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INTRODUCTION: The efficacy and safety of Ivabradine for patients with acute heart failure (AHF) is controversial, and there are few clinical trials addressing this topic. METHODS: We performed this meta-analysis to evaluate efficacy and safety of Ivabradine treatment for patients with acute heart failure. We obtained data for controlled trials using the PubMed, Cochrane Library, EMBASE, and Clinical Trials.gov databases. The efficacy endpoints included change in heart rate, brain natriuretic peptide (BNP) levels, N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, ejection fraction (EF) values, and a 6-min walk distance. The safety endpoints included mortality, cardiogenic mortality, incidents of hospital readmission, bradycardia, and atrial fibrillation. Ten randomized controlled trials (RCTs) met our criteria, and data from 656 patients were included for the study. RESULTS: Ivabradine treatment significantly decreased heart rate and BNP and NT-proBNP levels compared with those seen in the control group. EF values were significantly increased upon ivabradine treatment. No significant differences were observed in the endpoints of the 6-min walk distance, all-cause mortality, cardiogenic mortality, incidents of hospital readmission, bradycardia, and atrial fibrillation data between ivabradine treated and control groups. CONCLUSIONS: Ivabradine can reduce heart rate and BNP and NT-pro BNP levels and elevate EF values and 6-min walk distance data significantly in acute heart failure patients. It also exhibits a stable safety profile, with similar risks of all-cause mortality, cardiogenic mortality, incidents of readmission, and major adverse cardiovascular effects compared with those of the control group.
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Insuficiência Cardíaca , Ivabradina , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Ivabradina/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Doença Aguda , Resultado do Tratamento , Fármacos Cardiovasculares/uso terapêutico , Peptídeo Natriurético Encefálico/sangue , Frequência Cardíaca/efeitos dos fármacos , Fragmentos de PeptídeosRESUMO
There is limited research on the clinicopathological characteristics of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) currently. The aim of this study is to summerize the clinicopathological factors and prognosis of cHCC-CCA, which could help us understand this disease. 72 cases of cHCC-CCA from West China Hospital of Sichuan University were collected. Tissue components were reviewed by pathologists. Immunohistochemistry was used to detect the status of mismatch repair (MMR) and human epidermal growth factor receptor 2 (HER2) in cHCC-CCA, as well as the quantity and distribution of CD3+ T cells and CD8+ T cells. Fluorescence in situ hybridization was used to detect fibroblast growth factor receptor 2 (FGFR2) gene alteration. COX univariate and multivariate analyses were used to evaluate risk factors, and survival curves were plotted. 49 cases were classified as classic type cHCC-CCA and 23 cases as intermediate cell carcinoma. The cut-off value for diagnosing classic type was determined to be ≥ 30% for the cholangiocarcinoma component based on prognostic calculations. All tumors were MMR proficient. The rate of strong HER2 protein expression (3+) was 8.3%, and the frequency of FGFR2 gene alteration was 26.4%. CD3+ T cells and CD8+ T cells were mainly distributed at the tumor margin, and were protective factors for patients with cHCC-CCA. The overall survival of the 72 patients was 18.9 months, with a median survival of 12 months. Tumor size, TNM stage, and serum AFP level were prognostic factors for cHCC-CCA. The proportion of cholangiocarcinoma component reaching the threshold of 30%, may provide a reference for future pathology diagnosis. FGFR2 gene alteration was 26.4%, providing a clue for anti-FGFR2 therapy. However, more data is needed for further verification.
