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1.
Int J Chron Obstruct Pulmon Dis ; 17: 1031-1039, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35547779

RESUMO

Background: Serum total bilirubin has been reported to have antioxidant properties against chronic respiratory diseases. The objective of our study is to evaluate the association of total bilirubin (TB) with annual lung function decline in COPD patients with different GOLD stages. Methods: This study used pooled data from two observational and prospective cohorts of 612 COPD patients whose TB levels were measured at baseline. The associations between TB and postbronchodilator FEV1, FEV1pred, FVC, FVCpred, FEV1/FVC, and the rate of their decline were all determined using linear regression models in the total population and strata of GOLD stages. Results: Serum TB was positively related to FEV1 and FVC in the total group (ß 0.02, 95% CI 0.001~0.02, P = 0.025 and ß 0.02, 95% CI 0.002~0.03, P = 0.022, respectively). Additionally, TB was inversely associated with the annual decline in FEV1 and FEV1pred (ß 4.91, 95% CI 1.68~8.14, P = 0.025 and ß 0.21, 95% CI 0.06~0.36, P = 0.022, respectively) when adjusted for multivariables. After stratification, the significant associations merely persisted in COPD patients with GOLD 2 and GOLD 3-4. Conclusion: Increased TB level was related to less annual decline in FEV1 as well as FEV1pred in moderate-to-severe COPD but not mild COPD, which indicated the different status of TB in different COPD severity and the possible role as potential biomarker merely in moderate-to-severe COPD. Future researches to determine whether TB could be served as biomarker for COPD and the mechanisms should be focused on some target patients with a certain disease severity.

2.
Int J Chron Obstruct Pulmon Dis ; 17: 1069-1080, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35547782

RESUMO

Background: The effect of serum uric acid (SUA) levels on lung function in chronic obstructive pulmonary disease (COPD) people remained unclear. We aimed to investigate the association between SUA and lung function. Methods: A cross-sectional study was performed to measure the SUA levels and lung function in 2797 consecutive eligible individuals. Of these, individuals in our study were divided into two groups, the COPD group (n=1387) and the non-COPD group (n=1410). The diagnosis of COPD is defined as post-bronchodilator first second of forced expiratory volume (FEV1)/forced vital capacity (FVC) ratio of less than 0.70. Multivariable adjustment linear models were applied to estimate the effect of SUA levels on FEV1% predicted, FVC% predicted, and FEV1/FVC stratified by COPD status. Results: After multivariable adjustment, each 1 mg/dL increase of SUA was significantly associated with a decrease in FEV1% predicted (-1.63%, 95% confidence interval [CI] -2.37 to -0.90), FVC % predicted (-0.89%, 95% CI -1.55 to -0.24), and FEV1/FVC (-0.70%, 95% CI -1.10 to -0.30). In the COPD group, each 1 mg/dL increase of SUA was significantly associated with decreases in FEV1% predicted (-1.87%, 95% CI -2.91 to -0.84), FVC% predicted (-1.35%, 95% CI -2.35 to -0.34), and FEV1/FVC (-0.63%, 95% CI -1.18 to -0.08). However, no significant association between lung function and SUA was found among people without COPD. Conclusion: High SUA levels were associated with lower lung function, especially in COPD patients. However, no statistically significant effect of SUA on lung function was found in people without COPD.

3.
Front Med (Lausanne) ; 9: 811975, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35360751

RESUMO

Background and Objectives: Accumulating evidence suggests that oxidative stress is involved in the development of chronic obstructive pulmonary disease (COPD) and its progression. Activity of extracellular superoxide dismutase (ecSOD), the only extracellular enzyme eliminating superoxide radicals, has been reported to decline in acute exacerbations of COPD (AECOPD). However, the association between serum ecSOD activity and 1-year all-cause mortality in AECOPD patients remains unclear. The objective of our study was to explore the usefulness of ecSOD activity on admission in AECOPD as an objective predictor for 1-year all-cause mortality. Methods: We measured serum ecSOD activity in AECOPD patients on admission in a prospective cohort study. We also recorded their laboratory and clinical data. Multivariate Cox regression was used to analyze the association between ecSOD activity and the risk of 1-year all-cause mortality. Restricted cubic spline curves were used to visualize the relationship between ecSOD activity and the hazard ratio of 1-year all-cause mortality. Results: A total of 367 patients were followed up for 1 year, and 29 patients died during a 1-year follow-up period. Compared with survivors, the non-survivors were older (79.52 ± 8.39 vs. 74.38 ± 9.34 years old, p = 0.004) and had increased levels of tobacco consumption (47.07 ± 41.67 vs. 33.83 ± 31.79 pack-years, p = 0.037). Having an ecSOD activity ≤ 98.8 U/ml was an independent risk factor of 1-year all-cause mortality after adjustment for baseline differences, clinical variables and comorbidities [hazard ratio = 5.51, 95% confidence interval (CI): 2.35-12.95, p < 0.001]. Conclusion: Lower serum ecSOD activity was a strong and independent predictor of 1-year all-cause mortality in AECOPD patients.

