Chang Gung Memorial Hospital at Linkuo

Taoyuan, Taiwan

Chang Gung Memorial Hospital at Linkuo

Taoyuan, Taiwan
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Shen J.-J.,Chang Gung University | Shen J.-J.,Chang Gung Memorial Hospital at Linkuo | Chiang M.-S.,Chang Gung University | Kuo M.-L.,Chang Gung University | And 4 more authors.
Journal of Ethnopharmacology | Year: 2011

Aim of the study: Viscum coloratum Nakai is used in traditional Chinese medicine to treat various diseases, including hemorrhage, hypertension, and inflammatory diseases. A previous study demonstrated a partially purified extract (PPE-SVC) and viscolin from Viscum coloratum Nakai inhibited phosphodiesterase activity. In this study, we evaluated the anti-asthmatic effects of PPE-SVC and viscolin, from Viscum coloratum Nakai, in OVA-sensitized mice. Materials and methods: Female BALB/c mice were sensitized and challenged with ovalbumin (OVA). The mice were randomized into groups and treated with PPE-SVC, viscolin, or rolipram by intraperitoneal injection on 1 h before each inhalation of OVA and airway hyperresponsiveness (AHR). Results: PPE-SVC and viscolin suppressed AHR and reduced eosinophil infiltration of the lungs in OVA-sensitized mice. Moreover, PPE-SVC and viscolin inhibited chemokines, including CCL11 and CCL24, and Th2-associated cytokines in bronchoalveolar lavage fluid. However, PPE-SVC and viscolin could not decrease IL-4, IL-5, and IL-13 levels in cultures of OVA-activated spleen cells. Conclusion: PPE-SVC and viscolin attenuate airway inflammation and eosinophil infiltration in OVA-sensitized mice. © 2011 Elsevier Ireland Ltd. All rights reserved.


Chen H.-M.,Fu Jen Catholic University | Yang C.-M.,Chang Gung University | Yang C.-M.,Chang Gung Memorial Hospital at Linkuo | Chang J.-F.,Fu Jen Catholic University | And 4 more authors.
American Journal of Physiology - Lung Cellular and Molecular Physiology | Year: 2016

Adiponectin, an adipokine, accumulated in lung system via T-cadherin after allergens/ozone challenge. However, the roles of adiponectin on lung pathologies were controversial. Here we reported that adiponectin stimulated expression of inflammatory proteins, cytosolic phospholipase A2 (cPLA2), cyclooxygenase-2 (COX-2), and production of reactive oxygen species (ROS) in human alveolar type II A549 cells. AdipoR1/2 involved in adiponectin-activated NADPH oxidase and mitochondria, which further promoted intracellular ROS accumulation. Protein kinase C (PKC) may involve an adiponectin-activated NADPH oxidase. Similarly, p300 phosphorylation and histone H4 acetylation occurred in adiponectin-challenged A549 cells. Moreover, adiponectin-upregulated cPLA2 and COX-2 expression was significantly abrogated by ROS scavenger (N-acetylcysteine) or the inhibitors of NADPH oxidase (apocynin), mitochondrial complex I (rotenone), PKC (Ro31-8220, Gö-6976, and rottlerin), and p300 (garcinol). Briefly, we reported that adiponectin stimulated cPLA2 and COX-2 expression via AdipoR1/2-dependent activation of PKC/NADPH oxidase/ mitochondria resulting in ROS accumulation, p300 phosphorylation, and histone H4 acetylation. These results suggested that adiponectin promoted lung inflammation, resulting in exacerbation of pulmonary diseases via upregulating cPLA2 and COX-2 expression together with intracellular ROS production. Understanding the adiponectin signaling pathways on regulating cPLA2 and COX-2 may help develop therapeutic strategies on pulmonary diseases. © 2016 the American Physiological Society.


Han C.,Korea University | Wang S.-M.,Catholic University of Korea | Kwak K.-P.,Dongguk University | Won W.-Y.,Catholic University of Korea | And 5 more authors.
Journal of Psychiatric Research | Year: 2015

