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Motor imagery (MI) stands as a powerful paradigm within Brain-Computer Interface (BCI) research due to its ability to induce changes in brain rhythms detectable through common spatial patterns (CSP). However, the raw feature sets captured often contain redundant and invalid information, potentially hindering CSP performance. Methodology-wise, we propose the Information Fusion for Optimizing Temporal-Frequency Combination Pattern (IFTFCP) algorithm to enhance raw feature optimization. Initially, preprocessed data undergoes simultaneous processing in both time and frequency domains via sliding overlapping time windows and filter banks. Subsequently, we introduce the Pearson-Fisher combinational method along with Discriminant Correlation Analysis (DCA) for joint feature selection and fusion. These steps aim to refine raw electroencephalogram (EEG) features. For precise classification of binary MI problems, an Radial Basis Function (RBF)-kernel Support Vector Machine classifier is trained. To validate the efficacy of IFTFCP and evaluate it against other techniques, we conducted experimental investigations using two EEG datasets. Results indicate a notably superior classification performance, boasting an average accuracy of 78.14% and 85.98% on dataset 1 and dataset 2, which is better than other methods outlined in this article. The study's findings suggest potential benefits for the advancement of MI-based BCI strategies, particularly in the domain of feature fusion.
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OBJECTIVE: This study aims to explore alterations in corticomuscular and cortical coupling during the rehabilitation of stroke patients. METHODS: We initiated the analysis by employing variational modal decomposition (VMD) on electromyography (EMG) data, followed by the application of VDM-transfer entropy (VMD-TE) to quantify the coupling strength between electroencephalogram (EEG) and EMG signals. Subsequently, we constructed the VMD-TE connection matrix and analyzed the clustering coefficient and small-world attributes within the cortico-muscular functional network (CMFN). Finally, a random forest algorithm was employed to extract features from the VMD-TE connection matrix across different rehabilitation periods. RESULTS: Beta waves in EEG were emerged as the key information carrier between the cortex and muscle, and the CMFN of patients with the beta frequency band has small-world characteristics. During rehabilitation, we observed a decrease in coupling between the initially affected motor cortex and muscle, accompanied by an increase in coupling between the frontal region and muscle. CONCLUSION: Our findings suggest potential neuro-remodeling in stroke patients after rehabilitation, with CFMN serving as a valuable metric for assessing cortico-muscular coupling.
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DEAD-box helicase 53 (DDX53) is a member of the DEAD-box protein family of RNA helicases. Unlike other family members that are responsible for RNA metabolism, the biological function of DDX53 and its impact on the human condition are unclear. Herein, we found a full-length DDX53 deletion mutation in a hereditary spastic paraplegia-like (HSP-like) patient with lower extremity spasticity, walking disorder, visual impairment, and lateral ventricular white matter lesions. Bioinformatic analysis revealed that DDX53 was mainly expressed in the cerebellar cortex and may function as a tissue-specific RNA helicase. Transcriptome analysis showed that the expression of multiple brain-associated genes involved in synapse organization, neuron function, and neuromuscular junctions was affected by DDX53 depletion. Moreover, RNA immunoprecipitation sequencing (RIP-seq) analysis showed that DDX53 interacted with 176 genes, and 96 of these genes were associated with the execution of neurofunction, particularly in the regulation of cell projection organization and nervous system development. Collectively, although a more specified cell or animal model is required to fully understand the functional role of DDX53 in the human brain, we report for the first time that the patient with DDX53 defects exhibits HSP-like symptoms and that DDX53 is essential for maintaining neuronal function, with loss-of-function mutation in DDX53 potentially leading to HSP due to impaired RNA metabolism in the nervous system. KEY MESSAGES: DDX53 deficiency was first reported to be associated with HSP disorder. DDX53 exhibited minimal impact on mitochondrial function. DDX53 impaired RNA metabolism in the nervous system.
