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1.
Cancers (Basel) ; 13(21)2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34771509

RESUMO

Tobacco smoking is the top risk factor for lung cancer development. Nicotine in cigarettes can induce addiction, and its derivatives become potent carcinogens after metabolic activation and activate oncogenic signaling in lung epithelial cells through their expressed nicotinic acetylcholine receptors (nAChRs). However, the effects of smoking on the tumor immune microenvironment are under investigation. In the current study, we investigated whether nicotine activation of nicotinic acetylcholine receptor subunit α7 (nAChRα7, CHRNA7) would induce PD-L1 expression in lung epithelial cells. The expression levels of nAChRα7 and PD-L1 in eight human bronchial epithelial cell (HBEC) lines were measured after treatment with cigarette smoke extract (CSE) or nicotine derivatives. The results showed that PD-L1 expression levels increased in HBECs after exposure to CSE or nicotine derivatives. This induction of PD-L1 expression could be diminished by treatment with CHRNA7 small-interfering RNA, and the relevant signaling was mediated via STAT3 phosphorylation and NRF2 expression. In summary, this study demonstrated that the well-known nicotine derivative-activated nAChRα7 could induce STAT3/NRF2 pathways and subsequently promote PD-L1 expression in normal lung epithelial cells. This information provides mechanistic insight into cigarette smoke-induced immune evasion in lung epithelial cells.

2.
BMJ Open ; 11(10): e055575, 2021 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-34635536

RESUMO

OBJECTIVES: To compare the incidence and severity of invasive pneumococcal diseases (IPDs), pneumococcal pneumonia and all-cause pneumonia during the COVID-19 pandemic period with universal masking and social distancing with that of previous 5 years. DESIGN: Retrospective observational study on incidence of IPDs, pneumococcal pneumonia and all-cause pneumonia between January 2015-December 2019 and March 2020-March 2021. January-February 2020 was excluded from analysis as it was treated as a transitional period between normal time and pandemic. SETTING: Episode-based data by retrieval of hospitalisation records from the Hospital Authority's territory-wide electronic medical record database in Hong Kong. PARTICIPANTS: Hospitalised patients with IPD (n=742), pneumococcal pneumonia (n=2163) and all-cause pneumonia (including COVID-19 pneumonia, n=453 999) aged 18 years or above. Control diagnoses were included to assess confounding from health-seeking behaviours. PRIMARY AND SECONDARY OUTCOMES: Primary outcome is the incidence of diseases between two periods. Secondary outcomes include disease severity surrogated by length of stay and mortality. RESULTS: Monthly average number of IPD, pneumococcal pneumonia and all-cause pneumonia hospitalisation significantly decreased by 88.9% (95% CI 79.8% to 98.0%, p<0.0005), 72.5% (95% CI 65.9% to 79.1%, p<0.0005) and 17.5% (95% CI 16.8% to 18.2%, p<0.0005), respectively. Changes in trend from January 2015-December 2019 to March 2020-March 2021 were -70% (95% CI -87% to -35%, p=0.0025), -43% (95% CI -59% to -19%, p=0.0014) and -11% (95% CI -13% to -10%, p<0.0005), respectively. Length of stay for IPD and pneumococcal pneumonia episodes were insignificantly different in the two periods. No reductions in hospitalisations for control diagnoses were observed. CONCLUSIONS: Incidence of IPD, pneumococcal pneumonia and all-cause pneumonia decreased during the COVID-19 pandemic. This was observed with universal masking and social distancing. We postulated this is related to reduced transmission of respiratory viruses and bacteria.


Assuntos
COVID-19 , Infecções Pneumocócicas , Pneumonia Pneumocócica , Hong Kong/epidemiologia , Humanos , Incidência , Pandemias , Infecções Pneumocócicas/epidemiologia , Vacinas Pneumocócicas , Pneumonia Pneumocócica/epidemiologia , SARS-CoV-2
3.
J Stroke Cerebrovasc Dis ; 30(12): 106129, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34601243

