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Azacitidine maintenance therapy for blastic plasmacytoid dendritic cell neoplasm allograft: A case report

World Journal of clinical Cases 2024年第1期12卷 136-141页

作者： Li-Li Tao Hui-Ting Wen Zi-Yi Wang Juan Cheng Li Zhao department of Hematology The First Clinical Medical CollegeLanzhou UniversityLanzhou 730000Gansu ProvinceChina department of Hematology The First Hospital of Lanzhou UniversityLanzhou 730000Gansu ProvinceChina

BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare,highly invasive malignant *** is no universally accepted standard of care because of its rarity and the dearth of prospective *** is still challenging for some patients to achieve persistent clinical remission or cure,despite the success of allogeneic hematopoietic stem cell transplantation(allo-HSCT),indicating that there is still a significant recurrence *** report a case of prevention of BPDCN allograft recurrence by azacitidine maintenance therapy and review the relevant *** SUMMARY We report a 41-year-old man with BPDCN who was admitted to hospital due to skin sclerosis for>5 mo’*** was diagnosed by combined clinical assessment and laboratory *** diagnosis,the patients underwent induction consolidation chemotherapy to achieve the first complete remission,followed by bridging ***-transplantation,azacitidine(75 mg/m2 for 7 d)was administered as maintenance therapy,with repeat administration every 4–6 wk and appropriate extension of the chemotherapy *** 10 cycles,the patient has been disease free for 26 mo after *** assessments of bone marrow morphology,minimal residual disease,full donor chimerism,Epstein–Barr virus,and cytomegalovirus all yielded normal results with no abnormalities *** Azacitidine may be a safe and effective maintenance treatment for BPDCN following transplantation because there were no overt adverse events during the course of treatment.

关键词： Blastic plasmacytoid dendritic cell neoplasm Azacitidine Allogeneic hematopoietic stem cell transplantation Maintenance therapy Case report

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Nonalcoholic Fatty Liver Disease:Changes in Gut Microbiota and Blood Lipids

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Journal of clinical and Translational Hepatology 2024年第4期12卷 333-345页

作者： Keen Yang Jieying Zeng Huaiyu Wu Huiyu Liu Zhimin Ding Weiyu Liang Linghu Wu Ziwei Lin Wenhui Huang Jinfeng Xu Fajin Dong department of Ultrasound Shenzhen People’s Hospital(The Second Clinical Medical CollegeJinan UniversityThe First Affiliated HospitalSouthern University of Science and Technology)ShenzhenGuangdongChina

Background and Aims:The global prevalence of nonalcoholic fatty liver disease(NAFLD)is 25%.This study aimed to explore differences in the gut microbial community and blood lipids between normal livers and those affected by NAFLD using 16S ribosomal deoxyribonucleic acid ***:Gut microbiome profiles of 40 NAFLD and 20 non-NAFLD controls were *** about four blood lipids and 13 other clinical features was *** were divided into three groups by ultrasound and FibroScan,those with a normal liver,mild FL(FL1),and moderate-to-severe FL(FL2).FL1 and FL2 patients were divided into two groups,those with either hyperlipidemia or non-hyperlipidemia based on their blood *** keystone species within the groups were identified using univariate analysis and a specificity–occupancy *** difference in biochemical parameters ion NAFLD patients and healthy individuals were identified by detrended correspondence analysis and canonical correspondence ***:Decreased gut bacterial diversity was found in patients with ***/Bacteroidetes decreased as NAFLD *** and Ruminococcus 2 were the most representative fatty-related *** pyruvic transaminase,aspartate aminotransferase,and white blood cell count were selected as the most significant biochemical *** of areas under the curve identified two microbiomes combined with the three biochemical indexes that identified normal liver and FL2 very well but performed poorly in diagnosing ***:Faecalibacterium and Ruminococcus 2,combined with glutamate pyruvic transaminase,aspartate aminotransferase,and white blood cell count distinguished *** speculate that regulating the health of gut microbiota may release NAFLD,in addition to providing new targets for clinicians to treat NAFLD.