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ARN Helicasas DEAD-box , Paraplejía Espástica Hereditaria , Femenino , Humanos , Masculino , Encéfalo/metabolismo , Encéfalo/patología , ARN Helicasas DEAD-box/genética , ARN Helicasas DEAD-box/metabolismo , Mutación con Pérdida de Función , Linaje , Paraplejía Espástica Hereditaria/genética , Paraplejía Espástica Hereditaria/metabolismo , AdultoRESUMEN
Chinese cabbage, scientifically known as Brassica rapa subsp. pekinensis, is a highly popular vegetable in China for its delectable taste. However, the occurrence of bacterial soft rot disease poses a significant threat to its growth and overall development. Consequently, this study aimed to explore the defense mechanisms employed by Chinese cabbage against bacterial soft rot disease. Specifically, the investigation focused on understanding the relationship between the disease and the microbial communities present in the soil surrounding the roots of Chinese cabbage. Significant disparities were observed in the composition of microbial communities present in the root-zone soil of healthy Chinese cabbage plants compared to those affected by Pectobacterium brasiliense-caused soft rot disease. The analysis of 16S rRNA gene high-throughput sequencing results revealed a lower abundance of Proteobacteria (8.39%), Acidobacteriot (0.85), Sphingomonas (3.51%), and Vicinamibacteraceae (1.48%), whereas Firmicutes (113.76%), Bacteroidota (8.71%), Chloroflexi (4.89%), Actinobacteriota (1.71%), A4b (15.52%), Vicinamibacterales (1.62%), and Gemmatimonadaceae (1.35%) were more prevalent in healthy plant soils. Similarly, the analysis of ITS gene high-throughput sequencing results indicated a reduced occurrence of Chytridiomycota (23.58%), Basidiomycota (21.80%), Plectosphaerella (86.22%), and Agaricomycetes (22.57%) in healthy soils. In comparison, Mortierellomycota (50.72%), Ascomycota (31.22%), Podospora (485.08%), and Mortierella (51.59%) were more abundant in healthy plant soils. In addition, a total of 15 bacterial strains were isolated from the root-zone soil of diseased Chinese cabbage plants. These isolated strains demonstrated the ability to fix nitrogen (with the exception of ZT20, ZT26, ZT41, ZT45, and ZT61), produce siderophores and indole acetic acid (IAA), and solubilize phosphate. Notably, ZT14 (Citrobacter freundii), ZT33 (Enterobacter cloacae), ZT41 (Myroides odoratimimus), ZT52 (Bacillus paramycoides), ZT58 (Klebsiella pasteurii), ZT45 (Klebsiella aerogenes), and ZT32 (Pseudomonas putida) exhibited significant growth-promoting effects as determined by the plant growth promotion (PGP) tests. Consequently, this investigation not only confirmed the presence of the soft rot pathogen in Chinese cabbage plants in Hangzhou, China, but also advanced our understanding of the defense mechanisms employed by Chinese cabbage to combat soft rot-induced stress. Additionally, it identified promising plant-growth-promoting microbes (PGPMs) that could be utilized in the future to enhance the Chinese cabbage industry.
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The extraction of effective classification features from electroencephalogram (EEG) signals in motor imagery is a popular research topic. The Common Spatial Pattern (CSP) algorithm is widely employed in this field. However, the performance of the traditional CSP method depends significantly on the choice of a specific frequency band and channel number of EEG data. Furthermore, inter-class variance among these frequency bands and the limited number of available EEG channels can adversely affect the CSP algorithm's ability to extract meaningful features from the relevant signal frequency bands. We hypothesize that multiple Intrinsic Mode Functions (IMFS), into which the raw EEG signal is decomposed, can better capture the non-Gaussian characteristics of the signal, thus compensating for the limitations of the CSP algorithm when dealing with nonlinear and non-Gaussian distributed data with few channels. Therefore, this paper proposes a novel method that integrates Variational Mode Decomposition (VMD), Phase Space Reconstruction (PSR), and the CSP algorithm to address these issues. VMD is used to filter and enhance the quality of the collected data, PSR is employed to increase the effective data channels (data augmentation), and the subsequent CSP filtering can obtain signals with spatial features, which are decoded by Convolutional Neural Networks (CNN) for action decoding. This study utilizes self-collected EEG data to demonstrate that the new method can achieve a good classification accuracy of 82.30% on average, confirming the improved algorithm's effectiveness and feasibility. Furthermore, this study conducted validation on the publicly available BCI Competition IV dataset 2b, demonstrating an average classification accuracy of 87.49%.
