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BACKGROUND: Ischemic stroke (IS) is a major cause of disability and mortality worldwide. Increasing evidence suggests a strong association between blood pressure, blood glucose, circulating lipids, and IS. Nonetheless, the genetic association of these 3 risk factors with IS remains elusive. METHODS: We screened genetic instruments related to blood pressure, blood glucose, and circulating lipids and paired them with IS genome-wide association study data to conduct Mendelian randomization analysis. Positive Mendelian randomization findings were then subjected to colocalization analysis. Subsequently, we utilized the Gene Expression Omnibus data set to perform differential expression analysis, aiming to identify differentially expressed associated genes. We determined the importance scores of these differentially expressed associated genes through 4 machine learning models and constructed a nomogram based on these findings. RESULTS: The combined results of the Mendelian randomization analysis indicate that blood pressure (systolic blood pressure: odds ratio [OR], 1.02 [95% CI, 1.01-1.02]; diastolic blood pressure: OR, 1.03 [95% CI, 1.03-1.04]) and some circulating lipids (low-density lipoprotein cholesterol: OR, 1.06 [95% CI, 1.01-1.12]; apoA1: OR, 0.95 [95% CI, 0.92-0.98]; apoB: OR, 1.05 [95% CI, 1.01-1.09]; eicosapentaenoic acid: OR, 2.36 [95% CI, 1.41-3.96]) have causal relationships with the risk of IS onset. We identified 73 genes that are linked to blood pressure and circulating lipids in the context of IS, and 16 are differentially expressed associated genes. FURIN, MAN2A2, HDDC3, ALDH2, and TOMM40 were identified as feature genes for constructing the nomogram that provides a quantitative prediction of the risk of IS onset. CONCLUSIONS: This study indicates that there are causal links between blood pressure, certain circulating lipids, and the development of IS. The potential mechanisms underlying these causal relationships involve the regulation of lipid metabolism, blood pressure, DNA repair and methylation, cell apoptosis and autophagy, immune inflammation, and neuronal protection, among others.
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Presión Sanguínea , Biología Computacional , Estudio de Asociación del Genoma Completo , Accidente Cerebrovascular Isquémico , Análisis de la Aleatorización Mendeliana , Humanos , Factores de Riesgo , Accidente Cerebrovascular Isquémico/genética , Accidente Cerebrovascular Isquémico/epidemiología , Accidente Cerebrovascular Isquémico/sangre , Presión Sanguínea/genética , Glucemia/metabolismo , LDL-Colesterol/sangre , Apolipoproteína A-I/genética , Proteínas del Complejo de Importación de Proteínas Precursoras Mitocondriales , Polimorfismo de Nucleótido Simple , Predisposición Genética a la Enfermedad/genética , Apolipoproteína B-100/genética , Aprendizaje AutomáticoRESUMEN
BACKGROUND: This study compared the differences of microvesicles (MVs) and microvesicles-delivering Smad7 (Smad7-MVs) on macrophage M1 polarization and fibroblast differentiation in a model of Peyronie's disease (PD). METHODS: Overexpression of Smad7 in rat BMSCs was obtained by pCMV5-Smad7 transfection. MVs were collected from rat BMSCs using ultracentrifugation. In cells, 100 µg/mL of MVs or Smad7-MVs were used to treat the 100 ng/mL of lipopolysaccharide (LPS)-induced RAW264.7 cells or 10 ng/mL of recombinant transforming growth factor-ß1 (TGF-ß1)-induced fibroblasts. The pro-inflammatory cytokines and markers of M1 macrophages were measured in RAW264.7 cells, and the migration and markers of fibroblast differentiation were measured in fibroblasts. In rats, 50 µg of MVs or Smad7-MVs were used to treat the TGF-ß1-induced animals. The pathology of tunica albuginea (TA), the markers of M1 macrophages and fibroblast differentiation in the TA were measured. RESULTS: The MVs or Smad7-MVs treatment suppressed the LPS-induced macrophage M1 polarization and TGF-ß1-induced fibroblast differentiation. Moreover, the Smad7-MVs treatment decreased the fibroblast differentiation compared with the MVs treatment. In the TGF-ß1-induced TA of rats, MVs or Smad7-MVs treatment ameliorated the TA fibrosis by suppressing the macrophage M1 polarization and fibroblast differentiation. There was no significance on the M1-polarized macrophages between the MVs treatment and the Smad7-MVs treatment. Meanwhile, the Smad7-MVs treatment had an edge in terms of suppressing the fibroblast differentiation in the TGF-ß1-induced PD model compared with the MVs treatment. CONCLUSIONS: This study demonstrated that Smad7-MVs treatment had advantages over MVs treatment in suppressing of fibroblast differentiation in a model of PD.
