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Changing life expectancy in European countries 1990–2021: a subanalysis of causes and risk factors from the Global Burden of Disease Study 2021

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The Lancet Public health 2025年第3期10卷 e172-e188页

作者： Steel, Nicholas Bauer-Staeb, Clarissa Maria Mercedes Ford, John A. Abbafati, Cristiana Abdalla, Mohammed Altigani Abdelkader, Atef Abdi, Parsa Zuñiga, Roberto Ariel Abeldaño Abiodun, Olugbenga Olusola Abolhassani, Hassan Abu-Gharbieh, Eman Abukhadijah, Hana J. Abu-Zaid, Ahmed Addo, Isaac Yeboah Addolorato, Giovanni Adekanmbi, Victor Adetunji, Juliana Bunmi Adeyeoluwa, Temitayo Esther Agardh, Emilie E. Agyemang-Duah, Williams Ahmad, Danish Ahmed, Ayman Ahmed, Syed Anees Akinosoglou, Karolina Akkaif, Mohammed Ahmed Al Awaidy, Salah Al Hasan, Syed Mahfuz Al Zaabi, Omar Ali Mohammed Aldridge, Robert W. Algammal, Abdelazeem M. Al-Gheethi, Adel Ali Saeed Ali, Abid Ali, Mohammed Usman Ali, Syed Shujait Ali, Waad Alicandro, Gianfranco Alif, Sheikh Mohammad Al-Jumaily, Adel Allebeck, Peter Alrawashdeh, Ahmad Al-Rifai, Rami H. Alsabri, Mohammed A. Alshahrani, Najim Z. Aluh, Deborah Oyine Al-Wardat, Mohammad Al-Zyoud, Walid A. Amiri, Sohrab Anderlini, Deanna Andrei, Catalina Liliana Anil, Abhishek Anvari, Saeid Anyasodor, Anayochukwu Edward Appiah, Seth Christopher Yaw Aquilano, Michele Arabloo, Jalal Arafat, Mosab Areda, Demelash Aremu, Abdulfatai Armani, Keivan Armocida, Benedetta Ärnlöv, Johan Asaduzzaman, Muhammad Astell-Burt, Thomas Aujayeb, Avinash Ausloos, Marcel Azadnajafabad, Sina Aziz, Shahkaar Azzam, Ahmed Y. Babu, Giridhara Rathnaiah Badache, Andreea Corina Badiye, Ashish D. Bahramian, Saeed Baig, Atif Amin Baker, Jennifer L. Bansal, Hansi Bärnighausen, Till Winfried Barone, Mark Thomaz Ugliara Barrow, Amadou Barteit, Sandra Bashir, Shahid Bashiru, Hameed Akande Basso, João Diogo Bastan, Mohammad-Mahdi Basu, Sanjay Batra, Kavita Bauckneht, Matteo Baune, Bernhard T. Beghi, Massimiliano Beiranvand, Maryam Béjot, Yannick Bell, Michelle L. Bello, Olorunjuwon Omolaja Belo, Luis Beloukas, Apostolos Beneke, Alice A. Bettencourt, Paulo J.G. Bhagavathula, Akshaya Srikanth Bhala, Neeraj Bhaskar, Sonu Bisulli, Francesca Bjørge, Tone Bodunrin, Aadam Olalekan Carvajal, Alejandro Botero Bouaoud, Souad Brayne, Carol Brenner, H Department of Primary Care and Public Health University of East Anglia Norwich United Kingdom Office for Health Improvement and Disparities Department of Health and Social Care London United Kingdom Department of Legal and Economic Studies La Sapienza University Rome Italy Rome Italy Hull York Medical School University of Hull Hull United Kingdom Department of Mathematics and Sciences Ajman University Ajman United Arab Emirates Department of Medicine Memorial University St. John's NL Canada Postgraduate Department University of Sierra Sur Miahuatlan de Porfirio Diaz Mexico Yhteiskuntadatatieteen keskus (Centre for Social Data Science) Helsinki Finland Department of Internal Medicine Federal Medical Centre Abuja Nigeria Research Center for Immunodeficiencies Tehran University of Medical Sciences Tehran Iran Department of Medical Biochemistry and Biophysics Karolinska Institutet (Karolinska Institute) Stockholm Sweden Department of Clinical Sciences University of Sharjah Sharjah United Arab Emirates Department of Biopharmaceutics and Clinical Pharmacy University of Jordan Amman Jordan Medical Research Center Hamad Medical Corporation Doha Qatar Department of Biochemistry and Molecular Medicine Alfaisal University Riyadh Saudi Arabia College of Graduate Health Sciences University of Tennessee Memphis TN United States School of Medicine Sydney NSW Australia Centre for Social Research in Health University of New South Wales Sydney NSW Australia Internal Medicine and Alcohol Related Disease Unit Fondazione Policlinico Universitario A. Gemelli IRCCS Rome Italy Department of Medical and Surgical Sciences Università Cattolica di Roma (Catholic University of Rome) Rome Italy Department of Obstetrics and Gynecology University of Texas Medical Branch Galveston TX United States Department of Biochemistry Osun State University Osogbo Nigeria Department of Pharmacology and Therapeutics University of Medical Sciences Ondo Ondo Nigeria Department of Veteri