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Algoritmos , Electroencefalografía , Procesamiento de Señales Asistido por Computador , Humanos , Electroencefalografía/métodos , Redes Neurales de la Computación , Interfaces Cerebro-Computador , Imaginación/fisiología , Movimiento (Física)RESUMEN
Blockchain technology is increasingly being used in personal data protection. Inspired by the importance of data security, this paper proposes a personal data protection mechanism based on blockchain, combined with distributed hash tables and cryptography, to enhance users' control over the data generated using web applications. This paper designs this mechanism's system model and describes the three aspects in detail: data storage mechanism, data encryption mechanism, and data trading mechanism. Among them, the data storage mechanism restricts user data to be stored only in the local storage space of the user terminal, the decentralized blockchain network, and the distributed hash table network to ensure that enterprises providing network applications cannot privately store user interaction data, the encryption mechanism is responsible for encrypting all user data recorded in the network and allows users to control the key of the data to ensure the security of the user data in the blockchain and distributed hash tables, the data transaction mechanism allows users to trade their data, and to incentivize enterprises to assist users in collecting personal data, data transaction contracts are built into the data transaction mechanism, allowing enterprises to receive a share of the revenue from user data transactions. Then, for data transactions, use the Stackelberg game to simulate the revenue sharing between users and service providers in data trading to incentivize enterprises providing web services to assist users in collecting their data. The simulation results show that when the number of users is 1000, the revenues of this scheme for service providers are 31%, 561%, and 19% higher than the existing scheme. Finally, the personal data protection platform is implemented by code to verify the feasibility of the theory proposed in this paper in personal data protection.
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Objective: The objective of this study is to identify patients with sepsis who are at a high risk of respiratory failure. Methods: Data of 1,738 patients with sepsis admitted to Dongyang People's Hospital from June 2013 to May 2023 were collected, including the age at admission, blood indicators, and physiological indicators. Independent risk factors for respiratory failure during hospitalization in the modeling population were analyzed to establish a nomogram. The area under the receiver operating characteristic curve (AUC) was used to evaluate the discriminative ability, the GiViTI calibration graph was used to evaluate the calibration, and the decline curve analysis (DCA) curve was used to evaluate and predict the clinical validity. The model was compared with the Sequential Organ Failure Assessment (SOFA) score, the National Early Warning Score (NEWS) system, and the ensemble model using the validation population. Results: Ten independent risk factors for respiratory failure in patients with sepsis were included in the final logistic model. The AUC values of the prediction model in the modeling population and validation population were 0.792 and 0.807, respectively, both with good fit between the predicted possibility and the observed event. The DCA curves were far away from the two extreme curves, indicating good clinical benefits. Based on the AUC values in the validation population, this model showed higher discrimination power than the SOFA score (AUC: 0.682; p < 0.001) and NEWS (AUC: 0.520; p < 0.001), and it was comparable to the ensemble model (AUC: 0.758; p = 0.180). Conclusion: Our model had good performance in predicting the risk of respiratory failure in patients with sepsis within 48 h following admission.
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BACKGROUND: The emergence and wide spread of carbapenemase-producing Enterobacteriaceae (CPE) poses a growing threat to global public health. However, clinically derived carbapenemase-producing Citrobacter causing multiple infections has rarely been investigated. Here we first report the isolation and comparative genomics of two blaNDM-5 carrying Citrobacter freundii (C. freundii) isolates from a patient with bloodstream and urinary tract infections. RESULTS: Antimicrobial susceptibility testing showed that both blaNDM-5 carrying C. freundii isolates were multidrug-resistant. Positive modified carbapenem inactivation method (mCIM) and EDTA-carbapenem inactivation method (eCIM) results suggested metallo-carbapenemase production. PCR and sequencing confirmed that both metallo-carbapenemase producers were blaNDM-5 positive. Genotyping and comparative genomics analyses revealed that both isolates exhibited a high level of genetic similarity. Plasmid analysis confirmed that the blaNDM-5 resistance gene is located on IncX3 plasmid with a length of 46,161 bp, and could successfully be transferred to the recipient Escherichia coli EC600 strain. A conserved structure sequence (ISAba125-IS5-blaNDM-5-trpF-IS26-umuD-ISKox3) was found in the upstream and downstream of the blaNDM-5 gene. CONCLUSIONS: The data presented in this study showed that the conjugative blaNDM-5 plasmid possesses a certain ability to horizontal transfer. The dissemination of NDM-5-producing C. freundii isolates should be of close concern in future clinical surveillance. To our knowledge, this is the first study to characterize C. freundii strains carrying the blaNDM-5 gene from one single patient with multiple infections.
