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OBJECTIVE: To investigate the association of congenital heart disease (CHD) with morbidity and mortality of very low birth weight (VLBW) infants. STUDY DESIGN: This matched case-control study included VLBW infants born at a single institution between 2001 and 2015. The primary outcome was mortality. Secondary outcomes included necrotizing enterocolitis, bronchopulmonary dysplasia (BPD), sepsis, retinopathy of prematurity, and intraventricular hemorrhage. These outcomes were assessed by comparing VLBW-CHDs with control VLBW infants matched by gestational age within a week, birth weight within 500 g, sex, and birth date within a year using conditional logistic regression. Multivariable logistic regression analyzed differences in outcomes in the VLBW-CHD group between two birth periods (2001-2008 and 2009-2015) to account for changes in practice. RESULTS: In a cohort of 44 CHD infants matched with 88 controls, the mortality rate was 27% in infants with CHD and 1% in controls (p < 0.0001). The VLBW-CHDs had increased BPD; (odds ratio [OR]: 7.70, 95% confidence interval [CI]: 1.96-30.29) and sepsis (OR: 10.59, 95% CI: 2.99-37.57) compared with the control VLBWs. When adjusted for preoperative ventilator use, the VLBW-CHDs still had significantly higher odds of BPD (OR: 6.97, 95% CI: 1.73-28.04). VLBW-CHDs also had significantly higher odds of both presumed and culture-positive sepsis as well as late-onset sepsis than their matched controls. There were no significant differences in outcomes between the two birth periods. CONCLUSION: VLBW-CHDs showed higher odds of BPD, sepsis, and mortality than VLBW infants without CHD. Future research should focus on the increased mortality and specific complications encountered by VLBW infants with CHD and implement targeted strategies to address these risks. KEY POINTS: · Incidence of CHD is higher in preterm infants than in term infants but the incidence of their morbidities is not well described.. · VLBW infants with CHD have higher odds of mortality, bronchopulmonary dysplasia, and sepsis.. · Future research is needed to implement targeted preventive responses..
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OBJECTIVE: To determine the rate and trend of active treatment in a population-based cohort of infants born at 22-25 weeks of gestation and to examine factors associated with active treatment. STUDY DESIGN: This observational study evaluated 8247 infants born at 22-25 weeks of gestation at hospitals in the California Perinatal Quality Care Collaborative between 2011 and 2018. Multivariable logistic regression was used to relate maternal demographic and prenatal factors, fetal characteristics, and hospital level of care to the primary outcome of active treatment. RESULTS: Active treatment was provided to 6657 infants. The rate at 22 weeks was 19.4% and increased with each advancing week, and was significantly higher for infants born between days 4 and 6 at 22 or 23 weeks of gestation compared with those born between days 0 and 3 (26.2% and 78.3%, respectively, vs 14.1% and 65.9%, respectively; P < .001). The rate of active treatment at 23 weeks increased from 2011 to 2018 (from 64.9% to 83.4%; P < .0001) but did not change significantly at 22 weeks. Factors associated with increased odds of active treatment included maternal Hispanic ethnicity and Black race, preterm premature rupture of membranes, obstetrical bleeding, antenatal steroids, and cesarean delivery. Factors associated with decreased odds included lower gestational age and small for gestational age birth weight. CONCLUSIONS: In California, active treatment rates at 23 weeks of gestation increased between 2011 and 2018, but rates at 22 weeks did not. At 22 and 23 weeks, rates increased during the latter part of the week. Several maternal and infant factors were associated with the likelihood of active treatment.
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Recien Nacido Prematuro , Atención Prenatal , Peso al Nacer , Cesárea , Femenino , Edad Gestacional , Humanos , Lactante , Recién Nacido , EmbarazoRESUMEN
BACKGROUND: To investigate the role and its potential mechanism of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4) in lung adenocarcinoma. METHODS: Co-immunoprecipitation was performed to analyze the interaction between PFKFB4 and SRC-2. Western blot was used to investigate the phosphorylation of steroid receptor coactivator-2 (SRC-2) on the condition that PFKFB4 was knockdown. Transcriptome sequencing was performed to find the downstream target of SRC-2. Cell Counting Kit-8 (CCK-8) assay, transwell assay and transwell-matrigel assay were used to examine the proliferation, migration and invasion abilities in A549 and NCI-H1975 cells with different treatment. RESULTS: In our study we found that PFKFB4 was overexpressed in lung adenocarcinoma associated with SRC family protein and had an interaction with SRC-2. PFKFB4 could phosphorylate SRC-2 at Ser487, which altered SRC-2 transcriptional activity. Functionally, PFKFB4 promoted lung adenocarcinoma cells proliferation, migration and invasion by phosphorylating SRC-2. Furthermore, we identified that CARM1 was transcriptionally regulated by SRC-2 and involved in PFKFB4-SRC-2 axis on lung adenocarcinoma progression. CONCLUSIONS: Our research reveal that PFKFB4 promotes lung adenocarcinoma cells proliferation, migration and invasion via enhancing phosphorylated SRC-2-mediated CARM1 expression.
