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2.
Commun Biol ; 7(1): 442, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600349

RESUMO

Aryl hydrocarbon receptor (AHR) signalling integrates biological processes that sense and respond to environmental, dietary, and metabolic challenges to ensure tissue homeostasis. AHR is a transcription factor that is inactive in the cytosol but upon encounter with ligand translocates to the nucleus and drives the expression of AHR targets, including genes of the cytochrome P4501 family of enzymes such as Cyp1a1. To dynamically visualise AHR activity in vivo, we generated reporter mice in which firefly luciferase (Fluc) was non-disruptively targeted into the endogenous Cyp1a1 locus. Exposure of these animals to FICZ, 3-MC or to dietary I3C induced strong bioluminescence signal and Cyp1a1 expression in many organs including liver, lung and intestine. Longitudinal studies revealed that AHR activity was surprisingly long-lived in the lung, with sustained Cyp1a1 expression evident in discrete populations of cells including columnar epithelia around bronchioles. Our data link diet to lung physiology and also reveal the power of bespoke Cyp1a1-Fluc reporters to longitudinally monitor AHR activity in vivo.


Assuntos
Citocromo P-450 CYP1A1 , Receptores de Hidrocarboneto Arílico , Camundongos , Animais , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Luciferases/genética , Fígado/metabolismo , Pulmão/metabolismo
3.
Respir Res ; 25(1): 160, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600524

RESUMO

BACKGROUND: No effective therapies for pulmonary fibrosis (PF) exist because of the unclear molecular pathogenesis and the lack of effective therapeutic targets. Zinc finger protein 451 (ZNF451), a transcriptional regulator, plays crucial roles in the pathogenesis of several diseases. However, its expression pattern and function in PF remain unknown. This study was designed to investigate the role of ZNF451 in the pathogenesis of lung fibrosis. METHODS: GEO dataset analysis, RT‒PCR, and immunoblot assays were used to examine the expression of ZNF451 in PF; ZNF451 knockout mice and ZNF451-overexpressing lentivirus were used to determine the importance of ZNF451 in PF progression; and migration assays, immunofluorescence staining, and RNA-seq analysis were used for mechanistic studies. RESULTS: ZNF451 is downregulated and negatively associated with disease severity in PF. Compared with wild-type (WT) mice, ZNF451 knockout mice exhibited much more serious PF changes. However, ZNF451 overexpression protects mice from BLM-induced pulmonary fibrosis. Mechanistically, ZNF451 downregulation triggers fibroblast activation by increasing the expression of PDGFB and subsequently activating PI3K/Akt signaling. CONCLUSION: These findings uncover a critical role of ZNF451 in PF progression and introduce a novel regulatory mechanism of ZNF451 in fibroblast activation. Our study suggests that ZNF451 serves as a potential therapeutic target for PF and that strategies aimed at increasing ZNF451 expression may be promising therapeutic approaches for PF.


Assuntos
Fibrose Pulmonar , Animais , Camundongos , Bleomicina/toxicidade , Fibroblastos/metabolismo , Pulmão/metabolismo , Camundongos Knockout , Fosfatidilinositol 3-Quinases/metabolismo , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/genética , Fibrose Pulmonar/metabolismo , Transdução de Sinais
4.
J Cardiothorac Surg ; 19(1): 200, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600565

RESUMO

INTRODUCTION: The 8th edition lung cancer staging system was the first to describe the detailed diagnosis and staging of multiple primary lung cancers (MPLC). However, the characteristics and prognosis of MPLC categorized according to the new system have not been evaluated. METHOD: We retrospectively analyzed data from surgically treated MPLC patients in a single center from 2011 to 2013 and explored the characteristics and outcomes of different MPLC disease patterns. RESULTS: In total, 202 surgically treated MPLC patients were identified and classified into different groups according to disease categories and diagnostic time (multifocal ground glass/lepidic (GG/L) nodules: n = 139, second primary lung cancer (SPLC): n = 63, simultaneous MPLC (sMPLC): n = 171, and metachronous MPLC (mMPLC): n = 31). There were significant differences in clinical characteristics between SPLC and GG/L nodule patients and simultaneous and metachronous MPLC patients. The overall 1-, 3-, and 5-year lung cancer-specific survival rates of MPLC were 97.98%, 90.18%, and 82.81%, respectively. Five-year survival was better in patients with multiple GG/L nodules than in those with SPLC (87.94% vs. 71.29%, P < 0.05). Sex was an independent prognostic factor for sMPLC (5-year survival, female vs. male, 88.0% vs. 69.5%, P < 0.05), and in multiple tumors, the highest tumor stage was an independent prognostic factor for all categories of MPLC. CONCLUSIONS: The different disease patterns of MPLC have significantly different characteristics and prognoses. Clinicians should place treatment emphasis on the tumor with the highest stage as it is the main contributor to the prognosis of all categories of MPLC patients.


