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Intelligent Information Management 2015年第3期7卷 93-106页

作者： Adriano Torri Oscar Tamburis Teresa Abbate Alessandro Pepino department of Electrical Engineering and Information Technologies University Federico II Naples Italy department of Veterinary medicine and Animal Productions University Federico II Naples Italy

The management systems currently used in the Italian healthcare sector provide fragmented and incomplete information on this system and are generally unlikely to give accurate information on the performances of the healthcare processes. The present paper introduces a combined discrete event simulation (DES)/business process management (BPM) approach as innovative means to study the workflow of the activities within the department of laboratory medicine of the “San Paolo” Hospital in Naples (Italy). After a first “As-Is” analysis to identify the current workflows of the system and to gather information regarding its behaviour, a following DES-based “What-If” analysis is implemented to figure out alternative work hypotheses in order to highlight possible modifications to the system’s response under varying operating conditions and improve its overall performances. The structure of the simulation program is explained and the results of the scenario analysis are discussed. The paper starts with a brief exploration of the use of DES in healthcare and ends with general observations on the subject.

关键词： Healthcare Management Performance Evaluation Discrete Event Simulation Business Process Management department of laboratory medicine

Potential role of tubulin glutamylation in neurodegenerative diseases

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Neural Regeneration Research 2024年第6期19卷 1191-1192页

作者： Abdullah Md.Sheikh Shatera Tabassum department of laboratory medicine Shimane University Faculty of MedicineShimaneJapan

The differentiation of neuronal stem cells into mature neurons is a complex process that involves both structural and functional *** cells undergo differentiation,there are notable functional changes,including the expression of various transcription factors,cytokines,and ***,structural changes occur as the cells develop various processes from the cell body and establish synaptic contacts with other cells.

关键词： diseases degenerative cytokines

The m^(6)A regulator KIAA1429 stabilizes RAB27B mRNA and promotes the progression of chronic myeloid leukemia and resistance to targeted therapy

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Genes & Diseases 2024年第2期11卷 993-1008页

作者： Fangyi Yao Fangmin Zhong Junyao Jiang Ying Cheng Shuai Xu Jing Liu Jin Lin Jing Zhang Shuqi Li Meiyong Li Yanmei Xu Bo Huang Xiaozhong Wang Jiangxi Province Key laboratory of laboratory medicine Jiangxi Provincial Clinical Research Center for Laboratory MedicineDepartment of Clinical LaboratoryThe Second Affiliated Hospital of Nanchang UniversityNanchangJiangxi 330006China

Chronic myeloid leukemia(CML)is a common adult *** the acute phase of the disease and the adverse effects of anti-cancer treatments can lead to a poor *** N6-methyladenine(m^(6)A)modification plays an important regulatory role in various physiological and pathological ***1429 is a known m^(6)A regulator,but the biological role of KIAA1429 in CML is *** this study,we observed that the m^(6)A levels and KIAA1429 expression were significantly up-regulated in patients with blast phase ***,KIAA1429 regulated the total level of RNA m^(6)A modification in the CML cells and promoted the malignant biological behaviors of CML cells,including proliferation,migration,and imatinib *** KIAA1429 in CML cells reduced the stability of RAB27B mRNA through the m^(6)A/YTHDF1 axis,consequently inhibiting CML proliferation and drug efflux,ultimately increasing the sensitivity of CML cells to ***,the knockdown of RAB27B also inhibited the proliferation and drug resistance of CML cells and promoted their ***,a recently developed anti-cancer agent,suppressed the expression of KIAA1429 and CML cell proliferation and promoted cell *** also inhibited the tumorigenesis of CML cells in *** combined use of rucaparib and imatinib enhanced the sensitivity of CML cells to *** study provides evidence that elevated KIAA1429 expression in the blast phase of CML enhances the stability of RAB27B mRNA through the m^(6)A/YTHDF1 axis to up-regulate RAB27B expression,thereby promoting CML *** exerts inhibitory effects on KIAA1429 expression and thus reduces CML progression.

关键词： Chronic myeloid leukemia KIAA1429 N6-methyladenine RAB27B Rucaparib YTHDF1

MiR-4465-modified mesenchymal stem cell-derived small extracellular vesicles inhibit liver fibrosis development via targeting LOXL2 expression

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第7期25卷 594-604页

作者： Yanjin WANG Yifei CHEN Fuji YANG Xiaolong YU Ying CHU Jing ZHOU Yongmin YAN Jianbo XI department of laboratory medicine Wujin Hospital Affiliated with Jiangsu UniversityJiangsu UniversityChangzhou 213017China department of laboratory medicine School of MedicineJiangsu UniversityZhenjiang 212013China Changzhou Key laboratory of Molecular Diagnostics and Precision Cancer medicine Wujin Clinical College of Xuzhou Medical UniversityChangzhou 213017China

