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1.
Int J Obes (Lond) ; 48(4): 461-468, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38071395

RESUMO

BACKGROUND: There is some evidence to suggest that there may be a link between body mass index (BMI) and the development of kidney stones, it remains unclear whether weight change was associated with the presence of kidney stone. AIMS: The objective of this study was to investigate the potential association between changes patterns in weight during adulthood and the incidence of kidney stone. METHODS: This study included 14472 participants aged 30-75 years, whose BMI was recorded at both baseline and 10 years prior to the survey. We categorized individuals into five weight change patterns: stable healthy, non-obesity to obesity, obesity to non-obesity, stable obesity, and maximum overweight. Odds ratios (OR) and 95% confidence intervals (CI) relating weight change to incident kidney stone were calculated using logistic regression models adjusting for covariates. The non-linear association between absolute weight change was investigated using the restricted cubic spline (RCS) regression. The supposed population attributable fraction (PAF) for the weight change patterns was calculated. RESULTS: After adjusting for all confounders, participants changing from non-obesity to obesity, obesity to non-obesity, and stable obesity had significantly higher risks of kidney stone than those with healthy weight during adulthood (OR = 1.59, 95% CI:1.18-2.13; OR = 1.78, 95% CI: 1.47-2.16; OR = 1.80, 95% CI: 1.48-2.19, respectively). A U-shaped association was observed, and the risk of kidney stone was lowest in participants with stable healthy BMI. If the population had maintained a healthy BMI, a 28.7% (95% CI: 18.6%-37.5%) lower incidence of kidney stones was observed. CONCLUSIONS: This study found that changes in weight during adulthood are linked to the risk of developing kidney stones. Maintaining healthy weight during adulthood is important for reducing the risk of developing kidney stones.


Assuntos
Cálculos Renais , Obesidade , Humanos , Adulto , Incidência , Fatores de Risco , Obesidade/complicações , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Índice de Massa Corporal , Cálculos Renais/epidemiologia , Cálculos Renais/etiologia
2.
Respir Res ; 25(1): 313, 2024 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-39154161

RESUMO

BACKGROUND: Due to a special hemodynamic feature, pulmonary vascular disease in pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) has two stages: reversible and irreversible. So far, the mechanism involved in the transition from reversible to irreversible stage is elusive. Moreover, no recognized and reliable assessments to distinguish these two stages are available. Furthermore, we found that compared with control and reversible PAH, thrombospondin-4 (THBS4) was significantly upregulated in irreversible group by bioinformatic analysis. Hence, we further verify and investigate the expression and role of THBS4 in PAH-CHD. METHODS: We established the monocrotaline plus aorto-cava shunt-induced (MCT-AV) rat model. We measured the expression of THBS4 in lung tissues from MCT-AV rats. Double immunofluorescence staining of lung tissue for THBS4 and α-SMA (biomarker of smooth muscle cells) or vWF (biomarker of endothelial cells) to identify the location of THBS4 in the pulmonary artery. Primary pulmonary artery smooth muscle cells (PASMCs) were cultivated, identified, and used in this study. THBS4 was inhibited and overexpressed by siRNA and plasmid, respectively, to explore the effect of THBS4 on phenotype transformation, proliferation, apoptosis, and migration of PASMCs. The effect of THBS4 on pulmonary vascular remodeling was evaluated in vivo by adeno-associated virus which suppressed THBS4 expression. Circulating level of THBS4 in patients with PAH-CHD was measured by ELISA. RESULTS: THBS4 was upregulated in the lung tissues of MCT-AV rats, and was further upregulated in severe pulmonary vascular lesions. And THBS4 was expressed mainly in PASMCs. When THBS4 was inhibited, contractile markers α-SMA and MYH11 were upregulated, while the proliferative marker PCNA was decreased, the endothelial-mensenchymal transition marker N-cad was downregulated, proapototic marker BAX was increased. Additionally, proliferation and migration of PASMCs was inhibited and apoptosis was increased. Conversely, THBS4 overexpression resulted in opposite effects. And the impact of THBS4 on PASMCs was probably achieved through the regulation of the PI3K/AKT pathway. THBS4 suppression attenuated pulmonary vascular remodeling. Furthermore, compared with patients with simple congenital heart disease and mild PAH-CHD, the circulating level of THBS4 was higher in patients with severe PAH-CHD. CONCLUSIONS: THBS4 is a promising biomarker to distinguish reversible from irreversible PAH-CHD before repairing the shunt. THBS4 is a potential treatment target in PAH-CHD, especially in irreversible stage.


