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BACKGROUND: Stress hyperglycemia ratio (SHR) could provide accurate information on the acute status of hyperglycemia. The relationship between SHR and acute coronary syndrome (ACS) prognosis remains unclear. This study was conducted to identity the association between SHR and in-hospital outcomes in patients with ACS. METHODS: A total of 12,010 patients were eventually enrolled in the study. The relationship between SHR and in-hospital major adverse cardiovascular events (MACEs) was then modeled by restricted cubic spline (RCS) curves, and all patients were divided into three groups according to the results. The multivariate logistic regression analysis was used to determine the associations between the SHR and in-hospital outcomes, described as odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses were also performed on different diseases. RESULTS: The median age of this cohort was 63 (54, 71) years old, and 8942 (74.5%) were male. Group 1 was defined as SHR < 0.6 (n = 426), Group 2 was defined as SHR between 0.6 and 1 (n = 5821), and Group 3 was defined as SHR > 1 (n = 5763). Compared with Group 2, Group 1 (OR = 1.891, 95% CI: 1.028-3.479, P < 0.001) and Group 3 (OR = 1.868, 95% CI: 1.434-2.434, P < 0.001) had higher risks of suffering from in-hospital MACEs. SHR was associated with higher risks of in-hospital MACEs in the subgroups of DM [OR = 2.282, 95% CI: 1.477-3.524). CONCLUSIONS: Both low and high SHR levels were independently associated with in-hospital MACEs. Young males with DM, hypertension, and decreased renal function had much higher risks of suffering from SHR-correlated MACEs.
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BACKGROUND: We aim to identify the distinct lesion patterns and regions associated with functional outcome and inflammation in patients with acute ischemic stroke, and investigate whether the association between lesion patterns and functional outcome was mediated by inflammation. METHODS AND RESULTS: We performed nonnegative matrix factorization to derived low-dimensional lesion patterns (atoms), and Bayesian linear regression models were applied to explore the associations of lesion patterns with inflammatory factors including high-sensitivity C-reactive protein and interleukin-6, as well as functional outcome (defined as modified Rankin Scale score at 3 months). The difference distribution mean and 95% highest probability density interval (HPDI) were calculated. Mediation analysis was used to examine the mediating effects of inflammation on the relationships between lesion patterns and functional outcome. Seven lesion patterns were derived from 5914 patients with acute ischemic stroke. Lesion patterns distributed in the cortical regions were associated with inflammatory response, including atom 1 (interleukin-6: mean, 0.113 [95% HPDI, 0.073-0.162]; high-sensitivity C-reactive protein: mean, 0.082 [95% HPDI, 0.038-0.123]) and atom 4 (interleukin-6: mean, 0.113 [95% HPDI, 0.071-0.167]; high-sensitivity C-reactive protein: mean, 0.108 [95% HPDI, 0.058-0.165]). These lesion patterns were also significantly associated with functional outcome (atom 1: mean, 1.958 [95% HPDI, 1.538-2.383]; atom 4: mean, 2.245 [95% HPDI, 1.773-2.741]). Mediation analysis suggested that interleukin-6 explained 15.34% and 7.47% in the association of atom 1 and atom 4 with functional outcome, respectively. CONCLUSIONS: Certain lesion patterns that are associated with both inflammation and functional outcome of acute ischemic stroke, especially cortical infarction, may play a role in functional outcome through modulating inflammatory reactions.
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Proteína C-Reactiva , Inflamación , Interleucina-6 , Accidente Cerebrovascular Isquémico , Humanos , Masculino , Femenino , Estudios Retrospectivos , Anciano , Pronóstico , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Persona de Mediana Edad , Interleucina-6/sangre , Biomarcadores/sangre , Teorema de Bayes , Imagen por Resonancia Magnética , Infarto Cerebral/patologíaRESUMEN
Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that the cell invasion and migration assay data shown in Fig. 6 and the cell proliferation assay experiments shown in Fig. 2 were strikingly similar to data appearing in different form in other articles by different authors; furthermore, in Fig. 2, for the '10 mM metformin' experiment, certain of the glioma cells appeared to be strikingly similar to other cells contained within the same data panels. Owing to the fact that the contentious data in the above article had already been published elsewhere or were under consideration for publication prior to its submission to Molecular Medicine Reports, and owing to concerns with the authenticity of certain of the data, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 20: 887894, 2019; DOI: 10.3892/mmr.2019.10369].