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Adenocarcinoma del Pulmón/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/genética , Coactivador 2 del Receptor Nuclear/genética , Fosfofructoquinasa-2/genética , Células A549 , Adenocarcinoma del Pulmón/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Progresión de la Enfermedad , Perfilación de la Expresión Génica , Células HEK293 , Humanos , Neoplasias Pulmonares/patología , Invasividad Neoplásica/genética , Fosforilación , Activación Transcripcional/genéticaRESUMEN
PURPOSE: Macrophages are highly plastic cells. Under different stimuli, macrophages can be polarized into several different subsets. Two main macrophage subsets have been suggested: classically activated or inflammatory (M1) macrophages and alternatively activated or anti-inflammatory (M2) macrophages. Macrophage polarization is governed by a highly complex set of regulatory networks. Many recent studies have shown that macrophages are key orchestrators in the pathogenesis of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and that regulation of macrophage polarization may improve the prognosis of ALI/ARDS. A further understanding of the mechanisms of macrophage polarization is expected to be helpful in the development of novel therapeutic targets to treat ALI/ARDS. Therefore, we performed a literature review to summarize the regulatory mechanisms of macrophage polarization and its role in the pathogenesis of ALI/ARDS. METHODS: A computer-based online search was performed using the PubMed database and Web of Science database for published articles concerning macrophages, macrophage polarization, and ALI/ARDS. RESULTS: In this review, we discuss the origin, polarization, and polarization regulation of macrophages as well as the role of macrophage polarization in various stages of ARDS. According to the current literature, regulating the polarized state of macrophages might be a potential therapeutic strategy against ALI/ARDS.
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Lesión Pulmonar Aguda/etiología , Macrófagos/fisiología , Síndrome de Dificultad Respiratoria/etiología , Polaridad Celular , Humanos , Proteínas Quinasas JNK Activadas por Mitógenos/fisiología , FN-kappa B/fisiología , Transducción de Señal/fisiología , Factor de Crecimiento Transformador beta/fisiologíaRESUMEN
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common and potentially lethal clinical syndromes characterized by acute respiratory failure resulting from excessive pulmonary inflammation, noncardiogenic pulmonary edema, and alveolar-capillary barrier disruption. At present, there is no effective and specific therapy for ALI/ARDS. Mesenchymal stem cells (MSCs) have well-known therapeutic potential in patients with ALI/ARDS. Heme oxygenase-1 (HO-1), a cytoprotective enzyme, possesses antioxidative, anti-inflammatory, and antiapoptotic effects. Thus, a combination of MSC transplantation with HO-1 delivery may have an additional protective effect against ALI/ARDS. This study investigated the effect of HO-1-modified bone-marrow-derived MSCs (MSCs-HO-1) on lipopolysaccharide (LPS)-induced ALI and its underlying mechanisms. We established MSCs-HO-1 through lentiviral transduction. The ALI rat model was established by successive LPS inhalations following injection with MSCs-HO-1. The survival rate, histological changes in the lungs, total protein concentration and neutrophil counts in bronchoalveolar lavage fluid, lung wet/dry weight ratio, cytokine levels in serum and lungs, nuclear transcription factor-κB activity, and protein expression of Toll-like receptor 4 signaling adaptors were examined. Furthermore, the cell viability, apoptosis, and paracrine activity of MSCs-HO-1 were examined under inflammatory stimuli in vitro. MSCs-HO-1 injection improved these parameters compared with primary unmodified MSCs. Moreover, MSCs-HO-1 had superior prosurvival and antiapoptotic properties and enhanced paracrine functions in vitro. Therefore, MSCs-HO-1 exert an enhanced protective effect to alleviate LPS-induced ALI in rats, and the mechanisms may be partially associated with superior prosurvival, antiapoptosis, and enhanced paracrine functions of MSCs-HO-1. These findings provide a novel insight into MSC-based therapeutic strategies for treating ALI/ARDS.