Assuntos
Cardiopatias Congênitas , Hipertensão Arterial Pulmonar , Ratos Sprague-Dawley , Trombospondinas , Animais , Humanos , Masculino , Ratos , Células Cultivadas , Cardiopatias Congênitas/metabolismo , Cardiopatias Congênitas/complicações , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Hipertensão Arterial Pulmonar/metabolismo , Hipertensão Arterial Pulmonar/patologia , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Trombospondinas/metabolismo , Trombospondinas/biossíntese , Trombospondinas/genética
3.
BMC Pregnancy Childbirth ; 24(1): 658, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-39390395

RESUMO

OBJECTIVE: To investigate the structural abnormalities, genetic results, and postnatal clinical outcomes of fetuses with bovine aortic arch (Bovine Aortic Arch, BAA) to provide a basis for prenatal counseling and management. METHODS: A retrospective analysis was conducted on 216 fetuses diagnosed with bovine aortic arch through prenatal ultrasound screening at the First Affiliated Hospital of Anhui Medical University and the No.901 Hospital of the Joint Service of the People's Liberation Army from January 2019 to February 2023. Their family history of genetic diseases, prenatal screening results, and postnatal follow-up data were collected. The fetuses were divided into an isolated BAA group (n = 192) and a non-isolated BAA group (n = 24). Chromosomal karyotyping and copy number variation (CNV) testing were conducted, and statistical analysis was performed using SPSS 22.0 software. RESULTS: Of the 216 fetuses with BAA, 192 were isolated BAA (88.89%), and 24 were non-isolated BAA (11.11%). Among the isolated BAA fetuses, only 1 case (0.52%) had chromosomal karyotype and pathogenic CNV abnormalities. Among the non-isolated BAA fetuses, 4 cases (16.67%) had chromosomal or CNV abnormalities, but the overall risk was low. The postnatal outcomes of isolated BAA fetuses were good (99.48%), while 79.17% of non-isolated BAA fetuses had good postnatal outcomes. CONCLUSION: Most BAA fetuses are isolated, with a very low incidence of chromosomal abnormalities and pathogenic CNVs, and have good postnatal outcomes. The clinical value of isolated BAA is limited, and invasive prenatal diagnosis is not recommended for low-risk populations. Prenatal screening should focus on the risk of concurrent severe structural anomalies and chromosomal abnormalities.


Assuntos
Aorta Torácica , Ultrassonografia Pré-Natal , Feminino , Gravidez , Humanos , Estudos Retrospectivos , Ultrassonografia Pré-Natal/estatística & dados numéricos , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/anormalidades , Aorta Torácica/embriologia , Adulto , Cariotipagem , Variações do Número de Cópias de DNA , Aberrações Cromossômicas/estatística & dados numéricos , Diagnóstico Pré-Natal/métodos , Recém-Nascido , Resultado da Gravidez , Feto/anormalidades
4.
Future Oncol ; 15(36): 4207-4222, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31789059

RESUMO

Aim: To build a prognostic nomogram based on log odds of positive lymph nodes for patients with gastric carcinoma (GC) after resection, and to compare the predictive performance with the American Joint Committee on Cancer (AJCC) staging system and lymph node ratio (LNR). Methods: Multivariate analyses were performed to identify the independent variables for cancer-specific survival (CSS). A nomogram was constructed based on independent clinicopathological factors. Results: The C-indices for predicting CSS were 0.674 in development cohort and 0.647 in validation cohort, which were higher than that of the AJCC staging system and LNR. Conclusion: The nomogram was more accurate than the AJCC staging system and LNR for predicting CSS in patients undergoing resection for GC.