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Neoplasias dos Ductos Biliares , Carcinoma Hepatocelular , Colangiocarcinoma , Neoplasias Hepáticas , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos , Humanos , Colangiocarcinoma/patologia , Colangiocarcinoma/genética , Colangiocarcinoma/mortalidade , Colangiocarcinoma/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Idoso , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/diagnóstico , Adulto , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Biomarcadores Tumorais/genética , Reparo de Erro de Pareamento de DNA , Imuno-HistoquímicaRESUMO
Hepatitis B virus (HBV) is the most common chronic viral infection globally, affecting â¼360 million people and causing about 1 million deaths annually due to end-stage liver disease or hepatocellular carcinoma. Current antiviral treatments rarely achieve a functional cure for chronic hepatitis B, highlighting the need for improved monitoring and intervention strategies. This study explores the role of the sphingosine kinase 1 (SphK1)-sphingosine-1-phosphate (S1P) axis in HBV-related liver injury. We investigated the association between serum S1P concentration and HBV DNA levels in chronic hepatitis B patients, finding a significant positive correlation. Additionally, SphK1 was elevated in liver tissues of HBV-positive hepatocellular carcinoma patients, particularly in HBsAg-positive regions. HBV infection models in HepG2-sodium taurocholate cotransporting polypeptide cells confirmed that HBV enhances SphK1 expression and S1P production. Inhibition of HBV replication through antiviral agents and the CRISPR-Cas9 system reduced SphK1 and S1P levels. Further, we identified the transcription factor USF1 as a key regulator of SphK1 expression during HBV infection. USF1 binds to the SphK1 promoter, increasing its transcriptional activity, and is upregulated in response to HBV infection. In vivo studies in mice demonstrated that HBV exposure promotes the expression of USF1 and SphK1-S1P. These findings suggest that the SphK1-S1P axis, regulated by HBV-induced USF1, could serve as a potential biomarker and therapeutic target for HBV-related liver injury.
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BACKGROUND: Scant data are available on heterogenous staining of mismatch repair protein in colorectal cancer. OBJECTIVE: This study aimed to improve insights into clinicopathologic features and prognosis of colorectal cancer harboring heterogenous mismatch repair protein staining. DESIGN: A single-center retrospective observational study. SETTING: This study was conducted in a tertiary referral center in China between 2014 and 2018. PATIENTS: Colorectal cancers with heterogenous staining of mismatch repair protein were included. MAIN OUTCOMES MEASURES: Clinicopathologic and molecular features, and survival outcomes were analyzed. RESULTS: A total of 151 out of 6721 colorectal cancers (2.2%) exhibited heterogenous staining for at least one mismatch repair protein, with intraglandular heterogeneity being the most common pattern (89.4%). Heterogenous MLH1 staining was significantly associated with distant metastasis (p = 0.03), while heterogenous MSH2 staining was associated with left-sided (p = 0.03) and earlier pT stage tumors (p = 0.02). The rates of microsatellite instability-high, KRAS and BRAF mutation were 12.6%, 47.3% and 3.4%, respectively. Microsatellite instability-high was significantly associated with higher intraglandular MSH6 heterogeneity frequency (p < 0.001) and decreased MSH6 expression level (< 27.5%, p = 0.01). BRAF mutation was associated with the coexistence of intraglandular and clonal heterogeneity (p = 0.003) and decreased PMS2 expression level (p = 0.01). Multivariable analysis revealed that progression-free survival was significantly associated with tumor stage (p = 0.003), stroma fraction (p = 0.004), and heterogenous PMS2 staining (p = 0.02). Overall survival was linked to tumor stage (p = 0.006) and BRAF mutation (p = 0.01). LIMITATIONS: The limitations of this study include the absence of testing for MLH1 promoter methylation and mismatch repair gene mutations, its retrospective design, and insufficient data related to direct comparison with deficient mismatch repair and proficient mismatch repair colorectal cancer. CONCLUSIONS: Heterogenous mismatch repair protein staining in colorectal cancer exhibits distinct associations with tumor location, stage, microsatellite instability, BRAF mutation and prognosis. It is recommended to report MSH6 heterogeneity as it may indicate microsatellite instability-high. See Video Abstract.
