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Stretchable hybrid devices have enabled high-fidelity implantable1-3 and on-skin4-6 monitoring of physiological signals. These devices typically contain soft modules that match the mechanical requirements in humans7,8 and soft robots9,10, rigid modules containing Si-based microelectronics11,12 and protective encapsulation modules13,14. To make such a system mechanically compliant, the interconnects between the modules need to tolerate stress concentration that may limit their stretching and ultimately cause debonding failure15-17. Here, we report a universal interface that can reliably connect soft, rigid and encapsulation modules together to form robust and highly stretchable devices in a plug-and-play manner. The interface, consisting of interpenetrating polymer and metal nanostructures, connects modules by simply pressing without using pastes. Its formation is depicted by a biphasic network growth model. Soft-soft modules joined by this interface achieved 600% and 180% mechanical and electrical stretchability, respectively. Soft and rigid modules can also be electrically connected using the above interface. Encapsulation on soft modules with this interface is strongly adhesive with an interfacial toughness of 0.24 N mm-1. As a proof of concept, we use this interface to assemble stretchable devices for in vivo neuromodulation and on-skin electromyography, with high signal quality and mechanical resistance. We expect such a plug-and-play interface to simplify and accelerate the development of on-skin and implantable stretchable devices.
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Electromiografía , Electrónica Médica , Nanoestructuras , Docilidad , Polímeros , Prótesis e Implantes , Dispositivos Electrónicos Vestibles , Humanos , Nanoestructuras/química , Polímeros/química , Piel , Monitoreo Fisiológico , Electrónica Médica/instrumentación , Electrónica Médica/métodos , Electromiografía/instrumentaciónRESUMEN
OBJECTIVE: Few studies have investigated the impact of basal metabolic rate (BMR) on the development of urolithiasis, and the causal relationship is yet to be established. In this study, a two-sample Mendelian randomization (MR) analysis was utilized to identify the causal relationship between BMR and risk of urolithiasis. METHOD: Genetic instruments for BMR were drawn from a public genome-wide association study (GWAS). Summary dates on BMR and urolithiasis were obtained from a GWAS meta-analysis with sample sizes of 454,874 and 212,453, respectively. The inverse-variance weighted (IVW) method was provided as the main approach to estimate the causal relationship. The weighted-median method and the MR-Egger method were used as supplements to the IVW method. In addition, we conducted sensitivity analyses, including heterogeneity tests, pleiotropy tests and leave-one-out analysis, to assess the robustness of the outcomes. Furthermore, the funnel plot asymmetry was visually inspected to evaluate possible bias. RESULTS: The inverse-variance weighted data revealed that genetically predicted BMR significantly decreased the risk of urolithiasis [beta coefficient (beta): - 0.2366, odds ratio (OR): 0.7893, 95% confidence interval (CI) 0.6504-0.9579, p = 0.0166]. CONCLUSIONS: BMR has causal effects on urolithiasis in an MR study, and the risk of urolithiasis in patients with lower levels of BMR is higher.
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Metabolismo Basal , Urolitiasis , Humanos , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Suplementos Dietéticos , Urolitiasis/epidemiología , Urolitiasis/genéticaRESUMEN
BACKGROUND: Dietary sugar intake is gradually considered a risk factor for many diseases. A sugary diet was positively associated with risk of nephrolithiasis, but the specific relationships remain undefined. OBJECTIVES: To determine associations between risk of nephrolithiasis and dietary sugar intake. METHODS: This cross-sectional study involved 21,590 participants based on the National Health and Nutrition Examination Survey from 2007 to 2018. Amounts of dietary sugar intake (g/d) were the main exposure, including total sugar intake, added sugar intake, and food sources. Associations were analyzed by logistic regression models and restricted cubic splines using complex weighted designs. RESULTS: Weighted mean intake [standard error] of total sugar and added sugar were 111.2 [2.0] g/d and 73.7 [1.9] g/d in participants with nephrolithiasis, respectively. In the fully adjusted regression model, compared to those in quartile 1, the population in quartile 4 of total sugar intake showed a significant risk of nephrolithiasis [odds ratio (OR): 1.23; 95% confidence interval (CI): 1.00-1.51]; OR for added sugar intake was 1.56 (95% CI: 1.25-1.94). The risks of nephrolithiasis increased steadily when total sugar and added sugar intake exceeded â¼150 g/d and 63 g/d in restricted cubic spline analyses, respectively. The highest sugar intake from beverages was associated with an increased risk of nephrolithiasis (OR for total sugar: 1.36; 95% CI: 1.07-1.72; OR for added sugar: 1.37; 95% CI: 1.09-1.73). Added sugar intake from meat, egg, and oil was significantly associated with risk of nephrolithiasis (quartile 4, OR: 1.22; 95% CI: 1.02-1.47), whereas total sugar intake from dairy products was in reverse (quartile 4, OR: 0.67; 95% CI: 0.54-0.82). CONCLUSIONS: Total and added sugar intake, sugar intake from beverages, and added sugar intake from meat, egg, and oil were associated with an increased risk of nephrolithiasis, whereas total sugar intake from dairy products was negatively associated.