Assuntos
Neoplasias Pulmonares , Neoplasias Primárias Múltiplas , Segunda Neoplasia Primária , Humanos , Masculino , Feminino , Estadiamento de Neoplasias , Estudos Retrospectivos , Prognóstico , Segunda Neoplasia Primária/patologia , Neoplasias Primárias Múltiplas/patologia , Pulmão/patologia
5.
Respir Res ; 25(1): 159, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600600

RESUMO

BACKGROUND: Light chain deposition disease (LCDD) is a very rare entity. Clinical manifestations of LCDD vary according to the organs involved. Data on pulmonary LCDD are scarce and limited to small series or case reports. This study aimed to describe the characteristics and outcome of diffuse pulmonary non-amyloid LCDD localized to the lungs. STUDY DESIGN AND METHODS: A multicenter retrospective cohort study was conducted. Clinical characteristics were collected, and chest CTs were centrally reviewed. The diagnosis of pulmonary non-amyloid LCDD was confirmed by immunohistochemistry. RESULTS: Thirty-one cases were identified (68% female), with a median age at diagnosis of 50 years (IQR 20). Baseline FEV1/FVC was < 0.70 in 45% of patients. Mean (± SD) FEV1 and DLCO were 86% ± 26.2 and 52% ± 23.9, respectively. CT revealed peculiar patterns of thin-walled cysts (58%) and thin-walled cystic bronchiectases (27%). Increased serum kappa light chain was found in 87% of patients. Histological analysis showed kappa light chain deposits in all patients, except one with lambda chain deposits. Median annual FEV1 decline was 127 ml (IQR 178) and median DLCO decline was 4.3% (IQR 4.3). Sixteen patients received immunomodulatory treatment or chemotherapy; serum light chain levels decreased in 9 cases (75%), without significant improvement in FEV1 (p = 0.173). Overall, 48% of patients underwent bilateral lung transplantation. Transplant-free survival at 5 and 10 years were 70% and 30%, respectively. An annual FEV1 decline greater than 127 ml/year was associated with increased risk of death or transplantation (p = 0.005). CONCLUSIONS: Diffuse pulmonary LCDD is characterised by female predominance, a peculiar imaging pattern with bronchiectasis and/or cysts, progressive airway obstruction and severe DLCO impairment, and poor outcome. Lung transplantation is a treatment of choice.


Assuntos
Bronquiectasia , Cistos , Humanos , Feminino , Adulto Jovem , Adulto , Masculino , Cadeias Leves de Imunoglobulina , Estudos Retrospectivos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Cistos/patologia , Fenótipo
6.
Zhonghua Yi Xue Za Zhi ; 104(16): 1371-1380, 2024 Apr 23.
Artigo em Chinês | MEDLINE | ID: mdl-38644287

RESUMO

Lung cancer is the second most common malignancy with the highest mortality rate worldwide. In recent years, the rapid development of various bronchoscopic navigation techniques has provided conditions for the minimally invasive diagnosis and treatment of peripheral pulmonary nodules through the airway.Augmented reality optical lung navigation is a new technology that combined virtual bronchoscopy navigation (VBN) with augmented reality (AR) and optical navigation technology, which could assist bronchoscopist and has been widely applied in clinics. The clinical evidence certified that the navigation, has the advantages of safety and efficacy in guiding transbronchial diagnosis, localization, and treatment of pulmonary nodules. In order to standardize the clinical operation of augmented reality optical lung navigation technology and guide its application in clinical practice, Interventional Group, Society of Respiratory Diseases, Chinese Medical Association/Interventional Pulmonology Group of the Zhejiang Medical Association organized multidisciplinary experts to take the lead in formulating the Consensus of experts on transbronchial diagnosis, localization and treatment of peripheral pulmonary nodules guided by the augmented reality optical lung navigation after multiple rounds of discussion, and provided recommendation opinions and clinical guidance for the indications and contraindications, equipment and devices, perioperative treatment, operating process and complication management of peripheral pulmonary nodules applicable to augmented reality optical lung diagnosis navigation technology.


Assuntos
Realidade Aumentada , Broncoscopia , Neoplasias Pulmonares , Humanos , Broncoscopia/métodos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/cirurgia , Pulmão/cirurgia , Consenso , Nódulos Pulmonares Múltiplos/diagnóstico , Nódulos Pulmonares Múltiplos/cirurgia
7.
BMJ Open Respir Res ; 11(1)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38663888

RESUMO

OBJECTIVE: This study aimed to investigate the utility of CT quantification of lung volume for predicting critical outcomes in COVID-19 patients. METHODS: This retrospective cohort study included 1200 hospitalised patients with COVID-19 from 4 hospitals. Lung fields were extracted using artificial intelligence-based segmentation, and the percentage of the predicted (%pred) total lung volume (TLC (%pred)) was calculated. The incidence of critical outcomes and posthospitalisation complications was compared between patients with low and high CT lung volumes classified based on the median percentage of predicted TLCct (n=600 for each). Prognostic factors for residual lung volume loss were investigated in 208 patients with COVID-19 via a follow-up CT after 3 months. RESULTS: The incidence of critical outcomes was higher in the low TLCct (%pred) group than in the high TLCct (%pred) group (14.2% vs 3.3%, p<0.0001). Multivariable analysis of previously reported factors (age, sex, body mass index and comorbidities) demonstrated that CT-derived lung volume was significantly associated with critical outcomes. The low TLCct (%pred) group exhibited a higher incidence of bacterial infection, heart failure, thromboembolism, liver dysfunction and renal dysfunction than the high TLCct (%pred) group. TLCct (%pred) at 3 months was similarly divided into two groups at the median (71.8%). Among patients with follow-up CT scans, lung volumes showed a recovery trend from the time of admission to 3 months but remained lower in critical cases at 3 months. CONCLUSION: Lower CT lung volume was associated with critical outcomes, posthospitalisation complications and slower improvement of clinical conditions in COVID-19 patients.