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Diferenciación Celular , Micropartículas Derivadas de Células , Modelos Animales de Enfermedad , Fibroblastos , Macrófagos , Induración Peniana , Proteína smad7 , Factor de Crecimiento Transformador beta1 , Animales , Induración Peniana/metabolismo , Induración Peniana/tratamiento farmacológico , Diferenciación Celular/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/efectos de los fármacos , Ratas , Masculino , Proteína smad7/metabolismo , Proteína smad7/genética , Ratones , Micropartículas Derivadas de Células/metabolismo , Células RAW 264.7 , Factor de Crecimiento Transformador beta1/metabolismo , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Ratas Sprague-Dawley , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citologíaRESUMEN
The construction of novel structured Prussian blue analogs (PBAs) by chemical etching has attracted the most attention to PBA derivatives with outstanding performance. In this work, the unprecedented PBA orthogonal frustums are first prepared from nanocubes through a selective chemical etching approach using trisodium citrate as an etchant. The citrate ions can chelate with nickel species from the edges/corners of NiCo-PBA nanocubes and then disintegrate NiCo-PBAs resulting in the generation of NiCo-PBA orthogonal frustums. The derived CoNi2S4/Co0.91S composites still inherit the original orthogonal frustum structure and possess outstanding supercapacitor performance. This study develops a popularized method to construct novel structured PBAs and brings inspiration for designing PBA-based electrodes with advanced electrochemical performance.
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Developing tunable underwater adhesives that possess tough adhesion in service and easy detachment when required remains challenging. Herein, a strategy is proposed to design a near infrared (NIR) photothermal-responsive underwater adhesive by incorporating MXene (Ti3C2Tx)-based nanoparticles within isocyanate-modified polydimethylsiloxane (PDMS) polymer chains. The developed adhesive exhibits long-term and tough adhesion with an underwater adhesion strength reaching 5.478 MPa. Such strong adhesion is mainly attributed to the covalent bonds and hydrogen bonds at the adhesive-substrate interface. By making use of the photothermal-response of MXene-based nanoparticles and the thermal response of PDMS-based chains, the adhesive possesses photothermal-responsive performance, exhibiting sharply diminished adhesion under NIR irradiation. Such NIR-triggered tunable adhesion allows for easy and active detachment of the adhesive when needed. Moreover, the underwater adhesive exhibits photothermal antibacterial property, making it highly desirable for underwater applications. This work enhances the understanding of photothermal-responsive underwater adhesion, enabling the design of tunable underwater adhesives for biomedical and engineering applications.
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Adhesivos , Antibacterianos , Dimetilpolisiloxanos , Rayos Infrarrojos , Antibacterianos/farmacología , Antibacterianos/química , Adhesivos/química , Adhesivos/farmacología , Dimetilpolisiloxanos/química , Nanopartículas/química , Escherichia coli/efectos de los fármacosRESUMEN
Ovarian cancer is a prevalent gynecologic malignancy with the second-highest mortality rate among gynecologic malignancies. Platinum-based chemotherapy is the first-line treatment for ovarian cancer; however, a majority of patients with ovarian cancer experience relapse and develop platinum resistance following initial treatment. Despite extensive research on the mechanisms of platinum resistance at the nuclear level, the issue of platinum resistance in ovarian cancer remains largely unresolved. It is noteworthy that mitochondrial DNA (mtDNA) exhibits higher affinity for platinum compared to nuclear DNA (nDNA). Mutations in mtDNA can modulate tumor chemosensitivity through various mechanisms, including DNA damage responses, shifts in energy metabolism, maintenance of Reactive Oxygen Species (ROS) homeostasis, and alterations in mitochondrial dynamics. Concurrently, retrograde signals produced by mtDNA mutations and their subsequent cascades establish communication with the nucleus, leading to the reorganization of the nuclear transcriptome and governing the transcription of genes and signaling pathways associated with chemoresistance. Furthermore, mitochondrial translocation among cells emerges as a crucial factor influencing the effectiveness of chemotherapy in ovarian cancer. This review aims to explore the role and mechanism of mitochondria in platinum resistance, with a specific focus on mtDNA mutations and the resulting metabolic reprogramming, ROS regulation, changes in mitochondrial dynamics, mitochondria-nucleus communication, and mitochondrial transfer.
