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Little is known about the relationships between human genetics and the airway microbiome. Deeply sequenced airway metagenomics, by simultaneously characterizing the microbiome and host genetics, provide a unique opportunity to assess the microbiome-host genetic associations. Here we performed a co-profiling of microbiome and host genetics with the identification of over 5 million single nucleotide polymorphisms (SNPs) through deep metagenomic sequencing in sputum of 99 chronic obstructive pulmonary disease (COPD) and 36 healthy individuals. Host genetic variation was the most significant factor associated with the microbiome except for geography and disease status, with its top 5 principal components accounting for 12.11% of the microbiome variability. Within COPD individuals, 113 SNPs mapped to candidate genes reported as genetically associated with COPD exhibited associations with 29 microbial species and 48 functional modules (P < 1 × 10-5), where Streptococcus salivarius exhibits the strongest association to SNP rs6917641 in TBC1D32 (P = 9.54 × 10-8). Integration of concurrent host transcriptomic data identified correlations between the expression of host genes and their genetically-linked microbiome features, including NUDT1, MAD1L1 and Veillonella parvula, TTLL9 and Stenotrophomonas maltophilia, and LTA4H and Haemophilus influenzae. Mendelian randomization analyses revealed a potential causal link between PARK7 expression and microbial type III secretion system, and a genetically-mediated association between COPD and increased relative abundance of airway Streptococcus intermedius. These results suggest a previously underappreciated role of host genetics in shaping the airway microbiome and provide fresh hypotheses for genetic-based host-microbiome interactions in COPD.
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Microbiota , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Microbiota/genética , Esputo , Transcriptoma , Genética Humana , Proteínas Adaptadoras Transductoras de Señales/genéticaRESUMEN
This randomized controlled trial aimed to determine whether lung ultrasound-guided fluid resuscitation improves the clinical outcomes of neonates with septic shock. Seventy-two patients were randomly assigned to undergo treatment with lung ultrasound-guided fluid resuscitation (LUGFR), or with usual fluid resuscitation (Control) in the first 6 h since the start of the sepsis treatment. The primary study outcome was 14-day mortality after randomization. Fourteen-day mortalities in the two groups were not significantly different (LUGFR group, 13.89%; control group, 16.67%; p = 0.76; hazard ratio 0.81 [95% CI 0.27-2.50]). The LUGFR group experienced shorter length of neonatal intensive care unit (NICU) stays (21 vs. 26 days, p = 0.04) and hospital stays (32 vs. 39 days, p = 0.01), and less fluid was used in the first 6 h (77 vs. 106 mL/kg, p = 0.02). Further, our study found that ultrasound-guided fluid resuscitation can significantly reduce the incidence of acute kidney injury (25% vs. 47.2%, p = 0.05) and intracranial hemorrhage (grades I-II) within 72 h (13.9% vs. 36.1%, p = 0.03). However, no significant difference was found in the resolution of shock within 1 h or 6 h, use of mechanical ventilation or vasopressor support, time to achieve lactate level < 2 mmol/L, and the number of participants developing hepatomegaly in the first 6 h. CONCLUSION: Lung ultrasound is a noninvasive and convenient tool for predicting fluid overload in neonatal septic shock. Fluid resuscitation guided by lung ultrasound can shorten the length of hospital and NICU stays, reduce the amount of fluid used in the first 6 h, and reduce the risk of acute kidney injury and intracranial hemorrhage. TRIAL REGISTRATION: Registered in Guangdong Second Provincial General Hospital: 2021-IIT-156-EK, date of registration: November 13, 2021. And ClinicalTrials.gov: NCT06144463 (retrospectively registered). WHAT IS KNOWN: ⢠Excessive fluid resuscitation in neonates with septic shock had worse outcomes. WHAT IS NEW: ⢠Lung ultrasound should be routinely used to guide fluid resuscitation in neonatal septic shock.