Background: Decades of steady improvements in life expectancy in Europe slowed down from around 2011, well before the COVID-19 pandemic, for reasons which remain disputed. We aimed to assess how changes in risk factors and cause-specific death rates in different European countries related to changes in life expectancy in those countries before and during the COVID-19 pandemic. Methods: We used data and methods from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 to compare changes in life expectancy at birth, causes of death, and population exposure to risk factors in 16 European Economic Area countries (Austria, Belgium, Denmark, Finland, France, Germany, Greece, Iceland, Ireland, Italy, Luxembourg, the Netherlands, Norway, Portugal, Spain, and Sweden) and the four UK nations (England, Northern Ireland, Scotland, and Wales) for three time periods: 1990–2011, 2011–19, and 2019–21. Changes in life expectancy and causes of death were estimated with an established life expectancy cause-specific decomposition method, and compared with summary exposure values of risk factors for the major causes of death influencing life expectancy. Findings: All countries showed mean annual improvements in life expectancy in both 1990–2011 (overall mean 0·23 years [95% uncertainty interval [UI] 0·23 to 0·24]) and 2011–19 (overall mean 0·15 years [0·13 to 0·16]). The rate of improvement was lower in 2011–19 than in 1990–2011 in all countries except for Norway, where the mean annual increase in life expectancy rose from 0·21 years (95% UI 0·20 to 0·22) in 1990–2011 to 0·23 years (0·21 to 0·26) in 2011–19 (difference of 0·03 years). In other countries, the difference in mean annual improvement between these periods ranged from –0·01 years in Iceland (0·19 years [95% UI 0·16 to 0·21] vs 0·18 years [0·09 to 0·26]), to –0·18 years in England (0·25 years [0·24 to 0·25] vs 0·07 years [0·06 to 0·08]). In 2019–21, there was an overall decrease in mean annual life expectancy a

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CCL5 Protects Cortical Neuron Function by Regulating M2 Microglia Activation After Mild Traumatic Brain Injury