No study has directly compared the efficacy and tolerability of aripiprazole augmentation (AA) and antidepressant switching (SW) in patients with major depressive disorder (MDD). This is the first 6-week, randomized, rater-blinded, direct comparison study between AA and SW in outpatients. An inadequate response to antidepressants was defined as a total score ≥14 on the Hamilton Depression Rating Scale-item 17 (HDRS-17) despite adequate antidepressant dosage for at least 6 weeks in the current depressive episode. The primary endpoint was change in the total score of the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to the end of treatment. Secondary efficacy measures included the response and remission rates as priori defined at the end of treatment: changes in total scores of the HDRS-17, Iowa Fatigue Scale (IFS), and Sheehan Disability Scale (SDS) from baseline to the end of treatment and the proportion of patients who scored 1 or 2 on the Clinical Global Impression-Improvement Score (CGI-I) at the end of treatment. Tolerability was assessed with the Barnes Akathisia Rating Scale (BARS) and Arizona Sexual dysfunction scale (ASEX), and the numbers of adverse events were compared between the two groups. A total of 101 patients were randomized to either AA (n=52) or SW (n=49). The mean change in the MADRS score from baseline was significantly higher in the AA, with a difference in magnitude of-8.7 (p<0.0001). The intergroup difference was first evident in week 2. The numbers of responders (p=0.0086) and remitters (p=0.0005) were also significantly higher in the AA (60% and 54%, respectively) compared with the SW (32.6% and 19.6%, respectively). On most secondary endpoints, AA showed better clinical outcomes compared to SW. The tolerability profiles were comparable between the two groups. Overall, AA yielded potentially beneficial clinical outcomes compared to SW. Given the methodological shortcomings of the present study, adequately powered, more rigorously controlled clinical trials are strongly warranted to confirm the present findings. © 2015 Elsevier Ltd.


PubMed | Soonchunhyang University, Korea University, Catholic University of Korea, Dongguk University and 3 more.
Type: | Journal: Journal of psychiatric research | Year: 2015

No study has directly compared the efficacy and tolerability of aripiprazole augmentation (AA) and antidepressant switching (SW) in patients with major depressive disorder (MDD). This is the first 6-week, randomized, rater-blinded, direct comparison study between AA and SW in outpatients. An inadequate response to antidepressants was defined as a total score 14 on the Hamilton Depression Rating Scale-item 17 (HDRS-17) despite adequate antidepressant dosage for at least 6 weeks in the current depressive episode. The primary endpoint was change in the total score of the Montgomery-sberg Depression Rating Scale (MADRS) from baseline to the end of treatment. Secondary efficacy measures included the response and remission rates as priori defined at the end of treatment: changes in total scores of the HDRS-17, Iowa Fatigue Scale (IFS), and Sheehan Disability Scale (SDS) from baseline to the end of treatment and the proportion of patients who scored 1 or 2 on the Clinical Global Impression-Improvement Score (CGI-I) at the end of treatment. Tolerability was assessed with the Barnes Akathisia Rating Scale (BARS) and Arizona Sexual dysfunction scale (ASEX), and the numbers of adverse events were compared between the two groups. A total of 101 patients were randomized to either AA (n = 52) or SW (n = 49). The mean change in the MADRS score from baseline was significantly higher in the AA, with a difference in magnitude of -8.7 (p < 0.0001). The intergroup difference was first evident in week 2. The numbers of responders (p = 0.0086) and remitters (p = 0.0005) were also significantly higher in the AA (60% and 54%, respectively) compared with the SW (32.6% and 19.6%, respectively). On most secondary endpoints, AA showed better clinical outcomes compared to SW. The tolerability profiles were comparable between the two groups. Overall, AA yielded potentially beneficial clinical outcomes compared to SW. Given the methodological shortcomings of the present study, adequately powered, more rigorously controlled clinical trials are strongly warranted to confirm the present findings.


Lin C.-C.,Chang Gung Memorial Hospital at Linkuo | Lin C.-C.,Chang Gung University | Pan C.-S.,Chang Gung University | Wang C.-Y.,Chang Gung University | And 5 more authors.
Journal of Biomedical Science | Year: 2015

Background: Tumor necrosis factor-α (TNF-α) is a proinflammatory cytokine and elevated in the regions of tissue injury and inflammatory diseases. The deleterious effects of TNF-α on fibroblasts may aggravate heart inflammation mediated through the up-regulation of adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1). However, the mechanisms underlying TNF-α-induced VCAM-1 expression in cardiac fibroblasts remain unknown. This study aimed to investigate the roles of TNF-α in VCAM-1 expression and its effects on human cardiac fibroblasts (HCFs). Results: The primary culture HCFs were used in this study. The results obtained with Western blotting, real time-quantitative PCR, and promoter activity analyses showed that TNF-α-induced VCAM-1 expression was mediated through TNF receptor (TNFR) 1-dependent gene up-regulation. Activation of TNFR1 by TNF-α transactivated c-Src-dependent EGF receptor (EGFR) linking to PI3K/Akt cascade, and then led to transcriptional activity of NF-κB. Moreover, the results of promoter reporter assay demonstrated that the phosphorylated p65 NF-κB turned on VCAM-1 gene expression. Subsequently, up-regulation of VCAM-1 promoted monocytes adhesion to HCFs challenged with TNF-α determined by cell adhesion assay. Conclusions: Taken together, these results indicate that in HCFs, activation of NF-κB by c-Src-mediated transactivation of EGFR/PI3K/Akt cascade is required for TNF-α-induced VCAM-1 expression. Finally, increased VCAM-1 enhances monocytes adhering to HCFs challenged with TNF-α. Understanding the mechanisms of VCAM-1 up-regulated by TNF-α on HCFs may provide rationally therapeutic interventions for heart injury or inflammatory diseases. © 2015 Lin et al.


