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Amyloid-beta and tau protein beyond Alzheimer's disease

Neural Regeneration Research 2024年第6期19卷 1262-1276页

作者： Morteza Abyadeh Vivek Gupta Joao A.Paulo Arezoo Gohari Mahmoudabad Sina Shadfar Shahab Mirshahvaladi Veer Gupta Christine T.O.Nguyen David I.Finkelstein Yuyi You Paul A.Haynes Ghasem H.Salekdeh Stuart L.Graham Mehdi Mirzaei ProGene Technologies Pty Ltd. 2. Department of Clinical medicine Faculty of Medicine Health and Human Sciences Macquarie Medical School Macquarie University Department of Cell Biology Harvard Medical School school of medicine Deakin University Department of Optometry and Vision sciences School of Health Sciences Faculty of Medicine Dentistry and Health Sciences University of Melbourne The Florey Institute of Neuroscience and Mental health The University of Melbourne school of Natural sciences Macquarie University

The aggregation of amyloid-beta peptide and tau protein dysregulation are implicated to play key roles in Alzheimer’s disease pathogenesis and are considered the main pathological hallmarks of this devastating disease. Physiologically, these two proteins are produced and expressed within the normal human body. However, under pathological conditions, abnormal expression, posttranslational modifications, conformational changes, and truncation can make these proteins prone to aggregation, triggering specific disease-related cascades. Recent studies have indicated associations between aberrant behavior of amyloid-beta and tau proteins and various neurological diseases, such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, as well as retinal neurodegenerative diseases like Glaucoma and age-related macular degeneration. Additionally, these proteins have been linked to cardiovascular disease, cancer, traumatic brain injury, and diabetes, which are all leading causes of morbidity and mortality. In this comprehensive review, we provide an overview of the connections between amyloid-beta and tau proteins and a spectrum of disorders.

关键词： amyloid-beta cancer cardiovascular diseases diabetes neurodegeneration Tau traumatic brain injury

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Exosome-encapsulated lncRNA HOTAIRM1 contributes to PM_(2.5)-aggravated COPD airway remodeling by enhancing myofibroblast differentiation

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Science China(Life sciences) 2024年第5期67卷 970-985页

作者： Huaqi Guo Luo Fei Hengyi Yu Yan Li Yan Feng Shaowei Wu Yan Wang The Ninth People’s Hospital of Shanghai Jiao Tong University school of medicine Shanghai 200011China school of Public health Shanghai Jiao Tong University School of MedicineShanghai 200020China Department of Occupational and Environmental health sciences School of Public HealthXi’an Jiao Tong University Health Science CenterXi’an 710049China

Emphysema,myofibroblast accumulation and airway remodeling can occur in the lungs due to exposure to atmospheric pollution,especially fine particulate matter(PM_(2.5)),leading to chronic obstructive pulmonary disease(COPD).Specifically,bronchial epithelium-fibroblast communication participates in airway remodeling,which results in COPD.An increasing number of studies are now being conducted on the role of exosome-mediated cell-cell communication in disease pathogenesis.Here,we investigated whether exosomes generated from bronchial epithelial cells could deliver information to normal stromal fibroblasts and provoke cellular responses,resulting in airway obstruction in COPD.We studied the mechanism of exosome-mediated intercellular communication between human bronchial epithelial(HBE) cells and primary lung fibroblasts(pLFs).We found that PM_(2.5)-induced HBE-derived exosomes promoted myofibroblast differentiation in pLFs.Then,the exosomal lncRNA expression profiles derived from PM_(2.5)-treated HBE cells and nontreated HBE cells were investigated using an Agilent Human LncRNA Array.Combining coculture assays and direct exosome treatment,we found that HBE cell-derived exosomal HOTAIRM1 facilitated the myofibroblast differentiation of pLFs.Surprisingly,we discovered that exosomal HOTAIRM1 enhanced p LF proliferation to secrete excessive collagen secretion,leading to airway obstruction by stimulating the TGF-β/SMAD3 signaling pathway.Significantly,PM_(2.5)reduced FEV1/FVC and FEV1 and increased the level of serum exosomal HOTAIRM1 in healthy people;moreover,serum exosomal HOTAIRM1 was associated with PM_(2.5)-related reductions in FEV1/FVC and FVC.These findings show that PM_(2.5)triggers alterations in exosome components and clarify that one of the paracrine mediators of myofibroblast differentiation is bronchial epithelial cell-derived HOTAIRM1,which has the potential to be an effective prevention and therapeutic target for PM_(2.5)-induced COPD.

