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A facile and general method for synthesis of antibiotic-free protein-based hydrogel:Wound dressing for the eradication of drug-resistant bacteria and biofilms

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Bioactive Materials 2022年第12期7卷 446-458页

作者： Jiang Ouyang Qingyue Bu Na Tao Mingkai Chen Haijun Liu Jun Zhou Jinggong Liu Bo Deng Na Kong Xingcai Zhang Tianfeng Chen Yihai Cao Wei Tao The First Affiliated hospital Department of ChemistryJinan UniversityGuangzhou510632China center for Nanomedicine and Department of Anesthesiology Brigham and Women’s HospitalHarvard Medical SchoolBostonMA02115USA John A.Paulson school of Engineering and Applied sciences Harvard UniversityCambridgeMA02138USA College of Chemistry and Chemical Engineering Central South UniversityChangshaHunan410083China The second Affiliated hospital of Guangzhou University of Chinese Medicine Guangdong Provincial Academy of Chinese Medical SciencesGuangzhou510006China Department of Microbiology Tumor and Cell BiologyKarolinska InstituteStockholm17177Sweden

Antibacterial protein hydrogels are receiving increasing attention in the aspect of bacteria-infected-wound healing. However, bacterial drug resistance and biofilm infections lead to hard healing of wounds, thus the construction of biological agents that can overcome these issues is essential. Here, a simple and universal method to construct antibiotic-free protein hydrogel with excellent biocompatibility and superior antibacterial activity against drug-resistant bacteria and biofilms was developed. The green industrial microbicide tetrakis (hydroxymethyl) phosphonium sulfate (THPs) as cross-linking agent can be quickly cross-linked with model protein bovine serum albumin (BsA) to form antibacterial hydrogel through simple mixing without any other initiators, subsequently promoting drug-resistance bacteria-infected wound healing. This simple gelatinization strategy allows at least ten different proteins to form hydrogels (e.g. BsA, human serum albumin (HsA), egg albumin, chymotrypsin, trypsin, lysozyme, transferrin, myohemoglobin, hemoglobin, and phycocyanin) under the same conditions, showing prominent universality. Furthermore, drug-resistance bacteria and biofilm could be efficiently destroyed by the representative BsA hydrogel (B-Hydrogel) with antibacterial activity, overcoming biofilm-induced bacterial resistance. The in vivo study demonstrated that the B-Hydrogel as wound dressing can promote reepithelization to accelerate the healing of methicillin-resistant staphylococcus aureus (MRsA)-infected skin wounds without inducing significant side-effect. This readily accessible antibiotic-free protein-based hydrogel not only opens an avenue to provide a facile, feasible and general gelation strategy, but also exhibits promising application in hospital and community MRsA disinfection and treatment.

关键词： THPs Protein hydrogel Bacterial resistance Anti-Biofilm Wound dressing

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3D-bioprinted cholangiocarcinoma-on-a-chip model for evaluating drug responses

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Bio-Design and Manufacturing 2023年第4期6卷 373-389页

作者： Qiong Liu Luis sMille Cesar Villalobos Ingrid Anaya Matthias Vostatek sili Yi Wanlu Li Junlong Liao Huanghui Wu Yongteng song Lize Xiong Yu shrike Zhang Division of Engineering in Medicine Department of MedicineBrigham and Women’s HospitalHarvard Medical SchoolCambridgeMA 02139USA Translational Research Institute of Brain and Brain-Like Intelligence Shanghai Fourth People’s HospitalSchool of MedicineTongji UniversityShanghai 200434China shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation Shanghai 200434China Department of Bioengineering Stanford UniversityPalo AltoCA 94305USA Biotechnological Engineering Program Monterrey Institute of Technology and Higher Education64849 MonterreyNuevo LeónMexico Molecular Biotechnology University of Applied Sciences Campus Vienna1100 ViennaAustria Rapid Manufacturing Engineering center School of Mechatronical Engineering and AutomationShanghai UniversityShanghai 200444China