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OBJECTIVE: The objective of this meta-analysis is to evaluate the diagnostic performance of acoustic radiation force impulse (ARFI) in acute pancreatitis (AP) patients. METHODS: PubMed, Web of Science, Embase, Wanfang, Chinese Biological Medicine databases, and Chinese Biomedical Literature Service System were searched for relevant studies to explore the potential diagnostic performance of ARFI in AP from inception to November 2023. STATA 14.0 was used to analyze the standardized mean difference (SMD) with 95% confidence interval (CI), pooled sensitivity, specificity, area under the curve, meta-regression analysis, sensitivity analysis, and publication bias. RESULTS: Nine studies, involving 533 AP patients and 585 healthy controls, were included. AP patients had significantly higher ARFI levels than healthy controls (SMD: 3.13, 95% CI: 1.88-4.39, Pâ =â .001). The area under the curve of ARFI for diagnosing AP was 0.99 (95% CI: 0.98-1.00), with 98% sensitivity and 94% specificity. Meta-regression identified the study region and study period as the sources of heterogeneity. Sensitivity analysis showed that the exclusion of any single study did not materially alter the overall combined effect. No evidence of publication bias was observed in the included studies. CONCLUSION: This meta-analysis demonstrated that ARFI exerted satisfactory diagnostic performance in AP.
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Diagnóstico por Imagen de Elasticidad , Pancreatitis , Sensibilidad y Especificidad , Humanos , Pancreatitis/diagnóstico , Pancreatitis/diagnóstico por imagen , Diagnóstico por Imagen de Elasticidad/métodos , Enfermedad AgudaRESUMEN
Diabetes mellitus results in numerous complications. Diabetic pulmonary fibrosis (DPF), a late pulmonary complication of diabetes, has not attracted as much attention as diabetic nephropathy and cardiomyopathy. Mangiferin (MF) is a natural small molecular compound that exhibits a variety of pharmacological effects including anti-inflammatory, anti-cancer, anti-diabetes, and anti-fibrosis effects. In this study, we investigated whether long-term diabetes shock induces DPF, and explored whether MF had a protective effect against DPF. We first examined the lung tissues and sections of 20 diabetic patients obtained from discarded lung surgical resection specimens and found that pulmonary fibrosis mainly accumulated around the pulmonary vessels, accompanied by significantly enhanced endothelial-mesenchymal transition (EndMT). We established a mouse model of DPF by STZ injections. Ten days after the final STZ injection, the mice were administered MF (20, 60 mg/kg, i.g.) every 3 days for 4 weeks, and kept feeding until 16 weeks and euthanized. We showed that pulmonary fibrotic lesions were developed in the diabetic mice, which began around the pulmonary vessels, while MF administration did not affect long-term blood glucose levels, but dose-dependently alleviated diabetes-induced pulmonary fibrosis. In human umbilical vein endothelial cells (HUVECs), exposure to high glucose (33.3 mM) induced EndMT, which was dose-dependently inhibited by treatment with MF (10, 50 µM). Furthermore, MF treatment promoted SIRT3 expression in high glucose-exposed HUVECs by directly binding to AMPK to enhance the activity of FoxO3, which finally reversed diabetes-induced EndMT. We conclude that MF attenuates DPF by inhibiting EndMT through the AMPK/FoxO3/SIRT3 axis. MF could be a potential candidate for the early prevention and treatment of DPF.
