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Hepatocellular carcinoma presenting as an extrahepatic mass:A case report and review of literature

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2241-2252页

作者： Wei Kelly Wu Krutika Patel Chandrasekhar Padmanabhan Kamran Idrees Department of Surgery Vanderbilt University Medical CenterNashvilleTN 37232United States Department of Pathology Microbiology and ImmunologyVanderbilt University Medical CenterNashvilleTN 37232United States division of Surgical Oncology and Endocrine Surgery Department of SurgeryVanderbilt University Medical CenterNashvilleTN 37232United States

BACKGROUND Hepatocellular carcinoma(HCC)is a primary liver tumor generally diagnosed based on radiographic *** disease is typically associated with increased tumor diameter,multifocality,and vascular *** report a case of a patient who presented with extrahepatic HCC metastasis to a portocaval lymph node with occult hepatic primary on computed tomography(CT).We review the literature for cases of extrahepatic HCC presentation without known hepatic lesions and discuss strategies to differentiate between metastatic and ectopic *** SUMMARY A 67-year-old male with remotely treated hepatis C was referred for evaluation of an enlarging portocaval,mixed cystic-solid *** CT evaluations demonstrated steatosis,but no cirrhosis or liver *** ultrasound demonstrated a normal-appearing pancreas,biliary tree,and *** needle aspiration yielded atypical *** differential diagnosis included duodenal or pancreatic cyst,lymphoproliferative cyst,stromal or mesenchymal lesions,nodal involvement from gastrointestinal or hematologic malignancy,or duodenal gastrointestinal stromal *** review by a multidisciplinary tumor board,the patient underwent open surgical resection of a 5.2 cm×5.5 cm retroperitoneal mass with pathology consistent with moderately-differentiated *** resonance imaging(MRI)subsequently demonstrated a 1.2 cm segment VIII hepatic lesion with late arterial enhancement,fatty sparing,and intrinsic T1 *** fetoprotein was 23.3 ng/*** patient was diagnosed with HCC with portocaval nodal ***:We surveyed the literature for HCC presenting as extrahepatic masses without history of concurrent or prior intrahepatic *** identified 18 cases of extrahepatic HCC ultimately found to represent metastatic lesions,and 30 cases of extrahepatic HCC found to be primary,ectopic *** Hepatocellular carcinoma can seldomly present with extrahepatic metastasis in the setting of

关键词： Extrahepatic Metastasis Portocaval Lymph node Case report

Microbiome and intestinal pathophysiology in post-acute sequelae of COVID-19

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Genes & Diseases 2024年第3期11卷 220-231页

作者： Jilei Zhang Yongguo Zhang Yinglin Xia Jun Sun division of Gastroenterology and Hepatology Department of MedicineUniversity of Ilinois ChicagoIL60612USA Uic Cancer Center Department of Microbiology and ImmunologyUniversity of Ilinois ChicagoChicagoIL60612USA Jesse Brown VA medical Center ChicagoIL60612USA

Long CoVID,also known for post-acute sequelae of CovID-19,describes the people who have the signs and symptoms that continue or develop after the acute coviD-19 *** CovID patients suffer from an inflammation or host responses towards the virus approx-imately 4 weeks after initial infection with the SARS CoV-2 virus and continue for an unchar-acterized *** infected with CovID-19 before could experience long-CcovID conditions,including the patients who were infected with SARS CoV-2 virus confirmed by tests and those who never knew they had an infection *** with long CoviD may experience health problems from different types and combinations of symptoms over time,such as fa-tigue,dyspnea,cognitive impairments,and gastrointestinal(Gl)symptoms(e.g.,nausea,vom-iting,diarrhea,decreased or loss of appetite,abdominal pain,and dysgeusia).The critical role of the microbiome in these Gl symptoms and long CovID were reported in clinical patients and experimental ***,we provide an overall view of the critical role of the Gl tract and microbiome in the development of long COVID,including the clinical Gl symptoms in patients,dysbiosis,viral-microbiome interactions,barrier function,and inflammatory bowel disease patients with long *** highlight the potential mechanisms and possible treatment based on Gl health and ***,we discuss challenges and future direction in the long CoVID clinic and research.