关键词： Liver Gut microbiota Blood lipids Nonalcoholic fatty liver disease Hyperlipidemia

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Mitochondrial Regulation of Macrophages in Innate Immunity and Diverse Roles of Macrophages During Cochlear Inflammation

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Neuroscience Bulletin 2024年第2期40卷 255-267页

作者： Yuan Zhang Fanglei Ye Xiaolong Fu Shen Li Le Wang Yutian Chen Hongmin Li Shaojuan Hao Kun Zhao Qi Feng Peipei Li department of Otology The First Afliated Hospital of Zhengzhou UniversityZhengzhou 450052China Shandong Provincial hospital Shandong First Medical UniversityJinan 250000China department of Neurology The First Afliated Hospital of Zhengzhou UniversityZhengzhou 450052China The department of Endovascular Surgery The First Afliated Hospital of Zhengzhou UniversityZhengzhou 450052China department of Integrated Traditional and Western Nephrology The First Afliated Hospital of Zhengzhou UniversityZhengzhou 450052China Henan Province Research Center of Kidney Disease Zhengzhou 450052China

Macrophages are essential components of the innate immune system and constitute a non-specific first line of host defense against pathogens and *** regulate macrophage activation and innate immune responses in various inflammatory diseases,including cochlear *** distribution,number,and morphological characteristics of cochlear macrophages change significantly across different inner ear regions under various pathological conditions,including noise exposure,ototoxicity,and age-related ***,the exact mechanism underlying the role of mitochondria in macrophages in auditory function remains ***,we summarize the major factors and mitochondrial signaling pathways(e.g.,metabolism,mitochondrial reactive oxygen species,mitochondrial DNA,and the inflammasome)that influence macrophage activation in the innate immune *** particular,we focus on the properties of cochlear macrophages,activated signaling pathways,and the secretion of inflammatory cytokines after acoustic *** hope this review will provide new perspectives and a basis for future research on cochlear inflammation.

关键词： Macrophage Mitochondria Innate immunity Cochlea Infammation

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Lymph node-biomimetic scaffold boosts CAR-T therapy against solid tumor

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National Science Review 2024年第4期11卷 206-215页

作者： Ziyan Liao Jie Jiang Wei Wu Jiaqi Shi Yanfang Wang Yuejun Yao Tao Sheng Feng Liu Wei Liu Peng Zhao Feifei Lv Jie Sun Hongjun Li Zhen Gu National Key laboratory of Advanced Drug Delivery and Release Systems College of Pharmaceutical Sciences Zhejiang University Key laboratory of Advanced Drug Delivery Systems of Zhejiang Province College of Pharmaceutical SciencesZhejiang University Liangzhu laboratory Zhejiang University Bone Marrow Transplantation Center of the first Affiliated hospital and department of Cell Biology Zhejiang University School of Medicine department of Medical Oncology The First Affiliated Hospital School of Medicine Zhejiang University department of laboratory Medicine The First Affiliated Hospital Zhejiang University School of Medicine department of Hepatobiliary and Pancreatic Surgery The Second Affiliated HospitalSchool of MedicineZhejiang University Jinhua Institute of Zhejiang University MOE Key laboratory of Macromolecular Synthesis and Functionalization of Ministry of Education Department of Polymer Science and EngineeringZhejiang University department of General Surgery Sir Run Run Shaw Hospital School of Medicine Zhejiang University

The limited infiltration and persistence of chimeric antigen receptor(CAR)-T cells is primarily responsible for their treatment deficits in solid tumors. Here, we present a three-dimensional scaffold, inspired by the physiological process of T-cell proliferation in lymph nodes. This scaffold gathers the function of loading,delivery, activation and expansion for CAR-T cells to enhance their therapeutic effects on solid tumors. This porous device is made from poly(lactic-co-glycolic acid) by a microfluidic technique with the modification of T-cell stimulatory signals, including anti-CD3, anti-CD28 antibodies, as well as cytokines. This scaffold fosters a 50-fold CAR-T cell expansion in vitro and a 15-fold cell expansion in vivo. Particularly, it maintains long-lasting expansion of CAR-T cells for up to 30 days in a cervical tumor model and significantly inhibits the tumor growth. This biomimetic delivery strategy provides a versatile platform of cell delivery and activation for CAR-T cells in treating solid tumors.