关键词： PM2.5 exosomal lncRNAs HOTAIRM1 chronic obstructive pulmonary disease

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Approach to traumatic cardiac arrest in the emergency department: a narrative literature review for emergency providers

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World Journal of Emergency medicine 2024年第1期15卷 3-9页

作者： Rashed Alremeithi Quincy K.Tran Megan T.Quintana Soroush Shahamatdar Ali Pourmand Department of Emergency medicine George Washington University School of Medicine and Health SciencesWashington DC 20037USA Department of Emergency medicine University of Maryland School of MedicineBaltimore 21201USA Program in Trauma the R Adams Cowley Shock Trauma CenterUniversity of Maryland School of MedicineBaltimore 21201USA Center for Trauma and Critical Care Department of Surgerythe George Washington University School of Medicine&Health SciencesWashington DC 20037USA

BACKGROUND:Traumatic cardiac arrest(TCA)is a major contributor to mortality and morbidity in all age groups and poses a significant burden on the healthcare system.Although there have been advances in treatment modalities,survival rates for TCA patients remain low.This narrative literature review critically examines the indications and eff ectiveness of current therapeutic approaches in treating TCA.METHODS:We performed a literature search in the PubMed and Scopus databases for studies published before December 31,2022.The search was refi ned by combining search terms,examining relevant study references,and restricting publications to the English language.Following the search,943 articles were retrieved,and two independent reviewers conducted a screening process.RESULTS:A review of various studies on pre-and intra-arrest prognostic factors showed that survival rates were higher when patients had an initial shockable rhythm.There were conflicting results regarding other prognostic factors,such as witnessed arrest,bystander cardiopulmonary resuscitation(CPR),and the use of prehospital or in-hospital epinephrine.Emergency thoracotomy was found to result in more favorable outcomes in cases of penetrating trauma than in those with blunt trauma.Resuscitative endovascular balloon occlusion of the aorta(REBOA)provides an advantage to emergency thoracotomy in terms of occupational safety for the operator as an alternative in managing hemorrhagic shock.When implemented in the setting of aortic occlusion,emergency thoracotomy and REBOA resulted in comparable mortality rates.Veno-venous extracorporeal life support(V-V ECLS)and veno-arterial extracorporeal life support(V-A ECLS)are viable options for treating respiratory failure and cardiogenic shock,respectively.In the context of traumatic injuries,V-V ECLS has been associated with higher rates of survival to discharge than V-A ECLS.CONCLUSION:TCA remains a signifi cant challenge for emergency medical services due to its high morbidity and mortality rates.Pre-and intra-arres

关键词： Traumatic cardiac arrest Emergency thoracotomy Resuscitative endovascular balloon occlusion of the aorta

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The deterministic condition for the ground reaction force acting point on the combined knee valgus and tibial internal rotation moments in early phase of cutting maneuvers in female athletes

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Journal of Sport and health Science 2024年第3期13卷 376-386页

作者： Issei Ogasawara Ken Ohta Gajanan S.Revankar Shoji Konda Yohei Shimokochi Hideyuki Koga Ken Nakata Department of health and Sport sciences Graduate School of MedicineOsaka UniversityToyonaka 560-0043Japan Sports Sensing Co. LTD.Fukuoka 815-0035Japan Department of Neurology Graduate School of MedicineOsaka UniversitySuita 565-0871Japan Department of health and Sport Management Osaka University of Health and Sport SciencesSennan-gun 590-0496Japan Department of Joint Surgery and Sports medicine Graduate School of Medical and Dental SciencesTokyo Medical and Dental UniversityBunkyo-ku 113-8519Japan

