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To explore the differential cohort situation between preschool development of in vitro fertilization (IVF) and naturally conceived infants. From April 2014 to June 2022, 60 preschool IVFs were selected as the research subjects for follow-up at the pediatric health clinic of hospital's prevention and health department. They were set as the experimental group (Group S), and 60 naturally conceived infants of the same age were selected as the control group (Group Z). Data from both groups were collected through telephone follow-up and other methods. No significant difference showed between the 2 groups in age specific height, age specific weight, Gesell developmental score, Denver developmental screening test screening results, intellectual development index, and motor development index (Pâ >â .05). The influence of birth environment factors such as family background and maternal education level on children's height and weight was not significant (Pâ >â .05), while maternal education level had a significant impact on children's intellectual development index (Pâ <â .05). No significant difference showed in the development of preschool children in IVF compared to naturally conceived children, and the level of parental education has a significant impact on children's mental and motor development.
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Desenvolvimento Infantil , Fertilização in vitro , Humanos , Desenvolvimento Infantil/fisiologia , Fertilização in vitro/estatística & dados numéricos , Fertilização in vitro/métodos , Feminino , Pré-Escolar , Masculino , Escolaridade , Estudos de CoortesRESUMO
Tuberculosis, a fatal infectious disease caused by Mycobacterium tuberculosis (M.tb), is difficult to treat with antibiotics due to drug resistance and short drug half-life. Phototherapy represents a promising alternative to antibiotics in combating M.tb. Exploring an intelligent material allowing effective tuberculosis treatment is definitely appealing, yet a significantly challenging task. Herein, an all-in-one biomimetic therapeutic nanoparticle featured by aggregation-induced second near-infrared emission, granuloma-targeting, and self-oxygenation is constructed, which can serve for prominent fluorescence imaging-navigated combined phototherapy toward tuberculosis. After camouflaging the biomimetic erythrocyte membrane, the nanoparticles show significantly prolonged blood circulation and increased selective accumulation in tuberculosis granuloma. Upon laser irradiation, the loading photosensitizer of aggregation-induced emission photosensitizer elevates the production of reactive oxygen species (ROS), causing M.tb damage and death. The delivery of oxygen to relieve the hypoxic granuloma microenvironment supports ROS generation during photodynamic therapy. Meanwhile, the photothermal agent, Prussian blue nanoparticles, plays the role of good photothermal killing effect on M.tb. Moreover, the growth and proliferation of granuloma and M.tb colonies are effectively inhibited in the nanoparticle-treated tuberculous granuloma model mice, suggesting the combined therapeutic effects of enhancing photodynamic therapy and photothermal therapy.
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The alkaline hydrogen evolution reaction (HER) is intricately linked to the water dissociation kinetics. The quest for new strategies to accelerate this step is a pivotal aspect of enhancing the HER performance. Herein, we designed and synthesized a heterogeneous nickel phosphide/cobalt phosphide nanowire array grown on nickel foam (Ni2P/CoP/NF) to form a p-n junction structure. The built-in electric field (BEF) in the p-n junction optimizes the binding ability of hydrogen and hydroxyl intermediates, efficiently promoting water dissociation for the alkaline HER. Consequently, Ni2P/CoP/NF exhibits a lower overpotential of 58 and 118 mV at 30 and 100 mA cm-2, respectively, and high stability over 40 h at 300 mA cm-2 for the HER in 1 M KOH. Computational calculations combined with experiment results testify that the BEF presence in the p-n junction of Ni2P/CoP/NF effectively promotes water dissociation, regulates intermediate adsorption/desorption, and boosts electron transport. This study presents a rational design approach for high-performance heterogeneous electrocatalysts.