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Lesión Renal Aguda , Choque Séptico , Recién Nacido , Humanos , Choque Séptico/terapia , Fluidoterapia , Resucitación , Pulmón/diagnóstico por imagen , Hemorragias Intracraneales , Ultrasonografía IntervencionalRESUMEN
Introductionï¼Exacerbations of chronic obstructive pulmonary disease (COPD) have a significant impact on hospitalizations, morbidity, and mortality of patients. This study aimed to develop a model for predicting acute exacerbation in COPD patient (AECOPD) based on deep learning (DL) features. METHODS: We performed a retrospective study on 219 patients with COPD who underwent inspiratory and expiratory HRCT scans. By recording the acute respiratory events of the previous year, these patients were further divided into Non-AECOPD group and AECOPD group according to the presence of acute exacerbation events. 69 Quantitative CT (QCT) parameters of emphysema and airway were calculated by NeuLungCARE software and 2000 DL features were extracted by VGG-16 method. The Logistic regression method was employed to identify AECOPD patients and 29 patients of external validation cohort were used to access the robustness of the results. RESULTS: The Model 3-B achieved an AUC of 0.933, and 0.865 in the testing cohort and external validation cohort respectively. Model 3-I obtained AUC of 0.895 in the testing cohort and AUC of 0.774 in the external validation cohort. Model 7-B combined clinical characteristics, QCT parameters, and DL features achieved the best performance with an AUC of 0.979 in the testing cohort and demonstrating robust predictability with an AUC of 0.932 in the external validation cohort. Likewise, Model 7-I achieving an AUC of 0.938, and 0.872 in the testing cohort and external validation cohort respectively. CONCLUSIONS: DL features extracted from HRCT scans can effectively predict acute exacerbation phenotype in COPD patients.
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BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a prevalent and debilitating respiratory condition that imposes a significant healthcare burden worldwide. Accurate staging of COPD severity is crucial for patient management and treatment planning. METHODS: The retrospective study included 530 hospital patients. A lobe-based radiomics method was proposed to classify COPD severity using computed tomography (CT) images. First, we segmented the lung lobes with a convolutional neural network model. Secondly, the radiomic features of each lung lobe are extracted from CT images, the features of the five lung lobes are merged, and the selection of features is accomplished through the utilization of a variance threshold, t-Test, least absolute shrinkage and selection operator (LASSO). Finally, the COPD severity was classified by a support vector machine (SVM) classifier. RESULTS: 104 features were selected for staging COPD according to the Global initiative for chronic Obstructive Lung Disease (GOLD). The SVM classifier showed remarkable performance with an accuracy of 0.63. Moreover, an additional set of 132 features were selected to distinguish between milder (GOLD I + GOLD II) and more severe instances (GOLD III + GOLD IV) of COPD. The accuracy for SVM stood at 0.87. CONCLUSIONS: The proposed method proved that the novel lobe-based radiomics method can significantly contribute to the refinement of COPD severity staging. By combining radiomic features from each lung lobe, it can obtain a more comprehensive and rich set of features and better capture the CT radiomic features of the lung than simply observing the lung as a whole.
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Enfermedad Pulmonar Obstructiva Crónica , Índice de Severidad de la Enfermedad , Máquina de Vectores de Soporte , Tomografía Computarizada por Rayos X , Humanos , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico por imagen , Enfermedad Pulmonar Obstructiva Crónica/clasificación , Tomografía Computarizada por Rayos X/métodos , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Pulmón/diagnóstico por imagen , Pulmón/patología , Redes Neurales de la Computación , RadiómicaRESUMEN
RATIONALE: Chronic obstructive pulmonary disease (COPD) is a complicated chronic inflammatory disease. It is important to investigate the characteristics of acute exacerbation of COPD to develop new therapeutic strategies. OBJECTIVE: This study aimed to determine the relationship between the human beta-defensin-2 (hBD-2) levels and aggravation of COPD. METHODS: We detected the sputum hBD-2 level of 254 patients from Guangzhou, China, for 2 years. The study participants were categorized into the COPD group (n = 203, GOLD 0-4) and the control group (n = 51, 40-79 years old). At baseline, 12th month, and 24th month, we detected the sputum hBD-2 level and levels of cytokines, such as CXCL10, CXCL11, and IFN. RESULTS: At baseline, there were no significant differences in the sputum and serum hBD-2 levels between the patients and the controls. However, the sputum hBD-2 levels of patients who had at least one symptom aggravation over the next 2 years were significantly lower than those of patients without any exacerbations (1130.9 ± 858.4 pg/mL vs. 2103.7 ± 1294.2 pg/mL, respectively; p = 0.001). Nevertheless, there were no statistically significant differences in the sputum hBD-2 levels between patients (no aggravation history) and controls (2084.9 ± 1317.6 pg/mL vs. 2152.5 ± 1251.6 pg/mL, respectively; p = 0.626). We used a logistic regression model to assess the relationship between aggravation and sputum hBD-2 levels. Interestingly, we found that low hBD-2 level (< 1000 pg/mL) was significantly associated with exacerbations. Specifically, patients with low hBD-2 levels were more likely to experience exacerbations in the next 12 months (0.333 vs. 0.117; p = 0.001). Moreover, we compared the hBD-2 levels between controls and patients with GOLD 3-4 and found that participants with bacteria (+) and/or viruses (+) had an association between hBD-2 level and disease severity (p = 0.02). CONCLUSION: Patients at risk of exacerbations are more likely to have lower sputum hBD-2 levels. These results have important implications for future therapies for COPD.
