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The difference between dacomitinib and afatinib in effectiveness and safety in first-line treatment of patients with advanced EGFR-mutant non-small cell lung cancer: a real-world observational study

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BMC Cancer 2024年第1期24卷 1-11页

作者： Cheng, Wen-Chien Lin, Chi-Chien Liao, Wei-Chih Lin, Yu-Chao Chen, Chia-Hung Chen, Hung-Jen Tu, Chih-Yen Hsia, Te-Chun Division of Pulmonary and Critical Care Department of Internal Medicine China Medical University Hospital Taichung Taiwan School of Medicine College of Medicine China Medical University Taichung Taiwan Department of Life Science National Chung Hsing University Taichung Taiwan PhD Program in Translational Medicine National Chung Hsing University Taichung Taiwan Rong Hsing Research Center for Translational Medicine National Chung Hsing University Taichung Taiwan Institute of Biomedical Science the iEGG and Animal Biotechnology Center Advanced Plant and Food Crop Biotechnology Center National Chung-Hsing University Taichung Taiwan Department of Pharmacology College of Medicine Kaohsiung Medical University Kaohsiung Taiwan Department of Medical Research Taichung Veterans General Hospital Taichung Taiwan

Objectives: The irreversible epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) afatinib and dacomitinib are approved for first-line treatment of EGFR mutation-positive non-small cell lung cancer (NSCLC). We aimed to compare the efficacy and safety of afatinib and dacomitinib in this setting. Materials and methods: Between September 2020 and March 2023, we retrospectively recruited patients diagnosed with advanced-stage EGFR-mutant NSCLC who were treated with first-line irreversible EGFR-TKIs. The enrolled patients were assigned to two groups based on whether they received afatinib or dacomitinib. Results: A total of 101 patients were enrolled in the study (70 to afatinib and 31 to dacomitinib). The partial response rates (PR) for first-line treatment with afatinib and dacomitinib were 85.7 and 80.6% (p = 0.522). The median progression-free survival (PFS) (18.9 vs. 16.3 months, p = 0.975) and time to treatment failure (TTF) (22.7 vs. 15.9 months, p = 0.324) in patients with afatinib and dacomitinib treatment were similar. There was no significant difference observed in the median PFS (16.1 vs. 18.9 months, p = 0.361) and TTF (32.5 vs. 19.6 months, p = 0.182) between patients receiving the standard dose and those receiving the reduced dose. In terms of side effects, the incidence of diarrhea was higher in the afatinib group (75.8% vs. 35.5%, p < 0.001), while the incidence of paronychia was higher in the dacomitinib group (58.1% vs. 31.4%, p = 0.004). The PFS (17.6 vs. 24.9 months, p = 0.663) and TTF (21.3 vs. 25.1 months, p = 0.152) were similar between patients younger than 75 years and those older than 75 years. Conclusion: This study showed that afatinib and dacomitinib had similar effectiveness and safety profiles. However, they have slightly different side effects. Afatinib and dacomitinib can be safely administered to patients across different age groups with appropriate dose reductions. © The Author(s) 2024.

关键词： Afatinib Dacomitinib Epidermal growth factor receptor (EGFR) Non-small cell lung cancer (NSCLC)

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Artificial intelligence in gastrointestinal radiology: A review with special focus on recent development of magnetic resonance and computed tomography

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Artificial Intelligence in Gastroenterology 2021年第2期2卷 27-41页

作者： Kai-Po Chang Shih-Huan Lin Yen-Wei Chu PhD Program in Medical Biotechnology National Chung Hsing UniversityTaichung 40227Taiwan Department of Pathology China Medical University HospitalTaichung 40447Taiwan Institute of Genomics and Bioinformatics National Chung Hsing UniversityTaichung 40227Taiwan Institute of Molecular Biology National Chung Hsing UniversityTaichung 40227Taiwan Agricultural Biotechnology Center National Chung Hsing UniversityTaichung 40227Taiwan Biotechnology Center National Chung Hsing UniversityTaichung 40227Taiwan PhD Program in Translational Medicine National Chung Hsing UniversityTaichung 40227Taiwan Rong Hsing Research Center for Translational Medicine Taichung 40227Taiwan

