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      • KCI등재

        Interleukin-20 targets podocytes and is upregulated in experimental murine diabetic nephropathy

        Yu-Hsiang Hsu,Hsing-Hui Li,Junne-Ming Sung,Wei-Yu Chen,Ya-Chin Hou,Yun-Han Weng,Wei-Ting Lai,Chih-Hsing Wu,Ming-Shi Chang 생화학분자생물학회 2017 Experimental and molecular medicine Vol.49 No.-

        Interleukin (IL)-20, a proinflammatory cytokine of the IL-10 family, is involved in acute and chronic renal failure. The aim of this study was to elucidate the role of IL-20 during diabetic nephropathy development. We found that IL-20 and its receptor IL-20R1 were upregulated in the kidneys of mice and rats with STZ-induced diabetes. In vitro, IL-20 induced MMP-9, MCP-1, TGF-β1 and VEGF expression in podocytes. IL-20 was upregulated by hydrogen peroxide, high-dose glucose and TGF-β1. In addition, IL-20 induced apoptosis in podocytes by activating caspase-8. In STZ-induced early diabetic nephropathy, IL-20R1-deficient mice had lower blood glucose and serum BUN levels and a smaller glomerular area than did wild-type controls. Anti-IL-20 monoclonal antibody (7E) treatment reduced blood glucose and the glomerular area and improved renal functions in mice in the early stage of STZ-induced diabetic nephropathy. ELISA showed that the serum IL-20 level was higher in patients with diabetes mellitus than in healthy controls. The findings of this study suggest that IL-20 induces cell apoptosis of podocytes and plays a role in the pathogenesis of early diabetic nephropathy.

      • KCI등재

        The Association of Acquired T790M Mutation with Clinical Characteristics after Resistance to First-Line Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor in Lung Adenocarcinoma

        Yen-Hsiang Huang,Kuo-Hsuan Hsu,Jeng-Sen Tseng,Kun-Chieh Chen,Chia-Hung Hsu,Kang-Yi Su,Jeremy J. W. Chen,Huei-Wen Chen,Sung-Liang Yu,Tsung-Ying Yang,Gee-Chen Chang 대한암학회 2018 Cancer Research and Treatment Vol.50 No.4

        Purpose The main objective of this study was to investigate the relationship among the clinical characteristics and the frequency of T790M mutation in advanced epidermal growth factor receptor (EGFR)mutant lung adenocarcinoma patients with acquired resistance after firstline EGFRtyrosine kinase inhibitor (TKI) treatment. Materials and Methods We enrolled EGFR-mutant stage IIIB-IV lung adenocarcinoma patients, who had progressed to prior EGFR-TKI therapy, and evaluated their rebiopsy EGFRmutation status. Results A total of 205 patients were enrolled for analysis. The overall T790M mutation rate of rebiopsy was 46.3%. The T790M mutation rates among patients with exon 19 deletion mutation, exon 21 L858R point mutation, and other mutations were 55.0%, 37.3%, and 27.3%, respectively. Baseline exon 19 deletion was associated with a significantly higher frequency of T790M mutation (adjusted odds ratio, 2.14; 95% confidence interval [CI], 1.20 to 3.83; p=0.010). In the exon 19 deletion subgroup, there was a greater prevalence of T790M mutation than other exon 19 deletion subtypes in patients with the Del E746-A750 mutation (61.6% vs. 40.6%; odds ratio, 2.35; 95% CI, 1.01 to 5.49; p=0.049). The progression- free survival (PFS) of first-line TKI treatment > 11 months was also associated with a higher T790M mutation rate (54.1% vs. 39.3%; adjusted odds ratio, 1.82; 95% CI, 1.02 to 3.25; p=0.044). Patients who underwent rebiopsy at metastatic sites had more chance to harbor T790M mutation (52.6% vs. 33.8%; adjusted odds ratio, 1.97; 95% CI, 1.06 to 3.67; p=0.032). Conclusion PFS of first-line EGFR-TKI, rebiopsy site, EGFR exon 19 deletion and its subtype Del E746- A750 mutation are associated with the frequency of T790M mutation.

      • KCI등재

        The Clinical Outcomes of Different First-Line EGFR-TKIs Plus Bevacizumab in Advanced EGFR-Mutant Lung Adenocarcinoma

        Yen-Hsiang Huang,Kuo-Hsuan Hsu,Chun-Shih Chin,Jeng-Sen Tseng,Tsung-Ying Yang,Kun-Chieh Chen,Kang-Yi Su,Sung-Liang Yu,Jeremy J.W. Chen,Gee-Chen Chang 대한암학회 2022 Cancer Research and Treatment Vol.54 No.2