Cholangiocarcinoma(CCA)is characterized by heterogeneous mutations and a refractory ***,the development of a model for effective drug screening is urgently *** the established therapeutic testing models for CCA are often ineffective,we fabricated an enabling three-dimensional(3D)-bioprinted CCA-on-a-chip model that to a good extent resembled the multicellular microenvironment and the anatomical microstructure of the hepato-vascular-biliary system to perform high-content antitumor drug ***,cholangiocytes,hepatocytes,and vascular endotheliocytes were employed for 3D bioprinting of the models,allowing for a high degree of spatial and tube-like microstructural ***,it was possible to observe CCA cells attached to the surfaces of the gelatin methacryloyl(GelMA)hydrogelembedded microchannels and overgrown in a thickening manner,generating bile duct stenosis,which was expected to be analogous to the in vivo *** 4000 differentially expressed genes were detected in the CCA cells in our 3D coculture model compared to the traditional two-dimensional(2D)*** screening revealed that the CCA cells grown in the 3D traditional model were more sensitive to the antitumoral prodrug than those in the 2D monoculture due to drug biotransformation by the neighboring functional *** study provides proof-of-concept validation of our bioprinted CCA-on-a-chip as a promising drug screening model for CCA treatment and paves the way for potential personalized medicine strategies for CCA patients in the future.

关键词： Tumor-on-a-chip Biliary tumor 3D bioprinting Tumor microenvironment Drug screening

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Patterns of antidepressant therapy and clinical outcomes among ischaemic stroke survivors

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stroke & vascular Neurology 2021年第3期6卷 384-394,I0018-I0032页

作者： Mark R Etherton shreyansh shah Xu Haolin Ying Xian Lesley Maisch Deidre Hannah Brianna Lindholm Barbara Lytle Laine Thomas Eric E smith Gregg C Fonarow Lee H schwamm Deepak L Bhatt Adrian F Hernandez Emily C O'Brien Neurology Massachusetts General HospitalBostonMassachusettsUSA Neurology Duke University School of MedicineDurhamNorth CarolinaUSA Duke Clinical Research Institute Duke UniversityDurhamNorth CarolinaUSA American heart Association Inc DallasTexasUSA Clinical Neurosciences University of Calgary Cumming School of MedicineCalgaryAlbertaCanada Cardiology Ronald Reagan UCLA Medical CenterLos AngelesCaliforniaUSA Cardiovascular Medicine Brigham and Women's HospitalBostonMassachusettsUSA Cardiology Duke UniversityDurhamNorth CarolinaUSA Population Health Duke Clinical Research InstituteDurhamNorth CarolinaUSA

Background and purpose Depression is common after stroke and is often treated with antidepressant medications(AD).ADs have also been hypothesised to improve stroke recovery,although recent randomised trials were *** investigated the patterns of in-hospital AD initiation after ischaemic stroke and association with clinical and readmission *** All Medicare fee-for-service beneficiaries aged 65 or older hospitalised for ischaemic stroke in participating Get With The Guidelines-stroke hospitals between April and December 2014 were eligible for this *** measures included days alive and not in a healthcare institution(home time),all-cause mortality and readmission within 1-year *** score(Ps)-adjusted logistic regression models were used to evaluate the associations between AD use and each outcome *** also compared outcomes in patients prescribed selective serotonin reuptake inhibitors(ssRIs)AD versus those prescribed non-ssRI *** Of 21805 AD naive patients included in this analysis,1835(8.4%)were started on an AD at *** started on an AD had higher rates of depression and prior ischaemic stroke,presented with higher admission National Institutes of Health stroke scale score and were less likely to be discharged ***,patients started on an ssRI had lower rates of discharge to *** for stroke severity,patients started on an AD had worse all-cause mortality,all-cause readmission,major adverse cardiac events,readmission for depression and decreased ***,AD use was also associated with an increased risk for the sepsis,a falsification endpoint,suggesting the presence of residual *** Patients with ischaemic stroke initiated on AD therapy are at increased risk of poor clinical outcomes and readmission even after Ps adjustment,suggesting that poststroke depression requiring medication is a poor prognostic *** research is needed to explore

关键词： prescribed admission founding

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Long-term outcomes after catheter-based renal artery denervation for resistant hypertension:final follow-up of the randomised sYMPLICITY HTN-3 Trial