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OBJECTIVES: To determine whether relationship exists between overactive bladder (OAB) and sleep patterns through the cross-sectional study. PATIENTS AND METHODS: Patients from the National Health and Nutrition Examination Survey (NHANES) 2007-2014 were included in this study. Data were extracted through questionnaires, including demographics, dietary and health-related behaviors, body measurements and disease information. Three sleep factors were included to aggregate overall sleep scores, ranging from 0 to 3. A sleep score of 0 to 1, 2 or 3 was expressed as a bad, intermediate or healthy sleep pattern, respectively. The Overactive Bladder Symptom Score (OABSS) scale was applied to quantify the severity of OAB for each participant. Weighted logistic regression models were used to investigate the associations between sleep and OAB. RESULTS: A total of 16,978 participants were enrolled in this study. The relationship between OAB and sleep patterns was statistically significant. After fully adjusting for confounding factors, the OAB risk of patients with intermediate and poor sleep patterns obviously increased by 26% and 38%, respectively, and mild (OR = 1.21, 95% CI [1.03,1.42]), moderate (OR = 1.45, 95% CI [1.27,1.66]) and severe (OR = 1.57, 95% CI [1.18,2.09]) OAB were significantly associated with sleep pattern grouping. The prevalence of OAB is significantly higher in patients with bad sleep patterns, and vice versa. CONCLUSION: This study indicated that there is a positive relationship between OAB and worse sleep-related issues.
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Trastornos del Sueño-Vigilia , Vejiga Urinaria Hiperactiva , Humanos , Vejiga Urinaria Hiperactiva/epidemiología , Vejiga Urinaria Hiperactiva/diagnóstico , Encuestas Nutricionales , Estudios Transversales , Encuestas y Cuestionarios , Trastornos del Sueño-Vigilia/epidemiología , SueñoRESUMEN
The biomarkers have an important guiding role in prognosis and treatment of patients with bladder cancer (BC). The aim of the present study was to identify and evaluate a prognostic gene signature in BC patients. The gene expression profiles of BC samples and the corresponding clinicopathological data were downloaded from GEO and TCGA. The differentially expressed genes (DEGs) were identified by R software. Univariate Cox regression and the least absolute shrinkage and selection operator (LASSO) Cox regression were applied to construct the prognostic score model. A nomogram was established with the identified prognostic factors to predict the overall survival rates of BC patients. The discriminatory and predictive capacity of the nomogram was evaluated based on the concordance index (C-index), calibration curves and decision curve analysis (DCA). A 7-gene signature (KLRB1, PLAC9, SETBP1, NR2F1, GRHL2, ANXA1 and APOL1) was identified from 285 DEGs by univariate and LASSO Cox regression analyses. Univariate and multivariate Cox regression analyses showed that age, lymphovascular invasion, lymphatic metastasis, metastasis and the 7-gene signature risk score was an independent predictor of BC patient prognosis. A nomogram that integrated these independent prognostic factors was constructed. The C-index (0.73, CI 95%, 0.693-0.767) and calibration curve demonstrated the good performance of the nomogram. DCA of the nomogram further showed that this model exhibited good net benefit. The combined 7-gene signature could serve as a biomarker for predicting BC prognosis. The nomogram built by risk score and other clinical factors could be an effective tool for predicting the prognosis of patients with BC.