Artificial intelligence(AI),particularly the deep learning technology,have been proven influential to radiology in the recent *** ability in image classification,segmentation,detection and reconstruction tasks have substantially assisted diagnostic radiology,and has even been viewed as having the potential to perform better than radiologists in some *** radiology,an important subspecialty dealing with complex anatomy and various modalities including endoscopy,have especially attracted the attention of AI researchers and engineers ***,recently many tools have been developed for lesion detection and image construction in gastrointestinal radiology,particularly in the fields for which public databases are available,such as diagnostic abdominal magnetic resonance imaging(MRI)and computed tomography(CT).This review will provide a framework for understanding recent advancements of AI in gastrointestinal radiology,with a special focus on hepatic and pancreatobiliary diagnostic radiology with MRI and *** fields where AI is less developed,this review will also explain the difficulty in AI model training and possible strategies to overcome the technical *** authors’insights of possible future development will be addressed in the last section.

关键词： Artificial intelligence Deep learning Image diagnosis Radiology Magnetic resonance imaging Computed tomography

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Chlorine-containing polyacetoxybriarane diterpenoids from the octocoral Junceella fragilis

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RSC Advances 2024年第24期14卷 17195-17201页

作者： Do, Hai Nhat Chen, Yu-Ta Chien, Su-Ying Chen, You-Ying Zhang, Mingzi M. Tsou, Lun Kelvin Chen, Jih-Jung Wen, Zhi-Hong Lo, Yi-Hao Zheng, Li-Guo Sung, Ping-Jyun Department of Marine Biotechnology and Resources National Sun Yat-sen University Kaohsiung804201 Taiwan National Museum of Marine Biology & Aquarium Pingtung944401 Taiwan Department of Family Medicine Zuoying Armed Forces General Hospital Kaohsiung813204 Taiwan Instrumentation Center National Taiwan University Taipei106319 Taiwan Institute of Molecular and Genomic Medicine National Health Research Institutes Miaoli350401 Taiwan Institute of Biotechnology and Pharmaceutical Research National Health Research Institutes Miaoli350401 Taiwan Department of Pharmacy School of Pharmaceutical Sciences National Yang Ming Chia Tung University Taipei112304 Taiwan Shu-Zen Junior College of Medicine and Management Kaohsiung821004 Taiwan Institute of Medical Science and Technology National Sun Yat-sen University Kaohsiung804201 Taiwan Doctoral Degree Program in Marine Biotechnology National Sun Yat-sen University Kaohsiung804201 Taiwan Chinese Medicine Research and Development Center China Medical University Hospital Taichung404394 Taiwan Graduate Institute of Natural Products Kaohsiung Medical University Kaohsiung807378 Taiwan PhD Program in Pharmaceutical Biotechnology Fu Jen Catholic University New Taipei City242062 Taiwan

The chemical screening of an octocoral identifed as Junceella fragilis has led to the isolation of five chlorinated briarane-type diterpenoids, including three known metabolites, gemmacolide X (1), frajunolide I (2), and fragilide F (3), along with two new analogs, 12α-acetoxyfragilide F (4) and 12α-acetoxyjunceellin (5). Single-crystal X-ray diffraction analysis was carried out to determine the absolute configurations of 1 and 2, while the structures of new compounds 4 and 5 were ascertained with 2D NMR experiments. Briaranes 1 and 3-5 were active in enhancing alkaline phosphatase (ALP) activity. © 2024 The Royal Society of Chemistry.

关键词： Metabolites

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Ellagic acid protects against angiotensin II-induced hypertrophic responses through ROS-mediated MAPK pathway in H9c2 cells

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Environmental Toxicology 2024年第5期39卷 3253-3263页

作者： Lee, Ya-Che Jou, Yeong-Chin Chou, Wan-Ching Tsai, Kun-Ling Shen, Cheng-Huang Lee, Shin-Da Department of Urology Ditmanson Medical Foundation Chiayi Christian Hospital Chia-Yi City Taiwan Department of Urology St. Martin De Porres Hospital Chia-Yi City Taiwan Department of Health and Nutrition Biotechnology College of Medical and Health Science Asia University Taichung City Taiwan Department of Physical Therapy College of Medicine National Cheng Kung University Tainan City Taiwan Institute of Allied Health Science College of Medicine National Cheng Kung University Tainan City Taiwan Department of Biomedical Sciences National Chung Cheng University Chia-Yi Min Hsiung Taiwan Department of Physical Therapy College of Medical and Health Science Asia University Taichung City Taiwan Department of Physical Therapy PhD program in Healthcare Science China Medical University Taichung Taiwan