Assuntos
COVID-19 , Medidas de Volume Pulmonar , Pulmão , SARS-CoV-2 , Tomografia Computadorizada por Raios X , Humanos , COVID-19/diagnóstico por imagem , COVID-19/epidemiologia , Masculino , Feminino , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Japão/epidemiologia , Medidas de Volume Pulmonar/métodos , Pulmão/diagnóstico por imagem , Prognóstico , Estudos de Coortes , Idoso de 80 Anos ou mais
8.
BMJ Case Rep ; 17(4)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38663900

RESUMO

A pulmonary venous aneurysm (PVA) is extremely rare. A PVA can be either congenital or acquired. Possible symptoms include thoracic pain, dyspnoea, haemoptysis and palpitations but can also occur asymptomatically. Treatment can be conservative or surgical depending on growth and risk of rupture or development of mitral insufficiency, symptoms and thrombus formation. Only a few cases have been described in the literature. A recent case study and a literature review are described below.


Assuntos
Veias Pulmonares , Humanos , Veias Pulmonares/anormalidades , Veias Pulmonares/diagnóstico por imagem , Aneurisma/diagnóstico por imagem , Aneurisma/diagnóstico , Aneurisma/complicações , Masculino , Tomografia Computadorizada por Raios X , Pulmão/diagnóstico por imagem , Pulmão/patologia , Feminino
9.
Clin Respir J ; 18(4): e13742, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38664220

RESUMO

BACKGROUND: Allergic asthma is an important respiratory system problem characterized by airway inflammation, breathlessness, and bronchoconstriction. Allergic asthma and its outcomes are triggered by type 2 allergic immune responses. Tectorigenin is a methoxy-isoflavone with anti-inflammatory effects. In this study, we investigated the effects of tectorigenin on the pathophysiology of allergic asthma in an animal model. METHODS: Asthmatic mice were treated with tectorigenin. Then airway hyperresponsiveness (AHR), eosinophil percentage, levels of interleukin (IL)-33, IL-25, IL-13, IL-5, IL-4, total and ovalbumin (OVA)-specific immunoglobulin (Ig)E, and lung histopathology were evaluated. RESULT: Tectorigenin significantly (P 〈 0.05) reduced eosinophil infiltration (41 ± 7%) in the broncho-alveolar lavage fluid (BALF), serum IL-5 level (41 ± 5, pg/mL), and bronchial and vascular inflammation (scores of 1.3 ± 0.2 and 1.1 ± 0.3, respectively) but had no significant effects on AHR, serum levels of IL-33, -25, -13, and -4 (403 ± 24, 56 ± 7, 154 ± 11, and 89 ± 6 pg/mL, respectively), total and OVA-specific IgE (2684 ± 265 and 264 ± 19 ng/mL, respectively), goblet cell hyperplasia, and mucus production. CONCLUSION: Tectorigenin could control inflammation and the secretion of inflammatory mediators of asthma, so it can be regarded as a potential antiasthma treatment with the ability to control eosinophilia-related problems.


Assuntos
Anti-Inflamatórios , Antioxidantes , Asma , Modelos Animais de Doenças , Isoflavonas , Camundongos Endogâmicos BALB C , Ovalbumina , Animais , Asma/tratamento farmacológico , Asma/induzido quimicamente , Asma/metabolismo , Asma/imunologia , Asma/patologia , Camundongos , Ovalbumina/toxicidade , Ovalbumina/efeitos adversos , Isoflavonas/farmacologia , Isoflavonas/uso terapêutico , Antioxidantes/farmacologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Imunoglobulina E/sangue , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Feminino , Pulmão/patologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/imunologia , Citocinas/metabolismo
10.
Nat Commun ; 15(1): 3449, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664384

RESUMO

In 2017, a novel influenza A virus (IAV) was isolated from an Egyptian fruit bat. In contrast to other bat influenza viruses, the virus was related to avian A(H9N2) viruses and was probably the result of a bird-to-bat transmission event. To determine the cross-species spill-over potential, we biologically characterize features of A/bat/Egypt/381OP/2017(H9N2). The virus has a pH inactivation profile and neuraminidase activity similar to those of human-adapted IAVs. Despite the virus having an avian virus-like preference for α2,3 sialic acid receptors, it is unable to replicate in male mallard ducks; however, it readily infects ex-vivo human respiratory cell cultures and replicates in the lungs of female mice. A/bat/Egypt/381OP/2017 replicates in the upper respiratory tract of experimentally-infected male ferrets featuring direct-contact and airborne transmission. These data suggest that the bat A(H9N2) virus has features associated with increased risk to humans without a shift to a preference for α2,6 sialic acid receptors.


