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A pathological joint-liver axis mediated by matrikine-activated CD4^(+)T cells

Signal Transduction and Targeted Therapy 2024年第6期9卷 2679-2693页

作者： Junzhi Yi Hui Zhang Fangyuan Bao Zhichu Chen Yuliang Zhong Tianning Ye Xuri Chen Jingyi Qian Mengya Tian Min Zhu Zhi Peng Zongyou Pan Jianyou Li Zihao Hu Weiliang Shen Jiaqi Xu Xianzhu Zhang Youzhi Cai Mengjie Wu Hua Liu Jing Zhou Hongwei Ouyang Department of Sports medicine of the Second Affiliated Hospital and Liangzhu LaboratoryZhejiang University School of MedicineHangzhouChina Dr.Li Dak Sum&Yip Yio Chin Center for Stem Cells and Regenerative medicine Zhejiang University School of MedicineHangzhouChina Stomatology Hospital School of StomatologyZhejiang University School of MedicineZhejiang Provincial Clinical Research Center for Oral DiseasesHangzhouChina The MOE Key Laboratory of Biosystems Homeostasis&Protection The Key Laboratory of Cancer Molecular Cell Biology of Zhejiang ProvinceLife Sciences InstituteZhejiang UniversityHangzhouChina Department of Orthopedics Huzhou Central HospitalAffiliated Huzhou HospitalZhejiang University School of MedicineHuzhouChina China Orthopedic Regenerative medicine Group(CORMed) HangzhouChina Department of Orthopedics The First Affiliated HospitalZhejiang University School of MedicineHangzhouChina

The knee joint has long been considered a closed *** pathological effects of joint diseases on distant organs have not been ***,our clinical data showed that post-traumatic joint damage,combined with joint bleeding(hemarthrosis),exhibits a worse liver function compared with healthy *** mouse model,hemarthrosis induces both cartilage degeneration and remote liver ***,we found that hemarthrosis induces the upregulation in ratio and differentiation towards Th17 cells of CD4^(+)T cells in peripheral blood and *** of CD4^(+)T cells reverses hemarthrosis-induced liver *** of cartilage matrix induced by hemarthrosis upregulates serological type Ⅱ collagen(COL Ⅱ),which activates CD4^(+)T *** application of a COL Ⅱ antibody blocks the ***,bulk RNAseq and single-cell qPCR analysis revealed that the cartilage Akt pathway is inhibited by blood ***-articular application of Akt activator blocks the cartilage degeneration and thus protects against the liver impairment in mouse and pig *** together,our study revealed a pathological joint-liver axis mediated by matrikine-activated CD4^(+)T cells,which refreshes the organ-crosstalk axis and provides a new treatment target for hemarthrosis-related disease.

关键词： degeneration damage inhibited

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Pupillometry Analysis of Rapid Serial Visual Presentation at Five Presentation Rates

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Tsinghua Science and Technology 2024年第2期29卷 543-552页

作者： Xi Luo Yanfei Lin Rongxiao Guo Xirui Zhao Shangen Zhang Xiaorong Gao school of Integrated Circuits and Electronics Beijing Institute of TechnologyBeijing 100081China school of Computer and Communication Engineering University of Science and Technology BeijingBeijing 100083China school of medicine Tsinghua UniversityBeijing 100084China

In this study,the effect of presentation rates on pupil dilation is investigated for target recognition in the Rapid Serial Visual Presentation(RSVP)*** this experiment,the RSVP paradigm with five different presentation rates,including 50,80,100,150,and 200 ms,is *** pupillometry data of 15 subjects are collected and *** pupillometry results reveal that the peak and average amplitudes for pupil size and velocity at the 80-ms presentation rate are considerably higher than those at other presentation *** average amplitude of pupil acceleration at the 80-ms presentation rate is significantly higher than those at the other presentation *** latencies under 50-and 80-ms presentation rates are considerably lower than those of 100-,150-,and 200-ms presentation ***,no considerable differences are observed in the peak,average amplitude,and latency of pupil size,pupil velocity,and acceleration under 100-,150-,and 200-ms presentation *** results reveal that with the increase in the presentation rate,pupil dilation first increases,then decreases,and later reaches *** 80-ms presentation rate results in the largest point of pupil *** correlation is observed between pupil dilation and recognition accuracy under the five presentation rates.