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Background: People are constantly exposed to phthalates, but few reliable studies have focused on the connection between phthalate exposure and latent tuberculosis infection (LTBI). Methods: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) database (2011-2012). The LTBI was assessed by QuantiFERON®-TB Gold-In-Tube (QFT) or tuberculin skin testing (TST). The odds ratios (ORs) and 95% confidence intervals (CIs) per log10 unit change in the concentration of phthalate metabolites were calculated using crude and adjusted logistic regression models. The relationships between mixed phthalate concentrations and LTBI were assessed using Bayesian kernel machine regression (BKMR) models. Results: According to the results of the multivariable logistic regression, in a fully adjusted model, only monobenzyl phthalate (MBZP) was negatively associated with LTBI in Q3 (OR (95% CI): 0.485 (0.286,0.823), P = 0.007). According to the restricted cubic spline (RCS) model, there was a linear doseâresponse association between all 11 phthalate metabolites and LTBI (p for nonlinearity >0.05). We found a significant positive correlation between mixed phthalate metabolites and LTBI by using fully adjusted BKMR model. Conclusions: Our analysis demonstrated that LTBI in the general U.S. population is linearly linked with exposure to single or combined phthalates.
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Brain injury in preterm infants is a major cause of disability and mortality in children. GSK-3ß is a common pathogenic factor for cognitive dysfunction and involves in neuronal proliferation and differentiation. However, GSK-3ß affected neuronal differentiation and its molecular pathogenesis after hypoxic-ischemic brain damage in neonatal rats remains unclear. This study investigated the effects of GSK-3ß inhibitor (TWS119) on cell cycle regulatory proteins, a neuronal differentiation factor (CEND1), maturation neurons, T-box brain transcription factor 1 (TBR1)-positive neurons to clarify the mechanisms of hypoxic-ischemic brain damage in neonatal rats. We used hypoxic-ischemic Sprague-Dawley neonatal rats with brain damage as models. These rats were used for investigating the effect of GSK-3ß on cell cycle regulatory proteins, neuronal differentiation factor (CEND1), maturation neurons, TBR1-positive neurons by western blot and immunofluorescence. Cyclin D1 (a positive cell cycle regulator) expression decreased, and p21 (a negative cell cycle regulator) expression increased in the TWS119 group compared to the hypoxia-ischemia (HI) group 7 days after HI. Additionally, compared to the HI group, TWS119 treatment up-regulated CEND1 expression and promoted neuronal differentiation and cortex development based on NeuN and TBR1 expression. Our study suggests that the GSK-3ß inhibitor TWS119 promotes neuronal differentiation after hypoxic-ischemic brain damage in neonatal rats by inhibiting cell cycle pathway.
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Hipóxia-Isquemia Encefálica , Neurogênese , Pirimidinas , Pirróis , Animais , Ratos , Animais Recém-Nascidos , Proteínas de Ciclo Celular/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Pirróis/farmacologia , Pirróis/uso terapêutico , Ratos Sprague-Dawley , Neurogênese/efeitos dos fármacos , Neurônios/citologia , Neurônios/efeitos dos fármacosRESUMO
In recent years, more and more researchers have reflected on the undervaluation of emotion in data visualization and highlighted the importance of considering human emotion in visualization design. Meanwhile, an increasing number of studies have been conducted to explore emotion-related factors. However, so far, this research area is still in its early stages and faces a set of challenges, such as the unclear definition of key concepts, the insufficient justification of why emotion is important in visualization design, and the lack of characterization of the design space of affective visualization design. To address these challenges, first, we conducted a literature review and identified three research lines that examined both emotion and data visualization. We clarified the differences between these research lines and kept 109 papers that studied or discussed how data visualization communicates and influences emotion. Then, we coded the 109 papers in terms of how they justified the legitimacy of considering emotion in visualization design (i.e., why emotion is important) and identified five argumentative perspectives. Based on these papers, we also identified 61 projects that practiced affective visualization design. We coded these design projects in three dimensions, including design fields (where), design tasks (what), and design methods (how), to explore the design space of affective visualization design.