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Resistencia a Antineoplásicos , Mitocondrias , Neoplasias Ováricas , Platino (Metal) , Humanos , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Neoplasias Ováricas/metabolismo , Femenino , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Platino (Metal)/uso terapéutico , Platino (Metal)/farmacología , ADN Mitocondrial/genética , ADN Mitocondrial/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Mutación/genética , AnimalesRESUMEN
KEY MESSAGE: Our findings highlight a valuable breeding resource, demonstrating the potential to concurrently enhance grain shape, thermotolerance, and alkaline tolerance by manipulating Gγ protein in rice. Temperate Geng/Japonica (GJ) rice yields have improved significantly, bolstering global food security. However, GJ rice breeding faces challenges, including enhancing grain quality, ensuring stable yields at warmer temperatures, and utilizing alkaline land. In this study, we employed CRISPR/Cas9 gene-editing technology to knock out the GS3 locus in seven elite GJ varieties with superior yield performance. Yield component measurements revealed that GS3 knockout mutants consistently enhanced grain length and reduced plant height in diverse genetic backgrounds. The impact of GS3 on the grain number per panicle and setting rate depended on the genetic background. GS3 knockout did not affect milling quality and minimally altered protein and amylose content but notably influenced chalkiness-related traits. GS3 knockout indiscriminately improved heat and alkali stress tolerance in the GJ varieties studied. Transcriptome analysis indicated differential gene expression between the GS3 mutants and their wild-type counterparts, enriched in biological processes related to photosynthesis, photosystem II stabilization, and pathways associated with photosynthesis and cutin, suberine, and wax biosynthesis. Our findings highlight GS3 as a breeding resource for concurrently improving grain shape, thermotolerance, and alkaline tolerance through Gγ protein manipulation in rice.
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Grano Comestible , Oryza , Fitomejoramiento , Proteínas de Plantas , Termotolerancia , Álcalis , Sistemas CRISPR-Cas , Grano Comestible/genética , Grano Comestible/crecimiento & desarrollo , Edición Génica , Regulación de la Expresión Génica de las Plantas , Oryza/genética , Oryza/crecimiento & desarrollo , Oryza/metabolismo , Fenotipo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/genética , Termotolerancia/genéticaRESUMEN
Ovarian cancer (OC) is the second leading cause of gynecological cancer-related death in women worldwide. N6-methyladenosine (m6 A) is the most abundant internal modification in eukaryotic RNA. Human insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), an m6 A reader, can enhance mRNA stability and promote translation by recognizing m6 A modifications. Its tumor-promoting effects have been demonstrated in several cancers. However, the roles of m6 A modification and IGF2BP2 in OC remain unclear. Here, by using methylated RNA immunoprecipitation sequencing, we demonstrated that there is widespread dysregulation of m6 A modification in OC tissues. The m6 A modification and the mRNA and protein levels of IGF2BP2 were significantly elevated in OC. Overexpression of IGF2BP2 facilitated OC cell proliferation, migration, and invasion in vitro and accelerated tumor growth and metastasis in vivo. While IGF2BP2-knockdown showed the opposite effect. Mechanistically, we identified cytoskeleton-associated protein 2-like (CKAP2L) as a target of IGF2BP2. IGF2BP2 promoted CKAP2L translation dependent on m6 A modification, rather than affecting mRNA and protein stability. Overexpression of CKAP2L rescued the tumor-suppressive effect of IGF2BP2 knockdown in OC cells. In conclusion, this study revealed the potential role of IGF2BP2 in tumor progression, at least partially via promoting the translation of CKAP2L in an m6 A-dependent manner.
