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BACKGROUND: Abdominal CT scans are vital for diagnosing abdominal diseases but have limitations in tissue analysis and soft tissue detection. Dual-energy CT (DECT) can improve these issues by offering low keV virtual monoenergetic images (VMI), enhancing lesion detection and tissue characterization. However, its cost limits widespread use. PURPOSE: To develop a model that converts conventional images (CI) into generative virtual monoenergetic images at 40 keV (Gen-VMI40keV) of the upper abdomen CT scan. METHODS: Totally 444 patients who underwent upper abdominal spectral contrast-enhanced CT were enrolled and assigned to the training and validation datasets (7:3). Then, 40-keV portal-vein virtual monoenergetic (VMI40keV) and CI, generated from spectral CT scans, served as target and source images. These images were employed to build and train a CI-VMI40keV model. Indexes such as Mean Absolute Error (MAE), Peak Signal-to-Noise Ratio (PSNR), and Structural Similarity (SSIM) were utilized to determine the best generator mode. An additional 198 cases were divided into three test groups, including Group 1 (58 cases with visible abnormalities), Group 2 (40 cases with hepatocellular carcinoma [HCC]) and Group 3 (100 cases from a publicly available HCC dataset). Both subjective and objective evaluations were performed. Comparisons, correlation analyses and Bland-Altman plot analyses were performed. RESULTS: The 192nd iteration produced the best generator mode (lower MAE and highest PSNR and SSIM). In the Test groups (1 and 2), both VMI40keV and Gen-VMI40keV significantly improved CT values, as well as SNR and CNR, for all organs compared to CI. Significant positive correlations for objective indexes were found between Gen-VMI40keV and VMI40keV in various organs and lesions. Bland-Altman analysis showed that the differences between both imaging types mostly fell within the 95% confidence interval. Pearson's and Spearman's correlation coefficients for objective scores between Gen-VMI40keV and VMI40keV in Groups 1 and 2 ranged from 0.645 to 0.980. In Group 3, Gen-VMI40keV yielded significantly higher CT values for HCC (220.5HU vs. 109.1HU) and liver (220.0HU vs. 112.8HU) compared to CI (p < 0.01). The CNR for HCC/liver was also significantly higher in Gen-VMI40keV (2.0 vs. 1.2) than in CI (p < 0.01). Additionally, Gen-VMI40keV was subjectively evaluated to have a higher image quality compared to CI. CONCLUSION: CI-VMI40keV model can generate Gen-VMI40keV from conventional CT scan, closely resembling VMI40keV.
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Tomografía Computarizada por Rayos X , Humanos , Tomografía Computarizada por Rayos X/métodos , Femenino , Masculino , Persona de Mediana Edad , Radiografía Abdominal/métodos , Anciano , Adulto , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Neoplasias Hepáticas/diagnóstico por imagen , Relación Señal-Ruido , Imagen Radiográfica por Emisión de Doble Fotón/métodos , Carcinoma Hepatocelular/diagnóstico por imagen , Anciano de 80 o más Años , Medios de ContrasteRESUMEN
OBJECTIVE: To determine the effects of changes in serum luteinizing hormone (LH) levels in the early stages of the gonadotropin-releasing hormone antagonist (GnRH-A) protocol on in vitro fertilization and embryo transfer/intracytoplasmic sperm injection clinical outcomes. METHODS: Data from 2116 fresh embryo transfer cycles with the GnRH-A protocol were retrospectively analyzed. Patients were divided into two groups, ΔLH-increased and ΔLH-decreased, according to changes in serum LH levels on the day of GnRH-A addition compared with that on the start day of ovarian stimulation. Patients in whom ΔLH increased were categorized according to early-onset LH increases (serum LH level ≥10 mIU/mL or twice the baseline). RESULTS: ΔLH increased and decreased in 14.9% and 85.1% of patients, respectively. The fertilization rate was lower, and fewer oocytes were retrieved in patients with increased ΔLH compared to those with decreased ΔLH (p < .05). The number of AFC, oocytes retrieved, and AMH in patients with early-onset ΔLH increase was lower between the subgroups (p < .05). There were no significant differences in clinical pregnancy, early abortion, biochemical pregnancy, and live birth rates between the groups and subgroups (p > .05). CONCLUSIONS: Early increases in LH levels during GnRH-A protocol might affect the number of oocytes retrieved, but not the clinical outcomes.