Assuntos
Linfonodos/patologia , Neoplasias Gástricas/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Nomogramas , Razão de Chances , Vigilância da População , Cuidados Pós-Operatórios , Prognóstico , Pontuação de Propensão , Programa de SEER , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/cirurgia , Carga Tumoral
5.
Int J Immunogenet ; 46(6): 419-426, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31183977

RESUMO

Numerous published studies have investigated the relationship between the CD14-260C>T (rs2569190) polymorphism and the risk of myocardial infarction (MI). However, the results are still conflicting and inconclusive. Potentially eligible published articles were searched in four databases including PubMed, Web of Science, EMBASE and Chinese Biomedical Database (CBM). The odds ratio (OR) with its 95% confidence interval (CI) was used to estimate the strength of the associations. Thirteen papers including 17 case-control studies were included, reporting a total of 6,443 MI patients and 6,315 controls. A significant increase in overall MI susceptibility was identified in the homozygote model. In the subgroup analysis, with respect to the type of MI, a significantly increasing acute MI susceptibility was found in the homozygote model. In the subgroup analysis for ethnicity, a significant increased susceptibility was found in Asian populations in allele, homozygote, recessive and dominant models. However, no significant association was found among Caucasian populations. In conclusion, there may be a moderate association between the CD14-260C>T polymorphism and acute MI susceptibility. This association may be different between ethnicities with the CD14-260C>T polymorphism being a risk factor for myocardial infarction in Asian populations.


Assuntos
Povo Asiático/genética , Receptores de Lipopolissacarídeos/genética , Infarto do Miocárdio/genética , Polimorfismo de Nucleotídeo Único , Alelos , Estudos de Casos e Controles , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Infarto do Miocárdio/etnologia , Razão de Chances , Fatores de Risco , População Branca/genética
7.
Heliyon ; 10(1): e23429, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38170062

RESUMO

Objectives: While several indicators have been studied, the association of body roundness index (BRI) with non-alcoholic fatty liver disease (NAFLD) remains unclear. We aimed to explore the association between BRI and ultrasound-defined NAFLD. Methods: The sample dataset was extracted from the National Health and Nutrition Examination Survey (NHANES) during the period of 2017-2018. The diagnosis of NAFLD was determined based on the controlled attenuated parameter (CAP≥248 dB/m) score of liver ultrasound transient elastography (LUTE). Participants with excessive alcohol use and viral hepatitis were excluded. To delve deeper into the relationship, Multivariable logistic regression with adjustment for confounding variables and smoothing curve analysis was used to investigate the association and nonlinear relationships between BRI and NAFLD. Results: Among 4210 individuals aged 20 years or older included in the study, 28.2 % had NAFLD. Compared to the first tertile, BRI notably increased the risk of NAFLD 3.53-fold [95 % confidence interval (CI) = 2.73-4.57] in the second tertile and 7.00-fold (95%CI = 5.29-9.27) in the third tertile after adjusting for multiple covariates (P for trend <0.001). Furthermore, when BRI was treated as a continuous variable, one unit of increment in BRI was associated with 41 % higher odds of NAFLD [adjusted odds ratio (aOR) = 1.41; 95%CI = 1.34-1.48; P < 0.001]. The associations of BRI with NAFLD persisted in all subgroup analyses. A smoothing curve fitting demonstrated that the relationship between BRI and NAFLD was a nonlinear connection. The risk of NAFLD increased significantly when BRI was lower than 4.82, after which the curve showed a modest ascent. Conclusion: Higher BRI was consistently associated with an increased risk of NAFLD in US adults. BRI is a risk factor for NAFLD, and there is an imperative to give more attention to lowering the BRI.