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Proteínas del Citoesqueleto , Neoplasias Ováricas , Proteínas de Unión al ARN , Femenino , Humanos , Adenosina , Proliferación Celular , Proteínas del Citoesqueleto/genética , Inmunoprecipitación , Neoplasias Ováricas/genética , Proteínas de Unión al ARN/genéticaRESUMEN
The E3 ubiquitin ligase Tripartite-motif 3 (TRIM3) is known to play a crucial role in tumor suppression in various tumors through different mechanisms. However, its function and mechanism in ovarian cancer have yet to be elucidated. Our study aims to investigate the expression of TRIM3 in ovarian cancer and evaluate its role in the development of the disease. Our findings revealed a significant decrease in TRIM3 mRNA and protein levels in ovarian cancer tissues and cells when compared to normal ovarian epithelial tissues and cells. Furthermore, we observed a negative correlation between the protein level of TRIM3 and the FIGO stage, as well as a positive correlation with the survival of ovarian cancer patients. Using gain and loss of function experiments, we demonstrated that TRIM3 can inhibit cell proliferation, migration and invasion of the ovarian cancer cells in vitro, as well as suppress tumor growth in vivo. Mechanistic studies showed that TRIM3 interacts with lactate dehydrogenase A, a key enzyme in the glycolytic pathway, through its B-box and coiled-coil domains and induces its ubiquitination and proteasomal degradation, leading to the inhibition of glycolytic ability in ovarian cancer cells. RNA-sequencing analysis revealed significant alterations in the phosphatidylinositol signaling pathways upon TRIM3 overexpression. Additionally, overexpression of TRIM3 inhibited the phosphorylation of AKT. In conclusion, our study demonstrated that TRIM3 exerts a tumor-suppressive effect in ovarian cancer, at least partially, by downregulating LDHA and inhibiting the AKT signaling pathway, and thus leading to the inhibition of glycolysis and limiting the growth of ovarian cancer cells.
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Regulación hacia Abajo , Neoplasias Ováricas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Femenino , Humanos , Neoplasias Ováricas/patología , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Línea Celular Tumoral , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Proliferación Celular , Ratones , Regulación Neoplásica de la Expresión Génica , Animales , Progresión de la Enfermedad , Ratones Desnudos , Movimiento Celular , Proteínas Portadoras , L-Lactato DeshidrogenasaRESUMEN
PURPOSE: To evaluate the diagnostic performance of contrast-enhanced (CE) ultrasound using Sonazoid (SNZ-CEUS) by comparing with contrast-enhanced computed tomography (CE-CT) and contrast-enhanced magnetic resonance imaging (CE-MRI) for differentiating benign and malignant renal masses. MATERIALS AND METHODS: 306 consecutive patients (from 7 centers) with renal masses (40 benign tumors, 266 malignant tumors) diagnosed by both SNZ-CEUS, CE-CT or CE-MRI were enrolled between September 2020 and February 2021. The examinations were performed within 7 days, but the sequence was not fixed. Histologic results were available for 301 of 306 (98.37%) lesions and 5 lesions were considered benign after at least 2 year follow-up without change in size and image characteristics. The diagnostic performances were evaluated by sensitivity, specificity, positive predictive value, negative predictive value, and compared by McNemar's test. RESULTS: In the head-to-head comparison, SNZ-CEUS and CE-MRI had comparable sensitivity (95.60 vs. 94.51%, P = 0.997), specificity (65.22 vs. 73.91%, P = 0.752), positive predictive value (91.58 vs. 93.48%) and negative predictive value (78.95 vs. 77.27%); SNZ-CEUS and CE-CT showed similar sensitivity (97.31 vs. 96.24%, P = 0.724); however, SNZ-CEUS had relatively lower than specificity than CE-CT (59.09 vs. 68.18%, P = 0.683). For nodules > 4 cm, CE-MRI demonstrated higher specificity than SNZ-CEUS (90.91 vs. 72.73%, P = 0.617) without compromise the sensitivity. CONCLUSIONS: SNZ-CEUS, CE-CT, and CE-MRI demonstrate desirable and comparable sensitivity for the differentiation of renal mass. However, the specificity of all three imaging modalities is not satisfactory. SNZ-CEUS may be a suitable alternative modality for patients with renal dysfunction and those allergic to gadolinium or iodine-based agents.