RESUMO

OBJECTIVES: Recent meta-analyses have noted that ∼70% of transient ischemic attack (TIA)/stroke patients have sleep apnea. However, the heterogeneity between studies was high and did not appear to be accounted by the phase of stroke. We conducted an updated meta-analysis and aimed to determine whether the prevalence of sleep apnea amongst stroke patients differs by the subtype, etiology, severity and location of stroke and hence could account for some of the unexplained heterogeneity observed in previous studies. MATERIALS AND METHODS: We searched Medline, Embase, CINAHL and Cochrane Library (from their commencements to July 2020) for studies which reported the prevalence of sleep apnea by using polysomnography in TIA/stroke patients. We used random-effects model to calculate the pooled prevalence of sleep apnea and explored whether the prevalence differed by stroke characteristics. RESULTS: Seventy-five studies describing 8670 stroke patients were included in this meta-analysis. The overall prevalence of sleep apnea was numerically higher in patients with hemorrhagic vs. ischemic stroke [82.7% (64.4-92.7%) vs. 67.5% (63.2-71.5%), p=0.098], supratentorial vs. infratentorial stroke [64.4% (56.7-71.4%) vs. 56.5% (42.2-60.0%), p=0.171], and cardioembolic [74.3% (59.6-85.0%)] vs. other ischemic stroke subtypes [large artery atherosclerosis: 68.3% (52.5-80.7%), small vessel occlusion: 56.1% (38.2-72.6%), others/undetermined: 47.9% (31.6-64.6%), p=0.089]. The heterogeneity in sleep apnea prevalence was partially accounted by the subtype (1.9%), phase (5.0%) and location of stroke (14.0%) among reported studies. CONCLUSIONS: The prevalence of sleep apnea in the stroke population appears to differ by the subtype, location, etiology and phase of stroke.

4.
Biomed Pharmacother ; 143: 112101, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34474340

RESUMO

Chronic obstructive pulmonary disease (COPD) is among the leading causes of death worldwide, and is characterized by persistent respiratory symptoms and airflow limitation due to chronic airway inflammation. Cigarette smoking is a major risk factor for COPD. This study aims to determine the therapeutic effects of polysaccharides extracted from Dendrobium officinale (DOPs), a valuable traditional Chinese Medicinal herb, on cigarette smoke (CS)-induced airway inflammation in a rat passive smoking model. Male Sprague-Dawley rats were exposed to CS or sham air (SA) as control for a 56-day period. On Day 29, rats were subdivided and given water, DOPs or N-acetylcysteine (NAC) via oral gavage on a daily basis for the remaining duration. DOPs reduced CS-induced oxidative stress as evidenced by reducing malondialdehyde (MDA) levels in the lung. DOPs also exerted potent anti-inflammatory properties as evidenced by a reduction in the number of lymphocytes and monocytes in serum, significantly attenuating infiltration of inflammatory cells in lung tissue, as well as pro-inflammatory mediators in serum, bronchoalveolar lavage (BAL) and lung. Additionally, DOPs inhibited the CS-induced activation of ERK, p38 MAPK and NF-κB signaling pathways. These findings suggest that DOPs may have potentially beneficial effects in limiting smoking-related lung oxidative stress, and inflammation mediated via the inhibition of MAPK and NF-κB signaling pathways in smokers, without or with COPD.

5.
Front Psychiatry ; 12: 673531, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34220582

RESUMO

Background: The mental health of international students studying abroad has been neglected during the COVID-19 pandemic. Objective: This mixed-method study examined perceived public attitudes, personal beliefs, practice and stress toward facemask wearing as a preventive measure against COVID-19 among international University students from Hong Kong studying in the United Kingdom (UK) in the early stage (January-March 2020) of the pandemic. Methods: Our study included 2 parts: (i) an exponential, non-discriminative snowball sampling strategy was used to recruit 91 Chinese students studying in the UK to complete an online questionnaire survey, and (ii) online Zoom focus group interviews were conducted with 16 students who completed the online survey to gain an in-depth understanding of their experiences and coping methods during the pandemic. Results: Of the 91 students, 92.3% reported the UK public did not view facemask wearing as a preventive measure. 98.9% believed facemask wearing was an effective preventive measure, but 56% wore facemasks more than half of the time when out in public. 50.5% had internal conflicts of stress both when wearing and not wearing facemasks, which was more common in females than males [(62.5 vs. 31.5%), P = 0.004, Relative Risk (RR): 1.99 (1.17, 3.38)]. 61.5% reported public prejudiced attitudes against facemask wearing, also more common in females than males (71.4 vs. 45.7%), P = 0.02, RR: 1.56 (1.05, 2.32). The qualitative findings corroborated with the quantitative findings and reported that peer and family support were important for them to face such difficulties, and positive thinking and adaptability were effective methods on stress management. Conclusions: Since the outbreak of COVID-19, Chinese international students have been faced with a difficult, confusing, and sensitive situation. Owing to the ongoing pandemic, rising xenophobia and racist behaviors and the resumption of students' studies studies in the U.K., support from global communities are needed in their pursuit of quality education overseas. Our findings have significant implications on the proactive roles that governments should have, and the need for clear and accurate public health messaging to change public attitudes and mitigate prejudice. Academic institutions and mental health professionals need to proactively provide additional support to Chinese international students.