8.
Ann Med ; 55(1): 2197652, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37052341

RESUMO

OBJECTIVE: Systemic immune-inflammation index (SII), a novel inflammatory indicator based on platelets, neutrophils and lymphocytes, has been shown to be associated with prognostic value in several solid tumors. However, its prognostic value in nonalcoholic fatty liver disease (NAFLD) has not been reported yet. Therefore, the present study aimed to investigate the prognostic value of SII in individuals with NAFLD. METHODS: Data was collected from the 2005 to 2014 National Health and Nutrition Examination Survey (NHANES, https://www.cdc.gov/nchs/nhanes/index.htm), and vital status was derived from the National Death Index (NDI) up to 31 December 2015. NAFLD was diagnosed based on Hepatic Steatosis Index (HSI). Multivariate Cox regression and Kaplan-Meier survival curves were performed to measure the hazard ratios (HRs) and 95% confidence interval (CI). Our study investigated the relationship between SII and all-cause mortality by using two-part linear regression models with penalized splines, as well as Cox models with penalized splines. RESULTS: A total of 10,787 NAFLD participants (44.14% men) aged ≥20 years old were enrolled. There were 776 deaths from all causes after a mean follow-up period of 5.6 years. According to the full adjusted Cox regression analysis, the low log2-SII group (quartile 1) and the highest log2-SII group (quartile 4) were significantly associated with increased mortality from all causes (aHR =1.86; 95% CI: 1.47-2.37; p < 0.0001). After controlling for confounders, an increase in log2-SII was associated with an increased all-cause mortality risk of 41% for every unit raised (aHR = 1.41; 95% CI: 1.26-1.57; p < 0.0001). After adjusting for multiple potential confounders, the association between log2-SII and all-cause mortality was nonlinear, and the threshold value was 8.8. There was no association between an increase of one unit in log2-SII and all-cause mortality below the threshold (aHR = 0.90, 95% CI: 0.71-1.15, p = 0.419). However, a higher log2-SII was associated with a higher risk of death from any cause when it exceeded the threshold (aHR = 1. 73, 95% CI: 1.49-2.02, p < 0.001).Based on a study of US NAFLD patients, it was found that the baseline log2-SII is associated with all-cause mortality. Elevated SII is associated with poor survival among NAFLD patients.KEY MESSAGESUsing a large nationally representative survey of individuals among US adults, the study demonstrated that log2-SII was J-shaped and associated with all-cause death among individuals with NAFLD.Spline analyses demonstrated that the association between log2-SII and all-cause mortality was non-linear after adjusting for multiple potential confounders, and the threshold value was 8.8.Higher log2-SII associated with poor survival in NAFLD.


Assuntos
Neoplasias , Hepatopatia Gordurosa não Alcoólica , Adulto , Masculino , Humanos , Adulto Jovem , Feminino , Hepatopatia Gordurosa não Alcoólica/complicações , Inquéritos Nutricionais , Inflamação/complicações , Prognóstico
9.
Cell Metab ; 35(4): 585-600.e5, 2023 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-36931274

RESUMO

Breakthrough SARS-CoV-2 infections of vaccinated individuals are being reported globally, resulting in an increased risk of hospitalization and death among such patients. Therefore, it is crucial to identify the modifiable risk factors that may affect the protective efficacy of vaccine use against the development of severe COVID-19 and thus to initiate early medical interventions. Here, in population-based studies using the UK Biobank database and the 2021 National Health Interview Survey (NHIS), we analyzed 20,362 participants aged 50 years or older and 2,588 aged 18 years or older from both databases who tested positive for SARS-COV-2, of whom 33.1% and 67.7% received one or more doses of vaccine, respectively. In the UK Biobank, participants are followed from the vaccination date until October 18, 2021. We found that obesity and metabolic abnormalities (namely, hyperglycemia, hyperlipidemia, and hypertension) were modifiable factors for severe COVID-19 in vaccinated patients (all p < 0.05). When metabolic abnormalities were present, regardless of obesity, the risk of severe COVID-19 was higher than that of metabolically normal individuals (all p < 0.05). Moreover, pharmacological interventions targeting such abnormalities (namely, antihypertensive [adjusted hazard ratio (aHR) 0.64, 95% CI 0.48-0.86; p = 0.003], glucose-lowering [aHR 0.55, 95% CI 0.36-0.83; p = 0.004], and lipid-lowering treatments [aHR 0.50, 95% CI 0.37-0.68; p < 0.001]) were significantly associated with a reduced risk for this outcome. These results show that more proactive health management of patients with obesity and metabolic abnormalities is critical to reduce the incidence of severe COVID-19 after vaccination.


Assuntos
COVID-19 , Humanos , SARS-CoV-2 , Vacinação , Obesidade , Fatores de Risco
10.
Clin Res Hepatol Gastroenterol ; 46(10): 102002, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35973558

