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Background: Oxidative stress and cellular senescence (OSCS) have great impacts on the occurrence and progression of triple-negative breast cancer (TNBC). This study was intended to construct a prognostic model based on oxidative stress and cellular senescence related difference expression genes (OSCSRDEGs) for TNBC. Methods: The Cancer Genome Atlas (TCGA) databases and two Gene Expression Omnibus (GEO) databases were used to identify OSCSRDEGs. The relationship between OSCSRDEGs and immune infiltration was examined using single-sample gene-set enrichment analysis (ssGSEA), ESTIMATE, and the CIBERSORT algorithm. Least absolute shrinkage and selection operator (LASSO) regression analyses, Cox regression and Kaplan-Meier analysis were employed to construct a prognostic model. Receiver operating characteristic (ROC) curves, nomograms, and decision curve analysis (DCA) were used to evaluate the prognostic efficacy. Gene Set Enrichment Analysis (GSEA) Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) were utilized to explore the potential functions and mechanism. Results: A comprehensive analysis identified a total of 27 OSCSRDEGs, out of which 15 genes selected for development of a prognostic model. A high degree of statistical significance was observed for the riskscores derived from this model to accurately predict TNBC Overall survival. The decision curve analysis (DCA) and ROC curve analysis further confirmed the superior accuracy of the OSCSRDEGs prognostic model in predicting efficacy. Notably, the nomogram analysis highlighted that DMD exhibited the highest utility within the model. In comparison between high and low OSCScore groups, the infiltration abundance of immune cells was statistically different in the TCGA-TNBC dataset. Conclusion: These studies have effectively identified four essential OSCSRDEGs (CFI, DMD, NDRG2, and NRP1) and meticulously developed an OSCS-associated prognostic model for individuals diagnosed with TNBC. These discoveries have the potential to significantly contribute to the comprehension of the involvement of OSCS in TNBC.
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Exosomes are small lipid nanovesicles with a diameter of 30-150 nm. They are present in all body fluids and are actively secreted by the majority of cells through the process of exocytosis. Exosomes play an essential role in intercellular communication and act as significant molecular carriers in regulating various physiological and pathological processes, such as the emergence of drug resistance in tumors. Tumor-associated exosomes transfer drug resistance to other tumor cells by releasing substances such as multidrug resistance proteins and miRNAs through exosomes. These substances change the cell phenotype, making it resistant to drugs. Tumor-associated exosomes also play a role in impacting drug resistance in other cells, like immune cells and stromal cells. Exosomes alter the behavior and function of these cells to help tumor cells evade immune surveillance and form a tumor niche. In addition, exosomes also export substances such as tumoricidal drugs and neutralizing antibody drugs to help tumor cells resist drug therapy. In this review, we summarize the mechanisms of exosomes in promoting drug resistance by delivering cargo in the context of the tumor microenvironment (TME).
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BACKGROUND: Gastroesophageal reflux disease (GERD) is a common condition characterized by the reflux of stomach contents into the esophagus. Despite its widespread prevalence worldwide, the causal link between GERD and various cancer risks has not been fully established, and past medical research has often underestimated or overlooked this relationship. METHODS: This study performed Mendelian randomization (MR) to investigate the causal relationship between GERD and 19 different cancers. We leveraged data from 129,080 GERD patients and 473,524 controls, along with cancer-related data, obtained from the UK Biobank and various Genome-Wide Association Studies (GWAS) consortia. Single nucleotide polymorphisms (SNPs) associated with GERD were used as instrumental variables, utilizing methods such as inverse variance weighting, weighted median, and MR-Egger to address potential pleiotropy and confounding factors. RESULTS: GERD was significantly associated with higher risks of nine types of cancer. Even after adjusting for all known risk factors-including smoking, alcohol consumption, major depression, and body mass index (BMI)-these associations remained significant, with higher risks for most cancers. For example, the adjusted risk for overall lung cancer was (OR, 1.23; 95% CI: 1.14-1.33), for lung adenocarcinoma was (OR, 1.18; 95% CI: 1.03-1.36), for lung squamous cell carcinoma was (OR, 1.35; 95% CI: 1.19-1.53), and for oral cavity and pharyngeal cancer was (OR, 1.73; 95% CI: 1.22-2.44). Especially noteworthy, the risk for esophageal cancer increased to (OR, 2.57; 95% CI: 1.23-5.37). Mediation analyses further highlighted GERD as a significant mediator in the relationships between BMI, smoking, major depression, and cancer risks. CONCLUSIONS: This study identifies a significant causal relationship between GERD and increased cancer risk, highlighting its role in cancer development and underscoring the necessity of incorporating GERD management into cancer prevention strategies.