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Lesión Pulmonar Aguda/prevención & control , Terapia Genética , Hemo Oxigenasa (Desciclizante)/biosíntesis , Pulmón/enzimología , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/enzimología , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/enzimología , Lesión Pulmonar Aguda/genética , Animales , Apoptosis , Células Cultivadas , Modelos Animales de Enfermedad , Factor 7 de Crecimiento de Fibroblastos/metabolismo , Hemo Oxigenasa (Desciclizante)/genética , Factor de Crecimiento de Hepatocito/metabolismo , Mediadores de Inflamación/metabolismo , Interleucina-10/metabolismo , Lipopolisacáridos , Pulmón/patología , Comunicación Paracrina , Ratas Wistar , Transducción de SeñalRESUMEN
Caveolin-1 has been reported to play an important role in the pathogenesis of acute respiratory distress syndrome (ARDS). This study was designed to identify Caveolin-1-interacting proteins to reveal the molecular mechanisms of ARDS. Yeast two-hybrid screening was performed using Caveolin-1 as the bait, and Axin-1 was identified as a binding partner for Caveolin-1. Co-immunoprecipitation demonstrated that the binding domains were located in the N-terminal region (1-100 aa) of Caveolin-1 and the C-terminal region (710-797 aa) of Axin-1. Caveolin-1 gene knockout or Axin-1 knockdown significantly decreased the levels of TNF-α and IL-6 in the supernatants of alveolar type I (AT-I) epithelial cells treated with LPS. Disrupting the interaction between Caveolin-1 and Axin-1 using CRISPR/Cas9 technology led to a significant increase in TNF-α and IL-6 from AT-I cells, along with a significant reduction in ß-catenin expression. In conclusion, Axin-1 functions as an adaptor of Caveolin-1 and affects the production of inflammatory cytokines in AT-I cells challenged with LPS via ß-catenin-mediated negative regulation.
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Proteína Axina/inmunología , Caveolina 1/inmunología , Inflamación/inmunología , Lipopolisacáridos/inmunología , Animales , Células Cultivadas , Masculino , Ratones , Ratones Endogámicos C57BL , Mapas de Interacción de Proteínas , Alveolos Pulmonares/citología , Alveolos Pulmonares/inmunologíaRESUMEN
BACKGROUND/AIMS: Bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation has therapeutic effects on endothelial damage during acute lung injury (ALI). Heme oxygenase-1 (HO-1) can restore homeostasis and implement cytoprotective defense functions in many pathologic states. Therefore, we explored whether transduction of HO-1 into BM-MSCs (MSCs-HO-1) would have an increased beneficial effect on lipopolysaccharide (LPS)-induced inflammatory and oxidative damage in human pulmonary microvascular endothelial cells (PVECs). METHODS: MSCs were isolated from rat bone marrow and transfected with the HO-1 gene by a lentivirus vector. The phenotype and multilineage differentiation of MSCs were assessed. MSCs or MSCs-HO-1 were co-cultured with PVECs using a transwell system, and LPS was added to induce PVEC injury. The production of reactive oxygen species (ROS), and the activities of lipid peroxide (LPO), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in PVECs were determined by flow cytometry and colorimetric assays, respectively. The levels of human PVEC-derived tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß and IL-6 in the supernatants of the co-culture system, and the activity of nuclear transcription factor-κB and NF-E2-related factor 2 (Nrf2) in PVECs were examined by enzyme-linked immunosorbent assay (ELISA). The mRNA expression of TNF-α, IL-1ß and IL-6 in PVECs was detected by quantitative real-time polymerase chain reaction (qRT-PCR), HO-1 expression and enzymatic activity in PVECs and the influence of zinc protoporphyrin (ZnPP) or HO-1 small interfering RNA on the above inflammatory and oxidative stress markers were evaluated. In addition, the expression of rat MSC-derived hepatocyte growth factor (HGF) and IL-10 was determined by ELISA and qRT-PCR. RESULTS: MSCs showed no significant changes in phenotype or multilineage differentiation after transduction. LPS strongly increased the production of inflammatory and oxidative stress indicators, as well as decreased the levels of antioxidant components and the activity of Nrf2 in PVECs. MSC co-cultivation ameliorated these detrimental effects in PVECs and MSCs-HO-1 further improved the damage to PVECs induced by LPS when compared with MSCs alone. The beneficial effects of MSCs-HO-1 were dependent on HO-1 overexpression and may be attributed to the enhanced paracrine production of HGF and IL-10. CONCLUSION: MSCs-HO-1 have an enhanced ability to improve LPS-induced inflammatory and oxidative damage in PVECs, and the mechanism may be partially associated with the enhanced paracrine function of the stem cells. These data encourage further testing of the beneficial effects of MSCs-HO-1 in ALI animal models.