The early myocardial response of hypertension is an elevation of angiotensin-II (Ang-II) concentration, leading to heart failure and cardiac hypertrophy. This hypertrophic event of the heart is mediated by the interaction of Ang type 1 receptors (AT-R1), thereby modulating NADPH oxidase activity in cardiomyocytes, which alters redox status in cardiomyocytes. Ellagic acid (EA) has anti-inflammatory and anti-oxidative capacities. Thus, EA has potential preventive effects on cardiovascular diseases and diabetes. In the last decades, because the protective effect of EA on Ang-II-induced hypertrophic responses is unclear, this study aims to investigate the protective effect of EA in cardiomyocytes. H9c2 cells were treated to Ang-II 1 μM for 24 h to induce cellular damage. We found that EA protected against Ang-II-increased cell surface area and pro-hypertrophic gene expression in H9c2. EA reduced Ang-II-caused AT-R1 upregulation, thereby inhibiting oxidative stress NADPH oxidase activation. EA mitigated Ang-II-enhanced p38 and extracellular-signal-regulated kinase (ERK) phosphorylation. Moreover, EA treatment under Ang-II stimulation also reversed NF-κB activity and iNOS expression. This study shows that EA protects against Ang-II-induced myocardial hypertrophy and attenuates oxidative stress through reactive oxygen species-mediated mitogen-activated protein kinase signaling pathways in H9c2 cells. Thus, EA may be an effective compound for preventing Ang-II-induced myocardial hypertrophy. © 2024 Wiley Periodicals LLC.

关键词： Oxidative stress

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Interactive Effects of a Combination of the HDAC3 and HDAC9 Genes with Diabetes Mellitus on the Risk of Ischemic Stroke

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Thrombosis and Haemostasis 2020年第3期121卷 396-404页

作者： Hung-Yi Chiou Chyi-Huey Bai Li-Ming Lien Chaur-Jong Hu Jiann-Shing Jeng Sung-Chun Tang Huey-Juan Lin Yi-Chen Hsieh School of Public Health College of Public Health Taipei Medical University Taipei Taiwan Master Program in Applied Molecular Epidemiology College of Public Health Taipei Medical University Taipei Taiwan School of Medicine College of Medicine Taipei Medical University Taipei Taiwan Department of Neurology Shin Kong Wu Ho-Su Memorial Hospital Taipei Taiwan Stroke Center Department of Neurology Shuang Ho Hospital Taipei Medical University New Taipei City Taiwan Stroke Center and Department of Neurology National Taiwan University Hospital Taipei Taiwan Department of Emergency Medicine Chi-Mei Medical Center Tainan Taiwan Department of Biotechnology Southern Taiwan University of Science and Technology Tainan Taiwan PhD Program of Neural Regenerative Medicine College of Medical Science and Technology Taipei Medical University Taipei Taiwan PhD Program in Biotechnology Research and Development College of Pharmacy Taipei Medical University Taipei Taiwan

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Menarche - a journey into womanhood: age at menarche and health-related outcomes in East Asians

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Human Reproduction 2024年第6期39卷 1336-1350页