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Reflujo Gastroesofágico , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Neoplasias , Polimorfismo de Nucleótido Simple , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reflujo Gastroesofágico/epidemiología , Reflujo Gastroesofágico/genética , Reflujo Gastroesofágico/complicaciones , Neoplasias/genética , Neoplasias/epidemiología , Factores de Riesgo , Biobanco del Reino Unido , Reino Unido/epidemiologíaRESUMEN
Low-heat Portland cement and ground granulated blast furnace slag are widely used for the preparation of hydraulic concrete. Nevertheless, the effect and mechanism of corrosion on low-heat Portland cement paste mixed with ground granulated blast furnace slag need to be further explored. This paper investigated the impact of ground granulated blast furnace slag on the calcium leaching of low-heat Portland cement paste by evaluating its mass loss, porosity, leaching depth, compressive strength, and Vickers hardness, and comparing it with the leaching performance of ordinary Portland cement paste. Furthermore, the phase composition and morphology of low-heat Portland cement paste containing ground granulated blast furnace slag were analyzed by X-ray diffraction, mercury intrusion porosimetry, and scanning electron microscopy. The results indicate that, after 180 days of soaking in ammonium chloride solution, the mass loss rate, growth rate of porosity, leaching depth, and compressive strength loss rate of low-heat Portland cement paste were 8.0%, 43.6%, 9.1 mm, and 27.7%, respectively, while those of ordinary Portland cement paste were 7.4%, 37.8%, 8.4 mm, and 30.1%, indicating that low-heat Portland cement paste is slightly more damaging than ordinary Portland cement. The addition of ground granulated blast furnace slag could significantly improve the leaching resistance of low-heat Portland cement. For instance, after adding 20% ground granulated blast furnace slag, the above test values were 2.4%, 28.5%, 5.6 mm, and 20.8%, respectively. The reason for this is that ground granulated blast furnace slag has the potential to reduce the porosity of low-heat Portland cement paste, and it can also undergo the secondary hydration reaction with its hydration product Ca(OH)2 to enhance the paste structure. Considering the cost performance, the suitable dosage of low-heat Portland cement paste for satisfactory leaching resistance is about 20%.
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Residual normal plasma cells (NPCs), which compete with tumor plasma cells, play an important role in multiple myeloma. However, large-scale cohort studies investigating residual NPCs, especially at the minimal residual disease (MRD) phase, are currently lacking. In this study, we conducted a comprehensive investigation into the clinical significance of residual NPCs throughout the entire disease course in 1363 myeloma patients from the NICHE cohort (NCT04645199). Our results revealed that myeloma patients with high baseline NPCs ratio (≥5%) exhibited distinct indolent features, characterized by lower tumor burden, reduced frequencies of cytopenia, immunoparesis, and high-risk cytogenetics. Importantly, high residual NPCs ratio at diagnosis or relapse was independently associated with favorable survival. High absolute percentages of NPCs at undetectable MRD were related with superior clinical benefit and immune reconstitution. At MRD-positive phases, grouping based on NPCs ratio (<50%, 50-90%, ≥90%) demonstrated better risk stratification compared to residual tumor log levels. Based on the time-dependent NPCs ratio trend, we developed a dynamic MRD model that classifies patients into three groups with diverse longitudinal trends, leading to distinct prognoses. Collectively, residual NPCs serves not only as a valuable complementary biomarker for risk stratification but also provides valuable insights on reclassifications and kinetics of MRD.
