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Treatment of multisystem inflammatory syndrome in children

World Journal of Pediatrics 2024年第4期20卷 325-339页

作者： Tong Tong Yi-Hua Jin Min Wang Fang-Qi Gong Department of Cardiology Children's HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthNo.3333 Binsheng RoadHangzhou 310052China

Background Multisystem inflammatory syndrome in children(MIS-C),a relatively uncommon but severe pediatric complication,is associated with coronavirus disease 2019(COVID-19).A variety of treatment approaches,including intravenous immunoglobulins(IVIGs),glucocorticoids(GCs)and biologic agents,such as anakinra and infliximab,have been described for the management of COVID-19-related *** therapy is also ***,a well-developed treatment system has not been established,and many issues remain *** recently published articles related to the treatment of MIS-C have been ***,in this review,we identified relevant articles published recently and summarized the treatment of MIS-C more comprehensively and *** sources We reviewed the literature on the treatment of MIS-C through 20 September *** PubMed/Medline,Web of Science,EMBASE,and Cochrane Library databases were searched with the combination of the terms"multisystem inflammatory syndrome","MIS-C","PIMS-TS","therapy","treatment","drug","IVIG","GCs","intravenous immunoglobulin","corticosteroids","biological agent",and"aspirin".Results The severity of MIS-C varies,and different treatment schemes should be used according to the specific *** research and data collection are vital to better understand the pathophysiology and optimal management of *** MIS-Cis a disease involving multiple systems and has great *** the accumulation of additional experience,we have garnered fresh insights into its treatment ***,there remains a critical need for greater standardization in treatment protocols,alongside the pressing necessity for more robust and meticulously conducted studies to deepen our understanding of these protocols.

关键词： Coronavirus disease 2019-Corticosteroids Intravenous immunoglobulin Multisystem inflammatory syndrome in children-Treatment

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Mechanism Exploration of Euphorbia fischeriana Steud. for Liver Cancer Based on Aspartic Acid Identification in Metabolomics

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Chinese Journal of Integrative Medicine 2024年第6期30卷 507-514页

作者： ZHAO Jing TIAN Xin-chen ZHANG Jia-qi HUANG Chen SUN Yan QIAO Sen JIANG Shu-long clinical Medical Laboratory center Jining First People’s HospitalJiningShandong Province272000China Cheeloo College of Medicine Shandong UniversityJinan250000China

Objective:To investigate the anti-liver cancer effects and aspartic acid(Asp)-related action mechanism of Euphorbia fischeriana Steud.(LD).Methods:The mice model of liver cancer was established by injection of H22 *** 5 days,mice were randomly divided into model group,sorafenib group(20 mg/kg),LD high-dose(LDH,1.36 g/kg) group,LD medium-dose(LDM,0.68 g/kg) group,and LD low-dose(LDL,0.34 g/kg)group,10 mice each *** were intragastrically administered to the mice once daily for 10 days,*** weight,tumor size and tumor weight were *** index was *** changes of liver cancer tissues were evaluated by hematoxylin and eosin staining and TUNEL *** chromatography-mass spectrometer was used to analyze different metabolites between the model and LDH ***:After LD treatment,tumor weight,tumor size and hepatic index were reduced compared with the model *** and karyorrhexis of tumor cells were ***,61 differential metabolites(18 up-regulated,43 down-regulated) were affirmed and 20 pathways of KEGG(P<0.05) were *** addition,Bel-7402,HepG2 and H22 cell viabilities were significantly increased after adding Asp into the *** then,the cell proliferation effect induced by Asp was ameliorated by ***:The anti-liver cancer efficacy of LD extract was validated in H22 mice model,and inhibition of Asp level might be the underlying mechanism.

