Objective: To analyze the risk factors for testicular atrophy (TA) in children with testicular torsion (TT) following emergent orchiopexy. Methods: Clinical data of patients with TT undergoing orchiopexy were retrospectively reviewed, including age at surgery, affected side, delayed surgery (12–24 h and more than 24 h), echogenicity of testicular parenchyma on ultrasonography (ETPU), testicular blood flow on Color Doppler ultrasonography (CDUS), surgical findings (intraoperative blood supply, the degree of torsion, and surgical approaches), and follow-up. The primary outcome was the rate of TA after orchiopexy. The secondary outcome was the testicular volume loss (TVL) between the affected testis and the contralateral. Results: A total of 113 patients were enrolled in this study with a median age of 11 years. The median follow-up was 21 months. Patients had a median TVL of 51.02% and 44 (38.94%) of them developed severe TA during follow-up. TA was significantly associated with age at surgery ( P < 0.0001), delayed surgery ( P = 0.0003), ETPU ( P = 0.0001), and intraoperative blood supply ( P = 0.0005). Multivariate logistic regression analysis showed that school-age children (OR = 0.069, P < 0.001) and puberty (OR = 0.177, P = 0.007) had a decreased risk of TA compared with preschool children, and that heterogeneous ETPU (OR = 14.489, P = 0.0279) and delayed surgery >24 h (OR = 3.921, P = 0.040) increased the risk of TA. Multivariate analysis demonstrated that ETPU ( F = 16.349, P < 0.001) and delayed surgery ( F = 6.016, P = 0.003) were independent risk factors for TVL. Conclusions: Age at surgery, delayed surgery, and ETPU may play a crucial role in predicting the TA in children with TT following emergent orchiopexy. Moreover, blood flow measured by CDUS could not predict the outcome properly.
BackgroundWilms tumor (WT) is the most common tumor in children. We aim to construct a nomogram to predict the cancer-specific survival (CSS) of WT in children and externally validate in China.MethodsWe downloaded the clinicopathological data of children with WT from 2004 to 2018 in the SEER database. At the same time, we used the clinicopathological data collected previously for all children with WT between 2013 and 2018 at Children's Hospital of Chongqing Medical University (Chongqing, China). We analyzed the difference in survival between the patients in the SEER database and our hospital. Cox regression analysis was used to screen for significant risk factors. Based on these factors, a nomogram was constructed to predict the CSS of children with WT. Calibration curve, concordance index (C-index), the area under the receiver operating curve (AUC) and decision curve analysis (DCA) was used to evaluate the accuracy and reliability of the model.ResultsWe included 1,045 children with WT in the SEER database. At the same time, we collected 112 children with WT in our hospital. The Kaplan-Meier curve suggested that children in China with WT had a higher mortality rate than those in the United States. Cox regression analysis revealed that age, lymph node density (LND), and tumor stage were significant prognostic factors for the patients in the SEER database. However, the patients in our hospital only confirmed that the tumor stage and the number of positive regional lymph nodes were significant factors. The prediction model established by the SEER database had been validated internally and externally to prove that it had good accuracy and reliability.ConclusionWe have constructed a survival prognosis prediction model for children with WT, which has been validated internally and externally to prove accuracy and reliability.
ObjectiveProstate cancer (PC) is the most common non-cutaneous malignancy in men worldwide. Accurate predicting the survival of elderly PC patients can help reduce mortality in patients. We aimed to construct nomograms to predict cancer-specific survival (CSS) and overall survival (OS) in elderly PC patients.MethodsInformation on PC patients aged 65 years and older was downloaded from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox regression models were used to determine independent risk factors for PC patients. Nomograms were developed to predict the CSS and OS of elderly PC patients based on a multivariate Cox regression model. The accuracy and discrimination of the prediction model were tested by the consistency index (C-index), the area under the subject operating characteristic curve (AUC), and the calibration curve. Decision curve analysis (DCA) was used to test the clinical value of the nomograms compared with the TNM staging system and D’Amico risk stratification system.Results135183 elderly PC patients in 2010-2018 were included. All patients were randomly assigned to the training set (N=94764) and the validation set (N=40419). Univariate and multivariate Cox regression model analysis revealed that age, race, marriage, histological grade, TNM stage, surgery, chemotherapy, radiotherapy, biopsy Gleason score (GS), and prostate-specific antigen (PSA) were independent risk factors for predicting CSS and OS in elderly patients with PC. The C-index of the training set and the validation set for predicting CSS was 0.883(95%CI:0.877-0.889) and 0.887(95%CI:0.877-0.897), respectively. The C-index of the training set and the validation set for predicting OS was 0.77(95%CI:0.766-0.774)and 0.767(95%CI:0.759-0.775), respectively. It showed that the proposed model has excellent discriminative ability. The AUC and the calibration curves also showed good accuracy and discriminability. The DCA showed that the nomograms for CSS and OS have good clinical potential value.ConclusionsWe developed new nomograms to predict CSS and OS in elderly PC patients. The models have been internally validated with good accuracy and reliability and can help doctors and patients to make better clinical decisions.