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Asthma is a common chronic lung disease, and COVID-19 pandemic as a respiratory viral disease led to lung infection and resulted in millions of deaths. So, the impact of COVID-19 on asthma outcomes and the risk of being infected or hospitalized should be clarified. Systematic review and meta-analysis on the outcomes and risk of asthma for people with COVID-19 was done by searching electronic databases between 1 December 2019 and 31 July 2023. A total of 48 studies from 27 countries spread across all continents were included in the review. The prevalence of asthma among COVID-19 patients was 7.9%, and the analysis demonstrated a 16.5% reduction in the risk ratio for acquiring COVID-19 among subjects with asthma compared to those without asthma. There was no statistically significant difference in hospitalization risk, ICU admission risk, and death risk for COVID-19 patients with no asthma compared to those with asthma. The risk of death from COVID-19 was similar between nonasthmatics and asthmatics. The findings indicated that subjects with asthma may be at a lower risk of having infection with COVID-19 compared to those without asthma, but they have a similar risk of hospitalization and mortality.
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Asma , COVID-19 , Hospitalización , Humanos , COVID-19/epidemiología , COVID-19/mortalidad , COVID-19/complicaciones , Asma/epidemiología , Hospitalización/estadística & datos numéricos , Prevalencia , SARS-CoV-2RESUMEN
Gestational diabetes mellitus (GDM) disrupts glucolipid metabolism, endangering maternal and fetal health. Despite limited research on its pathogenesis and treatments, we conducted a study using serum samples from GDM-diagnosed pregnant women. We performed metabolic sequencing to identify key small molecule metabolites and explored their molecular interactions with FGF21. We also investigated FGF21's impact on GDM using blood samples from affected women. Our analysis revealed a novel finding: elevated levels of L-Cystine in GDM patients. Furthermore, we observed a positive correlation between L-Cystine and FGF21 levels, and found that L-Cystine induces NRF2 expression via FGF21 for a period of 96â¯h. Under high glucose (HG) conditions, FGF21 upregulates NRF2 and downstream genes NQO1 and EPHX1 via AKT phosphorylation induced by activation of IRS1, enhancing endothelial function. Additionally, we confirmed that levels of FGF21, L-Cystine, and endothelial function at the third trimester were effectively enhanced through appropriate exercise and diet during pregnancy in GDM patients (GDMâ¯+â¯ED). These findings suggest FGF21 as a potential therapeutic agent for GDM, particularly in protecting endothelial cells. Moreover, elevated L-Cystine via appropriate exercise and diet might be a potential strategy to enhance FGF21's efficacy.
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The Yangtze River (hereafter referred to as the YZR), the largest river in China, is of paramount importance for ensuring water resource security. The Yangtze River Basin (hereafter referred to as the YRB) is one of the most densely populated areas in China, and complex human activities have a significant impact on the ecological security of water resources. Therefore, this paper employs theories related to ecological population evolution and the Driving Force-Pressure-State-Impact-Response (DPSIR) model to construct an indicator system for the ecological security of water resources in the YRB. The report evaluates the ecological security status of water resources in each province of the YRB from 2010 to 2019, clarifies the development trend of its water resource ecological security, and proposes corresponding strategies for regional ecological security and coordinated economic development. According to the results of the ecological population evolution competition model, the overall indicator of the ecological security of water resources in the YRB continues to improve, with the safety level increasing annually. Maintaining sound management of water resources in the YRB is crucial for sustainable socioeconomic development. To further promote the ecological security of water resources in the YRB and the coordinated development of the regional economy, this paper proposes policy suggestions such as promoting the continuous advancement of sustainable development projects, actively adjusting industrial structure, continuously enhancing public environmental awareness, and actively participating in international ecological construction and seeking cooperation among multiple departments.