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Medios de Contraste , Compuestos Férricos , Hierro , Neoplasias Renales , Imagen por Resonancia Magnética , Óxidos , Tomografía Computarizada por Rayos X , Ultrasonografía , Humanos , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/patología , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Ultrasonografía/métodos , Tomografía Computarizada por Rayos X/métodos , Imagen por Resonancia Magnética/métodos , Anciano , Diagnóstico Diferencial , Adulto , Anciano de 80 o más AñosRESUMEN
We herein report the copper-catalyzed C-S bond coupling reaction of indoles with N-thiosuccinimides, resulting in moderate to excellent yields of mono- and bis-sulfenylated compounds such as arylthioindoles, alkylthioindoles, selenylated indoles, and cysteine-substituted indoles. Thioarylation and thioglycosylation at the C2 position of indole alkaloids in the Radix Isatidis were achieved via structural modification. The first total syntheses of isatindigotindolosides III and IV have been successfully carried out. The electrophilic sulfenyl bromides generated in situ can play an important role in the catalytic cycle.
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Hydrolytic nanozyme-based visual colorimetry has emerged as a promising strategy for the detection of aluminum ions. However, most studies focus on simulating the structure of natural enzymes while neglecting to regulate the rate of hydrolysis-related steps, leading to low enzyme-like activity for hydrolytic nanozymes. Herein, we constructed a ruthenium dioxide (RuO2) in situ embedded cerium oxide (CeO2) nanozyme (RuO2/CeO2) with a Lewis acid-base pair (Ce-O-Ru-OH), which can simulate the catalytic behavior of phosphatase (PPase) and can be quantitatively quenched by Al3+ to achieve accurate and sensitive Al3+ colorimetric sensing detection. The incorporation of Ru into CeO2 nanorods accelerates the dissociation of H2O, followed by subsequent combination of hydroxide species to Lewis acidic Ce-O sites. This synergistic effect facilitates substrate activation and significantly enhances the hydrolysis activity of the nanozyme. The results show that the RuO2/CeO2 nanozyme exhibits a limit of detection as low as 0.5 ng/mL. We also demonstrate their efficacy in detecting Al3+ in various practical food samples. This study offers novel insights into the advancement of highly sensitive hydrolytic nanozyme engineering for sensing applications.
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Aluminio , Cerio , Colorimetría , Límite de Detección , Colorimetría/métodos , Aluminio/análisis , Cerio/química , Hidrólisis , Compuestos de Rutenio/química , Iones/análisis , Técnicas Biosensibles/métodosRESUMEN
Highly circularly polarized (CP) infrared thermal radiation is greatly in demand because of its significant potential in mid-infrared (mid-IR) applications. To exploit the magnitude and quality factor of circular dichroism (CD) simultaneously, a lithography-free platform consisting of a Weyl semimetal (WSM)/dielectric (Ge)/WSM stack sitting on a metallic substrate (Mo) is proposed. A chiral response and varying CD values from -1 to 0.957 have been demonstrated. The numerical results from a generalized 4 × 4 transfer matrix algorithm verify that the chiral structure manifests a remarkably high quality factor (Q-factor) of 605. The effect of the thickness of each layer in the stack on the CD value is investigated. Moreover, it is identified that the design results in an angle-independent performance. A dual-channel chiral absorber operating in the 18-21 µm wavelength range has also been achieved. Our simple yet powerful paradigm could offer a new way of manipulating the Q-factor and resonance wavelength of a chiral absorber while maintaining near-unity CD, offering a new approach for the advancement of more efficient and tunable chiral optical devices. The approach is generally applicable to other planar configurations with different WSMs and can be extended to other wavelengths.
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Ketolides (3-keto) such as TE-802 and acylides (3-O-acyl) like TEA0929 are ineffective against constitutively resistant pathogens harboring erythromycin ribosomal methylation (erm) genes. Following our previous work on alkylides (3-O-alkyl), we explored the structure-activity relationships of hybrids combining (R/S) 3-descladinosyl erythromycin with 6/7-quinolone motifs, featuring extended ether-linked spacers, with a focus on their efficacy against pathogens bearing constitutive erm gene resistance. Optimized compounds 17a and 31f not only reinstated efficacy against inducibly resistant pathogens but also demonstrated significantly augmented activities against constitutively resistant strains of Streptococcus pneumoniae and Streptococcus pyogenes, which are typically refractory to existing C-3 modified macrolides. Notably, hybrid 31f (coded ZN-51) represented a pioneering class of agents distinguished by its dual modes of action, with ribosomes as the primary target and topoisomerases as the secondary target. As a novel chemotype of macrolide-quinolone hybrids, alkylide 31f is a valuable addition to our armamentarium against macrolide-resistant bacteria.