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Enfermedad Pulmonar Obstructiva Crónica , Virus , beta-Defensinas , Humanos , Adulto , Persona de Mediana Edad , Anciano , Esputo/microbiología , beta-Defensinas/uso terapéutico , CitocinasRESUMEN
Sensors have been used in various agricultural production scenarios due to significant advances in the Agricultural Internet of Things (Ag-IoT), leading to smart agriculture. Intelligent control or monitoring systems rely heavily on trustworthy sensor systems. Nonetheless, sensor failures are likely due to various factors, including key equipment malfunction or human error. A faulty sensor can produce corrupted measurements, resulting in incorrect decisions. Early detection of potential faults is crucial, and fault diagnosis techniques have been proposed. The purpose of sensor fault diagnosis is to detect faulty data in the sensor and recover or isolate the faulty sensors so that the sensor can finally provide correct data to the user. Current fault diagnosis technologies are based mainly on statistical models, artificial intelligence, deep learning, etc. The further development of fault diagnosis technology is also conducive to reducing the loss caused by sensor failures.
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In the orthodontics process, intervention and sliding of an orthodontic bracket during the orthodontic process can arise large response of the labio-cheek soft tissue. Soft tissue damage and ulcers frequently happen at the early stage of orthodontic treatment. In the field of orthodontic medicine, qualitative analysis is always carried out through statistics of clinical cases, while quantitative explanation of bio-mechanical mechanism is lacking. For this purpose, finite element analysis of a three-dimensional labio-cheek-bracket-tooth model is conducted to quantify the bracket-induced mechanical response of the labio-cheek soft tissue, which involves complex coupling of contact nonlinearity, material nonlinearity and geometric nonlinearity. Firstly, based on the biological composition characteristics of labio-cheek, a second-order Ogden model is optimally selected to describe the adipose-like material of the labio-cheek soft tissue. Secondly, according to the characteristics of oral activity, a two-stage simulation model of bracket intervention and orthogonal sliding is established, and the key contact parameters are optimally set. Finally, the two-level analysis method of overall model and submodel is used to achieve efficient solution of high-precision strains in submodels based on the displacement boundary obtained from the overall model calculation. Calculation results with four typical tooth morphologies during orthodontic treatment show that: â the maximum strain of soft tissue is distributed along the sharp edges of the bracket, consistent with the clinically observed profile of soft tissue deformation; â¡ the maximum strain of soft tissue is reduced as the teeth align, consistent with the clinical manifestation of common damage and ulcers at the beginning of orthodontic treatment and reduced patient discomfort at the end of treatment. The method in this paper can provide reference for relevant quantitative analysis studies in the field of orthodontic medical treatment at home and abroad, and further benefit to the product development analysis of new orthodontic devices.