关键词： liver cancer Euphorbia fischeriana Steud. aspartic acid metabolomics

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Development of antibody-drug conjugates in cancer:Overview and prospects

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Cancer Communications 2024年第1期44卷 3-22页

作者： Dan-Yun Ruan Hao-Xiang Wu Qi Meng Rui-Hua Xu Department of clinical Research Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerSun Yat-sen UniversityGuangzhouGuangdongP.R.China Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer Chinese Academy of Medical SciencesGuangzhouGuangdongP.R.China Department of Medical Oncology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerSun Yat-sen UniversityGuangzhouGuangdongP.R.China

In recent years,remarkable breakthroughs have been reported on antibody-drug conjugates(ADCs),with 15 ADCs successfully entering the market over the past *** substantial development has positioned ADCs as one of the fastest-growing domains in the realm of anticancer drugs,demonstrating their efficacy in treating awide array of ***,there is still an unmet clin-ical need forwider application,better efficacy,and fewer side effects of *** ADC generally comprises an antibody,a linker and a payload,and the combina-tion has profound effects on drug structure,pharmacokinetic profile and ***,optimization of the key components provides an opportunity to develop ADCs with higher potency and fewer side *** this review,we comprehen-sively reviewed the current development and the prospects of ADC,provided an analysis of marketed ADCs and the ongoing pipelines globally as well as in China,highlighted several ADC platforms and technologies specific to different pharmaceutical enterprises and biotech companies,and also discussed the new related technologies,possibility of next-generation ADCs and the directions of clinical research.

关键词： companies breakthrough payload

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Di-and tri-methylation of histone H3K36 play distinct roles in DNA double-strand break repair

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Science China(Life Sciences) 2024年第6期67卷 1089-1105页

作者： Runfa Chen Meng-Jie Zhao Yu-Min Li Ao-Hui Liu Ru-Xin Wang Yu-Chao Mei Xuefeng Chen Hai-Ning Du Hubei Key Laboratory of Cell Homeostasis College of Life SciencesTaiKang Center for Life and Medical SciencesFrontier Science Center for Immunology and MetabolismHubei Clinical Research Center of Emergency and ResuscitationEmergency Center of Zhongnan HospitalWuhan UniversityWuhan 430072China Hubei Key Laboratory of Cell Homeostasis College of Life SciencesTaiKang Center for Life and Medical SciencesFrontier Science Center for Immunology and MetabolismWuhan UniversityWuhan 430072China

Histone H3 Lys36(H3K36)methylation and its associated modifiers are crucial for DNA double-strand break(DSB)repair,but the mechanism governing whether and how different H3K36 methylation forms impact repair pathways is ***,we unveil the distinct roles of H3K36 dimethylation(H3K36me2)and H3K36 trimethylation(H3K36me3)in DSB repair via non-homologous end joining(NHEJ)or homologous recombination(HR).Yeast cells lacking H3K36me2 or H3K36me3 exhibit reduced NHEJ or HR efficiency.y Ku70 and Rfa1 bind H3K36me2-or H3K36me3-modified peptides and chromatin,*** these interactions impairs y Ku70 and Rfa1 recruitment to damaged H3K36me2-or H3K36me3-rich loci,increasing DNA damage sensitivity and decreasing repair ***,H3K36me2-enriched intergenic regions and H3K36me3-enriched gene bodies independently recruit y Ku70 or Rfa1 under DSB ***,human KU70 and RPA1,the homologs of y Ku70 and Rfa1,exclusively associate with H3K36me2 and H3K36me3 in a conserved *** findings provide valuable insights into how H3K36me2 and H3K36me3 regulate distinct DSB repair pathways,highlighting H3K36 methylation as a critical element in the choice of DSB repair pathway.

关键词： histone H3K36 methylation Ku70 RPA non-homologous end joining homologous recombination

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Drug repurposing for cancer therapy

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1981-2013页

作者： Ying Xia Ming Sun Hai Huang Wei-Lin Jin center for clinical Laboratories The Affiliated Hospital of Guizhou Medical UniversityGuiyang 550004PR China The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine Guiyang 550001PR China School of clinical Laboratory Science Guizhou Medical UniversityGuiyang 550004PR China Division of Gastroenterology and Hepatology Department of Medicine andDepartment of OncologySidney Kimmel Comprehensive Cancer CenterJohns Hopkins University School of MedicineBaltimoreMD 21287USA Institute of Cancer Neuroscience Medical Frontier Innovation Research CenterThe First Hospital of Lanzhou UniversityThe First Clinical Medical College of Lanzhou UniversityLanzhou 730000PR China