4.
Clin Epidemiol ; 14: 289-298, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35299727

RESUMO

Background: The potential protective role of serum total bilirubin (TB) for chronic obstructive pulmonary disease (COPD) is controversial. We aimed to investigate whether serum TB could prevent airflow limitation (reduce the risk of COPD) and whether these associations were causal or reversely causal. Methods: We conducted a multi-center and cross-sectional study including 3069 participants. Logistic regression model (LRM) with restricted cubic spline (RCS) and priori defined quintile categories were used to assess the associations of TB with COPD. Besides, ordinary least squares (OLS) regression model with RCS curves were applied to assess the dose-response relationship between serum TB and airflow limitation (FEV1/FVC). To verify the causal direction between TB and COPD, a bidirectional Mendelian randomization analysis was carried out with GWAS data from European ancestry. Results: In the cross-sectional study, the relationship between levels of TB and COPD risk was U shaped (P=0.001), and the low and high concentrations of TB apparently increasing the risk of COPD (OR 1.40, 95% CI 1.07 to 1.82 for less than 9 µmol/L; OR 1.36, 95% CI 1.06 to 1.76 for 9.01-1 0.88 µmol/L; OR 1.50, 95% CI 1.16 to 1.95 for more than 13 µmol/L). There was a significant non-linear relationship between TB and FEV1/FVC (non-linear p=0.004). Furthermore, results of bidirectional Mendelian randomization analysis (OR 1.000; 95% CI 0.983 to 1.017 for MR and OR 0.998; 95% CI 0.976 to 1.020 for reversal MR) did not support the causal effects between serum TB and FEV1/FVC after controlling the effect of potential confounders and revised causality. Conclusion: Our study reveals that there was non-linear does-response pattern between serum TB and COPD. However, there was little evidence for the linear causal associations of serum TB with airflow limitation. The relationship of TB with COPD needs further study and careful interpretation.

5.
BMC Pulm Med ; 22(1): 80, 2022 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-35248001

RESUMO

BACKGROUND: The lack of simple and affordable spirometry has led to the missed and delayed diagnoses of chronic respiratory diseases in communities. The PUS201P is a portable spirometry developed to solve this problem. OBJECTIVE: We aimed to verify the consistency of the PUS201P spirometer with conventional Jaeger spirometer. METHODS: In this cross-sectional study, we randomly recruited 202 subjects aged > 40 years. Testing with the portable spirometry and conventional spirometry were performed on all participants. We compared forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC measured by the PUS201P device with the conventional spirometer. Pearson correlation coefficient and Interclass Correlation Coefficient (ICC) were assessed to confirm the consistency of the measures from two instruments. Bland-Altman graph was created to assess the agreement of the measures from two devices. RESULTS: 202 participants were included in this study. The ICC on FEV1, FVC, FEV1/FVC measured by the portable spirometer and the conventional spirometer were 0.95 (95% confidence interval [CI]: 0.94-0.96), 0.92 (95% CI: 0.90-0.94], 0.93 (95% CI: 0.91-0.95), respectively. The Bland-Altman plots showed that the mean difference between the measures from two spirometers are always located in the 95% limits of agreement. CONCLUSIONS: Our results support that the measures from the portable spirometer and the conventional spirometer have a good agreement and reproducibility. And the portable spirometer is a reliable tool to screen and diagnose chronic airway diseases in the primary care settings.


Assuntos
Transtornos Respiratórios/diagnóstico , Espirometria/instrumentação , Idoso , China , Doença Crônica , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
6.
J Steroid Biochem Mol Biol ; 216: 106041, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34864206

RESUMO

The hypoxic microenvironment of cryptorchidism is an important factor to induce the impairment of the structure and function of Sertoli cells and thus lead to spermatogenesis loss or tumorigenesis. Dihydrotestosterone (DHT), as a potent nonaromatizable 5α-reduced androgen, has both positive and negative effect on pathological fibrosis process. However, it is still unknown whether DHT can regulate hypoxia-induced fibrosis of Sertoli cells. Herein, in this study, we evaluate the DHT level, two 5α-reductase isoforms, 5α-red1 and 5α-red2, as well as HIF-1α expression pattern in canine cryptorchidism and contralateral normal testis. Results showed that the abdominal testes presented low DHT levels and 5α-red1 and 5α-red2 expression, while significantly higher HIF-1α expression and ECM production compared with the scrotum. Moreover, we established a hypoxia-induced fibrosis model in canine Sertoli cells induced by cobalt chloride (CoCl2), and found that DHT inhibited the fibrosis of Sertoli cells in a dose-dependent manner. Meanwhile, DHT interfered with the TGF-ß signaling by reducing the expression of TGF-ßRI and TGF-ßRII and inhibiting the expression and phosphorylation of Smad2 and Smad3, while flutamide (androgen receptor inhibitor) inhibited these effects of DHT. Furthermore, use of LY2109761 (TGF-ß receptor type I/II inhibitor) to interfere with the TGF-ß/Smad pathway showed a similar effect with DHT suppression of the fibrosis in Sertoli cells. Our research data demonstrated that cryptorchidism is located in a hypoxic and DHT deficiency microenvironment. Moreover, supplementing DHT can alleviate the fibrosis process of Sertoli cells caused by hypoxia, which is associated with AR regulating the inhibition of TGF-ß/Smad signaling.


