Publications (45)86.23 Total impact
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Article: Sex Differences of Oxidative Stress to Cholestatic Liver and Kidney Injury in Young Rats.
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ABSTRACT: BACKGROUND: Sexual dimorphism plays a role in the liver and in renal injuries. However, whether sex is a risk factor in bile duct ligation (BDL) in young rats has never been examined. METHODS: Six male and six female rats treated with BDL were sacrificed 2 weeks after surgery and were designated as BDL-M and BDL-F groups. The other six male and six female rats that received sham ligation were designated as sham-M and sham-F groups. Plasma biochemistry and liver and kidney asymmetric dimethylarginine (ADMA)-related molecules were examined. RESULTS: Both BDL-M and BDL-F groups had elevated plasma aspartate transaminase (AST), alanine transaminase (ALT), bilirubin, and transforming growth factor-β1 levels. The BDL-F group had lower plasma AST and ALT levels than the BDL-M group. The BDL-M and BDL-F groups had elevated plasma ADMA levels. The cationic amino acid transporter 1 (CAT1) level was increased in the BDL-F group as compared to the sham-F group, whereas the CAT2 level was reduced in the both BDL-M and BDL-F groups. CONCLUSION: We found that young male rats were prone to higher degrees of biochemical liver and kidney injury to cholestasis. Sex differences in modulation of oxidative stress markers, such as ADMA, may play a role. Our results support careful monitoring and optimal treatment of cholestatic disease, especially in young male patients.Pediatrics & Neonatology 04/2013; 54(2):95-101. · 0.75 Impact Factor -
Article: Melatonin regulates L-arginine transport and NADPH oxidase in young rats with bile-duct ligation: role of protein kinase C.
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ABSTRACT: Background:Bile duct ligation (BDL) is a commonly used cholestatic liver disease model. We recently found that L-arginine levels were significantly raised by melatonin in young rats with BDL. We hypothesized thatPKC-α is involved in the increases of L-arginine in melatonin-treated BDL rats. Additionally, we tested whether melatonin prevents NADPH oxidase-induced ROS production is through PKC in rats with BDL.Methods:Four groups of young male rats were studied, shams (N = 6), untreated BDL rats (N = 9), melatonin-treated shams (N=6, M), and melatonin-treated BDL rats (N = 6, BDL + M). Melatonin-treated rats received daily melatonin 1 mg/kg/day via intraperitoneal injection. All surviving rats were killed 14 days after surgery.Results:Melatonin prevented BDL-induced mortality and kidney injury. Melatonin additionally increases L-arginine concentrations in BDL liver, which is correlated with decreased PKC-α translocation. Next, melatonin increases L-arginine levels in BDL kidneys, which is correlated with decreased renal level of arginase II. In the BDL kidney, melatonin decreases PKC-β translocation, reduces p47phox translocation, and diminishes NADPH-dependent superoxide production.Conclusion:Melatonin inhibits PKC-α to increase CAT-1-mediated L-arginine uptake in BDL liver, while it inhibits PKC-β to reduce NADPH-dependent superoxide production.Pediatric Research (2013); doi:10.1038/pr.2012.203.Pediatric Research 01/2013; · 2.70 Impact Factor -
Article: Roles of melatonin in fetal programming in compromised pregnancies.
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ABSTRACT: Compromised pregnancies such as those associated with gestational diabetes mellitus, intrauterine growth retardation, preeclampsia, maternal undernutrition, and maternal stress may negatively affect fetal development. Such pregnancies may induce oxidative stress to the fetus and alter fetal development through the epigenetic process that may affect development at a later stage. Melatonin is an oxidant scavenger that reverses oxidative stress during the prenatal period. Moreover, the role of melatonin in epigenetic modifications in the field of developmental programming has been studied extensively. Here, we describe the physiological function of melatonin in pregnancy and discuss the roles of melatonin in fetal programming in compromised pregnancies, focusing on its involvement in redox and epigenetic mechanisms.International Journal of Molecular Sciences 01/2013; 14(3):5380-401. · 2.60 Impact Factor -
Dataset: Chou JH, Chang TT and Chou TC. Models for Drug Develppment and Drug Resistence. Cancer Handbook, 2nd ed. Alison MR ed-in-chief Jhon Wiley & Son, Ltd, West Sussex, England. Chapter 75, Vol.2, 1027-1042, 2007.
