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High-density lipoprotein regulates angiogenesis by affecting autophagy via miRNA-181a-5p

Science China(Life Sciences) 2024年第2期67卷 286-300页

作者： Bi-Ang Kang Hua-Ming Li Ya-Ting Chen Meng-Jie Deng Yan Li Yue-Ming Peng Jian-Jun Gao Zhi-Wei Mo Jia-Guo Zhou Zhi-Jun Ou Jing-Song Ou division of Cardiac Surgery Cardiovascular Diseases InstituteThe First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular diseases Guangzhou 510080China NHC key Laboratory of Assisted Circulation(Sun Yat-sen University) Guangzhou 510080China Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular diseases Guangzhou 510080China division of Vascular Surgery The First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China department of Pharmacology Cardiac and Cerebral Vascular Research CenterZhongshan School of MedicineSun Yat-sen UniversityGuangzhou 510080China division of Hypertension and Vascular diseases Department of CardiologyCardiovascular Diseases InstituteThe First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China Guangdong Provincial Key Laboratory of Brain Function and Disease Zhongshan School of MedicineSun Yat-sen UniversityGuangzhou 510080China

We previously demonstrated that normal high-density lipoprotein(nHDL)can promote angiogenesis,whereas HDL from patients with coronary artery disease(d HDL)is dysfunctional and impairs *** plays a critical role in angiogenesis,and HDL regulates ***,it is unclear whether n HDL and d HDL regulate angiogenesis by affecting *** cells(ECs)were treated with n HDL and d HDL with or without an autophagy ***,endothelial nitric oxide synthase(e NOS)expression,miRNA expression,nitric oxide(NO)production,superoxide anion(O2^(·-))generation,EC migration,and tube formation were evaluated.n HDL suppressed the expression of miR-181a-5p,which promotes autophagy and the expression of e NOS,resulting in NO production and the inhibition of O2^(·-)generation,and ultimately increasing in EC migration and tube formation.d HDL showed opposite effects compared to n HDL and ultimately inhibited EC migration and tube *** found that autophagy-related protein 5(ATG5)was a direct target of ***5 silencing or miR-181a-5p mimic inhibited n HDL-induced autophagy,e NOS expression,NO production,EC migration,tube formation,and enhanced O2^(·-)generation,whereas overexpression of ATG5 or miR-181a-5p inhibitor reversed the above effects of d ***5 expression and angiogenesis were decreased in the ischemic lower limbs of hypercholesterolemic low-density lipoprotein receptor null(LDLr^(-/-))mice when compared to C57BL/6 ***5 overexpression improved angiogenesis in ischemic hypercholesterolemic LDLr^(-/-)*** together,nHDL was able to stimulate autophagy by suppressing miR-181a-5p,subsequently increasing e NOS expression,which generated NO and promoted *** contrast,d HDL inhibited angiogenesis,at least partially,by increasing miR-181a-5p expression,which decreased autophagy and e NOS expression,resulting in a decrease in NO production and an increase in O2^(·-)*** findings reveal a nov

关键词： high-density lipoprotein angiogenesis autophagy ATG5 miRNA endothelial nitric oxide synthase

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Autoimmune pancreatitis:Cornerstones and future perspectives

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World Journal of Gastroenterology 2024年第8期30卷 817-832页

作者： Camilla Gallo Giulia Dispinzieri Nicola Zucchini Pietro Invernizzi Sara Massironi division of Gastroenterology and Center for Autoimmune Liver diseases Department of Medicine and SurgeryFondazione IRCCS San Gerardo dei TintoriUniversity of Milano-BicoccaMonza 20900Italy department of Pathology Fondazione IRCCS San Gerardo dei TintoriMonza 20900Italy