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Proteínas Quinasas Activadas por AMP , Diabetes Mellitus Experimental , Proteína Forkhead Box O3 , Ratones Endogámicos C57BL , Fibrosis Pulmonar , Sirtuina 3 , Xantonas , Animales , Xantonas/farmacología , Xantonas/uso terapéutico , Fibrosis Pulmonar/tratamiento farmacológico , Fibrosis Pulmonar/metabolismo , Sirtuina 3/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/metabolismo , Proteína Forkhead Box O3/metabolismo , Masculino , Humanos , Ratones , Proteínas Quinasas Activadas por AMP/metabolismo , Transición Epitelial-Mesenquimal/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Estreptozocina , Transducción de Señal/efectos de los fármacos , Transición Endotelial-MesenquimatosaRESUMEN
CCDC88C gene, which encodes coiled-coil domain containing 88C, is essential for cell communication during neural development. Variants in the CCDC88C caused congenital hydrocephalus, some accompanied by seizures. In patients with epilepsy without acquired etiologies, we performed whole-exome sequencing (trio-based). Two de novo and two biallelic CCDC88C variants were identified in four cases with focal (partial) epilepsy. These variants did not present or had low frequencies in the gnomAD populations and were predicted to be damaging by multiple computational algorithms. Patients with de novo variants presented with adult-onset epilepsy, whereas patients with biallelic variants displayed infant-onset epilepsy. They all responded well to anti-seizure medications and were seizure-free. Further analysis showed that de novo variants were located at crucial domains, whereas one paired biallelic variants were located outside the crucial domains, and the other paired variant had a non-classical splicing and a variant located at crucial domain, suggesting a sub-molecular effect. CCDC88C variants associated with congenital hydrocephalus were all truncated, whereas epilepsy-associated variants were mainly missense, the proportion of which was significantly higher than that of congenital hydrocephalus-associated variants. CCDC88C is potentially associated with focal epilepsy with favorable outcome. The underlying mechanisms of phenotypic variation may correlation between genotype and phenotype.
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Epilepsias Parciales , Epilepsia , Hidrocefalia , Lactante , Adulto , Humanos , Epilepsias Parciales/genética , Epilepsia/genética , Hidrocefalia/genética , Genotipo , Estudios de Asociación Genética , Proteínas de Microfilamentos/genética , Péptidos y Proteínas de Señalización Intracelular/genéticaRESUMEN
Scaffold hopping strategy has become one of the most successful methods in the process of molecular design. Seeking to develop novel succinate dehydrogenase inhibitors (SDHIs), we employed a scaffold hopping strategy to design compounds featuring geminate dichloralkenes (gem-dichloralkenes) fragment. After stepwise modifications, a series of N-cyclopropyl-dichloralkenes-pyrazole-carboxamide derivatives was synthesized. Among them, compounds G28 (IC50 = 26.00 nM) and G40 (IC50 = 27.00 nM) were identified as the best inhibitory activity against porcine SDH, with IC50 values reaching the nanomolar range, outperforming the lead compound pydiflumetofen. Additionally, the greenhouse assay indicated that compounds G37 (EC90 = 0.031 mg/L) and G34 (EC90 = 1.67 mg/L) displayed extremely high activities against wheat powdery mildew (WPM) and cucumber powdery mildew (CPM), respectively. Computational results further revealed that the gem-dichloralkene fragment and fluorine substituted pyrazole form an extra hydrophobic interaction and dipolar-dipolar interaction with SDH. In summary, our study provides a novel gem-dichloralkene scaffold with outstanding fungicidal properties, obtained through scaffold hopping, that holds great potential for future research on PM control.
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Fungicidas Industriales , Succinato Deshidrogenasa , Animales , Porcinos , Fungicidas Industriales/farmacología , Fungicidas Industriales/química , Pirazoles/farmacología , Pirazoles/química , Relación Estructura-Actividad , Simulación del Acoplamiento MolecularRESUMEN
Introduction: Chronic diseases have become one of the main causes of premature death all around the world in recent years. The diagnosis of chronic diseases is time-consuming and costly. Therefore, timely diagnosis and prediction of chronic diseases are very necessary. Methods: In this paper, a new method for chronic disease diagnosis is proposed by combining convolutional neural network (CNN) and ensemble learning. This method utilizes random forest (RF) as the base classifier to improve classification performance and diagnostic accuracy, and then combines AdaBoost to successfully replace the Softmax layer of CNN to generate multiple accurate base classifiers while determining their optimal attributes, achieving high-quality classification and prediction of chronic diseases. Results: To verify the effectiveness of the proposed method, real-world Electronic Medical Records dataset (C-EMRs) was used for experimental analysis. The results show that compared with other traditional machine learning methods such as CNN, K-Nearest Neighbor, and RF, the proposed method can effectively improve the accuracy of diagnosis and reduce the occurrence of missed diagnosis and misdiagnosis. Conclusions: This study will provide effective information for the diagnosis of chronic diseases, assist doctors in making clinical decisions, develop targeted intervention measures, and reduce the probability of misdiagnosis.
