Chin-Fu Hsiao

National Health Research Institutes, Miao-li-chieh, Taiwan, Taiwan

Are you Chin-Fu Hsiao?

Claim your profile

Publications (97)349.17 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. One of the primary treatment goals for incurable advanced cases is to prolong quality of life (QoL). Thus, to determine which HCC therapies may be linked to a more favorable QoL, we assessed the association between QoL changes and different treatments in HCC patients. We analyzed a non-randomized multicenter longitudinal study, which included 171 patients treated with surgery (n = 53), ablation (n = 53) or embolization (n = 65) from seven centers: four Asian and three European sites. All participants completed the EORTC QLQ-C30 and QLQ-HCC18 questionnaires before and after treatment. Propensity scores were calculated and used in addition to race for adjustment in the logistic regression model to account for the confounding effects of patient characteristics including age, gender, race, employment, living with family, at least one comorbid condition, years since diagnosis, prior treatment history, BCLC stage, Child-Pugh grade, cirrhosis, bilirubin levels and QoL score before treatment. After adjustment for confounders, patients tended to have higher odds of QoL deterioration when treated with ablation versus embolization (dyspnea: p = 0.019; appetite loss: p = 0.018; body image: p = 0.035) or ablation versus surgery (dyspnea: p = 0.099; appetite loss: p = 0.100; body image: p = 0.038). There were significant differences in QoL deterioration across different treatment groups. This information may assist patients and providers when selecting patient-centered treatment approaches for HCC.
    Quality of Life Research 05/2015; DOI:10.1007/s11136-015-0985-8 · 2.86 Impact Factor
  • International journal of cardiology 05/2015; 194. DOI:10.1016/j.ijcard.2015.05.055 · 6.18 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We previously carried out a multi-stage genome-wide association study (GWAS) on lung cancer among never smokers in the Female Lung Cancer Consortium in Asia (FLCCA) (6,609 cases, 7,457 controls) that identified novel susceptibility loci at 10q25.2, 6q22.2, and 6p21.32, and confirmed two previously identified loci at 5p15.33 and 3q28. Household air pollution (HAP) attributed to solid fuel burning for heating and cooking, is the leading cause of the overall disease burden in Southeast Asia, and is known to contain lung carcinogens. To evaluate the gene-HAP interactions associated with lung cancer in loci independent of smoking, we analyzed data from studies participating in FLCCA with fuel use information available (n = 3; 1,731 cases; 1,349 controls). Coal use was associated with a 30 % increased risk of lung cancer (OR 1.3, 95 % CI 1.0-1.6). Among the five a priori SNPs identified by our GWAS, two showed a significant interaction with coal use (HLA Class II rs2395185, p = 0.02; TP63 rs4488809 (rs4600802), p = 0.04). The risk of lung cancer associated with coal exposure varied with the respective alleles for these two SNPs. Our observations provide evidence that genetic variation in HLA Class II and TP63 may modify the association between HAP and lung cancer risk. The roles played in the cell cycle and inflammation pathways by the proteins encoded by these two genes provide biological plausibility for these interactions; however, additional replication studies are needed in other non-smoking populations.
    Human Genetics 01/2015; 134(3). DOI:10.1007/s00439-014-1528-z · 4.52 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Recent evidence from several relatively small nested case-control studies in prospective cohorts shows an association between longer telomere length measured phenotypically in peripheral white blood cell (WBC) DNA and increased lung cancer risk. We sought to further explore this relationship by examining a panel of 7 telomere-length associated genetic variants in a large study of 5,457 never-smoking female Asian lung cancer cases and 4,493 never-smoking female Asian controls using data from a previously reported genome-wide association study. Using a group of 1,536 individuals with phenotypically measured telomere length in WBCs in the prospective Shanghai Women's Health study, we demonstrated the utility of a genetic risk score (GRS) of 7 telomere-length associated variants to predict telomere length in an Asian population. We then found that GRSs used as instrumental variables to predict longer telomere length were associated with increased lung cancer risk (OR = 1.51 (95% CI=1.34-1.69) for upper vs. lower quartile of the weighted GRS, P-value=4.54 × 10(-14) ) even after removing rs2736100 (P-value=4.81 × 10(-3) ), a SNP in the TERT locus robustly associated with lung cancer risk in prior association studies. Stratified analyses suggested the effect of the telomere-associated GRS is strongest among younger individuals. We found no difference in GRS effect between adenocarcinoma and squamous cell subtypes. Our results indicate that a genetic background that favors longer telomere length may increase lung cancer risk, which is consistent with earlier prospective studies relating longer telomere length with increased lung cancer risk. This article is protected by copyright. All rights reserved. © 2014 UICC.