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Immune escape is the main reason that immunotherapy is ineffective in hepatocellular carcinoma (HCC). Here, this study illustrates a pathway mediated by neutrophil extracellular traps (NETs) that can promote immune escape of HCC. Mechanistically, we demonstrated that NETs up-regulated CD73 expression through activating Notch2 mediated nuclear factor kappa B (NF-κB) pathway, promoting regulatory T cells (Tregs) infiltration to mediate immune escape of HCC. In addition, we found the similar results in mouse HCC models by hydrodynamic plasmid transfection. The treatment of deoxyribonuclease I (DNase I) could inhibit the action of NETs and improve the therapeutic effect of anti-programmed cell death protein 1 (PD-1). In summary, our results revealed that targeting of NETs was a promising treatment to improve the therapeutic effect of anti-PD-1.
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Phyllanthus emblica L. offers promising therapeutic potential for inflammatory diseases. This study revealed the molecular structure of a homogeneous polysaccharide purified from Phyllanthus emblica L. (PEP-1) and evaluated its anti-inflammatory effects on ulcerative colitis (UC) in mice. In the in vivo experiment, administered in varying dosages to dextran sulfate sodium (DSS)-induced UC models, PEP-1 significantly alleviated colonic symptoms, histological damages and reshaped the gut microbiota. Notably, it adjusted the Firmicutes/Bacteroidetes ratio and reduced pro-inflammatory species, closely aligning with shifts in the fecal metabolites and metabolic pathways such as the metabolism of pyrimidine, beta-alanine, and purine. These findings underscore the potential of PEP-1 as a therapeutic agent for UC, providing insights into the mechanisms through gut microbiota and metabolic modulation.
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BACKGROUND: Spontaneous abortion is a common complication of pregnancy that can lead to adverse physical and psychological outcomes for women. Vitamin D is reported to be associated with reproductive functions, whereas its casual effects on abortion remains unclear. MATERIALS AND METHODS: In this study, a two-sample Mendelian randomization (MR) analysis was performed to systematically assess the causal relationships between serum 25 hydroxyvitamin D [25(OH)D] concentration and the risk of spontaneous abortion. GWAS summary data of 25(OH)D were used as exposure, and data of spontaneous abortion was considered as outcome. A retrospective study was additionally conducted to verify the MR results. RESULTS: MR estimates showed that a higher 25(OH)D level was potentially associated with decreased risk of spontaneous abortion (IVW, OR = 0.98, 95%CI = 0.90-1.06; MR Egger, OR = 0.94, 95%CI = 0.84-1.05; Weighted median, OR = 0.93, 95%CI = 0.82-1.06; Weighted mode, OR = 0.93, 95%CI = 0.84-1.03), though the P-value was not statistically significant. The retrospective study also produced consistent result of Vitamin D's protective role to spontaneous abortion. The P-value was very close to statistical significance (P = 0.053). CONCLUSIONS: This study reports the potential protective role of serum 25(OH)D concentration to spontaneous abortion, suggesting that increased vitamin D levels may decrease the risk of abortion. Further larger prospective studies and/or even randomized controlled trials are needed to confirm causal relationship between vitamin D and abortion.
