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Large circuit models: opportunities and challenges

Science China(Information Sciences) 2024年第10期 25-66页

作者： Lei CHEN yiqi CHEN Zhufei CHU Wenji FANG tsung-yi ho Ru HUANG Yu HUANG Sadaf KHAN Min LI Xingquan LI Yu LI Yun LIANG Jinwei LIU yi LIU yibo LIN Guojie LUO hongyang PAN Zhengyuan SHI Guangyu SUN Dimitrios TSARAS Runsheng WANG Ziyi WANG Xinming WEI Zhiyao XIE Qiang XU Chenhao XUE Junchi YAN Jun YANG Bei YU Mingxuan YUAN Evangeline F.Y.YOUNG Xuan ZENG Haoyi ZHANG Zuodong ZHANG Yuxiang ZHAO Hui-Ling ZHEN Ziyang ZHENG Binwu ZHU Keren ZHU Sunan ZOU Huawei Noah’s Ark Lab School of Integrated Circuits Peking University Faculty of Electrical Engineering and Computer Science Ningbo University Department of Electronic and Computer Engineering Hong Kong University of Science and Technology Department of Computer Science and Engineering The Chinese University of Hong Kong School of Integrated Circuits Southeast University Huawei HiSilicon Peng Cheng Laboratory School of Computer Science Peking University School of Microelectronics State Key Laboratory of Integrated Chips and System Fudan University School of Artificial Intelligence Shanghai Jiao Tong University

Within the electronic design automation(EDA) domain, artificial intelligence(AI)-driven solutions have emerged as formidable tools, yet they typically augment rather than redefine existing methodologies. These solutions often repurpose deep learning models from other domains, such as vision, text, and graph analytics, applying them to circuit design without tailoring to the unique complexities of electronic circuits. Such an “AI4EDA” approach falls short of achieving a holistic design synthesis and understanding,overlooking the intricate interplay of electrical, logical, and physical facets of circuit data. This study argues for a paradigm shift from AI4EDA towards AI-rooted EDA from the ground up, integrating AI at the core of the design process. Pivotal to this vision is the development of a multimodal circuit representation learning technique, poised to provide a comprehensive understanding by harmonizing and extracting insights from varied data sources, such as functional specifications, register-transfer level(RTL) designs, circuit netlists,and physical layouts. We champion the creation of large circuit models(LCMs) that are inherently multimodal, crafted to decode and express the rich semantics and structures of circuit data, thus fostering more resilient, efficient, and inventive design methodologies. Embracing this AI-rooted philosophy, we foresee a trajectory that transcends the current innovation plateau in EDA, igniting a profound “shift-left” in electronic design methodology. The envisioned advancements herald not just an evolution of existing EDA tools but a revolution, giving rise to novel instruments of design-tools that promise to radically enhance design productivity and inaugurate a new epoch where the optimization of circuit performance, power, and area(PPA) is achieved not incrementally, but through leaps that redefine the benchmarks of electronic systems' capabilities.

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Detailed profiling of carbon fixation of in silico synthetic autotrophy with reductive tricarboxylic acid cycle and Calvin-Benson-Bassham cycle in Esherichia coli using hydrogen as an energy source

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Synthetic and Systems Biotechnology 2019年第3期4卷 165-172页

作者： Hsieh-Ting-Yang Cheng Shou-Chen Lo Chieh-Chen Huang tsung-yi ho Ya-Tang Yang Department of Computer Science National Tsing Hua UniversityHsinchu30013TaiwanR.O.C Department of Life Sciences National Chung-Hsing UniveristyTaichungTaiwanR.O.C Department of Electrical Engineering National Tsing Hua UniversityHsinchu30013TaiwanR.O.C Program in Microbial Genomics National Chung Hsing UniversityTaichungTaiwanR.O.C Innovation and Development Center of Sustainable Agriculture National Chung Hsing UniversityTaichungTaiwanR.O.C