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Hemo-Oxigenasa 1/metabolismo , Lipopolisacáridos/toxicidad , Estrés Oxidativo/efectos de los fármacos , Animales , Diferenciación Celular , Supervivencia Celular , Citocinas/análisis , Citocinas/metabolismo , Células Endoteliales/citología , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Hemo-Oxigenasa 1/antagonistas & inhibidores , Hemo-Oxigenasa 1/genética , Humanos , Inflamación/prevención & control , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/metabolismo , Comunicación Paracrina , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismoRESUMEN
OBJECTIVE: To investigate the effect of irradiated human lung fibroblasts (HLFs) on the canonical Wnt/ß-catenin signaling pathway in human umbilical cord mesenchymal stem cells (HUMSCs). METHODS: HUMSCs were cultured alone (single group) or co-cultured with HLFs exposed to 5Gy X-rays (co-culture group). The protein levels of GSK-3ß, p-GSK-3ß, FRAT1 and ß-catenin in HUMSCs were examined by Western blotting 3 days after culture or co-culture. WISP-1 protein levels in conditioned medium were examined by ELISA. RESULTS: The levels of p-GSK3ß/GSK3ß (0.15 ± 0.05), FRAT1 (0.48 ± 0.07) and ß-catenin (0.50 ± 0.07) in co-cultured HUMSCs significantly decreased compared to those in single group (0.55 ± 0.05, 1.16 ± 0.13 and 2.39 ± 0.15, all P<0.05). The supernatant level of WISP-1 in co-culture group was significantly decreased [(602.23 ± 161.47) ng/mL], compared to the single group [(977.77 ± 110.56) ng/mL, P<0.05]. CONCLUSION: Irradiated HLFs attenuate the activation of canonical Wnt/ß-catenin signaling pathway in HUMSCs in vitro.
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Fibroblastos/citología , Células Madre Mesenquimatosas/metabolismo , Vía de Señalización Wnt , Proteínas Adaptadoras Transductoras de Señales , Proteínas CCN de Señalización Intercelular/metabolismo , Células Cultivadas , Técnicas de Cocultivo , Fibroblastos/efectos de la radiación , Rayos gamma , Glucógeno Sintasa Quinasa 3/metabolismo , Glucógeno Sintasa Quinasa 3 beta , Humanos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Cordón Umbilical/citología , Rayos X , beta Catenina/metabolismoRESUMEN
Channelrhodospin-2 (ChR2), a light-sensitive ion channel, and its variants have emerged as new excitatory optogenetic tools not only in neuroscience, but also in other areas, including cardiac electrophysiology. An accurate quantitative model of ChR2 is necessary for in silico prediction of the response to optical stimulation in realistic tissue/organ settings. Such a model can guide the rational design of new ion channel functionality tailored to different cell types/tissues. Focusing on one of the most widely used ChR2 mutants (H134R) with enhanced current, we collected a comprehensive experimental data set of the response of this ion channel to different irradiances and voltages, and used these data to develop a model of ChR2 with empirically-derived voltage- and irradiance- dependence, where parameters were fine-tuned via simulated annealing optimization. This ChR2 model offers: 1) accurate inward rectification in the current-voltage response across irradiances; 2) empirically-derived voltage- and light-dependent kinetics (activation, deactivation and recovery from inactivation); and 3) accurate amplitude and morphology of the response across voltage and irradiance settings. Temperature-scaling factors (Q10) were derived and model kinetics was adjusted to physiological temperatures. Using optical action potential clamp, we experimentally validated model-predicted ChR2 behavior in guinea pig ventricular myocytes. The model was then incorporated in a variety of cardiac myocytes, including human ventricular, atrial and Purkinje cell models. We demonstrate the ability of ChR2 to trigger action potentials in human cardiomyocytes at relatively low light levels, as well as the differential response of these cells to light, with the Purkinje cells being most easily excitable and ventricular cells requiring the highest irradiance at all pulse durations. This new experimentally-validated ChR2 model will facilitate virtual experimentation in neural and cardiac optogenetics at the cell and organ level and provide guidance for the development of in vivo tools.