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Aborto Espontáneo , Análisis de la Aleatorización Mendeliana , Vitamina D , Humanos , Femenino , Aborto Espontáneo/epidemiología , Vitamina D/sangre , Vitamina D/análogos & derivados , Estudios Retrospectivos , Embarazo , Adulto , Estudio de Asociación del Genoma CompletoRESUMEN
Soft and stretchable electronics have garnered significant attention in various fields, such as wearable electronics, electronic skins, and soft robotics. However, current wearable electronics made from materials like conductive elastomers, hydrogels, and liquid metals face limitations, including low permeability, poor adhesion, inadequate conductivity, and limited stretchability. These issues hinder their effectiveness in long-term healthcare monitoring and exercise monitoring. To address these challenges, we introduce a novel design of web-droplet-like electronics featuring a semi-liquid metal coating for wearable applications. This innovative design offers high permeability, excellent stretchability, strong adhesion, and good conductivity for the electronic skin. The unique structure, inspired by the architecture of a spider web, significantly enhances air permeability compared to commercial breathable patches. Furthermore, the distribution of polyborosiloxane mimics the adhesive properties of spider web mucus, while the use of semi-liquid metals in this design results in remarkable conductivity (9 × 106 S/m) and tensile performance (up to 850% strain). This advanced electronic skin technology enables long-term monitoring of various physiological parameters and supports machine learning recognition functions with unparalleled advantages. This web-droplet structure design strategy holds great promise for commercial applications in medical health monitoring and disease diagnosis.
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AIMS: To evaluate the correlation between left atrial stiffness index (LASI) and left ventricular diastolic function in patients with coronary heart disease (CHD) by Autostrain LA technique. METHODS: This was a retrospective analysis that included a total of 82 CHD patients who had suitable image quality for left atrial strain measurement. According to the 2016 ASE/EACVI guidelines for the echocardiographic assessment of diastolic dysfunction, the patients were divided into three groups: normal left ventricular diastolic function group (n = 26), indeterminate left ventricular diastolic function (n = 36), and left ventricular diastolic dysfunction (LVDD) (n = 20). The left atrial conduit strain (LAScd), Left atrial contractile strain (LASct), left atrial reservoir strain (LASr) and its derived parameters, including LASI and left atrial filling index (LAFI), were compared among the three groups. Furthermore, we conduct a correlation analysis between LASI and left ventricular diastolic function in patients with CHD. RESULTS: LASr and LAScd in normal group were higher than those in indeterminate group, LASr and LAScd in indeterminate group were higher than those in LVDD group, LASI in normal group was lower than that in indeterminate group, and LASI in indeterminate group was lower than that in LVDD group (P < 0.001). LASct in both normal and indeterminate groups was higher than that in LVDD group (P < 0.05). The LAFI of normal group was lower than that of indeterminate group and LVDD group (P < 0.001). LASI was positively correlated with E/e'(r = 0.822) (P < 0.001). LASr and E/e' were negatively correlated (r = -0.637) (P < 0.001). CONCLUSION: LASI is closely related to the changes of left ventricular diastolic function in CHD patients.
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Función del Atrio Izquierdo , Enfermedad Coronaria , Diástole , Valor Predictivo de las Pruebas , Disfunción Ventricular Izquierda , Función Ventricular Izquierda , Humanos , Femenino , Masculino , Disfunción Ventricular Izquierda/fisiopatología , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/diagnóstico , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Enfermedad Coronaria/fisiopatología , Enfermedad Coronaria/diagnóstico por imagen , Enfermedad Coronaria/diagnóstico , Diagnóstico Precoz , Reproducibilidad de los Resultados , Atrios Cardíacos/fisiopatología , Atrios Cardíacos/diagnóstico por imagenRESUMEN
Early dietary patterns potentially influence the health status and lifespan throughout adulthood and the entire lifespan. However, dietary behaviors are difficult for everyone to control during adolescence. It is even more important to study the effects of interventions of early dietary patterns on the lifespan under arbitrary feeding conditions. The research involves observing the survival status and lifespan of rats from weaning to adulthood with three different dietary patterns (a high-carbohydrate diet (HC), a high-protein diet (HP), and a high-fat diet (HF)) under ad libitum feeding conditions. The administration of high-carbohydrate diets leads to a significant extension of both median and maximum survival times (P < 0.05) in Wistar rats. Furthermore, it markedly enhanced the spatial memory capacity, mitigated the occurrence of liver and kidney pathological outcomes in elderly rats, and increased the abundance of gut microbiota improving amino acid metabolism. Additionally, feeding rats a high-carbohydrate diet improved glutathione (GSH) synthesis and recycling and activated the expression and upregulation of the lifespan-related proteins Foxo3a/Sirt3 and the key metabolic enzyme GPX-4. The high-carbohydrate diet from weaning to adulthood may potentially extend the lifespan by enhancing rat systemic glutathione synthesis, recycling, and improving the redox state pathway.