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Carbapenémicos , Citrobacter freundii , Humanos , Citrobacter freundii/genética , Mapeo Cromosómico , Secuencia Conservada , Carbapenémicos/farmacología , Carbapenémicos/uso terapéutico , Escherichia coli , GenómicaRESUMEN
Respiratory complex IV (CIV, cytochrome c oxidase) is the terminal enzyme of the mitochondrial electron transport chain. Some CIV subunits have two or more isoforms, which are ubiquitously expressed or are expressed in specific tissues like the lung, muscle, and testis. Among the tissue-specific CIV isoforms, the muscle-specific isoforms are expressed in adult cardiac and skeletal muscles. To date, the physiological and biochemical association between the muscle-specific CIV isoforms and aerobic respiration in muscles remains unclear. In this study, we profiled the CIV organization and expression pattern of muscle-specific CIV isoforms in different mouse muscle tissues. We found extensive CIV-containing supramolecular organization in murine musculature at advanced developmental stages, while a switch in the expression from ubiquitous to muscle-specific isoforms of CIV was also detected. Such a switch was confirmed during the in vitro differentiation of mouse C2C12 myoblasts. Unexpectedly, a CIV expression decrease was observed during C2C12 differentiation, which was probably due to a small increase in the expression of muscle-specific isoforms coupled with a dramatic decrease in the ubiquitous isoforms. We also found that the enzymatic activity of CIV containing the muscle-specific isoform COX6A2 was higher than that with COX6A1 in engineered HEK293T cells. Overall, our results indicate that switching the expression from ubiquitous to muscle-specific CIV isoforms is indispensable for optimized oxidative phosphorylation in mature skeletal muscles. We also note that the in vitro C2C12 differentiation model is not suitable for the study of muscular aerobic respiration due to insufficient expression of muscle-specific CIV isoforms.
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Complejo IV de Transporte de Electrones , Músculo Esquelético , Masculino , Ratones , Animales , Humanos , Complejo IV de Transporte de Electrones/metabolismo , Células HEK293 , Músculo Esquelético/metabolismo , Mitocondrias/metabolismo , Isoformas de Proteínas/metabolismoRESUMEN
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a serious threat to global development. Rapid and accurate diagnosis is critical for containing the pandemic and treating patients in time. As the gold standard for SARS-CoV-2 diagnosis, the qualitative reverse transcription-PCR (RT-qPCR) test has long been criticized for its long detection time. In this study, we optimized the primers and probes targeting SARS-CoV-2 ORF1ab and N gene designed by the Chinese Center for Disease Control and Preventions (CDC) to increase their Tm values to meet the optimal elongation temperature of Taq DNA polymerase, thus greatly shortened the elongation time. The higher elongation temperature in turn narrowed the temperature range of the reaction and saved more time. In addition, by shortening the distance between the fluorophore at the 5' end and the quencher in the middle we got a probe with higher signal-to-noise ratio. Finally, by using all these measures and optimized RT-qPCR program we successfully reduced the time (nucleic acid extraction step is not included) for nucleic acid test from 74 min to 26 min.