SSRN

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SSRN 2022年

作者： Tsai, Yih-Jeng Ho, Man-Hau Yen, Chia-Hung Wang, Jia-Yi Burnouf, Thierry Chen, Chia-Yen Wang, Yun Chiang, Yung-Hsiao Hoffer, Barry J. Chou, Szu-Yi Department of Otolaryngology Head and Neck Surgery Shin Kong Wu HoSu Memorial Hospital Taipei Taiwan School of Medicine Fu Jen Catholic University New Taipei City Taiwan Ph.D. Program in Medical Neuroscience College of Medical Science and Technology Taipei Medical University National Health Research Institute Taiwan Graduate Institute of Neural Regenerative Medicine College of Medical Science and Technology Taipei Medical University Taipei Taiwan Department of Biological Science and Technology National Pingtung University of Science and Technology Neipu Pingtung91201 Taiwan Graduate Institute of Medical Sciences College of Medicine Taipei Medical University Taipei11031 Taiwan Department of Neurosurgery Taipei Medical University Hospital Taipei11031 Taiwan Neuroscience Research Center Taipei Medical University Taipei11031 Taiwan International PhD Program in Biomedical Engineering College of Biomedical Engineering Taipei Medical University Taipei Taiwan Graduate Institute of Biomedical Materials and Tissue Engineering College of Biomedical Engineering Taipei Medical University Taipei Taiwan NeuroTMULille International Laboratory Taipei Medical University Taipei Taiwan International PhD Program in Cell Therapy and Regeneration Medicine College of Medicine Taipei Medical University Taipei Taiwan Brain and Consciousness Research Centre TMU Shuang Ho Hospital New Taipei City Taiwan Center for Neuropsychiatric Research National Health Research Institutes Zhunan Miaoli County Taiwan Department of Surgery School of Medicine College of Medicine Taipei Medical University 11031 Taiwan Department of Neurosurgery Case Western Reserve University School of Medicine ClevelandOH United States Scientist Emeritus National Institutes of Health United States International Master Program in Medical Neuroscience College of Medical Science and Technology Taipei Medical University Taipei Taiwan

Cytokines and chemokines play important roles in inflammation and repair following brain injury. M1 microglia are pro-inflammatory which produce cytokines and lead to neural injury;in contrast, M2 microglia are anti-inflammatory, release neurotrophic factors, and promote neural repair processes. Chemokine CCL5, increased after TBI, shows a neuroprotective function by reducing oxidative stress. CCL5 may contribute to the balance between oxidative stress and immune responses after brain injury. Herein, we investigated the role of CCL5 in microglial polarization after mild traumatic brain injury, focusing on the cerebral cortex.C57BL/6 and CCL5 knockout (CCL5-KO) mice were given a mild traumatic brain injury (TBI) using weight-drop. Neurological parameters such as motor and sensory functions were analyzed by mNSS score, accelerating rotarod, beam walking, and adhesive removal tests. Oxidative stress and neuron damage were measured by NADPH oxidase activity, hypoxyloprobe staining and FJC. Performance of motor and sensory functions in both WT and CCL5-KO mice were impaired after brain injury which recovered after 7 days-post-injury (dpi) in the WT group but only after 14 days in the CCL5-KO mouse group. RT-qPCR analysis revealed that pro-inflammation cytokines - IL-1β, TNF-α, and IL-6 were higher in CCL5-KO mice compared to WT mice at 4 and 14 dpi. In contrast, M2-like microglia markers - IL-10 and Agr-1 were increased in WT mouse cortical tissue at 4 dpi. Oxidative stress increased both M1 and M2- related cytokine expression in BV2 cells treated with H 2 O 2;CCL5 treatment increased M2- but suppressed M1- related cytokine gene activation. Intranasal delivery of CCL5 reduced neuronal oxidative stress, increased IL-10 expression and improved motor and sensory functions in CCL5-KO mice after brain *** summary, CCL5, which alters immune responses and protects neurons from TBI damage, has an important function in regulating M2-like microglial polarization during post-

关键词： Polarization

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Agricultural All-Terrain Vehicle Safety: Hazard Control Methods Using the Haddon Matrix

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Journal of Agromedicine 2021年第4期26卷 420-435页