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Fertilización In Vitro , Hormona Liberadora de Gonadotropina , Femenino , Fertilización In Vitro/métodos , Antagonistas de Hormonas/farmacología , Antagonistas de Hormonas/uso terapéutico , Humanos , Hormona Luteinizante , Inducción de la Ovulación/métodos , Embarazo , Índice de Embarazo , Estudios RetrospectivosRESUMEN
BACKGROUND: The aim of this study was to investigate differences in clinical features and HLA genotypes between adult-onset and childhood-onset patients with type 1 diabetes in a Chinese population. MATERIALS AND METHODS: This study enrolled 716 Han Chinese patients with type 1 diabetes from Guangdong (258 childhood-onset and 458 adult-onset) to compare their clinical features. Of them 214 patients with classical type 1 diabetes (100 childhood-onset and 114 adult-onset) were selected for HLA DR and DQ genotyping by next-generation sequencing. RESULTS: Adult-onset patients were characterized by longer duration of symptoms before diagnosis, lower frequency of DKA at disease onset, less frequent autoantibody positivity, higher serum C-peptide concentrations, and better glycemic control. These findings were replicated in the restricted cohort of 214 patients with classical type 1 diabetes. Compared with childhood-onset patients, adult-onset patients had a lower frequency of the DR9 haplotype, as well as lower frequency of high-risk DR3/DR4 and DR3/DR9 genotypes, but higher frequency of DR3/DR3 genotype and DR3/X, DR4/X or DR9/X (X, non-risk) genotypes. CONCLUSIONS: Adult-onset type 1 diabetic patients with susceptible haplotypes (DR3, DR4 or DR9) were more likely to carry protective DR-DQ haplotypes than childhood-onset patients, which suggested the association between less risk DR-DQ genotypes and the less severe clinical manifestation in adult-onset patients.
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Diabetes Mellitus Tipo 1 , Antígenos HLA-DQ , Antígenos HLA-DR , Adulto , Edad de Inicio , Niño , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 1/genética , Genotipo , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Humanos , Gravedad del Paciente , Medición de RiesgoRESUMEN
PROBLEM: Does aquaporin 3 (AQP3) affect the migration and invasion of human extravillous trophoblast (HTR8/Svneo) cells? METHOD OF STUDY: A lentivirus infection system was used to construct stable cell lines with either AQP3 knockdown or overexpression. RT-PCR and western blotting were used to verify the efficiencies of AQP3 knockdown or overexpression in HTR8/Svneo cells at mRNA and protein levels, respectively. Cell Counting Kit-8 and flow cytometry assays were used to detect the influence of AQP3 knockdown or overexpression on proliferation and apoptosis of HTR8/Svneo cells. In addition, wound healing and Transwell invasion assays were used to detect the effects of AQP3 knockdown or overexpression on migration and invasion capabilities of HTR8/Svneo cells. An Agilent gene chip was used to screen for significant differentially expressed genes after AQP3 knockdown. Finally, mechanisms by which AQP3 influences the migration and invasion of HTR8/Svneo cells were explored using bioinformatic analysis. RESULTS: Compared with controls, migration and invasion capabilities of HTR8/Svneo cells were significantly reduced after AQP3 knockdown, and significantly increased after AQP3 overexpression. Subsequent bioinformatic analysis of gene chip expression profiles indicated downregulation of genes related to adhesion such as PDGF-B, as well as signaling pathways (such as PIK3/AKT, NF-κB, and TNF) after AQP3 knockdown. CONCLUSIONS: AQP3 could significantly promote migration and invasion capabilities of human extravillous trophoblasts, it may mediate embryo invasion and adhesion to endometrium by regulating PDGF-B, PIK3/AKT signaling pathways, although this requires further verification.