Assuntos
Quirópteros , Patos , Furões , Vírus da Influenza A Subtipo H9N2 , Infecções por Orthomyxoviridae , Receptores de Superfície Celular , Animais , Quirópteros/virologia , Humanos , Furões/virologia , Feminino , Masculino , Vírus da Influenza A Subtipo H9N2/fisiologia , Vírus da Influenza A Subtipo H9N2/patogenicidade , Vírus da Influenza A Subtipo H9N2/isolamento & purificação , Infecções por Orthomyxoviridae/virologia , Infecções por Orthomyxoviridae/transmissão , Camundongos , Patos/virologia , Replicação Viral , Influenza Humana/virologia , Influenza Humana/transmissão , Pulmão/virologia , Influenza Aviária/virologia , Influenza Aviária/transmissão , Neuraminidase/metabolismo
11.
Nat Commun ; 15(1): 3450, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664395

RESUMO

Influenza A viruses (IAVs) of subtype H9N2 have reached an endemic stage in poultry farms in the Middle East and Asia. As a result, human infections with avian H9N2 viruses have been increasingly reported. In 2017, an H9N2 virus was isolated for the first time from Egyptian fruit bats (Rousettus aegyptiacus). Phylogenetic analyses revealed that bat H9N2 is descended from a common ancestor dating back centuries ago. However, the H9 and N2 sequences appear to be genetically similar to current avian IAVs, suggesting recent reassortment events. These observations raise the question of the zoonotic potential of the mammal-adapted bat H9N2. Here, we investigate the infection and transmission potential of bat H9N2 in vitro and in vivo, the ability to overcome the antiviral activity of the human MxA protein, and the presence of N2-specific cross-reactive antibodies in human sera. We show that bat H9N2 has high replication and transmission potential in ferrets, efficiently infects human lung explant cultures, and is able to evade antiviral inhibition by MxA in transgenic B6 mice. Together with its low antigenic similarity to the N2 of seasonal human strains, bat H9N2 fulfils key criteria for pre-pandemic IAVs.


Assuntos
Quirópteros , Furões , Vírus da Influenza A Subtipo H9N2 , Infecções por Orthomyxoviridae , Replicação Viral , Animais , Furões/virologia , Vírus da Influenza A Subtipo H9N2/genética , Vírus da Influenza A Subtipo H9N2/fisiologia , Vírus da Influenza A Subtipo H9N2/patogenicidade , Vírus da Influenza A Subtipo H9N2/isolamento & purificação , Quirópteros/virologia , Humanos , Infecções por Orthomyxoviridae/transmissão , Infecções por Orthomyxoviridae/virologia , Infecções por Orthomyxoviridae/imunologia , Camundongos , Filogenia , Influenza Humana/transmissão , Influenza Humana/virologia , Pulmão/virologia , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue
12.
Respir Res ; 25(1): 179, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664685

RESUMO

BACKGROUND: Prolonged weaning from mechanical ventilation is associated with poor clinical outcome. Therefore, choosing the right moment for weaning and extubation is essential. Electrical Impedance Tomography (EIT) is a promising innovative lung monitoring technique, but its role in supporting weaning decisions is yet uncertain. We aimed to evaluate physiological trends during a T-piece spontaneous breathing trail (SBT) as measured with EIT and the relation between EIT parameters and SBT success or failure. METHODS: This is an observational study in which twenty-four adult patients receiving mechanical ventilation performed an SBT. EIT monitoring was performed around the SBT. Multiple EIT parameters including the end-expiratory lung impedance (EELI), delta Tidal Impedance (ΔZ), Global Inhomogeneity index (GI), Rapid Shallow Breathing Index (RSBIEIT), Respiratory Rate (RREIT) and Minute Ventilation (MVEIT) were computed on a breath-by-breath basis from stable tidal breathing periods. RESULTS: EELI values dropped after the start of the SBT (p < 0.001) and did not recover to baseline after restarting mechanical ventilation. The ΔZ dropped (p < 0.001) but restored to baseline within seconds after restarting mechanical ventilation. Five patients failed the SBT, the GI (p = 0.01) and transcutaneous CO2 (p < 0.001) values significantly increased during the SBT in patients who failed the SBT compared to patients with a successful SBT. CONCLUSION: EIT has the potential to assess changes in ventilation distribution and quantify the inhomogeneity of the lungs during the SBT. High lung inhomogeneity was found during SBT failure. Insight into physiological trends for the individual patient can be obtained with EIT during weaning from mechanical ventilation, but its role in predicting weaning failure requires further study.


