RESUMO
Tumor endothelial marker 1 (TEM1), an activated mesenchymal cell marker, is implicated in tissue remodeling and repair. Herein, we investigated the role and therapeutic implications of TEM1 in abdominal aortic aneurysm (AAA), a potentially life-threatening aortic disease characterized by vascular inflammation and matrix turnover. Characterization of human AAA revealed increased TEM1 expression derived mainly from medial vascular smooth muscle cells (VSMCs) and adventitial fibroblasts. Bioinformatics analysis demonstrated the association between TEM1-expressing VSMCs and fibroblasts and collagen gene expression. Consistently, collagen content and TEM1 expressed by VSMCs and fibroblasts were increased during CaCl2-induced AAA formation in mice. TEM1 silencing in VSMCs and fibroblasts inhibited transforming growth factor-ß1-induced phenotypic change, SMAD2 phosphorylation, and COL1A1 gene expression. Also, Tem1 deficiency reduced collagen synthesis and exacerbated CaCl2-induced AAA formation in mice without disturbing elastin destruction and inflammatory responses. In contrast, rTEM1 promoted phenotypic change and COL1A1 gene expression through SMAD2 phosphorylation in VSMCs and fibroblasts. Treatment with rTEM1 enhanced collagen synthesis, attenuated elastin fragmentation, and inhibited CaCl2-induced and angiotensin II-infused AAA formation. In summary, TEM1 in resident stromal cells regulates collagen synthesis to counteract aortic wall failure during AAA formation. Matrix integrity restored by rTEM1 treatment may hold therapeutic potential against AAA.
Assuntos
Aneurisma da Aorta Abdominal , Animais , Humanos , Masculino , Camundongos , Aneurisma da Aorta Abdominal/metabolismo , Fibroblastos/metabolismo , Camundongos Endogâmicos C57BL , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Proteína Smad2/metabolismoRESUMO
BACKGROUND: Low-dose computed tomography (LDCT) has been shown useful in early lung cancer detection. This study aimed to develop a novel deep learning model for detecting pulmonary nodules on chest LDCT images. METHODS: In this secondary analysis, three lung nodule datasets, including Lung Nodule Analysis 2016 (LUNA16), Lung Nodule Received Operation (LNOP), and Lung Nodule in Health Examination (LNHE), were used to train and test deep learning models. The 3D region proposal network (RPN) was modified via a series of pruning experiments for better predictive performance. The performance of each modified deep leaning model was evaluated based on sensitivity and competition performance metric (CPM). Furthermore, the performance of the modified 3D RPN trained on three datasets was evaluated by 10-fold cross validation. Temporal validation was conducted to assess the reliability of the modified 3D RPN for detecting lung nodules. RESULTS: The results of pruning experiments indicated that the modified 3D RPN composed of the Cross Stage Partial Network (CSPNet) approach to Residual Network (ResNet) Xt (CSP-ResNeXt) module, feature pyramid network (FPN), nearest anchor method, and post-processing masking, had the optimal predictive performance with a CPM of 92.2%. The modified 3D RPN trained on the LUNA16 dataset had the highest CPM (90.1%), followed by the LNOP dataset (CPM: 74.1%) and the LNHE dataset (CPM: 70.2%). When the modified 3D RPN trained and tested on the same datasets, the sensitivities were 94.6%, 84.8%, and 79.7% for LUNA16, LNOP, and LNHE, respectively. The temporal validation analysis revealed that the modified 3D RPN tested on LNOP test set achieved a CPM of 71.6% and a sensitivity of 85.7%, and the modified 3D RPN tested on LNHE test set had a CPM of 71.7% and a sensitivity of 83.5%. CONCLUSION: A modified 3D RPN for detecting lung nodules on LDCT scans was designed and validated, which may serve as a computer-aided diagnosis system to facilitate lung nodule detection and lung cancer diagnosis.
A modified 3D RPN for detecting lung nodules on CT images that exhibited greater sensitivity and CPM than did several previously reported CAD detection models was established.
Assuntos
Neoplasias Pulmonares , Nódulo Pulmonar Solitário , Humanos , Nódulo Pulmonar Solitário/diagnóstico por imagem , Reprodutibilidade dos Testes , Imageamento Tridimensional/métodos , Pulmão , Tomografia Computadorizada por Raios X/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodosRESUMO
OBJECTIVE: To investigate the correlation between body temperature and skin surface temperature in intensive care unit patients and to identify specific indicators of skin surface temperature for early fever detection. RESEARCH METHODOLOGY/DESIGN: This pilot study was a prospective, observational investigation conducted at National Cheng Kung University Hospital in Tainan, Taiwan. A total of 54 patients admitted to the Surgical Intensive Care Unit of a tertiary hospital between April and August 2020 were included. Patients utilized the wearable device HEARThremoTM to continuously monitor skin surface temperature and heart rate. Analysis of Variance was applied to identify the association of skin surface temperature with different body temperature groups. The comparison between skin surface temperature and fever over eight time intervals was studied using a generalized estimating equation. RESULTS: In 34 patients (63 %) with a fever (≥38 °C), skin surface temperature increased (P < 0.001) when body temperature increased. The maximum skin surface temperature was significantly associated with fever 180-210 min before the fever events occurred (OR: 2.22, 95 % CI: 1.30-3.80). The mean skin surface temperature was associated with fever 120-150 min before the fever events (OR: 8.70, 95 % CI: 2.08-36.36). CONCLUSIONS: Skin surface temperature can be an important early predictive sign before the onset of fever. Continuous temperature monitoring can detect fever early and initiate treatment in advance. This study serves as a preliminary exploration in this area, laying the groundwork for future comprehensive research. IMPLICATIONS FOR CLINICAL PRACTICE: Continuous monitoring of skin surface temperature empowers nurses to swiftly detect fever, transcending conventional methods. This proactive approach allows for the early identification of physiological abnormalities, facilitating the prompt initiation of further physical assessments and relevant examinations for early treatment commencement.