Carbon fixation is the main route of inorganic carbon in the form of CO2 into the *** nature,RuBisCO is the most abundant protein that photosynthetic organisms use to fix CO2 from the atmosphere through the Calvin-Benson-Bassham(CBB)***,the CBB cycle is limited by its low catalytic rate and low energy *** this work,we attempt to integrate the reductive tricarboxylic acid and CBB cycles in silico to further improve carbon fixation *** heterologous enzymes,mostly carboxylating enzymes,are inserted into the Esherichia coli core metabolic network to assimilate CO2 into biomass using hydrogen as energy ***,such a strain shows enhanced growth yield with simultaneous running of dual carbon fixation *** key results include the following.(i)We identified two main growth states:carbon-limited and hydrogenlimited;(ii)we identified a hierarchy of carbon fixation usage when hydrogen supply is limited;and(iii)we identified the alternative sub-optimal growth mode while performing genetic *** results and modeling approach can guide bioengineering projects toward optimal production using such a strain as a microbial cell factory.

关键词： Reductive tricarboxylic acid cycle Calvin-Benson-Bassham cycle Carbon fixation Metabolism

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The autophagy protein Atg9 functions in glia and contributes to parkinsonian symptoms in a Drosophila model of Parkinson’s disease

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Neural Regeneration Research 2024年第5期19卷 1150-1155页

作者： Shuanglong yi Linfang Wang Margaret S.ho Shiping Zhang School of Life Science and Technology ShanghaiTech UniversityShanghaiChina College of Life Sciences University of Chinese Academy of SciencesBeijingChina

Parkinson’s disease is a progressive neurodegenerative disease characterized by motor deficits,dopaminergic neuron loss,and brain accumulation ofα-synuclein aggregates called Lewy *** in protein degradation pathways,such as autophagy,has been demonstrated in neurons as a critical mechanism for eliminating protein aggregates in Parkinson’s ***,it is less well understood how protein aggregates are eliminated in glia,the other cell type in the *** the present study,we show that autophagy-related gene 9(Atg9),the only transmembrane protein in the autophagy machinery,is highly expressed in Drosophila glia from adult *** from immunostaining and live cell imaging analysis reveal that a portion of Atg9 localizes to the trans-Golgi network,autophagosomes,and lysosomes in ***9 is persistently in contact with these *** glial atg9 reduces the number of omegasomes and autophagosomes,and impairs autophagic substrate *** suggests that glial Atg9 participates in the early steps of autophagy,and hence the control of autophagic ***,loss of glial atg9 induces parkinsonian symptoms in Drosophila including progressive loss of dopaminergic neurons,locomotion deficits,and glial *** findings identify a functional role of Atg9 in glial autophagy and establish a potential link between glial autophagy and Parkinson’s *** results may provide new insights on the underlying mechanism of Parkinson’s disease.

关键词： Atg9 autophagy glia Parkinson’s disease

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Clean-DM1, a Korean Polyherbal Formula, Improves High Fat Diet-Induced Diabetic Symptoms in Mice by Regulating IRS/PI3K/AKT and AMPK Expressionsin Pancreas and Liver Tissues

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Chinese Journal of Integrative Medicine 2024年第2期30卷 125-134页

作者： Piao Wang yi Liu Seok Yong Kang Chenzi Lyu Xiang Han Tianjun ho Kyung Jae Lee Xianglong Meng Yong-Ki Park Hyo Won Jung Department of Herbology College of Korean MedicineDongguk UniversityGyeongju 38066Korea College of Pharmacy&Graduate School of Pharmaceutical Sciences Ewha Womans UniversitySeoul 03760Korea Korean Medicine R&D Center Dongguk UniversityGyeongju 38066Korea Shanxi Key Laboratory of Traditional Herbal Medicines Processing Shanxi University of Chinese MedicineJinzhong(030619)ShanxiProvinceChina

