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Lin Y.-W.,A-Life Medical | Tsao C.-M.,Graduate Institute of Medical science | Yu P.-N.,Graduate Institute of Medical science | Shih Y.-L.,Tri Service General Hospital | Yan M.-D.,Wan Fang Hospital
Gynecologic Oncology | Year: 2013

Objective. Abnormal activation of theWnt/β-catenin signaling pathway is common in human cancers, including cervical cancer.Many papers have shown that SRY (sex-determining region Y)-box (SOX) familygenes serve as either tumor suppressor genes (TSGs) or oncogenes by regulating the Wnt signaling pathway in different cancers. We have demonstrated recently that epigenetic silencing of SOX1 gene occurs frequently in cervical cancer. However, the possible role of SOX1 in cervical cancer remains unclear. This study aimed to explorewhether SOX1 functions as a TSG in cervical cancer. Methods.We established a constitutive and an inducible system that overexpressed SOX1 and monitored its function by in vitro experiments. To confirm SOX1 function,wemanipulated SOX1 using an inducible expression approach in cell lines. The effect of SOX1 on tumorigenesis was also analyzed in animal models. Results. Overexpression of SOX1 inhibited cell proliferation, anchorage independency, and invasion in vitro. SOX1 suppressed tumor growth in nonobese diabetic/severe combined immunodeficiency mice. After induction of SOX1 by doxycycline (DOX), SOX1 inhibited cell growth and invasion in the inducible system. Repression of SOX1 by withdrawal of DOX partially reversed the malignant phenotype in cervical cells. SOX1 inhibited TCF-dependent transcriptional activity and theWnt target genes. SOX1 also repressed the invasive phenotype by regulating the expression of invasion-related genes. Conclusions. Taken together, these data suggest that SOX1 can function as a tumor suppressor partly by interfering with Wnt/β-catenin signaling in cervical cancer. © 2013 Elsevier Inc. All rights reserved.


Wei H.-T.,Taipei Veterans General Hospital | Lai Y.-W.,Wan Fang Hospital | Chen M.-H.,Taipei Veterans General Hospital | Chen Y.-S.,Taipei Veterans General Hospital
General Hospital Psychiatry | Year: 2012

Objectives: Tardive dyskinesia (TD) is generally considered the most severe extrapyramidal sequelae of antipsychotic treatments. Method: Case report. Results: We present a 20-year-old woman with previous treatment of risperidone 6-7 mg daily for approximately 4 years. She developed TD 2 years later after switching to paliperidone 9 mg daily. To the best of our knowledge, she is the first case report of having direct paliperidone-induced TD. Immediate treatments including paliperidone dose reduction to 6 mg daily, clonazepam 1.5 mg daily and trihexyphenidyl 2 mg daily were performed for 1 month, and her symptoms were relieved eventually after switching to clozapine 75 mg daily. Conclusion: Although second-generation antipsychotics such as paliperidone are considered to have a lowered risk of developing TD, this case could bring awareness to clinicians of the possibility of TD with the use of any antipsychotics. © 2012 Elsevier Inc.


Bien M.-Y.,Taipei Medical University Hospital | Shih C.-H.,Taipei Medical University Hospital | Yang Y.-L.,Taipei Medical University Hospital | Lin H.-W.,Taipei Medical University Hospital | And 5 more authors.
Critical Care Medicine | Year: 2011