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Antibacterianos , Macrólidos , Pruebas de Sensibilidad Microbiana , Quinolonas , Streptococcus pneumoniae , Relación Estructura-Actividad , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Quinolonas/química , Quinolonas/farmacología , Quinolonas/síntesis química , Macrólidos/química , Macrólidos/farmacología , Streptococcus pneumoniae/efectos de los fármacos , Estructura Molecular , Diseño de Fármacos , Streptococcus pyogenes/efectos de los fármacos , Streptococcus pyogenes/enzimología , Relación Dosis-Respuesta a Droga , Éteres/química , Éteres/farmacología , Éteres/síntesis químicaRESUMEN
BACKGROUND: Accurate differentiation of extremity soft-tissue tumors (ESTTs) is important for treatment planning. PURPOSE: To develop and validate an ultrasound (US) image-based radiomics signature to predict ESTTs malignancy. MATERIAL AND METHODS: A dataset of US images from 108 ESTTs were retrospectively enrolled and divided into the training cohort (78 ESTTs) and validation cohort (30 ESTTs). A total of 1037 radiomics features were extracted from each US image. The most useful predictive radiomics features were selected by the maximum relevance and minimum redundancy method, least absolute shrinkage, and selection operator algorithm in the training cohort. A US-based radiomics signature was built based on these selected radiomics features. In addition, a conventional radiologic model based on the US features from the interpretation of two experienced radiologists was developed by a multivariate logistic regression algorithm. The diagnostic performances of the selected radiomics features, the US-based radiomics signature, and the conventional radiologic model for differentiating ESTTs were evaluated and compared in the validation cohort. RESULTS: In the validation cohort, the area under the curve (AUC), sensitivity, and specificity of the US-based radiomics signature for predicting ESTTs malignancy were 0.866, 84.2%, and 81.8%, respectively. The US-based radiomics signature had better diagnostic predictability for predicting ESTT malignancy than the best single radiomics feature and the conventional radiologic model (AUC = 0.866 vs. 0.719 vs. 0.681 for the validation cohort, all P <0.05). CONCLUSION: The US-based radiomics signature could provide a potential imaging biomarker to accurately predict ESTT malignancy.
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Extremidades , Neoplasias de los Tejidos Blandos , Ultrasonografía , Humanos , Femenino , Masculino , Ultrasonografía/métodos , Neoplasias de los Tejidos Blandos/diagnóstico por imagen , Persona de Mediana Edad , Estudios Retrospectivos , Adulto , Extremidades/diagnóstico por imagen , Anciano , Sensibilidad y Especificidad , Adulto Joven , Valor Predictivo de las Pruebas , Adolescente , Anciano de 80 o más Años , RadiómicaRESUMEN
Focal segmental glomerulosclerosis (FSGS) is a leading kidney disease, clinically associated with proteinuria and progressive renal failure. The occurrence of this disease is partly related to gene mutations. We describe a single affected family member who presented with FSGS. We used high-throughput sequencing, sanger sequencing to identify the pathogenic mutations, and a systems genetics analysis in the BXD mice was conducted to explore the genetic regulatory mechanisms of pathogenic genes in the development of FSGS. We identified high urinary protein (++++) and creatinine levels (149 µmol/L) in a 29-year-old male diagnosed with a 5-year history of grade 2 hypertension. Histopathology of the kidney biopsy showed stromal hyperplasia at the glomerular segmental sclerosis and endothelial cell vacuolation degeneration. Whole-exome sequencing followed by Sanger sequencing revealed a heterozygous missense mutation (c.643C > T) in exon 2 of TRPC6, leading to the substitution of arginine with tryptophan at position 215 (p.Arg215Trp). Systems genetics analysis of the 53 BXD mice kidney transcriptomes identified Pygm as the upstream regulator of Trpc6. Those two genes are jointly involved in the regulation of FSGS mainly via Wnt and Hippo signaling pathways. We present a novel variant in the TRPC6 gene that causes FSGS. Moreover, our data suggested TRPC6 works with PYGM, as well as Wnt and Hippo signaling pathways to regulate renal function, which could guide future clinical prevention and targeted treatment for FSGS outcomes.