6.
Eur Respir J ; 58(5)2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33795324

RESUMO

BACKGROUND: The impact of treatment for obstructive sleep apnoea (OSA) on reduction of cardiovascular risk is unclear. This study aimed to examine the effect of continuous positive airway pressure (CPAP) on ambulatory blood pressure (BP) and subclinical myocardial injury in subjects with OSA and hypertension. METHODS: This was a parallel-group randomised controlled trial. Subjects with hypertension requiring at least three antihypertensive medications and moderate-to-severe OSA were enrolled. Eligible subjects were randomised (1:1) to receive either CPAP treatment or control (no CPAP) for 8 weeks. Changes in ambulatory BP and serum biomarkers were compared. Stratified analysis according to circadian BP pattern was performed. RESULTS: 92 subjects (75% male; mean±sd age 51±8 years and apnoea-hypopnoea index 40±8 events·h-1, taking an average of 3.4 (range 3-6) antihypertensive drugs) were randomised. The group on CPAP treatment, compared with the control group, demonstrated a significant reduction in 24-h systolic BP (-4.4 (95% CI -8.7- -0.1) mmHg; p=0.046), 24-h diastolic BP (-2.9 (95% CI -5.5- -0.2) mmHg; p=0.032), daytime systolic BP (-5.4 (95% CI -9.7- -1.0) mmHg; p=0.016) and daytime diastolic BP (-3.4 (95% CI -6.1- -0.8) mmHg; p=0.012). CPAP treatment was associated with significant BP lowering only in nondippers, but not in dippers. Serum troponin I (mean difference -1.74 (95% CI -2.97- -0.50) pg·mL-1; p=0.006) and brain natriuretic peptide (-9.1 (95% CI -17.6- -0.6) pg·mL-1; p=0.036) were significantly reduced in CPAP compared with the control group. CONCLUSIONS: In a cohort with OSA and multiple cardiovascular risk factors including difficult-to-control hypertension, short-term CPAP treatment improved ambulatory BP, and alleviated subclinical myocardial injury and strain.


Assuntos
Hipertensão , Apneia Obstrutiva do Sono , Adulto , Biomarcadores , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial , Pressão Positiva Contínua nas Vias Aéreas , Feminino , Humanos , Hipertensão/complicações , Hipertensão/terapia , Masculino , Pessoa de Meia-Idade , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/terapia
7.
Respir Res ; 22(1): 132, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33910573

RESUMO

BACKGROUND: Pseudomonas aeruginosa is one of the commonest bacteria colonizing the airway in patients with non-cystic fibrosis bronchiectasis. Pseudomonas aeruginosa colonization is associated with poor outcomes in patients with bronchiectasis, including rapid decline in lung function, exacerbation frequency and hospitalization. METHODS: A cross-sectional study in Queen Mary Hospital, Hong Kong that included 350 Chinese patients with non-cystic fibrosis bronchiectasis to investigate the risk factors for Pseudomonas aeruginosa colonization and clinical implications on disease outcomes. DISCUSSIONS: Pseudomonas aeruginosa colonization was more commonly found in patients with longer duration of bronchiectasis and those on proton pump inhibitors (PPIs) with adjusted ORs of 1.066 (95% CI = 1.036-1.096, p < 0.001) and 2.815 (95% CI = 1.307-6.064, p = 0.008) respectively. Patients with Pseudomonas aeruginosa colonization have more extensive lung involvement and higher risks of exacerbation requiring hospitalization with adjusted ORs of 2.445 (95% CI = 1.283-4.657, p = 0.007) and 2.745 (95% CI = 1.012-7.449, p = 0.047) respectively. Pseudomonas aeruginosa colonization is more common among patients with longer duration of bronchiectasis and those on PPI. Pseudomonas aeruginosa colonization is associated with more extensive lung involvement and higher risks of exacerbation requiring hospitalization.


Assuntos
Bronquiectasia/microbiologia , Pulmão/microbiologia , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/crescimento & desenvolvimento , Idoso , Idoso de 80 Anos ou mais , Bronquiectasia/diagnóstico , Bronquiectasia/terapia , Estudos Transversais , Progressão da Doença , Feminino , Hong Kong , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Bomba de Prótons/uso terapêutico , Infecções por Pseudomonas/diagnóstico , Infecções por Pseudomonas/terapia , Medição de Risco , Fatores de Risco , Fatores de Tempo
8.
BMC Public Health ; 21(1): 643, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33794830

