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Pathological progression of osteoarthritis:a perspective on subchondral bone

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Frontiers of Medicine 2024年第2期18卷 237-257页

作者： Xuefei Li Wenhua Chen Dan Liu Pinghua Chen Shiyun Wang Fangfang Li Qian Chen Shunyi Lv Fangyu Li Chen Chen Suxia Guo Weina Yuan Pan Li Zhijun Hu Longhua hospital Affiliated to Shanghai University of Traditional Chinese Medicine Shanghai200032China research and development Center of Chinese Medicine Resources and Biotechnology Shanghai University of Traditional Chinese MedicineShanghai201203China

Osteoarthritis(OA)is a degenerative bone disease associated with *** rising global aging population has led to a surge in OA cases,thereby imposing a significant socioeconomic *** have been keenly investigating the mechanisms underlying *** studies have suggested that the disease starts with synovial inflammation and hyperplasia,advancing toward cartilage ***,subchondral-bone collapse,sclerosis,and osteophyte formation *** progression is deemed as“top to bottom.”However,recent research is challenging this perspective by indicating that initial changes occur in subchondral bone,precipitating cartilage *** this review,we elucidate the epidemiology of OA and present an in-depth overview of the subchondral bone’s physiological state,functions,and the varied pathological shifts during OA *** also introduce the role of multifunctional signal pathways(including osteoprotegerin(OPG)/receptor activator of nuclear factor-kappa B ligand(RANKL)/receptor activator of nuclear factor-kappa B(RANK),and chemokine(CXC motif)ligand 12(CXCL12)/CXC motif chemokine receptor 4(CXCR4))in the pathology of subchondral bone and their role in the“bottom-up”progression of *** vivid pattern maps and clinical images,this review highlights the crucial role of subchondral bone in driving OA progression,illuminating its interplay with the condition.

关键词： osteoarthritis subchondral bone OPG/RANKL/RANK CXCL12/CXCR4

Single-cell transcriptomics reveals the ameliorative effect of rosmarinic acid on diabetic nephropathy-induced kidney injury by modulating oxidative stress and inflammation

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1661-1676页

作者： Junhui Chen Qian Zhang Jinan Guo Di Gu Jing Liu Piao Luo Yunmeng Bai Jiayun Chen Xinzhou Zhang Sheng Nie Chunbo Chen Yulin Feng Jigang Wang National Pharmaceutical Engineering Center for Solid Preparation of Chinese Herbal Medicine Jiangxi University of Chinese MedicineNanchang 330006China Department of Pulmonary and Critical Care Medicine Shenzhen Institute of Respiratory Diseasesand Shenzhen Clinical Research Centre for GeriatricsShenzhen People's HospitalFirst Affiliated Hospital of Southern University of Science and TechnologySecond Clinical Medical College of Jinan UniversityShenzhen 518020China School of Traditional Chinese Medicine and School of Pharmaceutical Sciences Southern Medical UniversityGuangzhou 510515China Department of Urology and Shenzhen Clinical Research Centre for GeriatricsShenzhen People's Hospitalthe First Affiliated HospitalSouthern University of Science and TechnologyShenzhen 518020China Department of Urology the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510230China Department of Nephrology Shenzhen Key Laboratory of Kidney Diseasesand Shenzhen Clinical Research Centre for GeriatricsShenzhen People's Hospitalthe First Affiliated HospitalSouthern University of Science and TechnologyShenzhen 518020China Department of Nephrology Nanfang Hospitalthe First Affiliated Hospital of Southern Medical UniversityGuangzhou 510515China Department of Critical Care Medicine Shenzhen People's Hospital(the Second Clinical Medical CollegeJinan Universitythe First Affiliated HospitalSouthern University of Science and Technology)Shenzhen 518020China State Key Laboratory for Quality Esurance and Sustainable Use of Dao-di Herbs Artemisinin Research Centerand Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing 100700China Department of Oncology the Affiliated Hospital of Southwest Medical UniversityLuzhou 646000China

Diabetic nephropathy(DN)is a severe complication of diabetes,characterized by changes in kidney structure and *** natural product rosmarinic acid(RA)has demonstrated therapeutic effects,including anti-inflammation and anti-oxidative-stress,in renal damage or *** this study,we characterized the heterogeneity of the cellular response in kidneys to DN-induced injury and RA treatment at single cell *** results demonstrated that RA significantly alleviated renal tubular epithelial injury,particularly in the proximal tubular S1 segment and on glomerular epithelial cells known as podocytes,while attenuating the inflammatory response of macrophages,oxidative stress,and cytotox-icity of natural killer *** findings provide a comprehensive understanding of the mechanisms by which RA alleviates kidney damage,oxidative stress,and inflammation,offering valuable guidance for the clinical application of RA in the treatment of DN.