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Gráficos por Computador , Emoções , HumanosRESUMO
Electronics have greatly promoted the development of modern society and the exploration of new semiconducting materials with low cost and high mobility continues to attract interest in the advance of next-generation electronic devices. Among emerging semiconductors, the metal-halide perovskite, especially the nontoxic tin (Sn)-based candidates, has recently made breakthroughs in the field of diverse electronic devices due to its excellent charge transport properties and cost-effective large-area deposition capability at low temperatures. To enable a more comprehensive understanding of this emerging research field and promote the development of new-generation perovskite electronics, this review aims to provide an in-depth understanding with the discussion of unique physical properties of Sn-based perovskites and the summarization of recent research progress of Sn-based perovskite field-effect transistors (FETs) and diverse electronic devices. The unique character of negligible ion migration is also discussed, which is fundamentally different from the lead-based counterparts and provides a great prerequisite for device application. The following section highlights the potential broad applications of Sn-perovskite FETs as a competitive and feasible technology. Finally, an outlook and remaining challenges are given to advance the progression of Sn-based perovskite FETs, especially on the origin and solution of stability problems toward high-performance Sn-based perovskite electronics.
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OBJECTIVES: Innate and adaptive immunity play different roles in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, previous studies on the relationship between immune cells and COPD reported inconsistent results. METHODS: The causal connection between 731 immune cells and COPD was established using a two-sample Mendelian randomization (MR) analysis through publicly accessible genetic data. The heterogeneity and horizontal pleiotropism of the findings were confirmed using sensitivity analysis. RESULTS: In the B-cell panel, B-cell activating factor receptor (BAFF-R) on CD20- and CD20 on IgD-CD38bright (OR (95% CI): 0.93 (0.88, 0.99) and 0.97 (0.95, 0.98), respectively) were discovered to be protective. In the cDC panel, CD62L- plasmacytoid DC AC, CD80 on monocytes and CD11c on myeloid DCs (OR (95% CI): 0.94 (0.92, 0.97), 0.97 (0.94, 0.99) and (0.97 (0.95, 0.98), respectively) exerted protective effects. However, unswitched memory AC (OR (95%CI): 1.08 (1.01,1.15)) and CD 19 on IgD- CD 27- (OR (95%CI): 1.06 (1.02,1.10)) were hazardous in the B-cell panel. However, among the 731 immune cell phenotypes, no causal relationship was found for COPD on immune cells. CONCLUSION: This study found a potential causal relationship between immune cells in COPD, ruling out reverse causation. This study provides new avenues for studying the mechanisms of COPD.
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Análise da Randomização Mendeliana , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/genética , Imunidade Adaptativa , Linfócitos B , Antígeno B7-1 , Estudo de Associação Genômica AmplaRESUMO
BACKGROUND: Observational studies showed a bidirectional association between depression and chronic obstructive pulmonary disease (COPD). However, it is unclear whether the observed association is causal. Thus we estimated the relationship using observational studies combined with bidirectional Mendelian randomization [MR]. MATERIALS AND METHODS: The study included 9977 participants from the 2013-2018 National Health and Nutrition Examination Survey and used weighted logistic regression analysis to assess the association between depression and COPD, followed by a bidirectional Mendelian randomization analysis to verify their causality. RESULTS: Adjusted-weighted logistic regression in observational studies showed a significant association between COPD and mild depression (OR (95% CI): 1.81 (1.30, 2.52), P = 0.002) and COPD and depression (OR (95% CI): 1.93 (1.49, 2.50), P < 0.001). MR suggested depression may play a causal role in COPD risk (OR (95% CI): 1.45 (1.32, 1.60), P < 0.001), but more evidence for reverse causation is lacking (reverse MR OR (95% CI): 1.03 (0.99, 1.07), P = 0.151). CONCLUSION: In conclusion, our study found depression may play a potential causal role in the morbidity of COPD suggesting depression might be the etiology of COPD. This finding needs to be validated in further prospective cohort studies with large sample sizes and adequate follow-up time.