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Ligamento Periodontal , Diente , Humanos , Ligamento Periodontal/fisiología , Alambres para Ortodoncia , Mejilla , Úlcera , Análisis de Elementos FinitosRESUMEN
Bcl-2-associated athanogene 3 (BAG3) is a cochaperone protein that interacts with Bcl-2 and mediate cell death. However, little is known about the roles of fish BAG3 during viral infection. In this study, we characterized a BAG3 homolog from orange-spotted grouper (Epinephelus coioides) (EcBAG3) and investigated its roles during viral infection. The EcBAG3 protein encoded 579 amino acids with typical WW, PXXP and BAG domains, which shared high identities with reported fish BAG3. Quantitative real-time PCR (qRT-PCR) analysis revealed that EcBAG3 was highly expressed in brain and heart. And the expression of EcBAG3 was significantly up-regulated after red-spotted grouper nervous necrosis virus (RGNNV) stimulation in vitro. EcBAG3 overexpression could promoted the expression of viral genes (coat protein (CP) and RNA-dependent RNA polymerase (RdRp)), which was enhanced by co-transfection with Hsp70 and Hsp22. Also, EcBAG3 overexpression up-regulated the expression of LC3-â ¡ and down-regulated the expression of Bax and BNIP3, the IFN- (IRF1, IRF3, IRF7, IFP35, Mx1) or inflammation-related (IL-1ß and TNFα) factors, as well as decreased the activities of NF-κB, ISRE and IFN-3. While knockdown of EcBAG3 decreased the transcripts of RGNNV CP gene and RdRp gene. Further studies showed that EcBAG3 knockdown impaired the expression level of autophagy factor LC3-â ¡, and promoted the expression level of Bax and BNIP3, inflammatory factors and interferon factors. These data indicate that EcBAG3 can affect viral infection through modulating virus-induced cell death, regulating the expression of IFN- and inflammation-related factors, which will be helpful to further explore the immune response of fish during viral infection.
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Lubina , Enfermedades de los Peces , Nodaviridae , Infecciones por Virus ARN , Virosis , Secuencia de Aminoácidos , Animales , Proteínas de Peces/química , Regulación de la Expresión Génica , Inmunidad Innata/genética , Nodaviridae/fisiología , Alineación de SecuenciaRESUMEN
BACKGROUND: Transbronchial cryobiopsy (TBCB) is increasingly being identified as a potential alternative for the diagnosis of interstitial lung disease (ILD). The specimen size of TBCB is positively related to the freezing time. However, the proper initial freezing time for the clinical application of TBCB in ILD remains unknown. METHODS: A prospective randomized parallel group study was employed to investigate ILD patients with unclear diagnosis, who were admitted to the First Affiliated Hospital of Guangzhou Medical University from May 2019 to October 2020 and required TBCB. All patients were randomly divided into 4 groups according to the different freezing times of TBCB: 3 s, 4 s, 5 s, and 6 s groups. All operations were performed under intravenous anesthesia with endotracheal intubation, 60-65 bar pressure of freezing gas source, and 1.9-mm cryoprobe. Compare differences among groups in specimen size, complications, pathological diagnosis efficiency, and multidisciplinary discussion (MDD) diagnostic efficiency. RESULTS: A total of 100 patients were recruited and randomly assigned into 4 groups (n = 25 each group). The specimen sizes of TBCB in ILD were positively correlated with the freezing time (r = 0.639, p < 0.05). None of the patients experienced Grade 3 severe bleeding. Pneumothorax occurred in 1 patient in the 4 s, 5 s, and 6 s groups, respectively. The diagnostic yield of MDD in the 3 s, 4 s, 5 s, and 6 s groups were 64%, 88%, 88%, and 96%, respectively (p < 0.05), but showing no significant differences among 4 s, 5 s, and 6 s groups. CONCLUSIONS: The specimen size and diagnostic efficiency of TBCB in ILD increased with a longer freezing time. When the freezing gas pressure is 60-65 bar, we recommended 4 s as the initial freezing time of TBCB, and this time is associated with high diagnostic efficiency and low incidence of complications.