作者： Farzaneh Khorsandi Paul Ayers Gerene Denning Charles Jennissen Dee Jepsen Melvin Myers Stephen Oesch Michael Pate David J. White a Agricultural Safety and Health Engineering Assistant Specialist in Cooperative Extension Defpartment of Biological and Agricultural Engineering University of California Davis b Professor Department of Biosystems Engineering and Soil Science University of Tennessee Knoxville c Emeritus Research Scientist in Emergency Medicine Department of Emergency Medicine University of Iowa Carver College of Medicine d MD Clinical Professor of Pediatrics and Emergency Medicine Department of emergency medicine University of Iowa Carver College of Medicine e Associate Professor / State Agricultural Safety Leader Department of Food Agricultural and Biological Engineering agricultural safety and health program The Ohio State University f Associate Professor (Adjunct) Environmental Health Emory University Emory Rollins School of Public Health Atlanta Georgia g Retired highway and motor vehicle safety attorney h Associate Professor Applied Sciences Technology & Education Agricultural Systems Technology and Education program Utah State University i PhD Professor of Social and Behavioral Health Sciences College of Public Health and Human Sciences School of Social and Behavioral Health Sciences and Extension 4-H Youth Development Oregon State University

ABSTRACTABSTRACTAll-terrain vehicle (ATV) crashes are one of the leading causes of death and injury in agriculture across the United States. Use of ATVs is highly prevalent in rural areas and has seen an increase in their application for a variety of agricultural work tasks. Empirical research on the use of these vehicles for agricultural tasks and associated injuries is limited, especially in the United States. Moreover, little is known about the risk factors associated with ATV-related injuries while doing farm work. A comprehensive review was conducted to evaluate the current injury burden of ATV use in agriculture, the need for future research, and possible solutions related to agricultural ATV safety. Potential injury prevention approaches are evaluated based on the hierarchy of control, including elimination or substitution (using side-by-side vehicles instead of ATVs or modifying ATV design), engineering control (operator protection devices), administrative authority (regulations and standards in the United States and around the world), training, and use of personal protective equipment. In addition, vehicle nomenclature, risk factors, and crash mechanisms are reviewed. Recommendations to decrease the likelihood of ATV crashes and injuries are provided.

关键词： Agriculture all-terrain vehicle ATV quad bike safety

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Hydrogen sulfide coordinates glucose metabolism switch through destabilizing tetrameric pyruvate kinase M2

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Nature Communications 2024年第1期15卷 7463页

作者： Wang, Rong-Hsuan Chen, Pin-Ru Chen, Yue-Ting Chen, Yi-Chang Chu, Yu-Hsin Chien, Chia-Chen Chien, Po-Chen Lo, Shao-Yun Wang, Zhong-Liang Tsou, Min-Chen Chen, Ssu-Yu Chiu, Guang-Shen Chen, Wen-Ling Wu, Yi-Hsuan Wang, Lily Hui-Ching Wang, Wen-Ching Lin, Shu-Yi Kung, Hsing-Jien Wang, Lu-Hai Cheng, Hui-Chun Lin, Kai-Ti Institute of Biotechnology National Tsing Hua University Hsinchu Taiwan Institute of Bioinformatics and Structural Biology National Tsing Hua University Hsinchu Taiwan Institute of Molecular and Genomic Medicine National Health Research Institutes Zhunan Taiwan Institute of Molecular and Cellular Biology National Tsing Hua University Hsinchu Taiwan Department of Medical Science National Tsing Hua University Hsinchu Taiwan School of Medicine National Tsing Hua University Hsinchu Taiwan Department of Life Science National Tsing Hua University Hsinchu Taiwan Institute of Biomedical Engineering and Nanomedicine National Health Research Institutes Zhunan Taiwan College of Medical Science and Technology PhD Program for Cancer Biology and Drug Discovery Taipei Medical University Taipei Taiwan Chiese Medicine Research Center and Institute of Integrated Medicine China Medical University Taichung City Taiwan