Cancer,a complex and multifactorial disease,presents a significant challenge to global *** significant advances in surgical,radiotherapeutic and immunological approaches,which have improved cancer treatment outcomes,drug therapy continues to serve as a key therapeutic ***,the clinical efficacy of drug therapy is often constrained by drug resistance and severe toxic side effects,and thus there remains a critical need to develop novel cancer *** promising strategy that has received widespread attention in recent years is drug repurposing:the identification of new applications for existing,clinically approved *** repurposing possesses several inherent advantages in the context of cancer treatment since repurposed drugs are typically cost-effective,proven to be safe,and can significantly expedite the drug development process due to their already established safety *** light of this,the present review offers a comprehensive overview of the various methods employed in drug repurposing,specifically focusing on the repurposing of drugs to treat *** describe the antitumor properties of candidate drugs,and discuss in detail how they target both the hallmarks of cancer in tumor cells and the surrounding tumor *** addition,we examine the innovative strategy of integrating drug repurposing with nanotechnology to enhance topical drug *** also emphasize the critical role that repurposed drugs can play when used as part of a combination therapy *** conclude,we outline the challenges associated with repurposing drugs and consider the future prospects of these repurposed drugs transitioning into clinical application.

关键词： drugs integrating spite

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Comparison of clinical features and outcomes of proliferative,fibrotic,and mixed subtypes of IgG4-related disease:A retrospective cohort study

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Chinese Medical Journal 2024年第3期137卷 303-311页

作者： Linyi Peng Xinlu Zhang Jiaxin Zhou Jieqiong Li Zheng Liu Hui Lu Yu Peng Yunyun Fei Yan Zhao Xiaofeng Zeng Wen Zhang Department of Rheumatology and clinical Immunology Peking Union Medical College HospitalNational Clinical Research Center for Dermatologic and Immunologic DiseasesState Key Laboratory of Complex Severe and Rare DiseasesThe Ministry of Education Key LaboratoryBeijing 100730China Institute of clinical Medicine Peking Union Medical College Hospital(PUMCH)Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China

Background:Immunoglobulin G4-related disease(IgG4-RD)is a recently recognized immune-mediated disorder that can affect almost any organ in the human ***4-RD can be categorized into proliferative and fibrotic subtypes based on patients’clinicopathological *** study aimed to compare the clinical manifestations,laboratory findings,and treatment outcomes of IgG4-RD among different ***:We prospectively enrolled 622 patients with newly diagnosed IgG4-RD at Peking Union Medical College Hospital from March 2011 to August *** patients were divided into three groups according to their clinicopathological characteristics:proliferative,fibrotic,and mixed *** compared demographic features,clinical manifestations,organ involvement,laboratory tests,and treatment agents across three *** then assessed the differences in treatment outcomes among 448 patients receiving glucocorticoids alone or in combination with ***,risk factors of relapse were revealed by applying the univariate and multivariate Cox regression ***:We classified the 622 patients into three groups consisting of 470 proliferative patients,55 fibrotic patients,and 97 mixed patients,*** found that gender distribution,age,disease duration,and frequency of allergy history were significantly different among *** terms of organ involvement,submandibular and lacrimal glands were frequently involved in the proliferative subtype,while retroperitoneum was the most commonly involved site in both fibrotic subtype and mixed *** comparison of laboratory tests revealed that eosinophils(P=0.010),total IgE(P=0.006),high-sensitivity C-reactive protein(P<0.001),erythrocyte sedimentation rate(P<0.001),complement C4(P<0.001),IgG(P=0.001),IgG1(P<0.001),IgG4(P<0.001),and IgA(P<0.001),at baseline were significantly different among three *** with proliferative and mixed subtypes,the fibrotic subtype showed the

关键词： IgG4-related disease Proliferative subtype Fibrotic subtype clinical features Treatment outcome

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GRK2 inhibits Flt-1^(+)macrophage infiltration and its proangiogenic properties in rheumatoid arthritis

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Acta Pharmaceutica Sinica B 2024年第1期14卷 241-255页

作者： Xuezhi Yang Yingjie Zhao Qi Wei Xuemin Zhu Luping Wang Wankang Zhang Xiaoyi Liu Jiajie Kuai Fengling Wang Wei Wei Institute of clinical Pharmacology Anhui Medical UniversityKey Laboratory of Anti-Inflammatory and Immune MedicineAnhui Collaborative Innovation Center of Anti-Inflammatory and Immune MedicineMinistry of EducationHefei 230032China Department of clinical Pharmacology the Second Affiliated Hospital of Anhui Medical UniversityHefei 230601China