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COVID-19 , Ácidos Nucleicos , Humanos , SARS-CoV-2 , COVID-19/diagnóstico , Prueba de COVID-19 , ARN Viral/genética , Sensibilidad y Especificidad , Reacción en Cadena en Tiempo Real de la PolimerasaAsunto(s)
Virus de la Influenza A , Gripe Aviar , Gripe Humana , Animales , Humanos , Gripe Humana/diagnósticoRESUMEN
The coronavirus disease 2019 has been ravaging throughout the world for three years and has severely impaired both human health and the economy. The causative agent, severe acute respiratory syndrome coronavirus 2 employs the viral RNA dependent RNA polymerase (RdRp) complex for genome replication and transcription, making RdRp an appealing target for antiviral drug development. Systematic characterization of RdRp will undoubtedly aid in the development of antiviral drugs targeting RdRp. Here, our research reveals that RdRp can recognize and utilize nucleoside diphosphates as a substrate to synthesize RNA with an efficiency of about two thirds of using nucleoside triphosphates as a substrate. Nucleoside diphosphates incorporation is also template-specific and has high fidelity. Moreover, RdRp can incorporate ß-d-N4-hydroxycytidine into RNA while using diphosphate form molnupiravir as a substrate. This incorporation results in genome mutation and virus death. It is also observed that diphosphate form molnupiravir is a better substrate for RdRp than the triphosphate form molnupiravir, presenting a new strategy for drug design.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/metabolismo , ARN , Difosfatos , Nucleósidos , ARN Polimerasa Dependiente del ARN/metabolismo , Antivirales/química , Nucleótidos , ARN Viral/genética , Proteínas del Ojo , Proteínas del Tejido NerviosoRESUMEN
Billions of people suffer from dental caries every year in spite of the effort to reduce the prevalence over the past few decades. Streptococcus mutans is the leading member of a specific group of cariogenic bacteria that cause dental caries. S. mutans forms biofilm, which is highly resistant to harsh environment, host immunity, and antimicrobial treatments. In this study, we found that S. mutans biofilm is highly resistant to both antimicrobial agents and lysozyme. DexA70, the truncated form of DexA (amino acids 100-732), a dextranase in S. mutans, prevents S. mutans biofilm formation and disassembles existing biofilms within minutes at nanomolar concentrations when supplied exogenously. DexA70 treatment markedly enhances biofilm sensitivity to antimicrobial agents and lysozyme, indicating its great potential in combating biofilm-related dental caries.
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BACKGROUND: Angiopoietin-2 (Angpt2) is associated with the progression of coronary artery disease (CAD). This research aimed to investigate the possible association between single nucleotide polymorphisms (SNPs) of ANGPT2 and CAD. METHODS: This research was performed in a hospital from the eastern region of China. From February 2019 to June 2019, 222 patients with CAD were newly diagnosed and 403 healthy controls were confirmed by physical examinations. The distribution frequency of five SNPs of the ANGPT2 (rs11137037, rs2442598, rs12674822, rs1823375, and rs734701) in all participants was analyzed by real-time polymerase chain reaction (PCR) with SNP locus-specific probes. RESULTS: Our data showed that the participants with the TT genotype of rs2442598 were at reduced risk of CAD compared with wild-types (adjusted odds ratio [AOR] = 0.511, 95% CI: 0.283-0.923). The participants with the AC and AC+CC genotypes of rs11137037 were at greater risk of CAD compared to wild-types (AOR = 1.754, 95% CI: 1.140-2.699; AOR = 1.731, 95% CI: 1.165-2.573, respectively). In addition, carriers of the GG+TT genotypes of rs12674822, showed more significant high-density lipoprotein than those of GG genotype, in addition, carriers of the GG+TT genotypes of rs12674822, showed more significant high-density lipoprotein than those of GG genotype (P=0.037). CONCLUSION: These findings, as well as analysis of the haplotype, clearly indicate that ANGPT2 SNPs were highly correlated with susceptibility to CAD among the Han Chinese population.