Wilms tumour (WT) is the most common kidney malignancy in children. Chemoresistance is the leading cause of tumour recurrence and poses a substantial therapeutic challenge. Increasing evidence has underscored the role of the tumour immune microenvironment (TIM) in cancers and the potential for immunotherapy to improve prognosis. There remain no reliable molecular markers for reflecting the immune landscape and predicting patient survival in WT. Here, we examine differences in gene expression by high-throughput RNA sequencing, focused on differentially expressed immune-related genes (IRGs) based on the ImmPort database. Via univariate Cox regression analysis and Lasso-penalized Cox regression analysis, IRGs were screened out to establish an immune signature. Kaplan-Meier curves, time-related ROC analysis, univariate and multivariate Cox regression studies, and nomograms were used to evaluate the accuracy and prognostic significance of this signature. Furthermore, we found that the immune signature could reflect the immune status and the immune cell infiltration character played in the tumour microenvironment (TME) and showed significant association with immune checkpoint molecules, suggesting that the poor outcome may be partially explained by its immunosuppressive TME. Remarkably, TIDE, a computational method to model tumour immune evasion mechanisms, showed that this signature holds great potential for predicting immunotherapy responses in the TARGET-wt cohort. To decipher the underlying mechanism, GSEA was applied to explore enriched pathways and biological processes associated with immunophenotyping and Connectivity map (CMap) along with DeSigN analysis for drug exploration. Finally, four candidate immune genes were selected, and their expression levels in WT cell lines were monitored via qRT-PCR. Meanwhile, we validated the function of a critical gene, NRP2. Taken together, we established a novel immune signature that may serve as an effective prognostic signature and predictive biomarker for immunotherapy response in WT patients. This study may give light on therapeutic strategies for WT patients from an immunological viewpoint.
Herein, a chiral bispyridyl ligand (L) was designed and synthesized using a Schiff base condensation reaction, followed by a 1,3-H shift. Five complexes, [Zn2 L 2(OAc)4] (1), {[CdLCl2(DMF)]·4H2O} n (2), [Cd2 L 2I4]·4H2O (3), {[CdL 2(H2O)2](NO3)2·2CH3OH} n (4), and [Hg2 L 2Cl4]·2DMF (5), were synthesized and characterized upon its reaction with Zn(II), Cd(II), or Hg(II) ions, respectively. X-ray crystallography shows that the organic compound exists as a racemic ligand with equal amounts of its R- and S-isomers, and all of the synthesized complexes exhibit heterochiral self-assembly via a chiral self-discrimination process. Complexes 1, 3, and 5 exist as centrosymmetric binuclear metallamacrocycles, while complexes 2 and 4 exist as 1D looped-chain coordination polymers. Inspired by the assembled structures of the five complexes, I2 adsorption/desorption measurements for the complexes were carried out. The results show that complexes 1 and 5 exhibit good adsorption capacities toward I2 in n-hexane and in water, respectively.