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Depressão , Doença Pulmonar Obstrutiva Crônica , Humanos , Depressão/epidemiologia , Depressão/genética , Análise da Randomização Mendeliana , Inquéritos Nutricionais , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/genéticaRESUMO
BACKGROUND: Despite potential benefits and widespread prescription of aspirin among chronic obstructive pulmonary disease (COPD) patients, limited research has investigated its adverse effects (AEs) in COPD population. METHODS: We conducted a retrospective analysis of adverse drug events (ADEs) reported in the US Food and Drug Administration Adverse Event Reporting System (FAERS) between Q1 2013 and Q2 2022. COPD patients were categorized into two groups based on aspirin use. ADEs related to aspirin use were identified using combined reporting odds ratio (ROR), proportional reporting ratio (PRR), information component (IC) methods. RESULTS: A total of 56,660 ADEs reports associated with COPD patients were included in the study. Among these reports, 144 adverse events were linked to aspirin use in COPD patients, including fatigue (4.12%), diarrhea (3.13%), dyspnea exertional (2.03%), rhinorrhea (1.99%), weight increased (1.89%) and vomiting (1.84%), muscle spasms (1.79%), cardiac disorder (1.74%), heart rate increased (1.69%) and peripheral swelling (1.59%). Subgroup analysis indicates that age and gender might affect the AEs frequency in COPD patients using aspirin. CONCLUSIONS: Our findings identify 10 most frequently reported ADEs associated with aspirin use in COPD patients, thus offer valuable insights into the AEs of aspirin for safer clinical utilization in COPD management.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Doença Pulmonar Obstrutiva Crônica , Humanos , Aspirina/efeitos adversos , Sistemas de Notificação de Reações Adversas a Medicamentos , Estudos Retrospectivos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/epidemiologiaRESUMO
BACKGROUND: Pleural effusion (PE) is reported as a common complication in acute pancreatitis (AP), while the incidence of PE in AP varies widely among studies, and the association between PE and mortality is not clear. This study aimed to comprehensively analyze the pooled incidence of PE in patients with AP and to evaluate the influence of PE on mortality through a meta-analysis. METHOD: Six databases (PubMed, Web of Science, EMBASE, Cochrane, Scopus, and OVID) were searched thoroughly for relevant studies. Data were extracted, and Stata SE 16.0 software was applied to compute the pooled incidence of PE and assess the association between PE and mortality, taking the risk ratio (RR) as the effect size. RESULTS: Thirty-five articles involving 7,675 patients with AP were eventually included in this meta-analysis. The pooled incidence of PE was 34% (95% CI: 28%-39%), with significant heterogeneity among studies (I2=96.7%). Further analysis revealed that the pooled incidence of unilateral and small PE occupied 49% (95% CI: 21%-77%) and 59% (95% CI: 38%-81%) of AP patients complicated by PE, respectively. The subgroup analysis revealed that "region" and "examination method" may contribute to heterogeneity. PE may be associated with increased mortality in AP patients (RR 3.99, 95% CI: 1.73-9.2). CONCLUSION: This study suggested that PE is a common complication with high pooled incidence and that PE may be associated with increased mortality in AP patients. More studies should be performed to validate our findings.
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Pancreatite , Derrame Pleural , Humanos , Pancreatite/complicações , Pancreatite/epidemiologia , Prognóstico , Doença Aguda , Incidência , Derrame Pleural/epidemiologia , Derrame Pleural/etiologiaRESUMO
The inflammatory immune environment surrounding titanium bone implants determines the formation of osseointegration, and nanopatterning on implant surfaces modulates the immune microenvironment in the implant region. Among many related mechanisms, the mechanism by which nanopatterning controls macrophage inflammatory response still needs to be elucidated. In this paper, we found that inhibition of the nuclear envelope protein lamin A/C by titania nanotubes (TNTs) reduced the macrophage inflammatory response. Knockdown of lamin A/C reduced macrophage inflammatory marker expression, while overexpression of lamin A/C significantly elevated inflammatory marker expression. We further found that suppression of lamin A/C by TNTs limited actin polymerization, thereby reducing the nuclear translocation of the actin-dependent transcriptional cofactor MRTF-A, which subsequently reduced the inflammatory response. In addition, emerin, which is a key link between lamin A/C and actin, was delocalized from the nucleus in response to mechanical stimulation by TNTs, resulting in reduced actin organization. Under inflammatory conditions, TNTs exerted favourable osteoimmunomodulatory effects on the osteogenic differentiation of mouse bone marrow-derived stem cells (mBMSCs) in vitro and osseointegration in vivo. This study shows and confirms for the first time that lamin A/C-mediated nuclear mechanotransduction controls macrophage inflammatory response, and this study provides a theoretical basis for the future design of immunomodulatory nanomorphologies on the surface of metallic bone implants.