作者： Chiou, Jian-Shiun Lin, Ying-Ju Chang, Cherry Yin-Yi Liang, Wen-Miin Liu, Ting-Yuan Yang, Jai-Sing Chou, Chen-Hsing Lu, Hsing-Fang Chiu, Mu-Lin Lin, Ting-Hsu su Liao, Chiu-Chu Huang, Shao-Mei Chou, I-Ching Li, Te-Mao Huang, Peng-Yan Chien, Tzu-Shun Chen, Hou-Ren Tsai, Fuu-Jen PhD Program for Health Science and Industry College of Health Care China Medical University Taichung Taiwan Department of Health Services Administration China Medical University Taichung Taiwan Genetic Center Department of Medical Research China Medical University Hospital Taichung Taiwan School of Chinese Medicine College of Chinese Medicine China Medical University Taichung Taiwan Division of Minimal Invasive Endoscopy Surgery Department of Obstetrics and Gynecology China Medical University Hospital Taichung Taiwan School of Medicine College of Medicine China Medical University Taichung Taiwan Million-Person Precision Medicine Initiative Department of Medical Research China Medical University Hospital Taichung Taiwan Department of Medical Research China Medical University Hospital China Medical University Taichung Taiwan Laboratory for Statistical and Translational Genetics RIKEN Center for Integrative Medical Sciences Yokohama Japan Department of Pediatrics China Medical University Children's Hospital Taichung Taiwan Graduate Institute of Integrated Medicine China Medical University Taichung Taiwan Division of Medical Genetics China Medical University Children's Hospital Taichung Taiwan Department of Medical Laboratory Science and Biotechnology Asia University Taichung Taiwan

STUDY QUESTION: Are there associations of age at menarche (AAM) with health-related outcomes in East Asians? SUMMARY ANSWER: AAM is associated with osteoporosis, Type 2 diabetes (T2D), glaucoma, and uterine fibroids, as demonstrated through observational studies, polygenic risk scores, genetic correlations, and Mendelian randomization (MR), with additional findings indicating a causal effect of BMI and T2D on earlier AAM. WHAT IS KNOWN ALREADY: Puberty timing is linked to adult disease risk, but research predominantly focuses on European populations, with limited studies in other groups. STUDY DESIGN, SIZE, DURATION: We performed an AAM genome-wide association study (GWAS) with 57 890 Han Taiwanese females and examined the association between AAM and 154 disease outcomes using the Taiwanese database. Additionally, we examined genetic correlations between AAM and 113 diseases and 67 phenotypes using Japanese GWAS summary statistics. PARTICIPANTS/MATERIALS, SETTING, METHODS: We performed AAM GWAS and gene-based GWAS studies to obtain summary statistics and identify potential AAM-related genes. We applied phenotype, polygenic risk scores, and genetic correlation analyses of AAM to explore health-related outcomes, using multivariate regression and linkage disequilibrium score regression analyses. We also explored potential bidirectional causal relationships between AAM and related outcomes through univariable and multivariable MR analyses. MAIN RESULTS AND THE ROLE OF CHANCE: Fifteen lead single-nucleotide polymorphisms and 24 distinct genes were associated with AAM in Taiwan. AAM was genetically associated with later menarche and menopause, greater height, increased osteoporosis risk, but lower BMI, and reduced risks of T2D, glaucoma, and uterine fibroids in East Asians. Bidirectional MR analyses indicated that higher BMI/T2D causally leads to earlier AAM. LIMITATIONS, REASONS FOR CAUTION: Our findings were specific to Han Taiwanese individuals, with genetic correlatio

关键词： age at menarche genetic correlation genome-wide association study Mendelian randomization polygenic risk score

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Corrigendum to “Metal ratio and bimetal nanoarchitectonics of ammonia-based fluoride complex induced nickel hydroxide and manganese oxide composites as active materials of an energy storage device” [J. Energy Storage 80 (2024) 110316]

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Journal of Energy Storage 2025年 108卷

作者： Chuan-Chih Hsu You Zher Yu Chung-Hsien Wu Pin-Yan Lee Hung-Ming Chen Sadang Husain Chutima Kongvarhodom Yu-Cheng Hsiao Lu-Yin Lin Division of Cardiovascular Surgery Department of Surgery School of Medicine College of Medicine Taipei Medical University Taiwan Division of Cardiovascular Surgery Department of Surgery Taipei Medical University Hospital Taiwan Department of Chemical Engineering and Biotechnology National Taipei University of Technology Taipei Taiwan Gingen Technology Co. LTD. Rm. 7 10F. No.189 Sec. 2 Keelung Rd. Xinyi Dist. Taipei 11054 Taiwan Department of Physics Faculty of Mathematics and Natural Science Lambung Mangkurat University Banjarmasin 70124 Indonesia Department of Chemical Engineering King Mongkut's University of Technology Thonburi 126 Pracha-u-thit Toong-kru Bangkok 10140 Thailand Cell Physiology and Molecular Image Research Center Wan Fang Hospital Taipei Medical University Taipei 11696 Taiwan International PhD Program in Biomedical Engineering College of Biomedical Engineering Taipei Medical University Taipei 11031 Taiwan Stanford Byers Center for Biodesign Stanford University CA 94305-5428 USA Graduate Institute of Biomedical Optomechatronics College of Biomedical Engineering Taipei Medical University Taipei 11031 Taiwan