Assuntos
Hipóxia Celular/fisiologia , Di-Hidrotestosterona/farmacologia , Células de Sertoli/efeitos dos fármacos , Animais , Hipóxia Celular/efeitos dos fármacos , Células Cultivadas , Cães , Fibrose/patologia , Fibrose/prevenção & controle , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Masculino , Escroto/efeitos dos fármacos , Escroto/metabolismo , Escroto/patologia , Células de Sertoli/metabolismo , Células de Sertoli/patologia , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad/antagonistas & inibidores , Proteínas Smad/metabolismo , Testículo/efeitos dos fármacos , Testículo/metabolismo , Testículo/patologia , Fator de Crescimento Transformador beta/antagonistas & inibidores , Fator de Crescimento Transformador beta/metabolismo
7.
J Thromb Thrombolysis ; 53(2): 291-301, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34757546

RESUMO

Stroke is the third leading cause of death in the United States and the leading cause of adult disability. Despite enormous research efforts including many clinical trials, tissue plasminogen activator (tPA) remains the only FDA-approved treatment for acute ischemic stroke. Unfortunately, only 1-3% of stroke patients in the US receive this therapy because of the narrow time window and severe side effects for using tPA. The most deadly and damaging side effect is the risk of intracranial bleeding or hemorrhage. For that reason, the dose of tPA and its overall administration are under tight control, which may compromise the effect of thrombolysis. Studies have been focused on improving the effectiveness of tPA for higher rate of reperfusion, and the safety for less adverse bleeding episode. We studied how metal ions (zinc & iron) affect tPA-induced thrombolysis in vitro and in vivo, and proposed a method to improve the rate of thrombolysis. The amount of hemoglobin in the blood clot lysis was measured by a spectrophotometer. The tPA-induced thrombolysis was measured in vivo in femoral artery. Our results showed that Zn2+, Fe3+ and Fe2+ inhibited tPA-induced thrombolysis, with Zn2+ and Fe2+ being the most effective. Metal ion chelating agent EDTA when it was co-applied with tPA significantly enhanced the tPA-induced thrombolysis. The chelation alone did not have noticeable thrombolytic effect. In in vivo study of tPA-induced thrombosis following femoral artery thrombosis, the co-application of tPA and EDTA achieved significant higher rate of reperfusion than that by tPA treatment alone, suggesting that ion chelation facilitates tPA-induced thrombolysis and potentially improves the safety of tPA application by reducing the necessary dose of tPA application. Our results suggest that the co-application of a chelator and tPA improves the efficacy and, potentially, safety of tPA application, by reducing the necessary dose of tPA for thrombolysis.


Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Adulto , Quelantes/uso terapêutico , Fibrinolíticos/uso terapêutico , Humanos , Íons/uso terapêutico , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tecidual
8.
Environ Sci Technol ; 55(24): 16676-16686, 2021 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-34878772

RESUMO

Precisely tailoring the surface morphology characteristics of the active layers based on bionic inspirations can improve the performance of thin-film composite (TFC) membranes. The remarkable water adsorption and capture abilities of octopus tentacles inspired the construction of a novel TFC nanofiltration (NF) membrane with octopus arm-sucker morphology using carbon nanotubes (CNTs) and beta-cyclodextrin (ß-CD) during interfacial polymerization (IP). The surface morphology, chemical elements, water contact angle (WCA), interfacial free energy (ΔG), electronegativity, and pore size of the membranes were systematically investigated. The optimal membrane exhibited an enhanced water permeance of 22.6 L·m-2·h-1·bar-1, 180% better than that of the TFC-control membrane. In addition, the optimal membrane showed improved single salt rejections and monovalent/divalent ion selectivity and can break the trade-off effect. The antiscaling performance and stability of the membranes were further explored. The construction mechanism of the octopus arm-sucker structure was excavated, in which CNTs and ß-CD acted as arm skeletons and suckers, respectively. Furthermore, the customization of the membrane surface and performance was achieved through tuning the individual effects of the arm skeletons and suckers. This study highlights the noteworthy potential of the design and construction of the surface morphology of high-performance NF membranes for environmental application.