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四川生理科学杂志 2022年第9期44卷 1686-1686页

作者： Deepak L Bhatt brigham and women's hospital heart and vascular center and harvard medical school Boston MA USA Piedmont heart Institute Atlanta GA. USA New York Presbyterian hospital Columbia University Medical Center and Cardiovascular Research Foundation New York NY USA Prairie heart Institute Springfield IL USA Perelman school of Medicine University of Pennsylvania Philadelphia PA USA Miami Cardiac vascular Institute Miami FL USA University of Alabama at Birmingham Birmingham AL USA Medtronic Santa Rosa CA USA University of Chicago Medicine Chicago IL USA

Background:The sYMPLICITY HTN-3(Renal Denervation in Patients With Uncontrolled Hypertension)trial showed the safety but not efficacy of the symplicity system(Medtronic,santa Rosa,CA,UsA)at 6 months follow-up in patients with treatment-resistant *** final report presents the 36-month follow-up ***:sYMPLICITY HTN-3 was a single-blind,multicentre,sham-controlled,randomised clinical trial,done in 88 centres in the *** aged 18-80 years,with treatment-resistant hypertension on stable,maximally tolerated doses of three or more drugs including a diuretic,who had a seated office systolic blood pressure of 160 mm Hg or more and 24 h ambulatory systolic blood pressure of 135 mm Hg or more were randomly assigned(2:1)to receive renal artery denervation using the single electrode(Flex)catheter or a sham control.

关键词： hypertension drugs treatment

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Heritability of heart Rate Response to Arousals in Twins

Heritability of Heart Rate Response to Arousals in Twins

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中国睡眠研究会第十届全国学术年会

作者： Xiaoling Gao Ali Azarbarzin Brendan T.Keenan Michele Ostrowski Frances M.Pack Bethany staley Greg Maislin Allan I.Pack Magdy Younes samuel T.Kuna Department of Medicine and center for sleep and Circadian Neurobiology University of Pennsylvania Department of Respiration The Second Hospital of Shanxi Medical University Division of sleep Medicine Brigham and Women’s Hospital and Harvard Medical School sleep Disorders Centre University of Manitoba

Objectives: To determine if the large and highly reproducible interindividual differences in arousal intensity and heart rate response to arousal（ΔHR） during non-REM sleep are ***: Polysomnograms of 55 monozygotic（14 male and 41 female pairs） and 36 dizygotic（15 male and 21 female pairs） same-sex twin pairs were *** were scored using the 2012 American Academy of sleep Medicine *** intensity was scaled（between 0 and 9） using an automatic algorithm based on the change in electroencephalogram time and frequency *** ΔHR was determined at each *** calculated average arousal duration,average arousal intensity,average overall ΔHR,average ΔHR at a given arousal intensity,slope of ΔHR per arousal intensity,and arousal intensity threshold of Δ***: The intraclass correlations among monozygotic and dizygotic twin pairs were 0.663 and 0.146,respectively,for average arousal intensity,and 0.449 and 0,respectively,for arousal intensity threshold of ΔHR controlling for age,sex,and *** values imply large broad sense heritability（H2） for these *** evidence was confirmed by a robust maximum likelihood-based variance components estimation approach,with an additive genetic heritability of 0.64（95% confidence interval: 0.48 to 0.80） for average arousal intensity and a combined additive and dominance genetic heritability and of 0.46（0.25 to 0.68） for arousal intensity threshold of Δ*** also suggested significant additive genetic effects for average arousal duration,ΔHR at arousal intensity scale 4 and the overall average Δ***: Genetic factors explain a significant fraction of the phenotypic variability for average arousal intensity and arousal intensity threshold of Δ*** suggest that the duration of arousals and specific average ΔHR values may also be heritable traits.