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Ovarian cancer (OC) is one of the three major gynecologic malignancies and has the highest mortality rate because of the late diagnosis. Liquid biopsy based on serum protein biomarkers has demonstrated great potential for early diagnosis but remains limited by the analysis performance of conventional immunoassay technologies, such as chemiluminescence, and biomarkers, such as CA125. To address this challenge and achieve accurate early-stage diagnosis of OC, we developed a digital immunoassay on a SlipChip (DiSC) for quantitative analysis of a potential serum protein biomarker, Spondin-1 (SPON1). The DiSC system achieved a limit of detection (LoD) of 23 fg/µL for digital quantification of SPON1. The DiSC system was utilized to quantify the serum level of SPON1 in 357 clinical serum samples, including 63 from patients with benign ovarian tumors and 294 from patients with malignant ovarian cancer, ranging from stages I to IV. SPON1 concentrations were significantly different in samples from patients with malignant ovarian cancer. Notably, significantly different SPON1 levels were observed in early stages (I and II), in lymph node-negative cases (N0), and before metastasis (M0), suggesting that SPON1 could serve as a sensitive diagnostic biomarker for early-stage OC. The differential diagnostic model based on SPON1 levels quantified using DiSC demonstrated an area under the curve (AUC) of 0.8187 for early-stage OC, a significant improvement over CA-125 (AUC = 0.6967). For OC of all stages, the AUC was 0.8225, which could be further increased to 0.8750 when combined with CA-125. This showcases the potential of SPON1 as a novel biomarker for sensitive early-stage diagnosis of ovarian cancer and the capability of the DiSC system in discovering low-abundance biomarkers for disease diagnosis.
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Biomarcadores Tumorais , Detecção Precoce de Câncer , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/sangue , Imunoensaio/métodos , Biomarcadores Tumorais/sangue , Detecção Precoce de Câncer/métodos , Proteínas da Matriz Extracelular/sangue , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Adulto , IdosoRESUMO
Introduction: Chronic schizophrenia has a course of 5 years or more and has a widespread abnormalities in brain functional connectivity. This study aimed to find characteristic functional and structural changes in a long illness duration chronic schizophrenia (10 years or more). Methods: Thirty-six patients with a long illness duration chronic schizophrenia and 38 healthy controls were analyzed by independent component analysis of brain network functional connectivity. Correlation analysis with clinical duration was performed on six resting state networks: auditory network, default mode network, dorsal attention network, fronto-parietal network, somatomotor network, and visual network. Results: The differences in the resting state network between the two groups revealed that patients exhibited enhanced inter-network connections between default mode network and multiple brain networks, while the inter-network connections between somatomotor network, default mode network and visual network were reduced. In patients, functional connectivity of Cuneus_L was negatively correlated with illness duration. Furthermore, receiver operating characteristic curve of functional connectivity showed that changes in Thalamus_L, Rectus_L, Frontal_Mid_R, and Cerebelum_9_L may indicate a longer illness duration chronic schizophrenia. Discussion: In our study, we also confirmed that the course of disease is significantly associated with specific brain regions, and the changes in specific brain regions may indicate that chronic schizophrenia has a course of 10 years or more.
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With the intensive research on the pathogenesis of Alzheimer's disease (AD), inhibition of HDAC6 appears to be a potential therapeutic approach for AD. In this paper, a series of tetrahydro-ß-carboline derivatives with hydroxamic acid group were fast synthesized. Among all, the most potent 15 selectively inhibited HDAC6 with IC50 of 15.2 nM and markedly increased acetylated alpha-tubulin levels. In cellular assay, 15 showed excellent neurotrophic effect by increasing the expression of GAP43 and Beta-3 tubulin markers. Besides, 15 showed neuroprotective effects in PC12 or SH-SY5Y cells against H2O2 and 6-OHDA injury through activation of Nrf2, catalase and Prx II, and significantly reduced H2O2-induced reactive oxygen species (ROS) production. In vivo, 15 significantly attenuated zebrafish anxiety-like behaviour and memory deficits in a SCOP-induced zebrafish model of AD. To sum up, multifunctional 15 might be a good lead to develop novel tetrahydrocarboline-based agents for the treatment of AD.