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Dataset: leu2009248a-2
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Article: Alterations in NADPH oxidase expression and blood-brain barrier in bile duct ligation-treated young rats: effects of melatonin.
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ABSTRACT: Bile duct ligation (BDL)-treated rats exhibit cholestasis and increased systemic and brain oxidative stress. Activation of NADPH (nicotinamide adenine dinucleotide phosphate) oxidase and disruption of the blood-brain barrier (BBB) are implicated as the pathogenetic mechanisms of brain dysfunction in BDL-treated adult rats. Young rats underwent sham ligation or BDL at day 17 for 2 or 4weeks. Treatment group rats were administered melatonin between day 17 and 45. We found a progressive increase in prefrontal cortex NADPH-dependent superoxide anion (O(2)(-)) production and increased expression of NADPH oxidase subunits in either the prefrontal cortex or the hippocampus in BDL-treated young rats. In addition, expression of intercellular adhesion molecule-1 (ICAM) and tissue plasminogen activator (t-PA) genes were increased in either the prefrontal cortex or the hippocampus. Prefrontal cortex capillary junctional complex proteins expressions including occludin, claudin-5, platelet endothelial cell adhesion molecule-1 and vascular endothelial cadherin were not altered. Melatonin lowered the prefrontal cortex NADPH-dependent O(2)(-) production and t-PA gene expression. We conclude that alterations in NADPH oxidase expression and BBB are involved in brain dysfunction in BDL-treated young rats. In addition, melatonin regulates NADPH oxidase activity and t-PA gene expression.Neurochemistry International 06/2012; 60(8):751-8. · 2.86 Impact Factor -
Article: Predictors of anxiety and resilience in adolescents undergoing cancer treatment.
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ABSTRACT: Wu L.-M., Sheen J.-M., Shu H.-L., Chang S.-C. & Hsiao C.-C. (2012) Predictors of anxiety and resilience in adolescents undergoing cancer treatment. Journal of Advanced Nursing00(0), 000-000. doi: 10.1111/j.1365-2648.2012.06003.x ABSTRACT: Aims. To report a study examining the relationships among coping, anxiety and resilience and to identify predictors of anxiety and resilience in adolescents undergoing cancer treatment. Background. Anxiety is the main psychological disturbance in adolescents with cancer, but predictors in the context of anxiety related cancer treatments have not been investigated. Design. Cross-sectional study. Methods. Adolescents (n = 131) recruited from three medical centres between 2010-2011. The eligible participants were diagnosed with cancer, without mental disease and receiving chemotherapy. Participants were assessed with the paediatric cancer coping scale, revised children's manifest anxiety scale, second edition, and the Haase adolescent resilience in illness scale. Results. Over 20% of participants scored high on worry. The most commonly used coping strategy was cognitive coping, followed by problem-oriented coping and finally by defensive coping. There was a statistically significant correlation between defensive coping and level of worry. Resilience was positively correlated with cognitive coping and problem-oriented coping. The cognitive coping and defensive coping were found to predict anxiety and resilience significantly by a step-wise multiple regression analysis and accounted for 40·9% and 46·5% of total variance, respectively. Conclusions. Cognitive coping and defensive coping are predictors for the level of anxiety and resilience in adolescents undergoing cancer treatment. Health providers should evaluate coping behaviour in patients and work towards a cognitive and problem-oriented coping style that will benefit the patient's mental health during treatment.Journal of Advanced Nursing 04/2012; · 1.48 Impact Factor -
Article: Proteomic analysis of the effects of baicalein on colorectal cancer cells.