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Acuaporina 3/biosíntesis , Movimiento Celular/fisiología , Vellosidades Coriónicas/metabolismo , Trofoblastos/metabolismo , Acuaporina 3/antagonistas & inhibidores , Acuaporina 3/genética , Línea Celular , Proliferación Celular/fisiología , Femenino , Técnicas de Silenciamiento del Gen/métodos , Humanos , EmbarazoRESUMEN
BACKGROUND: The aim of our study is to investigate whether preproinsulin (PPI) could trigger a proinflammatory CD4+ T cell response in Chinese patients with type 1 diabetes (T1D). METHODS: Peripheral blood mononuclear cells were stimulated by a pool of 13 PPI peptides. Additional five PPI peptides previously proved to be antigenic in other cohorts of patients with T1D were also used. PPI reactive T cell responses were measured by interferon (IFN)-γ ELISPOT assay. RESULTS: Fifty-one Chinese patients with T1D were enrolled in this study and 72.34% of them were positive for at least one islet autoantibody. The stimulation index (SI) value of IFN-γ response to PPI peptide pool or peptides with dominant epitopes was below 3 in patients when SI≥3 was used as the positive cut-off value. Two peptides (B9-23 and C19-A3) restricted to DQ8 or DR4 molecule failed to induce positive IFN-γ response in patients with high-risk HLA-DQ8 or HLA-DR4/DR9 alleles. RNA-seq analysis of PPI specific CD4+ T cell lines further showed that most of the IFN-γ associated genes remained unchanged. CONCLUSIONS: This is the first report of CD4+ T cell epitope mapping of PPI in Chinese T1D. The lack of positive IFN-γ response to PPI peptides indicates that PPI might not be the principal antigenic candidate for autoreactive CD4+ T cells in Chinese T1D. Therefore, the efficacy of PPI-based immunotherapies in attenuating proinflammatory CD4+ T cell response requires further investigation.
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Diabetes Mellitus Tipo 1/inmunología , Epítopos de Linfocito T/inmunología , Antígenos HLA-DQ/inmunología , Insulina/inmunología , Leucocitos Mononucleares/inmunología , Precursores de Proteínas/inmunología , Linfocitos T/inmunología , Adolescente , Adulto , Niño , Preescolar , China/epidemiología , Diabetes Mellitus Tipo 1/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Proyectos Piloto , Pronóstico , Adulto JovenRESUMEN
AIM: This study aimed to investigate the impact of endometrial thickness (EMT) during menstruation and endometrial scratching on the pregnancy in frozen-thawed embryo transfer (FET). METHODS: About 1298 patients receiving FET were retrospectively analyzed and divided according to EMT on the 4th or 5th day of menstruation. Group A: EMT ≤ 3.0 mm; Group B: EMT 3.1-5.0 mm; Group C: EMT 5.1-7.0 mm and Group D: EMT > 7.0 mm. Patients in Group D were further divided to scratching group and nonscratching group. Endometrial growth was defined as the change in EMT from 4th or 5th day of menstruation to the day of embryo transferred. RESULTS: We found no significant differences in general conditions among four groups (P > 0.05). The average EMT during menstruation and differences in inter-group endometrial growth of four groups had statistical significance (P < 0.05). The pregnancy rate and implantation rate of Group D were significantly lower than other groups (P < 0.001). Pregnancy rate (68.29% vs 53.26%) and implantation rate (52.67% vs 36.34%) in endometrial scratching group were higher than those in nonscratching group (P < 0.05). CONCLUSION: Higher EMT during menstruation adversely affects pregnancy outcomes following FET. Endometrial scratching may improve the receptivity of endometrium and increase the rate of embryo implantation and pregnancy.