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Doença de Alzheimer , Carbolinas , Desacetilase 6 de Histona , Inibidores de Histona Desacetilases , Fármacos Neuroprotetores , Peixe-Zebra , Carbolinas/farmacologia , Carbolinas/química , Carbolinas/síntese química , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Humanos , Animais , Desacetilase 6 de Histona/antagonistas & inibidores , Desacetilase 6 de Histona/metabolismo , Ratos , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/síntese química , Inibidores de Histona Desacetilases/química , Relação Estrutura-Atividade , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/síntese química , Fármacos Neuroprotetores/química , Estrutura Molecular , Relação Dose-Resposta a Droga , Células PC12 , Espécies Reativas de Oxigênio/metabolismoRESUMO
Bronchoscopic-assisted discrimination of lung tumors presents challenges, especially in cases with contraindications or inaccessible lesions. Through meta-analysis and validation using the HumanMethylation450 database, this study identified methylation markers for molecular discrimination in lung tumors and designed a sequencing panel. DNA samples from 118 bronchial washing fluid (BWF) specimens underwent enrichment via multiplex PCR before targeted methylation sequencing. The Recursive Feature Elimination Cross-Validation and deep neural network algorithm established the CanDo classification model, which incorporated 11 methylation features (including 8 specific to the TBR1 gene), demonstrating a sensitivity of 98.6% and specificity of 97.8%. In contrast, bronchoscopic rapid on-site evaluation (bronchoscopic-ROSE) had lower sensitivity (87.7%) and specificity (80%). Further validation in 33 individuals confirmed CanDo's discriminatory potential, particularly in challenging cases for bronchoscopic-ROSE due to pathological complexity. CanDo serves as a valuable complement to bronchoscopy for the discriminatory diagnosis and stratified management of lung tumors utilizing BWF specimens.
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Particulate matter (PM) pollution has posed a serious threat to public health, especially the global spread of infectious diseases. Most existing air filtration materials are still subjected to a compromise between removal efficiency and air permeability on account of their stacking bulk structures. Here, we proposed a self-polarized assembly technique to create two-dimensional piezoelectric nanofibrous webs (PNWs) directly from polymer solutions. The strategy involves droplets deforming into ultrathin liquid films by inertial flow, liquid films evolving into web-like architectures by instantaneous phase inversion, and enhanced dipole alignment by cluster electrostatics. The assembled continuous webs exhibit integrated structural superiorities of nanoscale diameters (â¼20 nm) of the internal fibers and through pores (â¼100 nm). Combined with the wind-driven electrostatic property derived from the enhanced piezoelectricity, the PNW filter shows high efficiency (99.48%) and low air resistance (34 Pa) against PM0.3 as well as high transparency (84%), superlight weight (0.7 g m-2), and long-term stable service life. This creation of such versatile nanomaterials may offer insight into the design and upgrading of high-performance filters.
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BACKGROUND: Focal liver lesions (FLLs) are a common form of liver disease, and identifying accurate pathological types is required to guide treatment and evaluate prognosis. PURPOSE: To compare and analyze the application effect of contrast-enhanced ultrasound (CEUS) and conventional ultrasound (US) in the clinical diagnosis of focal liver lesions. MATERIAL AND METHODS: A retrospective analysis was performed on 682 patients with space-occupying liver lesions admitted to our hospital between December 2015 and August 2021. Of these, 280 underwent CEUS-guided biopsies and 402 underwent conventional US biopsies, with the results of each biopsy subsequently compared between the two groups. The success rate and accuracy of the biopsies and their relationship with different pathological features were also analyzed. RESULTS: The success rate, sensitivity, diagnostic accuracy, positive predictive value, and negative predictive value of the CEUS group were significantly higher than those of the US group (P < 0.05). Lesion size accuracy in the CEUS group was significantly higher than that in the US group (89.29% vs. 40.55%; P < 0.05). Lesion type accuracy in the CEUS group was significantly higher than that in the US group (86.49% vs. 43.59%), and the difference between the two groups was statistically significant (P < 0.05). The logistic regression analysis indicated that malignant lesions, lesions ≥5 cm, and lesions ≤1 cm were independent factors affecting the success rate of the puncture procedure (P < 0.05). CONCLUSION: The sensitivity, specificity, and diagnostic accuracy of lesion size and type in the CEUS group were higher than those in the US group.