Assuntos
Nanotubos de Carbono , Octopodiformes , Animais , Filtração , Membranas Artificiais
9.
Respir Med ; 190: 106681, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34784563

RESUMO

BACKGROUND: Small airway dysfunction (SAD) is an early lesion of chronic respiratory disease that is best detected using impulse oscillometry (IOS). Few studies have investigated risk factors for IOS-defined SAD (IOS-SAD) in a large population. We aimed to explore the clinical features of and risk factors for IOS-SAD in a community-based population. METHODS: We divided subjects into IOS-SAD and non-SAD groups based on a cutoff of >0.07 kPa/L/s in the difference between the resistance at 5 Hz versus the resistance at 20 Hz (R5-R20). All participants underwent spirometry, IOS, and completed a questionnaire; some participants underwent computed tomography (CT). We analyzed the risk factors for SAD based on binary logistic regression. RESULTS: The total cohort comprised 1327 subjects. The prevalence of IOS-SAD was 32.9% (437/1327). Compared with the non-SAD group, the IOS-SAD group was older (64.0 ± 7.8 vs. 59.6 ± 7.8 years, p < 0.001), included less never-smokers (30.2% vs. 35.8%, p < 0.001), had greater airway resistance and worse lung function, indicated by a larger R5-R20 (0.15 ± 0.08 vs. 0.03 ± 0.02 kPa/L/s, p < 0.001) and smaller forced expiratory volume in 1 s to forced vital capacity after bronchodilation (60.2 ± 14.4% vs. 72.6 ± 10.0%, p < 0.001); on CT, the IOS-SAD group had higher prevalences of emphysema and gas trapping. Risk factors for SAD were older age, high BMI, smoking, childhood cough, and asthma. CONCLUSION: Subjects with IOS-SAD had increased airway resistance and visible CT changes. Individuals with smoking exposure, advanced age, high BMI, childhood cough, and asthma were more prone to SAD. CLINICAL TRIAL REGISTRATION: ChiCTR1900024643.


Assuntos
Oscilometria , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Fatores Etários , Resistência das Vias Respiratórias , Asma/complicações , Índice de Massa Corporal , Tosse/complicações , Estudos Transversais , Enfisema/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória , Fatores de Risco , Fumar/efeitos adversos
10.
ACS Appl Mater Interfaces ; 13(48): 57998-58010, 2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34817167

RESUMO

Polyamide (PA) chemistry-based nanofiltration (NF) membranes have an important role in the field of seawater desalination and wastewater reclamation. Achieving an ultrathin and defect-free active layer via precisely controlled interfacial polymerization (IP) is an effective routine to improve the separation efficiencies of NF membranes. Herein, the morphologies and chemical structures of the thin-film composite (TFC) NF membranes were accurately regulated by tailoring the interfacial reaction temperature during the IP process. This strategy was achieved by controlling the temperature (-15, 5, 20, 35, and 50°) of the oil-phase solutions. The structural compositions, morphological variations, and separation features of the fabricated NF membranes were studied in detail. In addition, the formation mechanisms of the NF membranes featuring different PAs were also proposed and discussed. The temperature-assisted IP (TAIP) method greatly changed the compositions of the resultant PA membranes. A very smooth and thin PA film was obtained for the NF membranes fabricated at a low interfacial temperature; thus, a high 19.2 L m-2 h-1 bar-1 of water permeance and 97.7% of Na2SO4 rejection were observed. With regard to the NF membranes obtained at a high interfacial temperature, a lower water permeance and higher salt rejection with fewer membrane defects were achieved. Impressively, the high interfacial temperature-assisted NF membranes exhibited uniform coffee-ring-like surface morphologies. The special surface-featured NF membrane showed superior separation for selected heavy metals. Rejections of 93.9%, 97.9%, and 87.7% for Cu2+, Mn2+, and Cd2+ were observed with the optimized membrane. Three cycles of fouling tests indicated that NF membranes fabricated at low temperatures exhibited excellent antifouling behavior, whereas a high interface temperature contributed to the formation of NF membranes with high fouling tendency. This study provides an economical, facile, and universal TAIP strategy for tailoring the performances of TFC PA membranes for environmental water treatment.

11.
Front Cell Infect Microbiol ; 11: 736204, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34631604

RESUMO

The gastrointestinal (GI) tract has long been hypothesized to play an integral role in the pathophysiology of sepsis, and gut microbiota (GM) dysbiosis may be the key factor. Previous studies have shown that the gut flora was significantly altered in critically ill patients. This study aimed to observe what kind of GM dysbiosis is in the early stage of sepsis and whether the application of fecal microbiota transplantation (FMT) can reconstruct the GM of septic mice and restore its protective function on the intestinal mucosal barrier. The study investigated the effect of FMT on gut microbiota, mucosal barrier function, inflammatory response, and survival in a murine model of sepsis established by cecal ligation and puncture (CLP). It is found that FMT can not only reduce morbidity and mortality and restore the abundance and diversity of the gut flora in septic mice, but can also improve the intestinal barrier function by reducing epithelial cell apoptosis, improving the composition of the mucus layer, upregulating the expression of tight junction proteins, and reducing intestinal permeability and the inflammatory response. After FMT, Lachnospiraceae contributed the most to intestinal protection through enhancement of the L-lysine fermentation pathway. FMT offers a microbe-mediated survival advantage in a murine model of sepsis. Therefore, an improved understanding of the connection between microbiota, and systemic illness may yield new therapeutic strategies for patients with sepsis.