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Schistosomiasis japonicum can cause different degrees of organ damage and complex human immune pathological reactions, which often invade the intestine and liver. The purpose of this study was to explore the pathological types and pathological changes of Schistosomiasis and their correlation with some digestive system tumors. Hematoxylin eosin staining was performed on the diseased tissues of 1111 Schistosomiasis cases. We counted the deposition sites of Schistosoma eggs, analyzed the pathological characteristics, and compared the clinicopathological characteristics of Schistosomiasis associated digestive system tumors and non-Schistosomiasis digestive system tumors. We found that Schistosoma japonicum can cause multi organ and multi system damage, with 469 cases of inflammation, 47 cases of adenoma, and 519 cases of adenocarcinoma. Other types include cysts, stromal tumors, malignant lymphomas, and neuroendocrine tumors. Schistosomiasis associated tumors, including gastric cancer, liver cancer, colon cancer and rectal cancer, were compared with non-Schistosomiasis tumors. There were significant differences in age, gender and tumor differentiation between the two groups. Our study shows Schistosomiasis is a systemic disease, causing multiple organ and system damage in the human body. Its clinicopathological types are diverse, and there may be a pathological change process of "Inflammation-adenoma-carcinoma". Schistosomiasis associated digestive system tumors differ from non-Schistosomiasis tumors in some clinicopathological features.
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Carcinoma , Neoplasias del Sistema Digestivo , Neoplasias Gastrointestinales , Esquistosomiasis Japónica , Neoplasias Gástricas , Humanos , Esquistosomiasis Japónica/complicaciones , InflamaciónRESUMEN
The sea cucumber Holothuria leucospilota, a nutritive and commercial marine species, has a high protein and low lipid content. To date, the mechanisms underlying gender determination and differentiation in sea cucumbers remain unclear. Identifying gender-specific molecular markers is an effective method of revealing the genetic basis of gender determination and differentiation. The inability to distinguish between male and female individuals causes reproductive efficiency to decline in aquaculture. In this study, we used the gonads of the sea cucumber H. leucospilota as samples to conduct the experiment. The differentially abundant metabolites (DAMs) detected by liquid chromatography-mass spectrometry were enriched in pathways associated with prolactin metabolism, insulin metabolism, hypoxia-inducible factor-1 signaling, and calcium signaling. At the transcriptome level, Illumina sequencing was performed on H. leucospilota, demonstrating that gender-specific expression genes were enriched in the retinoic acid-inducible gene I-like receptor signaling pathway, C-type lectin receptor signaling pathway, alpha-linolenic acid metabolism, and ether lipid metabolism by the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. By analyzing the common pathways between DAMs and differentially expressed genes, we found that gender-related genes of H. leucospilota were mostly enriched in the necroptosis pathway and the cysteine and methionine metabolism pathways. According to the common pathways, uch-sc1 and uch-sc2 are male-specific expression genes, and uch-sc3 and bhmt are female-specific expression genes at the mRNA level. These results provide information on gender differences in H. leucospilota.
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Holothuria , Pepinos de Mar , Humanos , Animales , Femenino , Masculino , Transcriptoma , Metaboloma , Señalización del CalcioRESUMEN
An unprecedented N-alkylation of 3-nitroindoles with para-quinone methides was developed for the first time. Using potassium carbonate as the base, a wide range of structurally diverse N-diarylmethylindole derivatives were obtained with moderated to good yields via the protection group migration/aza-1,6-Michael addition sequences. The reaction process was also demonstrated by control experiments. Different from the previous advances where 3-nitrodoles served as electrophiles trapping by various nucleophiles, the reaction herein is featured that 3-nitrodoles is defined with latent N-centered nucleophiles to react with ortho-hydrophenyl p-QMs for construction of various N-diarylmethylindoles.