Objective:To investigate the effects of Clean-DM1(C-DM1),a polyherbal formulation of Radix Scrophulariae,Radix Astragali,Rhizoma Atractylodis,and Radix Salviae Miltiorrhizae,on high-fat diet(HFD)-induced diabetes ***:The information about active components of C-DM1 extract and molecular mechanism was obtained from network pharmacology *** compounds of C-DM1 extract by high performance liquid chromatography-mass spectrometry(HPLC-MS)analysis were conducted for quality *** in vivo study,mice were induced diabetes by HFD for 12 *** mice in the normal group(Nor)were maintained with a regular diet and treated with saline by *** HFD model mice were randomly divided into 3 groups,including a HFD diabetic model group,a C-DM1 extract-administered group(C-DM1,500 mg/kg),and metformin-administered groups(Met,500 mg/kg),8 mice in each *** intake,body weight(BW),and fasting blood glucose(FBG)levels were recorded weekly for 4 *** 4 weeks of treatment,alanine aminotransferase(ALT),aspartate aminotransferase(AST),blood glucose,low-density lipoprotein cholesterol(LDL-C)were determined using an automated clinical chemistry analyzer,and homeostatic model for assessing insulin resistance(hoMA-IR)levels and oral glucose tolerance test(OGTT)were *** histopathological changes of liver and pancreatic tissues were observed by hematoxylin-eosin *** receptor substrate(IRS)/phosphatidylinositol 3 kinase(PI3K)/protein kinase B(AKT)and adenosine 5'-monophosphate-activated protein kinase(AMPK)expressions in liver and pancreas tissues were detected by Western blot ***:HPLC-MS identified dihydroisotanshinone,dihydroisotanshinone I,cryptotanshinone,harpagoside,and atractyloside A in C-DM1 *** administration of C-DM1 extract significantly decreased body weight,calorie intake,and the levels of blood glucose and insulin in the diabetic mice(P<0.05 or P<0.01).The C-DM1 extract administration improved the im

关键词： high-fat diet type 2 diabetes mellitus herbal formulation insulin receptor substrate/phosphatidylinositol 3 kinase/protein kinase B adenosine 5'-monophosphate-activated protein kinase network pharmacology high performance liquid chromatography-mass spectrometry analysis

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Value of glucose transport protein 1 expression in detecting lymph node metastasis in patients with colorectal cancer

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World Journal of Clinical Cases 2024年第5期12卷 931-941页

作者： hongsik Kim Song-yi Choi Tae-Young Heo Kyeong-Rok Kim Jisun Lee Min Young Yoo Taek-Gu Lee Joung-ho Han Department of Internal Medicine Chungbuk National University HospitalCheongju 28644South Korea Department of Pathology Chungnam National University College of MedicineDaejeon 35015South Korea Information and Statistics Chungbuk National UniversityCheongju 28644South Korea Department of Radiology College of MedicineChungbuk National UniversityChungbuk National University HospitalCheongju-si 28644South Korea Department of Nuclear Medicine School of MedicineInha UniversityIncheon 22332South Korea Department of Surgery Chungbuk National UniversityCollege of MedicineCheongju-si 28644South Korea Department of Internal Medicen Chungbuk National UniversityCollege of medicineCheongju-si 28644South Korea