关键词： pupil dilation presentation rate Rapid Serial Visual Presentation(RSVP)

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From Perspective of Hippocampal Plasticity:Function of Antidepressant Chinese medicine Xiaoyaosan

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Chinese Journal of Integrative medicine 2024年第8期30卷 747-758页

作者： ZHANG Wu-jing GUO Ze-xuan WANG Yi-di FANG Shao-yi WAN Chun-miao YU Xiao-long GUO Xiao-fang CHEN Yue-yue ZHOU Xuan HUANG Jun-qing LI Xiao-juan CHEN Jia-xu FAN Li-li Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese medicine School of Traditional Chinese MedicineJinan UniversityGuangzhou510632China

The hippocampus is one of the most commonly studied brain regions in the context of *** volume of the hippocampus is significantly reduced in patients with depression,which severely disrupts hippocampal ***,antidepressant therapies that target hippocampal neuroplasticity have not been identified as *** medicine(CM)can slow the progression of depression,potentially by modulating hippocampal ***(XYS)is a CM formula that has been clinically used for the treatment of *** is known to protect Gan(Liver)and Pi(Spleen)function,and may exert its antidepressant effects by regulating hippocampal *** this review,we have summarized the association between depression and aberrant hippocampal ***,we have discussed the researches published in the last 30 years on the effects of XYS on hippocampal neuroplasticity in order to elucidate the possible mechanisms underlying its therapeutic action against *** results of this review can aid future research on XYS for the treatment of depression.

关键词： depression hippocampal neuroplasticity Xiaoyaosan Chinese medicine

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Adenosine triphosphate mediates the pain tolerance effect of manual acupuncture at Zusanli(ST36) in mice

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Journal of Traditional Chinese medicine 2024年第4期44卷 660-669页

作者： LI Zhongzheng ZHAO Yadan Ma Weigang Zhang Yonglong XU Zhifang XI Qiang LI Yanqi QIN Siru ZHANG Zichen WANG Songtao ZHAO Xue LIU Yangyang GUO Yi GUO Yongming Research Center of Experimental Acupuncture Science Tianjin University of Traditional Chinese MedicineTianjin 301617China National Clinical Research Center for Chinese medicine Acupuncture and Moxibustion Tianjin 301617China Department of Acupuncture and Moxibustion Qingdao Hiser Hospital Affiliated of Qingdao University(Qingdao Traditional Chinese Medicine Hospital)Qingdao 266033China school of Traditional Chinese medicine Tianjin University of Traditional Chinese MedicineTianjin 301617China school of Acupuncture and Moxibustion and Tuina Tianjin University of Traditional Chinese MedicineTianjin 301617China

OBJECTIVE:To investigate the mechanisms behind the effects of acupuncture in Traditional Chinese medicine,we delved into the adenosine triphosphate/peripheral purinergic P2X receptor 3(ATP/P2X3)receptor signaling system as an indicator of the body's energy state,commonly referred to as"Qi".METHODS:The tail-flick test was utilized to explore the impact of acupuncture on pain tolerance threshold(PTT)in mice,while also assessing adenosine(ADO)levels and adenylate energy charge(EC)at Zusanli(ST36).The study further investigated the dose-dependent effects of acupuncture on PTT and ADO levels at Zusanli(ST36).To shed light on the underlying mechanisms of acupuncture's effects,the study examined the impact of ATP,a P2X3 receptor antagonist,and adenosine disodium on PTT following acupuncture ***:Acupuncture at Zusanli(ST36)led to significant improvements in PTT in mice,with the most effective interventions being twirling for 2 min and needle retention for 28 *** interventions also resulted in significant increases in ATP *** effects of acupuncture were further augmented by administration of different doses of ATP at Zusanli(ST36),and pretreatment with a P2X3 receptor antagonist decreased *** EC peaked at 30 min after intraperitoneal injection of ATP,and pretreatment with various doses of *** 30 min prior to acupuncture increased PTT in a dose-dependent ***,pretreatment with an *** intramuscular injection of adenosine disodium enhanced the effects of ***:This research provides compelling evidence that ATP is involved in the regulation of PTT through acupuncture,revealing new avenues for achieving enhanced clinical outcomes.