关键词： polysomnogram monozygotic dizygotic

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Three-dimensional silk fibroin microsphere-nanofiber scaffolds for vascular tissue engineering

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Medicine in Novel Technology and Devices 2021年第1期9卷 52-59页

作者： Qiang Liu Guoliang Ying Nan Jiang Ali KYetisen Danyu Yao Xiaoying Xie Yubo Fan Haifeng Liu Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education School of Biological Science and Medical EngineeringBeijing Advanced Innovation Centre for Biomedical EngineeringBeihang UniversityBeijing100191People’s Republic of China Department of Chemistry Stanford UniversityCA94305USA school of Materials science and Engineering Wuhan Institute of TechnologyWuhan430205People’s Republic of China Division of Engineering in Medicine Department of MedicineBrigham and Women’s HospitalHarvard Medical SchoolCambridgeMA02139USA school of Engineering and Applied sciences Harvard UniversityCambridgeMA02138USA Department of Chemical Engineering Imperial College LondonLondonSW72AZUK school of Life Information science and Instrument Engineering Hangzhou Dianzi UniversityHangzhou310018Zhejiang ProvincePeople’s Republic of China

A significant limitation in the engineering of artificial small-diameter vascular scaffolds is that the number of endothelial cells(ECs)is not sufficient to generate a confluent coverage of the vascular scaffolds,so that the surfaces of vascular scaffolds form thrombus via platelet adhesion and *** decrease relies on three-dimensional(3D)scaffolds to mimic the natural extracellular matrix(ECM)as templates to regulate cell behavior and facilitate tissue ***,we developed 3D scaffolds consisting of silk fibroin(sF)nanofibers and homogeneous microspheres by electrospinning and *** nanofibers with diameters ranging from 250 to 350 nm doped with microspheres(2–10μm)formed bridge-shaped *** were seeded and maintained on the 3D microsphere-nanofiber scaffolds with a mean fiber diameter of 300 nm.A 10%higher ratio of cell proliferation on 3D microsphere-nanofiber sF scaffolds was noted as compared to that on microporous and sponge-like sF scaffolds with small surface network fabricated by ***,the gene transcript levels including CD146,VE-C and PECAM-1 were better preserved on 3D microsphere-nanofiber sF scaffolds than those on freeze-dried ***,the developed 3D microsphere-nanofiber structure may have a myriad of applications in vascular tissue engineering scaffolds and cardiovascular devices.

关键词： Microfluidics silk fibroin Electrospinning Micro/nanostructure Tissue engineering

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sleep Duration and Risk of Lung Cancer in the Physicians' Health study

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中国肺癌杂志 2014年第9期17卷 649-655页

作者： Owais KHAWAJA Andrew B. PETRONE sohaibATEEM Kamran MANZOOR John MGAZIANO Luc DJOUssE section of Pulmonary and Critical Care Medicine Dartmouth Hitchcock Medical Center Lebanon USA Divisions of Aging Brigham and Women's Hospital and Harvard Medical School Boston USA section of General Internal Medicine Dartmouth Hitchcodc Medical Center Lebanon USA Massachusetts Veterans Epidemiology and Research In/ormation center (MAVERIC) Boston Veterans Affairs Healthcare System Boston USA Preventive Medicine Brigham and Women's Hospital and Harvard Medical Schoolp Boston USA Geriatric Research Education and Clinical Center (GRECC) Boston Veterans Affairs Heatthcare System Boston USA

Background and Objectives:Lung cancer is the most common cancer and cancer related cause of death ***,the association between sleep duration and incident lung cancer has not been investigated in a prospective cohort ***:We prospectively examined the association between sleep duration and incident lung cancer in a cohort of 21,026 United states(Us)male ***-reported sleep duration was ascertained during 2002 annual follow-up *** lung cancer was ascertained through yearly follow-up *** regression was used to estimate relative risk of incident lung ***:The average age at baseline was 68.3±8.8 *** a mean follow up of 7.5(±2.2)yr,150 cases of lung cancer *** 7 h of sleep as the reference group,multivariable adjusted hazard ratios(95%CI)for lung cancer were 1.18(0.77-1.82),1.0(ref),and 0.97(0.67-1.41)from lowest to the highest category of sleep duration(P for quadratic trend 0.697),*** a secondary analysis,smoking status did not modify the sleep duration-lung cancer association(P=0.78).There was no evidence for an interaction between sleep duration and sleep apnea on the risk of lung cancer either(P=0.65).Conclusions:Our data failed to show a higher risk of lung cancer in association with altered sleep duration among Us male physicians.