RESUMO

OBJECTIVE: To determine the prognostic value of C-peptide in long-term nonalcoholic fatty liver disease (NAFLD) mortality. METHODS: A total of 4670 participants with NAFLD were enrolled in this study. Multivariable Cox regression models evaluated the links between C-peptide levels and all-cause and cardiovascular disease (CVD) mortality risk using adjusted hazard ratios (aHR). In addition, a two­piecewise Cox model with penalized splines was adapted to investigate the nonlinear relationships between C-peptide and mortality. RESULTS: After a mean follow­up period of 20 years, 1714 deaths from all causes were recorded. In an adjusted Cox regression analysis, using the low C-peptide group as the reference (quartile 1), higher C-peptide (quartile 4) was notably associated with increased all-cause mortality (aHR =1.39; 95% CI: 1.18-1.65) and CVD death (aHR = 1.97; 95% CI: 1.41-2.76). Spline analyses demonstrated that the association between C-peptide levels and all-cause mortality was U-shaped, with a threshold value of 0.41 nmol/L. Below the threshold, every one-unit increment in C-peptide had a 70% reduced risk of all-cause death (aHR = 0.30, 95% CI: 0.1-0.7). Above the threshold, the C-peptide levels were associated with a higher probability of all-cause death (aHR = 1. 3, 95% CI:1.2-1.4). CONCLUSIONS: In the US NAFLD population defined by ultrasound, a U-shaped association was detected between baseline serum C-peptide level and all-cause mortality.


Assuntos
Doenças Cardiovasculares , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Doenças Cardiovasculares/etiologia , Peptídeo C , Modelos de Riscos Proporcionais , Análise de Regressão , Fatores de Risco
12.
Clin Res Hepatol Gastroenterol ; 45(5): 101587, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33662631

RESUMO

OBJECTIVE: Epithelial-to-mesenchymal transition (EMT) is an essential biological process of cancer progression associated with increased metastatic potential and initiation. Herein, we aimed to develop and validate a robust EMT-related prognostic signature that could predict the prognosis of patients with hepatocellular carcinoma (HCC). METHODS: Messenger RNA expression matrix and clinicopathological data were retrieved from The Cancer Genome Atlas (TCGA) and identified differentially expressed genes (DEGs) between HCC tissues and adjacent non-tumor samples. Univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox regression analysis were performed to establish a prognosis signature. Kaplan-Meier survival curve, time-dependent receiver operating characteristic (ROC), multivariate Cox regression analysis, nomogram, C-index, and decision curve analysis (DCA) were performed to investigate the prognostic performance of the signature. The prognostic performance of the new signature was further validated in an independent external cohort. A support vector machine (SVM) approach was performed to evaluate the diagnostic value of the identified genes. RESULTS: A seven-gene signature was formulated to classify patients into high-risk and low-risk groups with discrepant overall survival (OS) in two cohorts (all P < 0.0001), and the former illustrated shorter survival time than the latter even stratified by various groups. The new signature has presented an excellent performance for predicting survival prognosis. Multivariate analysis showed that the signature was an independent risk factor for HCC. The SVM classifier based on the seven genes presented an excellent diagnostic power in differentiating early HCC and normal tissues. Gene Set Enrichment Analyses (GSEA) demonstrated multiple biological processes and pathways to provide novel insights into the development of HCC. CONCLUSION: We established and validated a prognostic signature based on EMT-related genes with good predictive value for HCC survival. The diagnostic performance of the signature had been demonstrated to accurately distinguish early HCC from control individuals.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Transição Epitelial-Mesenquimal/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Prognóstico
13.
J Comput Biol ; 28(1): 79-88, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32493063

RESUMO

Idiopathic pulmonary arterial hypertension (IPAH) is a fatal cardiovascular disease event with significant morbidity and mortality. However, its potential molecular mechanisms and potential key genes have not been totally evaluated. The gene expression profile of GSE33463, including 30 individuals diagnosed with IPAH and 41 normal controls, was downloaded from Gene Expression Omnibus database. The differentially expressed genes (DEGs) were identified using limma package in R. Gene Ontology (GO) annotation, the Kyoto Encyclopedia of Genes and Genomes (KEGG) were carried out to get further insight into the possible functions of the identified DEGs. Then, the protein-protein interaction (PPI) network of all DEGs was constructed. Nodes with higher degree centrality (≥10) were considered as hub proteins in the PPI network. Area under the curve (AUC) values obtained from the receiver operating characteristic (ROC) curve analysis was utilized to assess the diagnostic effectiveness of hub genes in discriminating IPAH from normal individuals. Sixty-nine DEGs were identified, including 41 upregulated and 28 downregulated DEGs. The GO enrichment analysis indicated that genes were significantly enriched in oxygen carrier activity, oxygen binding, heme binding, molecular carrier activity, and antioxidant activity. KEGG pathway enrichment showed that genes were mainly involved in cytokine and cytokine receptor, Chemokine signaling pathway, interleukin-17 signaling pathway, and Toll-like receptor (TLR) signaling pathway. JUN, ALAS2, HBD, EPB42, TLR7, SLC4A1, and CXCR4 were identified as the hub genes nodes. The area under the ROC curve indicated that three hub genes have high diagnostic value in IPAH with AUC of 0.934 [95% confidence interval (CI): 0.849-0.979] in TLR7, 0.910 (95% CI: 0.818-0.965) in JUN, and 0.895 (95% CI: 0.800-0.955) in CXCR4. The identified candidate key genes and pathways help us understand the molecular mechanisms underlying the pathogenesis of IPAH. TLR7, JUN, and CXCR4 may be novel biomarkers in IPAH diagnosis.