RESUMO

BACKGROUND: Nonrestorative sleep is a common sleep disorder with a prevalence ranging from 1.4 to 35%, and is associated with various psychological and physical health issues. Noise exposure and noise sensitivity have been proposed to contribute to nonrestorative sleep. This study aimed to examine the relationships among noise, noise sensitivity, nonrestorative sleep, and physiological sleep parameters in Chinese adults. METHODS: A cross-sectional household survey was conducted with randomly selected Chinese adults based on a frame stratified by geographical districts and types of quarters in Hong Kong. We administered a battery of questionnaires, including the Nonrestorative Sleep Scale, the Weinstein Noise Sensitivity Scale, the ENRICHD Social Support Instrument, the Patient Health Questionnaire, and the Perceived Stress Scale to assess nonrestorative sleep, noise sensitivity, social support, somatic symptoms and stress, respectively. Anxiety and depression were evaluated by the Hospital Anxiety and Depression Scale while sociodemographic and lifestyle characteristics were assessed with an investigator-developed sheet. Nocturnal noise level and physiological sleep parameters were measured during nighttime for a week by noise dosimetry and actigraphy, respectively. A structured multiphase linear regression was conducted to estimate associations. RESULTS: A total of 500 adults (66.4% female) with an average age of 39 years completed this study. Bivariate regressions showed that age, marital status, occupation, family income, season, exercise, cola and soda consumption, social support, somatic symptoms, stress, depression, noise sensitivity, total sleep time, and awakenings were associated with nonrestorative sleep. In the multivariable analysis, family income, season, exercise, social support, somatic symptoms, stress, and depression remained associated with nonrestorative sleep. Specifically, a one-unit increase of noise sensitivity was associated with 0.08 increase in nonrestorative sleep (95% confidence interval [CI]: 0.01, 0.15, p = 0.023). Nocturnal noise was negatively associated with time in bed (b = - 1.65, 95% CI: - 2.77, - 0.52, p = 0.004), total sleep time (b = - 1.61, 95% CI: - 2.59, - 0.62, p = 0.001), and awakenings (b = - 0.16, 95% CI: - 0.30, - 0.03, p = 0.018), but was not associated with nonrestorative sleep. CONCLUSIONS: Nonrestorative sleep was predicted by noise sensitivity in addition to family income, season, exercise, social support, somatic symptoms, stress, and depression.


Assuntos
Transtornos do Sono-Vigília , Sono , Adulto , Ansiedade , China/epidemiologia , Estudos Transversais , Depressão , Feminino , Hong Kong/epidemiologia , Humanos , Masculino , Inquéritos e Questionários
9.
Artigo em Inglês | MEDLINE | ID: mdl-33498550

RESUMO

This study developed a short form of the traditional Chinese version of the Weinstein Noise Sensitivity Scale (WNSS) through optimal test assembly (OTA). A total of 1069 Chinese adults (64.8% female) completed the territory-wide cross-sectional study. We first removed Items 12 and 5 which had negative factor loading and gender-related differential item functioning (DIF), respectively. The optimal length was then determined as the minimal one that reasonably resembled the reliability and validity of the scale without DIF items. OTA identified an 8-item WNSS (WNSS-8) which retained 67.2% of the test information of the original 21-item scale and had a Cronbach's alpha of 0.83. It also showed significant correlations of 0.272 and -0.115 with the neuroticism and extraversion scales of Chinese NEO-Five Factor Inventory, respectively. Adequate model fit of the WNSS-8 was demonstrated by the confirmatory factor analysis. The Chinese WNSS-8 can be used to assess noise sensitivity without compromising reliability and validity.


Assuntos
Adulto , China , Estudos Transversais , Análise Fatorial , Feminino , Humanos , Masculino , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários
10.
Asia Pac J Clin Oncol ; 17(2): e35-e39, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31802642

RESUMO

BACKGROUND: Osimertinib has been approved by the Food and Drug Administration (FDA) of the United States (US) for the treatment of progressive non-small cell lung cancer (NSCLC) that has acquired T790M mutation during treatment with first-line epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI). We compared the progression-free survival (PFS) of patients whose T790M mutation was identified by tissue rebiopsy with those by plasma-based biopsy. METHODS: This is a retrospective single-center cohort study conducted in Queen Mary Hospital, Hong Kong S.A.R. that included 118 Chinese patients with advanced NSCLC who had disease progression after treatment with a first-line EGFR tyrosine kinase inhibitor and received osimertinib upon detection of T790M mutation, either by tissue rebiopsy or plasma-based biopsy (by identification of circulating tumor DNA in the peripheral circulation). The primary endpoint is PFS. RESULTS: Patients with T790M mutation detected by tissue rebiopsy (n = 22) had significantly better PFS than those by plasma-based biopsy (n = 96) (median PFS: 415 vs 224 days, P = .018) Hazard ratio for PFS, in favor of the tissue rebiopsy group, was 0.496 (95% confidence interval [CI]: 0.277-0.889). CONCLUSIONS: For patients who have NSCLC that progressed after first-line EGFR-TKI, rebiopsy by peripheral blood liquid biopsy and tissue rebiopsy for T790M mutation may have prognostic implication in terms of differences in PFS.