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Nomogramas , Transcriptoma , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/mortalidad , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Tasa de SupervivenciaRESUMEN
BACKGROUND: As the main histological subtype of renal cell carcinoma, clear cell renal cell carcinoma (ccRCC) places a heavy burden on health worldwide. Autophagy-related long non-coding RNAs (ARlncRs) have shown tremendous potential as prognostic signatures in several studies, but the relationship between them and ccRCC still has to be demonstrated. METHODS: The RNA-sequencing and clinical characteristics of 483 ccRCC patients were downloaded download from the Cancer Genome Atlas and International Cancer Genome Consortium. ARlncRs were determined by Pearson correlation analysis. Univariate and multivariate Cox regression analyses were applied to establish a risk score model. A nomogram was constructed considering independent prognostic factors. The Harrell concordance index calibration curve and the receiver operating characteristic analysis were utilized to evaluate the nomogram. Furthermore, functional enrichment analysis was used for differentially expressed genes between the two groups of high- and low-risk scores. RESULTS: A total of 9 SARlncRs were established as a risk score model. The Kaplan-Meier survival curve, principal component analysis, and subgroup analysis showed that low overall survival of patients was associated with high-risk scores. Age, M stage, and risk score were identified as independent prognostic factors to establish a nomogram, whose concordance index in the training cohort, internal validation, and external ICGC cohort was 0.793, 0.671, and 0.668 respectively. The area under the curve for 5-year OS prediction in the training cohort, internal validation, and external ICGC cohort was 0.840, 0.706, and 0.708, respectively. GO analysis and KEGG analysis of DEGs demonstrated that immune- and inflammatory-related pathways are likely to be critically involved in the progress of ccRCC. CONCLUSIONS: We established and validated a novel ARlncRs prognostic risk model which is valuable as a potential therapeutic target and prognosis indicator for ccRCC. A nomogram including the risk model is a promising clinical tool for outcomes prediction of ccRCC patients and further formulation of individualized strategy.
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Carcinoma de Células Renales , Neoplasias Renales , ARN Largo no Codificante , Humanos , Pronóstico , Carcinoma de Células Renales/genética , ARN Largo no Codificante/genética , Autofagia , Factores de Riesgo , Neoplasias Renales/genéticaRESUMEN
BACKGROUND: Inflammation and long noncoding RNAs (lncRNAs) are gradually becoming important in the development of bladder cancer (BC). Nevertheless, the potential of inflammatory response-related lncRNAs (IRRlncRNAs) as a prognostic signature remains unexplored in BC. METHODS: The Cancer Genome Atlas (TCGA) provided RNA expression profiles and clinical information of BC samples, and GSEA Molecular Signatures database provided 1171 inflammation-related genes. IRRlncRNAs were identified using Pearson correlation analysis. After that, consensus clustering was performed to form molecular subtypes. After performing least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses, a risk model constructed based on the prognostic IRRlncRNAs was validated in an independent cohort. Kaplan-Meier (KM) analysis, univariate and multivariate Cox regression, clinical stratification analysis, and time-dependent receiver operating characteristic (ROC) curves were utilized to assess clinical effectiveness and accuracy of the risk model. In clusters and risk model, functional enrichment was investigated using GSEA and GSVA, and immune cell infiltration analysis was demonstrated by ESTIMATE and CIBERSORT analysis. RESULTS: A total of 174 prognostic IRRlncRNAs were confirmed, and 406 samples were divided into 2 clusters, with cluster 2 having a significantly inferior prognosis. Moreover, cluster 2 exhibited a higher ESTIMATE score, immune infiltration, and PD-L1 expression, with close relationships with the inflammatory response. Further, 12 IRRlncRNAs were identified and applied to construct the risk model and divide BC samples into low-risk and high-risk groups successfully. KM, ROC, and clinical stratification analysis demonstrated that the risk model performed well in predicting prognosis. The risk score was identified as an independently significant indicator, enriched in immune, cell cycle, and apoptosis-related pathways, and correlated with 9 immune cells. CONCLUSION: We developed an inflammatory response-related subtypes and steady prognostic risk model based on 12 IRRlncRNAs, which was valuable for individual prognostic prediction and stratification and outfitted new insight into inflammatory response in BC.
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ARN Largo no Codificante , Neoplasias de la Vejiga Urinaria , Regulación Neoplásica de la Expresión Génica , Humanos , Inflamación/genética , Pronóstico , ARN Largo no Codificante/genética , Neoplasias de la Vejiga Urinaria/genéticaRESUMEN
BACKGROUND: The objectives of this study were to screen out cut-off age value and age-related differentially expressed genes (DEGs) in clear cell renal cell carcinoma (CCRCC) from Surveillance Epidemiology and End Results (SEER) database and The Cancer Genome Atlas (TCGA) database. METHODS: We selected 45,974 CCRCC patients from SEER and 530 RNA-seq data from TCGA database. The age cut-off value was defined using the X-tile program. Propensity score matching (PSM) was used to balance the differences between young and old groups. Hazard ratio (HR) was applied to evaluate prognostic risk of age in different subgroups. Age-related DEGs were identified via RNA-seq data. Survival analysis was used to assess the relationship between DEGs and prognosis. RESULTS: In this study, we divided the patients into young (n = 14,276) and old (n = 31,698) subgroups according to cut-off value (age = 53). Age > 53 years was indicated as independent risk factor for overall survival (OS) and cancer specific survival (CSS) of CCRCC before and after PSM. The prognosis of old group was worse than that in young group. Eleven gene were differential expression between the younger and older groups in CCRCC. The expression levels of PLA2G2A and SIX2 were related to prognosis of the elderly. CONCLUSION: Fifty-three years old was cut-off value in CCRCC. The prognosis of the elderly was worse than young people. It remind clinicians that more attention and better treatment should be given to CCRCC patients who are over 53 years old. PLA2G2A and SIX2 were age-related differential genes which might play an important role in the poor prognosis of elderly CCRCC patients.