Assuntos
Microbioma Gastrointestinal , Sepse , Animais , Modelos Animais de Doenças , Transplante de Microbiota Fecal , Humanos , Mucosa Intestinal , Camundongos , Sepse/terapia
12.
J Mol Endocrinol ; 68(1): 23-33, 2021 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-34678756

RESUMO

Vascular endothelial growth factor (VEGF) plays a pivotal role in angiogenesis in ovaries, particularly during follicular development and ovulation. Interleukin-6 (IL-6) is one of the major pro-inflammatory factors that are involved in the angiogenesis process physiologically and pathologically. Previous studies have shown that 17ß-estradiol (E2) stimulates VEGF expression by upregulating hypoxia-inducible factor 1α (HIF-1α) in many cell types, and the high level of E2 causes an inflammatory-like microenvironment before ovulation. However, whether IL-6 signaling is involved in E2-regulating VEGF expression in swine granulosa cells (GCs) is still unknown. In this study, we found the estrogen membrane receptor, G-protein-coupled estrogen receptor 1 (GPER), was expressed in swine GCs, and the expression level of GPER, HIF-1α, and VEGF increased with follicular development. In vitro study showed that E2, ICI182780, and GPER agonist (G1) promoted the expressions of HIF-1α and VEGF in swine GCs, while GPER antagonist (G15) inhibited the stimulating effect of E2 and G1. Meanwhile, G15 inhibited the stimulating effect of E2 and G1 on IL-6 mRNA expression and secretion. Furthermore, IL-6 antibody and AG490 (JAK2/STAT3 inhibitor) attenuated G1-induced HIF-1α and VEGF expression. In conclusion, this study revealed how estrogen-induced HIF-1α and VEGF expressions in swine GCs are mediated through GPER-derived IL-6 secretion leading to JAK2/STAT3 activation.


Assuntos
Células da Granulosa/metabolismo , Interleucina-6/metabolismo , Janus Quinase 2/metabolismo , Receptores de Estrogênio/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/genética , Animais , Biomarcadores , Células Cultivadas , Feminino , Regulação da Expressão Gênica , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Imuno-Histoquímica , Ovário/metabolismo , Suínos , Fator A de Crescimento do Endotélio Vascular/metabolismo
13.
Front Microbiol ; 12: 727104, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34484169

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of both community- and hospital-associated infections. The antibiotic resistance and virulence characteristics of MRSA are largely regulated by two-component signal transduction systems (TCS) including the graRS TCS. To make a relatively comprehensive insight into graRS TCS in MRSA, the bioinformatics analysis of dataset GSE26016 (a S. aureus HG001 WT strain vs. the ΔgraRS mutant) from Gene Expression Omnibus (GEO) database was performed, and a total of 563 differentially expressed genes (DEGs) were identified. GO analysis revealed that the DEGs were mainly enriched in the "de novo" IMP biosynthetic process, lysine biosynthetic process via diaminopimelate, and pathogenesis; and they were mainly enriched in purine metabolism, lysine biosynthesis, and monobactam biosynthesis in KEGG analysis. WGCNA suggested that the turquoise module was related to the blue module, and the genes in these two modules were associated with S. aureus virulence and infection. To investigate the role of graRS in bacterial virulence, a graRS knockout mutant (ΔgraRS) was constructed using MRSA USA500 2,395 strain as a parent strain. Compared to the wild-type strain, the USA500ΔgraRS showed reduced staphyloxanthin production, retarded coagulation, weaker hemolysis on blood agar plates, and a decreased biofilm formation. These altered phenotypes were restored by the complementation of a plasmid-expressed graRS. Meanwhile, an expression of the virulence-associated genes (coa, hla, hlb, agrA, and mgrA) was downregulated in the ΔgraRS mutant. Consistently, the A549 epithelial cells invasion of the ΔgraRS mutant was 4-fold lower than that of the USA500 wild-type strain. Moreover, on the Galleria mellonella infection model, the survival rate at day 5 post infection in the USA500ΔgraRS group (55%) was obviously higher than that in the USA500 group (20%), indicating graRS knockout leads to a decreased virulence in vivo. In addition, the deletion of the graRS in the MRSA USA500 strain resulted in its increased susceptibilities to ampicillin, oxacillin, vancomycin, and gentamicin. Our work suggests that the graRS TCS plays an important role in regulating S. aureus virulence in vitro and in vivo and modulate bacterial resistance to various antibiotics.