Cheung Y.-C.,Chang Gung University | Tsai H.-P.,Chang Gung Memorial Hospital at Linkuo | Tsai H.-P.,Chang Gung University | Lo Y.-F.,Chang Gung Memorial Hospital at Linkuo | And 5 more authors.
European Radiology | Year: 2016

Objective: To assess the utility of dual-energy contrast-enhanced spectral mammography (DE-CESM) for evaluation of suspicious malignant microcalcifications. Methods: Two hundred and fifty-six DE-CESMs were reviewed from 2012–2013, 59 cases fulfilled the following criteria and were enrolled for analysis: (1) suspicious malignant microcalcifications (BI-RADS 4) on mammogram, (2) no related mass, (3) with pathological diagnoses. The microcalcification morphology and associated enhancement were reviewed to analyse the accuracy of the diagnosis and cancer size measurements versus the results of pathology. Results: Of the 59 microcalcifications, 22 were diagnosed as cancers, 19 were atypical lesions and 18 were benign lesions. Twenty (76.9 %) cancers, three (11.55 %) atypia and three (11.55 %) benign lesions revealed enhancement. The true-positive rate of intermediate- and high-concern microcalcifications was significantly higher than that of low-concern lesions (93.75 % vs. 50 %). Overall, the diagnostic sensitivity of enhancement was 90.9 %, with 83.78 % specificity, 76.92 % positive predictive value, 93.94 % negative predictive value and 86.4 % accuracy. Performance was good (AUC = 0.87) according to a ROC curve and cancer size correlation with a mean difference of 0.05 cm on a Bland-Altman plot. Conclusions: DE-CESM provides additional enhancement information for diagnosing breast microcalcifications and measuring cancer sizes with high correlation to surgicohistology. Key Points: • DE-CESM provides additional enhancement information for diagnosing suspicious breast microcalcifications. • The enhanced cancer size closely correlates to microscopy by Bland-Altman plot. • DE-CESM could be considered for evaluation of suspicious malignant microcalcifications. © 2015, European Society of Radiology.


Yeh K.-W.,Chang Gung University | Lee C.-M.,Chang Gung University | Chang C.-J.,Chang Gung University | Chang C.-J.,Chang Gung Memorial Hospital at Linkuo | And 2 more authors.
PLoS ONE | Year: 2014

Objective: Dyslipidemia with higher inflammatory states, disease activity, and longer disease duration in juvenile idiopathic arthritis (JIA) patients seemed to increase the risks of atherosclerosis. Tumor necrosis factor- α (TNF-α) receptor blocking agent etanercept has been proven to be effective in JIA. However, data about the correlation of anti-inflammatory treatment on lipid profiles and atherogenic index in JIA patients remains limited. This study aimed to investigate the longitudinal changes on lipid profiles and atherogenic index in JIA patients after etanercept treatment. Methods: Twenty-three patients diagnosed with JIA (polyarticular type n = 7; oligoarticular type, n = 2; systemic type, n = 10, Enthesitis-related arthritis = 4) received treatment with etanercept during the period 2004-012 in a medical center. We measured their serum lipid profiles at baseline and 2, 4, 6, 12 months later, and determined whether there were differences in complete blood counts, inflammatory mediators, lipid levels and atherogenic indices between patients who had inactive disease (responders) and those who were poor responders (non-responders) to etanercept treatment. Results: Analysis of dynamic change in total JIA patients before and after TNF inhibitor therapy showed modest increases in hemoglobin levels (P = 0.02) and decreases in WBC counts, Platelet and CRP levels progressively (p = 0.002, p = 0.006 and p = 0.006, respectively).Twelve of the 23 patients achieved inactive disease status (responders) after 12-months of treatment. In responders, compared to non-responders, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) increased significantly (P = 0.007,P = 0.044,P<0.001), whereas triglyceride and atherogenic index (TC/HDL-C ratio) significantly decreased (P = 0.04, P = 0.01, respectively) after etanercept treatment. Conclusion: Disease severity was associated with triglyceride level, atherogenic index and was inversely associated with total cholesterol, HDL-C, and LDL-C levels and can be improved substantially by using anti TNF-α treatment. Such treatment may have a beneficial effect on the cardiovascular risk in patients with JIA. © 2014 Yeh et al.