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Transferencia de Embrión , Endometrio/diagnóstico por imagen , Menstruación/fisiología , Adulto , Implantación del Embrión/fisiología , Femenino , Humanos , Inducción de la Ovulación , Embarazo , Resultado del Embarazo , Índice de Embarazo , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Prostate cancer is a heterogeneous disease, meaning patients would benefit from different treatment strategies based on their molecular stratification. In recent years, several genomic studies have identified prostate cancers with defects in DNA repair genes. It is known that the PARP inhibitor, olaparib, has a significant synthetic lethal effect on tumors with BRCA 1/2 mutations, particularly in ovarian and breast cancer. CASE PRESENTATION: In this study, we describe a patient with metastatic castration-resistant prostate cancer (mCRPC) containing a BRCA2 germline mutation who underwent olaparib treatment. The efficacy of the treatment was monitored by serum TPSA level as well as mutation levels of circulating tumor DNA (ctDNA) using next-generation sequencing (NGS). The patient responded to the olaparib treatment as indicated by the minimal residual levels of TPSA and tumor-specific mutations of ctDNA in plasma after four months of treatment, although the patient eventually progressed at six-month post-treatment with significantly elevated and newly acquired somatic mutations in ctDNA. CONCLUSIONS: Our study provides evidence that mCRPC with BRCA2 germline mutations could response to PARP inhibitor, which improves patient's outcome. We further demonstrated that NGS-based genetic testing on liquid biopsy can be used to dynamically monitor the efficacy of treatment.
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Adenocarcinoma/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Proteína BRCA2/genética , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Ftalazinas/uso terapéutico , Piperazinas/uso terapéutico , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Adenocarcinoma/sangre , Adenocarcinoma/genética , Adenocarcinoma/secundario , Anciano , ADN Tumoral Circulante/sangre , ADN Tumoral Circulante/genética , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Mutación de Línea Germinal , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Calicreínas/sangre , Calicreínas/genética , Biopsia Líquida , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundario , Masculino , Poli(ADP-Ribosa) Polimerasas/sangre , Poli(ADP-Ribosa) Polimerasas/genética , Antígeno Prostático Específico/sangre , Antígeno Prostático Específico/genética , Neoplasias de la Próstata Resistentes a la Castración/sangre , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/patologíaRESUMEN
The objectives of this study were to investigate the clinical efficacy of growth hormone (GH) in patients experiencing repeat implantation failure (RIF) and explore the possible mechanism. Forty-two RIF patients undergoing in vitro fertilization - embryo transfer (IVF-ET) were enrolled in the present trial: 22 patients who received GH (treatment group) and 20 who did not receive GH (controls). The clinical pregnancy and live birth rates in the treatment group were significantly higher than those in the control group (both P < 0.05). The treatment group expressed significantly higher levels of growth hormone receptor (GHR) mRNA than the control group (P < 0.05). Further analysis showed that GH levels in follicular fluid were positively correlated with the expression levels of mRNA encoding GHR in granulosa cells (r = 0.460, P < 0.05). GH treatment enhanced IVF pregnancy outcomes and increased the expression of GHR in granulosa cells in fluid. GH levels in follicular fluid were positively correlated with the expression levels of GHR.
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Implantación del Embrión , Fertilización In Vitro , Hormona de Crecimiento Humana/farmacología , Adulto , Implantación del Embrión/efectos de los fármacos , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Embarazo , Resultado del Embarazo , Receptores de Somatotropina/genéticaRESUMEN
A room temperature, efficient, and palladium-catalyzed azidative cycloisomerization of homoallenyl amides using TMSN3 as the azidation reagent and PhI(O2CCF3)2 as the oxidant is described, producing a variety of 2-amino-5-azidomethylfurans in moderate to excellent yields. The products can be applied to the concise synthesis of 1,2,3-triazoles via a Cu-catalyzed azide-alkyne cycloaddition.