关键词： drug delivery cell therapy bioinspired biomaterials cancer immunotherapy

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UniBind:a novel artificial intelligence-based prediction model for SARS-CoV-2 infectivity and variant evolution

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Signal Transduction and Targeted Therapy 2024年第1期9卷 14-15页

作者： Qihong Yan Jincun Zhao State Key laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory Healththe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina

In a recent study published in Nature Medicine,Wang et *** an excellent framework called UniBind based on artificial intelligence(AI),which enables accurately predicting infectivity of SARS-CoV-2 variants and evolutionary trends of future viral variants.1 This computational method holds the possibility to not only serve as a valuable early-warning tool for monitoring potential pathogenic SARS-CoV-2 variants but also facilitate fundamental research on protein-protein interactions(PPIs).

关键词： artificial Bind prediction

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ROR2 promotes invasion and chemoresistance of triple-negative breast cancer cells by activating PI3K/AKT/mTOR signaling

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Oncology Research 2024年第7期32卷 1209-1219页

作者： XIA DA HAN GE JUNFENG SHI CHUNHUA ZHU GUOZHU WANG YUAN FANG JIN XU department of Breast and Thyroid Nanjing First HospitalNanjing Medical UniversityNanjingChina department of General Surgery The First Affiliated Hospital of Nanjing Medical UniversityNanjingChina department of Oncology Nanjing First HospitalNanjing Medical UniversityNanjingChina department of Pathology Nanjing First HospitalNanjing Medical UniversityNanjingChina

Objective:This study aimed to investigate the role of receptor tyrosine kinase-like orphan receptor 2(ROR2)in triple-negative breast cancer(TNBC).Methods:ROR2 expression in primary TNBC and metastatic TNBC tissues was analyzed by immunohistochemical staining and ***2 expression in TNBC cell lines was detected by PCR and Western blot *** migration,invasion and chemosensitivity of TNBC cells with overexpression or knockdown of ROR2 were ***:ROR2 expression was high in metastatic TNBC ***2 knockdown suppressed the migration,invasion and chemoresistance of TNBC ***2 overexpression in MDA-MB-435 cells promoted the migration,invasion,and ***,ROR2 knockdown in HC1599 and MDA-MB-435 adriamycin-resistant cells enhanced chemosensitivity to ***2 could activate PI3K/AKT/mTOR signaling in TNBC ***:ROR2 is upregulated and promotes metastatic phenotypes of TNBC by activating PI3K/AKT/mTOR signaling.

关键词： Receptor tyrosine kinase-like orphan receptor 2 Triplet-negative breast cancer Proliferation Apoptosis PI3K/AKT/mTOR signaling Metastasis

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Recent advances to address challenges in extracellular vesicle-based applications for lung cancer

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Acta Pharmaceutica Sinica B 2024年第9期14卷 3855-3875页

作者： Gaigai Huang Wenshu Zheng Yu Zhou Meihua Wan Tony Hu department of clinical laboratory the First People’s Hospital of Shuangliu District(West China Airport Hospital of Sichuan University)Chengdu 610200China Center for Cellular and Molecular Diagnostics Tulane University School of MedicineNew OrleansLA 70112USA department of Integrated Traditional Chinese and Western Medicine West China Hospital of Sichuan UniversityChengdu 610200China The first People’s hospital of Shuangliu District(West China Airport hospital of Sichuan University) Chengdu 610200China

Lung cancer,highly prevalent and the leading cause of cancer-related death globally,persists as a significant challenge due to the lack of definitive tumor markers for early diagnosis and personalized therapeutic ***,extracellular vesicles(EVs),functioning as natural carriers for intercellular communication,have received increasing attention due to their ability to traverse biological barriers and deliver diverse biological cargoes,including cytosolic proteins,cell surface proteins,microRNA,lncRNA,circRNA,DNA,and *** are increasingly recognized as a valuable resource for non-invasive liquid biopsy,as well as drug delivery platforms,and anticancer vaccines for precision medicine in lung ***,given the diagnostic and therapeutic potential of tumor-associated EVs for lung cancer,we discuss this topic from a translational *** delve into the specific roles that EVs play in lung cancer carcinogenesis and offer a particular perspective on how advanced engineering technologies can overcome the current challenges and expedite and/or enhance the translation of EVs from laboratory research to clinical settings.