    International Journal of Cancer 12/2014; DOI:10.1002/ijc.29393 · 5.01 Impact Factor
  • Source
    Chieh Chiang · Chin-Fu Hsiao · Jen-Pei Liu
    [Show abstract] [Hide abstract]
    ABSTRACT: Statistical criterion for evaluation of individual bioequivalence (IBE) between generic and innovative products often involves a function of the second moments of normal distributions. Under replicated crossover designs, the aggregate criterion for IBE proposed by the guidance of the U.S. Food and Drug Administration (FDA) contains the squared mean difference, variance of subject-by-formulation interaction, and the difference in within-subject variances between the generic and innovative products. The upper confidence bound for the linearized form of the criterion derived by the modified large sample (MLS) method is proposed in the 2001 U.S. FDA guidance as a testing procedure for evaluation of IBE. Due to the complexity of the power function for the criterion based on the second moments, literature on sample size determination for the inference of IBE is scarce. Under the two-sequence and four-period crossover design, we derive the asymptotic distribution of the upper confidence bound of the linearized criterion. Hence the asymptotic power can be derived for sample size determination for evaluation of IBE. Results of numerical studies are reported. Discussion of sample size determination for evaluation of IBE based on the aggregate criterion of the second moments in practical applications is provided.
    PLoS ONE 10/2014; 9(10):e109746. DOI:10.1371/journal.pone.0109746 · 3.23 Impact Factor
  • Yuh-Jenn Wu · Te-Sheng Tan · Shein-Chung Chow · Chin-Fu Hsiao
    [Show abstract] [Hide abstract]
    ABSTRACT: In recent years, global collaboration has become a conventional strategy for new drug development. To accelerate the development process and shorten approval time, the design of multiregional clinical trials (MRCTs) incorporates subjects from many countries around the world under the same protocol. After showing the overall efficacy of a drug in all global regions, one can also simultaneously evaluate the possibility of applying the overall trial results to all regions and subsequently support drug registration in each of them. Several statistical methods have been proposed for the design and evaluation of MRCTs. Most of these approaches, however, assume a common variability of the primary endpoint across regions. In practice, this assumption may not be true, due to differences across regions (e.g., differences in ethnic factors and/or medical culture/practice). In this article, we use a random-effect model for modeling heterogeneous variability across regions for the design and evaluation of MRCTs. We also address consideration on the determination of the number of subjects in a specific region to establish the consistency of treatment effects between the specific region and the entire group.
    Journal of Biopharmaceutical Statistics 03/2014; 24(2):254-271. DOI:10.1080/10543406.2013.859150 · 0.72 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Methadone is a synthetic opioid that binds to the κ-opioid receptor with a low affinity. This study tested the hypotheses that the genetic polymorphisms in the κ-opioid receptor 1 (OPRK1) gene region are associated with methadone treatment responses in a Taiwan methadone maintenance treatment (MMT) cohort. Seventeen single nucleotide polymorphisms (SNPs) in OPRK1 were selected and genotyped on DNA of 366 MMT patients. Six SNPs from rs7843965 to rs1051660 (intron 2 to exon 2) were significantly associated with body weight (P < 0.007). A haplotype of 4 SNPs rs7832417-rs16918853-rs702764-rs7817710 (exon 4 to intron 3) was associated with bone or joint aches (P ≤ 0.004) and with the amount of alcohol use (standard drinks per day; global P < 0.0001). The haplotype rs10958350-rs7016778-rs12675595 was associated with gooseflesh skin (global P < 0.0001), yawning (global P = 0.0001), and restlessness (global P < 0.0001) withdrawal symptoms. The findings suggest that genetic polymorphisms in OPRK1 were associated with the body weight, alcohol use, and opioid withdrawal symptoms in MMT patients.