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Homeostasis , Longevidad , Oxidación-Reducción , Ratas Wistar , Destete , Animales , Ratas , Masculino , Microbioma Gastrointestinal , Carbohidratos de la Dieta/metabolismo , Hígado/metabolismo , Glutatión/metabolismo , Dieta Alta en Grasa , MultiómicaRESUMEN
A photoinduced EnT-mediated generation of sulfonamidyl radicals has been accomplished using rationally designed iminophenylacetic acid oxime ester reagents under metal-free conditions. This approach offers a mild, regio- and diastereoselective synthesis of N-sulfonyl diamines via diamination of alkenes and (hetero)arenes.
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Endomucin (MUC14), encoded by EMCN gene, is an O-glycosylated transmembrane mucin that is mainly found in venous endothelial cells (ECs) and highly expressed in type H vessels of bone tissue. Its main biological functions include promoting endothelial generation and migration through the vascular endothelial growth factor (VEGF) signaling pathway and inhibiting the adhesion of inflammatory cells to ECs. In addition, it induces angiogenesis and promotes bone formation. Due to the excellent functions of Endomucin in the above aspects, it provides a new research target for the treatment of vascular inflammatory-related diseases and bone diseases. Based on the current understanding of its function, the research of Endomucin mainly focuses on the above two diseases. As it is known, the progression of cancer is closely related to angiogenesis. Endomucin recently is found to be differentially expressed in a variety of tumors and correlated with survival rate. The biological role of Endomucin in cancer is opaque. This article introduces the research progress of Endomucin in vascular inflammatory-related diseases and bone diseases, discusses its application value and prospect in the treatment, and collects the latest research situation of Endomucin in tumors, to provide meaningful evidence for expanding the research field of Endomucin.
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Aging of hematopoietic stem cells (HSCs) is accompanied by impaired self-renewal ability, myeloid skewing, immunodeficiencies and increased susceptibility to malignancies. Although previous studies highlighted the pivotal roles of individual metabolites in hematopoiesis, comprehensive and high-resolution metabolomic profiles of different hematopoietic cells across ages are still lacking. In this study, we created a metabolome atlas of different blood cells across ages in mice. We reveal here that purine, pyrimidine and retinol metabolism are enriched in young hematopoietic stem and progenitor cells (HSPCs), whereas glutamate and sphingolipid metabolism are concentrated in aged HSPCs. Through metabolic screening, we identified uridine as a potential regulator to rejuvenate aged HSPCs. Mechanistically, uridine treatment upregulates the FoxO signaling pathway and enhances self-renewal while suppressing inflammation in aged HSCs. Finally, we constructed an open-source platform for public easy access and metabolomic analysis in blood cells. Collectively, we provide a resource for metabolic studies in hematopoiesis that can contribute to future anti-aging metabolite screening.
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Early detection of cancer markers is critical for cancer diagnosis and cancer therapy since these markers may indicate cancer risk, incidence, and disease prognosis. Carcinoembryonic antigen (CEA) is a type of non-specific and broad-spectrum cancer biomarker commonly utilized for early cancer diagnosis. Moreover, it serves as an essential tool to assess the efficacy of cancer treatment and monitor tumor recurrence as well as metastasis, thus garnering significant attention for precise and sensitive CEA detection. In recent years, photoelectrochemical (PEC) techniques have emerged as prominent methods in CEA detection due to the advantages of PEC, such as simple equipment requirements, cost-effectiveness, high sensitivity, low interference from background signals, and easy of instrument miniaturization. Different signal amplification methods have been reported in PEC sensors for CEA analysis. Based on these, this article reviews PEC sensors based on various signal amplification strategies for detection of CEA during the last five years. The advantages and drawbacks of these sensors were discussed, as well as future challenges.