Background:Combined knee valgus and tibial internal rotation(VL+IR)moments have been shown to stress the anterior cruciate ligament(ACL)in several in vitro cadaveric studies.To utilize this knowledge for non-contact ACL injury prevention in sports,it is necessary to elucidate how the ground reaction force(GRF)acting point(center of pressure(CoP))in the stance foot produces combined knee VL+IR moments in risky maneuvers,such as cuttings.However,the effects of the GRF acting point on the development of the combined knee VL+IR moment in cutting are still unknown.Methods:We first established the deterministic mechanical condition that the CoP position relative to the tibial rotational axis differentiates the GRF vector’s directional probability for developing the combined knee VL+IR moment,and theoretically predicted that when the CoP is posterior to the tibial rotational axis,the GRF vector is more likely to produce the combined knee VL+IR moment than when the CoP is anterior to the tibial rotational axis.Then,we tested a stochastic aspect of our theory in a lab-controlled in vivo experiment.Fourteen females performed 60˚cutting under forefoot/rearfoot strike conditions(10 trials each).The positions of lower limb markers and GRF data were measured,and the knee moment due to GRF vector was calculated.The trials were divided into anterior-and posterior-CoP groups depending on the CoP position relative to the tibial rotational axis at each 10 ms interval from 0 to 100 ms after foot strike,and the occurrence rate of the combined knee VL+IR moment was compared between trial groups.Results:The posterior-CoP group showed significantly higher occurrence rates of the combined knee VL+IR moment(maximum of 82.8%)at every time point than those of the anterior-CoP trials,as theoretically predicted by the deterministic mechanical condition.Conclusion:The rearfoot strikes inducing the posterior CoP should be avoided to reduce the risk of non-contact ACL injury associated with the combined knee VL+IR stress.

关键词： Center of pressure Deterministic condition Foot strike pattern Injury mechanism Moment of ground reaction force

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Therapeutic potential and pharmacological mechanism of visnagin

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Journal of Integrative medicine 2024年第4期22卷 399-412页

作者： Poonam Yadav Sumeet Kumar Singh Sayantap Datta Saloni Verma Aarti Verma Arnab Rakshit Anjana Bali Jasvinder Singh Bhatti Amit Khurana Umashanker Navik Department of Pharmacology School of Health SciencesCentral University of Punjab Department of Pharmacological and Pharmaceutical sciences College of PharmacyUniversity of Houston Department of Human Genetics and Molecular medicine School of Health SciencesCentral University of Punjab

Visnagin is a furanochromone and one of the most important compound in the Ammi visnaga (L.) Lam (a synonym of Visnaga daucoides Gaertn.) plant,which is used to cure various ailments.Many investigations into the bioactive properties of visnagin have been studied to date.The literature on visnagin demonstrates its biological properties,including anti-inflammatory,anti-diabetic,and beneficial effects in cardiovascular and renal diseases.Moreover,visnagin improves sperm quality parameters,stimulates steroidogenesis,and increases serum gonadotropins and testosterone levels,while decreasing proinflammatory cytokines,oxidative damage,genomic instability,and it modulates apoptosis.Thus,visnagin has emerged as an exciting lead for further research,owing to its potential in various unmet clinical needs.The current review summarized its basic structure,pharmacokinetics,and pharmacological effects,focusing on its mechanisms of action.The review will help to understand the potential of visnagin as an alternative treatment strategy for several diseases and provide insight into research topics that need further exploration for visnagin’s safe clinical use.