关键词： acupuncture point ST36(Zusanli) adenosine triphosphate receptors,purinergic P2X3 energy state

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Epigenetic modification in liver fibrosis:Promising therapeutic direction with significant challenges ahead

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1009-1029页

作者： Runping Liu Yajing Li Qi Zheng Mingning Ding Huiping Zhou Xiaojiaoyang Li school of Chinese Materia Medica Beijing University of Chinese MedicineBeijing 102400China school of Life Sciences Beijing University of Chinese MedicineBeijing 102400China Department of Microbiology and Immunology Virginia Commonwealth UniversityRichmondVA 22460USA

Liver fibrosis,characterized by scar tissue formation,can ultimately result in liver ***’s a major cause of morbidity and mortality globally,often associated with chronic liver diseases like hepatitis or alcoholic and non-alcoholic fatty liver ***,current treatment options are limited,highlighting the urgent need for the development of new *** a reversible regulatory mechanism,epigenetic modification is implicated in many biological processes,including liver *** the epigenetic mechanisms involved in liver fibrosis could provide valuable insights into developing new treatments for chronic liver diseases,although the current evidence is still *** review provides a comprehensive summary of the regulatory mechanisms and critical targets of epigenetic modifications,including DNA methylation,histone modification,and RNA modification,in liver fibrotic *** potential cooperation of different epigenetic modifications in promoting fibrogenesis was also ***,available agonists or inhibitors regulating these epigenetic mechanisms and their potential application in preventing liver fibrosis were *** summary,elucidating specific druggable epigenetic targets and developing more selective and specific candidate medicines may represent a promising approach with bright prospects for the treatment of chronic liver diseases.

关键词： Liver fibrosis Epigenetics regulation DNA methylation Histone acetylation Histone methylation mRNA methylation Non-coding RNA Drug development

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Jackknife Model Averaging for Composite Quantile Regression

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Journal of Systems Science & Complexity 2024年第4期37卷 1604-1637页

作者： YOU Kang WANG Miaomiao ZOU Guohua school of Mathematical Sciences Capital Normal UniversityBeijing 100089China school of Chinese Materia Medica Beijing University of Chinese MedicineBeijing 100105China

In this paper,the authors propose a frequentist model averaging method for composite quantile regression with diverging number of *** from the traditional model averaging for quantile regression which considers only a single quantile,the proposed model averaging estimator is based on multiple *** well-known delete-one cross-validation or jackknife approach is applied to estimate the model *** resultant jackknife model averaging estimator is shown to be asymptotically optimal in terms of minimizing the out-of-sample composite final prediction *** studies are conducted to demonstrate the finite sample performance of the new model averaging *** proposed method is also applied to the analysis of the stock returns data and the wage data.

关键词： Asymptotic optimality composite quantile regression cross-validation model averaging

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Comparison of biliary protein spectrum in gallstone patients with obesity and those with normal body weight

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 385-392页

作者： Min-Zhi Chen Ping Xie Xiao-Chang Wu Zhen-Hua Tan Hai Qian Zhi-Hong Ma Xing Yao Department of Hepatopancreatobiliary Surgery Huzhou Central HospitalAffiliated Huzhou HospitalZhejiang University School of MedicineHuzhou 313000China Huzhou Key Laboratory of Molecular medicine Huzhou Central HospitalAffiliated Huzhou HospitalZhejiang University School of MedicineHuzhou 313000China