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Enfermedad de la Arteria Coronaria , Angiopoyetina 2/genética , Pueblo Asiatico/genética , Estudios de Casos y Controles , China/epidemiología , Enfermedad de la Arteria Coronaria/genética , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Polimorfismo de Nucleótido SimpleRESUMEN
Pulmonary embolism (PE) is a leading cause of mortality in postoperative patients. Numerous PE prevention clinical practice guidelines are available but not consistently implemented. This study aimed to develop and validate a novel risk assessment model to assess the risk of PE in postoperative patients. Patients who underwent Grade IV surgery between September 2012 and January 2020 (n = 26,536) at the Affiliated Dongyang Hospital of Wenzhou Medical University were enrolled in our study. PE was confirmed by an identified filling defect in the pulmonary artery system in CT pulmonary angiography. The PE incidence was evaluated before discharge. All preoperative data containing clinical and laboratory variables were extracted for each participant. A novel risk assessment model (RAM) for PE was developed with multivariate regression analysis. The discrimination ability of the RAM was evaluated by the area under the receiver operating characteristic curve, and model calibration was assessed by the Hosmer-Lemeshow statistic. We included 53 clinical and laboratory variables in this study. Among them, 296 postoperative patients developed PE before discharge, and the incidence rate was 1.04%. The distribution of variables between the training group and the validation group was balanced. After using multivariate stepwise regression, only variable age (OR 1.070 [1.054-1.087], P < 0.001), drinking (OR 0.477 [0.304-0.749], P = 0.001), malignant tumor (OR 2.552 [1.745-3.731], P < 0.001), anticoagulant (OR 3.719 [2.281-6.062], P < 0.001), lymphocyte percentage (OR 2.773 [2.342-3.285], P < 0.001), neutrophil percentage (OR 10.703 [8.337-13.739], P < 0.001), red blood cell (OR 1.872 [1.384-2.532], P < 0.001), total bilirubin (OR 1.038 [1.012-1.064], P < 0.001), direct bilirubin (OR 0.850 [0.779-0.928], P < 0.001), prothrombin time (OR 0.768 [0.636-0.926], P < 0.001) and fibrinogen (OR 0.772 [0.651-0.915], P < 0.001) were selected and significantly associated with PE. The final model included four variables: neutrophil percentage, age, malignant tumor and lymphocyte percentage. The AUC of the model was 0.949 (95% CI 0.932-0.966). The risk prediction model still showed good calibration, with reasonable agreement between the observed and predicted PE outcomes in the validation set (AUC 0.958). The information on sensitivity, specificity and predictive values according to cutoff points of the score in the training set suggested a threshold of 0.012 as the optimal cutoff value to define high-risk individuals. We developed a new approach to select hazard factors for PE in postoperative patients. This tool provided a consistent, accurate, and effective method for risk assessment. This finding may help decision-makers weigh the risk of PE and appropriately select PE prevention strategies.
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Susceptibilidad a Enfermedades , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Embolia Pulmonar/epidemiología , Embolia Pulmonar/etiología , Humanos , Análisis Multivariante , Periodo Posoperatorio , Pronóstico , Embolia Pulmonar/diagnóstico , Curva ROC , Reproducibilidad de los Resultados , Estudios Retrospectivos , Medición de Riesgo , Factores de RiesgoRESUMEN
BACKGROUND: To assess the impact of lymph node dissection (LND) extent on overall survival (OS) and cancer-specific survival (CSS) in patients with pN0M0 renal cell carcinoma (RCC) treated with radical nephrectomy (RN). MATERIALS AND METHODS: Data queried for this study include RCC (2010-2014) from the Surveillance, Epidemiology, and End Results (SEER) program. Kaplan-Meier analyses and multivariate Cox regression models tested the effect of number of removed lymph node (NRN) ≥ 50th percentile on OS and CSS. The associations were evaluated using propensity score (PS) matching adjustment. RESULTS: A total of 5532 pN0M0 RCC patients were enrolled in our study. The median NRN was 2 (IQR 1-6), the 50th percentile defined patients with NRN ≥ 2. Following PS adjustment, there were no significant differences in clinicopathologic features between two groups of patients except for age. Multivariate model analysis showed that patients with NRN < 2 had worse OS than those with NRN ≥ 2 in pT3 group (HR 1.442; P = 0.032) but not in pT1 and pT2 groups (HR 0.859 and 1.393, P = 0.443 and P = 0.267, respectively). However, patients with NRN < 2 had better CCS than those with NRN ≥ 2 in pT1 group (HR 0.368; P = 0.016) but not in pT2 and pT3 groups (HR 1.674 and 1.325, P = 0.216 and P = 0.176, respectively). CONCLUSIONS: More extensive LND (NRN ≥ 2) at RN is associated with better OS in pT3N0M0 RCC patients while it exerts negative influence on CCS in pT1N0M0 group. Hence, more extensive LND has therapeutic value in pT3 individuals but not in pT1 group.