Assuntos
Impedância Elétrica , Tomografia , Desmame do Respirador , Humanos , Desmame do Respirador/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Tomografia/métodos , Monitorização Fisiológica/métodos , Adulto , Respiração Artificial/métodos , Respiração , Idoso de 80 Anos ou mais , Pulmão/fisiopatologia , Pulmão/diagnóstico por imagem , Pulmão/fisiologia
13.
Hum Exp Toxicol ; 43: 9603271241249990, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38664950

RESUMO

The disruption of the immune system by viral attack is a major influencing factor in the lethality of COVID-19. Baicalein is one of the key effective compounds against COVID-19. The molecular mechanisms regarding the anti-inflammatory properties of Baicalein are still unclear. In this study, we established LPS-induced mice to elucidate the role of Baicalein in the treatment of acute lung injury (ALI) and its potential molecular mechanisms. In vivo experiments showed that Baicalein could significantly ameliorate LPS-induced acute lung injury and reduce proteinous edema in lung tissue. In addition, Baicalein inhibited M1 macrophage polarization, promote M2 macrophage polarization, and regulate inflammatory responses. Furthermore, Baicalein could inhibit the expression of protein molecules associated with pyroptosis and mitigate the lung tissue injury. In summary, we revealed the therapeutic effects of Baicalein in acute lung injury, providing the theoretical basis for its clinical application.


Assuntos
Lesão Pulmonar Aguda , Flavanonas , Lipopolissacarídeos , Macrófagos , Piroptose , Flavanonas/farmacologia , Flavanonas/uso terapêutico , Animais , Piroptose/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Camundongos , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Camundongos Endogâmicos C57BL , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Modelos Animais de Doenças , Pneumonia/tratamento farmacológico , Pneumonia/induzido quimicamente , Pulmão/efeitos dos fármacos , Pulmão/patologia , Tratamento Farmacológico da COVID-19 , COVID-19/imunologia
14.
Discov Med ; 36(183): 816-826, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38665029

RESUMO

BACKGROUND: Pneumonia is a prevalent respiratory ailment involving complex physiological and pathological mechanisms. The tripartite motif containing 27 (TRIM27) plays a crucial role in regulating inflammation mechanisms. Therefore, the purpose of this study is to further explore the therapeutic potential of TRIM27 in pneumonia, based on its regulatory mechanisms in inflammation and autophagy. METHODS: This study established a mouse pneumonia animal model through lipopolysaccharide (LPS) administration, designating it as the LPS model group. Subsequently, adenovirus-mediated TRIM27 overexpression was implemented in the animals of the LPS model group, creating the TRIM27 treatment group. After a 7-day treatment period, lung tissues from the mice were collected. Various techniques, including immunohistochemistry, quantitative reverse transcription PCR (RT-qPCR), western blot, enzyme-linked immunosorbent assay (ELISA), and electron microscopy were utilized to analyze the impact of TRIM27 overexpression on inflammatory factors, oxidative stress, autophagy, and inflammatory processes in pulmonary tissues. Finally, an in vitro LPS cell model was established, and the effects of TRIM27 overexpression and autophagy inhibition on inflammatory cytokines and autophagosomes in LPS-induced inflammatory cells were examined through RT-qPCR and immunofluorescence techniques. RESULTS: The research findings demonstrate a significant reduction in the elevated levels of interleukin-6 (IL-6), IL-1ß, and Tumor necrosis factor-alpha (TNF-α) induced by LPS with TRIM27 overexpression (p < 0.01). Conversely, the autophagy inhibitor 3-Methyladenine (3-MA) diminished the effects induced by TRIM27 overexpression. Moreover, TRIM27 overexpression enhanced the expression of Microtubule-associated protein 1A/1B light chain 3 (LC3) II/I and Beclin-1 proteins in mice subjected to LPS stimulation (p < 0.01), while reducing the expression of the p62 protein (p < 0.01). The addition of 3-MA, however, decreased Beclin-1 expression and inhibited autophagy (p < 0.01). Additionally, TRIM27 overexpression decreased the expression of NOD-like receptor thermal protein domain associated protein 3 (NLRP3), cleaved caspase-1, IL-1ß, and Gasdermin D N-terminal fragment (GSDMD-N) proteins in LPS-stimulated mice (p < 0.05). TRIM27 overexpression also decreased the levels of malondialdehyde (MDA), Activating Transcription Factor 6 (ATF6), and C/EBP-homologous protein (CHOP), while increasing the levels of superoxide dismutase (SOD) and glutathione (GSH) in mice exposed to LPS (p < 0.01). CONCLUSION: The induction of TRIM27 overexpression emerges as a potential and effective pneumonia treatment. The underlying mechanism may involve inducing protective autophagy, thereby reducing oxidative stress and cell pyroptosis.