Assuntos
Febre , Unidades de Terapia Intensiva , Temperatura Cutânea , Humanos , Projetos Piloto , Masculino , Feminino , Estudos Prospectivos , Febre/fisiopatologia , Febre/diagnóstico , Febre/etiologia , Pessoa de Meia-Idade , Temperatura Cutânea/fisiologia , Idoso , Taiwan , Unidades de Terapia Intensiva/organização & administração , Adulto , Monitorização Fisiológica/métodos , Monitorização Fisiológica/instrumentação , Temperatura Corporal/fisiologiaRESUMO
BACKGROUND: Pathologic scars, including keloids and hypertrophic scars, represent a common form of exaggerated cutaneous scarring that is difficult to prevent or treat effectively. Additionally, the pathobiology of pathologic scars remains poorly understood. We aim at investigating the impact of TEM1 (also known as endosialin or CD248), which is a glycosylated type I transmembrane protein, on development of pathologic scars. METHODS: To investigate the expression of TEM1, we utilized immunofluorescence staining, Western blotting, and single-cell RNA-sequencing (scRNA-seq) techniques. We conducted in vitro cell culture experiments and an in vivo stretch-induced scar mouse model to study the involvement of TEM1 in TGF-ß-mediated responses in pathologic scars. RESULTS: The levels of the protein TEM1 are elevated in both hypertrophic scars and keloids in comparison to normal skin. A re-analysis of scRNA-seq datasets reveals that a major profibrotic subpopulation of keloid and hypertrophic scar fibroblasts greatly expresses TEM1, with expression increasing during fibroblast activation. TEM1 promotes activation, proliferation, and ECM production in human dermal fibroblasts by enhancing TGF-ß1 signaling through binding with and stabilizing TGF-ß receptors. Global deletion of Tem1 markedly reduces the amount of ECM synthesis and inflammation in a scar in a mouse model of stretch-induced pathologic scarring. The intralesional administration of ontuxizumab, a humanized IgG monoclonal antibody targeting TEM1, significantly decreased both the size and collagen density of keloids. CONCLUSIONS: Our data indicate that TEM1 plays a role in pathologic scarring, with its synergistic effect on the TGF-ß signaling contributing to dermal fibroblast activation. Targeting TEM1 may represent a novel therapeutic approach in reducing the morbidity of pathologic scars.
Assuntos
Cicatriz Hipertrófica , Queloide , Fator de Crescimento Transformador beta , Animais , Humanos , Camundongos , Antígenos CD , Antígenos de Neoplasias , Cicatriz Hipertrófica/metabolismo , Fibroblastos , Queloide/metabolismo , PeleRESUMO
OBJECTIVES: This systematic review and Bayesian network meta-analysis evaluated the efficacy and safety of hydrocortisone combined with fludrocortisone or hydrocortisone alone, compared with placebo in adult patients with septic shock. DATA SOURCES: By extending a prior Cochrane review, databases, including PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov , along with other relevant websites, were searched until August 31, 2023. STUDY SELECTION: Randomized controlled trials (RCTs) and observational studies using target trial emulation were included. DATA EXTRACTION: The primary outcome was short-term mortality with an emphasis on 28- or 30-day mortality as the main measure and in-hospital or ICU mortality as the nearest surrogate of this measure. Three of the most common adverse events, namely, gastroduodenal bleeding, superinfection, and hyperglycemia, were also considered. DATA SYNTHESIS: A total of 19 studies involving 95,841 patients were included. Hydrocortisone plus fludrocortisone showed the lowest short-term mortality versus placebo (odds ratio [OR]: 0.79; 95% credible interval [CrI], 0.64-0.99; number needed to treat [NNT]: 21, range: 12-500; low certainty of evidence) in terms of informative priors. The surface under the cumulative ranking curve values for hydrocortisone plus fludrocortisone, hydrocortisone alone, and placebo were 0.9469, 0.4542, and 0.0989, respectively. Consistent results were observed in RCTs alone and those using a daily 200-mg dose of hydrocortisone. Although gastroduodenal bleeding or superinfection showed no clear increase, hyperglycemia risk increased. The ORs were 0.53 for placebo versus hydrocortisone plus fludrocortisone and 0.64 for placebo versus hydrocortisone alone, with very low certainty of evidence. CONCLUSIONS: In adults with septic shock, hydrocortisone plus fludrocortisone improved short-term survival with minimal adverse events compared with hydrocortisone alone or placebo. However, these findings are not definitive due to the limited certainty of evidence and wide NNT range. Additional large-scale, placebo-controlled RCTs are needed to provide conclusive evidence.