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Betacoronavirus , Infecciones por Coronavirus/tratamiento farmacológico , Citocinas/metabolismo , Inflamación/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Antiinflamatorios/uso terapéutico , COVID-19 , Proteínas de Ciclo Celular/antagonistas & inhibidores , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/virología , Interacciones Microbiota-Huesped/efectos de los fármacos , Interacciones Microbiota-Huesped/inmunología , Humanos , Factores Inmunológicos/uso terapéutico , Inflamasomas/efectos de los fármacos , Inflamasomas/inmunología , Inflamación/inmunología , Inflamación/virología , Interleucina-6/antagonistas & inhibidores , Modelos Inmunológicos , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Pandemias , Neumonía Viral/inmunología , Neumonía Viral/virología , SARS-CoV-2 , Factores de Transcripción/antagonistas & inhibidores , Tratamiento Farmacológico de COVID-19RESUMEN
Down syndrome (DS) is the most common chromosomal disorder and a major cause of intellectual disability. The genetic etiology of DS is the extra copy of chromosome 21 (HSA21)-encoded genes; however, the contribution of specific HSA21 genes to DS pathogenesis remains largely unknown. Here, we identified ZBTB21, an HSA21-encoded zinc-finger protein, as a transcriptional repressor in the regulation of synaptic function. We found that normalization of the Zbtb21 gene copy number in DS mice corrected deficits in cognitive performance, synaptic function, and gene expression. Moreover, we demonstrated that ZBTB21 binds to canonical cAMP-response element (CRE) DNA and that its binding to CRE could be competitive with CRE-binding factors such as CREB. ZBTB21 represses CRE-dependent gene expression and results in the negative regulation of synaptic plasticity, learning and memory. Together, our results identify ZBTB21 as a CRE-binding protein and repressor in cAMP-dependent gene regulation, contributing to cognitive defects in DS.
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Síndrome de Down , Regulación de la Expresión Génica , Sinapsis , Factores de Transcripción , Animales , Humanos , Ratones , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/genética , Modelos Animales de Enfermedad , Síndrome de Down/genética , Síndrome de Down/metabolismo , Síndrome de Down/patología , Dosificación de Gen , Plasticidad Neuronal , Unión Proteica , Sinapsis/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Transcripción GenéticaRESUMEN
Objective: Complex chromosome rearrangements (CCR) are rare structural abnormalities involving at least three breakpoints, categorized into three types based on their structure: type A (three-way rearrangements), type B (double two-way translocations), and type C (exceptional CCR). However, thus far, limited data exists on preimplantation genetic testing for chromosomal structural rearrangements (PGT-SR) in CCR carriers. This study aims to evaluate the clinical outcomes and influencing factors of PGT-SR in couples with CCR. Methods: Fifteen couples with unique CCR recruited from 793 couples following PGT-SR between January 2017 and May 2023. In addition, a total of 54 CCR cases, 39 previously reported as well as 15 newly added, were included in the analysis of factors associate with normal/balanced embryos. Results: A total of 100 blastocysts were biopsied and analyzed in 15 CCR couples after 17 PGT-SR cycles, with 16.0% being euploid, 78.0% aneuploid and 6.0% mosaic. 11 normal/balanced embryos and one mosaic embryo were transferred, resulting in eight live births. Furthermore, based on the combined data from 54 CCR carriers, the proportion of normal/balanced embryos was 10.8%, with a significant decrease observed among female carriers compared to male heterozygotes (6.5% vs. 15.5%, p = 0.002). Type B exhibited the lowest rate of euploid embryos at only 6.7%, followed by type A at 11.6% and type C at 14.0%, although the differences were not significant (p = 0.182). After completing the multivariate generalized estimating equation (GEE) analysis, type B (p = 0.014) and female carrier (p = 0.002) were identified as independent risk factors for fewer euploid embryos. Conclusion: The occurrence of balanced CCR in patients with reproductive abnormalities may be more frequent than we expected. Despite the proportion of normal/balanced embryos being significantly low, which can be influenced by CCR type and carrier's sex, PGT-SR may improve the reproductive outcomes among CCR cases. These findings can optimize the clinical management and genetic counseling of CCR carriers seeking assisted reproductive technology (ART).