Objective: To investigate the influence of different ventilatory supports on the predictive performance of breathing pattern variability for extubation outcomes in intensive care unit patients. Design and Setting: A prospective measurement of retrospectively analyzed breathing pattern variability in a medical center. Patients: Sixty-eight consecutive and ready-for-weaning patients were divided into success (n = 45) and failure (n = 23) groups based on their extubation outcomes. Measurements: Breath-to-breath analyses of peak inspiratory flow, total breath duration, tidal volume, and rapid shallow breathing index were performed for three 30-min periods while patients randomly received T-piece, 100% inspiratory automatic tube compensation with 5 cm H2O positive end-expiratory pressure, and 5 cm H2O pressure support ventilation with 5 cm H2O positive end-expiratory pressure trials. Coefficient of variations and data dispersion (standard descriptor values SD1 and SD2 of the Poincaré plot) were analyzed to serve as breathing pattern variability indices. MAIN RESULTS:: Under all three trials, breathing pattern variability in extubation failure patients was smaller than in extubation success patients. Compared to the T-piece trial, 100% inspiratory automatic tube compensation with 5 cm H2O positive end-expiratory pressure and 5 cm H2O pressure support ventilation with 5 cm H2O positive end-expiratory pressure decreased the ability of certain breathing pattern variability indices to discriminate extubation success from extubation failure. The areas under the receiver operating characteristic curve of these breathing pattern variability indices were: T-piece (0.73-0.87) > 100% inspiratory automatic tube compensation with 5 cm H2O positive end-expiratory pressure (0.60-0.79) > 5 cm H2O pressure support ventilation with 5 cm H2O positive end-expiratory pressure (0.53-0.76). Analysis of the classification and regression tree indicated that during the T-piece trial, a SD1 of peak inspiratory flow >3.36 L/min defined a group including all extubation success patients. Conversely, the combination of a SD1 of peak inspiratory flow ≤3.36 L/min and a coefficient of variations of rapid shallow breathing index ≤0.23 defined a group of all extubation failure patients. The decision strategies using SD1 of peak inspiratory flow and coefficient of variations of rapid shallow breathing index measured during 100% inspiratory automatic tube compensation with 5 cm H2O positive end-expiratory pressure and 5 cm H2O pressure support ventilation with 5 cm H2O positive end-expiratory pressure trials achieved a less clear separation of extubation failure from extubation success. Conclusions: Since 100% inspiratory automatic tube compensation with 5 cm H2O positive end-expiratory pressure and 5 cm H2O pressure support ventilation with 5 cm H2O positive end-expiratory pressure reduce the predictive performance of breathing pattern variability, breathing pattern variability measurement during the T-piece trial is the best choice for predicting extubation outcome in intensive care unit patients patients. © 2011 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins.


Lee C.-J.,Taipei Medical University Hospital | Tai Y.-T.,Wan Fang Hospital | Lin Y.-L.,Taipei Medical University | Chen R.-M.,Wan Fang Hospital | Chen R.-M.,Taipei Medical University
Shock | Year: 2010

Propofol (PPF), a widely used intravenous anesthetic agent, has been reported to have immunosuppressive and antioxidative effects. NO plays crucial roles in mediating inflammatory reactions. This study was designed to evaluate the effects of PPF on regulation of iNOS and its possible signal-transducing mechanisms in LPS-activated macrophage-like Raw 264.7 cells. Exposure of Raw 264.7 cells to LPS significantly increased nitrite production, but PPF reduced such enhancement in concentration- and time-dependent manners. In parallel, treatment of Raw 264.7 cells with a clinically relevant concentration of PPF (50 μM) significantly inhibited iNOS mRNA and protein production in LPS-activated Raw 264.7 cells. Propofol at 50 μM decreased the LPS-caused augmentation in nuclear c-Jun levels. An electrophoretic mobility shift assay revealed that PPF significantly decreased the binding affinity of the nuclear extracts from LPS-treated Raw 264.7 cells to activator protein 1 (AP-1) consensus DNA elements. A reporter gene assay further showed that PPF ameliorated the transactivated activity of AP-1 in LPS-stimulated Raw 264.7 cells. LPS sequentially increased phosphorylation of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) 4 and c-Jun N-terminal kinase (JNK) 1/JNK-2. Meanwhile, a therapeutic concentration of PPF significantly decreased the activation of these two protein kinases. Application of Toll-like receptor 4 (TLR-4) siRNA to Raw 264.7 cells decreased cellular TLR-4 levels and LPS-caused activation of MEK-4. Cotreatment with PPF and TLR-4 siRNA synergistically lowered the LPS-induced increased biosynthesis of iNOS mRNA and nitrite. Therefore, a clinically relevant concentration of PPF can inhibit NO production and iNOS gene expression in LPS-activated Raw 264.7 cells. The suppressive mechanisms may occur through sequential down-regulation of TLR-4/MEK-4/JNK-1/JNK-2/AP-1 activation. © 2009 by the Shock Society.


Wang S.-H.,Taipei Medical University | Yang W.-B.,Academia Sinica, Taiwan | Liu Y.-C.,Academia Sinica, Taiwan | Chiu Y.-H.,Taipei Medical University | And 4 more authors.
Journal of Lipid Research | Year: 2011