    Journal of clinical psychopharmacology 02/2014; DOI:10.1097/JCP.0000000000000082 · 3.76 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Co-heritability of hypertension and insulin resistance within families not only implies genetic susceptibility may be responsible for these complex traits but also suggests a rational that biological candidate genes for hypertension may serve as markers for features of the metabolic syndrome. Thus we determined whether the T323C polymorphism (rs5333) of endothlein type A (ETA) receptor, a predominant receptor evoking potent vasoconstrictive action of endothelin-1, contributes to susceptibility to insulin resistance-associated hypertension in 1,694 subjects of Chinese and Japanese origins. Blood pressures and biochemistries were measured. Fasting insulin level, insulin-resistance homeostasis model assessment (HOMAIR) score, and area under curve of insulin concentration (AUCINS) were selected for assessing insulin sensitivity. Genotypes were obtained by methods of PCR-RFLP. Foremost findings were that minor allele frequency of the T323C polymorphism was noticeable lower in our overall Asian subjects compared to multi-national population reported in gene database; moreover both the genotypic and allelic frequencies of the polymorphism were significantly different between the two ethnic groups we studied. The genotype distributions at TT/TC/CC were 65%, 31%, 4% in Chinese and 51%, 41%, 8% in Japanese, respectively (p
    Frontiers in Endocrinology 11/2013; 4:172. DOI:10.3389/fendo.2013.00172
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Methadone maintenance therapy is an established treatment for heroin dependence. This study tested the influence of functional genetic polymorphisms in CYP2C19 gene encoding a CYP450 enzyme that contributes to methadone metabolism on treatment dose, plasma concentration, and side effects of methadone. Two single nucleotide polymorphisms (SNPs), rs4986893 (exon 4) and rs4244285 (exon 5), were selected and genotyped in 366 patients receiving methadone maintenance therapy in Taiwan. The steady-state plasma concentrations of both methadone and its EDDP metabolite enantiomers were measured. SNP rs4244285 allele was significantly associated with the corrected QT interval (QTc) change in the electrocardiogram (p=0.021), and the Treatment Emergent Symptom Scale (TESS) total score (p=0.021) in patients who continued using heroin, as demonstrated with a positive urine opiate test. Using the gene dose (GD) models where the CYP2C19 SNPs were clustered into poor (0 GD) versus intermediate (1 GD) and extensive (2 GD) metabolizers, we found that the extensive metabolizers required a higher dose of methadone (p=0.035), and showed a lower plasma R-methadone/methadone dose ratio (p=0.007) in urine opiate test negative patients, as well as a greater QTc change (p=0.008) and higher total scores of TESS (p=0.018) in urine opiate test positive patients, than poor metabolizers. These results in a large study sample from Taiwan suggest that the gene dose of CYP2C19 may potentially serve as an indicator for the plasma R-methadone/methadone dose ratio and cardiac side effect in patients receiving methadone maintenance therapy. Further studies of pharmacogenetic variation in methadone pharmacokinetics and pharmacodynamics are warranted in different world populations.
    Omics: a journal of integrative biology 09/2013; DOI:10.1089/omi.2012.0068 · 2.73 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: This is a single-blind, parallel, flexible-dose study to compare the efficacy and tolerability of escitalopram and paroxetine in the treatment of patients with major depressive disorder. We recruited 399 patients from the outpatient clinics of five hospitals in northern Taiwan. Patients were administered either escitalopram (10-30 mg) or paroxetine (20-40 mg) according to the judgment of clinicians. These patients were assessed using the Hamilton Rating Scale for Depression (HAM-D) and the Hamilton Rating Scale for Anxiety at weeks 0, 1, 2, 4, 6, and 8. A total of 302 patients fulfilled the evaluation criteria and were included in a statistical analysis. We found that escitalopram induced more significant symptom reduction and response rate in terms of the mean HAM-D scores at week 6 (P<0.05) and week 8 (P<0.05) than paroxetine, but that there were no significant differences between the two groups in the remission rate. Escitalopram induced significantly less frequency of adverse effects of weakness (P<0.01), nausea and vomiting (P<0.001), drowsiness (P<0.01) as well as somnolence (P<0.01) than paroxetine, although all these side effects were mild and tolerable. However for a more definitive result, future prospective trials with the inclusion of a placebo group and a double-blind design are needed. In patients who did not have severe depression (HAM-D score at baseline<21), but not in severely depressed patients, escitalopram was statistically superior to paroxetine, as shown by the mean change in the HAM-D score.