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Lamina Tipo A , Nanotubos , Camundongos , Animais , Actinas , Osteogênese , Mecanotransdução Celular , Macrófagos , Titânio/farmacologia , Propriedades de SuperfícieRESUMO
Extracellular matrix (ECM) stiffness is a key stimulus affecting cellular differentiation, and osteoblasts are also in a three-dimensional (3D) stiff environment during the formation of bone tissues. However, it remains unclear how cells perceive matrix mechanical stiffness stimuli and translate them into intracellular signals to affect differentiation. Here, for the first time, we constructed a 3D culture environment by GelMA hydrogels with different amino substitution degrees and found that Piezo1 expression was significantly stimulated by the stiff matrix with high substitution; meanwhile, the expressions of osteogenic markers OSX, RUNX2, and ALP were also observably improved. Moreover, knockdown of Piezo1 in the stiff matrix revealed significant reduction of the abovementioned osteogenic markers. In addition, in this 3D biomimetic ECM, we also observed that Piezo1 can be activated by the static mechanical conditions of the stiff matrix, leading to the increase of the intracellular calcium content and accompanied with a continuous change in cellular energy levels as ATP was consumed during cellular differentiation. More surprisingly, we found that in the 3D stiff matrix, intracellular calcium as a second messenger promoted the activation of the AMP-activated protein kinase (AMPK) and unc-51-like autophagy-activated kinase 1 (ULK1) axis and modestly modulated the level of autophagy, bringing it more similar to differentiated osteoblasts, with increased ATP energy metabolism consumption. Our study innovatively clarifies the regulatory role of the mechanosensitive ion channel Piezo1 in a static mechanical environment on cellular differentiation and verifies the activation of the AMPK-ULK1 axis in the cellular ATP energy metabolism and autophagy level. Collectively, our research develops the understanding of the interaction mechanisms of biomimetic extracellular matrix biomaterials and cells from a novel perspective and provides a theoretical basis for bone regeneration biomaterials design and application.
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Proteínas Quinases Ativadas por AMP , Osteogênese , Trifosfato de Adenosina , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Autofagia/genética , Materiais Biocompatíveis , Cálcio , Diferenciação Celular/genética , Osteogênese/genética , Animais , CamundongosRESUMO
Matrix stiffness plays an important role in determining cell differentiation. The expression of cell differentiation-associated genes can be regulated by chromatin remodeling-mediated DNA accessibility. However, the effect of matrix stiffness on DNA accessibility and its significance for cell differentiation have not been investigated. In this study, gelatin methacryloyl (GelMA) hydrogels with different degrees of substitution were used to simulate soft, medium, and stiff matrices, and it was found that a stiff matrix promoted osteogenic differentiation of MC3T3-E1 cells by activating the Wnt pathway. In the soft matrix, the acetylation level of histones in cells was decreased, and chromatin condensed into a closed conformation, affecting the activation of ß-catenin target genes (Axin2, c-Myc). Histone deacetylase inhibitor (TSA) was used to decondense chromatin. However, there was no significant increase in the expression of ß-catenin target genes and the osteogenic protein Runx2. Further studies revealed that ß-catenin was restricted to the cytoplasm due to the downregulation of lamin A/C in the soft matrix. Overexpression of lamin A/C and concomitant treatment of cells with TSA successfully activated ß-catenin/Wnt signaling in cells in the soft matrix. The results of this innovative study revealed that matrix stiffness regulates cell osteogenic differentiation through multiple pathways, which involve complex interactions between transcription factors, epigenetic modifications of histones, and the nucleoskeleton. This trio is critical for the future design of bionic extracellular matrix biomaterials.