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Structural insights into the molecular mechanism of phytoplasma immunodominant membrane protein

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IUCrJ 2024年第PT 3期11卷 384-394页

作者： Chang Yi Liu Han Pin Cheng Chan Pin Lin Yi Ting Liao Tzu Ping Ko Shin Jen Lin Shih Shun Lin Hao Ching Wang The PhD Program for Translational Medicine College of Medical Science and Technology Taipei Medical University and Academia Sinica Taipei Taiwan. Institute of Biotechnology National Taiwan University Taipei Taiwan. Institute of Biological Chemistry Academia Sinica Taipei Taiwan. International Center for the Scientific Development of Shrimp Aquaculture National Cheng Kung University Tainan Taiwan.

Immunodominant membrane protein (IMP) is a prevalent membrane protein in phytoplasma and has been confirmed to be an F-actin-binding protein. However, the intricate molecular mechanisms that govern the function of IMP require further elucidation. In this study, the X-ray crystallographic structure of IMP was determined and insights into its interaction with plant actin are provided. A comparative analysis with other proteins demonstrates that IMP shares structural homology with talin rod domain-containing protein 1 (TLNRD1), which also functions as an F-actin-binding protein. Subsequent molecular-docking studies of IMP and F-actin reveal that they possess complementary surfaces, suggesting a stable interaction. The low potential energy and high confidence score of the IMP-F-actin binding model indicate stable binding. Additionally, by employing immunoprecipitation and mass spectrometry, it was discovered that IMP serves as an interaction partner for the phytoplasmal effector causing phyllody 1 (PHYL1). It was then shown that both IMP and PHYL1 are highly expressed in the S2 stage of peanut witches' broom phytoplasma-infected Catharanthus roseus. The association between IMP and PHYL1 is substantiated through in vivo immunoprecipitation, an in vitro cross-linking assay and molecular-docking analysis. Collectively, these findings expand the current understanding of IMP interactions and enhance the comprehension of the interaction of IMP with plant F-actin. They also unveil a novel interaction pathway that may influence phytoplasma pathogenicity and host plant responses related to PHYL1. This discovery could pave the way for the development of new strategies to overcome phytoplasma-related plant diseases.

关键词： X-ray crystallography actin-binding proteins immunodominant membrane proteins phytoplasma protein structure α-helix bundles

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Bat organoids reveal antiviral responses at epithelial surfaces

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Nature Immunology 2025年 1-13页

作者： Max J. Kellner Patrick Zelger Masahiro Onji Josef M. Penninger Vanessa M. Monteil Ali Mirazimi Gang Pei Anca Dorhoi Jie Jiao Komal Nayak Matthias Zilbauer Anne Balkema-Buschmann Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA) Vienna BioCenter (VBC) Vienna Austria Vienna BioCenter PhD Program Doctoral School of the University of Vienna and Medical University of Vienna Vienna Austria Department of Laboratory Medicine Medical University of Vienna Vienna Austria Helmholtz Centre for Infection Research Braunschweig Germany Department of Medical Genetics Life Sciences Institute University of British Columbia Vancouver British Columbia Canada Division of Clinical Microbiology Department of Laboratory Medicine Karolinska Institute and Karolinska University Hospital Stockholm Sweden Public Health Agency of Sweden Solna Sweden National Veterinary Institute Uppsala Sweden Institute of Immunology Friedrich-Loeffler-Institut Greifswald-Insel Riems Germany Faculty of Mathematics and Natural Sciences University of Greifswald Greifswald Germany Wellcome – MRC Cambridge Stem Cell Institute University of Cambridge Cambridge UK Department of Paediatrics University of Cambridge Cambridge UK Institute of Novel and Emerging Infectious Diseases Friedrich-Loeffler-Institut Greifswald-Insel Riems Germany

