-associated autophagic pathway.

Identification of a prognostic biomarker predicting biochemical recurrence and construction of a novel nomogram for prostate cancer.

Background: Biochemical recurrence (BCR) is common in prostate cancer (PCa), but its prediction is based predominantly on clinicopathological characteristics with low accuracy. We intend to identify a potential prognostic biomarker related to the BCR and construct a nomogram for improving the risk stratification of PCa patients. Methods: The transcriptome and clinical data of PCa patients were obtained from TCGA and GEO databases. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were used to screen out differentially expressed genes (DEGs) related to the BCR of PCa. Cox regression analysis was further applied to screen out DEGs related to BCR-free survival (BFS). Time-dependent receiver operating curve (ROC) analysis and Kaplan-Meier (K-M) survival analysis were conducted to assess the prognostic value. Then, a prognostic nomogram was established and evaluated. The clinicopathological correlation analysis, GSEA analysis, and immune analysis were used to explore the biological and clinical significance of the biomarker. Finally, the qRT-PCR, western blotting, and immunohistochemistry (IHC) were conducted to validate the expression of the biomarker. Results: BIRC5 was identified to be the potential prognostic biomarker. The clinical correlation analysis and K-M survival analysis found that the BIRC5 mRNA expression was positively associated with disease progression and negatively associated with the BFS rate. Time-dependent ROC curves verified its accurate prediction performance. The GSEA and immune analysis suggested that the BIRC5 was related to immunity. A nomogram with an accurate prediction for BFS of PCa patients was constructed. qRT-PCR, western blotting, and IHC results validated the expression level of BIRC5 in PCa cells and tissues. Conclusion: Our study identified BIRC5 as a potential prognostic biomarker related to BCR of PCa and constructed an efficacy nomogram for predicting BFS to assist clinical decision-making.

Construction and internal validation of a novel nomogram for predicting prognosis of infective endocarditis.

To develop a nomogram prediction model capable of early identification of high-risk infective endocarditis (IE) patients. We retrospectively analyzed the clinical data of 383 patients with IE and divided them into survival and non-survival groups according to different hospitalization outcomes. Univariate and multivariate logistic regression methods were used to screen independent risk factors affecting the survival outcome of IE, and a Nomogram prediction model was constructed by these factors. The Hosmer-Lemeshow goodness-of-fit test was applied to assess the model fit, the discrimination and calibration of the model were evaluated by plotting ROC curves and calibration curves. Advanced age, embolic symptoms, abnormal leukocyte count, low hemoglobin level and double-sided IE were associated with higher in-hospital mortality in patients with IE (P < 0.05). The Hosmer-Lemeshow goodness-of-fit test for the model was χ2 = 7.107, P = 0.311. The AUC of the ROC curve of the model was 0.738 (95% CI 0.677-0.800). The bootstrap method was used to validate the prediction model. The results showed that the prediction accuracy of the model in the validation cohort was 0.842. The nomogram prediction model can accurately predict the in-hospital mortality risk of IE and can help clinicians identify high-risk IE patients early.

Nomogram for Predicting In-hospital Mortality in Infective Endocarditis Based on Early Clinical Features and Treatment Options.

Aim: The aim of this study was to develop a nomogram based on early clinical features and treatment options for predicting in-hospital mortality in infective endocarditis (IE). Methods: We retrospectively analyzed the data of 294 patients diagnosed with IE in our hospital from June 01, 2012 to November 24, 2021, determined independent risk factors for in-hospital mortality by univariate and multivariate logistic regression analysis, and established a Nomogram prediction model based on these factors. Finally, the prediction performance of nomogram is evaluated by C-index, bootstrapped-concordance index, and calibration plots. Results: Age, abnormal leukocyte count, left-sided IE, right-sided IE, and no surgical treatment were independent risk factors for in-hospital mortality in patients with IE, and we used these independent risk factors to construct a nomogram prediction model to predict in-hospital mortality in IE. The C-index of the model was 0.878 (95% CI: 0.824-0.931), and the internal validation of the model by bootstrap validation method showed a prediction accuracy of 0.852 and a bootstrapped-concordance index of 0.53. Conclusion: Our nomogram can accurately predict in-hospital mortality in IE patients and can be used for early identification of high-risk IE patients.

A novel and sensitive DNA methylation marker for the urine-based liquid biopsies to detect bladder cancer.