Autoimmune pancreatitis(AIP)is an autoimmune subtype of chronic pancreatitis resulting from the aberrant immune response against the pancreas,leading to inflammation and *** AIP is rare,its incidence is increasing and is often misdiagnosed as other pancreatic *** is commonly classified into two *** 1 AIP(AIP-1)is typically associated with elevated serum immunoglobulin G4(IgG4)levels and systemic manifestations,while type 2 AIP is typically a more localized form of the disease,and may coexist with other autoimmune disorders,especially inflammatory bowel ***,there is emerging recognition of a third type(type 3 AIP),which refers to immunotherapy-triggered AIP,although this classification is still gaining acceptance in medical *** clinical manifestations of AIP mainly include painless jaundice and weight *** serum IgG4 levels are particularly characteristic of *** relies on a combination of clinical,laboratory,radiological,and histological findings,given the similarity of AIP symptoms to other pancreatic *** mainstay of treatment for AIP is steroid therapy,which is effective in most *** cases might require additional imm-unosuppressive *** review aims to summarize the current knowledge of AIP,encompassing its epidemiology,etiology,clinical presentation,diagnosis,and treatment *** also address the challenges and controversies in diagnosing and treating AIP,such as distinguishing it from pancreatic cancer and managing long-term treatment,highlighting the need for increased awareness and knowledge of this complex disease.

关键词： Autoimmunity Pancreatitis Autoimmune pancreatitis Immunoglobulin G4 Steroids Relapse

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Identification of novel small-molecule inhibitors of SARS-CoV-2 by chemical genetics

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Acta Pharmaceutica Sinica B 2024年第9期14卷 4028-4044页

作者： Chris Chun-Yiu Chan Qian Guo Jasper Fuk-Woo Chan Kaiming Tang Jian-Piao Cai Kenn Ka-Heng Chik Yixin Huang Mei Dai Bo Qin Chon Phin Ong Allen Wing-Ho Chu Wan-Mui Chan Jonathan Daniel Ip Lei Wen Jessica Oi-Ling Tsang Tong-Yun Wang Yubin Xie Zhenzhi Qin Jianli Cao Zi-Wei Ye Hin Chu Kelvin Kai-Wang To Xing-Yi Ge Tao Ni Dong-Yan Jin Sheng Cui Kwok-Yung Yuen Shuofeng Yuan State Key Laboratory of Emerging infectious diseases Carol Yu Centre for InfectionDepartment of MicrobiologySchool of Clinical MedicineLi Ka Shing Faculty of Medicinethe University of Hong KongPokfulamHong Kong SAR 999077China department of infectious diseases and Microbiology the University of Hong Kong-Shenzhen HospitalShenzhen 518000China Centre for Virology Vaccinology and TherapeuticsHong Kong Science and Technology ParkHong Kong SAR 999077China Academician Workstation of Hainan Province Hainan Medical University-the University of Hong Kong Joint Laboratory of Tropical Infectious DiseasesHaikou 571100China School of Biomedical Sciences Li Ka Shing Faculty of Medicinethe University of Hong KongPokfulamHong Kong SAR 999077China NHC Key Laboratory of Systems Biology of Pathogens Institute of Pathogen Biology Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China College of Biology Hunan Provincial Key Laboratory of Medical VirologyHunan UniversityChangsha 410082China

There are only eight approved small molecule antiviral drugs for treating *** them,four are nucleotide analogues(remdesivir,JT001,molnupiravir,and azvudine),while the other four are protease inhibitors(nirmatrelvir,ensitrelvir,leritrelvir,and simnotrelvir-ritonavir).Antiviral resistance,unfavourable drug‒drug interaction,and toxicity have been reported in previous *** there is a dearth of new treatment options for *** this work,a three-tier cell-based screening was employed to identify novel compounds with anti-SARS-CoV-2 *** compound,designated 172,demonstrated broad-spectrum antiviral activity against multiple human pathogenic coronaviruses and different SARS-CoV-2 variants of *** studies validated by reverse genetics showed that compound 172 inhibits the 3-chymotrypsin-like protease(3CLpro)by binding to an allosteric site and reduces 3CLpro dimerization.A drug synergistic checkerboard assay demonstrated that compound 172 can achieve drug synergy with nirmatrelvir in *** vivo studies confirmed the antiviral activity of compound 172 in both Golden Syrian Hamsters and K18 humanized ACE2 ***,this study identified an alternative druggable site on the SARS-CoV-23CLpro,proposed a potential combination therapy with nirmatrelvir to reduce the risk of antiviral resistance and shed light on the development of allosteric protease inhibitors for treating a range of coronavirus diseases.