Bats can host viruses of pandemic concern without developing disease. The mechanisms underlying their exceptional resilience to viral infections are largely unresolved, necessitating the development of physiologically relevant and genetically tractable research models. Here, we developed respiratory and intestinal organoids that recapitulated the cellular diversity of the in vivo epithelium present inRousettus aegyptiacus, the natural reservoir for the highly pathogenic Marburg virus (MARV). In contrast to human counterparts, bat organoids and mucosal tissue exhibited elevated constitutive expression of innate immune effectors, including type I interferon-ε (IFNε) and IFN-stimulated genes (ISGs). Upon infection with diverse zoonotic viruses, including MARV, bat organoids strongly induced type I and III IFN responses, which conferred robust antiviral protection. Type III IFNλ3 additionally displayed virus-independent self-amplification, acting as an ISG to enhance antiviral immunity. Our organoid platform reveals key features of bat epithelial antiviral immunity that may inform therapeutic strategies for viral disease resilience.

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Global epidemiology and antimicrobial resistance of Enterobacterales harbouring genes encoding OXA-48-like carbapenemases: insights from the results of the Antimicrobial Testing Leadership and Surveillance (ATLAS) programme 2018-2021

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The Journal of antimicrobial chemotherapy 2024年第7期79卷 1581-1589页

作者： Yu-Lin Lee Wei-Yao Wang Wen-Chien Ko Po-Ren Hsueh Division of Infectious Disease Department of Internal Medicine Chung Shan Medical University Hospital Taichung Taiwan. PhD Program in Medical Biotechnology Institute of Genomics and Bioinformatics National Chung-Hsing University Taichung Taiwan. School of Medicine Chung Shan Medical University Taichung Taiwan. Department of Medicine College of Medicine National Cheng Kung University Tainan Taiwan. Departments of Laboratory Medicine and Internal Medicine China Medical University Hospital Chin Medical University Taichung Taiwan. School of Medicine China Medical University Taichung Taiwan. PhD Program for Ageing School of Medicine China Medical University Taichung Taiwan. Departments of Laboratory Medicine and Internal Medicine National Taiwan University Hospital National Taiwan University College of Medicine Taipei Taiwan.

OBJECTIVES:The recent emergence of carbapenem-resistant Enterobacterales poses a major and escalating threat to global public health. This study aimed to analyse the global distribution and antimicrobial resistance of Enterobacterales harbouring variant OXA-48-like carbapenemase-related genes. METHODS:Enterobacterales isolates were collected from the Antimicrobial Testing Leadership and Surveillance (ATLAS) programme during 2018-2021. Comprehensive antimicrobial susceptibility testing and β-lactamase gene detection were also conducted, along with statistical analysis of the collected data. RESULTS:Among the 72 244 isolates, 1934 Enterobacterales isolates were identified to harbour blaOXA-48-like genes, predominantly Klebsiella spp. (86.9%). High rates of multidrug resistance were observed, with only ceftazidime/avibactam and tigecycline showing favourable susceptibility. A discrepancy between the genotype and phenotype of carbapenem resistance was evident: 16.8% (233 out of 1384) of the Enterobacterales isolates with blaOXA-48-like genes exhibited susceptibility to meropenem. Specifically, 37.4% (64/95) of Escherichia coli strains with blaOXA-48-like genes displayed meropenem susceptibility, while the corresponding percentages for Klebsiella pneumoniae and Enterobacter cloacae complex were 25.2% (160/1184) and 0% (0/36), respectively (P < 0.05). Geographical analysis revealed that the highest prevalence of blaOXA-48-like genes occurred in Asia, the Middle East and Eastern Europe. The proportion of K. pneumoniae isolates harbouring blaOXA-232 increased from 23.9% in 2018 to 56.0% in 2021. By contrast, the proportion of blaOXA-48 decreased among K. pneumoniae isolates during 2018-2021. CONCLUSIONS:This study underscores the widespread and increasing prevalence of blaOXA-48-like genes in Enterobacterales and emphasizes the need for enhanced surveillance, improved diagnostic methods and tailored antibiotic stewardship to combat the spread of these resistant pathogens.

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