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Broncoscopía , Enfermedades Pulmonares Intersticiales , Biopsia , Congelación , Humanos , Pulmón/patología , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/patología , Estudios ProspectivosRESUMEN
BACKGROUND: Accumulating evidence indicated the crucial role for interleukin 6 (IL-6) signaling in the development of allergic asthma. Yet, the role of IL-6 signaling in toluene diisocyanate (TDI)-induced mixed granulocytic airway inflammation still remains unclear. Thus, the aims of this study were to dissect the role of IL-6 signaling and to evaluate the effect of tocilizumab on TDI-induced steroid-resistant asthma. METHODS: TDI-induced asthma model was prepared and asthmatic mice were respectively given IL-6 monoclonal antibody, IL-6R monoclonal antibody (tocilizumab, 5 mg/kg, i.p. after each challenge) for therapeutic purposes or isotype IgG as control. RESULTS: TDI exposure just elevated IL-6R expression in the infiltrated inflammatory cells around the airway, but increased glycoprotein 130 expression in the whole lung, especially in bronchial epithelium. Moreover, TDI inhalation increased airway hyperresponsiveness (AHR) to methacholine, coupled with mixed granulocytic inflammation, exaggerated epithelial denudation, airway smooth muscle thickening, goblet cell metaplasia, extensive submucosal collagen deposition, dysregulated Th2/Th17 responses, as well as innate immune responses and raised serum IgE. And almost all these responses except for raised serum IgE were markedly ameliorated by the administration of IL-6 neutralizing antibody or tocilizumab, but exhibited poor response to systemic steroid treatment. Also, TDI challenge induced nucleocytoplasm translocation of HMGB1 and promoted its release in the BALF, as well as elevated lung level of STAT3 phosphorylation, which were inhibited by anti-IL-6 and anti-IL-6R treatment. CONCLUSIONS: Our data suggested that IL-6 monoclonal antibody and tocilizumab might effectively abrogate TDI-induced airway inflammation and remodeling, which could be used as a clinical potential therapy for patients with severe asthma.
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Anticuerpos Monoclonales Humanizados/administración & dosificación , Asma/tratamiento farmacológico , Interleucina-6/efectos adversos , Animales , Asma/patología , Modelos Animales de Enfermedad , Resistencia a Medicamentos , Humanos , Interleucina-6/administración & dosificación , Ratones , Ratones Endogámicos BALB C , Hipersensibilidad Respiratoria/diagnóstico , Transducción de Señal , 2,4-Diisocianato de ToluenoRESUMEN
Background: The adaptive immune system plays a role in the pathogenesis of idiopathic pulmonary fibrosis (IPF) has been reported previously. However, the association between airway and circulating autoantibodies (AAbs) levels is unclear. The aim of this study is to investigate the link between the AAb levels in airway and circulation in stable patients with IPF. Materials and Methods: From June 2016 to March 2017, 21 stable IPF patients and 22 healthy volunteers were recruited. We established Luminex interacting AAbs with bead-antigen complex to detect the immunoglobulin G antibodies levels of ten autoantigens which were matched serum (Se) and sputum (Sp) samples collected from recruited subjects, including Smith (Sm), Anti-ribosomal P antibody (P0), Sjögren syndrome type A antigen (SSA), La/Sjögren syndrome type B antigen (SSB), DNA topoisomerase (Scl-70), histidyl-tRNA synthetase (Jo-1), U1 small nuclear ribonucleoprotein (U1-SnRNP), thyroid peroxidase, Proteinase 3, and Myeloperoxidase. Spearman's rank correlation matrix was applied to explore the associations of Ab profiles between Se and Sp. Results: For IPF patients, Spearman's correlation matrix showed multiple intercorrelations among Sp-AAbs and Sp-AAbs (P < 0.05), while only the levels of AAb against Sm and anti-La in Se were correlated with those Sp-AAb counterparts (P < 0.05). For healthy individuals, only anti-La in Se was associated with those Sp-AAb counterparts (P < 0.05). For IPF patients, there was a positive correlation between carbon monoxide diffusing capacity (DLCO)% predicted and Sp-anti-P0 level (r = 0.464, P = 0.034). Forced vital capacity% predicted was positively correlated with Sp-anti-Scl-70 level (r = 0.466, P = 0.033). Conclusion: Comparing to Se-AAbs, Sp-AAbs are more associated with clinical parameters in the patients with IPF. In order to better understand the role of autoimmunity in the pathogenesis of IPF, detection of Sp-AAbs for local autoimmune responses may be a good choice.