Most cancer cells reprogram their glucose metabolic pathway from oxidative phosphorylation to aerobic glycolysis for energy production. By reducing enzyme activity of pyruvate kinase M2 (PKM2), cancer cells attain a greater fraction of glycolytic metabolites for macromolecule synthesis needed for rapid proliferation. Here we demonstrate that hydrogen sulfide (H₂S) destabilizes the PKM2 tetramer into monomer/dimer through sulfhydration at cysteines, notably at C326, leading to reduced PKM2 enzyme activity and increased PKM2-mediated transcriptional activation. Blocking PKM2 sulfhydration at C326 through amino acid mutation stabilizes the PKM2 tetramer and crystal structure further revealing the tetramer organization of PKM2-C326S. The PKM2-C326S mutant in cancer cells rewires glucose metabolism to mitochondrial respiration, significantly inhibiting tumor growth. In this work, we demonstrate that PKM2 sulfhydration by H₂S inactivates PKM2 activity to promote tumorigenesis and inhibiting this process could be a potential therapeutic approach for targeting cancer metabolism. © The Author(s) 2024.

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The Role of Animal-Assisted Therapy in Enhancing Patients' Well-Being: Systematic Study of the Qualitative and Quantitative Evidence

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JMIRx med 2024年 5卷 e51787页

作者： Ramendra Pati Pandey Riya Mukherjee Chung-Ming Chang School of Health Sciences & Technology University of Petroleum and Energy Studies Dehradun Uttarakhand India. Graduate Institute of Biomedical Sciences Chang Gung University Taoyuan Taiwan. Master & PhD Program in Biotechnology Industry Chang Gung University Taoyuan Taiwan. Department of Medical Biotechnology and Laboratory Science Chang Gung University Taoyuan Taiwan.

Background:Animal-assisted therapy, also known as pet therapy, is a therapeutic intervention that involves animals to enhance the well-being of individuals across various populations and settings. Objective:This systematic study aims to assess the outcomes of animal-assisted therapy interventions and explore the associated policies. Methods:A total of 16 papers published between 2015 and 2023 were selected for analysis. These papers were chosen based on their relevance to the research topic of animal-assisted therapy and their availability in scholarly databases. Thematic synthesis and meta-analysis were used to synthesize the qualitative and quantitative data extracted from the selected papers. Results:The analysis included 16 studies that met the inclusion criteria and were deemed to be of moderate or higher quality. Among these studies, 4 demonstrated positive results for therapeutic mediation and one for supportive mediation in psychiatric disorders. Additionally, all studies showed positive outcomes for depression and neurological disorders. Regarding stress and anxiety, 3 studies indicated supportive mediation, while 2 studies showed activating mediation. Conclusions:The overall assessment of animal-assisted therapy shows promise as an effective intervention in promoting well-being among diverse populations. Further research and the establishment of standardized outcome assessment measures and comprehensive policies are essential for advancing the field and maximizing the benefits of animal-assisted therapy.

关键词： animal-assisted therapy outcome assessment pet therapy policies systematic study

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Robustness and Stability of Spin Glass Ground States to Perturbed Interactions

arXiv

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arXiv 2020年

作者： Mohanty, Vaibhav Louis, Ard A. Rudolf Peierls Centre for Theoretical Physics University of Oxford OxfordOX1 3NP United Kingdom MD-PhD Program and Program in Health Sciences and Technology Harvard Medical School BostonMA02125 United States Massachusetts Institute of Technology CambridgeMA02139 United States

Across many scientific and engineering disciplines, it is important to consider how much the output of a given system changes due to perturbations of the input. Here, we investigate the glassy phase of ±J spin glasses at zero temperature by calculating the robustness of the ground states to flips in the sign of single interactions. For random graphs and the Sherrington-Kirkpatrick model, we find relatively large sets of bond configurations that generate the same ground state. These sets can themselves be analyzed as subgraphs of the interaction domain, and we compute many of their topological properties. In particular, we find that the robustness, equivalent to the average degree, of these subgraphs is much higher than one would expect from a random model. Most notably, it scales in the same logarithmic way with the size of the subgraph as has been found in genotype-phenotype maps for RNA secondary structure folding, protein quaternary structure, gene regulatory networks, as well as for models for genetic programming. The similarity between these disparate systems suggests that this scaling may have a more universal origin. © 2020, CC BY.