BACKGROUND There are limited data on the use of glucose transport protein 1(GLUT-1)expre-ssion as a biomarker for predicting lymph node metastasis in patients with colorectal ***-1 and GLUT-3,hexokinase(HK)-II,and hypoxia-induced factor(HIF)-1 expressions may be useful biomarkers for detecting primary tumors and lymph node metastasis when combined with fluorodeoxyglucose(FDG)uptake on positron emission tomography/computed tomography(PET/CT).AIM To evaluate GLUT-1,GLUT-3,HK-II,and HIF-1 expressions as biomarkers for detecting primary tumors and lymph node metastasis with 18F-FDG-PET/*** This retrospective study included 169 patients with colorectal cancer who underwent colectomy and preoperative 18F-FDG-PET/CT at Chungbuk National University hospital between January 2009 and May *** tissue cores from the central and peripheral areas of the tumors were obtained and were examined by a dedicated pathologist,and the expressions of GLUT-1,GLUT-3,HK-II,and HIF-1 were determined using immunohisto-chemical *** analyzed the correlations among their expressions,various clinicopathological factors,and the maximum standardized uptake value(SUVmax)of PET/*** GLUT-1 was found at the center or periphery of the tumors in 109(64.5%)of the 169 ***-1 positivity was significantly correlated with the SUVmax of the primary tumor and lymph nodes,regardless of the biopsy site(tumor center,Phould consider GLUT-1 expression in preoperative endoscop

关键词： 18F-FDG-PET-CT Biomarker Colorectal neoplasms Glucose transporter type 1 Lymph node

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Genomics-driven derivatization of the bioactive fungal sesterterpenoid variecolin:Creation of an unnatural analogue with improved anticancer properties

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Acta Pharmaceutica Sinica B 2024年第1期14卷 421-432页

作者： Dexiu Yan Jemma Arakelyan Teng Wan Ritvik Raina Tsz Ki Chan Dohyun Ahn Vladimir Kushnarev Tsz Kiu Cheung ho Ching Chan Inseo Choi Pui yi ho Feijun Hu Yujeong Kim Hill Lam Lau ying Lo Law Chi Seng Leung Chun yin Tong Kai Kap Wong Wing Lam yim Nikolay S.Karnaukhov Richard Y.C.Kong Maria V.Babak Yudai Matsuda Department of Chemistry City University of Hong KongHong Kong SARChina iGEM Team“VarieCure” City University of Hong KongHong Kong SARChina Department of Biomedical Engineering City University of Hong KongHong Kong SARChina Moscow Clinical Research Center Named After A.S.Loginov Moscow 111123Russian Federation

A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin(1)and variecolactone(2)was identified in Aspergillus aculeatus ATCC *** production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 ***,the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues(5-7).Analysis of the compounds’anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities,5 was associated with significantly reduced toxic side effects in cancer-bearing mice,indicating its potentially broader therapeutic *** study describes the first tests of variecolin and its analogues in animals and demonstrates the utility of synthetic biology for creating molecules with improved biological activities.

关键词： Animal studies Anticancer properties Biosynthesis Natural products Sesterterpenoids Synthetic biology Terpene synthases Variecolin

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Regulated polarization degree of upconversion luminescence and multiple anti-counterfeit applications

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Rare Metals 2024年第5期43卷 2172-2183页

作者： Dong-Ping Wen Ping Chen yi Liang Xiao-Ming Mo Cao-Feng Pan Center On Nanoenergy Research Guangxi Key Laboratory for Relativistic AstrophysicsSchool of Physical Science and TechnologyGuangxi UniversityNanning 530004China Key Laboratory of Micronano Energy and Sensor CAS Center for Excellence in NanoscienceBeijing Institute of Nanoenergy and NanosystemsChinese Academy of SciencesBeijing 100140China

Polarization upconversion luminescence(PUCL)of lanthanide ions(Ln^(3+))has been widely used in single particle tracking,microfluidics detection,three-dimensional displays,and so ***,no effective strategy has been developed for modulating *** we report a strategy to regulate PUCL in ho^(3+)-doped NaYF4single nanorods based on the number of upconversion *** constructing a multiphoton upconversion system for ho^(3+),we regulate the degree of polarization(DOP)of PUCL from 0.590 for two-photon luminescence to 0.929 for three-photon upconversion luminescence(UCL).Furthermore,our strategy is verified from cross-relaxation between ho^(3+)and Yb^(3+),excitation wavelength,excitation power density,and local site *** this regulation strategy of PUCL has also been achieved in Tm^(3+),with the DOP ranging from 0.233 for two-photon luminescence to 0.925 for four-photon UCL Besides,multi-dimensional anti-counterfeiting display has been explored with *** work provides an effective strategy for regulating PUCL and also provides more opportunities for the development of polarization display optical encoding,anti-counterfeiting,and integrated optical devices.