    International clinical psychopharmacology 07/2013; 28(6). DOI:10.1097/YIC.0b013e32836458e2 · 3.10 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Aim: The liver CYP1A2 enzyme may metabolize antidepressant escitalopram (S-CIT) to S-desmethylcitalopram (S-DCIT) and S-didesmethylcitalopram (S-DDCIT). This study tested whether genetic polymorphisms in the CYP1A2 gene are associated with the treatment responses to S-CIT. Materials & methods: Ten SNPs in CYP1A2 were selected and genotyped in 158 patients under S-CIT treatment. The serum levels of S-CIT and its metabolites were measured by HPLC. Results:CYP1A2 SNPs rs2069521, rs2069526, rs4646425 and rs4646427 are significantly associated with the metabolic ratios of S-DDCIT/S-DCIT (p = 0.002, 0.018, 0.008 and 0.004, respectively) at week 2 of treatment. Carriers of the allele types associated with higher S-DDCIT/S-DCIT ratios had more severe side effects. Conclusion: These results suggest that genetic variants in CYP1A2 may be indicators for S-CIT metabolism and that the fast metabolizers may experience more severe adverse reactions in the early stages of S-CIT treatment. Original submitted 27 December 2012; Revision submitted 15 May 2013.
    Pharmacogenomics 07/2013; 14(10):1191-201. DOI:10.2217/pgs.13.105 · 3.43 Impact Factor
  • Yufen Huang · Wan-Jung Chang · Chin-Fu Hsiao
    [Show abstract] [Hide abstract]
    ABSTRACT: To accelerate the drug development process and shorten approval time, the design of multiregional clinical trials (MRCTs) incorporates subjects from many countries/regions around the world under the same protocol. After showing the overall efficacy of a drug in all global regions, one can also simultaneously evaluate the possibility of applying the overall trial results to all regions and subsequently support drug registration in each of them. In this paper, we focus on a specific region and establish a statistical criterion to assess the consistency between the specific region and overall results in an MRCT. More specifically, we treat each region in an MRCT as an independent clinical trial, and each perhaps has different treatment effect. We then construct the empirical prior information for the treatment effect for the specific region on the basis of all of the observed data from other regions. We will conclude similarity between the specific region and all regions if the posterior probability of deriving a positive treatment effect in the specific region is large, say 80%. Numerical examples illustrate applications of the proposed approach in different scenarios. Copyright © 2013 John Wiley & Sons, Ltd.
    Pharmaceutical Statistics 03/2013; 12(2). DOI:10.1002/pst.1553 · 1.10 Impact Factor
  • Journal of clinical psychopharmacology 02/2013; 33(1):137-140. DOI:10.1097/01.jcp.0000426186.34421.de · 3.76 Impact Factor
  • Journal of clinical psychopharmacology 12/2012; DOI:10.1097/JCP.0b013e31827935e0 · 3.76 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hormone replacement therapy (HRT) and EGFR single nucleotide polymorphisms (SNPs) have been reported as risk factors for lung cancer in never smokers. We investigate the interaction of EGFR SNPs and HRT for lung adenocarcinoma risk in never-smoking women. This study included 532 never-smoking female lung adenocarcinoma patients and 532 controls, with EGFR SNPs retrieved from a genome-wide association study. The associations of EGFR SNPs with the lung adenocarcinoma risk were estimated by multivariate-adjusted logistic regression. The Haploview program was used to select tagged EGFR SNPs interacted with HRT and construct haplotype blocks. The Benjamini and Hochberg method was used to reduce the multiple testing effects. Among 84 EGFR SNPs retrieved, 11 tagging EGFR SNPs showed an interaction with HRT and lung adenocarcinoma risk, which were mostly located near the tyrosine kinase domain. Eight of the tagged SNPs were in two haplotype blocks. The interactions between HRT and numbers of protective EGFR SNP genotypes are significant in both blocks (p for interaction = 0.0004 and 0.0032, respectively). A trend of decrease in lung adenocarcinoma risk was found in subjects with HRT harboring an increasing number of protective EGFR SNP genotypes in both blocks (p = 0.0032 and 0.0046, respectively). In conclusion, HRT use may modify the association of EGFR SNPs with lung adenocarcinoma risk. The EGFR SNPs have a cumulative effect on decreasing lung adenocarcinoma risk in never-smoking women with HRT use.