14.
Int J Chron Obstruct Pulmon Dis ; 16: 2039-2047, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34267511

RESUMO

Purpose: The use of simple and affordable screening tools for chronic obstructive pulmonary disease (COPD) is limited. We aimed to assess the validity of a handheld expiratory flowmeter (Vitalograph Ltd., COPD-6®, Ireland) for COPD screening in Chinese primary care settings. Methods: In our cross-sectional study, subjects were randomly selected in eight primary care settings. Tests with the handheld expiratory flowmeter and the conventional spirometry were sequentially performed on all participants. The correlation between the handheld expiratory flowmeter and the conventional spirometry was determined. Validity was determined by the area under the receiver operator characteristic curve (AUC) of the forced expiratory volume in one second (FEV1)/forced expiratory volume in six seconds (FEV6) that used to detect airway obstruction. The sensitivity, specificity, predictive values, and likelihood ratio were calculated according to different FEV1/FEV6 cut-off points. Results: A total of 229 subjects (15.4%) were diagnosed with airflow limitation by conventional spirometry. FEV1, FEV6, and FEV1/FEV6 measured by the handheld expiratory flowmeter were correlated with FEV1, FVC, and FEV1/FVC measured by the conventional spirometry (r=0.889, 0.835 and 0.647, p<0.001), respectively. AUC of the FEV1/FEV6 to determine airflow obstruction was 0.857 (95% CI: 0.826 to 0.888). No significant difference of AUC was observed between the symptomatic group and the asymptomatic group (AUC=0.869 vs 0.843, P=0.425). A similar phenomenon was found in the AUC of smokers and never-smokers (AUC=0.862 vs 0.840; P=0.515). The cut-off point for FEV1/FEV6 was 0.77 and the corresponding sensitivity and specificity were 71.2% and 89.8%, respectively. Conclusion: The handheld expiratory flowmeter might be used as a screening device for COPD in Chinese primary care settings.


Assuntos
Fluxômetros , Doença Pulmonar Obstrutiva Crônica , China , Estudos Transversais , Volume Expiratório Forçado , Humanos , Atenção Primária à Saúde , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Espirometria , Capacidade Vital
15.
Environ Res ; 201: 111544, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34157271

RESUMO

BACKGROUND: While temperature changes have been confirmed as one of the contributory factors affecting human health, the association between high-frequency temperature variability (HFTV, i.e., temperature variation at short time scales such as 1, 2, and 5 days) and the hospitalization of chronic obstructive pulmonary disease (COPD) was rarely reported. OBJECTIVES: To evaluate the associations between high-frequency temperature variabilities (i.e., at 1, 2, and 5-day scales) and daily COPD hospitalization. METHODS: We collected daily records of COPD hospitalization and meteorological variables from 2013 to 2017 in 21 cities of Guangdong Province, South China. A quasi-Poisson regression with a distributed lag nonlinear model was first employed to quantify the effects of two HFTV measures, i.e., the day-to-day (DTD) temperature change and the intraday-interday temperature variability (IITV), on COPD morbidity for each city. Second, we used multivariate meta-analysis to pool the city-specific estimates, and stratified analyses were performed by age and sex to identify vulnerable groups. Then, the meta-regression with city-level characteristics was employed to detect the potential sources of the differences among 21 cities. RESULTS: A monotonic increasing curve of the overall exposure-response association was observed, suggesting that positive HFTV (i.e., increased DTD and IITV) will significantly increase the risk of COPD admission. Negative DTD was associated with reduced COPD morbidity while positive DTD elevated the COPD risk. An interquartile range (IQR) increase in DTD was associated with a 24% (95% CI: 12-38%) increase in COPD admissions. An IQR increase in IITV0-1 was associated with 18% (95% CI: 7-27%) increase in COPD admissions. Males and people aged 0-64 years appeared to be more vulnerable to the DTD effect than others. Potential sources of the disparity among different cities include urbanization level, sex structure, industry structure, gross domestic product (GDP), health care services, and air quality. CONCLUSIONS: The increases of DTD and IITV have significant adverse impacts on COPD hospitalization. As climate change intensifies, precautions need to be taken to mitigate the impacts of high-frequency temperature changes.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Doença Pulmonar Obstrutiva Crônica , Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/análise , China/epidemiologia , Cidades , Hospitalização , Humanos , Masculino , Morbidade , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/etiologia , Temperatura
16.
Ann Transl Med ; 9(5): 390, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33842611