Background: Obesity is a common public health issue and is currently deemed a disease. Research has shown that the risk of gallstones in individuals with obesity is elevated. This study aimed to explore the bile proteomics differences between cholelithiasis patients with obesity and normal body weight. Methods: Bile samples from 20 patients(10 with obesity and 10 with normal body weight) who underwent laparoscopic cholecystectomy at our center were subjected to tandem mass tag labeling(TMT) and liquid chromatography-tandem mass spectrometry(LC-MS/MS), followed by further bioinformatic analysis. Results: Among the differentially expressed proteins, 23 were upregulated and 67 were downregulated. Bioinformatic analysis indicated that these differentially expressed proteins were mainly involved in cell development, inflammatory responses, glycerolipid metabolic processes, and protein activation cascades. In addition, the activity of the peroxisome proliferator-activated receptor(PPAR, a subfamily of nuclear receptors) signaling pathway was decreased in the Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis. Two downregulated proteins in the PPAR signaling pathway, APO A-Ⅰ and APO A-Ⅱ, were confirmed using enzyme-linked immunosorbent assay. Conclusions: The PPAR signaling pathway may play a crucial role in the development of cholelithiasis among patients with obesity. Furthermore, biliary proteomics profiling of gallstones patients with obesity is revealed, providing a reference for future research.

关键词： Proteome profiling Gallstones Obesity-associated gallstones Tandem mass tag labeling PPAR signaling

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Dynamic Treatment Strategy of Chinese medicine for Metastatic Colorectal Cancer Based on Machine Learning Algorithm

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Chinese Journal of Integrative medicine 2024年第11期30卷 993-1000页

作者： XU Yu-ying LI Qiu-yan YI Dan-hui CHEN Yue ZHAI Jia-wei ZHANG Tong SUN Ling-yun YANG Yu-fei Department of Oncology Xiyuan Hospital China Academy of Chinese Medical Sciences school of Statistics Renmin University of China Graduate school Beijing University of Chinese Medicine

Objective: To establish the dynamic treatment strategy of Chinese medicine(CM) for metastatic colorectal cancer(m CRC) by machine learning algorithm, in order to provide a reference for the selection of CM treatment strategies for m CRC. Methods: From the outpatient cases of m CRC in the Department of Oncology at Xiyuan Hospital, China Academy of Chinese Medical Sciences, 197 cases that met the inclusion criteria were screened. According to different CM intervention strategies, the patients were divided into 3 groups: CM treatment alone, equal emphasis on Chinese and Western medicine treatment(CM combined with local treatment of tumors, oral chemotherapy, or targeted drugs), and CM assisted Western medicine treatment(CM combined with intravenous regimen of Western medicine). The survival time of patients undergoing CM intervention was taken as the final evaluation index. Factors affecting the choice of CM intervention scheme were screened as decision variables. The dynamic CM intervention and treatment strategy for m CRC was explored based on the cost-sensitive classification learning algorithm for survival(CSCLSurv). Patients' survival was estimated using the Kaplan-Meier method, and the survival time of patients who received the model-recommended treatment plan were compared with those who received actual treatment plan. Results: Using the survival time of patients undergoing CM intervention as the evaluation index, a dynamic CM intervention therapy strategy for m CRC was established based on *** CM intervention strategies for m CRC can be selected according to dynamic decision variables, such as gender, age, Eastern Cooperative Oncology Group score, tumor site, metastatic site, genotyping, and the stage of Western medicine treatment at the patient's first visit. The median survival time of patients who received the modelrecommended treatment plan was 35 months, while those who receive the actual treatment plan was 26.0 months(P=0.06). Conclusions:

关键词： Chinese medicine cost sensitive classification learning for survival dynamic treatment strategy metastatic colorectal cancer

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Experimental models for preclinical research in kidney disease

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Zoological Research 2024年第5期45卷 1161-1174页

作者： Jin Miao Huanhuan Zhu Junni Wang Jianghua Chen Fei Han Weiqiang Lin Kidney Disease Center First Affiliated HospitalZhejiang University School of MedicineInstitute of NephrologyZhejiang UniversityKey Laboratory of Kidney Disease Prevention and Control TechnologyZhejiang ProvinceZhejiang Clinical Research Center of Kidney and Urinary System DiseaseHangzhouZhejiang 310003China Department of Nephrology Center for Regeneration and Aging MedicineFourth Affiliated Hospital of School of Medicineand International School of MedicineInternational Institutes of MedicineZhejiang UniversityYiwuZhejiang 322000China