        Purpose The aim of this study was to investigate the efficacy of various epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitors (TKIs) plus bevacizumab in advanced EGFR-mutant lung adenocarcinoma patients. Materials and Methods From August 2016 to October 2020, we enrolled advanced lung adenocarcinoma patients harboring exon 19 deletion or L858R receiving gefitinib, erlotinib and afatinib plus bevacizumab as the first-line treatment for the purposes of analysis. Results A total of 36 patients were included in the final analysis. Three patients received gefitinib, 17 received erlotinib, and 16 received afatinib combined with bevacizumab as the first-line treatment. The objective response rate was 77.8%, and disease control rate was 94.4%. The overall median progression-free survival (PFS) was 16.4 months, while the median PFS was 17.1 months in patients with exon 19 deletion, and 16.2 months in patients with L858R mutation (p=0.311). Regarding the use of different EGFR-TKIs, the median PFS was 17.1 months in the erlotinib group and 21.6 months in the afatinib group (p=0.617). In patients with brain metastasis at baseline, the median PFS was 18.9 months in the erlotinib group and 16.4 months in the afatinib group (p=0.747). Amongst patients harboring exon 19 deletion, the median PFS was 16.2 months in the erlotinib group and not-reached in the afatinib group (p=0.141). In patients with L858R mutation, the median PFS was 18.9 months in the erlotinib group and 16.2 months in the afatinib group (p=0.481). Conclusion Our research demonstrates that not only erlotinib combined with bevacizumab, but also afatinib plus bevacizumab as first-line treatment, provides solid clinical efficacy in advanced EGFR-mutant lung adenocarcinoma patients. PurposeThe aim of this study was to investigate the efficacy of various epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitors (TKIs) plus bevacizumab in advanced <i>EGFR</i>-mutant lung adenocarcinoma patients.Materials and MethodsFrom August 2016 to October 2020, we enrolled advanced lung adenocarcinoma patients harboring exon 19 deletion or L858R receiving gefitinib, erlotinib and afatinib plus bevacizumab as the first-line treatment for the purposes of analysis.ResultsA total of 36 patients were included in the final analysis. Three patients received gefitinib, 17 received erlotinib, and 16 received afatinib combined with bevacizumab as the first-line treatment. The objective response rate was 77.8%, and disease control rate was 94.4%. The overall median progression-free survival (PFS) was 16.4 months, while the median PFS was 17.1 months in patients with exon 19 deletion, and 16.2 months in patients with L858R mutation (p=0.311). Regarding the use of different EGFR-TKIs, the median PFS was 17.1 months in the erlotinib group and 21.6 months in the afatinib group (p=0.617). In patients with brain metastasis at baseline, the median PFS was 18.9 months in the erlotinib group and 16.4 months in the afatinib group (p=0.747). Amongst patients harboring exon 19 deletion, the median PFS was 16.2 months in the erlotinib group and not-reached in the afatinib group (p=0.141). In patients with L858R mutation, the median PFS was 18.9 months in the erlotinib group and 16.2 months in the afatinib group (p=0.481).ConclusionOur research demonstrates that not only erlotinib combined with bevacizumab, but also afatinib plus bevacizumab as first-line treatment, provides solid clinical efficacy in advanced <i>EGFR</i>-mutant lung adenocarcinoma patients.

      • KCI등재

        Analysis of the Interdecadal and Interannual Variability of Autumn Extreme Rainfall in Taiwan Using a Deep-Learning-Based Weather Typing Approach

        Li‑Huan Hsu,Yi‑chao Wu,Chou‑Chun Chiang,Jung‑Lien Chu,Yi‑Chiang Yu,An‑Hsiang Wang,Ben Jong‑Dao Jou 한국기상학회 2023 Asia-Pacific Journal of Atmospheric Sciences Vol.59 No.2

        This study sought to assess the interdecadal and interannual variability of autumn extreme rainfall (ER) in Taiwan from 1979to 2019. Three types of ER events were identified based on a clustering analysis augmented by a deep autoencoder-basedneural network model. This method outperforms other methods in obtaining the optimal number of clusters by extractingthe synoptic features in advance. The patterns associated with these three types include a tropical cyclone covering Taiwan(TC), a TC-like circulation in the South China Sea (SCS) accompanied by northeasterly near northern Taiwan (TC-NE), andnortheasterly near northern Taiwan (NE). The differences in the rainfall pattern caused by the three types were discernableover Taiwan. How the PDO or ENSO modulates the regional large-scale environment to favor the occurrence of these ERevents was investigated. The occurrence of TC-NE events was simultaneously correlated with the negative phases of PDO/ENSO in the interdecadal/interannual scale. In the negative phases of PDO/ENSO, a low-level anomalous cyclone overSCS accompanied by background northeasterly favored the regional TC activities and may cause more TC-NE events. Theoccurrence of NE events is simultaneously correlated with the cold phase of ENSO. An anomalous low-level anticyclone inNortheast Asia strengthened the northeasterly toward northern Taiwan, and with the seasonal background moisture, providedfavorable conditions for the occurrence of the NE events. Overall, the occurrence of the TC events did not correlate with thePDO or ENSO signals; the reasons for the lack of correlation were discussed herein.