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This paper concentrates on the problem of H ∞ state estimation for quaternion-valued inertial neural networks (QVINNs) with nonidentical time-varying delay. Without reducing the original second order system into two first order systems, a non-reduced order method is developed to investigate the addressed QVINNs, which is different from the majority of existing references. By constructing a new Lyapunov functional with tuning parameters, some easily checked algebraic criteria are established to ascertain the asymptotic stability of error-state system with the desired H ∞ performance. Moreover, an effective algorithm is provided to design the estimator parameters. Finally, a numerical example is given out to illustrate the feasibility of the designed state estimator.
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A control strategy containing Lyapunov functions is proposed in this paper. Based on this strategy, the fixed-time synchronization of a time-delay quaternion-valued neural network (QVNN) is analyzed. This strategy is extended to the prescribed-time synchronization of the QVNN. Furthermore, an improved two-step switching control strategy is also proposed based on this flexible control strategy. Compared with some existing methods, the main method of this paper is a non-decomposition one, does not contain a sign function in the controller, and has better synchronization accuracy. Two numerical examples verify the above advantages.
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Algoritmos , Redes Neurais de Computação , Fatores de TempoRESUMO
As an effective form of narrative visualization, visual data stories are widely used in data-driven storytelling to communicate complex insights and support data understanding. Although important, they are difficult to create, as a variety of interdisciplinary skills, such as data analysis and design, are required. In this work, we introduce Erato, a human-machine cooperative data story editing system, which allows users to generate insightful and fluent data stories together with the computer. Specifically, Erato only requires a number of keyframes provided by the user to briefly describe the topic and structure of a data story. Meanwhile, our system leverages a novel interpolation algorithm to help users insert intermediate frames between the keyframes to smooth the transition. We evaluated the effectiveness and usefulness of the Erato system via a series of evaluations including a Turing test, a controlled user study, a performance validation, and interviews with three expert users. The evaluation results showed that the proposed interpolation technique was able to generate coherent story content and help users create data stories more efficiently.
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Exosomes are considered as biomarkers reflecting the physiological state of the human body. Studies have revealed that the expression levels of specific exosomal RNAs are closely associated with certain cancers. Thus, detection of exosomal RNA offers a new avenue for liquid biopsy of cancers. Many exosomal RNA detection methods based on various principles have been developed, and most of the methods detect the extracted RNAs after lysing exosomes. Besides complex and time-consuming extraction steps, a major drawback of this approach is the degradation of the extracted RNAs in the absence of plasma membrane and cytosol. In addition, there is considerable loss of RNAs during their extraction. In situ detection of exosomal RNAs can avoid these drawbacks, thus allowing higher diagnostic reliability. In this paper, in situ detection of exosomal RNAs was systematically reviewed from the perspectives of detection methods, transport methods of the probe systems, probe structures, signal amplification strategies, and involved functional materials. Furthermore, the limitations and possible improvements of the current in situ detection methods for exosomal RNAs towards the clinical diagnostic application are discussed. This review aims to provide a valuable reference for the development of in situ exosomal RNA detection strategies for non-invasive diagnosis of cancers. STATEMENT OF SIGNIFICANCE: Certain RNAs have been identified as valuable biomarkers for some cancers, and sensitive detection of cancer-related RNAs is expected to achieve better diagnostic efficacy. Currently, the detection of exosomal RNAs is receiving increasing attention due to their high stability and significant concentration differences between patients and healthy individuals. In situ detection of exosomal RNAs has greater diagnostic reliability due to the avoidance of RNA degradation and loss. However, this mode is still limited by some factors such as detection methods, transport methods of the probe systems, probe structures, signal amplification strategies, etc. This review focuses on the progress of in situ detection of exosomal RNAs and aims to promote the development of this field.