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ABSTRACT: Baicalein is the flavonoids with multiple pharmacological activities. The aim of our study was to investigate the effects of baicalein on colorectal cancer (CRC) and to recognize the targets of baicalein treatment. To better understand baicalein's target, proteomic approaches were used to purify and identify the protein substrates using 2D difference gel electrophoresis (2D SDS-PAGE) to elucidate proteins differential display. Results from this study investigate that baicalein treatment of CRC cells results in reduced cell proliferation. As a result, differential protein displays between baicalein-treated and untreated CRC were determined and validated. There were 11 differentially expressed proteins between baicalein-treated and untreated CRC. Furthermore, we demonstrate that baicalein inhibits cancer cell proliferation and reduced reactive oxygen species (ROS) by up-regulating the levels of peroxiredoxin-6 (PRDX6). Knockdown of PRDX6 in baicalein-treated CRC cells by specific small interfering RNA resulted in ROS production and proliferation, opposite of the baicalein treatment scenario as indicated by cell cycle distribution. These results illustrate that baicalein up-regulates the expression of PRDX6, which attenuates the generation of ROS and inhibits the growth of CRC cells, whereas baicalein treatment have no effect on normal epithelial cells.Proteomics 03/2012; 12(6):810-9. · 4.43 Impact Factor -
Article: Melatonin utility in neonates and children.
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ABSTRACT: Melatonin (N-acetyl-5-methoxytryptamine) is an endogenously produced indoleamine secreted by the pineal gland and the secretion is suppressed by light. Melatonin is a highly effective antioxidant, free radical scavenger, and has anti-inflammatory effect. Plenty of evidence supports the utility of melatonin in adults for cancer, neurodegenerative disorders, and aging. In children and neonates, melatonin has been used widely, including for respiratory distress syndrome, bronchopulmonary dysplasia, periventricular leukomalacia (PVL), hypoxia-ischemia encephalopathy and sepsis. In addition, melatonin can be used in childhood sleep and seizure disorders, and in neonates and children receiving surgery. This review article discusses the utility of melatonin in neonates and children.Journal of the Formosan Medical Association 02/2012; 111(2):57-66. · 1.13 Impact Factor -
Article: Different modulating effects of adenosine on neonatal and adult polymorphonuclear leukocytes.
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ABSTRACT: Polymorphonuclear leukocytes (PMNs) are the major leukocytes in the circulation and play an important role in host defense. Intact PMN functions include adhesion, migration, phagocytosis, and reactive oxygen species (ROS) release. It has been known for a long time that adenosine can function as a modulator of adult PMN functions. Neonatal plasma has a higher adenosine level than that of adults; however, little is known about the modulating effects of adenosine on neonatal PMNs. The aim of this study was to investigate the effects of adenosine on neonatal PMN functions. We found that neonatal PMNs had impaired adhesion, chemotaxis, and ROS production abilities, but not phagocytosis compared to adult PMNs. As with adult PMNs, adenosine could suppress the CD11b expressions of neonatal PMNs, but had no significant suppressive effect on phagocytosis. In contrast to adult PMNs, adenosine did not significantly suppress chemotaxis and ROS production of neonatal PMNs. This may be due to impaired phagocyte reactions and a poor neonatal PMN response to adenosine. Adenosine may not be a good strategy for the treatment of neonatal sepsis because of impaired phagocyte reactions and poor response.TheScientificWorldJOURNAL 01/2012; 2012:387923. · 1.66 Impact Factor -
Article: Absence of biallelic TCRγ deletion predicts induction failure and poorer outcomes in childhood T-cell acute lymphoblastic leukemia.
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ABSTRACT: The absence of biallelic TCRγ deletion (ABD) is a characteristic of early thymocyte precursors before V(D)J recombination. The ABD was reported to predict early treatment failure in T-cell acute lymphoblastic leukemia (ALL). This study aimed to investigate its prognostic value in Taiwanese patients with T-cell ALL. Forty-five children with T-cell ALL were enrolled from six medical centers in Taiwan. Quantitative DNA polymerase chain reaction (Q-PCR) was performed to check the status of TCRγ deletion. The threshold for homozygous deletions by Q-PCR was defined as a fold-change <0.35. ABD was found in 20 patients [20:45] who had higher incidences of induction failure than those without ABD (P = 0.03; hazard ratio [HR] = 8.13; 95% confidence interval [95% CI] = 1.23-53.77) after multivariate regression analysis. Patents with ABD also had inferior EFS and OS (P = 0.071 and 0.0196, respectively). Multivariate Cox analysis indicated that the association between ABD and overall survival was independent of age and leukocyte count on presentation (P = 0.036; HR = 4.25; 95% CI = 1.10-16.42). The absence of TCRγ deletion is a predictor of a poor response to induction chemotherapy for pediatric patients with T-cell ALL in Taiwan. Providing patients with T-cell ALL and ABD with alternative regimens may be worthwhile to test in future clinical trials.Pediatric Blood & Cancer 12/2011; 58(6):846-51. · 1.89 Impact Factor -
Article: Identification of immunodeficient molecules in neonatal mononuclear cells by proteomic differential displays.