BACKGROUND: Better prognostic outcome is closely correlated with early detection of bladder cancer. Current non-invasive urianalysis relies on simultaneously testing multiple methylation markers to achieve relatively high accuracy. Therefore, we have developed an easy-to-use, convenient, and accurate single-target urine-based DNA methylation test for the malignancy. METHODS: By analyzing TCGA data, 344 candidate markers with 424 primer pairs and probe sets synthesized were systematically screened in cancer cell lines, paired tissue specimens, and urine sediments from bladder cancer patients and normal controls. The identified marker was further validated in large case-control cohorts. Wilcoxon rank sum tests and c2 tests were performed to compare methylation levels between case-control groups and correlate methylation levels with demographic and clinical characteristics. In addition, MSP, qMSP, RT-PCR, western blot analysis, and immunohistochemistry were performed to measure levels of DNA methylation, mRNA transcription, and protein expression in cancer cell lines and tissues. RESULTS: A top-performing DMRTA2 marker identified was tested in both discovery and validation sets, showing similar sensitivity and specificity for bladder cancer detection. Overall sensitivity in the aggregate set was 82.9%(179/216). The specificity, from a control group consisting of patients with lithangiuria, prostatoplasia, and prostatitis, is 92.5%(468/506). Notably, the methylation assay had the highest sensitivities for tumors at stages of T1(90.4%) and T2(95.0%) compared with Ta (63.0%), T3(81.8%), and T4(81.8%). Furthermore, the test showed admirable detection rate of 80.0%(24/30) for recurring cancers. While methylation was observed in 39/54(72.2%) urine samples from patients with carcinomas of renal pelvis and ureter, it was detected at extremely low rate of 6.0%(8/133) in kidney and prostate cancers. Compared with SV-HUC-1, the normal bladder epithelial cell line, DMRTA2 was hypermethylated in 8/9 bladder cancer cell lines, consistent with the results of MSP and qMSP, but not correlated with mRNA and protein expression levels in these cell lines. Similarly, DMRTA2 immunostaining was moderate in some tissues but weak in others. Further studies are needed to address functional implications of DMRTA2 hypermethylation. CONCLUSIONS: Our data demonstrated that a single-target DNA methylation signature, mDMRTA2, could be highly effective to detect both primary and recurring bladder cancer via urine samples.

A Novel Neobladder-Urethral Drag-and-Bond Anastomosis Technique During Laparoscopic Radical Cystectomy for Ileal Orthotopic Neobladder: Surgical Technique and Initial Research.

PURPOSE: To explore the application of the neobladder-urethral drag-and-bond anastomosis technique in laparoscopic radical cystectomy (LRC) with ileal orthotopic neobladder (IONB) reconstruction. PATIENTS AND METHODS: This is a retrospective cohort study on a procedure performed by a single surgeon. From January 2014 to December 2018, we identified 43 male bladder cancer patients who received LRC with IONB reconstruction. These patients were divided into two groups, with 22 patients undergoing neobladder-urethral drag-and-bond anastomosis (NUDA) and 21 patients undergoing neobladder-urethral anastomosis under laparoscopy (NUAL). Anastomosis time, catheter removal time, postvoid residual (PVR), maximum urinary flow rate (Q-max), urine leakage and anastomotic stenosis were used to evaluate the simplicity and surgical effect of the two groups. RESULTS: Both groups demonstrated similar tumor characteristics. A significant difference in neobladder-urethral anastomosis time was found between the NUDA group and the NUAL group (14.6 ± 0.4 vs 70 ± 2.5 min, P<0.0001), and there was no significant difference in other characteristics. CONCLUSION: The neobladder-urethral drag-and-bond anastomosis technique in LRC and IONB reconstruction, with its shorter learning curve, was easier and more convenient than neobladder-urethral anastomosis under laparoscopy.

Efficacy and Side Effects of Drugs Commonly Used for the Treatment of Lower Urinary Tract Symptoms Associated With Benign Prostatic Hyperplasia.

Benign prostatic hyperplasia (BPH) is the most common benign disease of the prostate gland and is caused by benign hyperplasia of the smooth muscle cells and stromal cells in this important gland. BPH is also the most common disease underlying lower urinary tract symptoms (LUTS). The incidence of BPH increases with age and affects more than half of all men 50 years or older. BPH mainly exerts effects on urinary function and can seriously reduce a patient's quality of life. At present, treatment for BPH aims primarily to improve the quality of life and reduce the risk of BPH-related complications. Pharmacological therapy is recommended for moderate-to-severe cases of LUTS that are suggestive of BPH. A range of drugs is currently available to treat this condition, including α1-adrenoceptor antagonists, 5α-reductase inhibitors (5-ARIs), phosphodiesterase type 5 inhibitors (PDE5Is), muscarinic receptor antagonists (MRAs), ß3-adrenoceptor agonists, and plant extracts. Of these, the most commonly used drugs in the clinic are α1-adrenoceptor antagonists, 5-ARIs, and combination therapy. However, these drugs exert their effects via various mechanisms and are associated with adverse reactions. The purpose of this review is to provide current comprehensive perspectives on the mechanisms of action, efficacy, and adverse reactions associated with the drugs most commonly used for the treatment of BPH.

A Preliminary, Multicenter, Prospective and Real World Study on the Hemostasis, Coagulation, and Safety of Hemocoagulase Bothrops Atrox in Patients Undergoing Transurethral Bipolar Plasmakinetic Prostatectomy.