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Envejecimiento/genética , Biomarcadores de Tumor/genética , Carcinoma de Células Renales/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Renales/genética , Factores de Edad , Anciano , Carcinoma de Células Renales/mortalidad , Fosfolipasas A2 Grupo II/genética , Proteínas de Homeodominio/genética , Humanos , Estimación de Kaplan-Meier , Neoplasias Renales/mortalidad , Masculino , Persona de Mediana Edad , Proteínas del Tejido Nervioso/genética , Pronóstico , Modelos de Riesgos Proporcionales , RNA-Seq , Estándares de Referencia , Estudios Retrospectivos , Factores de Riesgo , Programa de VERF/estadística & datos numéricos , Análisis de SupervivenciaRESUMEN
INTRODUCTION: Psoriasis is a chronic, inflammatory, and papulo-squamous skin disorder without a radical cure. Although previous observational analyses have discovered a relationship between medication intake and increased risk of psoriasis, they are susceptible to confounders. OBJECTIVES: We intend to ascertain if there is a causal association between specific medication intake and increased risk of psoriasis by utilizing the Mendelian randomization (MR) method. METHODS: We obtained the genome-wide association study (GWAS) data for medication intake (23 types, N = 1809) from UK Biobank samples. And we sourced the GWAS data for psoriasis from the 8th release of the FinnGen database, which included 8,075 psoriasis cases and 330,975 healthy control cases. Then a two-sample MR study was performed to determine their causal association, and inverse-variance-weighted MR (IVW-MR) was applied to calculate the effect estimates. RESULTS: The IVW-MR analysis uncovered a positive correlation between the intake of HMG CoA reductase inhibitors and the increased risk of psoriasis (odds ratio [OR] = 1.167, 95% confidence interval [CI] = 1.084-1.257). Similarly, the use of thyroid preparations (OR=1.080, 95% CI=1.026-1.138), nonsteroidal anti-inflammatory and antirheumatic products (OR=1.406, 95% CI=1.037-1.908), anilides (OR=1.379, 95% CI=1.004-1.894), antihistamines for systemic use (OR=1.341, 95% CI=1.104-1.630), and antihypertensives (OR=1.099, 95% CI=1.016-1.190) were associated with an increased risk of psoriasis. We did not find evidence from IVW-MR for other associations. CONCLUSIONS: Our study offers a causal testimony that the intake of HMG CoA reductase inhibitors, thyroid preparations, nonsteroidal anti-inflammatory and antirheumatic products, anilides, antihistamines for systemic use, and antihypertensives will potentially increase the risk of psoriasis.
