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Evaluation of mitral chordae tendineae length using four-dimensional computed

World Journal of Cardiology 2024年第5期16卷 274-281页

作者： Takuya Mori Satoshi Matsushita Terumasa Morita Abulaiti Abudurezake Junji Mochizuki Atsushi Amano department of Cardiovascular surgery Juntendo University Faculty of MedicineTokyo 113-8421Japan department of Cardiovascular surgery JACCT Japan Animal Cardiovascular Care TeamOsaka 533-0033Japan department of Radiology Minamino Cardiovascular HospitalTokyo 192-0918Japan

BACKGROUND Mitral valvuloplasty using artificial chordae tendineae represents an effective surgical approach for treating mitral regurgitation.Achieving precise measurements of artificial chordae tendineae length(CL)is an important factor in the procedure;however,no objective index currently exists to facilitate this measurement.Therefore,preoperative assessment of CL is critical for surgical planning and support.Four-dimensional x-ray micro-computed tomography(4D-CT)may be useful for accurate CL measurement considering that it allows for dynamic three-dimensional(3D)evaluation compared to that with transthoracic echocardiography,a conventional inspection method.AIM To investigate the behavior and length of mitral chordae tendineae during systole using 4D-CT.METHODS Eleven adults aged>70 years without mitral valve disease were evaluated.A 64-slice CT scanner was used to capture 20 phases in the cardiac cycle in electrocardiographic synchronization.The length of the primary chordae tendineae was measured from early systole to early diastole using the 3D image.The primary chordae tendineae originating from the anterior papillary muscle and attached to the A1-2 region and those from the posterior papillary muscle and attached to the A2-3 region were designated as cA and cP,respectively.The behavior and maximum lengths[cA(ma),cP(max)]were compared,and the correlation with body surface area(BSA)was evaluated.RESULTS In all cases,the mitral anterior leaflet chordae tendineae could be measured.In most cases,the cA and cP chordae tendineae could be measured visually.The mean cA(max)and cP(max)were 20.2 mm±1.95 mm and 23.5 mm±4.06 mm,respectively.cP(max)was significantly longer.The correlation coefficients(r)with BSA were 0.60 and 0.78 for cA(max)and cP(max),respectively.Both cA and cP exhibited constant variation in CL during systole,with a maximum 1.16-fold increase in cA and a 1.23-fold increase in cP from early to mid-systole.For cP,CL reached a plateau at 15%and remained elongated until end-systole,whereas for cA,aft

关键词： Mitral valve Chordae tendineae Computed tomography Four-dimensional Cardiac cycle

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The incidence rate and histological characteristics of intimal hyperplasia in elastase-induced experimental abdominal aortic aneurysms in mice

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animal Models and Experimental medicine 2024年第3期7卷 388-395页

作者： Meng Li Panpan Wei Kexin Li Haole Liu Naqash Alam Haiwen Hou Jie Deng Baohui Xu Enqi Liu Sihai Zhao Yankui Li Laboratory animal Center Xi'an Jiaotong UniversityXi'anChina department of Vascular surgery The Second Hospital of Tianjin Medical UniversityTianjinChina department of Cardiology The Second Affiliated Hospital of Xi'an Jiaotong UniversityXi'anChina department of Vascular surgery Stanford University School of MedicineStanfordCaliforniaUSA

Intimal hyperplasia(IH)is a negative vascular remodeling after arterial injury.IH occasionally occurs in elastase-induced abdominal aortic aneurysm(AAA)mouse models.This study aims to clarify the incidence and histological characteristics of IH in aneurysmal mice.A retrospective study was conducted by including 42 male elastaseinduced mouse AAA models.The IH incidence,aortic diameters with or without IH,and hyperplasia lesional features of mice were analyzed.Among 42 elastase-induced AAA mouse models,10 mice developed mild IH(24%)and severe IH was found in only 2 mice(5%).The outer diameters of the AAA segments in mice with and without IH did not show significant difference.Both mild and severe IH lesions show strong smooth muscle cell positive staining,but endothelial cells were occasionally observed in severe IH lesions.There was obvious macrophage infiltration in the IH lesions of the AAA mouse models,especially in mice with severe IH.However,only a lower numbers of T cells and B cells were found in the IH lesion.Local cell-secreted matrix metalloproteinases(MMP)2 was highly expressed in all IH lesions,but MMP9 was only overexpressed in severe lesions.In conclusion,this study is the first to demonstrate the occurrence of aneurysmal IH and its histological characteristics in an elastaseinduced mouse AAA model.This will help researchers better understand this model,and optimize it for use in AAA-related research.