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Meios de Contraste , Sensibilidade e Especificidade , Ultrassonografia , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ultrassonografia/métodos , Adulto , Idoso , Fígado/diagnóstico por imagem , Fígado/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Hepatopatias/diagnóstico por imagem , Hepatopatias/patologia , Aumento da Imagem/métodos , Reprodutibilidade dos Testes , Valor Preditivo dos Testes , Adulto JovemRESUMO
Elastic aerogels can dissipate aerodynamic forces and thermal stresses by reversible slipping or deforming to avoid sudden failure caused by stress concentration, making them the most promising candidates for thermal protection in aerospace applications. However, existing elastic aerogels face difficulties achieving reliable protection above 1500 °C in aerobic environments due to their poor thermomechanical stability and significantly increased thermal conductivity at elevated temperatures. Here, a multiphase sequence and multiscale structural engineering strategy is proposed to synthesize mullite-carbon hybrid nanofibrous aerogels. The heterogeneous symbiotic effect between components simultaneously inhibits ceramic crystalline coarsening and carbon thermal etching, thus ensuring the thermal stability of the nanofiber building blocks. Efficient load transfer and high interfacial thermal resistance at crystalline-amorphous phase boundaries on the microscopic scale, coupled with mesoscale lamellar cellular and locally closed-pore structures, achieve rapid stress dissipation and thermal energy attenuation in aerogels. This robust thermal protection material system is compatible with ultralight density (30 mg cm-3), reversible compression strain of 60%, extraordinary thermomechanical stability (up to 1600 °C in oxidative environments), and ultralow thermal conductivity (50.58 mW m-1 K-1 at 300 °C), offering new options and possibilities to cope with the harsh operating environments faced by space exploration.
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Introduction: This study investigates the intricate relationship between parents' education anxiety and children's learning anxiety, examining the mediating role of parenting style and the moderating effect of extracurricular tutoring. Methods: Utilizing data from the "Survey of Parents and Students in Primary and Secondary Schools," the study employs stratified sampling (n = 3,298) and various psychological scales to measure education anxiety, parenting styles, and extracurricular tutoring. Results: This study reveals that parents' education anxiety significantly influences children's learning anxiety, with a notable positive correlation (r = 0.301**). Parenting styles particularly rejection and overprotection style increase this anxiety, while emotional warmth style decreases it. Academic tutoring serves as a moderator, reducing the impact of parental anxiety on children's learning anxiety (ß = -0.033, p < 0.05). Discussion: The study underscores the importance of addressing internal family dynamics to alleviate education anxiety. It advocates for a balanced approach to tutoring, emphasizing the benefits of arts and sports activities in reducing learning anxiety. Parents should be encouraged to adopt emotionally warm parenting styles and to engage their children in a variety of extracurricular activities.
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Background and Aim: To evaluate the efficacy and safety of minocycline, vonoprazan, amoxicillin, and bismuth quadruple therapy for Helicobacter pylori (H. pylori) treatment. Methods: From August 2022 to May 2023, clinical data were collected from patients who received H. pylori eradication treatment at West China Fourth Hospital, Sichuan University. One group received the MVAB regimen (amoxicillin, minocycline, vonoprazan, and colloidal bismuth pectin), while another group received the FOAB regimen (amoxicillin, furazolidone, omeprazole, and colloidal bismuth pectin), both administered for 14 days. Follow-up assessments of safety and compliance were conducted within 1 week after treatment completion. One and a half months after treatment, the success of eradication was evaluated using the urea breath test. Results: For the MVAB regimen as a first-line treatment, the eradication rate was 90.1% (127/141, 95% CI: 85.1-95.1%) in the ITT analysis and 93.4% (127/136, 95% CI: 89.2-97.6%) in the PP analysis as a first-line treatment. As a second-line treatment, the eradication rate was 91.3% (21/23, 95% CI: 78.8-103.8%) in both analyses. For the FOAB regimen as a first-line treatment, the eradication rate was 98.0% (50/51, 95% CI: 94.1-101.2%) in the ITT analysis and 100% (50/50, 95% CI: 100%) in the PP analysis. As a second-line treatment, the eradication rate was 100% (6/6, 95% CI: 100%) in both analyses. Moreover, there was no significant difference in the incidence of adverse events between the two groups (MVAB regimen: 5.5% and FOAB regimen: 8.8%; P > 0.05). Conclusions: The MVAB regimen could indeed be a viable alternative treatment option to conventional therapies.