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MicroRNAs , Neoplasias , RNA Longo não Codificante , Humanos , Reprodutibilidade dos Testes , Biomarcadores Tumorais/genética , MicroRNAs/genética , Neoplasias/diagnóstico , Neoplasias/genética , RNA Longo não Codificante/genéticaRESUMO
BACKGROUND: N-acetylcysteine (NAC), which is specifically involved in airway mucus clearance and antioxidation, is recommended by the treatment guideline for non-cystic fibrosis bronchiectasis (NCFB). However, there is little clinical evidence of its long-term efficacy concerning quality of life (QoL) and exacerbation in patients with NCFB. In addition, the influences of NAC on airway bacterial colonization, chronic inflammation and oxidative stress in NCFB are also unclear. METHODS: NINCFB is a prospective, multicentre, double-blind, randomised, placebo-controlled trial that will recruit 119 patients with NCFB and randomly divide them into an NAC group (n = 79) and a control group (n = 40). Participants in the NAC group will receive 600 mg oral NAC twice daily for 52 weeks, while patients in the control group will receive 600 mg placebo twice daily for 52 weeks. The information at baseline will be collected once participants are enrolled. The primary endpoints are the changes in St George's Respiratory Questionnaire scores and the number of exacerbations in 52 weeks. The secondary endpoints are the 16S rRNA of sputum and the levels of inflammatory factors and oxidative stressors in sputum and serum. Other data related to radiography, lung function tests, number of oral and/or intravenous antibiotic therapies and adverse events (AEs) will also be analysed. Further subgroup analysis distinguished by the severity of disease, severity of lung function, airway bacterial colonization and exacerbation frequency will be performed. DISCUSSION: The objective of this study is to determine the long-term efficacy of NAC on QoL and exacerbation of NCFB and to explore the effectiveness of NAC for antibiosis, anti-inflammation and antioxidation in NCFB. The study results will provide high-quality clinical proof for the revision and optimization of treatment guidelines and for expert consensus on NCFB treatment. TRIAL REGISTRATION: The trial was registered on the Chinese Clinical Trial Register at April 11, 2020 ( chictr.org.cn , ChiCTR2000031817).
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Bronquiectasia , Fibrose Cística , Humanos , Acetilcisteína/uso terapêutico , Qualidade de Vida , Estudos Prospectivos , RNA Ribossômico 16S , Antibacterianos , Bronquiectasia/complicações , Método Duplo-Cego , Fibrose Cística/complicações , Fibrose , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
Background: Some clinical indicators have been reported to be useful in differentiating asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) from pure asthma/COPD, but the results were inconsistent. This study aims to evaluate the diagnostic value of these indicators for ACO. Methods: Databases of PubMed, EMBASE, Ovid and Web of Science were retrieved. Pooled standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated in random-effects models. Results: 48 eligible studies were included. The pooled results indicated, compared with pure asthma, ACO patients had lower levels of forced expiratory volume in the first second (FEV1)% predicted (pred) (SMD=-1.09, 95% CI -1.3 to -0.87), diffusion lung capacity for carbon monoxide (DLCO)% pred (SMD=-0.83, 95% CI -1.24 to -0.42), fractional exhaled nitric oxide (FeNO) (SMD=-0.23, 95% CI -0.36 to -0.11), and higher levels of induced sputum neutrophil (SMD = 0.51, 95% CI 0.21 to 0.81), circulating YKL-40 (SMD = 0.96, 95% CI 0.27 to 1.64). However, relative to COPD alone, ACO patients had higher levels of FEV1% pred (SMD = 0.15, 95% CI 0.05 to 0.26), DLCO% pred (SMD = 0.38, 95% CI 0.16 to 0.6), FeNO (SMD = 0.59, 95% CI 0.40 to 0.78), serum total immunoglobulin (Ig)E (SMD = 0.42, 95% CI 0.1 to 0.75), blood eosinophil (SMD = 0.44, 95% CI 0.29 to 0.59), induced sputum eosinophil (SMD = 0.62, 95% CI 0.42 to 0.83), and lower levels of induced sputum neutrophil (SMD=-0.48, 95% CI -0.7 to -0.27), circulating YKL-40 (SMD=-1.09, 95% CI -1.92 to -0.26). Conclusion: Compared with pure asthma/COPD, ACO patients have different levels of FEV1% pred, DLCO% pred, FeNO, serum total IgE, blood eosinophil, induced sputum eosinophil/neutrophil, and circulating YKL-40, which could be helpful to establish a clinical diagnosis of ACO.