Wilms’ tumor (WT) is a common embryonal tumor, and nephrogenic rests play a critical role in WT development. The transforming growth factor β (TGF-β) signaling pathway is fundamental to embryo development and cell growth and proliferation. Moreover, TGF-β contributes to WT development, but the mechanisms of disease pathogenicity are unknown. This study investigated whether the TGF-β signaling pathway was involved in WT and whether blocking TβRI receptor inhibited WT growth, proliferation, and invasion. A total of 60 WT patients with clinical data and surgical specimens were evaluated. Immunohistochemistry (IHC) was used to detect the expression of TGF-β1 and P-smad2/3. In vitro, the proliferation, migration, apoptosis, and epithelial-mesenchymal transition (EMT) protein expression were analyzed using the CCK8 assay, wound healing assay, transwell assay, flow cytometry, and western blot, respectively. In vivo, tumor morphology, tumor size, toxicity, and EMT protein expression were analyzed in tumor-bearing mice treated with a TβRI kinase inhibitor or PBS. High protein levels of TGF-β1 and P-samd2/3 were associated with clinical stage and metastasis or invasion. TβRI inhibition effectively suppressed WT proliferation and migration and promoted apoptosis in the human WT cell line G401, consequently decreasing EMT protein expression. In addition, the TβRI kinase inhibitor significantly impaired the subcutaneous growth of WT. It is worth noting that treatment with the TβRI kinase inhibitor did not cause liver and kidney injury. Our results indicate that the TGF-β/Smad signaling pathway plays a crucial role in WT progression. Blocking the TβRI receptor may be a novel strategy to treat and prevent WT.
Circular RNA (circRNA), which is a newly discovered non-coding RNA, has been documented to play important roles in miRNA sponges, and the dysregulation of which is involved in cancer development. However, circRNA expression profiles and their role in initiation and progression of Wilms tumor (WT) remain largely unclear at present. Here, we used paired WT samples and high-throughput RNA sequencing to identify differentially expressed circRNAs (DE-circRs) and mRNAs (DE-mRs). A total of 314 DE-circRs and 1612 DE-mRs were identified. The expression of a subset of differentially expressed genes was validated by qRT–PCR. A complete circRNA-miRNA-mRNA network was then constructed based on the common miRNA targets of DE-circRs and DE-mRs identified by miRanda prediction tool. The Gene set enrichment analysis (GSEA) indicated that several signaling pathways involving targeted DE-mRs within the ceRNA network were associated with cell cycle and immune response, which implies their participation in WT development to some extent. Subsequently, these targeted DE-mRs were subjected to implement PPI analysis and to identify 10 hub genes. Four hub genes were closely related to the survival of WT patients. We then filtered prognosis-related hub genes by Cox regression and least absolute shrinkage and selection operator (LASSO) regression analysis to construct a prognosis-related risk score system based on a three-gene signature, which showed good discrimination and predictive ability for WT patient survival. Additionally, we analyzed the mutational landscape of these genes and the associations between their expression levels and those of immune checkpoint molecules and further demonstrated their potential impact on the efficacy of immunotherapy. qRT–PCR and western blotting (WB) analysis were used to validate key differentially expressed molecules at the RNA and protein levels, respectively. Besides these, we selected a key circRNA, circEYA1, for function validation. Overall, the current study presents the full-scale expression profiles of circRNAs and the circRNA-related ceRNA network in WT for the first time, deepening our understanding of the roles and downstream regulatory mechanisms of circRNAs in WT development and progression. We further constructed a useful immune-related prognostic signature, which could improve clinical outcome prediction and guide individualized treatment.
Background: Neurogenic bladder (NB) patients exhibit varying degrees of bladder fibrosis, and the thickening and hardening of the bladder wall induced by fibrosis will further affect bladder function and cause renal failure. Our study aimed to investigate the mechanism of bladder fibrosis caused by a spinal cord injury (SCI). Methods: NB rat models were created by cutting the bilateral lumbar 6 (L6) and sacral 1 (S1) spinal nerves. RNA-seq, Western blotting, immunofluorescence, cell viability and ELISA were performed to assess the inflammation and fibrosis levels. Results: The rats showed bladder dysfunction, upper urinary tract damage and bladder fibrosis after SCI. RNA-seq results indicated that hypoxia, EMT and pyroptosis might be involved in bladder fibrosis induced by SCI. Subsequent Western blot, ELISA and cell viability assays and immunofluorescence of bladder tissue confirmed the RNA-seq findings. Hypoxic exposure increased the expression of HIF-1α and induced EMT and pyroptosis in bladder epithelial cells. Furthermore, HIF-1α knockdown rescued hypoxia-induced pyroptosis, EMT and fibrosis. Conclusion: EMT and pyroptosis were involved in the development of SCI-induced bladder fibrosis via the HIF-1α pathway. Inhibition of the HIF-1α pathway may serve as a potential target to alleviate bladder fibrosis caused by SCI.
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