关键词： SARS-CoV-2 High throughput screening Broad-spectrum antiviral treatment 3CLpro inhibitor Allosteric-site inhibitor Animal models Chemical genetics Reverse genetics

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Engineering nanomedicine. for immunogenic eradication of cancer cells:Recent trends and synergistic approaches

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2475-2504页

作者： Ahmed O.Elzoghby Omar Samir Hagar E.Emam Ahmed Soliman Riham M.Abdelgalil Yomna M.Elmorshedy Kadria A.Elkhodairy Mahmoud L.Nasr division of Engineering in medicine.and division of Renal medicine Department of MedicineBrigham and Women's HospitalHarvard Medical SchoolBoston 02115MAUSA Cancer Nanotechnology Research Laboratory(CNRL) Faculty of PharmacyAlexandria UniversityAlexandria 21521Egypt

Resistance to cancer immunotherapy is mainly attributed to poor tumor immunogenicity as well as the immunosuppressive tumor microenvironment(TME)leading to failure of immune *** therapeutic strategies including chemotherapy,radiotherapy,photodynamic,photothermal,magnetic,chemodynamic,sonodynamic and oncolytic therapy,have been developed to induce immunogenic cell death(ICD)of cancer cells and thereby elicit immunogenicity and boost the antitumor immune ***,many challenges hamper the clinical application of ICD inducers resulting in modest immunogenic ***,we outline the current state of using nanomedicine. for boosting ICD of cancer ***,synergistic approaches used in combination with ICD inducing nanomedicine. for remodeling the TME via targeting immune checkpoints,phagocytosis,macrophage polarization,tumor hypoxia,autophagy and stromal modulation to enhance immunogenicity of dying cancer cells were *** further highlight the emerging trends of using nanomaterials for triggering amplified ICD-mediated antitumor immune *** reticulum localized ICD,focused ultrasound hyperthermia,cell membrane camouflaged nanomedicine.,amplified reactive oxygen species(ROS)generation,metallo-immunotherapy,ion modulators and engineered bacteria are among the most innovative *** challenges,merits and demerits of ICD inducer nanomedicine. were also discussed with shedding light on the future role of this technology in improving the outcomes of cancer immunotherapy.

关键词： Immunogenic cell death Immunogenic eradication Nanomedicine. Drug delivery Cancer immunotherapy Antitumor immunity T cells Tumor associated antigens Synergistic immune response

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Is medical management useful in Moyamoya disease?

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World Journal of Clinical Cases 2024年第3期12卷 466-473页

作者： Sombat Muengtaweepongsa Vatcharasorn Panpattanakul Center of Excellence in Stroke Division of NeurologyDepartment of MedicineFaculty of MedicineThammasat UniversityRangsit CampusKlonglaung 12120Pathum ThaniThailand division of Neurology Department of Internal MedicineSchool of MedicineUniversity of PhayaoPhayao 56000Thailand

Moyamoya disease(MMD),characterized by progressive internal carotid artery stenosis and collateral vessel formation,prompts cerebral perfusion complications and is stratified into idiopathic and Moyamoya syndrome subtypes.A multifa-ceted approach toward MMD management addresses cerebral infarctions through revascularization surgery and adjunctive medical therapy,while also navigating risks such as intracranial hemorrhage and cerebral infarction resulting from arte-rial stenosis and fragile collateral *** antithrombotic management reveals a potential role for treatments like antiplatelet agents and anticoagulants,despite the ambiguous contribution of thrombosis to MMD-related infarctions and the critical balance between preventing ischemic events and averting hemo-rrhagic *** doppler has proven useful in thromboembolic detection,despite persisting challenges concerning the efficacy and safety of an-tithrombotic ***,antihypertensive interventions aim to ma-nage blood pressure meticulously,especially during intracerebral hemorrhage,with recommendations and protocols varying based on the patient’s hypertension ***,lipid-lowering therapeutic strategies,particularly employing statins,are appraised for their possible beneficial role in MMD management,even as comprehensive data from disease-specific clinical trials remains ***-prehensive guidelines and protocols to navigate the multifaceted therapeutic ave-nues for MMD,while maintaining a delicate balance between efficacy and safety,warrant further meticulous research and *** protocol manuscript seeks to elucidate the various aspects and challenges imbued in managing and navigating through the complex landscape of MMD treatment.