关键词： Polarization upconversion luminescence Degree of polarization Population density of excited state Number of upconversion photons Polarization anti-counterfeitingdisplay

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Quantitative and qualitative subgenomic RNA profiles of SARS-CoV-2 in respiratory samples: A comparison between Omicron BA.2 and non-VOC-D614G

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Virologica Sinica 2024年第2期39卷 218-227页

作者： Zigui Chen Rita Way yin Ng Grace Lui Lowell Ling Agnes S.Y.Leung Chit Chow Siaw Shi Boon Wendy C.S.ho Maggie Haitian Wang Renee Wan yi Chan Albert Martin Li David Shu Cheong Hui Paul Kay Sheung Chan Department of Microbiology Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Medicine and Therapeutics Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Anaesthesia and Intensive Care Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Paediatrics Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Anatomical and Cellular Pathology Faculty of MedicineThe Chinese University of Hong KongHong KongChina Jockey Club School of Public Health and Primary Care Faculty of MedicineThe Chinese University of Hong KongHong KongChina Stanley ho Centre for Emerging Infectious Diseases Faculty of MedicineThe Chinese University of Hong KongHong KongChina

The SARS-CoV-2 Omicron variants are notorious for their transmissibility,but little is known about their subgenomic RNA(sgRNA)*** study applied RNA-seq to delineate the quantitative and qualitative profiles of canonical sgRNA of 118 respiratory samples collected from patients infected with Omicron BA.2 and compared with 338 patients infected with non-variant of concern(non-VOC)-D614G.A unique characteristic profile depicted by the relative abundance of 9 canonical sgRNAs was reproduced by both BA.2 and non-VOCD614G regardless of host gender,age and presence of ***,such profile was lost in samples with low viral load,suggesting a potential application of sgRNA pattern to indicate viral activity of individual patient at a specific time point.A characteristic qualitative profile of canonical sgRNAs was also reproduced by both BA.2 and *** presence of a full set of canonical sgRNAs carried a coherent correlation with crude viral load(AUC¼0.91,95%CI 0.88–0.94),and sgRNA ORF7b was identified to be the best surrogate marker allowing feasible routine application in characterizing the infection status of individual *** potentials in using sgRNA as a target for vaccine and antiviral development are worth pursuing.

关键词： Coronavirus SARS-CoV-2 Omicron BA.2 Non-VOC-D614G RNA-seq Subgenomic RNA(sgRNA)

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The evolving roles of Wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities

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Genes & Diseases 2024年第3期11卷 155-187页

作者： Michael Yu Kevin Qin Jiaming Fan Guozhi Zhao Piao Zhao Wei Zeng Connie Chen Annie Wang Yonghui Wang jiamin Zhong yi Zhu William Wagstaff Rex C.Haydon Hue H.Luu Sherwin ho Michael J.Lee Jason Strelzow Russell R.Reid Tong-Chuan He School of Medicine Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA Molecular Oncology Laboratory Department of Orthopedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Department of Orthopedic Surgery The First Affliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China Department of Orthopaedic Surgery Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Laboratory of Craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA Department of Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China