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A novel colorimetric-fluorescent dual-mode chemosensor (JT5) based on rhodamine B has been produced for monitoring Sn4+ in the DMSO/H2O (4:1, v/v) medium. It has high sensitivity, a low detection limit, a short response time (1â¯s) and high stability, and can still be maintained after two weeks with the red dual fluorescence/ colorimetric response. Enhancement of red fluorescence (591â¯nm) and red colorimetric (567â¯nm) response of JT5 by Sn4+ addition. The electrostatic potential of the sensor JT5 molecule was simulated to speculate on the sensing mechanism, and the IR, mass spectrometry and 1H NMR titration were utilized to further demonstrate that JT5 was coordinated to Sn4+ with a 1:1 type, the rhodamine spironolactam ring of JT5 opens up to form a penta-membered ring with Sn4+, meanwhile, its system may have chelation enhanced fluorescence (CHEF) effect. In addition, theoretical calculations were carried out to give the energy gaps of JT5 and [JT5â¯+â¯Sn4+] as well as to simulate the electronic properties of the maximal absorption peaks. Notably, the sensor JT5 was successfully applied to monitoring Sn4+ in zebrafish, and the JT5-loaded filter paper provided a solid-state platform for detecting Sn4+ by both naked eye and fluorescent methods. In summary, this work contributes to monitoring Sn4+ in organisms and solid-state materials and promotes understanding of Sn4+ functions in biological systems, environments, and solid-state materials.
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Técnicas Biossensoriais , Corantes Fluorescentes , Rodaminas , Espectrometria de Fluorescência , Peixe-Zebra , Rodaminas/química , Animais , Corantes Fluorescentes/química , Técnicas Biossensoriais/métodos , Água/química , Colorimetria/métodos , Limite de DetecçãoRESUMO
Dual/multimodal imaging strategies are increasingly recognized for their potential to provide comprehensive diagnostic insights in cancer imaging by harnessing complementary data. This study presents an innovative probe that capitalizes on the synergistic benefits of afterglow luminescence and magnetic resonance imaging (MRI), effectively eliminating autofluorescence interference and delivering a superior signal-to-noise ratio. Additionally, it facilitates deep tissue penetration and enables noninvasive imaging. Despite the advantages, only a limited number of probes have demonstrated the capability to simultaneously enhance afterglow luminescence and achieve high-resolution MRI and afterglow imaging. Herein, we introduce a cutting-edge imaging platform based on semiconducting polymer nanoparticles (PFODBT) integrated with NaYF4@NaGdF4 (Y@Gd@PFO-SPNs), which can directly amplify afterglow luminescence and generate MRI and afterglow signals in tumor tissues. The proposed mechanism involves lanthanide nanoparticles producing singlet oxygen (1O2) upon white light irradiation, which subsequently oxidizes PFODBT, thereby intensifying afterglow luminescence. This innovative platform paves the way for the development of high signal-to-background ratio imaging modalities, promising noninvasive diagnostics for cancer.