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Luz , Modelos Biológicos , Miocitos Cardíacos/fisiología , Channelrhodopsins , Humanos , Optogenética , Técnicas de Placa-ClampRESUMEN
Cryoablation, as a minimally invasive technology for the treatment of tumors, destroys target tumors with lethal low temperatures. It simultaneously releases a large number of tumor-specific antigens, pro-inflammatory cytokines, and nucleoproteins, known as "danger signals", activating the body's innate and adaptive immune responses. However, tumor cells can promote the inactivation of immune effector cells by reprogramming immune checkpoints, leading to the insufficiency of these antigens to induce an immune response capable of eradicating the tumor. Immune checkpoint blockers rejuvenate exhausted T cells by blocking immune checkpoints that induce programmed death of T cells, and are therefore considered a promising therapeutic strategy to enhance the immune effects of cryoablation. In this review, we provide a detailed explanation of the immunological mechanisms of cryoablation and articulate the theoretical basis and research progress of the treatment of cancer with cryoablation combined with immune checkpoint blockers. Preliminary data indicates that this combined treatment strategy exhibits good synergy and has been proven to be safe and effective.
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The long non-coding RNA (lncRNA) Small Nucleolar RNA Host Gene 4 (SNHG4) has been demonstrated to be significantly downregulated in various inflammatory conditions, yet its role in chronic obstructive pulmonary disease (COPD) remains elusive. This study aims to elucidate the biological function of SNHG4 in COPD and to unveil its potential molecular targets. Our findings reveal that both SNHG4 and Four and a Half LIM Domains 1 (FHL1) were markedly downregulated in COPD, whereas microRNA-409-3p (miR-409-3p) was upregulated. Importantly, SNHG4 exhibited a negative correlation with inflammatory markers in patients with COPD, but a positive correlation with forced expiratory volume in 1s percentage (FEV1%). SNHG4 distinguished COPD patients from non-smokers with high sensitivity, specificity, and accuracy. Overexpression of SNHG4 ameliorated cigarette smoke extract (CSE)-mediated inflammation, apoptosis, oxidative stress, and airway remodeling in 16HBE bronchial epithelial cells. These beneficial effects of SNHG4 overexpression were reversed by the overexpression of miR-409-3p or the silencing of FHL1. Mechanistically, SNHG4 competitively bound to miR-409-3p, mediating the expression of FHL1, and consequently improving inflammation, apoptosis, oxidative stress, and airway remodeling in 16HBE cells. Additionally, SNHG4 regulated the miR-409-3p/FHL1 axis to inhibit the activation of the mitogen-activated protein kinase (MAPK) pathway induced by CSE. In a murine model of COPD, knockdown of SNHG4 exacerbated CSE-induced pulmonary inflammation, apoptosis, and oxidative stress. In summary, our data affirm that SNHG4 mitigates pulmonary inflammation, apoptosis, and oxidative damage mediated by COPD through the regulation of the miR-409-3p/FHL1 axis.
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Remodelación de las Vías Aéreas (Respiratorias) , Apoptosis , Proliferación Celular , MicroARNs , Enfermedad Pulmonar Obstructiva Crónica , ARN Largo no Codificante , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Apoptosis/genética , Remodelación de las Vías Aéreas (Respiratorias)/genética , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/patología , Proliferación Celular/genética , Animales , Ratones , Masculino , Sistema de Señalización de MAP Quinasas/genética , Células Epiteliales Alveolares/metabolismo , Células Epiteliales Alveolares/patología , Inflamación/metabolismo , Inflamación/genética , Femenino , Proteínas con Dominio LIM/genética , Proteínas con Dominio LIM/metabolismo , Persona de Mediana Edad , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: Acute lung injury (ALI) involves severe lung damage and respiratory failure, which are accompanied by alveolar macrophage (AM) activation. The aim of this article is to verify the influence of paralemmin-3 (PALM3) on alveolar macrophage (AM) polarization in ALI and the underlying mechanism of action. METHODS: An ALI rat model was established by successive lipopolysaccharide (LPS) inhalations. The influence of PALM3 on the survival rate, severity of lung injury, and macrophage polarization was analyzed. Furthermore, we explored the underlying mechanism of PALM3 in regulating macrophage polarization. RESULTS: PALM3 overexpression increased mortality of ALI rats, augmented lung pathological damage, and promoted AM polarization toward M1 cells. Conversely, PALM3 knockdown had the opposite effects. Mechanistically, PALM3 might promote M1 polarization by acting as an adaptor to facilitate transduction of Notch signaling. CONCLUSION: PALM3 aggravates lung injury and induces macrophage polarization toward M1 cells by activating the Notch signaling pathway in LPS-induced ALI, which may shed light on ALI/ARDS treatments.