关键词： Lung cancer Extracellular vesicles Therapy resistance Delivery Diagnostics Therapeutics Nanotechnology Engineering

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Black phosphorus quantum dots induce myocardial inflammatory responses and metabolic disorders in mice

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Journal of Environmental Sciences 2024年第3期137卷 53-64页

作者： Chao Shen Xiaoyan Ding Jinpeng Ruan Fengkai Ruan Weiping Hu Jiyi Huang Chengyong He Yi Yu Zhenghong Zuo department of Nephrology State Key Laboratory of Cellular Stress BiologySchool of Life SciencesFaculty of Medicine and Life SciencesFujian Clinical Research Center for Chronic Glomerular DiseaseThe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen 361102China

As an ultrasmall derivative of black phosphorus(BP)sheets,BP quantum dots(BP-QDs)have been effectively used in many ***,information on the cardiotoxicity induced by BP-QDs remains *** aimed to evaluate BP-QD-induced cardiac toxicity in *** examination of heart tissue sections was *** sequencing,real-time quantitative PCR(RT–qPCR),western blotting,and enzyme-linked immunosorbent assay(ELISA)assays were used to detect the m RNA and/or protein expression of proinfammatory cytokines,nuclear factor kappa B(NF-κB),phosphatidylinositol3 kinase-protein kinase B(PI3K-AKT),peroxisome proliferator-activated receptor gamma(PPARγ),and glucose/lipid metabolism pathway-related *** found that heart weight and heart/body weight index(HBI)were significantly reduced in mice after intragastric administration of 0.1 or 1 mg/kg BP-QDs for 28 *** addition,obvious infammatory cell infiltration and increased cardiomyocyte diameter were observed in the BP-QD-treated *** expression of proinfammatory cytokines and genes related to the NF-κB signaling pathway further confirmed that BP-QD exposure induced infammatory *** addition,BP-QD treatment also affected the PI3K-AKT,PPARγ,thermogenesis,oxidative phosphorylation,and cardiac muscle contraction signaling *** expression of genes related to glucose/lipid metabolism signaling pathways was dramatically affected by BP-QD exposure,and the effect was primarily mediated by the PPAR signaling *** study provides new insights into the toxicity of BP-QDs to human health.

关键词： BP-QDs Cardiac toxicity Infammatory responses NF-κB signaling pathway PPARγsignaling pathway Glucose/lipid metabolism

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Single-cell transcriptomic analysis reveals transcript enrichment in oxidative phosphorylation,fluid sheer stress,and inflammatory pathways in obesity-related glomerulopathy

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Genes & Diseases 2024年第4期11卷 314-326页

作者： Yinyin Chen Yushun Gong Jia Zou Guoli Li Fan Zhang Yiya Yang Yumei Liang Wenni Dai Liyu He Hengcheng Lu department of Nephrology Hunan Provincial People's HospitalThe First Affliated Hospital of Hunan Normal UniversityHunan Clinical Research Center for Chronic Kidney DiseaseChangshaHunan 410000China department of Nephrology The Second Xiangya Hospital of Central South UniversityHunan Key Laboratory of Kidney Disease and Blood PurificationChangshaHunan 410011China Cardiovascular Research Institute of Jiangxi Province Jiangxi Provincial People's HospitalThe First Affiliated Hospital of Nanchang Medical CollegeNanchangJiangxi 330006China