Assuntos
Adenina/análogos & derivados , Autofagia , Proteínas de Ligação a DNA , Modelos Animais de Doenças , Lipopolissacarídeos , Pneumonia , Proteínas com Motivo Tripartido , Ubiquitina-Proteína Ligases , Animais , Autofagia/efeitos dos fármacos , Autofagia/genética , Camundongos , Pneumonia/patologia , Pneumonia/metabolismo , Lipopolissacarídeos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Pulmão/patologia , Pulmão/metabolismo , Adenina/farmacologia , Masculino , Camundongos Endogâmicos C57BL , Proteína Beclina-1/metabolismo , Proteína Beclina-1/genética
15.
BMC Pulm Med ; 24(1): 188, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38641768

RESUMO

BACKGROUND: Dyspnea impairs quality of life (QOL) in patients with fibrotic hypersensitivity pneumonitis (FHP). The Living with Pulmonary Fibrosis questionnaire (L-PF) assesses symptoms, their impacts and PF-related QOL in patients with any form of PF. Its scores have not undergone validation analyses in an FHP cohort. METHODS: We used data from the Pirfenidone in FHP trial to examine reliability, validity and responsiveness of the L-PF-35 Dyspnea domain score (Dyspnea) and to estimate its meaningful within-patient change (MWPC) threshold for worsening. Lack of suitable anchors precluded conducting analyses for other L-PF-35 scores. RESULTS: At baseline, Dyspnea's internal consistency (Cronbach's coefficient alpha) was 0.85; there were significant correlations with all four anchors (University of California San Diego Shortness of Breath Questionnaire scores r = 0.81, St. George's Activity domain score r = 0.82, percent predicted forced vital capacity r = 0.37, and percent predicted diffusing capacity of the lung for carbon monoxide r = 0.37). Dyspnea was significantly different between anchor subgroups (e.g., lowest percent predicted forced vital capacity (FVC%) vs. highest, 33.5 ± 18.5 vs. 11.1 ± 9.8, p = 0.01). There were significant correlations between changes in Dyspnea and changes in anchor scores at all trial time points. Longitudinal models further confirmed responsiveness. The MWPC threshold estimate for worsening was 6.6 points (range 5-8). CONCLUSION: The L-PF-35 Dyspnea domain appears to possess acceptable psychometric properties for assessing dyspnea in patients with FHP. Because instrument validation is never accomplished with one study, additional research is needed to build on the foundation these analyses provide. TRIAL REGISTRATION: The data for the analyses presented in this manuscript were generated in a trial registered on ClinicalTrials.gov; the identifier was NCT02958917.


Assuntos
Alveolite Alérgica Extrínseca , Qualidade de Vida , Humanos , Reprodutibilidade dos Testes , Pulmão , Dispneia/etiologia , Dispneia/diagnóstico , Inquéritos e Questionários , Alveolite Alérgica Extrínseca/complicações , Alveolite Alérgica Extrínseca/tratamento farmacológico
16.
BMC Vet Res ; 20(1): 145, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38641793

RESUMO

BACKGROUND: Human records describe pulmonary edema as a life-threatening complication of electric shock. Successful management requires prompt recognition and intensive care. However, in companion animals, electrocutions are rarely reported, even though domestic environments are full of electrical devices and there is always the possibility of accidental injury. Therefore, it is important for veterinarians to know more about this condition in order to achieve successful patient outcomes. CASE PRESENTATION: A 3-month-old male Labrador Retriever was presented with a history of transient loss of consciousness after chewing on a household electrical cord. On admission, the puppy showed an orthopneic position with moderate respiratory distress. Supplemental oxygen via nasal catheter was provided, but the patient showed marked worsening of respiratory status. Point-of-care ultrasound exams suggested neurogenic pulmonary edema due to electrical shock close to the central nervous system and increased B-lines without evidence of cardiac abnormalities. Mechanical ventilation of the patient was initiated using volume-controlled mode with a tidal volume of 9 to 15 ml/kg until reaching an end-tidal carbon dioxide ≤ 40 mm Hg, followed by a stepwise lung-recruitment maneuver in pressure-controlled mode with increases of the peak inspiratory pressure (15 to 20 cm H2O) and positive end-expiratory pressure (3 to 10 cm H2O) for 30 min, and return to volume-controlled mode with a tidal volume of 15 ml/kg until reaching a peripheral oxygen saturation ≥ 96%. Weaning from the ventilator was achieved in six hours, and the patient was discharged two days after admission without neurological or respiratory deficits. CONCLUSIONS: We present a rather unusual case of a neurogenic pulmonary edema subsequent to accidental electrocution in a dog. Timely diagnosis by ultrasound and mechanical ventilation settings are described. Our case highlights that pulmonary edema should be considered a potentially life-threatening complication of electrical shock in small animal emergency and critical care medicine.


Assuntos
Doenças do Cão , Traumatismos por Eletricidade , Edema Pulmonar , Síndrome do Desconforto Respiratório , Humanos , Cães , Masculino , Animais , Edema Pulmonar/etiologia , Edema Pulmonar/terapia , Edema Pulmonar/veterinária , Síndrome do Desconforto Respiratório/veterinária , Pulmão , Respiração Artificial/veterinária , Traumatismos por Eletricidade/complicações , Traumatismos por Eletricidade/terapia , Traumatismos por Eletricidade/veterinária , Doenças do Cão/etiologia , Doenças do Cão/terapia
17.
BMC Infect Dis ; 24(1): 414, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38641804