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The current work was developed to explore the functions and possible mechanism of PRG4 in cardiac hypertrophy and heart failure. Ang II-stimulated H9c2 cells and AC16 cells were used as in vitro cell models. The binding relation between genes in cells was explored using luciferase reporter assays and RNA immunoprecipitation assay. The cardiac functions of rats received transverse-ascending aortic constriction (TAC) surgery and adeno-associated virus (AAV) injection were examined with echocardiography. The myocardial histological changes were observed using H&E, wheat germ agglutinin, and sirius red staining. It was discovered that PRG4 silencing attenuated cell hypertrophy and fibrosis and inactivated the Smad pathway under Ang II treatment. PRG4 was targeted by miR-758-3p, and miR-758-3p interacted with long noncoding RNA DANCR. DANCR silencing inhibited cardiac dysfunction, fibrosis, and TGFß1/Smad pathway. In addition, DANCR was highly expressed in myocardial extracellular vesicles. Overall, DANCR depletion prevents heart failure by inhibiting cardiac hypertrophy and fibrosis via the miR-758-3p/PRG4/Smad pathway.
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Insuficiencia Cardíaca , MicroARNs , ARN Largo no Codificante , Ratas , Animales , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Cardiomegalia/genética , Cardiomegalia/prevención & control , Cardiomegalia/metabolismo , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/prevención & control , FibrosisRESUMEN
Radiofrequency (RF) current is used as an effective non-ablative method for skin rejuvenation. However, mixed results have been reported using different home-use RF devices. In order to evaluate the safety and effectiveness of home-use RF devices, this study has provided a three-dimensional (3D) simulation procedure based on the electrothermal coupling model for home-use RF devices. Firstly, the tissue geometric model with the setting electrode shapes was established and then imported into the simulation software. Secondly, electrical and thermal boundary conditions with excitation voltages were loaded to the corresponding components. In addition, the items of 3D temperatures at all locations and key temperatures of the tissue were assessed. The results have shown the temperature distributions of four commercial RF products, respectively. This 3D RF electrothermal coupling simulation can be conducted quickly and effectively to obtain the temperature and electric distribution of the home-use RF devices at different using periods, which is also useful for the design of home-use RF devices.Clinical Relevance- This study provides a simple and effective simulation procedure for device developers to evaluate the home-use RF devices when designing products. This simulation is also helpful for customer decision-making and performance evaluation considering different devices.
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Rejuvenecimiento , Piel , Simulación por Computador , Temperatura , Ondas de RadioRESUMEN
Pleural contact in lung cancers does not always imply pleural invasion (PI). This study was designed to determine whether specific invasive CT characteristics or iodine uptake can aid in the prediction of PI. The sample population comprised patients with resected solid lung adenocarcinomas between April 2019 and May 2022. All participants underwent a contrast enhanced spectral CT scan. Two proficient radiologists independently evaluated the CT features and iodine uptake. Logistic regression analyses were employed to identify predictors for PI, via CT features and iodine uptake. To validate the improved diagnostic efficiency, accuracy analysis and ROC curves were subsequently used. A two-tailed P value of less than 0.05 was considered statistically significant. We enrolled 97 consecutive patients (mean age, 61.8 years ± 10; 48 females) in our study. The binomial logistic regression model revealed that a contact length > 10 mm (OR 4.80, 95% CI 1.92, 11.99, p = 0.001), and spiculation sign (OR 2.71, 95% CI 1.08, 6.79, p = 0.033) were independent predictors of PI, while iodine uptake was not. Enhanced sensitivity (90%) and a greater area under the curve (0.73) were achieved by integrating the two aforementioned CT features in predicting PI. We concluded that the combination of contact length > 10 mm and spiculation sign can enhance the diagnostic performance of PI.