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BACKGROUND: The prognostic assessment of patients after surgical resection of gastric cancer (GC) patients is critical. However, the role of the circadian clock gene NPAS2 expression in GC remains unknown. AIM: To explore the relationship between NPAS2 and the survival prognosis of GC patients and clarify its role in evaluating GC prognosis. METHODS: The tumor tissues and clinical data of 101 patients with GC were collected retrospectively. Immunohistochemical staining (IHC) was used to detect the expression of NPAS2 protein in GC and adjacent tissues. Univariate and multivariate Cox regression analysis was used to determine the independent prognostic factors of GC, and a nomogram prediction model was established. The receiver operating characteristic (ROC) curve, the ROC area under the curve, the calibration curve, and C-index were used to evaluate the predictive effectiveness of the model. Kaplan Meier analysis was used to compare the risk stratification of subgroups according to the median score in the nomogram model of each patient. RESULTS: Microarray IHC analysis showed that the positive rate of NPAS2 protein expression in GC tissues was 65.35%, which was significantly higher than 30.69% in adjacent tissues. The high expression of NPAS2 was correlated with tumor-node-metastasis (TNM) stage (P < 0.05), pN stage (P < 0.05), metastasis (P < 0.05), venous invasion (P < 0.05), lymphatic invasion (P < 0.05), and lymph node positive (P < 0.05) of GC. Kaplan Meier survival analysis showed that the 3-year overall survival (OS) of patients with high NPAS2 expression was significantly shortened (P < 0.0001). Univariate and multivariate COX regression analysis showed that TNM stage (P = 0.009), metastasis (P = 0.009), and NPAS2 expression (P = 0.020) were independent prognostic factors of OS in GC patients for 3 years. The nomogram prediction model based on independent prognostic factors has a C-Index of 0.740 (95%CI: 0.713-0.767). Furthermore, subgroup analysis showed that the 3-year OS time of the high-risk group was significantly lower than that of the low-risk group (P < 0.0001). CONCLUSION: NPAS2 is highly expressed in GC tissues and is closely related to worse OS in patients. Therefore, the evaluation of NPAS2 expression may be a potential marker for GC prognosis evaluation. Notably, the nomogram model based on NPAS2 can improve the accuracy of GC prognosis prediction and assist clinicians in postoperative patient management and decision-making.
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Relojes Circadianos , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Estudios Retrospectivos , Metástasis Linfática , Pronóstico , Proteínas del Tejido Nervioso/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genéticaRESUMEN
Introduction: Urolithiasis is one of the most common diseases for urologists and it is a heavy burden for stone formers and society. The theory of the oral-genitourinary axis casts novel light on the pathological process of genitourinary system diseases. Hence, we performed this study to characterize the crosstalk between oral health conditions and urolithiasis to provide evidence for prevention measures and mechanisms of stone formation. Materials and methods: This population-based cross-sectional study included 86,548 Chinese individuals who had undergone a comprehensive examination in 2017. Urolithiasis was diagnosed depending on the results of ultrasonographic imaging. Logistic models were utilized to characterize the association between oral health conditions and urolithiasis. We further applied bidirectional Mendelian randomization to explore the causality between oral health conditions and urolithiasis. Results: We observed that presenting caries indicated a negative correlation with the risk for urolithiasis while presenting gingivitis [OR (95% CI), 2.021 (1.866-2.187)] and impacted tooth [OR (95% CI), 1.312 (1.219-1.411)] shown to be positively associated with urolithiasis. Furthermore, we discovered that genetically predicted gingivitis was associated with a higher risk of urolithiasis [OR (95% CI), 1.174 (1.009-1.366)] and causality from urolithiasis to impacted teeth [OR(95% CI), 1.207 (1.027-1.418)] through bidirectional Mendelian randomization. Conclusion: The results cast new light on the risk factor and pathogenesis of kidney stone formation and could provide novel evidence for the oral-genitourinary axis and the systematic inflammatory network. Our findings could also offer suggestions for tailored clinical prevention strategies against stone diseases.