关键词： Moyamoya disease Cerebral infarction Antithrombotic management Transcranial doppler Revascularization Intracerebral hemorrhage Antihypertensive intervention Lipid-lowering therapies

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Uridine diphosphate glucuronosyltransferase 1A1 prevents the progression of liver injury

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World Journal of Gastroenterology 2024年第9期30卷 1189-1212页

作者： Jin-Lian Jiang Yi-Yang Zhou Wei-Wei Zhong Lin-Yan Luo Si-Ying Liu Xiao-Yu Xie Mao-Yuan Mu Zhi-Gang Jiang Yuan Xue Jian Zhang Yi-Huai He department of infectious diseases Affiliated Hospital of Zunyi Medical UniversityZunyi 563000Guizhou ProvinceChina department of infectious diseases Jingmen Central HospitalJingmen 448000Hubei ProvinceChina department of Respiratory medicine Anshun People’s HospitalAnshun 561099Guizhou ProvinceChina department of General Practice Affiliated Hospital of Zunyi Medical UniversityZunyi 563000Guizhou ProvinceChina department of Intervention Radiology Affiliated Hospital of Zunyi Medical UniversityZunyi 563000Guizhou ProvinceChina School of Public Health Zunyi Medical UniversityZunyi 563099Guizhou ProvinceChina department of Liver diseases Third People’s Hospital of ChangzhouChangzhou 213000Jiangsu ProvinceChina department of Digestion Dafang County People’s HospitalBijie 551600Guizhou ProvinceChina

BACKGROUND Uridine diphosphate glucuronosyltransferase 1A1(UGT1A1)plays a crucial role in metabolizing and detoxifying endogenous and exogenous ***,its contribution to the progression of liver damage remains *** To determine the role and mechanism of UGT1A1 in liver damage *** We investigated the relationship between UGT1A1 expression and liver injury through clinical ***,the impact and mechanism of UGT1A1 on the progression of liver injury was analyzed through a mouse model *** Patients with UGT1A1 gene mutations showed varying degrees of liver damage,while patients with acute-onchronic liver failure(ACLF)exhibited relatively reduced levels of UGT1A1 protein in the liver as compared to patients with chronic *** suggests that low UGT1A1 levels may be associated with the progression of liver *** mouse models of liver injury induced by carbon tetrachloride(CCl_(4))and concanavalin A(ConA),the hepatic levels of UGT1A1 protein were found to be *** mice with lipopolysaccharide or liver steatosis-mediated liver-injury progression,the hepatic protein levels of UGT1A1 were decreased,which is consistent with the observations in patients with ***1A1 knockout exacerbated CCl_(4)-and ConA-induced liver injury,hepatocyte apoptosis and necroptosis in mice,intensified hepatocyte endoplasmic reticulum(ER)stress and oxidative stress,and disrupted lipid *** UGT1A1 is upregulated as a compensatory response during liver injury,and interference with this upregulation process may worsen liver ***1A1 reduces ER stress,oxidative stress,and lipid metabolism disorder,thereby mitigating hepatocyte apoptosis and necroptosis.

关键词： Uridine diphosphate glucuronosyltransferase 1A1 Liver injury progression Endoplasmic reticulum stress Oxidative stress Lipid metabolism disorders

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Antifungal pipeline:Is there light at the end of the tunnel?