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Lesión Pulmonar Aguda , Lipopolisacáridos , Animales , Ratas , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/metabolismo , Lipopolisacáridos/toxicidad , Lipopolisacáridos/metabolismo , Pulmón/metabolismo , Macrófagos , Transducción de SeñalRESUMEN
Acute respiratory distress syndrome (ARDS), a progressive status of acute lung injury (ALI), is primarily caused by an immune-mediated inflammatory disorder, which can be an acute pulmonary complication of rheumatoid arthritis (RA). As a chronic inflammatory disease regulated by the immune system, RA is closely associated with the occurrence and progression of respiratory diseases. However, it remains elusive whether there are shared genes between the molecular mechanisms underlying RA and ARDS. The objective of this study is to identify potential shared genes for further clinical drug discovery through integrated analysis of bulk RNA sequencing datasets obtained from the Gene Expression Omnibus database, employing differentially expressed genes (DEGs) analysis and weighted gene co-expression network analysis (WGCNA). The hub genes were identified through the intersection of common DEGs and WGCNA-derived genes. The Random Forest (RF) and least absolute shrinkage and selection operator (LASSO) algorithms were subsequently employed to identify key shared target genes associated with two diseases. Additionally, RA immune infiltration analysis and COVID-19 single-cell transcriptome analysis revealed the correlation between these key genes and immune cells. A total of 59 shared genes were identified from the intersection of DEGs and gene clusters obtained through WGCNA, which analyzed the integrated gene matrix of ALI/ARDS and RA. The RF and LASSO algorithms were employed to screen for target genes specific to ALI/ARDS and RA, respectively. The final set of overlapping genes (FCMR, ADAM28, HK3, GRB10, UBE2J1, HPSE, DDX24, BATF, and CST7) all exhibited a strong predictive effect with an area under the curve (AUC) value greater than 0.8. Then, the immune infiltration analysis revealed a strong correlation between UBE2J1 and plasma cells in RA. Furthermore, scRNA-seq analysis demonstrated differential expression of these nine target genes primarily in T cells and NK cells, with CST7 showing a significant positive correlation specifically with NK cells. Beyond that, transcriptome sequencing was conducted on lung tissue collected from ALI mice, confirming the substantial differential expression of FCMR, HK3, UBE2J1, and BATF. This study provides unprecedented evidence linking the pathophysiological mechanisms of ALI/ARDS and RA to immune regulation, which offers novel understanding for future clinical treatment and experimental research.
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Background: Antenatal cardiovascular disease is a major cause of maternal morbidity and mortality. Severe rheumatic mitral stenosis is especially poorly tolerated during pregnancy. Case Summary: We present a young woman with severe pulmonary hypertension secondary to rheumatic mitral stenosis. She presented at 25 weeks 4 days gestation for evaluation of a pregnancy complicated by placenta accreta spectrum disorder. Invasive hemodynamic testing was carried out to delineate her hemodynamics, and a multidisciplinary cardio-obstetrics team collaborated closely with the patient and her partner to create a management plan. Ultimately, the patient was initiated on veno-arterial extracorporeal membrane oxygenation and underwent caesarean section delivery followed by hysterectomy and subsequent valve replacement surgery. Discussion: This case describes the treatment options considered to balance the risk of decompensation in the setting of severe pulmonary hypertension with hemorrhage associated with placenta accreta spectrum disorder. It highlights the importance of a multidisciplinary, team-based approach to the management of high-risk cardiac conditions throughout pregnancy.
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OBJECTIVE: Neoadjuvant chemotherapy (NACT) is one kind of treatment for advanced stage ovarian cancer patients. However, due to the nature of tumor heterogeneity, the clinical outcomes to NACT vary significantly among different subgroups. Partial responses to NACT may lead to suboptimal debulking surgery, which will result in adverse prognosis. To address this clinical challenge, the purpose of this study is to develop a novel image marker to achieve high accuracy prognosis prediction of NACT at an early stage. METHODS: For this purpose, we first computed a total of 1373 radiomics features to quantify the tumor characteristics, which can be grouped into three categories: geometric, intensity, and texture features. Second, all these features were optimized by principal component analysis algorithm to generate a compact and informative feature cluster. This cluster was used as input for developing and optimizing support vector machine (SVM) based classifiers, which indicated the likelihood of receiving suboptimal cytoreduction after the NACT treatment. Two different kernels for SVM algorithm were explored and compared. A total of 42 ovarian cancer cases were retrospectively collected to validate the scheme. A nested leave-one-out cross-validation framework was adopted for model performance assessment. RESULTS: The results demonstrated that the model with a Gaussian radial basis function kernel SVM yielded an AUC (area under the ROC [receiver characteristic operation] curve) of 0.806 ± 0.078. Meanwhile, this model achieved overall accuracy (ACC) of 83.3%, positive predictive value (PPV) of 81.8%, and negative predictive value (NPV) of 83.9%. CONCLUSION: This study provides meaningful information for the development of radiomics based image markers in NACT treatment outcome prediction.