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Adenocarcinoma del Pulmón , Adenocarcinoma , Yodo , Neoplasias Pulmonares , Femenino , Humanos , Persona de Mediana Edad , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma del Pulmón/diagnóstico por imagen , Neoplasias Pulmonares/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
Background: Although observational studies have shown that patients who experienced transient ischemic attacks (TIAs) had a higher risk of coronary artery disease (CAD), the causal relationship is ambiguous. Methods: We conducted a two-sample Mendelian randomization (MR) study to analyze the causal relationship between TIA and CAD using data from the FinnGen genome-wide association study. Analysis was performed using the inverse-variance weighted (IVW) method. The robustness of the results was evaluated using MR-Egger regression, the weighted median, MR pleiotropy residual sum, and outlier (MR-PRESSO) and multivariable MR analysis. Results: Results from IVW random-effect model showed that TIA was associated with an increased risk of coronary artery atherosclerosis (OR 1.17, 95% CI 1.06-1.28, P = 0.002), ischemic heart disease (OR 1.15, 95% CI 1.04-1.27, P = 0.007), and myocardial infarction (OR1.15, 95% CI 1.02-1.29, P = 0.025). In addition, heterogeneity and horizontal pleiotropy were observed in the ischemic heart disease results, while the sensitivity analysis revealed no evidence of horizontal pleiotropy in other outcomes. Conclusions: This MR study demonstrated a potential causal relationship between TIA and CAD. Further research should be conducted to investigate the mechanism underlying the association.
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Background: Sjögren's syndrome (SS) is a chronic autoimmune disease characterized by exocrine and extra-glandular symptoms. The literature indicates that SS is an independent risk factor for atherosclerosis (AS); however, its pathophysiological mechanism remains undetermined. This investigation aimed to elucidate the crosstalk genes and pathways influencing the pathophysiology of SS and AS via bioinformatic analysis of microarray data. Methods: Microarray datasets of SS (GSE40611) and AS (GSE28829) were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were acquired using R software's "limma" packages, and the functions of common DEGs were determined using Gene Ontology and Kyoto Encyclopedia analyses. The protein-protein interaction (PPI) was established using the STRING database. The hub genes were assessed via cytoHubba plug-in and validated by external validation datasets (GSE84844 for SS; GSE43292 for AS). Gene set enrichment analysis (GSEA) and immune infiltration of hub genes were also conducted. Results: Eight 8 hub genes were identified using the intersection of four topological algorithms in the PPI network. Four genes (CTSS, IRF8, CYBB, and PTPRC) were then verified as important cross-talk genes between AS and SS with an area under the curve (AUC) ≥0.7. Furthermore, the immune infiltration analysis revealed that lymphocytes and macrophages are essentially linked with the pathogenesis of AS and SS. Moreover, the shared genes were enriched in multiple metabolisms and autoimmune disease-related pathways, as evidenced by GSEA analyses. Conclusion: This is the first study to explore the common mechanism between SS and AS. Four key genes, including CTSS, CYBB, IRF8, and PTPRC, were associated with the pathogenesis of SS and AS. These hub genes and their correlation with immune cells could be a potential diagnostic and therapeutic target.
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Background: Observational studies have reported the association between fatigue and coronary artery disease (CAD), but the causal association between fatigue and CAD is unclear. Method: We conducted a bidirectional Mendelian randomization (MR) study using publicly available genome-wide association studies (GWAS) data. The inverse-variance weighted (IVW) method was used as the primary analysis. We performed three complementary methods, including weighted median, MR-Egger regression, and MR pleiotropy residual sum and outlier (MR-PRESSO) to evaluate the sensitivity and horizontal pleiotropy of the results. Result: Self-reported fatigue had a causal effect on coronary artery atherosclerosis (CAA) (OR 1.047, 95%CI 1.033-1.062), myocardial infarction (MI) (OR 1.027 95%CI 1.014-1.039) and coronary heart disease (CHD) (OR 1.037, 95%CI 1.021-1.053). We did not find a significant reverse causality between self-reported fatigue and CAD. Given the heterogeneity revealed by MR-Egger regression, we employed the IVW random effect model. For the examination of fatigue on CHD and the reverse analysis of CAA, and MI on fatigue, the MR-PRESSO test found horizontal pleiotropy. No significant outliers were found. Conclusion: The MR analysis reveals a causal relationship between self-reported fatigue and CAD. The results should be interpreted with caution due to horizontal pleiotropy.