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Biomarcadores de Tumor , Técnicas Biosensibles , Antígeno Carcinoembrionario , Técnicas Electroquímicas , Neoplasias , Antígeno Carcinoembrionario/sangre , Antígeno Carcinoembrionario/análisis , Técnicas Biosensibles/instrumentación , Humanos , Técnicas Electroquímicas/métodos , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/análisis , Diseño de Equipo , AnimalesRESUMEN
BACKGROUND: Although endovascular stenting is considered an effective and safe therapeutic option for symptomatic intracranial atherosclerotic disease (sICAD), an elevated rate of restenosis remains an important issue for the conventional bare-metal stent (BMS). Recent evidence from observational studies suggests that applying drug-coated balloons (DCB) in sICAD may decrease restenosis occurrence. Additional large randomised studies are warranted to provide firmer evidence and to determine which patients would benefit most from DCB. AIM: To design a randomised trial to examine DCB angioplasty (Taijieweiye intracranial paclitaxel-coated balloon catheter) versus BMS stenting (Wingspan intracranial stent system) in patients with sICAD. DESIGN: This is a multicentre, prospective, randomised, open-label, blinded end-point study to assess whether DCB angioplasty reduces the risk of restenosis compared with BMS stenting in sICAD patients with high-grade stenosis (≥70%-99%). Our goal is to randomly assign 198 eligible individuals at a 1:1 ratio to undergo DCB angioplasty (intervention group) or BMS stenting (control group). OUTCOME: The primary efficacy outcome is restenosis at 6 months post treatment, that is, >50% stenosis in or within 5 mm of the treated segment and >20% absolute luminal loss. The primary safety outcome is stroke or death within 30 days post treatment. DISCUSSION: The DRug-coated Balloon for Endovascular treatment of sYmptOmatic intracraNial stenotic Disease trial aims to produce strong evidence on the efficacy and safety of DCB angioplasty as a promising therapeutic option for sICAD cases with high-grade stenosis.
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Despite advances in targeted therapies, primary and acquired resistance make the treatment of colorectal cancer (CRC) a pressing issue to be resolved. According to reports, the development of CRC is linked to miRNA dysregulation. Multiple studies have demonstrated that miR-135b-5p has an aberrant expression level between CRC tissues and adjacent tissues. However, it is unclear whether there is a correlation between miR-135b-5p and cetuximab (CTx) resistance in CRC. Use the GEO database to measure miR-135b-5p expression in CRC. Additionally, RT-qPCR was applied to ascertain the production level of miR-135b-5p in three human CRC cells and NCM460 cells. The capacity of cells to migrate and invade was examined utilizing the wound-healing and transwell assays, while the CCK-8 assay served for evaluating cell viability, as well as colony formation assays for proliferation. The expected target protein of miR-135b-5p in CRC cell cetuximab resistance has been investigated using western blot. Suppression of miR-135b-5p could increase the CTx sensitivity of CTx-resistant CRC cells, as manifested by the attenuation of proliferation, migration, and invasion ability. Mechanistic studies revealed miR-135b-5p regulates the epithelial-to-mesenchymal transition (EMT) process and Wnt/ß-catenin signaling pathway through downgulating FOXN3. In short, knockdowning miR-135b-5p could increase FOXN3 expression in CRC cells, promote the EMT process, and simultaneously activate the Wnt/ß-catenin signaling pathway to elevate CTx resistance in CRC cells.