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Increasingly serious pollution of antibiotic resistance genes (ARGs) caused by the abuse of antibiotics in livestock and poultry industry has raised worldwide concerns. ARGs could spread among various farming environmental media through adsorption, desorption, migration, and also could transfer into human gut microbiome by hori-zontal gene transfer (HGT), posing potential threats to public health. However, the comprehensive review on the pollution patterns, environmental behaviors, and control techniques of ARGs in livestock and poultry environments in view of One Health is still inadequate, resulting in the difficulties in effectively assessing ARGs transmission risk and developing the efficient control strategies. Here, we analyzed the pollution characteristics of typical ARGs in various countries, regions, livestock species, and environmental media, reviewed the critical environmental fate and influencing factors, control strategies, and the shortcomings of current researches about ARGs in the livestock and poultry farming industry combined with One Health philosophy. In particular, we addressed the importance and urgency of identifying the distribution characteristics and environmental process mechanisms of ARGs, and developing green and efficient ARG control means in livestock farming environments. We further proposed gaps and prospects for the future research. It would provide theoretical basis for the research on health risk assessment and technology exploitation of alleviating ARG pollution in livestock farming environment.
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Antibacterianos , Aves de Corral , Animales , Humanos , Aves de Corral/genética , Antibacterianos/farmacología , Ganado/genética , Genes Bacterianos , Farmacorresistencia Microbiana/genética , AgriculturaRESUMEN
Purpose: To identify risk factors of secondary cancer in nasopharyngeal carcinoma (NPC) patients after radiotherapy. Materials and methods: The data of NPC patients with secondary cancer were extracted from the Surveillance, Epidemiology, and End Results database from 2004 to 2016. Univariate and multivariate logistic regression analysis was performed to identify risk factors of secondary cancer. Risk factors selected from the multivariable logistic regression analysis were used to build a predicting model. Results: A total of 3931 patients were included: 329 (8.37%) patients developed secondary cancers and 3602 (91.63%) patients did not have secondary cancers. Univariate logistic regression analysis revealed that age, race, and the American Joint Committee on Cancer (AJCC) stage were risk factors of secondary cancer. Multivariable analysis demonstrated that age [Odds ratio (OR) = 1.03, P < 0.001], race (OR = 1.17, P = 0.010), AJCC stage (OR = 0.82, P = 0.002), and chemotherapy (OR = 1.55, P = 0.028) were independent risk factors of secondary cancer. Age, race, AJCC stage, and chemotherapy were entered into a nomogram for predicting secondary cancer. The area under the ROC curve of the nomogram was 0.645 [95% confidence interval (CI): 0.617-0.673]. The decision curve showed that if the threshold probability is between 4% and 25%, using the nomogram added more benefit than either the treat-all-patients scheme or the treat-none scheme. Conclusion: Age, race, AJCC stage, and chemotherapy were independent risk factors of secondary cancer in nasopharyngeal carcinoma patients after radiotherapy.
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BACKGROUND: Myocardial ischemia-reperfusion injury (MIRI) caused by the reperfusion therapy of myocardial ischemic diseases is a kind of major disease that threatens human health and lives severely. There are lacking of effective therapeutic measures for MIRI. MicroRNAs (miRNAs) are abundant in mammalian species and play a critical role in the initiation, promotion, and progression of MIRI. However, the biological role and molecular mechanism of miRNAs in MIRI are not entirely clear. METHODS: We used bioinformatics analysis to uncover the significantly different miRNA by analyzing transcriptome sequencing data from myocardial tissue in the mouse MIRI model. Multiple miRNA-related databases, including miRdb, PicTar, and TargetScan were used to forecast the downstream target genes of the differentially expressed miRNA. Then, the experimental models, including male C57BL/6J mice and HL-1 cell line, were used for subsequent experiments including quantitative real-time polymerase chain reaction analysis, western blot analysis, hematoxylin and eosin staining, flow cytometry, luciferase assay, gene interference, and overexpression. RESULTS: MiR-582-5p was found to be differentially upregulated from the transcriptome sequencing data. The elevated levels of miR-582-5p were verified in MIRI mice and hypoxia/reperfusion (H/R)-induced HL-1 cells. Functional experiments revealed that miR-582-5p promoted apoptosis of H/R-induced HL-1 cells via downregulating cAMP-response element-binding protein 1 (Creb1). The inhibiting action of miR-582-5p inhibitor on H/R-induced apoptosis was partially reversed after Creb1 interference. CONCLUSIONS: Collectively, the research findings reported that upregulation of miR-582-5p promoted H/R-induced cardiomyocyte apoptosis by inhibiting Creb1. The potential diagnostic and therapeutic strategies targeting miR-582-5p and Creb1 could be beneficial for the MIRI treatment.