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Elementos da Série dos Lantanídeos , Imageamento por Ressonância Magnética , Nanopartículas , Polímeros , Semicondutores , Imageamento por Ressonância Magnética/métodos , Animais , Elementos da Série dos Lantanídeos/química , Polímeros/química , Nanopartículas/química , Camundongos , Humanos , Gadolínio/química , Luminescência , Oxigênio Singlete/química , Ítrio/química , Fluoretos/química , Camundongos NusRESUMO
BACKGROUND: Uniparental disomy is the inheritance of a homologous chromosome pair or part of homologous chromosomes from only one parent. However, the clinical significance of uniparental disomy and the difference among the prognosis of involvement of different chromosomes remain unclear. OBJECTIVE: To assess the associated prenatal ultrasound presentations and clinical outcomes of uniparental disomy on different chromosomes and to analyze the relationship between prenatal ultrasound markers and clinical outcomes. STUDY DESIGN: We retrospectively analyzed data from fetuses with uniparental disomy diagnosed using chromosome microarray analysis with the Affymetrix CytoScan HD array at our institution between January 2013 and September 2022. The relationship between prenatal ultrasound findings, the involved chromosome(s), and clinical outcomes was evaluated. RESULTS: During the study period, 36 fetuses with uniparental disomy were diagnosed, and two cases were excluded for non-available postnatal data. Finally, 34 fetuses were included in our study, of which 30 (88.2%) had uniparental disomy occurring on a single chromosome, while four (11.8%) were identified with uniparental disomy on different chromosomes. The most frequently involved chromosomes were chromosomes 16, X and 2, which presented in 8 (23.5%), 5 (14.7%) and 4 (11.8%), respectively. Prenatal ultrasound abnormalities were detected in 21 fetuses, with the most common category being multiple abnormalities (12 (57.1%)). Fetal growth restriction was identified in 14 (41.2%) fetuses, all of which coexisted with other abnormal findings. The rate of adverse perinatal outcomes in patients with uniparental disomy and fetal abnormalities was significantly higher than those without abnormalities (76.2% versus 15.4%, P = 0.002). The incidence of fetal or neonatal death was significantly higher in fetuses with fetal growth restriction than those without (85.7% versus 30.0%, P = 0.004). CONCLUSIONS: The prognosis of fetuses with uniparental disomy combined with fetal abnormalities, especially fetal growth restriction, was much poorer than those without.
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Anormalidades Múltiplas , Dissomia Uniparental , Feminino , Recém-Nascido , Gravidez , Humanos , Dissomia Uniparental/genética , Estudos Retrospectivos , Retardo do Crescimento Fetal/genética , Ultrassonografia Pré-Natal , Diagnóstico Pré-NatalRESUMO
Diquat (DQ) is a typical bipyridine herbicide widely used to control weeds in fields and orchards. The severe toxicity of diquat poses a serious threat to the environment and human health. Metal-organic frameworks (MOFs) have received widespread attention due to their unique physical and chemical properties and applications in the detection of toxic and harmful substances. In this work, a two-dimensional (2D) Tb(III) functionalized MOF Tb(III)@1 (1 = [Cd(HTATB)(bimb)]n·H2O (Cd-MOF), H3TATB = 4,4',4â³-triazine-2,4,6-tribenzoicacid, bimb = 1,4-bis((1H-imidazol-1-yl)methyl)benzene) has been prepared and characterized. Tb(III)@1 has excellent optical properties and high water and chemical stability. After the Tb(III) is fixed by the uncoordinated -COO- in the 1 framework, Tb(III)@1 emits the typical green fluorescence of the lanthanide ion Tb(III) through the "antenna effect". It is worth noting that Tb(III)@1 can be used as a dual emission fluorescence chemical sensor for the ratio fluorescence detection of pesticide DQ, exhibiting a relatively low detection limit of 0.06 nM and a wide detection range of 0-50 nM. After the addition of DQ, a rapid color change of Tb(III)@1 fluorescence from green to blue was observed due to the combined effects of IFE, FRET and dynamic quenching. Therefore, a simple test paper box has been designed for direct on-site determination of pesticide DQ. In addition, the developed sensor has been successfully applied to the detection of DQ in real samples (fruits a Yin-Xia Sun and Bo-Tao Ji contributed equally to this work and should be considered co-first authors.nd vegetables) with satisfactory results. The results indicate that the probe developed in this study has broad application prospects in both real sample detection and actual on-site testing.