    Carcinogenesis 12/2012; 34(3). DOI:10.1093/carcin/bgs385 · 5.27 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Majority of the heroin-dependent patients smoke cigarettes. Although it has been reported that the OPRM1 genetic polymorphism is associated with the brain mu-opioid receptor binding potential in cigarette smokers, there is no direct evidence showing the impact of plasma cotinine, a nicotine metabolite, on treatment responses to methadone maintenance treatment (MMT). In this study, we aimed to test the hypothesis that the genetic polymorphisms in the OPRM1 are associated with the methadone treatment responses and the severity of cigarette smoking directly measured by the plasma concentration of cotinine in a Taiwanese MMT cohort. Fifteen OPRM1 single-nucleotide polymorphisms (SNPs) were selected and genotyped on DNA samples of 366 MMT patients. Plasma concentrations of cotinine were measured by cotinine enzyme-linked immunosorbent assay. The plasma cotinine concentration had positive correlation with concentrations of methadone (P=0.042) and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenyl-pyrrolidine (P=0.037). Methadone treatment non-responders, defined by a positive urine morphine test, had a higher plasma concentration of cotinine (P=0.005), but a lower plasma concentration-to-dose ratio of both R- and S-methadone (P=0.001 and 0.012, respectively) than the responders. OPRM1 genetic variants, rs1074287, rs6912029, rs1799971, rs12209447, rs510769, rs3798676, rs553202, rs7748401, rs495491, rs10457090, rs589046, rs3778152 and rs563649, were significantly associated with the plasma concentration of cotinine when using recessive model for genotypes (general linear model (GLM), P<0.038; false discovery rate (FDR)<0.035) and additive model for allele types (GLM, P<0.03; FDR<0.049) in association analyses. The G allele carriers of SNP rs1799971 (A118G) on exon 1 of OPRM1 gene had a lower plasma cotinine concentration than the A allele carriers (GLM, P=0.029). OPRM1 genetic polymorphisms are associated with the plasma concentration of cotinine in a Taiwanese MMT cohort. Carriers with the major allele of SNP rs1799971 had a higher plasma cotinine concentration.Journal of Human Genetics advance online publication, 6 December 2012; doi:10.1038/jhg.2012.139.
    Journal of Human Genetics 12/2012; 58(2). DOI:10.1038/jhg.2012.139 · 2.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To identify common genetic variants that contribute to lung cancer susceptibility, we conducted a multistage genome-wide association study of lung cancer in Asian women who never smoked. We scanned 5,510 never-smoking female lung cancer cases and 4,544 controls drawn from 14 studies from mainland China, South Korea, Japan, Singapore, Taiwan and Hong Kong. We genotyped the most promising variants (associated at P < 5 × 10(-6)) in an additional 1,099 cases and 2,913 controls. We identified three new susceptibility loci at 10q25.2 (rs7086803, P = 3.54 × 10(-18)), 6q22.2 (rs9387478, P = 4.14 × 10(-10)) and 6p21.32 (rs2395185, P = 9.51 × 10(-9)). We also confirmed associations reported for loci at 5p15.33 and 3q28 and a recently reported finding at 17q24.3. We observed no evidence of association for lung cancer at 15q25 in never-smoking women in Asia, providing strong evidence that this locus is not associated with lung cancer independent of smoking.