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ABSTRACT: Human newborns are known to be susceptible to microbial infection. This susceptibility is generally attributed to immaturity of the newborn immune system. However, the mechanisms for impaired immunity in newborns are still incompletely defined. In this study, we sought to elucidate the protein differential display between adult and neonatal mononuclear cells (MNC) using a proteomic approach. MNC samples from cord blood and adult peripheral blood were subjected to 2-D PAGE analysis. Differential protein displays between cord blood and adult MNC were determined and validated. There were 34 differentially expressed proteins between cord blood and adult MNC identified by 2-D PAGE. The differentially displayed proteins were clustered into two major signal pathways, cellular processing and purine metabolism. After validation by Western blot, we found more abundant arginase-1 (ARG1) and Rho GDP-dissociation inhibitor 2 (RhoGDI2), while less adenosine deaminase (ADA) and β-actin in cord blood MNC. In functional validation, we found that lower ADA was proven to enhance the TNF-α production by cord blood monocytes. The results from this study discovered the proteomic displays for altered immunity between adult and neonatal MNC that support a understanding of the correction of impaired immune response in newborns.Proteomics 09/2011; 11(17):3491-500. · 4.43 Impact Factor -
Article: IKZF1 deletions predict a poor prognosis in children with B-cell progenitor acute lymphoblastic leukemia: a multicenter analysis in Taiwan.
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ABSTRACT: Despite current risk-directed therapy, approximately 15-20% of pediatric patients with acute lymphoblastic leukemia (ALL) have relapses. Recent genome-wide analyses have identified that an alteration of IKZF1 is associated with very poor outcomes in B-cell progenitor ALL. In this study, we determined the prognostic significance of IKZF1 deletions in patients with childhood ALL. This study analyzed 242 pediatric B-cell progenitor ALL patients in Taiwan. We developed a simple yet sensitive multiplex quantitative PCR coupled with capillary electrophoresis to accurately determine the allele dose of IKZF1, and high resolution melting was used for mutation screening for all coding exons of IKZF1. Twenty-six (10.7%) pediatric B-cell progenitor ALL patients were found to harbor these deletions. Most of the deletions were broader deletions that encompassed exon 3 to exon 6, consistent with previous reports. Genomic sequencing of IKZF1 was carried out in all cases and no point mutations were identified. Patients with IKZF1 deletions had inferior event-free survival (P < 0.001), and overall survival (P = 0.0016). The association between IKZF1 deletions and event-free survival was independent of age, leukocyte count at presentation, and cytogenetic subtype by multivariate Cox analysis (P = 0.003, hazard ratio = 2.45). This study indicates that detection of IKZF1 deletions upon diagnosis of B-cell progenitor ALL may help to identify patients at risk of treatment failure. IKZF1 deletions could be incorporated as a new high-risk prognostic factor in future treatment protocols. To the best of our knowledge, this is the first study to examine the poor prognosis of IKZF1 deletions in an Asian population.Cancer Science 07/2011; 102(10):1874-81. · 3.33 Impact Factor -
Article: High glucose-treated macrophages augment E-selectin expression in endothelial cells.
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ABSTRACT: E-selectin expression by endothelial cells (ECs) is crucial for leukocyte recruitment during the inflammatory response. Macrophage accumulation and serum E-selectin elevation are features of type 2 diabetes mellitus. However, the interactions between macrophages and ECs in regulating vascular endothelial function are not clearly understood. We investigated the mechanisms underlying the modulation of EC E-selectin expression by high glucose (HG)-treated macrophages. Macrophage-conditioned media (MCM) were prepared from HG-treated macrophages. EC stimulation with HG-MCM induced increases the expression and secretion of E-selectin. By using specific inhibitors and small interfering RNAs, we demonstrate that the activation of the JNK and p38 MAPK pathways are critical for HG-MCM-induced E-selectin expression. Transcription factor ELISA and chromatin immunoprecipitation assays further showed that HG-MCM increases the NF-κB- and AP-1 DNA-binding activities in ECs. The inhibition of NF-κB and AP-1 activation by specific siRNAs blocks the HG-MCM-induced E-selectin promoter activity and expression. Protein arrays and blocking assays using neutralizing antibodies demonstrated that macrophage inflammatory protein 1α and 1β in HG-MCM are major mediators for the induction of EC E-selectin expression. These data support the hypothesis that E-selectin up-regulation stimulated by macrophages may play an active role in atherogenesis in the HG condition and suggest a new mechanism by which arterial disease is accelerated in diabetes.Journal of Biological Chemistry 06/2011; 286(29):25564-73. · 4.77 Impact Factor -
Article: Pediatric malignant ovarian tumors: 15 years of experience at a single institution.