RESUMO

BACKGROUND: Lobar pneumonia caused by Mycoplasma pneumoniae is a relatively difficult-to-treat pneumonia in children. The time of radiographic resolution after treatment is variable, a long recovery time can result in several negative effects, and it has attracted our attention. Therefore, exploring factors associated with delayed radiographic resolution will help to identify these children at an early stage and prepare for early intervention. METHODS: The data of 339 children with lobar pneumonia caused by Mycoplasma pneumoniae were collected from the Department of Pediatrics of Fu Yang People's Hospital, China from January 2021 to June 2022. After discharge, the children were regularly followed up in the outpatient department and on the WeChat platform for > 8 weeks. According to whether pulmonary imaging (chest radiography or plain chest computed tomography) returned to normal within 8 weeks, the children were divided into the delayed recovery group (DRG) (n = 69) and the normal recovery group (NRG) (n = 270). The children's general information, laboratory examination findings, bronchoscopy results, and imaging findings were retrospectively analyzed. Single-factor analysis was performed to identify the risk factors for delayed radiographic resolution of lobar pneumonia caused by Mycoplasma pneumoniae, and the factors with statistically significant differences underwent multiple-factor logistic regression analysis. Receiver operating characteristic (ROC) analysis was then performed to calculate the cutoff value of early predictive indicators of delayed radiographic resolution. RESULTS: Single-factor analysis showed that the following were significantly greater in the DRG than NRG: total fever duration, the hospitalization time, C-reactive protein (CRP) level, lactate dehydrogenase (LDH) level, D-dimer level, pulmonary lesions involving two or more lobes, a large amount of pleural effusion, the time to interventional bronchoscopy, and mucus plugs formation. Multivariate logistic regression analysis showed that the hospitalization time, CRP level, LDH level, pulmonary lesions involving two or more lobes, and a large amount of pleural effusion were independent risk factors for delayed radiographic resolution of lobar pneumonia caused by Mycoplasma pneumoniae. The cutoff values on the receiver operating characteristic curve were a hospitalization time of ≥ 10.5 days, CRP level of ≥ 25.92 mg/L, and LDH level of ≥ 378 U/L. CONCLUSION: If patients with lobar pneumonia caused by Mycoplasma pneumoniae have a hospitalization time of ≥ 10.5 days, CRP level of ≥ 25.92 mg/L, and LDH level ≥ 378 U/L, the time of radiographic resolution is highly likely to exceed 8 weeks. Pediatricians must maintain a high level of vigilance for these factors, control the infection as early as possible, strengthen airway management, and follow up closely to avoid complications and sequelae of Mycoplasma pneumoniae pneumonia.


Assuntos
Derrame Pleural , Pneumonia por Mycoplasma , Pneumonia Pneumocócica , Criança , Humanos , Mycoplasma pneumoniae , Estudos Retrospectivos , Pneumonia por Mycoplasma/complicações , Pulmão/diagnóstico por imagem , Pulmão/patologia , Pneumonia Pneumocócica/patologia , Derrame Pleural/complicações
18.
BMC Geriatr ; 24(1): 354, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38643091

RESUMO

AIM: Diagnosing and classifying heart failure (HF) in the oldest-old patients has technical and interpretation issues, especially in the acute setting. We assessed the usefulness of both N-terminal pro-brain natriuretic peptide (NT-proBNP) and lung ultrasound (LUS) for confirming HF diagnosis and predicting, among hospitalized HF patients, those with reduced ejection fraction (HFrEF). METHODS: We performed a cross-sectional study on 148 consecutive patients aged ≥ 80 years admitted to our Internal Medicine and Geriatrics ward with at least one symptom/sign compatible with HF and NT-proBNP ≥ 125 pg/mL. We measured serum NT-proBNP levels and performed LUS and transthoracic echocardiography (TTE) on admission before diuretic therapy. We divided our cohort into three subgroups according to the left ventricular ejection fraction (LVEF): reduced (LVEF ≤ 40%), mildly-reduced (LVEF = 41-49%) and preserved (LVEF ≥ 50%). RESULTS: The mean age was 88±5 years. Male prevalence was 42%. Patients with HFrEF were 19%. Clinical features and laboratory parameters did not differ between the three subgroups, except for higher NT-proBNP in HFrEF patients, which also had a higher number of total B-lines and intercostal spaces of pleural effusion at LUS. Overall, NT-proBNP showed an inverse correlation with LVEF (r = -0.22, p = 0.007) and a direct correlation with age, total pulmonary B-lines, and intercostal spaces of pleural effusion. According to the ROCs, NT-proBNP levels, pulmonary B-lines and pleural effusion extension were poorly predictive for HFrEF. The best-performing cut-offs were 9531 pg/mL for NT-proBNP (SP 0.70, SE 0.50), 13 for total B-lines (SP 0.69, SE 0.85) and one intercostal space for pleural effusion (SP 0.55, SE 0.89). Patients with admission NT-proBNP ≥ 9531 pg/mL had a 2-fold higher risk for HFrEF (OR 2.5, 95% CI 1.3-4.9), while we did not find any association for total B-lines ≥ 13 or pleural effusion ≥ 1 intercostal space with HFrEF. A significant association with HFrEF emerged for the combination of NT-proBNP ≥ 9531 pg/mL, total B-lines ≥ 13 and intercostal spaces of pleural effusion ≥ 1 (adjusted OR 4.3, 95% CI 1.5-12.9). CONCLUSIONS: Although NT-proBNP and LUS help diagnose HF, their accuracy in discriminating HFrEF from non-HFrEF was poor in our real-life clinical study on oldest-old hospitalized patients, making the use of TTE still necessary to distinguish HF phenotypes in this peculiar setting. These data require confirmation in more extensive and longer prospective studies.