RESUMO

BACKGROUND: Prior pulmonary tuberculosis (TB) can cause permanent changes in lung anatomy and is associated with lung function loss. However, it remains unclear whether pulmonary function impairment owing to TB is associated with airflow obstruction, the hallmark of chronic obstructive pulmonary disease (COPD). The aim of this systematic review and meta-analysis was to assess the association and quantify the magnitudes of association between pulmonary TB and COPD, and to evaluate the prevalence of COPD in patients with prior pulmonary TB. METHODS: We searched the PubMed, Embase, and Web of Science databases for studies published from inception to January 1, 2020. Pooled effect sizes were calculated according to a random effects model or fixed effect model depending on heterogeneity. Specific subgroups (different diagnostic criteria, smoking status, income level) were examined. RESULTS: A total of 23 articles were included in this study. Compared with controls, patients with pulmonary TB had an odds ratios (ORs) of 2.59 [95% confidence interval (CI): 2.12-3.15; P<0.001] for developing COPD. In jackknife sensitivity analyses, the increased risk of prior pulmonary TB remained consistent for COPD; when the meta-analysis was repeated and one study was omitted each time, the ORs and corresponding 95% CIs were greater than 2. Funnel plots of ORs with Egger's linear regression (t=2.00, P=0.058) and Begg's rank correlation (Z=0.75, P=0.455) showing no significant publication bias. Subgroup analysis showed that the same conclusion was still present in never smokers (ORs 2.41; 95% CI: 1.74-3.32; P<0.001), patients with pulmonary TB diagnosed using chest X-ray (ORs 2.47; 95% CI: 1.23-4.97; P<0.001), and low- and middle-income country (LMIC) settings (ORs 2.70; 95% CI: 2.08-3.51; P<0.001). The pooled prevalence of COPD in patients with prior pulmonary TB was 21% (95% CI: 16-25%; P<0.001). CONCLUSIONS: Individuals with prior pulmonary TB have an increased risk and high prevalence of COPD. Future studies identifying the underlying mechanisms for TB-associated COPD and therapeutic strategies are required.

17.
Biochem Biophys Res Commun ; 545: 195-202, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33571908

RESUMO

Epilepsy is accompanied by abnormal neurotransmission, and microRNAs, as versatile players in the modulation of gene expression, are important in epilepsy pathology. Here, we found that miR-128 expression was elevated in the acute seizure phase and decreased during the recurrent seizure phase after status epilepticus in mice. Both SNAP-25 and SYT1 are regulated by miR-128 in vitro and in vivo. Overexpressing miR-128 in cultured neurons decreased neurotransmitter released by suppressing SNAP-25 and SYT1 expression. Anti-miR-128 injection before kainic acid (KA) injection increased the sensitivity of mice to KA-induced seizures, while overexpressing miR-128 at the latent and recurrent phases had a neuroprotective effect in KA-induced seizures. Our study shows for the first time that miR-128, a key regulator of neurotransmission, plays an important role in epilepsy pathology and that miR-128 might be a potential candidate molecular target for epilepsy therapy.


Assuntos
Epilepsia/genética , Hipocampo/metabolismo , MicroRNAs/genética , Proteína 25 Associada a Sinaptossoma/genética , Sinaptotagmina I/genética , Animais , Regulação para Baixo , Epilepsia/metabolismo , Técnicas de Silenciamento de Genes , Hipocampo/efeitos dos fármacos , Ácido Caínico/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Convulsões/induzido quimicamente , Convulsões/genética , Convulsões/metabolismo , Estado Epiléptico/genética , Estado Epiléptico/metabolismo , Transmissão Sináptica/genética , Transmissão Sináptica/fisiologia , Proteína 25 Associada a Sinaptossoma/metabolismo , Sinaptotagmina I/metabolismo
18.
Ecotoxicol Environ Saf ; 208: 111590, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396113

RESUMO

AIMS: To assess possible effect of air quality improvements, we investigated the temporal change in hospital admissions for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) associated with pollutant concentrations. METHODS: We collected daily concentrations of particulate matter (i.e., PM2.5, PM10 and PMcoarse), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), ozone (O3), and admissions for AECOPD for 21 cities in Guangdong from 2013 to 2017. We examined the association of air pollution with AECOPD admissions using two-stage time-series analysis, and estimated the annual attributable fractions, numbers, and direct hospitalization costs of AECOPD admissions with principal component analysis. RESULTS: From 2013-2017, mean daily concentrations of SO2, PM10 and PM2.5 declined by nearly 40%, 30%, and 26% respectively. As the average daily 8 h O3 concentration increased considerably, the number of days exceeding WHO target (i.e.,100 µg/m³) increased from 103 in 2015-152 in 2017. For each interquartile range increase in pollutant concentration, the relative risks of AECOPD admission at lag 0-3 were 1.093 (95% CI 1.06-1.13) for PM2.5, 1.092 (95% CI 1.08-1.11) for O3, and 1.092 (95% CI 1.05-1.14) for SO2. Attributable fractions of AECOPD admission advanced by air pollution declined from 9.5% in 2013 to 4.9% in 2016, then increased to 6.0% in 2017. A similar declining trend was observed for direct AECOPD hospitalization costs. CONCLUSION: Declined attributable hospital admissions for AECOPD may be associated with the reduction in concentrations of PM2.5, PM10 and SO2 in Guangdong, while O3 has emerged as an important risk factor. Summarizes the main finding of the work: Reduction in PM may result in declined attributable hospitalizations for AECOPD, while O3 has emerged as an important risk factor following an intervention.