关键词： Gastrointestinal symptoms Gl tract Gut microbiome Inflammatorybowel diseases Intestinal barrier Long CoVID Metabolites Tight junctions

An Update on the Clinical Pipelines of New Antibacterial Drugs Developed in China

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Engineering 2024年第7期38卷 52-68页

作者： Xinyi Yang Congran Li Xiukun Wang Zhonghui Zheng Peiyi Sun Chunjie Xu Luni Chen Jiandong Jiang Staffan Normark Birgitta Henriques-Normark Xuefu You Beijing Key Laboratory of Antimicrobial Agents/Laboratory of Pharmacology Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China division for Medicinal Microorganism-Related Strains CAMS Collection Center of Pathogenic MicroorganismsChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Shandong Xinhua Pharmaceutical Co. Ltd.Zibo 255005China Department of microbiology Tumor and Cell BiologyKarolinska InstitutetStockholm SE-17177Sweden State Key Laboratory of Bioactive Substances and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Clinical microbiology Karolinska University HospitalBioclinicumStockholm SE-17176Sweden

Antibacterial resistance is a global health threat that requires further concrete action on the part of all *** this context,one of the biggest concerns is whether enough new antibacterial drugs are being discovered and *** several high-quality reviews on clinical antibacterial drug pipelines from a global perspective were published recently,none provides comprehensive information on original antibacterial drugs at clinical stages in *** this review,we summarize the latest progress of novel antibacterial drugs approved for marketing and under clinical evaluation in China since *** was obtained by consulting official websites,searching commercial databases,retrieving literature,asking personnel from institutions or companies,and other means,and a considerable part of the data covered here has not been included in other *** of June 30,2023,a total of 20 antibacterial projects from 17 Chinese pharmaceutical companies or developers were identified and *** them,two new antibacterial drugs that belong to traditional antibiotic classes were approved by the National medical Products Administration(NMPA)in China in 2019 and 2021,respectively,and 18 antibacterial agents are in clinical development,with one under regulatory evaluation,five in phase-3,six in phase-2,and six in *** of the clinical candidates are new analogs or monocomponents of traditional antibacterial pharmacophore types,including two dual-acting hybrid antibiotics and a recombinant antibacterial ***,despite there being 17 antibacterial clinical candidates,our analysis indicates that there are still relatively few clinically differentiated antibacterial agents in stages of clinical development in ***,Chinese pharmaceutical companies and institutions will develop more innovative and clinically differentiated candidates with good market potential in the future research and development(R&D)of original antibacterial drugs.

关键词： Antimicrobial resistance New antibiotics Clinical pipelines WHO priority pathogens National Mega-Project for Innovative Drugs

肠上皮细胞Axin1缺失可调节肠道微生态预防结肠炎

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Engineering 2024年第4期35卷 241-256页

作者： Shari Garrett Yongguo Zhang Yinglin Xia Jun Sun division of Gastroenterology and Hepatology Department of MedicineUniversity of Illinois ChicagoChicagoIL 60612USA Department of microbiology and immunology College of MedicineUniversity of Illinois ChicagoChicagoIL 60612USA Cancer Center University of Illinois ChicagoChicagoIL 60612USA Jesse Brown VA medical Center ChicagoIL 60612USA