Acute kidney injury(AKI)and chronic kidney disease(CKD)are significant public health issues associated with a long-term increase in mortality risk,resulting from various etiologies including renal ischemia,sepsis,drug toxicity,and diabetes *** preclinical models have been developed to deepen our understanding of the pathophysiological mechanisms and therapeutic approaches for kidney *** these,rodent models have proven to be powerful tools in the discovery of novel therapeutics,while the development of kidney organoids has emerged as a promising advancement in the *** review provides a comprehensive analysis of the construction methodologies,underlying biological mechanisms,and recent therapeutic developments across different AKI and CKD ***,this review summarizes the advantages,limitations,and challenges inherent in these preclinical models,thereby contributing robust evidence to support the development of effective therapeutic strategies.

关键词： Acute kidney injury Chronic kidney disease Mouse models

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Growth differentiation factor-15 serum concentrations reflect disease severity and anemia in patients with inflammatory bowel disease

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World Journal of Gastroenterology 2024年第13期30卷 1899-1910页

作者： Ante Tonkic Marko Kumric Ivna Akrapovic Olic Doris Rusic Piero Marin Zivkovic Daniela Supe Domic Zeljko Sundov Ivan Males Josko Bozic Biology of Neoplasms University of Split School of MedicineSplit 21000Croatia Department of Pathophysiology University of Split School of MedicineSplit 21000Croatia Department of Gastroenterology University Hospital of SplitSplit 21000Croatia Department of Pharmacy University of Split School of MedicineSplit 21000Croatia Department of Medical Laboratory Diagnostics University Hospital of SplitSplit 21000Croatia Department of Health Studies University of SplitSplit 21000Croatia Department of Internal medicine University of Split School of MedicineSplit 21000Croatia Department of Surgery University Hospital of SplitSplit 21000Croatia

BACKGROUND Population of patients with inflammatory bowel disease(IBD)is burdened by various extraintestinal manifestations which substantially contribute to greater morbidity and ***-differentiation factor-15(GDF-15)is often overexpressed under stress conditions,such as inflammation,malignancies,heart failure,myocardial ischemia,and many *** To explore the association between GDF-15 and IBD as serum concentrations of GDF-15 were shown to be an independent predictor of poor outcomes in multiple *** additional aim was to determine possible associations between GDF-15 and multiple clinical,anthropometric and laboratory parameters in patients with *** This cross-sectional study included 90 adult patients diagnosed with IBD,encompassing both Crohn’s disease(CD)and ulcerative colitis(UC),and 67 healthy age-and sex-matched *** patients underwent an extensive workup,including colonoscopy with subsequent histopathological *** activity was assessed by two independent gastroenterology consultants specialized in IBD,employing well-established clinical and endoscopic scoring ***-15 serum concentrations were determined following an overnight fasting,using electrochemiluminescence *** In patients with IBD,serum GDF-15 concentrations were significantly higher in comparison to the healthy controls[800(512-1154)pg/mL vs 412(407-424)pg/mL,P<0.001],whereas no difference in GDF-15 was found between patients with CD and UC[807(554-1451)pg/mL vs 790(509-956)pg/mL,P=0.324].Moreover,multiple linear regression analysis showed that GDF-15 levels predict CD and UC severity independent of age,sex,and C-reactive protein levels(P=0.016 and P=0.049,respectively).Finally,an association between GDF-15 and indices of anemia was ***,negative correlations were found between GDF-15 and serum iron levels(r=-0.248,P=0.021),as well as GDF-15 and hemoglobin(r=-0.351,P=0.021).Accordingly,in comparison to I

关键词： Inflammatory bowel disease Crohn’s disease Ulcerative colitis Growth-differentiation factor-15 Anemia Extraintestinal manifestations

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