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Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/cirugía , Neoplasias Renales/mortalidad , Neoplasias Renales/cirugía , Escisión del Ganglio Linfático/métodos , Nefrectomía , Anciano , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/secundario , Femenino , Humanos , Neoplasias Renales/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Nefrectomía/métodos , Puntaje de Propensión , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Lung cancers have a predilection for metastasizing to bone. The matricellular glycoprotein thrombospondin (TSP)-2 regulates multiple biological functions and has a critical role in tumor development and metastasis, although its effects are uncertain in lung cancer bone metastasis. This study demonstrates that TSP-2 expression is highly correlated with lung cancer tumor stage and that the TSP-2 neutralizing antibody reduces osteoclast formation in conditioned medium obtained from lung cancer cells. We also found that TSP-2 promotes osteoclastogenesis through the RANKL-dependent pathway and that TSP-2-mediated osteoclastogenesis involves the transactivation of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) via the inhibition of miR-486-3p expression. Osteoblasts played a critical role in osteoclast differentiation and incubation of osteoblasts with TSP-2 altered the RANKL:OPG ratio. Furthermore, TSP-2 knockdown inhibited lung cancer osteolytic metastasis in vivo. TSP-2 appears to be worth targeting for the prevention of bone metastasis in lung cancer.
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Neoplasias Óseas/metabolismo , Neoplasias Pulmonares/metabolismo , Osteoclastos/metabolismo , Osteogénesis/fisiología , Ligando RANK/metabolismo , Trombospondinas/metabolismo , Células A549 , Animales , Neoplasias Óseas/patología , Neoplasias Óseas/secundario , Humanos , Neoplasias Pulmonares/patología , Ratones , Ratones Desnudos , Osteoclastos/patología , Ligando RANK/farmacología , Células RAW 264.7 , Trombospondinas/deficiencia , Trombospondinas/farmacologíaRESUMEN
BACKGROUND: Etoposide-induced gene 24 (EI24) is an induction target of TP53-mediated apoptosis in human cancer cells. The hypothesis of this study is that EI24 might be a prognostic biomarker of non-small cell lung carcinoma (NSCLC). MATERIAL AND METHODS: Fourteen gene expression NSCLC datasets with follow-up information (a total of 2582 accessible cases) were collected from Asia, Europe and North America. The Kaplan-Meier and Cox analyses were applied to evaluate the relation between EI24 and the outcomes of NSCLC. A gene set enrichment analysis (GSEA) was used to explore EI24 and cancer-related gene signatures. RESULTS: EI24 was significantly upregulated in mutated TP53 NSCLC samples and significantly downregulated with the increase in the TP53 expression level in NSCLC. GSEA results suggested that EI24 significantly enriched metastasis and poor prognosis gene signatures. Meanwhile, EI24 was significantly upregulated in lung adenocarcinoma compared with normal lungs (p < 0.01). It was also highly expressed in the later TNM stages and the ALK fusion+, higher MYC gene copy and EGFR wild type subgroups (p < 0.05). The Kaplan-Meier analysis demonstrated that the expression of EI24 was significantly associated with poor overall survival and disease-free survival in a dose-dependent manner in GSE31210 dataset. The C-index of Cox model with EI24 is 0.70, that is better than that with MYC (0.51), KRAS (0.51) and EGFR (0.59), which indicates better prognostic performance of EI24. The prognostic significance of EI24 for overall survival of NSCLC was validated by pooled and meta-analysis on 14 datasets. The stratification analysis revealed that EI24 prognosticated poor overall survival (HR = 3.37, 95% CI = 1.39-9.62, p < 0.05) in the TP53 wild type subgroup, but not in the mutated TP53 NSCLC subgroup. Moreover, YY1 might transcriptionally regulate EI24 in a positive manner. CONCLUSION: EI24 is a potential prognostic biomarker and impacts poor outcome in NSCLC. The prognostic significance of EI24 might rely on TP53 status.