Assuntos
Acrilamidas/uso terapêutico , Compostos de Anilina/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Acrilamidas/farmacologia , Idoso , Compostos de Anilina/farmacologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Coortes , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Mutação , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/farmacologia , Estudos Retrospectivos , Análise de Sobrevida
11.
Lung Cancer ; 152: 15-20, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33338923

RESUMO

BACKGROUND: Pemetrexed was approved by United States Food and Drug Administration (US FDA) in combination with platinum for the treatment of advanced non-squamous non-small cell lung carcinoma (NSCLC) and malignant mesothelioma. Due to the structural similarity with methotrexate, there has been concern about the accumulation of pemetrexed in third space fluid that may result in increased toxicity. Previous small-scale studies have yet to conclusively prove this association. METHODS: This was a retrospective single-center cohort study conducted in Queen Mary Hospital in Hong Kong. The study included 329 patients with advanced stage non-squamous NSCLC that received first line pemetrexed and platinum. Patients who had non-evacuated third-space fluid, evacuated third-space fluid and without third-space fluid were compared. The primary endpoint was the occurrence of hematological toxicity. RESULTS: The presence of non-evacuated third-space fluid was shown to be associated with significantly more hematological toxicities, namely grade 3 or above hematological toxicities [Odd ratio (OR) = 2.450, p = 0.002], postponement of chemotherapy (OR = 3.837, p = 0.000) and need for dose adjustment (OR = 2.436, p = 0.022) when compared with those without third-space fluid. For patients with evacuated third-space fluid, these adverse effects were nullified. CONCLUSIONS: Presence of non-evacuated third-space fluid in patients with advanced non-squamous NSCLC predispose patients to significant hematological toxicity when pemetrexed and platinum chemotherapy is used. Evacuation of third-space fluid should be considered before starting pemetrexed and platinum doublet.


Assuntos
Neoplasias Pulmonares , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Estudos de Coortes , Humanos , Pulmão , Neoplasias Pulmonares/tratamento farmacológico , Pemetrexede/efeitos adversos , Estudos Retrospectivos
12.
Front Psychiatry ; 11: 584240, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33329126

RESUMO

Background: The coronavirus disease 2019 (COVID-19) pandemic has disrupted university teaching globally. The mental health impacts on international university students have been overlooked. Aims: This study examined the differences in COVID-19-related stressors and mental health impacts between international university students studying in the UK or USA who returned to their home country or region (returnees) and those who stayed in their institution country (stayers), and identified COVID-19-related stressors and coping strategies that were predictors of mental health. Method: An online questionnaire survey was conducted from April 28 through May 12, 2020 using an exponential, non-discriminative snowball sampling strategy (registered at the National Institutes of Health: NCT04365361). Results: A total of 124 full-time international university students (36.3% male) were included: 75.8% had returned to their home country or region for reasons related to COVID-19; 77.4% were pursuing a bachelor's program, and 53.2% were in programs with practicum component. 84.7% of all students had moderate-to-high perceived stress, 12.1% had moderate-to-severe symptoms of anxiety and depression, and 17.7% had moderate-to-severe symptoms of insomnia. Compared with returnees, stayers had significantly higher stress from COVID-19-related stressors such as personal health and lack of social support (Cohen's d: 0.57-1.11), higher perceived stress [10-item Perceived Stress Scale (PSS-10)] {22.6 ± 6.2 vs. 19.1 ± 6.1, ß [95% confidence interval (CI)]: 4.039 (0.816, 7.261), Cohen's d: 0.52}, and more severe insomnia symptoms [Insomnia Severity Index (ISI)] [11.8 ± 6.1 vs. 7.6 ± 5.2, ß (95% CI): 3.087 (0.262, 5.912), Cohen's d: 0.45], with moderate-to-large effect sizes. Compared with males, females reported significantly higher stress from uncertainties about academic program (Cohen's d: 0.45) with a small effect size. In the total sample, stress related to academics (e.g., personal attainment, uncertainties about academic program, and changes in teaching/learning format), health (including personal health and health of family and friends), availability of reliable COVID-19-related information, and lack of social support predicted more negative mental health impacts. Resilience, positive thinking, and exercise were predictors of less severe mental health impacts. Conclusions: Stayers experienced more adverse mental health impacts than returnees. We call on educators and mental health professionals to provide appropriate support for international students, particularly the stayers, during the pandemic.