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MicroARNs , Daño por Reperfusión Miocárdica , Masculino , Ratones , Humanos , Animales , Miocitos Cardíacos/metabolismo , Ratones Endogámicos C57BL , Daño por Reperfusión Miocárdica/genética , Daño por Reperfusión Miocárdica/metabolismo , Apoptosis/genética , MicroARNs/genética , Hipoxia/genética , Hipoxia/metabolismo , Modelos Animales de Enfermedad , Reperfusión , Mamíferos/genética , Mamíferos/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/genética , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/farmacologíaRESUMEN
PURPOSE: This study investigated the effect of real-time feedback on the restoration of spontaneous circulation, survival to hospital discharge, and favorable functional outcomes after hospital discharge. METHODS: PubMed, ScienceDirect, and China National Knowledge Infrastructure databases were searched to screen the relevant studies up to June 2020. Fixed-effects or random-effects model were used to calculate the pooled estimates of relative ratios (RRs) with 95% confidence intervals (CIs). RESULTS: Ten relevant articles on 4281 cardiac arrest cases were identified. The pooled analyses indicated that real-time feedback did not improve restoration of spontaneous circulation (RR: 1.13, 95% CI: 0.92-1.37, and P = .24; I2 = 81%; P < .001), survival to hospital discharge (RR: 1.27, 95% CI: 0.90-1.79, and P = .18; I2 = 74%; P < .001), and favorable neurological outcomes after hospital discharge (RR: 1.09, 95% CI: 0.87-1.38; P = .45; I2 = 16%; P = .31). The predefined subgroup analysis showed that the sample size and arrest location may be the origin of heterogeneity. Begg's and Egger's tests showed no publication bias, and sensitivity analysis indicated that the results were stable. CONCLUSION: The meta-analysis had shown that the implementation of real-time audiovisual feedback was not associated with improved restoration of spontaneous circulation, increased survival, and favorable functional outcomes after hospital discharge.
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Reanimación Cardiopulmonar , Paro Cardíaco Extrahospitalario , Reanimación Cardiopulmonar/métodos , China , Humanos , Alta del PacienteRESUMEN
The aim of this study was to explore the allelic association between genetic polymorphisms of the NF-κB pathway and the variance of clinical effects of zoledronic in postmenopausal Chinese women with osteoporosis. In the study, 110 Chinese postmenopausal women with osteoporosis were recruited. Every patient received zoledronic once a year. BMD was measured at baseline and after one year of treatment. The 13 tagger SNPs of five genes in the NF-κB pathway were genotyped. In the study, 101 subjects completed the one-year follow-up. The ITCTG and DTCTG haplotypes, which are constituted of rs28362491, rs3774937, rs230521, rs230510 and rs4648068 of the NF-κB1 gene, were associated with improvement in BMD at L1-4 and femoral neck (p < 0.001, p = 0.008, respectively). The CGC haplotype, which is constituted of rs7119750, rs2306365 and rs11820062 of the RELA gene, was associated with improvement in BMD at total hip (p < 0.001). After Bonferroni correction, haplotypes ITCTG and CGC still showed significant association with the % change of BMD at L1-4 and total hip. Therefore, NF-κB1 and RELA gene were significantly associated with bone response to the treatment of zoledronic in postmenopausal Chinese women with osteoporosis.