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OBJECTIVE: To compare clinical outcomes of flexible and rigid bronchoscopies for the management of foreign body aspiration (FBA) in different airway locations, especially in unilateral main bronchus, in children, so as to provide some suggestions to assist clinical decisions. METHODS: The medical records of children diagnosed with FBA in Qingdao Women and Children's Hospital Affiliated to Qingdao University from January 2020 to June 2022 were retrospectively reviewed. The following information was collected: demographics, radiological findings, endoscopic findings, foreign body locations, duration of operation, operation cost, and intraoperative and postoperative complications. RESULTS: 182 children were included in the study with the median age of 1.3 years (interquatile range, 1.0-1.8). Among whom, 124 cases (68.1 %) were male and 58 cases (31.9 %) were female. 11 cases (6.0 %) had the foreign bodies located in the trachea (larynx to carina), 3 cases (1.6 %) located in the trachea and lower bronchus, 1 case (0.5 %) located in bilateral main bronchus, 135 cases (74.2 %) located in unilateral main bronchus, 4 cases (2.2 %) located in main and lobar bronchus, and 28 cases (15.4 %) located in the lobar or segmental bronchus. Among all the included children, 84 cases (46.2 %) received rigid bronchoscopy (RB) and 98 cases (53.8 %) received flexible bronchoscopy (FB). 131 cases with the foreign bodies located in unilateral main bronchus received one type of bronchoscopy (RB or FB). They were divided into two groups according to the location of foreign body relative to the midpoint of main bronchus, the proximal bronchus group and the distal bronchus group. In the proximal bronchus group, duration of operation using RB and FB was 15 (12.5-27.5) min and 15 (14.5-30.0) min, respectively (Z = 0.000, P = 1.000). The intraoperative and postoperative complication rate using RB and FB was 15.4 % and 9.1 %, respectively (χ2 = 0.008, P = 0.927). Operation cost of FB was significantly higher than that of RB (t = -13.396, P = 0.000). In the distal bronchus group, duration of operation using RB was 20 (13.5-25.0) min, which was drastically shorter than that of FB (25 (20.0-35.0) min) (Z = -2.947, P=0.003). Operation cost of FB was still found to be significantly higher than RB (t = -20.456, P=0.000). No significant difference was found in complication rate of RB (14.3%) compared to FB (8.3%) (χ2=0.251, P=0.616). CONCLUSIONS: When foreign bodies are lodged in unilateral main bronchus, RB could be chosen as the first-choice procedure with advantages in duration of operation and operation cost, especially for patients in China. Regardless of duration of operation and operation cost, FB is also a safe and efficient therapeutic procedure to remove inhaled foreign bodies in children, except for those located in the trachea and asphyxiating foreign bodies.
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Broncoscopía , Cuerpos Extraños , Niño , Humanos , Masculino , Femenino , Lactante , Estudios Retrospectivos , Bronquios/cirugía , Tráquea/cirugía , Aspiración Respiratoria/etiología , Aspiración Respiratoria/cirugía , Cuerpos Extraños/diagnóstico por imagen , Cuerpos Extraños/cirugíaRESUMEN
BACKGROUND: Autoimmune encephalitis (AE) is a group of autoimmune diseases targeting the central nervous system, characterized by severe clinical symptoms and substantial consumption of medical resources. Neuroinflammation plays a crucial role in disease progression, and detecting inflammatory responses can provide insights into disease status and disease severity. The systemic immune-inflammation index (SII), a novel marker of inflammatory status, has been rarely studied in AE. METHODS: Retrospective analysis of data from AE patients admitted to the First Affiliated Hospital of Zhengzhou University between January 2019 and September 2023 was conducted. Univariate analysis and logistic regression were used to assess the association between SII and patient severity. Nomograms for predicting AE severity were established, and receiver operating characteristic (ROC) curves, concordance index (C-index), calibration curves, and decision curve analysis were employed to evaluate predictive accuracy. Additionally, the Clinical Assessment Scale in Autoimmune Encephalitis (CASE) score was used to assess patient severity. RESULTS: This study enrolled 157 patients, of whom 57 were classified as severe according to the CASE score. SII, cerebrospinal fluid (CSF) cell counts, disturbance of consciousness, and behavioural abnormalities independently associated with the occurrence of severe cases. The C-index of the nomograms was 0.87, indicating strong association with disease severity, as supported by the calibration. Additionally, SII levels were highest within seven days of onset and decreased after one month. In subgroup analyses of different antibodies, SII also associations with severe cases in NMDAR encephalitis. CONCLUSIONS: Higher SII levels are associated with an increased likelihood of developing severe AE, peaking within 7 days of disease onset and decreasing thereafter, potentially offering a prognostic marker to assess disease progression early in its course.