A novel water-soluble polysaccharide fraction, CME-1, with a molecular mass of 27.6 kDa and containing mannose and galactose in a respective ratio of 4:6, was prepared from Cordyceps sinensis mycelia and identified by NMR and GC-MS. In the current study, we examined whether CME-1 has anti-inflammatory effects in RAW264.7 cells. The ability of CME-1 to inhibit H2O 2-induced cell death in RAW264.7 cells was assessed by using an MTT assay and annexin V/propidium iodide double staining; we found that CME-1 protected cells against H2O2-induced injury. H 2O2-induced intracellular oxidative stress and mitochondrial membrane depolarization were also diminished with CME-1 treatment. We evaluated the hydroxyl radical scavenging ability of CME-1 by using the DMPO-electron spin resonance technique, which indicated that CME-1 acts as an intracellular antioxidant in a concentration-dependent manner through a mechanism other than its scavenging activity. Activities of both neutral and acid sphingomyelinases (SMases) were assessed in vitro, and results showed that the CME-1 inhibited activities of both neutral and acid SMases in a concentration-dependent manner. CME-1 reduced H2O2 treatment-elevated C16- and C18-ceramide levels measured by LC/MS/MS in RAW264.7 cells. Results suggest that CME-1 protects RAW264.7 cells against oxidative stress through inhibition of SMase activity and reduction of C16-and C18-ceramide levels. Copyright © 2011 by the American Society for Biochemistry and Molecular Biology, Inc.


Chuang C.-C.,Chung Yuan Christian University | Ye J.-J.,Chung Yuan Christian University | Lin W.-C.,Chung Yuan Christian University | Lee K.-T.,Chung Yuan Christian University | Tai Y.-T.,Wan Fang Hospital
Journal of Clinical Monitoring and Computing | Year: 2015

Heart rate variability (HRV) is a well-known method for the assessment of autonomic nervous function of the heart. Previous study suggested that pulse rate variability (PRV) determined by photoplethysmography could be used instead of HRV to more simply assess autonomic nervous function. However, most research studies included healthy subjects. Thus, the aim of this study was to investigate the feasibility for PRV as a surrogate index for patients with chronic pain. This study investigated the correlation coefficient (by Pearson correlation) and agreement (by Bland–Altman analysis) between PRV and HRV in chronic pain patients in the clinical setting. The results showed high significant correlations (p < 0.001, r > 0.86) between all the HRV and PRV parameters and good agreements (ratio < 0.1) between the parameters in terms of HR, mean RR, VLF, LF, nLF, nHF, and SD1/SD2. Our study suggests that HRV can also be reliably estimated using the photoplethysmography-based PP interval in elderly patients with chronic pain. © 2015, Springer Science+Business Media New York.


Lin S.-I.,National Cheng Kung University | Hsu L.-J.,Karolinska Institutet | Wang H.-C.,Wan Fang Hospital
Archives of Physical Medicine and Rehabilitation | Year: 2012

Objective: To examine the effects of vibration-induced ankle proprioceptive interference on the locomotion of patients with stroke with intact and impaired ankle joint position sense (JPS). Design: Cross-sectional. Setting: Rehabilitation department in a tertiary hospital. Participants: Ambulatory patients (N=35) with unilateral stroke received an ankle joint repositioning test and were classified into intact (n=16) or impaired (n=19) JPS group. Interventions: None. Main Outcome Measures: The plantar sensitivity and leg muscle strength were tested. Patients were instructed to walk at a self-selected pace on a computerized pressure sensor walkway under 3 conditions: no, affected, or unaffected Achilles' tendon vibration. The stride characteristics of the affected limb were analyzed. Results: Patients with intact and impaired JPS did not differ in their plantar sensitivity or leg muscle strength. The differences in the stride characteristics were nonsignificant between vibration and nonvibration conditions. Shorter single support and longer swing phase were found with the affected side vibration compared with the unaffected side vibration. Patients with intact and impaired JPS did not respond to the proprioceptive interference differently. Conclusions: After stroke, there could be changes in the central sensory regulation for locomotion control and vibration-induced afferent inputs from the ankle might be viewed as sensory disturbances. Further studies that manipulate other sensory inputs are needed to gain a better understanding of the central sensory integration for locomotion control after stroke. © 2012 American Congress of Rehabilitation Medicine.


Yen T.-H.,Taipei Medical University | Liou T.-H.,Taipei Medical University | Chang K.-H.,Wan Fang Hospital | Wu N.-N.,Taipei Medical University | And 2 more authors.
Disability and Rehabilitation | Year: 2014

Purpose: This study systemically reviewed the published literature on the ICF core set. Method: A computer search of the MEDLINE, PubMed and SCOPUS databases was conducted between 2001 and December 2012. Articles reporting on the development of a set or sets of ICF categories for specific disease or health conditions were selected for a systematic review. Results: The analysis included 116 articles from 36 journals, with the majority of papers having been published in 2011 and 2012. In these studies, spinal cord injury was the most frequently reported disease. The majority of the experts involved in the consensus process were physicians and physical therapists. Conclusion: This systematic review of studies on ICF core sets provided background information on the current developmental status of ICF core sets. Our findings also highlight possible directions for future research.Implications for RehabilitationThe aim to develop ICF core sets is to provide a practical way to address a specific patient population in daily practice.This review showed the development of ICF core set in last decade and provide directions for future research.Development of ICF core set is still limited in area outside Europe and incomplete in number of major diseases. © 2014 Informa UK Ltd All rights reserved.