关键词： abdominal aortic aneurysms animal model histology intimal hyperplasia

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Chromatin condensation but not DNA integrity of pig sperm is greater in the sperm-rich fraction

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Journal of animal Science and Biotechnology 2024年第1期15卷 171-181页

作者： Estel Viñolas-Vergés Jordi Ribas-Maynou Isabel Barranco Camila Peres Rubio Sergi Bonet Jordi Roca Marc Yeste Unit of Cell Biology Department of BiologyFaculty of SciencesUniversity of GironaGironaSpain Biotechnology of animal and Human Reproduction(TechnoSperm) Institute of Food and Agricultural TechnologyUniversity of GironaGironaSpain department of medicine and animal surgery Faculty of Veterinary ScienceUniversity of MurciaMurciaSpain Catalan Institution for Research and Advanced Studies(ICREA) S08010 BarcelonaSpain

Background Protamination and condensation of sperm chromatin as well as DNA integrity play an essential role during fertilization and embryo development.In some mammals,like pigs,ejaculates are emitted in three separate fractions:pre-sperm,sperm-rich(SRF)and post sperm-rich(PSRF).These fractions are known to vary in volume,sperm concentration and quality,as well as in the origin and composition of seminal plasma(SP),with differences being also observed within the SRF one.Yet,whether disparities in the DNA integrity and chromatin condensation and pro-tamination of their sperm exist has not been interrogated.Results This study determined chromatin protamination(Chromomycin A3 test,CMA_(3)),condensation(Dibromobi-mane test,DBB),and DNA integrity(Comet assay)in the pig sperm contained in the first 10 m L of the SRF(SRF-P1),the remaining portion of the sperm-rich fraction(SRF-P2),and the post sperm-rich fraction(PSRF).While chromatin protamination was found to be similar between the different ejaculate fractions(P>0.05),chromatin condensation was seen to be greater in SRF-P1 and SRF-P2 than in the PSRF(P=0.018 and P=0.004,respectively).Regarding DNA integrity,no differences between fractions were observed(P>0.05).As the SRF-P1 has the highest sperm concentra-tion and ejaculate fractions are known to differ in antioxidant composition,the oxidative stress index(OSi)in SP,calcu-lated as total oxidant activity divided by total antioxidant capacity,was tested and confirmed to be higher in the SRF-P1 than in SRF-P2 and PSRF(0.42±0.06 vs.0.23±0.09 and 0.08±0.00,respectively;P<0.01);this index,in addition,was observed to be correlated to the sperm concentration of each fraction(Rs=0.973;P<0.001).Conclusion While sperm DNA integrity was not found to differ between ejaculate fractions,SRF-P1 and SRF-P2 were observed to exhibit greater chromatin condensation than the PSRF.This could be related to the OSi of each fraction.

关键词： Chromatin Condensation DNA integrity Ejaculate fractions Pig Protamination Sperm

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Quercetin Alleviates Lipopolysaccharide-Induced Cardiac Inflammation via Inhibiting Autophagy and Programmed Cell Death

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Biomedical and Environmental Sciences 2024年第1期37卷 54-70页

作者： YU Jin Hai HU Guo Liang GUO Xiao Quan CAO Hua Bin XIA Zhao Fei AMIN Buhe Jiangxi Provincial Key Laboratory for animal Health Institute of Animal Population HealthCollege of Animal Science and TechnologyJiangxi Agricultural UniversityNanchang 330045JiangxiChina Internal medicine Laboratory Department of Veterinary Clinical MedicineCollege of Veterinary MedicineChina Agricultural UniversityBeijing 100091China department of Cancer surgery Beijing Shijitan Hospital Affiliated with Capital Medical UniversityBeijing 100038China