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Diquat , Contaminação de Alimentos , Malus , Estruturas Metalorgânicas , Solanum tuberosum , Térbio , Zea mays , Estruturas Metalorgânicas/química , Zea mays/química , Malus/química , Contaminação de Alimentos/análise , Diquat/química , Diquat/análise , Térbio/química , Solanum tuberosum/química , Herbicidas/análise , Herbicidas/química , Cádmio/análise , Limite de DetecçãoRESUMO
Background: Primary liver cancer (PLC) is a prevalent malignancy of the digestive system characterized by insidious symptom onset and a generally poor prognosis. Recent studies have highlighted a significant correlation between the initiation and prognosis of liver cancer and the immune function of PLC patients. Purpose: Revealing the expression of PLC-related immune genes and the characteristics of immune cell infiltration provides assistance for the analysis of clinical pathological parameters and prognosis of PLC patients. Methods: PLC-related differentially expressed genes (DEGs) with a median absolute deviation (MAD > 0.5) were identified from TCGA and GEO databases. These DEGs were intersected with immune-related genes (IRGs) from the ImmPort database to obtain PLC-related IRGs. The method of constructing a prognostic model through immune-related gene pairs (IRGPs) is used to obtain IRGPs and conduct the selection of central immune genes. The central immune genes obtained from the selection of IRGPs are validated in PLC. Subsequently, the relative proportions of 22 types of immune cells in different immune risk groups are evaluated, and the differential characteristics of PLC-related immune cells are verified through animal experiments. Results: Through database screening and the construction of an IRGP prognosis model, 84 pairs of IRGPs (P < 0.001) were ultimately obtained. Analysis of these 84 IRGPs revealed 11 central immune genes related to PLC, showing differential expression in liver cancer tissues compared to normal liver tissues. Results from the CiberSort platform indicate differential expression of immune cells such as naive B cells, macrophages, and neutrophils in different immune risk groups. Animal experiments demonstrated altered immune cell proportions in H22 tumor-bearing mice, validating findings from peripheral blood and spleen homogenate analyses. Conclusion: Our study successfully predicted and validated PLC-related IRGs and immune cells, suggesting their potential as prognostic indicators and therapeutic targets for PLC.
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Poria cocos is a natural source of fungal food raw materials. Processing method is a key effecting the aroma of Poria cocos. In this study, the aroma compounds of Poria cocos products processed using sweating-low-temperature drying (SW-LD), sweating-high-temperature drying (SW-HD), steaming-low-temperature drying (ST-LD), and steaming-high-temperature drying (ST-HD) were compared by headspace solid-phase microextraction (HS-SPME) combined with gas chromatography-mass spectrometry (GC-MS), and the changes in aroma compounds of Poria cocos products during processing were analyzed. GC-MS analysis showed SW-HD product had highest content of aroma compounds. Aroma activity value (OAV) analysis indicated that 9 aroma compounds contributed to the overall aroma of Poria cocos. Among 9 compounds of Poria cocos, 1-octen-3-ol, hexanal, nonanal, octanal, trans-2-octenal, and heptanal contributed to mushroom, refreshing, sweet and fatty characters. In addition, the aroma compound changes during the processing were analyzed, revealing that steaming and sweating were the key processes affecting the aroma of Poria cocos products. The findings of this study provide valuable theoretical guidance for the development of Poria cocos processing technology.
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Endometrial cancer (EC) stands as the most prevalent gynecological tumor in women worldwide. Notably, differentiation diagnosis of abnormity detected by ultrasound findings (e.g., thickened endometrium or mass in the uterine cavity) is essential and remains challenging in clinical practice. Herein, we identified a metabolic biomarker panel for differentiation diagnosis of EC using machine learning of high-performance serum metabolic fingerprints (SMFs) and validated the biological function. We first recorded the high-performance SMFs of 191 EC and 204 Non-EC subjects via particle-enhanced laser desorption/ionization mass spectrometry (PELDI-MS). Then, we achieved an area-under-the-curve (AUC) of 0.957-0.968 for EC diagnosis through machine learning of high-performance SMFs, outperforming the clinical biomarker of cancer antigen 125 (CA-125, AUC of 0.610-0.684, p < 0.05). Finally, we identified a metabolic biomarker panel of glutamine, glucose, and cholesterol linoleate with an AUC of 0.901-0.902 and validated the biological function in vitro. Therefore, our work would facilitate the development of novel diagnostic biomarkers for EC in clinics.