13.
Oxid Med Cell Longev ; 2020: 8217642, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33144914

RESUMO

Chronic obstructive pulmonary disease (COPD), characterized by oxidative stress and inflammation, is one of the leading causes of death worldwide, in which cigarette smoke (CS) is the major risk factor. Dendrobium officinale polysaccharides (DOPs) are the main active ingredients extracted from Dendrobium officinale, which have been reported to have antioxidant and anti-inflammatory activity as well as inhibition of mucin gene expression. This study is aimed at investigating the effect of DOPs on CS-induced mucus hypersecretion and viscosity in vitro and in vivo. For in vitro study, primary normal human bronchial epithelial cells (HBECs) differentiated at the air-liquid interface (ALI) culture for 28 days were stimulated with cigarette smoke medium (CSM) in the absence or presence of various concentrations of DOPs or N-acetylcysteine (NAC) for 24 hours. For in vivo study, male Sprague-Dawley rats were randomized to sham air (SA) as control group or CS group for 56 days. At day 29, rats were subdivided and given water as control, DOPs, or NAC as positive control as a mucolytic drug via oral gavage for the remaining duration. Samples collected from apical washing, cell lysates, bronchoalveolar lavage (BAL), and lung tissues were evaluated for mucin gene expression, mucus secretion, and viscosity. DOPs ameliorated the CS-induced mucus hypersecretion and viscosity as shown by the downregulation of MUC5AC mRNA, MUC5AC secretary protein, and mucus viscosity via inhibition of mucus secretory granules in both in vitro and in vivo models. DOPs produced its effective effects on the CS-induced mucus hypersecretion and viscosity via the inhibition of the mucus secretory granules. These findings could be a starting point for considering the potential role of DOPs in the management of the smoking-mediated COPD. However, further research is needed.


Assuntos
Fumar Cigarros/efeitos adversos , Dendrobium/química , Muco/metabolismo , Polissacarídeos/farmacologia , Animais , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Células Epiteliais/ultraestrutura , Receptores ErbB/metabolismo , Células Caliciformes/patologia , Humanos , Hiperplasia , Masculino , Ratos Sprague-Dawley , Traqueia/patologia , Traqueia/ultraestrutura , Viscosidade
14.
J Chemother ; 32(8): 429-436, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33043860

RESUMO

Maintenance chemotherapy was studied in first line setting for advanced stage non-small cell lung carcinoma (NSCLC). There has not been any data on the role of continuation maintenance chemotherapy in second line setting. A retrospective cohort study that included 226 patients with advanced stage NSCLC that received second line gemcitabine ± platinum was conducted. Patients who had continuation maintenance gemcitabine were compared with those who went on drug holiday. The primary endpoint was progression-free survival (PFS), counted from the end of induction therapy. The median PFS was significantly longer for patients who continued with maintenance gemcitabine when compared with those on drug holiday (5.6 vs 1.7 months, HR 0.392, p-value < 0.001). The overall survival was also significantly longer (21.4 vs 15.8 months, HR 0.508, p-value 0.047). There was no increase in incidence of adverse events for patients who underwent maintenance gemcitabine. Continuation maintenance therapy with gemcitabine in second line setting is a potentially feasible and safe option for patients with advanced NSCLC.

15.
Int J Infect Dis ; 101: 74-82, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32947055

RESUMO

OBJECTIVES: To develop: (1) two validated risk prediction models for coronavirus disease-2019 (COVID-19) positivity using readily available parameters in a general hospital setting; (2) nomograms and probabilities to allow clinical utilisation. METHODS: Patients with and without COVID-19 were included from 4 Hong Kong hospitals. The database was randomly split into 2:1: for model development database (n = 895) and validation database (n = 435). Multivariable logistic regression was utilised for model creation and validated with the Hosmer-Lemeshow (H-L) test and calibration plot. Nomograms and probabilities set at 0.1, 0.2, 0.4 and 0.6 were calculated to determine sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). RESULTS: A total of 1330 patients (mean age 58.2 ± 24.5 years; 50.7% males; 296 COVID-19 positive) were recruited. The first prediction model developed had age, total white blood cell count, chest x-ray appearances and contact history as significant predictors (AUC = 0.911 [CI = 0.880-0.941]). The second model developed has the same variables except contact history (AUC = 0.880 [CI = 0.844-0.916]). Both were externally validated on the H-L test (p = 0.781 and 0.155, respectively) and calibration plot. Models were converted to nomograms. Lower probabilities give higher sensitivity and NPV; higher probabilities give higher specificity and PPV. CONCLUSION: Two simple-to-use validated nomograms were developed with excellent AUCs based on readily available parameters and can be considered for clinical utilisation.