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ABSTRACT: Malignant ovarian tumors in children are relatively rare. We reviewed our 15-year experience to understand their clinical presentations, managements, and prognoses. There were 15 children who were diagnosed to have malignant ovarian tumors from January 1994 to June 2009 in our hospital. The presenting symptoms, treatments, and outcomes were obtained retrospectively from the medical records. The median age at presentation was 13 years. The most common presenting symptom was abdominal pain, occurring in 10 patients (66.7%). The tumors were in the left side in 10 patients (66.7%). The pathologic diagnoses were yolk sac tumors in four patients, immature teratomas in four, dysgerminomas in three, malignant mixed germ cell tumors in three, and carcinosarcoma in one patient. According to the Federation Internationale de Gynecologie Oncologique classification, seven girls had Stage I, one had Stage II, and seven had Stage III disease. Thirteen patients received chemotherapy with platinum-based regimens. Three patients died of their disease: one of yolk sac tumor, one of malignant mixed germ cell tumor, and one of carcinosarcoma. They all had Stage III disease at diagnosis. The 10-year overall survival and disease-free survival rates were 77% and 69%, respectively. Pediatric malignant ovarian tumors were highly curable disease if they were not in the advanced stage at presentation. Earlier consideration of malignant ovarian tumor in the differential diagnosis of young girls with abdominal pain is important.Pediatrics & Neonatology 06/2011; 52(3):140-4. · 0.75 Impact Factor -
Article: Acute lymphoblastic leukemia presented as severe jaundice and hyperferritinemia: a case report.
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ABSTRACT: Children with acute lymphoblastic leukemia (ALL) frequently present with hepatomegaly and mild liver functional impairment. Severe jaundice is rarely seen as a presenting feature. Such patients often present diagnostic dilemmas and therapeutic difficulties. Here we report a 15-year-old boy presenting with severe jaundice and hyperferritinemia, whose bone marrow smear showed B-lineage precursor ALL. We treated him with intravenous immunoglobulin, steroid, and etoposide; then his condition improved. ALL should be considered as a possible diagnosis in severely jaundiced children. Steroid and etoposide can be used as first aid when many chemotherapeutic drugs are contraindicated.Journal of Pediatric Hematology/Oncology 03/2011; 33(3):e117-9. · 1.16 Impact Factor -
Article: IFN-α production by human mononuclear cells infected with varicella-zoster virus through TLR9-dependent and -independent pathways.
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ABSTRACT: Understanding the defense mechanisms of the host of an organism is important for infection control. In previous studies, we demonstrated that interferon-α (IFN-α), but not IL-12, was produced by human peripheral blood mononuclear cells infected with varicella-zoster virus (VZV). Here, we investigated what kind of cell(s) and which signal molecule(s) are involved in IFN-α production. Using cell isolation and ELISA, we found that plasmacytoid dendritic cells (pDCs) were responsible for IFN-α production during VZV infection. We also found that Toll-like receptor 9 (TLR9) was involved in VZV-induced IFN-α production because inhibitory CpG oligodeoxynucleotide inhibited IFN-α production. UV-inactivated VZV-induced IFN-α production was lower than that of active VZV, indicating another TLR9-independent pathway. Further studies demonstrated that double-stranded RNA-dependent protein kinase, but not DNA-dependent protein kinase was involved in VZV-induced IFN-α production. Together, these results suggest that pDCs play an important role in IFN-α production during VZV infection through TLR9-dependent and -independent pathways.Cellular & molecular immunology 02/2011; 8(2):181-8. · 2.99 Impact Factor -
Article: Isolated gastric varices with upper gastrointestinal bleeding 11 years after distal pancreatectomy for ruptured pancreatic pseudocyst.