关键词： Ground state

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Outdoor Air Pollution Relates to Amygdala Subregion Volume and Apportionment in Early Adolescence

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Biological Psychiatry Global Open Science 2025年

作者： Jessica Morrel L. Nate Overholtzer Kirthana Sukumaran Devyn L. Cotter Carlos Cardenas-Iniguez J. Michael Tyszka Joel Schwartz Daniel A. Hackman Jiu-Chiuan Chen Megan M. Herting Department of Population and Public Health Sciences Keck School of Medicine University of Southern California Los Angeles CA USA Neuroscience Graduate Program University of Southern California Los Angeles CA USA USC-Caltech MD-PhD Program Los Angeles CA USA Division of the Humanities and Social Sciences California Institute of Technology Pasadena CA USA Department of Environmental Health Harvard T.H. Chan School of Public Health Boston MA USA USC Suzanne Dworak-Peck School of Social Work University of Southern California Los Angeles CA USA Department of Neurology Keck School of Medicine of University of Southern California Los Angeles CA USA

Background Outdoor air pollution exposure is associated with structural and functional brain differences, and an increased risk for psychopathology. Although the neural mechanisms remain unclear, air pollutants may impact mental health by altering brain regions implicated in psychopathology, such as the amygdala. Here, we examine the association between ambient air pollution exposure and amygdala subregion volumes in 9–10-year-olds. Methods Cross-sectional data from 4,473 (55.4% male) Adolescent Brain Cognitive Development SM (ABCD) Study® participants were leveraged. Air pollution exposure was estimated based on each participant’s primary residential address. Using the CIT168 atlas, we quantified total amygdala and 9 subregion volumes from T1- and T2-weighted images. We investigated associations between criteria pollutants (i.e., fine particulate matter [PM 2.5 ], nitrogen dioxide, and ground-level ozone), 15 PM 2.5 components, and amygdala subregion volumes and relative volume fractions using both single-pollutant linear mixed-effects regression and partial least squares correlation (PLSC) co-exposure modeling approaches. Results No significant associations were detected using single-pollutant models. Rather, in examining mixtures of exposures with PLSC, one latent dimension (52% variance explained) captured a positive association between calcium and several basolateral subregions. Latent dimensions were also identified for amygdala relative volume fractions (ranging from 30% to 82% variance explained), with PM 2.5 and component co-exposure associated with increases in lateral, but decreases in medial and central, relative volume fractions. Conclusions Fine particulate matter and its components are associated with distinct amygdala differences, potentially playing a role in risk for adolescent mental health problems.

关键词： amygdala air pollution PM 2.5 neuroimaging ABCD Study brain development

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Analysis of in-flight spatial disorientation among military pilots in taiwan

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Journal of Medical Sciences (Taiwan) 2021年第1期41卷 22-28页

作者： Tu, Min-Yu Cheng, Chao-Chien Hsin, Yi-Hsiang Huang, Wun-Wei Li, Fang-Ling Hu, Je-Ming Chiang, Kwo-Tsao Lai, Chung-Yu Aviation Physiology Research Laboratory Kaohsiung Armed Forces General Hospital Gangshan Branch Kaohsiung City Taiwan Department of Health Business Administration Meiho University Pingtung County Taiwan Department of Life Sciences and PhD Program in Translational Medicine National Chung Hsing University Taichung City Taiwan Institute of Medical Science and Technology National Sun Yat-sen University Kaohsiung City Taiwan Department of Psychiatry Tri-Service General Hospital Beitou Branch National Defense Medical Center Taipei City Taiwan Division of Colorectal Surgery Department of Surgery Tri-Service General Hospital National Defense Medical Center Taipei City Taiwan Graduate Institute of Medical Sciences National Defense Medical Center Taipei City Taiwan Graduate Institute of Aerospace and Undersea Medicine National Defense Medical Center Taipei City Taiwan