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BACKGROUND & AIMS: Previous studies have reported an inconsistent relationship between overactive bladder (OAB) and the consumption of tea, coffee, and caffeine. Our study aims to determine these associations in a large and nationally representative adult sample. METHODS: This cross-sectional study included 15,379 participants from the 2005-2018 US National Health and Nutrition Examination Survey (NHANES) database. The outcome was the risk of wet OAB that was diagnosed when the OAB symptom score was ≥3 with urgent urinary incontinence and excluded other diseases affecting diagnosis. The exposures were the consumption of tea, coffee, and caffeine. Weighted logistic regression models were established to explore these associations by calculating odds ratios (OR) and 95% confidence intervals (CI), as did restricted cubic splines (RCS) used to analyze the nonlinear associations. RESULT: Of all the participants (n = 15,379), 2207 had wet OAB. Mean [SE] consumption of tea, total coffee, caffeinated coffee, decaffeinated coffee, and caffeine was 233.6 [15.7] g/day, 364.3 [15.5] g/day, 301.6 [14.9] g/day, 62.7 [7.9] g/day, 175.5 [6.6] mg/day in participants with wet OAB, respectively. In the fully adjusted model, compared to those without tea consumption, the high consumption of tea (>481 g/day) was associated with an increased risk of wet OAB (OR: 1.29; 95%CI: 1.01-1.64). Low decaffeinated coffee (0.001-177.6 g/day) had a negative association with the risk (OR: 0.66; 95%CI: 0.49-0.90). In the RCS analysis, tea consumption showed a positive linear association with the risk of wet OAB, and decaffeinated coffee showed a nonlinear relationship with the risk and had a turning point of 78 g/day in the U-shaped curve between 0 and 285 g/day. Besides, total coffee, caffeinated coffee, and caffeine consumption had no significant association with the risk. Interestingly, in the high tea consumption, participants with high total coffee consumption [>527.35 g/day, OR and 95%CI: 2.14(1.16-3.94)] and low caffeine consumption [0.1-74.0 mg/day, OR and 95%CI: 1.50(1.03-2.17)] were positively associated with the risk of wet OAB. CONCLUSION: High tea consumption was associated with the increased risk of wet OAB, especially intake together with high total coffee and low caffeine consumption, but no significant association with the single consumption of total coffee and caffeine. Low decaffeinated coffee was associated with a decreased risk of wet OAB. It is necessary to control tea intake when managing the liquid intake of wet OAB patients.
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Cafeína , Café , Encuestas Nutricionales , Té , Vejiga Urinaria Hiperactiva , Humanos , Café/efectos adversos , Té/efectos adversos , Femenino , Masculino , Vejiga Urinaria Hiperactiva/epidemiología , Cafeína/efectos adversos , Cafeína/administración & dosificación , Estudios Transversales , Adulto , Persona de Mediana Edad , Estados Unidos/epidemiología , Anciano , Factores de Riesgo , Adulto JovenRESUMEN
Background: As an inevitable event after kidney transplantation, ischemiaâreperfusion injury (IRI) can lead to a decrease in kidney transplant success. The search for signature genes of renal ischemiaâreperfusion injury (RIRI) is helpful in improving the diagnosis and guiding clinical treatment. Methods: We first downloaded 3 datasets from the GEO database. Then, differentially expressed genes (DEGs) were identified and applied for functional enrichment analysis. After that, we performed three machine learning methods, including random forest (RF), Lasso regression analysis, and support vector machine recursive feature elimination (SVM-RFE), to further predict candidate genes. WGCNA was also executed to screen candidate genes from DEGs. Then, we took the intersection of candidate genes to obtain the signature genes of RIRI. Receiver operating characteristic (ROC) analysis was conducted to measure the predictive ability of the signature genes. KaplanâMeier analysis was used for association analysis between signature genes and graft survival. Verifying the expression of signature genes in the ischemia cell model. Results: A total of 117 DEGs were screened out. Subsequently, RF, Lasso regression analysis, SVM-RFE and WGCNA identified 17, 25, 18 and 74 candidate genes, respectively. Finally, 3 signature genes (DUSP1, FOS, JUN) were screened out through the intersection of candidate genes. ROC analysis suggested that the 3 signature genes could well diagnose and predict RIRI. KaplanâMeier analysis indicated that patients with low FOS or JUN expression had a longer OS than those with high FOS or JUN expression. Finally, we validated using the ischemia cell model that compared to the control group, the expression level of JUN increased under hypoxic conditions. Conclusions: Three signature genes (DUSP1, FOS, JUN) offer a good prediction for RIRI outcome and may serve as potential therapeutic targets for RIRI intervention, especially JUN. The prediction of graft survival by FOS and JUN may improve graft survival in patients with RIRI.
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In this study, we aimed to identify transplantation tolerance (TOL)-related gene signature and use it to predict the different types of renal allograft rejection performances in kidney transplantation. Gene expression data were obtained from the Gene Expression Omnibus (GEO) database, differently expressed genes (DEGs) were performed, and the gene ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were also conducted. The machine learning methods were combined to analyze the feature TOL-related genes and verify their predictive performance. Afterward, the gene expression levels and predictive performances of TOL-related genes were conducted in the context of acute rejection (AR), chronic rejection (CR), and graft loss through heatmap plots and the receiver operating characteristic (ROC) curves, and their respective immune infiltration results were also performed. Furthermore, the TOL-related gene signature for graft survival was conducted to discover gene immune cell enrichment. A total of 25 TOL-related DEGs were founded, and the GO and KEGG results indicated that DEGs mainly enriched in B cell-related functions and pathways. 7 TOL-related gene signature was constructed and performed delightedly in TOL groups and different types of allograft rejection. The immune infiltration analysis suggested that gene signature was correlated with different types of immune cells. The Kaplan-Meier (KM) survival analysis demonstrated that BLNK and MZB1 were the prognostic TOL-related genes. Our study proposed a novel gene signature that may influence TOL in kidney transplantation, providing possible guidance for immunosuppressive therapy in kidney transplant patients.