关键词： Ammi visnaga L. Anti-inflammatory Cancer Phytochemical Visnaga daucoides Gaertn Visnagin

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Cannabinoids and endocannabinoids as therapeutics for nervous system disorders:preclinical models and clinical studies

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Neural Regeneration Research 2024年第4期19卷 788-799页

作者： R.Scott Duncan Sean M.Riordan Matthew C.Gernon Peter Koulen Department of Ophthalmology School of MedicineUniversity of Missouri Department of Biomedical sciences School of MedicineUniversity of Missouri

Cannabinoids are lipophilic substances derived from Cannabis sativa that can exert a variety of effects in the human body.They have been studied in cellular and animal models as well as in human clinical trials for their therapeutic benefits in several human diseases.Some of these include central nervous system(CNS)diseases and dysfunctions such as forms of epilepsy,multiple sclerosis,Parkinson’s disease,pain and neuropsychiatric disorders.In addition,the endogenously produced cannabinoid lipids,endocannabinoids,are critical for normal CNS function,and if controlled or modified,may represent an additional therapeutic avenue for CNS diseases.This review discusses in vitro cellular,ex vivo tissue and in vivo animal model studies on cannabinoids and their utility as therapeutics in multiple CNS pathologies.In addition,the review provides an overview on the use of cannabinoids in human clinical trials for a variety of CNS diseases.Cannabinoids and endocannabinoids hold promise for use as disease modifiers and therapeutic agents for the prevention or treatment of neurodegenerative diseases and neurological disorders.

关键词： anandamide cannabidiol cannabinoid endocannabinoid epilepsy multiple sclerosis neurodegeneration neuroprotection tetrahydrocannabinol

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MicroRNA-502-3p regulates GABAergic synapse function in hippocampal neurons

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Neural Regeneration Research 2024年第12期19卷 2698-2707页

作者： Bhupender Sharma Melissa MTorres Sheryl Rodriguez Laxman Gangwani Subodh Kumar Center of Emphasis in Neuroscience Department of Molecular and Translational MedicinePaul L.Foster School of MedicineTexas Tech University Health Sciences CenterEl PasoTXUSA Bond Life sciences Center and Department of Veterinary Pathobiology University of MissouriColumbiaMOUSA L.Frederick Francis Graduate school of Biomedical sciences Texas Tech University Health Sciences CenterEl PasoTXUSA

Gamma-aminobutyric acid(GABA)ergic neurons,the most abundant inhibitory neurons in the human brain,have been found to be reduced in many neurological disorders,including Alzheimer's disease and Alzheimer's disease-related dementia.Our previous study identified the upregulation of microRNA-502-3p(miR-502-3p)and downregulation of GABA type A receptor subunitα-1 in Alzheimer's disease synapses.This study investigated a new molecular relationship between miR-502-3p and GABAergic synapse function.In vitro studies were perfo rmed using the mouse hippocampal neuronal cell line HT22 and miR-502-3p agomiRs and antagomiRs.In silico analysis identified multiple binding sites of miR-502-3p at GABA type A receptor subunitα-1 mRNA.Luciferase assay confirmed that miR-502-3p targets the GABA type A receptor subunitα-1 gene and suppresses the luciferase activity.Furthermore,quantitative reve rse transcription-polymerase chain reaction,miRNA in situ hybridization,immunoblotting,and immunostaining analysis confirmed that overexpression of miR-502-3p reduced the GABA type A receptor subunitα-1 level,while suppression of miR-502-3p increased the level of GABA type A receptor subunitα-1 protein.Notably,as a result of the overexpression of miR-502-3p,cell viability was found to be reduced,and the population of necrotic cells was found to be increased.The whole cell patch-clamp analysis of human-GABA receptor A-α1/β3/γ2L human embryonic kidney(HEK)recombinant cell line also showed that overexpression of miR-502-3p reduced the GABA current and overall GABA function,suggesting a negative correlation between miR-502-3p levels and GABAergic synapse function.Additionally,the levels of proteins associated with Alzheimer s disease were high with miR-502-3p overexpression and reduced with miR-502-3p suppression.The present study provides insight into the molecular mechanism of regulation of GABAergic synapses by miR-502-3p.We propose that micro-RNA,in particular miR-502-3p,could be a potential therapeutic to rget to modulate GABAergic synapse f