Assuntos
Redes Reguladoras de Genes , Mapas de Interação de Proteínas , Hipertensão Arterial Pulmonar/genética , Biologia Computacional/métodos , Loci Gênicos , Predisposição Genética para Doença , Humanos , Hipertensão Arterial Pulmonar/metabolismo , Transcriptoma
14.
Clin Res Hepatol Gastroenterol ; 45(1): 101455, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32505732

RESUMO

OBJECTIVE: Flap endonuclease 1 (FEN1) overexpression has been reported to be closely associated with cancer prognosis. However, its diagnostic and prognostic significance in gastric cancer (GC) has not yet been explored. METHODS: FEN1 expression, its correlation with clinical parameters, and prognostic significance were investigated by data mining of The Cancer Genome Atlas (TCGA) datasets. Patients were divided into low- and high-expression groups using the median value of FEN1 expression as the cut-off. The diagnostic value of FEN1 expression in GC tissues was determined via receiver operating characteristic (ROC) curve analysis. Univariate and multivariate Cox regression analyses were used to identify the prognostic indicators. Gene set enrichment analysis (GSEA) was used to explore FEN1-related signalling pathways in GC. Furthermore, the Human Protein Atlas (HPA) database and GSE62254 dataset were used for further external validation. RESULTS: FEN1 was expressed at a higher level in GC tissues than in normal gastric tissues with high diagnostic accuracy (area under the ROC=0.909). Higher FEN1 expression was also validated at the protein level using the HPA database. High FEN1 expression in GC was correlated with older age (P<0.05). Patients with high FEN1 expression had a favourable prognosis compared to patients with low FEN1 expression (P=0.0048). Univariate and multivariate analyses revealed that FEN1 was an independent predictive factor associated with overall survival in both the TCGA cohort and the GSE62254 dataset (P=0.0004 and P=0.011, respectively). GSEA identified that the FEN1 expression was related to DNA replication, cell cycle, cytosolic and sensing pathways, oocyte meiosis, and the P53 signalling pathway. CONCLUSION: The results revealed high expression of FEN1 in GC; thus, it could be a promising early diagnostic and independent prognostic biomarker for GC.


Assuntos
Neoplasias Gástricas , Idoso , Biomarcadores Tumorais/genética , Endonucleases Flap/genética , Humanos , Prognóstico , Curva ROC , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética
15.
Dis Markers ; 2020: 8852388, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32952743

RESUMO

OBJECTIVE: We aimed at identifying the key genes of prognostic value in clear cell renal cell carcinoma (ccRCC) microenvironment and construct a risk score prognostic model. MATERIALS AND METHODS: Immune and stromal scores were calculated using the ESTIMATE algorithm. A total of 539 ccRCC cases were divided into high- and low-score groups. The differentially expressed genes in immune and stromal cells for the prognosis of ccRCC were screened. The relationship between survival outcome and gene expression was evaluated using univariate and multivariate Cox proportional hazard regression analyses. A risk score prognostic model was constructed based on the immune/stromal scores. RESULTS: The median survival time of the low immune score group was longer than that of the high immune score group (p = 0.044). Ten tumor microenvironment-related genes were selected by screening, and a predictive model was established, based on which patients were divided into high- and low-risk groups with markedly different overall survival (p < 0.0001). Multivariate Cox analyses showed that the risk score prognostic model was independently associated with overall survival, with a hazard ratio of 1.0437 (confidence interval: 1.0237-1.0641, p < 0.0001). CONCLUSIONS: Low immune scores were associated with extended survival time compared to high immune scores. The novel risk predictive model based on tumor microenvironment-related genes may be an independent prognostic biomarker in ccRCC.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Renais/mortalidade , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes , Neoplasias Renais/mortalidade , Idoso , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Estadiamento de Neoplasias , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , Análise de Sobrevida , Microambiente Tumoral
16.
Biomed Res Int ; 2020: 7434737, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32280701