Liver fibrosis is a significant health burden,marked by the consistent deposition of ***,the currently available treatment approaches for this condition are far from *** oxidase-like protein 2(LOXL2)secreted by hepatic stellate cells(HSCs)is a crucial player in the cross-linking of matrix collagen and is a significant target for treating liver *** stem cell-derived small extracellular vesicles(MSC-sEVs)have been proposed as a potential treatment option for chronic liver *** studies have found that MSC-sEV can be used for microRNA delivery into target cells or *** is currently unclear whether microRNA-4465(miR-4465)can target LOXL2 and inhibit HSC ***,it is uncertain whether MSC-sEV can be utilized as a gene therapy vector to carry miR-4465 and effectively inhibit the progression of liver *** study explored the effect of miR-4465-modified MSC-sEV(MSC-sEVmiR-4465)on LOXL2 expression and liver fibrosis *** results showed that miR-4465 can bind specifically to the promoter of the LOXL2 gene in ***,MSC-sEVmiR-4465 inhibited HSC activation and collagen expression by downregulating LOXL2 expression in ***-sEVmiR-4465 injection could reduce HSC activation and collagen deposition in the CCl4-induced mouse ***-sEVmiR-4465 mediating via LOXL2 also hindered the migration and invasion of HepG2 *** conclusion,we found that MSC-sEV can deliver miR-4465 into HSC to alleviate liver fibrosis via altering LOXL2,which might provide a promising therapeutic strategy for liver diseases.

关键词： Mesenchymal stem cell(MSC) Small extracellular vesicle(sEV) MicroRNA-4465(miR-4465) Hepatic stellate cell(HSC) Liver fibrosis

Circ_0004592:An auxiliary diagnostic biomarker for gastric cancer

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2757-2768页

作者： Shan Kong Yan-Hua Xu Ming Zheng Shao-Qing Ju Heng-Chuan Shi department of laboratory medicine Jiangsu Province Official HospitalNanjing 210000Jiangsu ProvinceChina department of laboratory medicine Northern Jiangsu People’s HospitalYangzhou 225000Jiangsu ProvinceChina department of laboratory medicine The Affiliated Hospital of Nantong UniversityNantong 226001Jiangsu ProvinceChina

BACKGROUND Gastric cancer(GC)has a high mortality rate,and robust diagnostic biomarkers are currently ***,the clinical relevance of circular RNAs(circRNAs)as GC biomarkers remains largely *** To evaluate the potential of novel circRNA circ_0004592 in the early screening and prognosis of *** High-throughput sequencing of circRNAs was performed to screen for potential target ***_0004592 expression was examined in GC tissues,cells,and *** samples were collected from healthy subjects’patients,as well as from patients with benign lesions,precancerous lesions,and GC,whereafter the diagnostic accuracy of circ_0004592 was *** correlation between circ_0004592 levels in plasma and clinicopathological data of patients with GC was further *** Circ_0004592 was upregulated in both the tissue and plasma of patients with ***,circ_0004592 expression was higher in patients with precancerous lesions than in healthy controls while being highest in patients with *** the same patient,the postoperative plasma level of circ_0004592 was lower than that in the preoperative ***,circ_0004592 level was significantly correlated with tumor differentiation,tumor depth,and lymph node *** area under the curve(AUC)of plasma circ_0004592 exhibited high sensitivity and specificity for differentiating patients with GC from healthy *** based on circ_0004592,carcinoembryonic antigen,and cancer antigen 199 achieved a superior AUC and was highly *** Plasma circ_0004592 may represent a potential non-invasive auxiliary diagnostic biomarker for patients with GC.

关键词： Biomarker Circular RNA Diagnosis Gastric cancer Plasma

Syrosingopine,an anti-hypertensive drug and lactate transporter(MCT1/4)inhibitor,activates hepatic stellate cells and exacerbates liver fibrosis in a mouse model

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Genes & Diseases 2024年第4期11卷 28-30页

作者： Meichun Guo Yannian Gou Xiangyu Dong Jiamin Zhong Aohua Li Ailing Hao Tongchuan He Jiaming Fan Ministry of Education Key laboratory of Diagnostic medicine and the School of Laboratory Diagnostic MedicineChongqing Medical UniversityChongqing 400016China Molecular Oncology laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA

Syrosingopine is an anti-hypertensive drug and can cause high intracellular lactate levels and end-product inhibition of lactate dehydrogenase by inhibiting the lactate transporters MCT1 and *** studies have shown that syrosingopine plays an essential role in the process of glycolytic blockade,ATP depletion,and cell death in cancer due to high intracellular levels of lactate.