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Trasplante de Riñón , Humanos , Trasplante de Riñón/efectos adversos , Tolerancia al Trasplante , Pronóstico , Trasplante Homólogo , Aprendizaje AutomáticoRESUMEN
Bladder cancer (BLCA) is a common and difficult-to-manage disease worldwide. Most common type of BLCA is urothelial carcinoma (UC). Fibrillin 2 (FBN2) was first discovered while studying Marfan syndrome, and its encoded products are associated with elastin fibres. To date, the role of FBN2 in BLCA remains unclear. The authors first downloaded data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The patients were divided into high FBN2 expression and low FBN2 expression groups, and the survival curve, clinical characteristics, tumour microenvironment (TME), and immune cell differences were analysed between the two groups. Then, the differentially expressed genes (DEGs) were filtered, and functional enrichment for DEGs was performed. Finally, chemotherapy drug susceptibility analysis based on the high and low FBN2 groups was conducted. The authors found upregulated expression of FBN2 in BLCA and proved that FBN2 could be an independent prognostic factor for BLCA. TME analysis showed that the expression of FBN2 affects several aspects of the TME. The upregulated expression of FBN2 was associated with a high stromal score, which may lead to immunosuppression and be detrimental to immunotherapy. In addition, the authors found that NK cells resting, macrophage M0 infiltration, and other phenomena of immune cell infiltration appeared in the high expression group of FBN2. The high expression of FBN2 was related to the high sensitivity of some chemotherapy drugs. The authors systematically investigated the effects and mechanisms of FBN2 on BLCA and provided a new understanding of the role of FBN2 as a risk factor and TME influencer in BLCA.
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Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/genética , Fibrilina-2 , Microambiente Tumoral , Factores de RiesgoRESUMEN
OBJECTIVE: Bladder cancer (BC) is the most common malignancy in the urinary system and is prone to recurrence and metastasis. Pyroptosis is a kind of cell necrosis that is triggered by the gasdermin protein family. lncRNAs are noncoding RNAs that are more than 200 nucleotides long. Both pyroptosis and lncRNAs are associated with tumor development and progression. This study is aimed at exploring and establishing a prognostic signature of BC based on pyroptosis-related lncRNAs. METHODS: In this study, The Cancer Genome Atlas (TCGA) database provided us with the RNA sequencing transcriptome data of bladder cancer patients, and we identified differentially expressed pyroptosis-related lncRNAs in bladder cancer. Then, the prognostic significance of these lncRNAs was assessed using univariate Cox regression analysis and LASSO regression analysis. Subsequently, 4 pyroptosis-related lncRNAs, namely, AL121652.1, AL161729.4, AC007128.1, and AC124312.3, were identified by multivariate Cox regression analysis, thus constructing the prognostic risk model. Then, we compared the levels of immune infiltration, differences in cell function, immune checkpoints, and m6A-related gene expression levels between the high- and low-risk groups. RESULT: Patients were divided into low-risk or high-risk groups based on the median risk score. Kaplan-Meier survival analysis indicated that the overall survival of bladder cancer patients in the low-risk group was substantially superior to that in the high-risk group (p < 0.001). The receiver operating characteristic (ROC) curve further confirmed the credibility of our model. Moreover, gene set enrichment analysis (GSEA) indicated that these were different signal pathways significantly enriched between the two groups. Immune infiltration, immune checkpoint, and N6-methyladenosine-related gene analysis also reflected that there were notable differences between the two groups. CONCLUSION: Therefore, this prognostic risk model is based on the level of pyroptotic lncRNAs, which is conducive to individualized assessment of the risk of patients and provides a reference for clinical treatment. This will also help provide insights into the prognosis and treatment of bladder cancer.