关键词： Rosmarinic acid Diabetic nephropathy scRNA sequencing Injury Oxidative stress Infiammation Proteomics

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

From Entry to Evasion:A Comprehensive Analysis of Host-Virus Interactions for Monkeypox

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Infectious Microbes & Diseases 2024年第2期6卷 56-64页

作者： Vahideh Hamidi Sofiani Mohammad Rezaei Zadeh Rukerd Javad Charostad Mohammad Pardeshenas Reza Ghazi Nasir Arefinia Sara Shafieipour Faranak Salajegheh Mohsen Nakhaie Department of Microbiology Golestan University of Medical SciencesGorganIran Gastroenterology and Hepatology research Center Institute of Basic and Clinical Physiology SciencesKerman University of Medical SciencesKermanIran Universal Scientific Education and research Network(USERN) TehranIran Department of Microbiology Faculty of MedicineShahid Sadoughi University of Medical SciencesYazdIran Department of Microbiology School of MedicineKerman University of Medical SciencesKermanIran Department of Biotechnology Golestan University of Medical SciencesGorganIran Student research Committee Jiroft University of Medical SciencesJiroftIran Physiology research Center Institute of NeuropharmacologyKerman University of Medical SciencesKermanIran clinical research development unit School of MedicineAfzalipour HospitalKerman University of Medical SciencesKermanIran

Monkeypox(Mpox)has posed a novel challenge and emerged as a threat to global public health since the onset of its outbreak in *** is spreading throughout the world in both endemic and non-endemic countries,indicating that its behavior is *** prevalence of Mpox and the risk of a global pandemic necessitate a better understanding of Mpox virus replications and interactions with the ***,we attempted to provide a detailed comprehensive review of Mpox virus behavior at the molecular level from the entry level to the establishment of a successful infection,including attachment and entry,DNA replication,protein expression and viron assembly and *** review also describes its strategies to evade host immune responses and inhibit apoptosis,and uncovers underlying molecular mechanisms such as subverted signaling pathways and cellular factors behind host-viral interactions.

关键词： monkeypox immunity apoptosis virus-host interaction

Role of mitochondrial dysfunction in kidney disease:Insights from the cGAS-STING signaling pathway

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Chinese Medical Journal 2024年第9期137卷 1044-1053页

作者： Lu Li Fei Liu Chunyue Feng Zhenjie Chen Nan Zhang Jianhua Mao Department of Nephrology Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhouZhejiang 310052China Department of Pediatric Intensive Care unit Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhouZhejiang 310052China

Over the past decade,mitochondrial dysfunction has been investigated as a key contributor to acute and chronic kidney ***,the precise molecular mechanisms linking mitochondrial damage to kidney disease remain *** recent insights into the cyclic guanosine monophosphate-adenosine monophosphate(GMP-AMP)synthetase(cGAS)-stimulator of interferon gene(STING)signaling pathway have revealed its involvement in many renal *** of these findings is that mitochondrial DNA(mtDNA)induces inflammatory responses via the cGAS-STING ***,we provide an overview of the mechanisms underlying mtDNA release following mitochondrial damage,focusing specifically on the association between mtDNA release-activated cGAS-STING signaling and the development of kidney ***,we summarize the latest findings of cGAS-STING signaling pathway in cell,with a particular emphasis on its downstream signaling related to kidney *** review intends to enhance our understanding of the intricate relationship among the cGAS-STING pathway,kidney diseases,and mitochondrial dysfunction.

关键词： Mitochondrial dysfunction Mitochondrial DNA cGAS-STING pathway Kidney diseases Chronic kidney disease

Macrocyclic trichothecenes from Myrothecium verrucaria PA 57 and their cytotoxic activity

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Chinese Journal of Natural Medicines 2024年第9期22卷 854-863页

作者： MO Jisong TAN Yufen AI Wenjing LI Yunyun YUAN Yiyun JIANG Yueping XU Kangping TAN Guishan WANG Wenxuan LI Jing LIU Shao Department of Pharmacy National Clinical Research Center for Geriatric DisordersXiangya HospitalCentral South UniversityChangsha 410008China Xiangya School of Pharmaceutical Sciences Central South UniversityChangsha 410008China

Four novel macrocyclic trichothecenes,termed mytoxins D-G(1-4),along with four known analogs(5-8),were isolated from the ethyl acetate extract of fermented rice inoculated with the fungus Myrothecium verrucaria *** compound features a tricyclic 12,13-epoxytrichothec-9-ene(EPT)***,mytoxin G(4)represents the first instance of a macrocyclic trichothecene incorporating a glucosyl unit within the trichothecene *** structures of the newly identified compounds were elucidated through comprehensive spectroscopic analysis combined with quantum chemical *** isolated compounds demonstrated cytotoxic activity against the CAL27 and HCT116 cell lines,which are models for human oral squamous cell carcinoma and colorectal cancer,***,mytoxin D(1)and mytoxin F(3)exhibited pronounced cytotoxic effects against both cancer cell lines,with IC_(50)values ranging from 3 to 6 nmol·L^(-1).Moreover,compounds 1 and 3 were found to induce apoptosis in HCT116 cells by activating caspase-3.