Assuntos
Poluentes Atmosféricos/toxicidade , Poluição do Ar/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Poluição do Ar/análise , Monóxido de Carbono/análise , China , Hospitais , Humanos , Dióxido de Nitrogênio/análise , Ozônio/análise , Material Particulado/análise , Doença Pulmonar Obstrutiva Crônica/etiologia , Fatores de Risco , Dióxido de Enxofre/análise
19.
J Clin Pharm Ther ; 46(1): 4-16, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33085789

RESUMO

WHAT IS KNOWN AND OBJECTIVE: The incidence of diabetes has been rising worldwide and is expected to increase to affect 591.9 million people by 2035 in China. Strict control of blood glucose can significantly reduce the risk of diabetic complications, but traditional interventions lack continuity, timeliness and teleonomy. The development of mobile health management has become a hot topic, as a very popular app in China, WeChat platform, has a large number of users every day. Many studies show the health management of patients with diabetes through WeChat can achieve the ideal effect. This study aims to evaluate the application of WeChat based on clinical research data, provide clinical evidence for medical staff and promote the self-management of patients with diabetes. METHODS: The PubMed, EMBASE, Cochrane Library, CNKI and Wanfang database were searched to identify related reports that were published up to 9 March 2020. The quality of included studies was assessed by Cochrane Collaboration risk assessment tool. Measures of interest were mean difference (MD) and 95% confidence interval (CI). Random-effect model was used according to the absence or presence of significant heterogeneity. Heterogeneity among trials was evaluated by I2 test. Publication bias was assessed by funnel plots. RESULTS AND DISCUSSION: Thirty-eight articles involved 2,709 controls and 2,709 patients who used WeChat were identified. Relative to the traditional group, WeChat group had a lower level in fasting plasma glucose (FPG in mmol/L; MD: 1.36, 95% CI 1.10-1.62, P < .00001), so did 2hPG (MD: 1.91, 95% CI 1.48-2.35, P < .00001) and HbA1C (MD: 1.07, 95% CI 0.86-1.27, P < .00001). Self-efficacy scale improved significantly, including diet score (MD: -1.31, 95% CI -1.77 to -0.86, P < .00001), exercise score (MD: -1.92, 95% CI -2.44 to -1.40, P < .00001), medication taking score (MD: -1.45, 95% CI: -1.94 to -0.97, P < .00001), monitoring of blood glucose score (MD: -1.17, 95% CI -1.83--0.51, P = .0005) and foot care score (MD: -1.71, 95% CI -2.08 to -1.34, P < .00001). Patients' understanding of the disease and satisfaction with follow-up increased significantly, whereas the incidence of adverse reactions and complications decreased. WHAT IS NEW AND CONCLUSION: WeChat follow-up appears to be helpful to improve the level of blood glucose and self-management, reduce the incidence of adverse reactions and complications, and improve the satisfaction rate of patients with type 2 diabetes. It should be noted that this meta-analysis has limitations, such as small sample sizes and the low quality of included literature, as well as the lack of research in Western countries. Therefore, more high-quality studies with larger samples are needed in the future to verify our results.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Aplicativos Móveis , Autocuidado , Humanos , Hipoglicemiantes/administração & dosagem
20.
Int J Hyg Environ Health ; 231: 113654, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33157415

RESUMO

The relation of acute fluctuations of air pollution to hospital admission for bronchiectasis remained uncertain, and large-scale studies were needed. We collected daily concentrations of particulate matter (PM), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), ozone (O3), and daily hospitalizations for bronchiectasis for 21 cities across Guangdong Province from 2013 through 2017. We examined their association using two-stage time-series analysis. Our analysis was stratified by specific sub-diagnosis, sex and age group to assess potential effect modifications. Relative risks of hospitalization for bronchiectasis were 1.060 (95%CI 1.014-1.108) for PM10 at lag0-6, 1.067 (95%CI 1.020-1.116) for PM2.5 at lag0-6, 1.038 (95%CI 1.005-1.073) for PMcoarse at lag0-6, 1.058 (95%CI 1.015-1.103) for SO2 at lag0-4, 1.057 (95%CI 1.030-1.084) for NO2 at lag0 and 1.055 (95%CI 1.025-1.085) for CO at lag0-6 per interquartile range increase of air pollution. Specifically, acute fluctuations of air pollution might be a risk factor for bronchiectasis patients with lower respiratory infection but not with hemoptysis. Patients aged ≥65 years, and female patients appeared to be particularly susceptible to air pollution. Acute fluctuations of air pollution, particularly PM may increase the risk of hospital admission for bronchiectasis exacerbations, especially for the patients complicated with lower respiratory infection. This study strengthens the importance of reducing adverse impact on respiratory health of air pollution to protect vulnerable populations.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Bronquiectasia , Ozônio , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Bronquiectasia/epidemiologia , China/epidemiologia , Exposição Ambiental , Feminino , Hospitalização , Hospitais , Humanos , Dióxido de Nitrogênio/análise , Ozônio/efeitos adversos , Ozônio/análise , Material Particulado/efeitos adversos , Material Particulado/análise , Dióxido de Enxofre/análise
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