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Piroptosis/genética , ARN Largo no Codificante/genética , Neoplasias de la Vejiga Urinaria/genética , Humanos , Modelos Teóricos , Pronóstico , Medición de Riesgo , Tasa de Supervivencia , Neoplasias de la Vejiga Urinaria/mortalidadRESUMEN
The primary subtypes of renal cell carcinoma (RCC) include clear cell, papillary and chromophobe RCC. RCC occurs often due to loss of von HippelLindau (VHL) and accumulation of lipids and glycogen, and RCC cells may exhibit sensitivity to the disruption of normal metabolism or homologous recombination gene defect. Although the application of moleculartargeted drugs (tyrosine kinase inhibitors) and immune checkpoint inhibitors has been recommended for the treatment of advanced RCC, more targets of DNA damage repair (DDR) signaling pathway involved in the synthetic lethal effect have been investigated. However, although achievements has been made in the exploration of the roles of DDR genes on RCC progression, their association has not been systematically summarized. Poly (ADPribose) polymerase (PARP) 1 inhibitors are used in tumors with BRCA1/2 DNA repairassociated mutations. PARP family enzymes perform posttranslational modification functions and participate in DDR and cell death. Inhibitors of PARP, ataxia telangiectasia mutant gene and polymerase θ serve key roles in the treatment of specific RCC subtypes. PARP1 may serve as an important biological marker to predict the therapeutic effect of immune checkpoint inhibitors and evaluate the prognosis of patients with ccRCC with polybromo 1 mutation. Therefore, the roles of DDR pathway on RCC progression or treatment may hold promises for the treatment of certain specific types of RCC.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/metabolismo , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Inhibidores de Puntos de Control Inmunológico , Ribosa , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/genética , Neoplasias Renales/metabolismo , Reparación del ADN , Poli(ADP-Ribosa) Polimerasas/metabolismo , Daño del ADN , Inhibidores de Proteínas Quinasas , Glucógeno , Lípidos , Adenosina DifosfatoRESUMEN
Background: Renal transplantation can significantly improve the survival rate and quality of life of patients with end-stage renal disease, but the probability of acute rejection (AR) in adult renal transplant recipients is still approximately 12.2%. Machine learning (ML) is superior to traditional statistical methods in various clinical scenarios. However, the current AR model is constructed only through simple difference analysis or a single queue, which cannot guarantee the accuracy of prediction. Therefore, this study identified and validated new gene sets that contribute to the early prediction of AR and the prognosis prediction of patients after renal transplantation by constructing a more accurate AR gene signature through ML technology. Methods: Based on the Gene Expression Omnibus (GEO) database and multiple bioinformatic analyses, we identified differentially expressed genes (DEGs) and built a gene signature via LASSO regression and SVM analysis. Immune cell infiltration and immunocyte association analyses were also conducted. Furthermore, we investigated the relationship between AR genes and graft survival status. Results: Twenty-four DEGs were identified. A 5 gene signature (CPA6, EFNA1, HBM, THEM5, and ZNF683) were obtained by LASSO analysis and SVM analysis, which had a satisfied ability to differentiate AR and NAR in the training cohort, internal validation cohort and external validation cohort. Additionally, ZNF683 was associated with graft survival. Conclusion: A 5 gene signature, particularly ZNF683, provided insight into a precise therapeutic schedule and clinical applications for AR patients.
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Trasplante de Riñón , Adulto , Humanos , Trasplante de Riñón/efectos adversos , Calidad de Vida , Supervivencia de Injerto , Pronóstico , RiñónRESUMEN
Wilms tumor (WT) is a common pediatric renal cancer, with a poor prognosis and high-risk recurrence in some patients. The inflammatory microenvironment is gradually gaining attention in WT. In this study, novel inflammation-related signatures and prognostic model were explored and integrated using bioinformatics analysis. The mRNA profile of pediatric patients with WT and inflammation-related genes (IRGs) were acquired from Therapeutically Available Research to Generate Effective Treatments (TARGET) and Gene Set Enrichment Analysis (GSEA) databases, respectively. Then, a novel prognostic model founded on 7-IRGs signature (BICC1, CSPP1, KRT8, MYCN, NELFA, NXN, and RNF113A) was established by the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression to stratify pediatric patients with WT into high- and low-risk groups successfully. And a stable performance of the prognostic risk model was verified in predicting overall survival (OS) by receiver-operating characteristic (ROC) curves, Kaplan-Meier (KM) curves, and independent prognostic analysis (p < 0.05). In addition, a novel nomogram integrating risk scores with good robustness was developed and validated by C-index, ROC, and calibration plots. The potential function and pathway were explored via Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and GSEA, with mainly inflammation and immune-related biological processes. The higher-risk scores, the lower immune infiltration, as shown in the single-sample GSEA (ssGSEA) and tumor microenvironment (TME) analysis. The drug sensitivity analysis showed that regulating 7-IRGs signature has a significant correlation with the chemotherapy drugs of WT patients. In summary, this study defined a prognostic risk model and nomogram based on 7-IRGs signature, which may provide novel insights into clinical prognosis and inflammatory study in WT patients. Besides, enhancing immune infiltration based on inflammatory response and regulating 7-IRGs signature are beneficial to ameliorating the efficacy in WT patients.