RESUMO

OBJECTIVE: Numerous microRNAs (miRNAs) have been identified in ccRCC and recommended to be used for predicting clear cell renal cell carcinoma (ccRCC) prognosis. However, it is not clear whether a miRNA-based nomogram results in improved survival prediction in patients with ccRCC. METHODS: miRNA profiles from tumors and normal tissues were downloaded from The Cancer Genome Atlas (TCGA) database and analyzed using the "limma" package. The association between differentially expressed miRNAs and patient prognosis was identified using univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses. Next, all patients were randomly divided into development and validation cohorts at a ratio of 1 : 1. A nomogram was established based on independent prognostic factors in the development cohort. The prognostic performance of the nomogram was validated in both cohorts using the concordance index (C-index) and calibration plots. RESULTS: Multivariate Cox analysis identified the 13-miRNA signature, as well as AJCC stage and age, as independent prognostic factors after adjusting for other clinical covariates. The nomogram was built based on the independent variables. In the development cohort, the C-index for the constructed nomogram to predict overall survival (OS) was 0.792, which was higher than the C-index (0.731) of the AJCC staging system and C-index (0.778) of the miRNA signature. The nomogram demonstrated good discriminative ability in the validation cohort in predicting OS, with a C-index of 0.762. The calibration plots indicated an excellent agreement between the nomogram predicted survival probability and the actual observed outcomes. Furthermore, decision curve analysis (DCA) indicated that the nomogram was superior to the AJCC staging system in increasing the net clinical benefit. CONCLUSIONS: The novel proposed nomogram based on a miRNA signature is a more reliable and robust tool for predicting the OS of patients with ccRCC compared to AJCC staging system, thus, improving clinical decision-making.


Assuntos
Carcinoma de Células Renais/metabolismo , MicroRNAs/metabolismo , Nomogramas , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/patologia , Estudos de Coortes , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , MicroRNAs/genética , Estadiamento de Neoplasias , Probabilidade , Prognóstico
17.
Front Neurol ; 11: 593074, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33193059

RESUMO

Objective: This study aimed to develop and validate a nomogram to predict cessation of patent foramen ovale (PFO) patients with migraine headache after percutaneous closure. Methods: A total of 247 eligible patients with PFO and migraine after percutaneous closure between May, 2016 and May, 2018 were divided into a development cohort (n = 149) and a validation cohort (n = 98). The primary end point was cessation of migraine at follow-up of 1 year after the procedure measured by the Migraine Disability Assessment Score (MIDAS). In the development cohort, the LASSO regression was used data dimension reduction. A multivariable logistic regression analysis was used to develop the predicting nomogram. The performance of the nomogram was assessed by concordance index (C-index), calibration and clinical usefulness. The results were validated in the validation cohort. Results: Migraine with aura, history of antiplatelet, and the right-to-left shunt (RLS) at rest were identified as significant predictors based on the analysis of multivariate logistic regression. The nomogram incorporating these variables showed good calibration and discrimination in the development cohort with C-index of 0.906 (95% CI: 0.847-0.965), which was confirmed using the validation cohort with C-index of 0.827 (95% CI: 0.751-0.903). The nomogram showed good agreement between prediction by nomogram and actual observation. Furthermore, the decision curve indicated that the novel nomogram was clinically useful. Conclusion: The novel nomogram showed favorable predictive accuracy for cessation of migraine among patients with PFO after percutaneous closure and might provide constructive guidance in clinical decision making.