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World Journal of Clinical Cases 2024年第16期12卷 2686-2691页

作者： Georgios Schinas Nikolaos Spernovasilis Karolina Akinosoglou department of medicine University of PatrasPatras 26504Greece department of infectious diseases German Oncology CenterLimassol 4108Cyprus

The misuse and overuse of classic antifungals have accelerated the development of resistance mechanisms,diminishing the efficacy of established therapeutic pathways and necessitating a shift towards alternative *** this pressing need for new treatments,the antifungal drug pipeline has been largely stagnant for the past three decades,primarily due to the high risks and costs associated with antifungal drug development,compounded by uncertain market *** research durations,special patient populations and rigorous regulatory demands pose significant barriers to bringing novel antifungal agents to *** response,the“push-pull”incentive model has emerged as a vital strategy to invigorate the pipeline and encourage *** editorial critically examines the current clinical landscape and spotlights emerging antifungal agents,such as Fosmanogepix,Ibrexafungerp,and Olorofim,while also unraveling the multifaceted challenges faced in new antifungal drug *** generation of novel antifungals offers a beacon of hope in the battle against antimicrobial resistance,but it is premature to declare them as definitive *** future role hinges on thorough clinical validation,costeffectiveness assessments,and continuous post-marketing *** through strategic implementation and integration with market strategies we can transform the landscape of antifungal development,addressing both the resistance crisis and the treatment challenges.

关键词： Antifungals Resistance Fosmanogepix Ibrexafungerp Olorofim

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Correlations between serum kidney injury molecule-1,cystatin C and immunosuppressants:A cross-sectional study of renal transplant patients in Bahrain

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Journal of Biomedical Research 2024年第3期38卷 269-277页

作者： Kannan Sridharan Shamik Shah Mona Al Hammad Fatima Ali Mohammed Sindhan Veeramuthu Mona Abdulla Taher Mustafa Mohamed Hammad Lamees Jawad Eman Farid department of Pharmacology and Therapeutics College of Medicine and Medical SciencesArabian Gulf UniversityManamaKingdom of Bahrain department of Nephrology Salmaniya Medical ComplexManamaKingdom of Bahrain department of Internal medicine College of Medicine and Medical SciencesArabian Gulf UniversityManamaKingdom of Bahrain Salmaniya Medical Complex ManamaKingdom of Bahrain department of Laboratory medicine Salmaniya Medical ComplexManamaKingdom of Bahrain department of Microbiology Immunologyand Infectious DiseasesCollege of Medicine and Medical SciencesArabian Gulf UniversityManamaKingdom of Bahrain

Renal transplant patients receive several immunosuppressive drug regimens that are potentially nephrotoxic for *** creatinine is the standard for monitoring kidney function;however,cystatin C(Cys C)and kidney injury molecule-1(KIM-1)have been found to indicate kidney injury earlier than serum creatinine and provide a better reflection of kidney ***,we assessed Cys C and KIM-1 serum levels in renal transplant patients receiving mycophenolate mofetil,tacrolimus,sirolimus,everolimus,or cyclosporine to evaluate kidney *** used both the Chronic Kidney Disease Epidemiology Collaboration(CKD-EPI)2021 equation,which is based on creatinine and combined creatinine with Cys C,and the CKD-EPI 2012 equation,which is based on Cys C alone,to estimate glomerular filtration rate(GFR).Then,we assessed the association between serum KIM-1 and GFR<90 mL per minute per 1.73 *** observed significantly higher serum Cys C levels in patients with the elevated serum creatinine,compared with those with normal serum *** estimated GFRs based on creatinine were significantly higher than those based on the other equations,while a significant positive correlation was observed among all *** KIM-1 levels were negatively correlated with the estimated GFRs by the CKD-EPI Cys C and the combined creatinine with Cys C equations.A serum KIM-1 level above 0.71 ng/mL is likely to indicate GFR<90 mL per minute per 1.73 *** observed a significant correlation between serum creatinine and Cys C in our renal transplant ***,serum KIM-1 may be used to monitor renal function when using potentially nephrotoxic drugs in renal transplants.