关键词： hypertensive MCT1 drug

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

Clinical applications of metagenomics next-generation sequencing in infectious diseases

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第6期25卷 471-484页

作者： Ying LIU Yongjun MA department of Clinical laboratory Affiliated Jinhua HospitalZhejiang University School of MedicineJinhua 321000China

Infectious diseases are a great threat to human *** and accurate detection of pathogens is important in the diagnosis and treatment of infectious *** next-generation sequencing(mNGS)is an unbiased and comprehensive approach for detecting all RNA and DNA in a *** the development of sequencing and bioinformatics technologies,mNGS is moving from research to clinical application,which opens a new avenue for pathogen *** studies have revealed good potential for the clinical application of mNGS in infectious diseases,especially in difficult-to-detect,rare,and novel ***,there are several hurdles in the clinical application of mNGS,such as:(1)lack of universal workflow validation and quality assurance;(2)insensitivity to high-host background and low-biomass samples;and(3)lack of standardized instructions for mass data analysis and report ***,a complete understanding of this new technology will help promote the clinical application of mNGS to infectious *** review briefly introduces the history of next-generation sequencing,mainstream sequencing platforms,and mNGS workflow,and discusses the clinical applications of mNGS to infectious diseases and its advantages and disadvantages.

关键词： Metagenomics next-generation sequencing(mNGS) Infectious disease Cerebrospinal fluid(CSF) Oxford Nanopore Technologies(ONT) Microbiome

Extracellular vesicles(EVs)’journey in recipient cells:from recognition to cargo release

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第8期25卷 633-655页

作者： Huayuan XIANG Chenxuan BAO Qiaoqiao CHEN Qing GAO Nan WANG Qianqian GAO Lingxiang MAO department of laboratory medicine Affiliated Kunshan Hospital of Jiangsu UniversityKunshan 215300China

Extracellular vesicles(EVs)are nano-sized bilayer vesicles that are shed or secreted by virtually every cell type.A variety of biomolecules,including proteins,lipids,coding and non-coding RNAs,and mitochondrial DNA,can be selectively encapsulated into EVs and delivered to nearby and distant recipient cells,leading to alterations in the recipient cells,suggesting that EVs play an important role in intercellular *** play effective roles in physiology and pathology and could be used as diagnostic and therapeutic *** present,although the mechanisms of exosome biogenesis and secretion in donor cells are well understood,the molecular mechanism of EV recognition and uptake by recipient cells is still *** review summarizes the current understanding of the molecular mechanisms of EVs’biological journey in recipient cells,from recognition to uptake and cargo ***,we highlight how EVs escape endolysosomal degradation after uptake and thus release cargo,which is crucial for studies applying EVs as drug-targeted delivery *** of the cellular processes that govern EV uptake is important to shed light on the functions of EVs as well as on related clinical applications.

关键词： Extracellular vesicle(EV) Exosome Endocytosis Uptake Release

RNA modifications in cellular metabolism:implications for metabolism-targeted therapy and immunotherapy

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1565-1594页

作者： Wei-Wei Liu Si-Qing Zheng Tian Li Yun-Fei Fei Chen Wang Shuang Zhang Fei Wang Guan-Min Jiang Hao Wang department of laboratory medicine The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiChina School of Clinical medicine Shandong UniversityJinanChina Core Unit of National Clinical Research Center for laboratory medicine HefeiChina Neurosurgical department The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiChina department of Clinical laboratory The Fifth Affiliated HospitalSun Yat-sen UniversityZhuhaiChina

Cellular metabolism is an intricate network satisfying bioenergetic and biosynthesis requirements of *** studies have been constantly making inroads in our understanding of pathophysiology,and inspiring development of *** a crucial component of epigenetics at post-transcription level,RNA modification significantly determines RNA fates,further affecting various biological processes and cellular *** be noted,immunometabolism defines the metabolic alterations occur on immune cells in different stages and immunological *** this review,we characterize the distribution features,modifying mechanisms and biological functions of 8 RNA modifications,including N6-methyladenosine(m6A),N6,2'-O-dimethyladenosine(m6Am),N1-methyladenosine(m1A),5-methylcytosine(m5C),N4-acetylcytosine(ac4C),N7-methylguanosine(m7G),Pseudouridine(V),adenosine-to-inosine(A-to-l)editing,which are relatively the most studied *** regulatory roles of these RNA modification on metabolism in diverse health and disease contexts are comprehensively described,categorized as glucose,lipid,amino acid,and mitochondrial *** we highlight the regulation of RNA modifications on immunometabolism,further influencing immune *** all,we provide a thorough discussion about clinical implications of RNA modification in metabolism-targeted therapy and immunotherapy,progression of RNA modification-targeted agents,and its potential in RNAtargeted ***,we give legitimate perspectives for future researches in this field from methodological requirements,mechanistic insights,to therapeutic applications.

关键词： metabolism targeted alterations