Chan P.-Y.S.,Chang Gung University | von Leupoldt A.,Catholic University of Leuven | von Leupoldt A.,University of Hamburg | Liu C.-Y.,Chang Gung Memorial Hospital at Linkuo | And 3 more authors.
Respiratory Physiology and Neurobiology | Year: 2014

There has been evidence for the effect of anxiety on the neural processing of respiratory sensation using the respiratory-related evoked potentials (RREP) elicited by inspiratory occlusions. This study tested the RREP elicited by inspiratory occlusions in a group of outpatients with generalized anxiety disorder (GAD) and a group of healthy controls. We hypothesized that the RREP P3 peak would be modulated in the GAD patients.A RREP oddball paradigm of 150-ms inspiratory occlusion protocol was used in 15 GAD patients and 11 healthy adults with normal lung functions. The RREP was recorded with a 40-channel electroencephalography (EEG) system. A minimum of 100 occlusions was collected for data analysis.We found that the averaged P3 latency of the GAD patients was significantly longer than the P3 latency of the healthy controls. In addition, the GAD group showed significantly reduced P3 amplitudes compared to the control group. No group differences in latency and amplitudes were found for earlier RREP components.These results demonstrated that a delayed and reduced attention peak (P3) is present in patients with GAD. This suggests that GAD as a disease state modulates the higher order processing of respiratory perception. © 2014 Elsevier B.V.All rights reserved.


Yeh K.-W.,Chang Gung University | Chang C.-J.,Chang Gung Memorial Hospital at Linkuo | Huang J.-L.,Chang Gung University
Asian Pacific Journal of Allergy and Immunology | Year: 2011

Background: The impact of air pollution on asthma in children in different age group has not been well defined. Objective: This study aimed to evaluate the association between seasonal variations in air pollution and asthma hospitalization of children within a two-year period. Methods: Using the National Health Insurance database, seasonal variations in hospitalization trends in children with a primary diagnosis of asthma (International Classification of Disease 9th revision, code 493) for patients aged < 18 years from 2001 to 2002 were investigated. Data on the average concentration of nitrogen dioxide (NO2), carbon monoxide (CO), ozone(O3), sulphur dioxide (SO2), and particles with aerodynamic diameter < 10 μm (PM10) for each month were obtained from the Environmental Protection Department through 71 stations of air quality monitor distributed nationwide. PSI value (pollutants standard index) > 100 was considered poor air quality. Seasonal variations in asthma admissions were compared to the air pollution quality data using Spearman's rank correlation. Results: Asthma hospitalization was not related to the number of days when the PSI was > 100 during the 24-months period (r = -0.361; p = 0.083). However, it was significantly associated wi th seasonal changes in the concentration of each pollutant. The most strongly related air pollutant variable was PM10 (standardized coefficients 0.384), followed by O3 (standardized coefficients 0.255) and SO2 (standardized coefficients 0.162) concentrations. The association of seasonal changes in asthma hospitalization with these pollutants was greater in pre-school and school age children. Temperature and rainfall in all seasons were not related to asthma hospitalization. None of the pollutants were associated with seasonal variations in admission rate for adolescents. Conclusion: Seasonal variations of asthma hospitalization among preschool children are associated with concentration of air pollutants.


PubMed | Chang Gung University and Chang Gung Memorial Hospital at Linkuo
Type: Journal Article | Journal: European radiology | Year: 2016

To assess the utility of dual-energy contrast-enhanced spectral mammography (DE-CESM) for evaluation of suspicious malignant microcalcifications.Two hundred and fifty-six DE-CESMs were reviewed from 2012-2013, 59 cases fulfilled the following criteria and were enrolled for analysis: (1) suspicious malignant microcalcifications (BI-RADS 4) on mammogram, (2) no related mass, (3) with pathological diagnoses. The microcalcification morphology and associated enhancement were reviewed to analyse the accuracy of the diagnosis and cancer size measurements versus the results of pathology.Of the 59 microcalcifications, 22 were diagnosed as cancers, 19 were atypical lesions and 18 were benign lesions. Twenty (76.9 %) cancers, three (11.55 %) atypia and three (11.55 %) benign lesions revealed enhancement. The true-positive rate of intermediate- and high-concern microcalcifications was significantly higher than that of low-concern lesions (93.75 % vs. 50 %). Overall, the diagnostic sensitivity of enhancement was 90.9 %, with 83.78 % specificity, 76.92 % positive predictive value, 93.94 % negative predictive value and 86.4 % accuracy. Performance was good (AUC=0.87) according to a ROC curve and cancer size correlation with a mean difference of 0.05 cm on a Bland-Altman plot.DE-CESM provides additional enhancement information for diagnosing breast microcalcifications and measuring cancer sizes with high correlation to surgicohistology. DE-CESM provides additional enhancement information for diagnosing suspicious breast microcalcifications. The enhanced cancer size closely correlates to microscopy by Bland-Altman plot. DE-CESM could be considered for evaluation of suspicious malignant microcalcifications.

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