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Glyphosate-based herbicides (GBHs) are used extensively around the world and have become the leading agrochemicals. However, study about the association between glyphosate exposure and the risk of diabetes mellitus (DM) is scarce. This study used 4 years of NHANES data (2013-2016) to further investigate the association. A total of 2535 participants were enrolled in this cross-sectional study. The baseline information and urinary glyphosate levels in diabetic and non-diabetic groups were compared. Using multivariable logistic regression mode, we explored the association between both the continuous and categorical forms of urinary glyphosate and DM risk. Further subgroup analyses based on categorical covariates were also conducted. Urinary glyphosate levels were 0.42 ng/ml in participants with diabetes and 0.34 ng/ml in participants without diabetes (P < 0.05). As a continuous variable, ln-transformed urinary glyphosate was significantly associated with an increased risk of DM in the most adjusted model (OR 1.28, 95% CI 1.03-1.57). However, the association was not significant in the most adjusted categorical model (P > 0.05).In further subgroup analyses, the associations remained significant in several subgroups. This study provides new evidence that glyphosate exposure was associated with a higher risk of diabetes in the American general adult population.
Asunto(s)
Diabetes Mellitus , Herbicidas , Adulto , Humanos , Estados Unidos , Glifosato , Estudios Transversales , Glicina , Encuestas Nutricionales , Diabetes Mellitus/epidemiologíaRESUMEN
Objective: The relationship between remnant-like particle cholesterol (RLP-C) levels and the progression of atrial fibrillation (AF) is not known. This research aimed to explore the association of RLP-C with long-term AF recurrence events post-radiofrequency catheter ablation (RFCA) of AF. Methods: In total 320 patients with AF who were subjected to the first RFCA were included in this research. Baseline information and laboratory data of patients were retrospectively collected, and a 1-year follow-up was completed. The follow-up endpoint was defined as an AF recurrence event occurring after 3 months. Afterward, a multivariate Cox regression model was constructed to analyze the risk factors that affect AF recurrence. Results: AF recurrence occurred in 103 patients (32.2%) within 3-12 months after RFCA. Based on the multivariate Cox regression analysis, Early recurrence (ER) [hazard ratio (HR) =1.57, 95% confidence interval (CI): 1.04-2.36, P = 0.032)], coronary artery disease (CAD) (HR = 2.03, 95% CI: 1.22-3.38, P = 0.006), left atrium anterior-posterior diameter (LAD) (HR = 1.07, 95% CI: 1.03-1.10, P < 0.001), triglyceride (TG) (HR = 1.51, 95% CI: 1.16-1.96, P = 0.002), low-density lipoprotein cholesterol (LDL-C) (HR = 0.74, 95% CI: 0.55-0.98, P = 0.036), and RLP-C (HR = 0.75 per 0.1â mmol/L increase, 95% CI: 0.68-0.83, P < 0.001) were linked to the risk of AF recurrence. Among them, the relationship between RLP-C and AF recurrence was found for the first time. The predictive value of RLP-C for AF recurrence was analyzed utilizing receiver operating characteristic (ROC) curves [area under the curve (AUC) = 0.81, 95% CI: 0.77-0.86, P < 0.001]. Subsequently, the optimal threshold value of RLP-C was determined to be 0.645â mmol/L with a sensitivity of 87.4% and a specificity of 63.6% based on the Youden index. Additionally, Kaplan-Meier analysis indicated a lower AF recurrence rate in the >0.645â mmol/L group than in the ≤0.645â mmol/L group (Log-rank P < 0.001). Conclusion: Low levels of RLP-C are associated with a higher risk of AF recurrence post-RFCA, suggesting that RLP-C may be a biomarker that helps to identify long-term AF recurrence.