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Terapia Neoadyuvante , Neoplasias Ováricas , Humanos , Femenino , Estudios Retrospectivos , Neoplasias Ováricas/diagnóstico por imagen , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/cirugía , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Carcinoma Epitelial de Ovario/cirugía , Valor Predictivo de las PruebasRESUMEN
Cryoablation is a therapeutic modality for lung adenocarcinoma that destroys target tumors using lethal levels of cold, resulting in the release of large amounts of specific antigens that activate immune responses. However, tumor immune checkpoint escape mechanisms prevent these released self-antigens from inducing effective anti-tumor immune responses. To overcome this challenge, we propose the use of immune checkpoint inhibitors to relieve T cell inhibition by immune checkpoints and enhance the anti-tumor immune response mediated by cryoablation. We used bilateral tumor-bearing mouse models and a specific cryoablation instrument to study the efficacy of cryoablation combined with PD-1 inhibitors in Lewis lung adenocarcinoma model mice. We found that cryoablation combined with PD-1 inhibitors significantly inhibited the growth of mouse lung adenocarcinoma, prolonged mouse survival, and enhanced the anti-tumor immune response. Moreover, this combined regimen could synergistically promote the activation and proliferation of T cells via the PI3K/AKT/mTOR pathway. The present study provides a strong theoretical basis for the clinical combination of cryoablation and PD-1 inhibitors.
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Carcinoma Pulmonar de Lewis , Criocirugía , Inhibidores de Puntos de Control Inmunológico , Neoplasias Pulmonares , Fosfatidilinositol 3-Quinasas , Receptor de Muerte Celular Programada 1 , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Serina-Treonina Quinasas TOR , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Criocirugía/métodos , Ratones , Carcinoma Pulmonar de Lewis/inmunología , Carcinoma Pulmonar de Lewis/patología , Carcinoma Pulmonar de Lewis/tratamiento farmacológico , Serina-Treonina Quinasas TOR/metabolismo , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Fosfatidilinositol 3-Quinasas/metabolismo , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/inmunología , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Transducción de Señal/efectos de los fármacos , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Ratones Endogámicos C57BL , Línea Celular Tumoral , Terapia Combinada , Linfocitos T/inmunología , Linfocitos T/efectos de los fármacos , Linfocitos T/metabolismo , Femenino , Adenocarcinoma del Pulmón/inmunología , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/cirugíaRESUMEN
BACKGROUND: Developing computer aided diagnosis (CAD) schemes of mammograms to classify between malignant and benign breast lesions has attracted a lot of research attention over the last several decades. However, unlike radiologists who make diagnostic decisions based on the fusion of image features extracted from multi-view mammograms, most CAD schemes are single-view-based schemes, which limit CAD performance and clinical utility. PURPOSE: This study aims to develop and test a novel CAD framework that optimally fuses information extracted from ipsilateral views of bilateral mammograms using both deep transfer learning (DTL) and radiomics feature extraction methods. METHODS: An image dataset containing 353 benign and 611 malignant cases is assembled. Each case contains four images: the craniocaudal (CC) and mediolateral oblique (MLO) view of the left and right breast. First, we extract four matching regions of interest (ROIs) from images that surround centers of two suspicious lesion regions seen in CC and MLO views, as well as matching ROIs in the contralateral breasts. Next, the handcrafted radiomics (HCRs) features and VGG16 model-generated automated features are extracted from each ROI resulting in eight feature vectors. Then, after reducing feature dimensionality and quantifying the bilateral and ipsilateral asymmetry of four ROIs to yield four new feature vectors, we test four fusion methods to build three support vector machine (SVM) classifiers by an optimal fusion of asymmetrical image features extracted from four view images. RESULTS: Using a 10-fold cross-validation method, results show that a SVM classifier trained using an optimal fusion of four view images yields the highest classification performance (AUC = 0.876 ± 0.031), which significantly outperforms SVM classifiers trained using one projection view alone, AUC = 0.817 ± 0.026 and 0.792 ± 0.026 for the CC and MLO view of bilateral mammograms, respectively (p < 0.001). CONCLUSIONS: The study demonstrates that the shift from single-view CAD to four-view CAD and the inclusion of both DTL and radiomics features significantly increases CAD performance in distinguishing between malignant and benign breast lesions.