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ABSTRACT: Isolated gastric varices with upper gastrointestinal bleeding are an unusual event, particularly in children in whom obstruction of the splenic vein is an infrequent occurrence. We describe a 19-year-old man with bleeding isolated gastric varices 11 years after he underwent distal pancreatectomy with preservation of the spleen for a ruptured pancreatic pseudocyst. The disorder was cured with splenectomy.Journal of Pediatric Surgery 01/2011; 46(1):e33-5. · 1.45 Impact Factor -
Article: Glyceraldehyde-3-phosphate dehydrogenase is a reliable internal control in Western blot analysis of leukocyte subpopulations from children.
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ABSTRACT: To study differences in the development of immunity, leukocytes from cord blood are often compared with those from adult peripheral blood. Western blot analysis is a common method for detecting proteins. In this study, we investigated the reliability of using different housekeeping proteins (β-actin, β-tubulin, and glyceraldehyde-3-phosphate dehydrogenase [GAPDH]) as internal controls for different leukocyte subpopulations from infants, children, and adults. Our results showed that the expression levels of β-actin and β-tubulin were much lower in cord blood leukocytes than in adult leukocytes, and this expression pattern persisted in children up to 3 years old. Further study revealed that the β-actin expression level in newborns was especially lower in CD14-positive monocytes. However, cord blood and adult peripheral blood monocytes had similar expression levels of β-actin messenger RNA (mRNA). Further experiments showed that posttranslational regulation was responsible for the low β-actin expression level in neonatal monocytes. Thus, researchers should carefully assess the appropriate use of housekeeping gene-encoded proteins as internal standards to normalize samples for comparisons of different leukocyte populations from subjects of different ages. In this study, we determined that GAPDH was a more reliable internal control than others in Western blot analysis for comparing the development of immunity among infants, children, and adults.Analytical Biochemistry 01/2011; 413(1):24-9. · 3.00 Impact Factor -
Article: Use of proteomic differential displays to assess functional discrepancies and adjustments of human bone marrow- and Wharton jelly-derived mesenchymal stem cells.
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ABSTRACT: Mesenchymal stem cells (MSCs) from bone marrow are suitable for the reconstruction of connective tissues and even brain tissue but have limitations in terms of cell expansion and fully specific differentiation. In our current study, we have attempted to adjust and improve the cell expansion and differentiation properties of human MSCs from different tissues. MSCs from normal bone marrow and Wharton jelly were subjected to proteomic differential displays, followed by functional adjustments based on these displays. Bone marrow MSCs expressed more transgelin-2 and differentiated more rapidly into bone nodules but showed a slower growth rate. A knockdown of transgelin-2 expression by specific small interfering RNA (siRNA) significantly increased the growth rate of these cells, the G1/S phase cell cycle transition, and the interaction of cyclin D1 with cdk2. Wharton jelly MSCs expressed the chaperone protein HSP90β at higher levels and differentiated slowly toward an osteogenic lineage. However, the knockdown of HSP90β expression significantly increased bone nodule formation, inhibited cell growth, decreased the number of cells in the G1/S phase of the cell cycle, and decreased the interaction of cyclin D1 with cdk2 and of cyclin E with cdk2. These results were validated by the in vivo repair of segmental bone defects in a mouse model with severe combined immunodeficiency. We thus demonstrate an improvement in the cell expansion and tissue regeneration properties of human MSCs through specific adjustments.Journal of Proteome Research 01/2011; 10(3):1305-15. · 5.11 Impact Factor
Top co-authors
Top Journals
Institutions
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2010–2013
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Chang Gung University
- • Department of Anesthesiology
- • College of Medicine
Taoyuan, Taiwan, Taiwan
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2004–2013
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Chang Gung Memorial Hospital
- Division of Hematology and Oncology
Taipei, Taipei, Taiwan
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2010–2011
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National Taiwan University Hospital
Taipei, Taipei, Taiwan
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2008
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Kaohsiung Medical University
- Department of Pediatrics
Kaohsiung, Kaohsiung, Taiwan
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