Intestinal homeostasis is maintained by specialized host cells and the gut ***/β-catenin signaling is essential for gastrointestinal development and homeostasis,and its dysregulation has been implicated in inflammation and colorectal ***1 negatively regulates activated Wnt/β-catenin signaling,but little is known regarding its role in regulating host–microbial interactions in health and ***,we aim to demonstrate that intestinal Axin1 determines gut homeostasis and host response to ***1 expression was analyzed in human inflammatory bowel disease *** explore the effects and mechanism of intestinal Axin1 in regulating intestinal homeostasis and colitis,we generated new mouse models with Axin1 conditional knockout in intestinal epithelial cell(IEC;Axin1^(ΔIEC))and Paneth cell(PC;Axin1^(ΔPC))to compare with control(Axin1^(LoxP);LoxP:locus of X-over,P1)*** found increased Axin1 expression in the colonic epithelium of human inflammatory bowel disease(IBD).Axin1^(ΔIEC) mice exhibited altered goblet cell spatial distribution,PC morphology,reduced lysozyme expression,and enriched Akkermansia muciniphila(***).The absence of intestinal epithelial and PC Axin1 decreased susceptibility to dextran sulfate sodium(DSS)-induced colitis in ***1^(ΔIEC) and Axin1^(ΔPC)mice became more susceptible to DSS-colitis after cohousing with control *** with *** reduced DSS-colitis *** treatment did not change the IEC proliferation in the Axin1Loxp ***,the intestinal proliferative cells in Axin1^(ΔIEC)mice with antibiotic treatment were reduced compared with those in Axin1^(ΔIEC) mice without *** data suggest non-colitogenic effects driven by the gut *** conclusion,we found that the loss of intestinal Axin1 protects against colitis,likely driven by epithelial Axin1 and Axin1-associated *** study demonstrates a novel role of Axin1 in mediating intes

关键词： Axin1 Bacteria Microbiome inflammation Inflammatory bowel disease Immunity Microbiome Paneth cells Akkermansia muciniphila Wnt

Nuclear receptor coactivator 6 is a critical regulator of NLRP3 inflammasome activation and gouty arthritis

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Cellular & Molecular immunology 2024年第3期21卷 227-244页

作者： Kang-Gu Lee Bong-Ki Hong Saseong Lee Naeun Lee Seung-Whan Kim Donghyun Kim Wan-Uk Kim Center for Integrative Rheumatoid Transcriptomics and Dynamics The Catholic University of KoreaSeoul 06591Republic of Korea Department of Biomedicine&Health Sciences The Catholic University of KoreaSeoul 06591Republic of Korea Department of Pharmacology Asan Medical CenterUniversity of Ulsan College of MedicineSeoul 05505Republic of Korea Bio-medical Institute of Technology University of UlsanSeoul 05505Republic of Korea Department of microbiology and immunology Seoul National University College of MedicineSeoul 03080Republic of Korea Institute of Infectious Diseases Seoul National University College of MedicineSeoul 03080Republic of Korea division of Rheumatology Department of Internal MedicineThe Catholic University of KoreaSeoul 06591Republic of Korea

Transcriptional coactivators regulate the rate of gene expression in the *** receptor coactivator 6(NCOA6),a coactivator,has been implicated in embryonic development,metabolism,and cancer pathogenesis,but its role in innate immunity and inflammatory diseases remains ***,we demonstrated that NCOA6 was expressed in monocytes and macrophages and that its level was increased under proinflammatory ***,nuclear NCOA6 was found to translocate to the cytoplasm in activated monocytes and then become incorporated into the inflammasome with NLRP3 and ASC,forming cytoplasmic ***,NCOA6 associated with the ATP hydrolysis motifs in the NACHT domain of NLRP3,promoting the oligomerization of NLRP3 and ASC and thereby instigating the production of IL-1βand active *** note,Ncoa6 deficiency markedly inhibited NLRP3 hyperactivation caused by the Nlrp3^(R258W) gain-of-function mutation in *** ablation of Ncoa6 substantially attenuated the severity of two NLRP3-dependent diseases,folic-induced acute tubular necrosis and crystal-induced arthritis,in *** with these findings,NCOA6 was highly expressed in macrophages derived from gout patients,and NCOA6-positive macrophages were significantly enriched in gout macrophages according to the transcriptome profiling ***,NCOA6 is a critical regulator of NLRP3 inflammasome activation and is therefore a promising target for NLRP3-dependent diseases,including gout.