      • Effects of an Anti-Smoking Program to Prevent Lung Cancer among Urban Aboriginals in Taiwan

        Lin, Mei-Hsiang,Huang, Sheu-Jen,Shih, Whei-Mei Jean,Wang, Pao-Yu,Lin, Li-Hui,Hsu, Hsiu-Chin Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.11

        Background and Purpose: Indigenous people who leave their hometowns and move to the city to earn a living became urban aboriginals. During the process of adapting to urban living situations, they may use various coping strategies such as smoking to overcome their stress. Therefore, it is crucial to provide health education including smoking prevention, increasing knowledge regarding of tobacco hazard, self-efficacy of anti-smoking, and adjusting smoking behavior so as to empower their anti-smoking motivation to prevent lung cancer. The purpose of this study was to explore the effectiveness of an anti-smoking program on urban aboriginals in Taiwan. Methods: A quasi-experimental study design with purposeful sampling was employed. A total of 125 aboriginal subjects were recruited from two local churches at Shu Lin area in northern Taiwan. Subjects were divided into an experimental group (n =64 ) and a control group (n = 61). Both took pre-tests in order to set baseline values, and only the experimental group participated for 3-weeks in the anti-smoking program classes. Both groups took post-tests immediately after the intervention in order to evaluate the immediate effects of the teaching program, and a follow-up test was conducted four weeks after the intervention. Data were analyzed using descriptive statistics, one-way ANCOVA, and repeat measure ANCOVA. Results: After controlling for confounding variables, the results showed that there were statistically significant differences in the self-efficacy of anti-smoking and smoking behavior between experimental and control groups in the immediately post-test and the follow-up test (p < 0.05). However, there was no significant differences in the recognition of hazards of smoking at eiter time point. Conclusions and Implications for Practice: The findings of this study revealed that the anti-smoking program effectively improved self-efficacy of anti-smoking, and decreased the smoking behavior in urban aboriginals. They provide useful information as a reference regarding of aboriginal health promotion to health providers. It is imperative that anti-smoking be reinforced for those regular smokers to prevent induction of lung cancer.

      • KCI등재

        How Are Migrants Viewed in the Eyes of Employers? Double Exclusion among Immigrants in Taiwan

        김혜나,Yun Hsiang Hsu,Chih-Yu Chen,Kuo-Jung Lin 숙명여자대학교 아시아여성연구원 2020 OMNES: The Journal of Multicultural Society Vol.10 No.2

        While many countries are open to those born elsewhere being part of their nation, surveys find that this acceptance comes with a certain prerequisite—that it is important to speak the dominant language. This prerequisite has been continuously observed and studied in the field of labor market performance. This study surveys 1,043 employers in Taiwan for their willingness to hire foreign brides from Southeast Asia or Mainland China. The link between the proficiency of the use of language among immigrants and direct job discrimination in Taiwanese workplaces is confirmed. Results show that vocational trainings provided by the government to immigrants are not positively associated with a willingness to hire among employers. Policy recommendations are provided with regard to the establishment of language courses.

      • Efficacy and Safety of 12 Weeks of Daclatasvir, Asunaprevir Plus Ribavirin for the Treatment of HCV Genotype 1b Infection without Baseline NS5A Resistance-Associated Variants (DARING)-Interim Report

        ( Ming-lung Yu ),( Chao-hung Hung ),( Yi-hsiang Huang ),( Cheng-yuan Peng ),( Chun-yen Lin ),( Pin-nan Cheng ),( Rong-nan Chien ),( Shih-jer Hsu ),( Chen-hua Liu ),( Jee-fu Huang ),( Chung-feng Huang 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