Background: In-flight spatial disorientation (SD) is a predominant threat to flight safety in aviation. This study was conducted to understand the prevalence, severity, and frequency of in-flight SD among military pilots in Taiwan. Methods: A survey was conducted to collect tri-service pilots' experiences of SD during flight. Participants completed anonymous SD questionnaires during refresher physiology training. There were 486 questionnaires delivered to trainees and the completion rate was 97.1% (n = 472). All data were processed using SPSS version 24 software (IBM, Armonk, NY, USA). Results: Of the 472 participants, the average age of the pilots was 36.7 so 7.3 years and 97.7% were male. About 80% of participants experienced in-flight SD events. There was a significant difference between prevalence of SD in fighter (87.0%), trainer (89.8%), transporter (70.6%), and helicopter (66.7%) pilots (P < 0.001). Less than 10% of the events were severe, and there was no obvious variation between aircraft types (P = 0.126). Pilots were sensitive to SD in clouds and under low visibility. Over 70% of pilots experienced visual illusions, especially loss of horizon during bad weather (45.1%), followed by leans (44.5%), false horizon (44.1%), false sense in clouds (39.6%), Coriolis illusion (25.0%), and confusion on entry to instrument meteorological conditions (25.0%). Conclusions: Our survey showed that SD is a common physiological problem among military pilots, who were easily disoriented by in-flight SD without visual cues. Visual illusion was relatively more frequent, especially for trainer and fighter pilots. © 2021 Wolters Kluwer Medknow Publications. All rights reserved.

关键词： coriolis illusion illusion instrument meteorological conditions Spatial disorientation visibility

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ABCB1 Regulates Immune Genes in Breast Cancer

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Breast cancer (Dove Medical Press) 2023年 15卷 801-811页

作者： Han-Kun Chen Yi-Ling Chen Chih-Yang Wang Wei-Pang Chung Jung-Hua Fang Ming-Derg Lai Hui-Ping Hsu Department of Surgery Chi Mei Medical Center Tainan Taiwan. Department of Health and Nutrition Chia Nan University of Pharmacy and Science Tainan Taiwan. PhD Program for Cancer Molecular Biology and Drug Discovery College of Medical Science and Technology Taipei Medical University Taipei Taiwan. Graduate Institute of Cancer Biology and Drug Discovery College of Medical Science and Technology Taipei Medical University Taipei Taiwan. Department of Oncology National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan 70403 Taiwan. Center of Applied Nanomedicine National Cheng Kung University Tainan Taiwan. Laboratory Animal Center College of Medicine National Cheng Kung University Tainan Taiwan. Department of Biochemistry and Molecular Biology National Cheng Kung University Tainan Taiwan. Institute of Basic Medical Sciences College of Medicine National Cheng Kung University Tainan Taiwan. Department of Surgery National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan Taiwan.

Background:Resistance to standard chemotherapy is a critical problem for breast cancer patients. The ATP-binding cassette (ABC) superfamily transporters actively pump out drugs and play an important role in chemoresistance. ABCB1 (ABC subfamily B, member 1, also named as multidrug resistance protein 1, MDR1) and suppressive myeloid-derived suppressor cells (MDSCs) potentially involve in chemoresistance of breast cancer. The relationship between ABCB1 and immune genes in breast cancer has not been widely studied. Methods:Microarray and RNA sequencing data were obtained from The Cancer Genome Atlas Breast Invasive Carcinoma in Genomic Data Commons Data Portal and Gene Expression Omnibus database. A patient-derived xenograft (PDX) model of HER2 breast cancer was established to investigate the association between and immune genes in breast cancer. Results:Expression of increased in doxorubicin-selected MCF-7/ADR cells. High expression of mRNA is correlated with lymph-node metastasis and worse overall survival in patients with breast cancer. is positively correlated with , and . In the HER2 stage IIA breast cancer PDX model, both doxorubicin and paclitaxel suppressed growth of P2 tumors. IL6, CSF1, CSF3, and PTGS2 expression were suppressed by paclitaxel but not doxorubicin. Intrasplenic MDSCs, including CD11bLy6G and CD11bLy6C cells, were more abundant than intratumor MDSCs in PDX-carrying nude mice. Clinically, the patient developed cancer recurrence after adjuvant chemotherapy with doxorubicin-based regimen and was well controlled after paclitaxel-trastuzumab combined therapy. Conclusion:ABCB1 was a poor predictor of HER2 LN breast cancer. Regulation of immune genes by ABCB1 contributed to cancer recurrence and treatment effect. The PDX model was suitable for investigation the expression of target genes and expansion of immune cells.