Asunto(s)
Perfilación de la Expresión Génica , Tumor de Wilms , Biomarcadores de Tumor/genética , Niño , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Inflamación/genética , Estimación de Kaplan-Meier , Masculino , Microambiente Tumoral/genética , Tumor de Wilms/genéticaRESUMEN
Background: As an epigenetic alteration, DNA methylation plays an important role in early Wilms tumorigenesis and is possibly used as marker to improve the diagnosis and classification of tumor heterogeneity. Methods: Methylation data, RNA-sequencing (RNA-seq) data, and corresponding clinical information were downloaded from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. The prognostic values of DNA methylation subtypes in Wilms tumor were identified. Results: Four prognostic subtypes of Wilms tumor patients were identified by consensus cluster analysis performed on 312 independent prognostic CpG sites. Cluster one showed the best prognosis, whereas Cluster two represented the worst prognosis. Unique CpG sites identified in Cluster one that were not identified in other subtypes were assessed to construct a prognostic signature. The prognostic methylation risk score was closely related to prognosis, and the area under the curve (AUC) was 0.802. Furthermore, the risk score based on prognostic signature was identified as an independent prognostic factor for Wilms tumor in univariate and multivariate Cox regression analyses. Finally, the abundance of B cell infiltration was higher in the low-risk group than in the high-risk group, based on the methylation data. Conclusion: Collectively, we divided Wilms tumor cases into four prognostic subtypes, which could efficiently identify high-risk Wilms tumor patients. Prognostic methylation risk scores that were significantly associated with the adverse clinical outcomes were established, and this prognostic signature was able to predict the prognosis of Wilms tumor in children, which may be useful in guiding clinicians in therapeutic decision-making. Further independent studies are needed to validate and advance this hypothesis.
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To predict survival outcomes for individual patients with clinical T1 high-grade (T1HG) bladder cancer (BC), data from the Surveillance Epidemiology and End Results (SEER) database were analyzed in the present study. The data of 6,980 cases of T1HG BC between 2004 and 2014 were obtained from the SEER database. Uni- and multivariate Cox analyses were performed to identify significant prognostic factors. Subsequently, prognostic nomograms for predicting 3- and 5-year overall survival (OS) and cancer-specific survival (CSS) rates were constructed based on the SEER database. Clinical information from the SEER database was divided into internal and external groups and used to validate the nomograms. In addition, calibration plot diagrams and concordance indices (C-indices) were used to verify the predictive performance of the nomogram. A total of 6,980 patients were randomly allocated to the training cohort (n=4,886) or the validation cohort (n=2094). Univariate and multivariate Cox analyses indicated that age, ethnicity, tumor size, marital status, radiation and surgical status were independent prognostic factors. These characteristics were used to establish nomograms. The C-indices for OS and CSS rate predictions for the training cohort were 0.707 (95% CI, 0.693-0.721) and 0.700 (95% CI, 0.679-0.721), respectively. Internal and external calibration plot diagrams exhibited an excellent consistency between actual survival rates and nomogram predictions, particularly for 3- and 5-year OS and CSS. The significant prognostic factors in patients with T1HG BC were age, ethnicity, marital status, tumor size, status of surgery and use of radiation. In the present study, a nomogram was developed that may serve as an effective and convenient evaluation tool to help surgeons perform individualized survival evaluations and mortality risk determination for patients with T1HG BC.
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High-resolution observation of biological process is vital for biological researches and diagnosing diseases, which requires accurate diagnosis that involves coordinating imaging technologies such as fluorescence and magnetic resonance (MR). Nowadays, metal-based labels have been used for dual modality imaging. However, heavy metal ions are not environment-and organism-friendly. Therefore, it is a desirable to fabricate a metal-free label with fluorescence and MR properties. Herein, we synthesized boron-doped carbon dots (B-CDs) with dual modal properties through a one-pot solvothermal process. Compared with boron-free CDs, B-CDs exhibited apparent red-shift fluoresence emission, higher fluorescence intensity, and higher longitudinal relaxivity (r1 = 5.13â¯mM-1 s-1). It demonstrated that boron doping can enhance the fluorescence intensity of CDs, and maybe lead to form paramagnetic centers. The fluorescence and MR imaging of B-CDs make them a prospective label for clinical applications as a result of their oversimplified synthesis process, low cost, good biocompatibility and low toxicity. It will open a new window for building novel imaging labels.