关键词： KIM-1 cystatin C mycophenolate mofetil tacrolimus everolimus sirolimus cyclosporine

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Hepatitis B virus infection, infertility, and assisted reproduction

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Journal of Zhejiang University-Science B(Biomedicine.& Biotechnology) 2024年第8期25卷 672-685页

作者： Lingjian ZHANG Fangfang ZHANG Zhiyuan MA Jie JIN department of infectious diseases Affiliated Hangzhou First People’s HospitalSchool of MedicineZhejiang UniversityHangzhou 310003China Women’s Hospital School of MedicineZhejiang UniversityHangzhou 310003China Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province Affiliated Hangzhou First People’s HospitalZhejiang University School of MedicineHangzhou 310003China

Background:Hepatitis B virus(HBV)is one of the most widespread viruses worldwide and a major cause of hepatitis,cirrhosis,and hepatocellular *** studies have revealed the impacts of HBV infection on *** increasing number of infertile couples with chronic hepatitis B(CHB)virus infection choose assisted reproductive technology(ART)to meet their fertility *** the high prevalence of HBV,the effects of HBV infection on assisted reproduction treatment remain limited and ***:The aim of this study was to provide a comprehensive overview of the effect of HBV infection on fertility and discuss its effects on pregnancy outcomes,vertical transmission,pregnancy complications,and viral activity during ART ***:We conducted a literature search in PubMed for studies on HBV infection and ART published from 1996 to ***:HBV infection negatively affected fertility in both males and *** research shows that HBV infection may increase the risk of pregnancy complications in couples undergoing assisted reproduction *** impact of HBV infection on the pregnancy outcomes of ART is still *** evidence does not support that ART increases the risk of vertical transmission of HBV,while relevant studies are *** the development of ART,the risk of HBV reactivation(HBVr)is increasing,especially due to the wide application of immunosuppressive ***:Regular HBV infection screening and HBVr risk stratification and management are essential to prevent HBVr during *** determination of optimal strategy and timing of prophylactic anti-HBV therapy during ART still needs further investigation.

关键词： Assisted reproductive technology(ART) Hepatitis B virus(HBV) Immunosuppressive agent Pregnancy

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Systemic lupus erythematosus in a 15-year-old female with multiple splenic nodules:A case report

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World Journal of Clinical Cases 2024年第12期12卷 2128-2133页

作者： Mi Il Kang Hyeok Chan Kwon division of Rheumatology Department of Internal MedicineDankook University College of MedicineCheonan-si 31116South Korea division of Rheumatology Department of Internal MedicineDankook University HospitalDankook University College of MedicineCheonan-si 31116South Korea

BACKGROUND Systemic lupus erythematosus(SLE)is a chronic inflammatory disease primarily affecting young *** can invade any organ,and various forms of splenic invasion have been *** include splenomegaly and splenic infarction,rupture,and *** study encountered a rare case of splenic involvement,with nodules of various sizes without calcifications or *** SUMMARY A 15-year-old girl presented with arthralgia,weight loss,fever,increased levels of inflammatory markers,and positive antinuclear antibody test *** patient was diagnosed with *** was asymptomatic while taking steroids and *** months after discharge,the patient developed a fever and abdominal *** enteritis was suspected,and abdominopelvic computed tomography(AP-CT)was *** were no specific findings in the gastrointestinal tract,but multiple splenic nodules were *** or hemangioma was considered;however,no specific radiological findings were observed.A biopsy of the spleen was performed to determine the possibility of *** histological findings of the spleen included extensive periarteriolar necrosis with hematoxylin bodies and numerous karyorrhectic *** on the biopsy results,the patient was diagnosed with an SLE flare-up and was maintained on high-dose steroids and *** As disease activity increased,multiple nodules in the spleen that were previously unseen were observed using AP-CT and histologically *** invasion by SLE can appear in multiple nodular forms and ***,physicians should consider these findings when differentiating these nodules from infections and malignancies.

关键词： Multiple nodules Spleen Splenectomy Systemic lupus erythematosus Differential diagnosis Case report

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