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Chronic obstructive pulmonary disease (COPD) is a complex and progressive respiratory disease. Autoimmune processes have been hypothesized to contribute to disease progression; however, the presence of autoantibodies in the serum has been variable. Given that COPD is a lung disease, we sought to investigate whether autoantibodies in sputum supernatant would better define pulmonary autoimmune processes. Matched sputum and serum samples were obtained from the Airways Disease Endotyping for Personalized Therapeutics (ADEPT) study and at the Guangzhou Institute of Respiratory Health (GIRH). Samples were collected from patients with varying severity of COPD, asymptomatic smokers, and healthy control subjects. IgG and IgM autoantibodies were detected in sputum and serum of all subjects in both cohorts using a broad-spectrum autoantigen array. No differences were observed in sputum autoantibodies between COPD and asymptomatic smokers in either cohort. In contrast, 16% of detectable sputum IgG autoantibodies were decreased in subjects with COPD compared to healthy controls in the ADEPT cohort. Compared to asymptomatic smokers, approximately 13% of detectable serum IgG and 40% of detectable serum IgM autoantibodies were differentially expressed in GIRH COPD subjects. Of the differentially expressed specificities, anti-nuclear autoantibodies were predominately decreased. A weak correlation between increased serum IgM anti-tissue autoantibodies and a measure of airspace enlargement was observed. The differential expression of specificities varied between the cohorts. In closing, using a comprehensive autoantibody array, we demonstrate that autoantibodies are present in subjects with COPD, asymptomatic smokers, and healthy controls. Cohorts displayed high levels of heterogeneity, precluding the utilization of autoantibodies for diagnostic purposes.
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Autoanticuerpos/inmunología , Pulmón/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Esputo/metabolismo , Estudios de Casos y Controles , Progresión de la Enfermedad , Humanos , Inmunoglobulina G/inmunología , Inmunoglobulina M/sangre , Pulmón/inmunología , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Fumadores , Fumar/metabolismoRESUMEN
BACKGROUND: Hyperoxia induces lung injury through lung inflammation in premature infants, leading to bronchopulmonary dysplasia (BPD). Semaphorin 3A (SEMA3A) participates in diverse biological processes, including cell migration, angiogenesis, and inflammation. The effect of SEMA3A on hyperoxic lung injury of neonatal rats with BPD was investigated in this study. METHODS: Neonatal rats with BPD were established through hyperoxia treatment. Hematoxylin-eosin staining was used to evaluate histopathological analysis in lung tissues. SEMA3A expression was assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot assay. Adeno-associated virus (AAV)-mediated over-expression of SEMA3A (AAV-SEMA3A) was administrated into hyperoxia-induced rats, and apoptosis was evaluated by TUNEL staining. Levels of inflammatory cytokines were investigated by enzyme-linked-immunosorbent serologic assay (ELISA). RESULTS: Hyperoxia-induced histopathological changes in lung tissue reduced alveolar number and enhanced alveolar interval and alveolar volume. SEMA3A was downregulated in lung tissue of hyperoxia-induced rats. AAV-SEMA3A injection attenuated hyperoxia-induced cell apoptosis in lung tissues by increasing Bcl-2 and decreasing Bax and cleaved caspase-3. Moreover, the enhanced levels of Interleukin (IL)-1ß, monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor-α (TNF-α) in hyperoxia-induced rats were restored by AAV-SEMA3A injection by the downregulation of nuclear factor kappa B (NF-κB) phosphorylation. AAV-SEMA3A injection also ameliorated histopathological changes in lung tissues of hyperoxia-induced rats by increasing the number of radial alveolar count and decreasing the volume of mean linear intercept. Besides, the protein expression levels of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) phosphorylation were reduced in hyperoxia-induced rats post-AAV-SEMA3A injection. CONCLUSION: Ectopical expression of SEMA3A suppressed hyperoxia-induced apoptosis and inflammation in neonatal rats, and ameliorated the histopathological changes through inactivation of ERK/JNK pathway.