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Algoritmos , Aprendizaje Profundo , Mamografía/métodos , Diagnóstico por ComputadorRESUMEN
This study aims to develop a high throughput Fourier ptychographic microscopy (FPM) technique based on symmetric illumination and a color detector, which is able to accelerate image acquisition by up to 12 times. As an emerging technology, the efficiency of FPM is limited by its data acquisition process, especially for color microscope image reconstruction. To overcome this, we built an FPM prototype equipped with a color camera and a 4×/0.13 NA objective lens. During the image acquisition, two symmetric LEDs illuminate the sample simultaneously using white light, which doubles the light intensity and reduces the total captured raw patterns by half. A standard USAF 1951 resolution target was used to measure the system's modulation transfer function (MTF) curve, and the H&E-stained ovarian cancer samples were then imaged to assess the feature qualities depicted on the reconstructed images. The results showed that the measured MTF curves of red, green, and blue channels are generally comparable to the corresponding curves generated by conventional FPM, while symmetric illumination FPM preserves more tissue details, which is superior to the results captured by conventional 20×/0.4 NA objective lens. This investigation initially verified the feasibility of symmetric illumination based color FPM.
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Iluminación , Microscopía , Microscopía/métodos , Análisis de Fourier , Procesamiento de Imagen Asistido por Computador/métodos , LuzRESUMEN
OBJECTIVE: Neoadjuvant chemotherapy (NACT) is one kind of treatment for advanced stage ovarian cancer patients. However, due to the nature of tumor heterogeneity, the patients' responses to NACT varies significantly among different subgroups. To address this clinical challenge, the purpose of this study is to develop a novel image marker to achieve high accuracy response prediction of the NACT at an early stage. METHODS: For this purpose, we first computed a total of 1373 radiomics features to quantify the tumor characteristics, which can be grouped into three categories: geometric, intensity, and texture features. Second, all these features were optimized by principal component analysis algorithm to generate a compact and informative feature cluster. Using this cluster as the input, an SVM based classifier was developed and optimized to create a final marker, indicating the likelihood of the patient being responsive to the NACT treatment. To validate this scheme, a total of 42 ovarian cancer patients were retrospectively collected. A nested leave-one-out cross-validation was adopted for model performance assessment. RESULTS: The results demonstrate that the new method yielded an AUC (area under the ROC [receiver characteristic operation] curve) of 0.745. Meanwhile, the model achieved overall accuracy of 76.2%, positive predictive value of 70%, and negative predictive value of 78.1%. CONCLUSION: This study provides meaningful information for the development of radiomics based image markers in NACT response prediction.
RESUMEN
Background and Objective: 2D and 3D tumor features are widely used in a variety of medical image analysis tasks. However, for chemotherapy response prediction, the effectiveness between different kinds of 2D and 3D features are not comprehensively assessed, especially in ovarian-cancer-related applications. This investigation aims to accomplish such a comprehensive evaluation. Methods: For this purpose, CT images were collected retrospectively from 188 advanced-stage ovarian cancer patients. All the metastatic tumors that occurred in each patient were segmented and then processed by a set of six filters. Next, three categories of features, namely geometric, density, and texture features, were calculated from both the filtered results and the original segmented tumors, generating a total of 1403 and 1595 features for the 2D and 3D tumors, respectively. In addition to the conventional single-slice 2D and full-volume 3D tumor features, we also computed the incomplete-3D tumor features, which were achieved by sequentially adding one individual CT slice and calculating the corresponding features. Support vector machine (SVM)-based prediction models were developed and optimized for each feature set. Five-fold cross-validation was used to assess the performance of each individual model. Results: The results show that the 2D feature-based model achieved an AUC (area under the ROC curve (receiver operating characteristic)) of 0.84 ± 0.02. When adding more slices, the AUC first increased to reach the maximum and then gradually decreased to 0.86 ± 0.02. The maximum AUC was yielded when adding two adjacent slices, with a value of 0.91 ± 0.01. Conclusions: This initial result provides meaningful information for optimizing machine learning-based decision-making support tools in the future.