The evolutionarily conserved Wnt signaling pathway plays a central role in develop-ment and adult tissue homeostasis across *** proteins are secreted,lipid-modified signaling molecules that activate the canonical(β-catenin dependent)and non-canonical(β-catenin independent)Wnt signaling *** behaviors such as proliferation,differ-entiation,maturation,and proper body-axis specification are carried out by the canonical pathway,which is the best characterized of the known Wnt signaling *** signaling has emerged as an important factor in stem cell biology and is known to affect the self-renewal of stem cells in various *** includes but is not limited to embryonic,hematopoietic,mesenchymal,gut,neural,and epidermal stem *** signaling has also been implicated in tumor cells that exhibit stem cell-like *** signaling is crucial for bone formation and presents a potential target for the development of therapeutics for bone *** surprisingly,aberrant Wnt signaling is also associated with a wide variety of diseases,including *** of Wnt pathway members in cancer can lead to unchecked cell proliferation,epithelial-mesenchymal transition,and ***,advances in the understand-ing of dysregulated Wnt signaling in disease have paved the way for the development of novel therapeutics that target components of the Wnt *** with a brief overview of the mechanisms of canonical and non-canonical Wnt,this review aims to summarize the cur-rent knowledge of Wnt signaling in stem cells,aberrations to the Wnt pathway associated with diseases,and novel therapeutics targeting the Wnt pathway in preclinical and clinical studies.

关键词： β-Catenin Cancer Canonical Wnt Disease Non-canonical Wnt Stem cells Targeted therapy Wnt signaling

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Effects of SARS-CoV-2 infection on incidence and treatment strategies of hepatocellular carcinoma in people with chronic liver disease

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World Journal of Hepatology 2024年第2期16卷 211-228页

作者： Lung-yi Mak Matthew Shing Hin Chung Xue Li Francisco Tsz Tsun Lai Eric Yuk Fai Wan Celine Sze Ling Chui Franco Wing Tak Cheng Esther Wai yin Chan Ching Lung Cheung Ivan Chi ho Au Xi Xiong Wai-Kay Seto Man-Fung Yuen Carlos King ho Wong Ian Chi Kei Wong Department of Medicine The University of Hong KongHong KongChina State Key Laboratory of Liver Research The University of Hong KongHong KongChina Department of Pharmacology and Pharmacy The University of Hong KongHong KongChina Laboratory of Data Discovery for Health(D24H) Hong Kong Science and Technology ParkHong KongChina Department of Family Medicine and Primary Care The University of Hong KongHong KongChina School of Nursing The University of Hong KongHong KongChina School of Public Health The University of Hong KongHong KongChina Research Department of Practice and Policy University College LondonLondon WC1E 6BTUnited Kingdom Aston School of Pharmacy Aston UniversityBirmingham B47ETUnited Kingdom

BACKGROUND Chronic liver disease(CLD)was associated with adverse clinical outcomes among people with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)*** To determine the effects of SARS-CoV-2 infection on the incidence and treatment strategy of hepatocellular carcinoma(HCC)among patients with *** A retrospective,territory-wide cohort of CLD patients was identified from an electronic health database in hong *** with confirmed SARS-CoV-2 infection[coronavirus disease 2019(COVID-19)+CLD]between January 1,2020 and October 25,2022 were identified and matched 1:1 by propensity-score with those without(COVID-19-CLD).Each patient was followed up until death,outcome event,or November 15,*** outcome was incidence of *** outcomes included all-cause mortality,adverse hepatic outcomes,and different treatment strategies to HCC(curative,non-curative treatment,and palliative care).Analyses were further stratified by acute(within 20 d)and post-acute(21 d or beyond)phases of SARS-CoV-2 *** rate ratios(IRRs)were estimated by Poisson regression *** Of 193589 CLD patients(>95%non-cirrhotic)in the cohort,55163 patients with COVID-19+CLD and 55163 patients with COVID-19-CLD were included after 1:1 propensity-score *** 249-d median follow-up,COVID-19+CLD was not associated with increased risk of incident HCC(IRR:1.19,95%CI:0.99-1.42,P=0.06),but higher risks of receiving palliative care for HCC(IRR:1.60,95%CI:1.46-1.75,Phough CLD patients with SARS-CoV-2 infection were not associated with increased risk of HCC,they

关键词： SARS-CoV-2 infection Chronic liver disease Long COVID Post-COVID-19 syndrome Cirrhosis Hepatocellular carcinoma

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