关键词： Nuclear receptor coactivator 6 Nuclear-to-cytoplasmic translocation NLRP3 inflammasome NACHT domain Gouty arthritis

Effects of COVID-19 pandemic on human fertility:A scientometric and visualized evaluation

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Genes & Diseases 2024年第4期11卷 113-115页

作者： Xiangxiu Wang Yifan Rao Lili Tan Ziqiu Hu Lin Wen Weixi Qin Bingyi Li Keqiao He Tieying Yin Juhui Qiu Yuming Wang Yaokai Chen Xiancai Rao Guixue Wang Key Laboratory of Biorheological and Technology of the Ministry of Education State and Local Joint Engineering LaboratoryforVascular ImplantsModern LifeScience Experiment Teaching Center at Bioengineering College of Chongqing UniversityChongqing 400030China Department of microbiology College of Basic Medical SciencesKey Laboratory of Microbial Engineering Under the Educational Committee in ChongqingArmy Medical University(Third Military Medical University)Chongqing 400038China Jinfeng Laboratory Chongqing 401329China division of Infectious Diseases Chongqing Public Health Medical CenterChongqing 400036China

CovID-19,also known as coronavirus disease 2019,is a novel coronavirus disease with high infectivity,strong heterogeneity,and long incubation period(generally 3-14 days).Its main symptoms and signs include fever,dry cough,nasal congestion,fatigue,disorientation,lymphopenia,and *** short-term and long-term impacts of covID-19 on human health,particularly its effects on human reproduction and offspring development,continue to receive significant concerns,as they may lead to potential sequelae for several decades or even centuries.

关键词： nasal fertility fever

Cancer-associated fibroblasts express CD1d and activate invariant natural killer T cells under cellular stress

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Cellular & Molecular immunology 2024年第1期21卷 91-94页

作者： Shengduo Pei Jonas Sjölund Yueyun Pan Kristian Pietras Mikael C.I.Karlsson Department of microbiology Tumor and Cell BiologyKarolinska InstitutetStockholmSweden division of Translational Cancer Research Department of Laboratory MedicineLund University Cancer CentreLund UniversityLundSweden

Invariant natural killer T(iNKT)cells are part of the family of unconventional T cells,and they recognize glycolipid antigens presented on the MHC class I like molecule CD1^([1]).In humans there are five CD1 molecules named CD1a to CD1e,whereas mice use only CD1d for lipid ***,iNKT cells can elicit both cytotoxicity similarly to conventional CD8 T cells and secrete cytokines that influence the adaptive immune response including providing direct T cell help to B cells^([2]).In the context of tumors,they can use both release of granzyme B and use Fas-mediated mechanisms for killing of tumor *** iNKT cells use a restricted TCR repertoire and CD1 molecules are non-heterogenous the risk of graft vs host disease is limited and thus these T cells have been an attractive option for off the shelf immunotherapy to treat cancer^([3]).

关键词： killer CD1d Cancer

Metabolic reprogramming by Syntenin-1 directs RA FLS and endothelial cell-mediated inflammation and angiogenesis

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Cellular & Molecular immunology 2024年第1期21卷 33-46页

作者： Anja Meyer Stephanie R.Zack Wes Nijim Adel Burgos Vishwa Patel Brian Zanotti Michael V.Volin M.Asif Amin Myles J.Lewis Costantino Pitzalis Shiva Arami Joseph A.Karam Nadera J.Sweiss Shiva Shahrara Jesse Brown VA medical Center ChicagoILUSA Department of Medicine Division of RheumatologyThe University of Illinois at ChicagoChicagoILUSA Department of microbiology and immunology Midwestern UniversityDowners GroveILUSA division of Rheumatology and Clinical Autoimmunity Center of Excellence University of MichiganAnn ArborMIUSA Centre for Experimental Medicine and Rheumatology William Harvey Research InstituteBarts and The London School of Medicine and DentistryQueen Mary University of LondonLondonUnited Kingdom Centre for Experimental Medicine&Rheumatology William Harvey Research InstituteQueen Mary University of London and Barts NIHR BRC&NHS TrustLondonUK Department of Biomedical Sciences Humanitas Universityand Humanitas Research HospitalMilanItaly Department of Orthopedic Surgery the University of Illinois at ChicagoChicagoILUSA