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Displasia Broncopulmonar , Hiperoxia , Lesión Pulmonar , Semaforina-3A , Animales , Animales Recién Nacidos , Displasia Broncopulmonar/terapia , Modelos Animales de Enfermedad , Quinasas MAP Reguladas por Señal Extracelular , Inflamación , Pulmón , Sistema de Señalización de MAP Quinasas , Ratas , Semaforina-3A/genéticaRESUMEN
Identification of risk factors for antibiotic treatment failure is urgently needed in acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Here we investigated the relationship between sputum microbiome and clinical outcome of choice of initial antibiotics during hospitalization of AECOPD patients. Sputum samples of 41 AECOPD patients and 26 healthy controls were collected from Guangzhou Medical University, China. Samples were processed for 16S rRNA gene-based microbiome profiling. Thirty patients recovered with initial antibiotic treatment (antibiotic success or AS), while 11 patients showed poor outcome (antibiotic failure or AF). Substantial differences in microbiome were observed in AF versus AS patients and healthy controls. There was significantly decreased alpha diversity and increased relative abundances of Pseudomonas, Achromobacter, Stenotrophomonas and Ralstonia in AF patients. Conversely, Prevotella, Peptostreptococcus, Leptotrichia and Selenomonas were depleted. The prevalence of Selenomonas was markedly reduced in AF versus AS patients (9.1 % versus 60.0 %, P = 0.004). The AF patients with similar microbiome profiles in general responded well to the same new antibiotics in the adjusted therapy, indicating sputum microbiome may help guide the adjustment of antibiotics. Random forest analysis identified five microbiome operational taxonomic units together with C-reactive protein, procalcitonin and blood neutrophil count showing best predictability for antibiotic treatment outcome (area under curve 0.885). Functional inference revealed an enrichment of microbial genes in xenobiotic metabolism and antimicrobial resistance in AF patients, whereas genes in DNA repair and amino acid metabolism were depleted. Sputum microbiome may determine the clinical outcome of initial antibiotic treatment and be considered in the risk management of antibiotics in AECOPD.
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Antibacterianos/uso terapéutico , Bacterias/efectos de los fármacos , Hospitalización , Pulmón/microbiología , Microbiota , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Esputo/microbiología , Anciano , Antibacterianos/efectos adversos , Bacterias/genética , Bacterias/crecimiento & desarrollo , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Humanos , Pacientes Internos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Proyectos Piloto , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/microbiología , Ribotipificación , Resultado del TratamientoRESUMEN
Steroid insensitivity constitutes a major problem for asthma management. Toluene diisocyanate (TDI) is one of the leading allergens of asthma that induces both T-helper Th2 and Th17 responses, and is often associated with poor responsiveness to steroid treatment in the clinic.We sought to evaluate the effects of inhaled and systemic steroids on a TDI-induced asthma model and to find how interleukin (IL)-17A and IL-17F function in this model. BALB/c mice were exposed to TDI for generating an asthma model and were treated with inhaled fluticasone propionate, systemic prednisone, anti-IL-17A, anti-IL-17F, recombinant IL-17A or IL-17F.Both fluticasone propionate and prednisone showed no effects on TDI-induced airway hyperresponsiveness (AHR), bronchial neutrophilia and eosinophilia, and epithelial goblet cell metaplasia. TDI-induced Th2 and Th17 signatures were not suppressed by fluticasone propionate or prednisone. Treatment with anti-IL-17A after TDI exposure led to increased AHR, aggravated mucus production and airway eosinophil recruitment, accompanied by amplified Th2 responses, whereas anti-IL-17F ameliorated TDI-induced AHR and airway neutrophilia, with decreased Th17 responses. Recombinant IL-17A and IL-17F showed opposite effects to the monoclonal antibodies.IL-17A and IL-17F exert distinct biological effects during airway inflammation of a TDI-induced asthma model, which is unresponsive to both inhaled and systemic steroids.