关键词： ABC transporters ABCB1 breast cancer myeloid-derived suppressor cells patient-derived xenograft

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Comparison of endoscopic third ventriculostomy versus cerebrospinal fluid shunt procedures for the treatment of pediatric hydrocephalus in Taiwan

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Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery 2024年第9期40卷 2883-2891页

作者： Shu-Mei Chen Li-Ying Chen Jiann-Her Lin Nicole Salazar Tu-Hsueh Yeh Wei-Lun Lo Tai-Ngar Lui Yi-Chen Hsieh Li-Nien Chien Department of Neurosurgery Taipei Medical University Hospital Taipei Medical University Taipei Taiwan. Department of Surgery School of Medicine Taipei Medical University Taipei Taiwan. Health Data Analytics and Statistics Center Office of Data Science Taipei Medical University Taipei Taiwan. Julius L. Chambers Biomedical/Biotechnology Institute and Department of Biological & Biomedical Sciences North Carolina Central University Durham NC USA. Department of Neurology Taipei Medical University Hospital Taipei Taipei Medical University Taipei Taiwan. Department of Neurology School of Medicine College of Medicine Taipei Medical University Taipei Taiwan. Department of Neurosurgery Shuang Ho Hospital Taipei Medical University Taipei Taiwan. The PhD Program in Medical Neuroscience College of Medical Science and Technology Taipei Medical University 250 Wu-Hsing Street Taipei Taiwan. ychsieh@tmu.edu.tw. Institute of Health and Welfare Policy College of Medicine National Yang Ming Chiao Tung University No.155 Sec. 2 Linong St. Beitou District Taipei Taiwan. linien.chien@nycu.edu.tw. Graduate Institute of Data Science College of Management Taipei Medical University Taipei Taiwan. linien.chien@nycu.edu.tw.

PURPOSE:Pediatric hydrocephalus is the most common cause of surgically treatable neurological disease in children. Controversies exist whether endoscopic third ventriculostomy (ETV) or cerebrospinal fluid (CSF) shunt placement is the most appropriate treatment for pediatric hydrocephalus. This study aimed to compare the risk of re-operation and death between the two procedures. METHODS:We performed a retrospective population-based cohort study and included patients younger than 20-years-old who underwent CSF shunt or ETV for hydrocephalus from the Taiwan National health Insurance Research Database. RESULTS:A total of 3,555 pediatric patients from 2004 to 2017 were selected, including 2,340 (65.8%) patients that received CSF shunt placement and 1215 (34.2%) patients that underwent ETV. The incidence of all-cause death was 3.31 per 100 person-year for CSF shunt group and 2.52 per 100 person-year for ETV group, with an adjusted hazard ratio (HR) of 0.79 (95% confidence interval [CI] = 0.66-0.94, p = 0.009). The cumulative incidence competing risk for reoperation was 31.2% for the CSF shunt group and 26.4% for the ETV group, with an adjusted subdistribution HR of 0.82 (95% CI = 0.70-0.96, p = 0.015). Subgroup analysis showed that ETV was beneficial for hydrocephalus coexisting with brain or spinal tumor, central nervous system infection, and intracranial hemorrhage. CONCLUSION:Our data indicates ETV is a better operative procedure for pediatric hydrocephalus when advanced surgical techniques and instruments are available.

关键词： Cerebrospinal shunt Pediatric hydrocephalus Reoperation Third ventriculostomy

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