A novel rheumatoid arthritis(RA)synovial fluid protein,Syntenin-1,and its receptor,Syndecan-1(SDC-1),are colocalized on RA synovial tissue endothelial cells and fibroblast-like synoviocytes(FLS).Syntenin-1 exacerbates the inflammatory landscape of endothelial cells and RA FLS by upregulating transcription of IRF1/5/7/9,IL-1β,IL-6,and CCL2 through SDC-1 ligation and HIF1α,or mTOR ***,Syntenin-1 orchestrates RA FLS and endothelial cell invasion via SDC-1 and/or mTOR *** Syntenin-1 reprogrammed endothelial cells,the dynamic expression of metabolic intermediates coincides with escalated glycolysis along with unchanged oxidative factors,AMPK,PGC-1α,citrate,and inactive oxidative ***,RA FLS rewired by Syntenin-1 displayed a modest glycolytic-ATP accompanied by a robust mitochondrial-ATP *** enriched mitochondrial-ATP detected in Syntenin-1 reprogrammed RA FLS was coupled with mitochondrial fusion and fission recapitulated by escalated Mitofusin-2 and DRP1 *** found that VEGFR1/2 and Notch1 networks are responsible for the crosstalk between Syntenin-1 rewired endothelial cells and RA FLS,which are also represented in RA *** to RA explants,morphological and transcriptome studies authenticated the importance of VEGFR1/2,Notch1,RAPTOR,and HIF1αpathways in Syntenin-1 arthritic mice and their obstruction in SDC-1 deficient ***,dysregulation of SDC-1,mTOR,and HIF1αnegated Syntenin-1 inflammatory phenotype in RA explants,while inhibition of HIF1αimpaired synovial angiogenic imprint amplified by *** conclusion,since the current therapies are ineffective on Syntenin-1 and SDC-1 expression in RA synovial tissue and blood,targeting this pathway and its interconnected metabolic intermediates may provide a novel therapeutic strategy.

关键词： Syntenin-1 Syndecan-1 RA FLS RA explants immunometabolism

New insights into the therapeutic approaches for the treatment of tauopathies

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Neural Regeneration Research 2024年第5期19卷 1020-1026页

作者： Himanshi Singh Asmita Das Mohammad Moshahid Khan Tayebeh Pourmotabbed Department of microbiology Immunology and BiochemistryUniversity of Tennessee Health Science CenterMemphisTNUSA Department of Biotechnology Delhi Technological UniversityShahbad DaulatpurDelhiIndia Department of Neurology College of MedicineUniversity of Tennessee Health Science CenterMemphisTNUSA Neuroscience Institute University of Tennessee Health Science CenterMemphisTNUSA Center for Muscle Metabolism and NeuropathologyDivision of Regenerative and Rehabilitation Sciences and Department of Physical TherapyCollege of Health ProfessionsUniversity of Tennessee Health Science CenterMemphisTNUSA

Tauopathies are a group of neurological disorders,including Alzheimer’s disease and frontotemporal dementia,which involve progressive neurodegeneration,cognitive deficits,and aberrant tau protein *** development of tauopathies cannot currently be stopped or slowed down by treatment *** the significant contribution of tau burden in primary tauopathies and the strong association between pathogenic tau accumulation and cognitive deficits,there has been a lot of interest in creating therapies that can alleviate tau pathology and render neuroprotective ***,small molecules,immunotherapies,and gene therapy have been used to reduce the pathological tau burden and prevent neurodegeneration in animal models of ***,the major pitfall of the current therapeutic approach is the difficulty of drugs and gene-targeting modalities to cross the blood-brain barrier and their unintended side *** this review,the current therapeutic strategies used for tauopathies including the use of oligonucleotide-based gene therapy approaches that have shown a promising result for the treatment of tauopathies and Alzheimer’s disease in preclinical animal models,have been discussed.

关键词： dementia gene therapies immunotherapy neurodegeneration oligonucleotides tau tauopathies therapies