Assuntos
COVID-19/diagnóstico , SARS-CoV-2 , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , COVID-19/etiologia , Feminino , Hospitais , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Nomogramas , Probabilidade
16.
Respir Med ; 171: 106085, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32917356

RESUMO

BACKGROUND: Chronic respiratory diseases are risk factors for severe disease in coronavirus disease 2019 (COVID-19). Respiratory tract infection is one of the commonest causes of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). There has not been evidence suggesting the link between COVID-19 and AECOPD, especially in places with dramatic responses in infection control with universal masking and aggressive social distancing. METHODS: This is a retrospective study to assess the number of admissions of AECOPD in the first three months of 2020 in Queen Mary Hospital with reference to the admissions in past five years. Log-linear model was used for statistical inference of covariates, including percentage of masking, air quality health index and air temperature. RESULTS: The number of admissions for AECOPD significantly decreased by 44.0% (95% CI 36.4%-52.8%, p < 0.001) in the first three months of 2020 compared with the monthly average admission in 2015-2019. Compare to same period of previous years, AECOPD decreased by 1.0% with each percent of increased masking (p < 0.001) and decreased by 3.0% with increase in 1 °C in temperature (p = 0.045). The numbers of admissions for control diagnoses (heart failure, intestinal obstruction and iron deficiency anaemia) in the same period in 2020 were not reduced. CONCLUSIONS: The number of admissions for AECOPD decreased in first three months of 2020, compared with previous years. This was observed with increased masking percentage and social distancing in Hong Kong. We postulated universal masking and social distancing during COVID-19 pandemics both contributed in preventing respiratory tract infections hence AECOPD.


Assuntos
COVID-19 , Infecções por Coronavirus , Pandemias , Admissão do Paciente/estatística & dados numéricos , Pneumonia Viral , Doença Pulmonar Obstrutiva Crônica , Infecções Respiratórias , Poluição do Ar/análise , Betacoronavirus/isolamento & purificação , COVID-19/epidemiologia , COVID-19/terapia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Feminino , Hong Kong/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/terapia , Dispositivos de Proteção Respiratória/estatística & dados numéricos , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/etiologia , Infecções Respiratórias/prevenção & controle , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Exacerbação dos Sintomas
17.
J Patient Rep Outcomes ; 4(1): 32, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32372244

RESUMO

BACKGROUND: Alertness is an important part of attention which is different from the opposite of sleepiness. This study aimed to translate and assess the measurement properties of the Toronto Hospital Alertness Test (THAT) in Hong Kong Chinese population. METHODS: The standard forward-backward translation procedure and cognitive debriefing were conducted to obtain the Chinese THAT. One hundred Chinese adults completed the Chinese THAT, the Center for Epidemiological Studies Depression Scale (CES-D), the Pittsburgh Sleep Quality Index (PSQI), and the Athens Insomnia Scale (AIS) by telephone interviews. RESULTS: The factorial validity was assessed by confirmatory factor analysis, and the internal reliability was examined by coefficient omega. The two negatively worded items of the THAT had low factor loadings and were removed. One more item was removed based on the modification indices of the eight-item model. The remaining seven-item THAT showed satisfactory unidimensionality with root mean square error of approximation (RMSEA) = 0.06, standardized root mean square residual (SRMR) = 0.08, and comparative fit index (CFI) = 1.00. The coefficient omega of the seven-item Chinese THAT was 0.80 (95% CI: 0.74-0.86). Convergent validity was demonstrated with THAT moderately associated with CES-D (r = - 0.45, P < 0.01), PSQI (r = - 0.40, P < 0.01), and AIS (r = - 0.45, P < 0.01). CONCLUSIONS: The Chinese version of THAT demonstrated acceptable reliability and validity in a Chinese population.

18.
Transl Lung Cancer Res ; 9(2): 294-305, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32420069

RESUMO

Background: The Hippo signalling pathway plays an important role in regulating organ size and cell proliferation. Down-regulation of large tumour suppressor (LATS) protein homologs LATS1 or LATS2 has been found in lung cancer. LATS1 and LATS2 are the core components of the Hippo signalling pathway. LATS1 and LATS2 share some conserved structural features and exhibit redundant biological functions. The aim of this study was to dissect the interaction between these two homologs. Methods: In lung adenocarcinoma (AD) cells, protein expression of LATS1 and LATS2 were determined by western blotting; cell viability and apoptosis were measured by MTT and annexin V staining after treatment with cisplatin; subcellular distributions of LATS proteins were determined by immunofluorescence microscopy; LATS2 expression was modulated by shRNA-mediated knockdown or ectopic expression in cancer cell lines. Results: Manipulation of the expression of these two LATS kinases influenced cisplatin response in advanced lung AD cell lines. High LATS2-to-LATS1 ratio in H2023 cells was associated with cisplatin resistance, while low LATS2-to-LATS1 ratio in CL1-0 and CL83 cells was associated with sensitivity to cisplatin. Manipulating the LATS2-to-LATS1 ratio by LATS2 over-expression in CL1-0 and CL83 rendered them resistant to cisplatin treatment, whereas LATS2 knockdown in H2023 alleviated the LATS2-to-LATS1 ratio and sensitized cancer cells to cisplatin exposure. Conclusions: Our data suggested that the ratio of expression of LATS kinases played a role in the modulation of cisplatin sensitivity in advanced lung AD, and targeting of LATS proteins as a novel therapeutic strategy for lung AD deserves further investigation.