关键词： Macrocyclic trichothecenes Myrothecium verrucaria Cytotoxicity Secondary metabolite Soil fungi

Distinct but correct: generating diversified and entity-revised medical response

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Science China(Information Sciences) 2024年第3期67卷 94-113页

作者： Bin LI Bin SUN Shutao LI Encheng CHEN Hongru LIU Yixuan WENG Yongping BAI Meiling HU College of Electrical and Information Engineering Hunan University School of Mathematics Sun Yat-sen University JD Technology National Laboratory of Pattern Recognition Institute of AutomationChinese Academy of Sciences Xiangya hospital of Central South University Teaching and research Section of clinical Nursing Xiangya Hospital of Central South University

Medical dialogue generation(MDG) is applied for building medical dialogue systems for intelligent consultation. Such systems can communicate with patients in real time, thereby improving the efficiency of clinical diagnosis. However, predicting correct entities and correctly generating distinct responses remain a great challenge. Inspired by actual doctors’ responses to patients, we consider MDG a two-stage task: entity prediction and dialogue generation. For entity prediction, we design an ent-mac post pre-training strategy by leveraging external medical entity knowledge to enhance the pre-trained model. For dialogue generation, we propose an entity-aware fusion MDG method in which predicted entities are integrated into the dialogue generation model through different encoding fusion mechanisms, using information from different sources. Because the diverse beam search algorithm can produce responses with entities that deviate from the predicted entities, an entity-revised diverse beam search is proposed to correct the entities entailed in the generated responses and make the generated responses more distinct. The experimental results on the China Conference on Knowledge Graph and Semantic Computing 2021(A/B tests) and the International Conference on Learning Representations 2021(online test) datasets show that the proposed method outperforms several state-of-the-art methods, which demonstrates its practicability and effectiveness.

关键词： medical entity prediction ent-mac post pre-training strategy entity-aware fusion medical dialogue generation encoding fusion mechanism entity-revised diverse beam search

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

Model based on single-nucleotide polymorphism to discriminate aspirin resistance patients

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Stroke & Vascular Neurology 2024年第3期9卷 212-220,I0110-I0129页

作者： Qingyuan Liu Shuaiwei Guo Nuochuan Wang Kaiwen Wang Shaohua Mo Xiong Li Yanan Zhang Hongwei He Shuo Wang Jun Wu Department of Neurosurgery and China National clinical research Center for Neurological Diseases Beijing Tiantan HospitalBeijingChina Department of Blood Transfusion Beijing Tiantan HospitalBeijingChina Department of Neurosurgery Beijing Chao-Yang Hospital Capital Medical UniversityBeijingChina Beijing Neurosurgical institution Capital Medical UniversityBeijingChina

Background Aspirin is widely used for preventing ischaemic *** 20%–40%of patients have aspirin resistance(ASR),which prevents them from benefiting from aspirin *** study aimed to develop and validate a model based on single-nucleotide polymorphism(SNP)to distinguish ASR *** We included patients with spontaneous intracerebral haemorrhage and continuing antiplatelet therapy from a multicentre,prospective cohort study as the derivation ***(inhibition of arachidonic acid channel<50%)was used to identify *** was performed to identify the ASR-related *** on the result of the logistic analysis,the aspirin resistance in the Chinese population score(ASR-CN score)was established,and its accuracy was evaluated using the area under the curve(AUC).Patients receiving dual antiplatelet therapy for unruptured intracranial aneurysm embolism were prospectively included in the validation *** embolism,30-day ischaemic events,including ischaemic stroke,new or more frequent transient ischaemic attack,stent thrombosis and cerebrovascular death,were *** The derivation cohort included 212 patients(155 male patients and the median age as 59).87(41.0%)individuals were identified with *** multivariate logistic analysis demonstrated six SNPs of GP1BA,TBXA2R,PTGS2 and NOS3 as risk factors related to *** ASR-CN score integrating these SNPs performed well to discriminate ASR patients from non-ASR patients(AUC as 0.77).Based on the validation cohort of 372 patients receiving antiplatelet therapy after embolism(including 130 ASR patients),the ASR-CN score continued to distinguish ASR patients with good accuracy(AUC as 0.80).Patients with high a ASR-CN score were more likely to suffer from 30-day ischaemic events after embolism(OR,1.28;95%CI,1.10 to 1.50;p=0.002).Conclusion GP1BA,TBXA2R,PTGS2 and NOS3 were SNPs related to *** ASR-CN score is an effective tool to discriminate ASR patients,which

关键词： patients aspirin resistance