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Densidad Ósea , Osteoporosis , Densidad Ósea/genética , China , Femenino , Humanos , FN-kappa B/genética , Osteoporosis/tratamiento farmacológico , Osteoporosis/genética , Polimorfismo de Nucleótido Simple , Posmenopausia/genética , Ácido Zoledrónico/farmacología , Ácido Zoledrónico/uso terapéuticoRESUMEN
NPM1 plays an important role in the occurrence and development of leukemia and various solid tumors. This study aimed to investigate the expression of NPM1 in gastric cancer (GC) and adjacent normal tissues, study the relationship between NPM1 expression and clinicopathological characteristics in GC patients, and explore the impact of NPM1 expression on the diagnosis and prognosis of GC. We used tissue microarray immunohistochemical analysis to examine the expression level of NPM1 in GC and adjacent tissues and analyzed the relationship between NPM1 expression, clinicopathological factors, and GC prognosis. Prognostic values of NPM1 mRNA were also investigated using an online database. qRT-PCR was used to detect the expression of NPM1 mRNA in cancer and adjacent tissues. According to microarray immunohistochemical analysis and qRT-PCR results, NPM1 had a high expression in all adjacent normal tissues. Microarray immunohistochemical analyses demonstrated that the NPM1 was lowly expressed in 75.5% of GC tissues but highly expressed in 24.5% of GC tissues. qRT-PCR results showed NPM1 mRNA low expression in most GC tissues. NPM1 high expression group was associated with a better overall survival rate and disease-free survival rate than the NPM1 low expression group (p<0.01). This result is consistent with that of the online database. The receiver operating characteristics curve showed that NPM1 was valuable in the diagnosis of GC. The assessment of NPM1 expression in GC samples may represent a useful tool for GC diagnosis and prognosis assessment.
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Neoplasias Gástricas , Biomarcadores de Tumor/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Nucleofosmina , Pronóstico , ARN Mensajero/genética , ARN Mensajero/metabolismo , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismoRESUMEN
Background: Esophageal cancer is one of the most common gastrointestinal malignancies worldwide, with high morbidity and mortality in China. The clinical importance of the interaction between hypoxia and immune status in the tumor microenvironment has been established in esophageal squamous cell carcinoma (ESCC). This study aims to develop a new hypoxia- and immune-based gene signature to predict the survival of ESCC patients. Methods: The RNA-sequencing and clinical data of 173 cases of ESCC and 271 normal tissues were obtained from The Cancer Genome Atlas (TCGA) data portal and the Genotype-Tissue Expression (GTEx) database. Hypoxia-related genes (HRGs) and immune-related genes (IRGs) were retrieved from publicly shared data. Differentially expressed gene (DEG) analyses were carried out by the DESeq2 method using the edgeR package in R. Based on the intersection of the DEGs and HRGs/IRGs, differentially expressed HRGs (DEHRGs) and differentially expressed IRGs (DEIRGs) were obtained. DEHRGs and DEIRGs associated with prognosis were evaluated using univariate Cox proportional hazards analysis. A prognostic risk score model was constructed according to the genes acquired through Cox regression. Univariate analysis and Cox proportional hazards analysis were used to determine the independent prognostic factors related to prognosis. A nomogram was developed to predict the 1-, 2-, and 3-year overall survival (OS) probability. Results: A total of 73 intersecting genes were obtained as DEHRGs and a total of 548 intersecting genes were obtained as DEIRGs. The risk score was established using 8 genes (FABP7, TLR1, SYTL1, APLN, OSM, EGFR, IL17RD, MYH9) acquired from univariate Cox analysis. Based on this 8-gene-based risk score, a risk prognosis classifier was constructed to classify the samples into high- and low-risk groups according to the median risk score. The nomogram model was constructed to predict the OS of ESCC patients. Conclusions: The hypoxia- and immune-based gene signature might serve as a prognostic classifier for clinical decision-making regarding individualized management, follow-up plans, and treatment strategies for ESCC patients.