        Aims: The current study aims to elucidate the treatment efficacy (defined as undetectable HCV RNA throughout 12 weeks of post-treatment follow-up, SVR12) and safety DCV/ASV plus ribavirin for 12 weeks in HCV-1b patients without NS5A RAS. Methods: This is a single-arm, open-label phase 2 study. Seventy directly acting antivirals (DAA)-naïve HCV-1b patients without L31/Y93 RAS are planned to receive daclatasvir (60 mg/ day) and asunaprevir (100 mg twice daily) plus weight-based ribavirin (1000-1200 mg/day) for 12 weeks. After treatment they were followed up for 12 weeks. Results: As of 31 Oct 2017, 58 eligible patients are allocated to treatment, with a mean age of 59.3 years and female predominance (67.2%, 39/58). The mean HCV RNA was 5.87+0.77 log10 IU/mL; 23 patients (39.7 %) had significant hepatic fibrosis (>F2). In the modified intention-to-treat analysis, the rate of undetectable HCV at week 1, week 2, week 4, week 8 and endof- treatment was 25 % (14/56), 84.8 % (39/46), 100 % (46/46), 100 % (38/38) and 100 % (27/27), respectively. Undetectable HCV RNA were observed in all of the patients with HCV RNA assessable 4 weeks (SVR4, 18/18) and 12 weeks (SVR12, 12/12) post treatment. None of the 18 patients who completed the 12-week treatment experienced relapse during post-treatment follow-up. The most common adverse event was fatigue (78.3 %), followed by pruritus (65.2 %) and dizziness (52.2 %), of which were considered as ribavirin related. None of the participating subjects withdrew treatment or follow-up throughout the trial peroid. Three serious adverse events were reported which included urosepsis, appendicitis and left ureteral stone. All were unrelated to the investigating drugs. Conclusions: 12 weeks of DCV/ASV plus ribavirin was highly effective and safe in HCV-1b patients without NS5A RAS in the interim analysis. The satisfactory results would be anticipated in the full patient set.

      • KCI등재

        Clinical Features and Computed Tomography Characteristics of Non-Klebsiella pneumoniae Liver Abscesses in Elderly (>65 Years) and Nonelderly Patients

        Chih-Weim Hsiang,Wei-Chou Chang,Chang-Hsien Liu,Hsiu-Lung Fan,Kai-Hsiung Ko,Chih-Yung Yu,Hong-Hau Wang,Wen-I Liao,Hsian-He Hsu 연세대학교의과대학 2015 Yonsei medical journal Vol.56 No.2

        Purpose: To compare the clinical and computed tomography (CT) appearances of liver abscesses caused by non-Klebsiella pneumoniae bacterial pathogens in elderly and nonelderly patients. Materials and Methods: Eighty patients with confirmed non-Klebsiella pneumoniae liver abscesses (non-KPLAs) were enrolled and dividedinto two age groups: elderly (age ≥65 years, n=42) and nonelderly (age <65 years, n=38). Diagnosis of non-KPLA was established by pus and/or blood culture. We compared clinical presentations, outcomes, and CT characteristics of the two groups, and performed multivariate analysis for significant variables and receiver-operating-characteristic analysis to determine the cutoff value of abscess diameter for predicting non-KPLA. Results: Elderly patients with non-KPLA were associatedwith a longer hospital stay (p<0.01). Regarding etiology, biliary sources had a strong association in the elderly group (p<0.01), and chronic liver diseases were relatedto the nonelderly group (p<0.01). Non-KPLAs (52.5%) tended to show a large, multiloculated appearance in the elderly group and were associated with bile duct dilatation (p<0.01), compared with the nonelderly group. The abscess diameter (cutoff value, 5.2 cm; area under the curve, 0.78) between the two groups was predicted. In multivariate analysis, underlying biliary tract disease [odds ratio (OR), 3.58, p<0.05], abscess diameter (OR, 2.40, p<0.05), and multiloculated abscess (OR, 1.19, p<0.01) independently predicted elderly patients with non-KPLA. Conclusion:In the elderly patients with non-KPLA, a large, multiloculated abscess with a diameter greater than 5.2 cm was the predominant imaging feature.

      • SCOPUSKCI등재

        Screening of Nitrosamine Impurities in Sartan Pharmaceuticals by GC-MS/MS

        ( Shu-Han Chang ),( Hui-Yu Ho ),( Chi-Zong Zang ),( Ya-Hui Hsu ),( Mei-Chih Lin ),( Su-Hsiang Tseng ),( Der-Yuan Wang ) 한국질량분석학회 2021 Mass spectrometry letters Vol.12 No.2

        Probable human carcinogenic compounds nitrosamines, have been detected as by-product impurities in sartan pharmaceuticals in recent years which has drawn worries for medication safety. To provide a sensitive and effective method for the quality control of sartan pharmaceuticals, this study established a feasible gas chromatography-tandem mass spectrometry (GC-MS/MS) method for simultaneous determination of 13 nitrosamines. The target analytes were separated on a DB-WAX Ultra Inert column (30 m × 0.25 mm; i.d., 0.25 μm) and were then subjected to electron impact ionization in multiple reaction monitoring mode. The established method was validated and further employed to analyze authentic samples. Limits of detection (LODs) and limits of quantification (LOQs) of the 13 nitrosamines were 15-250 ng/g and 50-250 ng/g, respectively, which also exhibited intra-day and inter-day accuracies of 91.4-104.8%, thereby satisfying validation criteria. Five nitrosamines, viz., Nnitrosodiethylamine, N-nitrosodimethylamine, N-nitrosodiphenylamine, N-nitrosomorpholine, and N-nitrosopiperidine were detected at concentrations above their LODs in 68 positive samples out of 594 authentic samples from seven sartans.

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