Objective: To evaluate the hemostasis and coagulation effect of Hemocoagulase Bothrops Atrox in benign prostatic hyperplasia (BPH) patients undergoing transurethral bipolar plasmakinetic prostatectomy (TUPKP). Methods: This study adopted a multicenter, prospective, and real world design. BPH patients undergoing TUPKP were divided into two groups according to whether they adopted Hemocoagulase Bothrops Atrox (group B) or not (group A) during perioperative period. The electronic clinical data on every included subject, including the international prostate symptom score (IPSS) and the quality of life scale (QoL), maximum urinary flow rate (Qmax), complete blood count, coagulation screening test and adverse events, were measured and compared between the two groups. Results: Finally, 695 patients, 443 in group A and 252 in group B were included. Baseline characteristics showed no significant difference between two groups. In group A, compared with baseline, IPSS decreased 15.66 (95% CI = -16.45 to -14.87), QoL decreased 3.08 (95% CI = -3.30 to -2.87), prothrombin time prolonged 1.02 s (95% CI = 0.56 to 1.48), while white blood cells, neutrophils, lymphocytes, and hemoglobin also significantly changed; white blood cells, neutrophils and platelets increased, while lymphocytes decreased by 0.14×109/L (95% CI = -0.21 to -0.08) before discharge. In group B, compared with baseline, IPSS decreased 16.12 (95% CI = -17.02 to -15.21), QoL decreased 3.32 (95% CI = -3.56 to -3.07), and white blood cells, neutrophils, lymphocytes, and hemoglobin were also significantly changed, along with white blood cells and lymphocytes that tested before discharge (p < 0.01); however, prothrombin time was not significant prolonged (MD= 0.48, 95% CI = -0.05 to 1.01). When compared with group A and group B, the average hospitalization time in group A was longer than group B (p < 0.01), transfusion risk was similar in the two groups (OR = 1.582, 95% CI = 0.552 to 4.538). Parameters had no substantial difference between the two subgroups whether prostate volume was more than 80 mL or not. Conclusion: Our study indicated that Hemocoagulase Bothrops Atrox can shorten the prothrombin time, hospitalization time and is probably safe among BPH patients undergoing TUPKP, exhibiting fine hemostasis and coagulation efficacy, and would not be influenced by prostate volume.

MEX3C regulates lipid metabolism to promote bladder tumorigenesis through JNK pathway.

Purpose: Bladder cancer (BC) is the most common urinary cancer among men with a high rate of deaths despite the improved medical technology and treatment. Recent evidence demonstrated that Mex-3 RNA-Binding Family Member C (MEX3C) plays various roles in different biological activities, but its molecular mechanisms underlying the pathogenesis of BC remain unclear yet. The aim of this research was to explore the expression patterns of MEX3C and its biological functions in human BC. Materials and methods: The Cancer Genome Atlas (TCGA) and Oncomine databases were jointly used to analyze the expression of MEX3C in BC and its correlation with the clinicopathological features, while real-time PCR and immunohistochemistry analysis were used to verify the predicted results. Wound-healing assay, Matrigel invasion assay, BODIPY staining and Western blot analysis were used in a cell model to assess the effect of MEX3C on the lipid metabolism, invasion and migration of BC and its mechanisms. Results: MEX3C was highly expressed in BC tissues and cells compared with their normal counterparts, and its expression was positively correlated with the clinicopathological features, especially the invasiveness phenotype. Overexpression of MEX3C accumulated lipid droplets and promoted cell adhesion, invasion and migration. We further demonstrated that MEX3C regulated lipid metabolism and promoted tumor development and progression through activation of JNK signaling and upregulating the JNK downstream protein levels of sterol regulatory element-binding proteins-1, fatty acid synthase and acetyl-CoA carboxylase-1. Conclusion: Here we identified MEX3C as a new oncogene to promote bladder tumorigenesis by regulating lipid metabolism through Mitogen-activated protein kinase/c-Jun N-terminal kinase (MAPK/JNK) pathway. These findings suggest a new role of MEX3C in promoting BC tumorigenesis and provide a novel biomarker or molecular target for diagnosis or treating BC.

Crystal structure of poly[[hexa-qua-1κ(4) O,2κ(2) O-bis-(µ3-pyridine-2,4-di-car-box-ylato-1κO (2):2κ(2) N,O (2');1'κO (4))cobalt(II)-strontium(II)] dihydrate].

In the title polymeric complex, {[CoSr(C7H3NO4)2(H2O)6]·2H2O} n , the Co(II) ion, which is situated on a crystallographic centre of inversion, is six-coordinated by two O atoms and two N atoms from two pyridine-2,4-di-carboxyl-ate (pydc(2-)) ligands and two terminal water mol-ecules in a slightly distorted octa-hedral geometry, to form a trans-[Co(pydc)2(H2O)2](2-) unit. The Sr(II) ion, situated on a C 2 axis, is coordinated by four O atoms from four pydc(2-) ligands and four water mol-ecules. The coordination geometry of the Sr(II) atom can be best described as a distorted dodeca-hedron. Each Sr(II) ion bridges four [Co(pydc)2(H2O)2](2-) units by four COO(-) groups of four pydc(2-) ligands to form a three-dimensional network structure. Two additional solvent water mol-ecules are observed in the crystal structure and are connected to the three-dimensional coordination polymer by O-H⋯O hydrogen bonds. Further intra- and intermolecular O-H⋯O hydrogen bonds consolidate the overall structure.