    Nature Genetics 11/2012; DOI:10.1038/ng.2456 · 29.65 Impact Factor
  • Shein-Chung Chow · Chieh Chiang · Jen-Pei Liu · Chin-Fu Hsiao
    [Show abstract] [Hide abstract]
    ABSTRACT: In 1998, the International Conference on Harmonization (ICH) published a guidance to facilitate the registration of medicines among ICH regions including the European Union, the United States, and Japan by recommending a framework for evaluating the impact of ethnic factors on a medicine's effect, such as its efficacy and safety at a particular dosage and dose regimen (ICH E5, 1998). The purpose of ICH E5 is not only to evaluate the ethnic factor influence on safety, efficacy, dosage, and dose regimen, but also more importantly to minimize duplication of clinical data and allow extrapolation of foreign clinical data to a new region. In this article, statistical methods for evaluation of bridging studies based on the concepts of consistency (Shih, 2001 ), reproducibility/generalizability (Shao and Chow, 2002 ), the weighted Z-tests for the design of bridging studies (Lan et al., 2005 ), and similarity between the new and original region based in terms of positive treatment effect (Hsiao et al., 2007 ) are studied. The relative merits and disadvantages of these methods are compared by several examples.
    Journal of Biopharmaceutical Statistics 09/2012; 22(5):903-15. DOI:10.1080/10543406.2012.701578 · 0.72 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: One of the challenges of multiregional drug development program is to design and analyze a multiple regional clinical trial with the objective being to satisfy different regional requirements on primary endpoints. Considered in this article is a multiregional clinical trial (MRCT) designed to test for two primary endpoints. Data of a regular fixed-size well-controlled parallel arm trial are used to test for two null hypotheses in terms of two distinct yet correlated endpoints. The two hypotheses may be tested sequentially or simultaneously. Depending on the structure of the hypotheses to be tested and the understanding of type I error rate control, various scenarios of type I error rate adjustments may be applied. Furthermore, for the objective of getting approval from regional authorities for different primary endpoints, various sample size and power determinations may be applied. In this article, comparisons of different approaches are discussed systematically.
    Journal of Biopharmaceutical Statistics 09/2012; 22(5):1051-9. DOI:10.1080/10543406.2012.701586 · 0.72 Impact Factor
  • Source
    Chi-Tian Chen · H. M. James Hung · Chin-Fu Hsiao
    [Show abstract] [Hide abstract]
    ABSTRACT: To speed up drug development to allow faster access to medicines for patients globally, conducting multiregional trials incorporating subjects from many countries around the world under the same protocol may be desired. Several statistical methods have been proposed for the design and evaluation of multiregional trials. However, in most of the recent approaches for sample size determination in multiregional trials, a common treatment effect of the primary endpoint across regions is usually assumed. In practice, it might be expected that there is a difference in treatment effect due to regional difference (e.g., ethnic difference). In this article, a random effect model for heterogeneous treatment effect across regions is proposed for the design and evaluation of multiregional trials. We also address consideration of the determination of the number of subjects in a specific region to establish the consistency of treatment effects between the specific region and the entire group.
    Journal of Biopharmaceutical Statistics 09/2012; 22(5):1037-50. DOI:10.1080/10543406.2012.701585 · 0.72 Impact Factor

Publication Stats

1k Citations
349.17 Total Impact Points

Institutions

  • 2002–2014
    • National Health Research Institutes
      • Institute of Population Health Sciences
      Miao-li-chieh, Taiwan, Taiwan
  • 2009
    • Taipei Medical University
      • Department of Internal Medicine
      T’ai-pei, Taipei, Taiwan
  • 2005–2009
    • Stanford University
      Palo Alto, California, United States
  • 2004–2007
    • National Taiwan University Hospital
      • Department of Internal Medicine
      Taipei, Taipei, Taiwan
  • 2006
    • Kaohsiung Medical University
      Kao-hsiung-shih, Kaohsiung, Taiwan
  • 2003
    • Tri-Service General Hospital
      T’ai-pei, Taipei, Taiwan
    • National Chiao Tung University
      • Department of Biological Science and Technology
      Hsinchu, Taiwan, Taiwan