关键词： Alzheimer's disease GABAergic synapse gamma-aminobutyric acid type A receptor subunitα-1(GABRα1) microRNA-502-3p(miR-502-3p) miRNA in situ hybridization Patch-clamp

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Physical activity volume,frequency,and intensity:Associations with hypertension and obesity over 21 years in Australian women

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Journal of Sport and health Science 2024年第5期13卷 631-641页

作者： Gregore I.Mielke Ding Ding Shelley E.Keating Bruno P.Nunes Ruth Brady Wendy J.Brown school of Public health The University of QueenslandBrisbaneQLD 4006Australia Sydney school of Public health Faculty of Medicine and HealthThe University of SydneySydneyNSW 2006Australia The Charles Perkins Centre The University of SydneySydneyNSW 2006Australia school of Human Movement and Nutrition sciences The University of QueenslandBrisbaneQLD 4072Australia school of Nursing Federal University of PelotasPelotasRio Grande do Sul 96010-610Brazil Faculty of health sciences and medicine Bond UniversityGold CoastQLD 4226Australia

Background:Optimal patterns of accrual of recommended levels of physical activity(PA)for prevention of hypertension and obesity are not known.The overall aim of this study was to investigate whether different patterns of accumulation of PA are differentially associated with hypertension and obesity in Australian women over 21 years.Specifically,we investigated whether,for the same weekly volume of PA,the number of sessions(frequency)and vigorousness of PA(intensity)were associated with a reduction in the occurrence of hypertension and obesity in women.Methods:Data from the 1973-1978 and 1946-1951 cohorts of the Australian Longitudinal Study on Women's health were analyzed(n=20,588;12%-16%with a Bachelor's or higher degree).Self-reported PA,hypertension,height,and weight were collected using mail surveys every 3 years from 1998/2000 to 2019/2021.Generalized Estimating Equation models with a 3-year lag model were used to investigate the association of PA volume(metabolic equivalent min/week)(none;33-499;500-999;≥1000,weekly frequency(none;1-2 times;3-4times;5-7 times;≥8 times),and the proportion of vigorous PA to total volume of PA(none;0%;1%-33%;34%-66%;67%-100%)with odds of hypertension and obesity from 2000 to 2021.Results:The cumulative incidence of hypertension was 6%in the 1973-1978 and 23%in the 1946-1951 cohort;27%of women in the 1973-1978;and 15%in the 1946-1951 cohort developed obesity over the period.Overall,a higher volume of PA was associated with reduced odds of hypertension and obesity.When the volume of PA was considered,the odds of hypertension did not vary according to the frequency or intensity of PA.However,increased proportion of vigorous PA to the total volume of PA was associated with a small additional reduction in the risk of obe sity.Conclusion:PA volume appears to be more important than the pattern of accumulation for the prevention of hypertension and obesity.Incorporating more sessions,particularly of vigorous-intensity PA,may provide extra benefits for the prevention of obesity.

关键词： Physical activity Frequency Intensity Incidences Epidemiology Women

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Prediction of cell-cell communication patierns of dorsal root ganglion cells: single-cell RNA sequencing data analysis

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Neural Regeneration Research 2024年第6期19卷 1367-1374页

作者： Yanna Lian Cheng Wu Li Liu Xiangyao Li National health Commission and Chinese Academy of Medical sciences Key Laboratory of Medical Neurobiology Ministry of Education Frontier Science Center for Brain Research and Brain-Machine Integration School of Brain Science and Brain Medicine Zhejiang University International Institutes of medicine the Fourth Affiliated Hospital of Zhejiang University School of Medicine Zhejiang University-University of Edinburgh Institute Zhejiang University School of Medicine Zhejiang University 4. Biomedical Sciences College of Medicine and Veterinary Medicine The University of Edinburgh Core Facilities of the school of medicine Zhejiang University