Rheumatoid arthritis(RA)is an autoimmune disease with a complex ***-derived macrophages(MDMs)infiltration are associated with RA *** have reported the deletion of G-protein-coupled receptor kinase 2(GRK2)reprograms macrophages toward an anti-inflammatory phenotype by recovering G-protein-coupled receptor ***,as more GRK2-interacting proteins were discovered,the GRK2 interactome mechanisms in RA have been ***,in the collagen-induced arthritis mouse model,we performed genetic GRK2 deletion using GRK2^(f/f)Lyz2-Cre^(+/−)*** inflammation and M1 polarization were improved in GRK2^(f/f)Lyz2-Cre^(+/−)*** experiments with RNA-seq and dual-luciferase reporter assays identified peroxisome proliferator-activated receptorγ(PPARγ)as a new GRK2-interacting *** further confirmed that fms-related tyrosine kinase 1(Flt-1),which promoted macrophage migration to induce angiogenesis,was inhibited by GRK2-PPARγ***,excess GRK2 membrane recruitment in CIA MDMs reduced the activation of PPARγligand-binding domain and enhanced Flt-1 ***,the treatment of mice with GRK2 activity inhibitor resulted in significantly diminished CIA pathology,Flt-1^(+)macrophages induced-synovial inflammation,and ***,we anticipate to facilitate the elucidation of previously unappreciated details of GRK2-specific intracellular *** GRK2 activity is a viable strategy to inhibit MDMs infiltration,affording a distinct way to control joint inflammation and angiogenesis of RA.

关键词： GRK2 Monocyte-derived macrophages Rheumatoid arthritis PPARg Flt-1

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Genomic medicine in clinical practice:national genomic medicine program in Japan

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Cancer Biology & Medicine 2024年第1期21卷 4-9页

作者： Teruhiko Yoshida Yasushi Yatabe Ken Kato Genichiro Ishii Akinobu Hamada Hiroyuki Mano Kuniko Sunami Noboru Yamamoto Takashi Kohno Department of Genetic Medicine and Services National Cancer Center HospitalTokyo 104-0045Japan Department of Diagnostic Pathology National Cancer Center HospitalTokyo 104-0045Japan clinical Research Support Offce Clinical Research Coordinating SectionBiobank Translational Research Support SectionNational Cancer Center HospitalTokyo 104-0045Japan Department of Pathology and clinical Laboratories National Cancer Center Hospital EastChiba 277-8577Japan Division of Molecular Pharmacology National Cancer Center Research InstituteTokyo 104-0045Japan National Cancer center Research Institute Tokyo 104-0045Japan Department of Laboratory Medicine National Cancer Center HospitalTokyo 104-0045Japan Department of Experimental Therapeutics National Cancer Center HospitalTokyo 104-0045Japan Division of Genome Biology National Cancer Center Research InstituteTokyo 104-0045Japan

Cancer statistics in Japan Cancer is the most common cause of death in Japan based on Statistics 2021~*** statistics were first gathered,infectious diseases,such as tuberculosis,and cerebrovascular disease have been the main causes of death in *** surpassed cerebrovascular disease as the main cause of death in 1981,and the number of cancer deaths has *** 38,000 people died of cancer in *** National Cancer center(NCC)reported that the 5-year survival rate for patients with cancer was improving(62%for males and 66.9%for females)in a population-based cancer registry.

关键词： Cancer cancer death

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PCK1 attenuates tumor stemness via activating the Hippo signaling pathway in hepatocellular carcinoma

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Genes & Diseases 2024年第4期11卷 340-352页

作者： Rui Liu Yi Liu Wenlu Zhang Guiji Zhang Zhirong Zhang Luyi Huang Ni Tang Kai Wang Key Laboratory of Molecular Biology for Infectious Diseases(Ministry of Education) Institute for Viral HepatitisDepartment of Infectious DiseasesThe Second Affiliated HospitalChongqing Medical UniversityChongqing 400016China Department of clinical Laboratory Sichuan Clinical Research Center for CancerSichuan Cancer Hospital&InstituteSichuan Cancer CenterAffiliated Cancer Hospital of University of Electronic Science and Technology of ChinaChengduSichuan 610041China