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Dynamic contrast-enhanced ultrasound (DCE-US) is a technique to quantify tissue perfusion based on phase-specific enhancement after the injection of microbubble contrast agents for diagnostic ultrasound. The guidelines of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) published in 2004 and updated in 2008, 2011, and 2020 focused on the use of contrast-enhanced ultrasound (CEUS), including essential technical requirements, training, investigational procedures and steps, guidance regarding image interpretation, established and recommended clinical indications, and safety considerations. However, the quantification of phase-specific enhancement patterns acquired with ultrasound contrast agents (UCAs) is not discussed here. The purpose of this EFSUMB Technical Review is to further establish a basis for the standardization of DCE-US focusing on treatment monitoring in oncology. It provides some recommendations and descriptions as to how to quantify dynamic ultrasound contrast enhancement, and technical explanations for the analysis of time-intensity curves (TICs). This update of the 2012 EFSUMB introduction to DCE-US includes clinical aspects for data collection, analysis, and interpretation that have emerged from recent studies. The current study not only aims to support future work in this research field but also to facilitate a transition to clinical routine use of DCE-US.
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Medios de Contraste , Neoplasias , Humanos , Ultrasonografía/métodos , PerfusiónRESUMEN
The low-cost daily monitoring of C-reactive protein (CRP) levels is crucial for screening acute inflammation or infections as well as managing chronic inflammatory diseases. In this study, we synthesized novel 2-Methacryloyloxy ethyl phosphorylcholine (MPC)-based biomimetic nanoparticles with a large surface area to develop a visual CRP-quantification assay using affordable glass capillaries. The PMPC nanoparticles, synthesized via reflux precipitation polymerization, demonstrated multivalent binding capabilities, enabling rapid and specific CRP capture. In the presence of CRP, PMPC nanoparticles formed sandwich structures with magnetic nanoparticles functionalized with CRP antibodies, thereby enhancing detection sensitivity and specificity. These sandwich complexes were magnetically accumulated into visible and quantifiable stacks within the glass capillaries, allowing for the rapid, sensitive, and specific quantification of CRP concentrations with a detection limit of 57.5 pg/mL and a range spanning from 0 to 5000 ng/mL. The proposed visual distance-based capillary biosensor shows great potential in routine clinical diagnosis as well as point-of-care testing (POCT) in resource-limited settings.
Asunto(s)
Proteína C-Reactiva , Nanopartículas , Polímeros , Proteína C-Reactiva/análisis , Inmunoensayo/métodos , Nanopartículas/química , Humanos , Polímeros/química , Materiales Biomiméticos/química , Técnicas Biosensibles/métodos , Límite de Detección , Fosforilcolina/química , Fosforilcolina/análogos & derivadosRESUMEN
Objective: To assess the effects of comprehensive nursing intervention on quality of life, self-efficacy, gastrointestinal reaction and immune function of patients with breast cancer undergoing chemotherapy. Methods: This was a retrospective study. One hundred and twenty patients receiving chemotherapy after breast cancer surgery were randomly divided into the experimental group and the control group(n=60) from January 2021 to January 2023. Patients in the perioperative period, the experimental group were given comprehensive nursing intervention, while those in the control group were given conventional specialist nursing intervention. The differences in quality of life, self-efficacy, gastrointestinal reaction, immune function and patient satisfaction between the two groups were compared and analyzed. Results: After the intervention, the SF-36 scores in the experimental group were significantly higher than those in the control group (P=0.00), the efficacy indicators were significantly improved compared to the control group(P=0.00); the scores of gastrointestinal symptoms in the experimental group were significantly lower than those in the control group after the intervention(P<0.05). The indexes of CD3+, CD4+ and CD4+/CD8+ in the experimental group after the intervention were significantly higher than those in the control group(P=0.00); The patient satisfaction in the experimental group was 100%, which was significantly higher than 92% in the control group, with statistically significant differences(P=0.02). Conclusion: Comprehensive nursing intervention leads to a variety of benefits in the treatment of patients with breast cancer during postoperative chemotherapy, such as relieving patients' gastrointestinal reactions, improving their immune function and quality of life, besides effectively improving their self-efficacy, which is worthy of clinical application.