Dorsal root ganglion neurons transmit peripheral somatic information to the central nervous system, and dorsal root ganglion neuron excitability affects pain perception. Dorsal root ganglion stimulation is a new approach for managing pain sensation. Knowledge of the cell-cell communication among dorsal root ganglion cells may help in the development of new pain and itch management strategies. Here, we used the single-cell RNA-sequencing(scRNA-seq) database to investigate intercellular communication networks among dorsal root ganglion cells. We collected scRNA-seq data from six samples from three studies, yielding data on a total of 17,766 cells. Based on genetic profiles, we identified satellite glial cells, Schwann cells, neurons, vascular endothelial cells, immune cells, fibroblasts, and vascular smooth muscle cells. Further analysis revealed that eight types of dorsal root ganglion neurons mediated proprioceptive, itch, touch, mechanical, heat, and cold sensations. Moreover, we predicted several distinct forms of intercellular communication among dorsal root ganglion cells, including cell-cell contact, secreted signals, extracellular matrix, and neurotransmitter-mediated signals. The data mining predicted that Mrgpra3-positive neurons robustly express the genes encoding the adenosine Adora2b(A2B) receptor and glial cell line-derived neurotrophic factor family receptor alpha 1(GFRα-1). Our immunohistochemistry results confirmed the coexpression of the A2B receptor and GFRα-1. Intrathecal injection of the A2B receptor antagonist PSB-603 effectively prevented histamine-induced scratching behaviour in a dose-dependent manner. Our results demonstrate the involvement of the A2B receptor in the modulation of itch sensation. Furthermore, our findings provide insight into dorsal root ganglion cell-cell communication patterns and mechanisms. Our results should contribute to the development of new strategies for the regulation of dorsal root ganglion excitability.

关键词： cell-cell communications CellChat dorsal root ganglion scRNA-Seq database

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Relationships between blood chromium exposure and liver injury:Exploring the mediating role of systemic inflammation in a chromate-exposed population

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Journal of Environmental sciences 2024年第9期143卷 224-234页

作者： Zekang Su Yali Zhang Shiyi Hong Qiaojian Zhang Jiayu Xu Guiping Hu Xiaojun Zhu Fang Yuan Shanfa Yu Tianchen Wang Guang Jia Department of Occupational and Environmental health sciences School of Public HealthPeking UniversityBeijing 100191China school of Engineering medicine and Beijing Advanced Innovation Center for Big Data-Based Precision medicine Beihang UniversityBeijing 100191China National Center for Occupational Safety and health Beijing 102308China Department of Occupational health and Radiological health Chongqing Centers for Disease Control and PreventionChongqing 400042China Henan Institute for Occupational medicine Zhengzhou 450052China Department of Clinical Laboratory Third Hospital of Peking UniversityBeijing 100191China

Hexavalent chromium and its compounds are prevalent pollutants,especially in the work environment,pose a significant risk for multisystem toxicity and cancers.While it is known that chromium accumulation in the liver can cause damage,the dose-response relationship between blood chromium(Cr)and liver injury,as well as the possible potential toxic mechanisms involved,remains poorly understood.To address this,we conducted a follow-up study of 590 visits from 305 participants to investigate the associations of blood Cr with biomarkers for liver injury,including serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL),and direct bilirubin(DBIL),and to evaluate the mediating effects of systemic inflammation.Platelet(PLT)and the platelet-to-lymphocyte ratio(PLR)were utilized as biomarkers of systemic inflammation.In the linear mixed-effects analyses,each 1-unit increase in blood Cr level was associated with estimated effect percentage increases of 0.82%(0.11%,1.53%)in TBIL,1.67%(0.06%,3.28%)in DBIL,0.73%(0.04%,1.43%)in ALT and 2.08%(0.29%,3.87%)in AST,respectively.Furthermore,PLT mediated 10.04%,11.35%,and 10.77%increases in TBIL,DBIL,and ALT levels induced by chromate,respectively.In addition,PLR mediated 8.26%and 15.58%of the association between blood Cr and TBIL or ALT.These findings shed light on the mechanisms underlying blood Cr-induced liver injury,which is partly due to worsening systemic inflammation.

关键词： Blood chromate Liver injury Systemic inflammation Mediation analysis

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