关键词：摘要编辑部编辑工作读者

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he Natural Progression of Parkinson＇s Disease in a small Cohort with 15 Drug-na＇~＇ve Patients

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Chinese medical Journal 2015年第13期128卷 1761-1764页

作者： Ying Liu Jin-Hu Fan Xiang Gao Li Ma You-Lin Qiao Lin Zhang Department of Neurology Dalian Municipal Friendship Hospital Dalian Liaoning 116001 China Department of Cancer Epidemiology Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100021 China Department of Medicine Channing Laboratory Brigham and Women's Hospital and Harvard Medical School Boston MA 02115 USA Department of Nutrition Harvard University School of Public Health Boston MA 02115 USA Department of Epidemiology Dalian Medical University Dalian Liaoning 116044 China Department of Neurology University of California Davis School of Medicine Sacramento CA 95817 USA

The studies of the natural progression of Parkinson＇s disease （PD） in Chinese populations have been lacking. To address this issue and obtain a preliminary data, we conducted a PD progression assessment in 15 adults with de novo PD from a nutritional intervention trial （NIT） cohort in Lin County China. Methods： Using the Copiah County screening questionnaire and United Kingdom Parkinson＇s Disease society Brain Bank diagnostic criteria, we surveyed the available N IT cohort members in 2000 and diagnosed 86 patients as PD. In 2010, we resurveyed all PD patients and confirmed definite PD diagnosis in 15 cases with the rest of them being dead （54）： having probable （10） PD or vascular Parkinsonism （3）; relilsing to participate （2）; or being away （2）. In both surveys, we used Hoehn and Yahr （HY） scale and assessed the disease progression. Unified Parkinson＇s Disease Rating scale （UPDRs） was added to the second survey. Results： In 2010, the average disease duration for 15 definite PD patients was 13.6 ~ 7.3 years. Over a 10-year time span, 9 out of 15 patients remained at the same HY stage while the remaining 6 progressed. Rigidity （47% vs. 100%; P 0.002） and postural instability （7% vs. 47%; P - 0.005） worsened significantly. The mean UPDRs motor scores in 2010 were 39.4 ± 23.7. Conclusions： Overall worsening of motor timction in PD seems to be the rule in this untreated cohort, and their rate of progression seemed to be slower than those reported in the western populations.

关键词： Drug-naive Epidemiology Parkinson's Disease Progression

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The role of circulating miRNAs in diagnosis of acute myocardial infarction and the pathological significance

The role of circulating miRNAs in diagnosis of acute myocard...

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第十一届全国免疫学学术大会

作者： Zhu Ping Md sayed Ali sheikh Li Chuanchang Xia Ke Li Fei Deng Xu salma Umme Yang Tianlun Peng Jun Department of Cardiovascular surgery Guangdong Cardiovascular InstituteGuangdong General HospitalGuangdong Academy of Medical Sciences Department of Cardiology Xiangya HospitalCentral South University center for vascular Biology and Inflammation Cardiovascular DivisionDepartment of MedicineBrigham and Women's HospitalHarvard Medical School Department of Gynecology and obstetrics Xiangya 3rd HospitalCentral South University Department of Pharmacology School of Pharmaceutical SciencesCentral South University