Obesity-related glomerulopathy(ORG)is an independent risk factor for chronic kid-ney disease and even progression to end-stage renal *** have been undertaken to elucidate the mechanisms underlying the development of ORG and substantial advances have been made in the treatment of ORG,but relatively little is known about cell-specific changes in gene *** define the transcriptomic landscape at single-cell resolution,we analyzed kidney samples from four patients with ORG and three obese control subjects without kidney disease using single-cell RNA *** report for the first time that immune cells,including T cells and B cells,are decreased in ORG *** analysis indicated that SPP1 was significantly up-regulated in T cells and B *** gene is related to inflammation and cell *** of differential gene expression in glomerular cells(endothelial cells,mesangial cells,and podocytes)showed that these cell types were mainly enriched in genes related to oxidative phosphorylation,cell adhesion,thermogenesis,and inflammatory pathways(PI3K-Akt signaling,MAPK signaling).Furthermore,we found that the podocytes of ORG patients were enriched in genes related to the fluid shear stress ***,an evaluation of cell-cell communications revealed that there were interactions between glomerular parietal epithelial cells and other cells in ORG patients,with major interactions between parietal epithelial cells and ***,our identification of molecular events,cell types,and differentially expressed genes may facilitate the development of new preventive or therapeutic approaches for ORG.

关键词： Fluid shear stress Inflammation Obesity-related glomerulopathy Oxidative phosphorylation Single-cell RNA seq

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The activity and immune dynamics of PD-1 inhibition on high-risk pulmonary ground glass opacity lesions:insights from a single-arm,phase II trial

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2202-2214页

作者： Bo Cheng Caichen Li Jianfu Li Longlong Gong Peng Liang Ying Chen Shuting Zhan Shan Xiong Ran Zhong Hengrui Liang Yi Feng Runchen Wang Haixuan Wang Hongbo Zheng Jun Liu Chengzhi Zhou Wenlong Shao Yuan Qiu Jiancong Sun Zhanhong Xie Zhu Liang Chenglin Yang Xiuyu Cai Chunxia Su Wei Wang Jianxing He Wenhua Liang department of Thoracic Surgery and Oncology the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Institute of Respiratory HealthState Key Laboratory of Respiratory DiseaseNational Clinical Research Center for Respiratory DiseaseGuangzhouChina Medical department Genecast Biotechnology Co.LtdWuxiChina department of Radiation Oncology the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina department of Respiratory Medicine the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Institute of Respiratory HealthState Key Laboratory of Respiratory DiseaseNational Clinical Research Center for Respiratory DiseaseGuangzhouChina department of Cardiothoracic Surgery Affiliated Hospital of Guangdong Medical UniversityZhanjiangChina department of Thoracic Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhenChina department of VIP Inpatient Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaSun Yat-sen UniversityGuangzhouChina department of Medical Oncology Shanghai Pulmonary HospitalSchool of MedicineTongji UniversityShanghaiChina

Immune checkpoint inhibitors targeting the programmed cell death-1(PD-1)protein significantly improve survival in patients with advanced non-small-cell lung cancer(NSCLC),but its impact on early-stage ground-glass opacity(GGO)lesions remains *** is a single-arm,phase II trial(NCT04026841)using Simon’s optimal two-stage design,of which 4 doses of sintilimab(200 mg per 3 weeks)were administrated in 36 enrolled multiple primary lung cancer(MPLC)patients with persistent high-risk(Lung-RADS category 4 or had progressed within 6 months)*** primary endpoint was objective response rate(ORR).T/B/NK-cell subpopulations,TCR-seq,cytokines,exosomal RNA,and multiplexed immunohistochemistry(mIHC)were monitored and compared between responders and ***,two intent-to-treat(ITT)lesions(pure-GGO or GGO-predominant)showed responses(ORR:5.6%,2/36),and no patients had progressive disease(PD).No grade 3-5 TRAEs *** total response rate considering two ITT lesions and three non-intent-to-treat(NITT)lesions(pure-solid or solid-predominant)was 13.9%(5/36).The proportion of CD8^(+)T cells,the ratio of CD8^(+)/CD4^(+),and the TCR clonality value were significantly higher in the peripheral blood of responders before treatment and decreased over ***,the mIHC analysis showed more CD8^(+)T cells infiltrated in ***,responders’cytokine concentrations of EGF and CTLA-4 increased during *** exosomal expression of fatty acid metabolism and oxidative phosphorylation gene signatures were down-regulated among ***,PD-1 inhibitor showed certain activity on high-risk pulmonary GGO lesions without safety *** effects were associated with specific T-cell re-distribution,EGF/CTLA-4 cytokine compensation,and regulation of metabolism pathways.

关键词： lesions metabolism doses

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