19.
Respirology ; 25(11): 1167-1173, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32249488

RESUMO

BACKGROUND AND OBJECTIVE: The advent of effective anti-cancer therapy has brought about uncertainty on the benefit of early definitive measures for newly diagnosed MPE from lung cancer. This study aims to investigate the outcomes of MPE in this setting. METHODS: Lung cancer patients with MPE at first presentation to a tertiary care hospital were followed up till death or censored from 2011 to 2018. Early MPE control measures included chemical pleurodesis or IPC before or shortly after oncological treatment. Predictors of time to MPE re-intervention were identified with Cox proportional hazard analyses. RESULTS: Of the 509 records screened, 233 subjects were eligible. One hundred and twenty-seven subjects received oral targeted therapy as first-line treatment and 34 (26.8%) underwent early definitive MPE control measures. Early MPE control measures in addition to targeted therapy, as compared to targeted therapy alone, significantly reduced the subsequent need of MPE re-intervention (23.5% vs 53.8%, P = 0.002). Similar benefits from MPE control measures were found in groups receiving systemic anti-cancer therapy or best supportive care (0% vs 52%, P = 0.003; 18% vs 56.7%, P = 0.024, respectively). In the group with targetable mutations, both early MPE control measures (HR: 0.25, 95% CI: 0.12-0.53, P < 0.001) and the use of targeted therapy (HR: 0.22, 95% CI: 0.10-0.46, P < 0.001) were independently associated with longer time to MPE re-interventions. CONCLUSION: Early MPE control measures in lung cancer has additional benefits on reducing the need and prolonging the time to MPE re-intervention, independent of anti-cancer therapies.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Pulmonares , Derrame Pleural Maligno , Pleurodese/métodos , Toracentese/métodos , Idoso , Feminino , Humanos , Estudos Longitudinais , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/patologia , Masculino , Terapia de Alvo Molecular/métodos , Avaliação de Resultados em Cuidados de Saúde , Derrame Pleural Maligno/etiologia , Derrame Pleural Maligno/fisiopatologia , Derrame Pleural Maligno/terapia , Retratamento/estatística & dados numéricos , Tempo para o Tratamento
20.
Life Sci ; 238: 116959, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31628916

RESUMO

AIMS: This study was to investigate the degree of susceptibility to intermittent hypoxia (IH), a hallmark of obstructive sleep apnea (OSA), between the two mice inbred lines C57BL/6N (6N) and C57BL/6J (6J). MATERIALS AND METHODS: Four-week old male mice of 6N and 6J substrains (n = 8) were randomized to standard diet (SD) group or high fat (HF) diet group. At the age of 13-week, all two groups of mice were subjected to either air or IH (IH30; thirty hypoxic events per hour) for one week. KEY FINDINGS: All mice fed with HF diet exhibited obesity with more body weight and fat mass (percentage to body weight) gain. IH reduced serum LDL, HDL and total cholesterol levels in lean 6J mice. In obese mice, IH lowered obesity-induced serum total cholesterol level in 6J substrain but raised further in 6N substrain. Furthermore, IH caused elevation of serum FFA and MDA levels, and pro-inflammatory cytokines MCP-1 and IL-6 levels in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) of lean 6J but not lean 6N mice. There was reduced number of adipocytes and elevation of macrophages in SAT and VAT of HF-induced obese mice of both substrains. IH led to increased number of adipocytes and macrophages in SAT of lean 6J mice. SIGNIFICANCE: The genetic difference between 6N and 6J mice may have direct impact on metabolic and inflammatory responses after IH. Therefore, attention must be given for the selection of C57BL mice substrains in the experimental IH-exposed mouse model.


Assuntos
Biomarcadores/metabolismo , Hipóxia/complicações , Mediadores da Inflamação/metabolismo , Inflamação/etiologia , Gordura Intra-Abdominal/metabolismo , Obesidade/metabolismo , Magreza/metabolismo , Adiponectina/metabolismo , Animais , Glicemia/metabolismo , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Inflamação/metabolismo , Inflamação/patologia , Resistência à Insulina , Gordura Intra-Abdominal/imunologia , Gordura Intra-Abdominal/patologia , Leptina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/etiologia , Obesidade/patologia , Magreza/etiologia , Magreza/patologia , Ganho de Peso
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