Ho M.-H.,National Taiwan University of Science and Technology | Liao M.-H.,Taipei Medical University | Lin Y.-L.,Wan Fang Hospital | Lai C.-H.,Taipei Medical University | And 2 more authors.
International journal of nanomedicine | Year: 2014

Osteoblast maturation plays a key role in regulating osteogenesis. Electrospun nanofibrous products were reported to possess a high surface area and porosity. In this study, we developed chitosan nanofibers and examined the effects of nanofibrous scaffolds on osteoblast maturation and the possible mechanisms. Macro- and micro observations of the chitosan nanofibers revealed that these nanoproducts had a flat surface and well-distributed fibers with nanoscale diameters. Mouse osteoblasts were able to attach onto the chitosan nanofiber scaffolds, and the scaffolds degraded in a time-dependent manner. Analysis by scanning electron microscopy further showed mouse osteoblasts adhered onto the scaffolds along the nanofibers, and cell-cell communication was also detected. Mouse osteoblasts grew much better on chitosan nanofiber scaffolds than on chitosan films. In addition, human osteoblasts were able to adhere and grow on the chitosan nanofiber scaffolds. Interestingly, culturing human osteoblasts on chitosan nanofiber scaffolds time-dependently increased DNA replication and cell proliferation. In parallel, administration of human osteoblasts onto chitosan nanofibers significantly induced osteopontin, osteocalcin, and alkaline phosphatase (ALP) messenger (m)RNA expression. As to the mechanism, chitosan nanofibers triggered runt-related transcription factor 2 mRNA and protein syntheses. Consequently, results of ALP-, alizarin red-, and von Kossa-staining analyses showed that chitosan nanofibers improved osteoblast mineralization. Taken together, results of this study demonstrate that chitosan nanofibers can stimulate osteoblast proliferation and maturation via runt-related transcription factor 2-mediated regulation of osteoblast-associated osteopontin, osteocalcin, and ALP gene expression.


Lo W.-T.,Tri Service General Hospital | Wang C.-C.,Tri Service General Hospital | Lin W.-J.,Tri Service General Hospital | Wang S.-R.,Wan Fang Hospital | And 3 more authors.
PLoS ONE | Year: 2010

Background: Staphylococcus aureus is an important cause of infection, particularly in persons colonized with this organism. This study compared the annual prevalence and microbiological characteristics of methicillin-resistant S. aureus (MRSA) nasal colonization in Taiwanese children from 2004 through 2009. Risk factors for MRSA were determined for the overall study period. Methods: Children from birth to ≤14 years of age presenting for health maintenance visits or attending 1 of 57 kindergartens were recruited. Nasal swabs were obtained, and a questionnaire was administered. The prevalence and microbiological characteristics of MRSA colonization were also calculated for two 3-year periods: 2004-2006 and 2007-2009. Results: Cultures of the anterior nares were positive for S. aureus in 824 (25.8%) of the 3,200 children, and MRSA colonization was found in 371 (11.6%) children. The prevalence of S. aureus colonization decreased from 28.1% in 2004- 2006 to 23.3% in 2007-2009 (p<0.01), whereas the prevalence of MRSA colonization increased from 8.1% to 15.1% during this period (p<0.0001). Multivariate analysis revealed that the independent risk factors for MRSA carriage were different for male and female children, and also among age groups. Most MRSA isolates belonged to sequence type 59 (ST59) (86.3%); however, a multiresistant MRSA clone with ST338 background emerged in 2007-2009. Ten (62.5%) of the 16 MRSA isolates expressed the genotypic profile ST338/staphylococcal cassette chromosome mec VT/Panton-Valentine leukocidin-positive/ staphylococcal enterotoxin B-positive, and differed only in their antimicrobial susceptibility patterns. Conclusion: The prevalence of nasal colonization by MRSA increased among healthy Taiwanese children from 2004-2006 to 2007-2009, despite an overall decrease in the prevalence of nasal colonization by S. aureus. A multiresistant MRSA clone characterized as ST338 was identified from these children. © 2010 Lo et al.

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