18.
Front Mol Biosci ; 7: 620765, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33553243

RESUMO

Objective: The purpose of this study was to develop and validate a novel immune checkpoint-related gene signature for prediction of overall survival (OS) in hepatocellular carcinoma (HCC). Methods: mRNA expression profiles and clinical follow-up information were obtained in the International Cancer Genome Consortium database. An external dataset from The Cancer Genome Atlas (TCGA) Liver Hepatocellular Carcinoma database was used to validate the results. The univariate and multivariate Cox regression analyses were performed based on the differentially expressed genes. We generated a four-mRNA signature to predict patient survival. Furthermore, the reliability and validity were validated in TCGA cohort. An integrated bioinformatics approach was performed to evaluate its diagnostic and prognostic value. Results: A four-gene (epidermal growth factor, mutated in colorectal cancer, mitogen-activated protein kinase kinase 2, and NRAS proto-oncogene, GTPase) signature was built to classify patients into two risk groups using a risk score with different OS in two cohorts (all P < 0.0001). Multivariate regression analysis demonstrated the signature was an independent predictor of HCC. Furthermore, the signature presented an excellent diagnostic power in differentiating HCC and adjacent tissues. Immune cell infiltration analysis revealed that the signature was associated with a number of immune cell subtypes. Conclusion: We identified a four-immune checkpoint-related gene signature as a robust biomarker with great potential for clinical application in risk stratification and OS prediction in HCC patients and could be a potential indicator of immunotherapy in HCC. The diagnostic signature had been validated to accurately distinguish HCC from adjacent tissues.

19.
Front Cardiovasc Med ; 7: 586871, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33195475

RESUMO

Objective: The present study was designed to identify potential diagnostic markers for acute myocardial infarction (AMI) and determine the significance of immune cell infiltration in this pathology. Methods: Two publicly available gene expression profiles (GSE66360 and GSE48060 datasets) from human AMI and control samples were downloaded from the GEO database. Differentially expressed genes (DEGs) were screened between 80 AMI and 71 control samples. The LASSO regression model and support vector machine recursive feature elimination (SVM-RFE) analysis were performed to identify candidate biomarkers. The area under the receiver operating characteristic curve (AUC) value was obtained and used to evaluate discriminatory ability. The expression level and diagnostic value of the biomarkers in AMI were further validated in the GSE60993 dataset (17 AMI patients and 7 controls). The compositional patterns of the 22 types of immune cell fraction in AMI were estimated based on the merged cohorts using CIBERSORT. Results: A total of 27 genes were identified. The identified DEGs were mainly involved in carbohydrate binding, Kawasaki disease, atherosclerosis, and arteriosclerotic cardiovascular disease. Gene sets related to atherosclerosis signaling, primary immunodeficiency, IL-17, and TNF signaling pathways were differentially activated in AMI compared with the control. IL1R2, IRAK3, and THBD were identified as diagnostic markers of AMI (AUC = 0.877) and validated in the GSE60993 dataset (AUC = 0.941). Immune cell infiltration analysis revealed that IL1R2, IRAK3, and THBD were correlated with M2 macrophages, neutrophils, monocytes, CD4+ resting memory T cells, activated natural killer (NK) cells, and gamma delta T cells. Conclusion: IL1R2, IRAK3, and THBD can be used as diagnostic markers of AMI, and can provide new insights for future studies on the occurrence and the molecular mechanisms of AMI.

20.
Cardiovasc Ther ; 2020: 9416803, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32099583

RESUMO

OBJECTIVE: This study aimed to establish a clinical prognostic nomogram for predicting major adverse cardiovascular events (MACEs) after primary percutaneous coronary intervention (PCI) among patients with ST-segment elevation myocardial infarction (STEMI). METHODS: Information on 464 patients with STEMI who performed PCI procedures was included. After removing patients with incomplete clinical information, a total of 460 patients followed for 2.5 years were randomly divided into evaluation (n = 324) and validation (n = 324) and validation (. RESULTS: Apelin-12 change rate, apelin-12 level, age, pathological Q wave, myocardial infarction history, anterior wall myocardial infarction, Killip's classification > I, uric acid, total cholesterol, cTnI, and the left atrial diameter were independently associated with MACEs (all P < 0.05). After incorporating these 11 factors, the nomogram achieved good concordance indexes of 0.758 (95%CI = 0.707-0.809) and 0.763 (95%CI = 0.689-0.837) in predicting MACEs in the evaluation and validation cohorts, respectively, and had well-fitted calibration curves. The decision curve analysis (DCA) revealed that the nomogram was clinically useful. CONCLUSIONS: We established and validated a novel nomogram that can provide individual prediction of MACEs for patients with STEMI after PCI procedures in a Chinese population. This practical prognostic nomogram may help clinicians in decision making and enable a more accurate risk assessment.


Assuntos
Técnicas de Apoio para a Decisão , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Nomogramas , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Idoso , Biomarcadores/sangue , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/epidemiologia , Fatores de Tempo , Resultado do Tratamento
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