Objectives: We aimed to explore the diagnostic value of circulating miRNAs(miR-149, miR-208 b, miR-378, miR-424, miR-499 and miR-765) in AMI patients, and protective role of miR-208 b or miR-378 or metoprolol during H/R injury in H9c2 cell with their underlying mechanisms. Methods: 205 AMI patients and 85 healthy subjects, twelve week-old C57BL/6 mice AMI and H9c2 cells were included in this study. Total RNA was isolated from plasma and cardiac cell with TRIzol reagent. Circulating miRNAs levels were measured by quantitative real-time polymerase chain reaction. Results: We found that miR-208 b, miR-499 and miR-765 levels were significantly up-regulated by 9.6 fold, 5.2 fold, and 5.1 fold in AMI patients compared with healthy subjects(psma miR-149, miR-378 and miR-424 levels were markedly downregulated by 5.5 fold, 4.9 fold and 5 fold in AMI patients compared with controls(psma levels of these miRNAs were returned towards normal at 96 h after PCI(pso found that plasma miR-208 b, miR-499 and miR-765 levels were significantly elevated by 11.5 fold, 3.9 fold, and 4.7 fold, while miR-149, miR-378 and miR-424 levels were noticeably decreased by 3.7 fold, 4.1 fold and 3.8 fold in Mice AMI compared with controls(ps of plasma miR-208 b, miR-499, miR-765, miR-149, miR-378 and miR-424 represented a strong discrimination between AMI patients and healthy subjects, with an area under curve(AUC) of 0.974, 0.971, 0.965, 0.963 0.969 and 0.973, respectively. Conclusions: Our findings suggested that miR-208 b, miR-499, miR-765, miR-149, miR-378, miR-424 may be used as a novel and sensitive diagnostic biomarker for AMI patients. Inhibition of miR-208 b and overexpression of miR-378 were effectively protected cardiomyocyte damage during H/R injury through their potential targets NLK and TRAF6, represents a new therapeutic approach for ischemic heart disease. Furthermore, metoprolol protected cardiomyocytes damage against H/R in

关键词： cardiomyocytes damage circulating miRNAs AMI pathological new therapeutic approach

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Interleukin-18, matrix metalloproteinase-22 and -29 are independent risk factors of human coronary heart disease

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Journal of Zhejiang University-science B(Biomedicine & Biotechnology) 2017年第8期18卷 685-695页

作者： Dong-Yi JIN Cong-Lin LIU Jun-Nan TANG Zhao-Zhong ZHU Xue-Xi XUAN Xiao-Dan ZHU Yun-Zhe WANG Tian-Xia ZHANG De-Liang sHEN Xiao-Fang WANG Guo-Ping sHI Jin-Ying ZHANG Department of Cardiology the First Affiliated Hospital of Zhengzhou University Zhengzhou 450052 China Department of Medicine Brigham and Women's Hospital and Harvard Medical School Boston MA 02115 USA Department of Molecular Biomedical sciences and center for Comparative Medicine and Translational Research College of Veterinary Medicine North Carolina State University Raleigh NC 27695 USA Department of Environmental Health Harvard T.I~ Chan School of Public Health Boston MA 02115 USA Department of Biology Pennsylvania State University University Park PA 16802 USA

Background: Coronary heart disease(CHD) is characterized by arterial wall inflammation and matrix degradation. Matrix metalloproteinase(MMP)-22 and-29 and pro-inflammatory cytokine interleukin-18(IL18) are present in human hearts. IL18 may regulate MMP-22 and-29 expression, which may correlate with CHD progression. Methods and results: Immunoblot analysis showed that IL18 induced MMP-22 expression in human aortic smooth muscle cells. The Mann Whitney test from a prospective study of 194 CHD patients and 68 non-CHD controls demonstrated higher plasma levels of IL18, MMP-22 and-29 in CHD patients than in the controls. A logistic regression test suggested that plasma IL18(odds ratio(OR)=1.131, P=0.007), MMP-22(OR=1.213, P=0.040), and MMP-29(OR=1.198, P=0.033) were independent risk factors of CHD. Pearson's correlation test showed that IL18(coefficient(r)=0.214, P=0.045; r=0.246, P=0.031) and MMP-22(r=0.273, P=0.006; r=0.286, P=0.012) were associated with the Gensini score before and after adjusting for potential confounding factors. The multivariate Pearson's correlation test showed that plasma MMP-22 levels correlated positively with high-sensitive-C-reactive protein(hs-CRP)(r=0.167, P=0.023), and MMP-29 levels correlated negatively with triglyceride(r=-0.169, P=0.018). spearman's correlation test indicated that plasma IL18 levels associated positively with plasma MMP-22(r=0.845, Psions: Our observations suggest that IL18, MMP-22 and-29 serve as biomarkers and independent risk factors of CHD. Increased systemic IL18 in CHD patients may contribute to elevated plasma MMP-22 and-29 levels in these patients.

关键词： Interleukin-18 Matrix metalloproteinase (MMP)-22 MMP-29 Coronary heart disease Risk factor

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