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Asma/tratamiento farmacológico , Asma/inmunología , Interleucina-17/fisiología , Animales , Broncodilatadores/uso terapéutico , Modelos Animales de Enfermedad , Resistencia a Medicamentos , Fluticasona/uso terapéutico , Glucocorticoides/uso terapéutico , Ratones , Ratones Endogámicos BALB C , Prednisona/uso terapéutico , 2,4-Diisocianato de Tolueno/administración & dosificaciónRESUMEN
Ghost imaging has gone through from quantum to classical pseudothermal to computational field over the last two decades. As a kernel part in computational ghost imaging (CGI), the reconstruction algorithm plays a decisive role in imaging quality and system practicality. In order to introduce more prior knowledge into the reconstruction algorithm, existing research adds image patch prior into CGI and improves the imaging efficiency. In this paper, the total variation minimization algorithm via adaptive deep dictionary learning (TVADDL) is proposed to update an adaptive deep dictionary through the CGI reconstruction process. The proposed algorithm framework is able to capture more precise texture features with a multi-layer architecture dictionary and adapt the learned dictionary by gradient descent on CGI reconstruction loss value. The results of simulation and experiment show that TVADDL can achieve higher peak signal-to-noise ratio than the algorithms without patch prior and the algorithms using the shallow dictionary or non-adaptive deep dictionary.
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BACKGROUND: The prevalence of type 2 diabetes (T2DM) in China is over 10%, affecting around 114 million people. Despite the inclusion of T2DM in the National Basic Public Health Service Program (NBPHSP), most people with T2DM experience challenges in achieving optimal management targets. This study aimed to identify barriers and facilitators of diabetes management from the perspectives of primary health care (PHC) service providers and recipients. METHODS: This mixed-methods study was conducted in Shijiazhuang City, Hebei Province, China. A quantitative PHC facility assessment survey was conducted in all administrative districts and qualitative in-depth interviews were conducted in one district to government officials, medical staff, patients with T2DM, and their family members. Interviews were thematically analyzed, and all findings were synthesized using Michie's COM-B theory. RESULTS: A total of 197 village/community level PHC facilities and 66 township/street level PHC facilities answered the survey, and 42 in-depth interviews were conducted. The key facilitators stemmed from the NBPHSP policy, which standardized the basic infrastructure, medical equipment, and medication for the PHC facilities, provided training on NCD prevention and control, and compensated the PHC workers. However, we identified a detrimental cycle among PHC providers characterized by inadequate capacity, overwhelming workloads, insufficient income, limited career development opportunities, and challenges in attracting young talents. Although patients were covered by the national medical insurance schemes, they experienced capability constraints primarily driven by low education levels, advanced age, low health literacy, and a proliferation of misinformation. These factors influenced patients' motivation to be actively engaged in care and contributed to inertia to intensify treatment and achieve their clinical management goals. CONCLUSION: This study identifies several major facilitators and barriers from the perspectives of both PHC providers and patients with T2DM. Our findings suggest there are substantial opportunities to strengthen the NBPHSP, including improving the capacity and the income level of the PHC providers, attracting and retaining skilled health workers in rural areas, supporting patients to improve their health literacy and take a more active role in their health care, and improving access to high-quality care through digital health approaches. TRIAL REGISTRATION: ClinicalTrials.gov (record NCT02726100, 03/22/2016).
Asunto(s)
Diabetes Mellitus Tipo 2 , Atención Primaria de Salud , Humanos , Instituciones de Atención Ambulatoria , Atención a la Salud , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/terapia , Investigación CualitativaRESUMEN
Biosafety laboratories are critical in many fields. However, experimenters associated the infection risk from biological aerosols. In this study, by conducting experiments on the release and collection of bioaerosols within a typical BSL-2 + laboratory, the spatial distribution of bioaerosols was tracked. Numerical calculations were employed to obtain and visualize the airflow patterns and aerosol dispersion paths of four ventilation methods. The results indicated that equipment and tables led to uneven airflow distribution within the laboratory. The comparison results of the four evaluation indicators showed that the air age distribution of UU (Upward supply and upward return) mode and CD (Cross-supply and downward return) mode was superior, with air change efficiency values of 0.595 and 0.603, respectively. Additionally, the contaminant removal index of CD mode was 1.48, significantly higher than the other ventilation methods. The statistical results of the contaminant dispersion index also indicated that CD mode was most conducive to diluting aerosols in the spatial environment. The LD (lateral supply and downward return) mode may lead to airflow short-circuiting. The UD (upward supply and downward return) mode can provide balanced protection for laboratory. Overall, CD mode performed the best among the four ventilation methods, followed by UU mode.