Assuntos
Insuficiência Cardíaca , Derrame Pleural , Humanos , Masculino , Idoso de 80 Anos ou mais , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/epidemiologia , Peptídeo Natriurético Encefálico , Volume Sistólico , Estudos Transversais , Estudos Prospectivos , Função Ventricular Esquerda , Biomarcadores , Fragmentos de Peptídeos , Pulmão/diagnóstico por imagem
19.
J Cardiothorac Surg ; 19(1): 253, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38643197

RESUMO

OBJECTIVE: Chest drainage is a standard procedure in thoracoscopic surgery for lung cancer. However, chest tube placement may deteriorate the ventilation capacity and increase difficulty of postoperative management of patients. The study investigated on the effects of enhanced recovery after surgery (ERAS) program focusing on chest tube management on surgical recovery of lung cancer patients. METHODS: The study population consisted of 60 patients undergoing video-assisted thoracoscopic surgery (VATS) after implementation of ERAS program and another group of 60 patients undergoing VATS before implementation of ERAS program. RESULTS: The mean time of first food intake was 12.9 h required for the ERAS group, which was significantly shorter than 18.4 h required for the control group (p < 0.0001). The mean time of out-of-bed activity was 14.2 h taken for the ERAS group, which was notably shorter than 22.8 h taken for the control group (p < 0.0001). The duration of chest tube placement was 68.6 h in the ERAS group, which was remarkably shorter than 92.8 h in the control group (p < 0.0001). The rate overall postoperative complications were notably lower in the ERAS group than in the control group (p = 0.018). The visual analogue score (VAS) scores on the second postoperative day exhibited significant differences between the ERAS group and the control group (p = 0.017). The patients in the ERAS group had a shorter hospitalization stay than those in the control group (p < 0.0001). CONCLUSION: The study suggests the ERAS program focusing on chest tube management could improve surgical recovery, remove patient chest tube earlier, and relieve patient pain after VATS.


Assuntos
Recuperação Pós-Cirúrgica Melhorada , Neoplasias Pulmonares , Humanos , Tubos Torácicos , Cirurgia Torácica Vídeoassistida/métodos , Neoplasias Pulmonares/cirurgia , Pulmão , Tempo de Internação , Estudos Retrospectivos
20.
PLoS One ; 19(4): e0299495, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38635535

RESUMO

This study evaluated the effect of 24-week Taichi training and Taichi plus resistance band training on pulmonary diffusion capacity and glycemic control in patients with Type 2 diabetes mellitus (T2DM). Forty-eight patients with T2DM were randomly divided into three groups: Group A-Taichi training: practiced Taichi 60 min/day, 6 days/week for 24 weeks; Group B-Taichi plus resistance band training: practiced 60-min Taichi 4 days/week plus 60-min resistance band training 2 days/week for 24 weeks; and Group C-controls: maintaining their daily lifestyles. Stepwise multiple regression analysis was applied to predict diffusion capacity of the lungs for carbon monoxide (DLCO) by fasting blood glucose, insulin, glycosylated hemoglobin (HbA1c), tumour necrosis factor alpha (TNF-α), von Willebrand Factor (vWF), interleukin-6 (IL-6), intercellular adhesion molecule 1 (ICAM-1), endothelial nitric oxide synthase (eNOS), nitric oxide (NO), endothelin-1 (ET-1), vascular endothelial growth factor, and prostaglandin I-2. Taichi with or without resistance band training significantly improved DLCO, increased insulin sensitivity, eNOS and NO, and reduced fasting blood glucose, insulin, HbA1c, TNF-α, vWF, IL-6, ICAM-1, and ET-1. There was no change in any of these variables in the control group. DLCO was significantly predicted (R2 = 0.82) by insulin sensitivity (standard-ß = 0.415, P<0.001), eNOS (standard-ß = 0.128, P = 0.017), TNF-α (standard-ß = -0.259, P = 0.001), vWF (standard-ß = -0.201, P = 0.007), and IL-6 (standard-ß = -0.175, P = 0.032) in patients with T2DM. The impact of insulin sensitivity was the most important predictor for the variation of DLCO based on the multiple regression modeling. This study demonstrates that 24-week Taichi training and Taichi plus resistance band training effectively improve pulmonary diffusion capacity and blood glycemic control in patients with T2DM. Variation of DLCO is explained by improved insulin sensitivity and endothelial function, and reduced inflammatory markers, including TNF-α, vWF, and IL-6.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Humanos , Molécula 1 de Adesão Intercelular , Glicemia/metabolismo , Hemoglobinas Glicadas , Interleucina-6 , Fator de Necrose Tumoral alfa , Controle Glicêmico , Fator de von Willebrand , Fator A de Crescimento do Endotélio Vascular , Insulina , Pulmão/metabolismo
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