Liver cancer stem cells were found to rely on glycolysis as the preferred metabolic *** carboxylase 1(PCK1),a gluconeogenic metabolic enzyme,is down-regulated in hepatocellular carcinoma and is closely related to poor *** onco-genesis and progression of tumors are closely related to cancer stem *** is not completely clear whether the PCK1 deficiency increases the stemness of hepatoma cells and promotes the oncogenesis of hepatocellular ***,the results showed that PCK1 inhibited the self-renewal property of hepatoma cells,reduced the mRNA level of cancer stem cell markers,and inhibited ***,PCK1 increased the sensitivity of hepatocellular carci-noma cells to ***,we found that PCK1 activated the Hippo pathway by enhancing the phosphorylation of YAP and inhibiting its nuclear *** reduced the stemness of hepatoma cells and promoted the pro-apoptotic effect of ***,combined treatment with verteporfin and sorafenib may be a potential anti-tumor strat-egy in hepatocellular carcinoma.

关键词： Cancer stem cells Chemoresistance Gluconeogenesis Hepatocellular carcinoma YAP

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Immunomodulation of adipose-derived mesenchymal stem cells on peripheral blood mononuclear cells in colorectal cancer patients with COVID-19

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2113-2122页

作者： Jun-Feng Wang Xiao-Xia Yang Jian Zhang Yan Zheng Fu-Qing Zhang Xiao-Feng Shi Yu-Liang Wang Department of Colorectal Oncology Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerTianjin’s Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjin 300060China Department of Neurology Tianjin First Center HospitalTianjin 300192China Prosthodontics Studio Tianjin Stomatological HospitalTianjin 300041China Department of clinical Laboratory Medicine Tianjin Institute of UrologyThe Second Hospital of Tianjin Medical UniversityTianjin 300211China Department of Emergency Tianjin First Central HospitalTianjin 300192China

BACKGROUND Accumulating evidence has shown that adipose tissue-derived mesenchymal stem cells(ADSCs)are an effective therapeutic approach for managing coronavirus disease 2019(COVID-19);however,further elucidation is required to determine their underlying immunomodulatory effect on the mRNA expression of T helper cell-related transcription factors(TFs)and cytokine release in peripheral blood mononuclear cells(PBMCs).AIM To investigate the impact of ADSCs on the mRNA expression of TFs and cytokine release in PBMCs from colorectal cancer(CRC)patients with severe COVID-19(CRC^(+)patients).METHODS PBMCs from CRC^(+)patients(PBMCs-C+)and age-matched CRC patients(PBMCs-C)were stimulated and cultured in the presence/absence of *** mRNA levels of T-box TF TBX21(T-bet),GATA binding protein 3(GATA-3),RAR-related orphan receptor C(RORC),and forkhead box P3(FoxP3)in the PBMCs were determined by reverse transcriptase-polymerase chain *** supernatants were evaluated for levels of interferon gamma(IFN-γ),interleukin 4(IL-4),IL-17A,and transforming growth factor beta 1(TGF-β1)using an enzyme-linked immunosorbent *** Compared with PBMCs-C,PBMCs-C+exhibited higher mRNA levels of T-bet and RORC,and increased levels of IFN-γ and ***,a significant decrease in FoxP3 mRNA and TGF-β1,as well as an increase in Tbet/GATA-3,RORC/FoxP3,IFN-γ/IL-4,and IL-17A/TGF-β1 ratios were observed in PBMCs-C+.Furthermore,ADSCs significantly induced a functional regulatory T cell(Treg)subset,as evidenced by an increase in FoxP3 mRNA and TGF-β1 release *** was accompanied by a significant decrease in the mRNA levels of T-bet and RORC,release of IFN-γ and IL-17A,and T-bet/GATA-3,RORC/FoxP3,IFN-γ/IL-4,and IL-17A/TGF-β1 ratios,compared with the PBMCs-C+*** The present in vitro studies showed that ADSCs contributed to the immunosuppressive effects on PBMCs-C+,favoring Treg ***,ADSC-based cell therapy could be a beneficial approach for p

关键词： Colorectal cancer COVID-19 Adipose-derived mesenchymal stem cells T helper cell Immunomodulation

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