Objective The aim of this study is to explore the potential modulatory role of quercetin against Endotoxin or lipopolysaccharide(LPS)induced septic cardiac dysfunction.Methods Specific pathogen-free chicken embryos(n=120)were allocated untreated control,phosphate buffer solution(PBS)vehicle,PBS with ethanol vehicle,LPS(500 ng/egg),LPS with quercetin treatment(10,20,or 40 nmol/egg,respectively),Quercetin groups(10,20,or 40 nmol/egg).Fifteenday-old embryonated eggs were inoculated with abovementioned solutions via the allantoic cavity.At embryonic day 19,the hearts of the embryos were collected for histopathological examination,RNA extraction,real-time polymerase chain reaction,immunohistochemical investigations,and Western blotting.Results They demonstrated that the heart presented inflammatory responses after LPS induction.The LPS-induced higher mRNA expressions of inflammation-related factors(TLR4,TNFα,MYD88,NF-κB1,IFNγ,IL-1β,IL-8,IL-6,IL-10,p38,MMP3,and MMP9)were blocked by quercetin with three dosages.Quercetin significantly decreased immunopositivity to TLR4 and MMP9 in the treatment group when compared with the LPS group.Quercetin significantly decreased protein expressions of TLR4,IFNγ,MMP3,and MMP9 when compared with the LPS group.Quercetin treatment prevented LPS-induced increase in the mRNA expression of Claudin 1 and ZO-1,and significantly decreased protein expression of claudin 1 when compared with the LPS group.Quercetin significantly downregulated autophagyrelated gene expressions(PPARα,SGLT1,APOA4,AMPKα1,AMPKα2,ATG5,ATG7,Beclin-1,and LC3B)and programmed cell death(Fas,Bcl-2,CASP1,CASP12,CASP3,and RIPK1)after LPS induction.Quercetin significantly decreased immunopositivity to APOA4,AMPKα2,and LC3-II/LC3-I in the treatment group when compared with the LPS group.Quercetin significantly decreased protein expressions of AMPKα1,LC3-I,and LC3-II.Quercetin significantly decreased the protein expression to CASP1 and CASP3 by immunohistochemical investigation or Western blotting in treatment group when compar

关键词： Quercetin Lipopolysaccharide Inflammation Autophagy Programmed cell death Myocardiocytes permeability

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In‑depth proteome characterization of endometrium and extraembryonic membranes during implantation in pig

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Journal of animal Science and Biotechnology 2024年第3期15卷 1027-1055页

作者： Maria A.Gil Josep M.Cambra Heriberto Rodriguez‑Martinez Cristina Cuello Inmaculada Parrilla Emilio A.Martinez department of medicine and animal surgery International Excellence Campus for Higher Education and Research“Campus Mare Nostrum”University of MurciaMurciaSpain Institute for Biomedical Research of Murcia(IMIB-Pascual Parrilla) MurciaSpain Technical University of Munich MunichGermany department of Biomedical&Clinical Sciences(BKV) BKH/Obstetrics&GynaecologyLinkoping UniversityLinkopingSweden

Background Proteome characterization of the porcine endometrium and extraembryonic membranes is important to understand mother-embryo cross-communication.In this study,the proteome of the endometrium and cho-rioallantoic membrane was characterized in pregnant sows(PS)during early gestation(d 18 and 24 of gestation)and in the endometrium of non-pregnant sows(NPS)during the same days using LC-MS/MS analysis.The UniProtKB database and ClueGO were used to obtain functional Gene Ontology annotations and biological and functional networks,respectively.Results Our analysis yielded 3,254 and 3,457 proteins identified in the endometrium of PS and NPS,respectively;of these,1,753 being common while 1,501 and 1,704 were exclusive to PS and NPS,respectively.In addition,we iden-tified 3,968 proteins in the extraembryonic membranes of PS.Further analyses of function revealed some proteins had relevance for the immune system process and biological adhesion in endometrium while the embryonic chorion displayed abundance of proteins related to cell adhesion and cytoskeletal organization,suggesting they dominated the moment of endometrial remodeling,implantation and adhesion of the lining epithelia.Data are available via Pro-teomeXchange with identifier PXD042565.Conclusion This is the first in-depth proteomic characterization of the endometrium and extraembryonic mem-branes during weeks 3 to 4 of gestation;data that contribute to the molecular understanding of the dynamic environ-ment during this critical period,associated with the majority of pregnancy losses.

关键词： Endometrium Extraembryonic membranes Implantation Pig Proteome

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The neutrophil–osteogenic cell axis promotes bone destruction in periodontitis

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International Journal of Oral Science 2024年第1期16卷 154-162页

作者： Yutaro Ando Masayuki Tsukasaki Nam Cong-Nhat Huynh Shizao Zang Minglu Yan Ryunosuke Muro Kazutaka Nakamura Masatsugu Komagamine Noriko Komatsu Kazuo Okamoto Kenta Nakano Tadashi Okamura Akira Yamaguchi Kazuyuki Ishihara Hiroshi Takayanagi department of Immunology Graduate School of Medicine and Faculty of MedicineThe University of Tokyo7-3-1HongoBunkyo-kuTokyoJapan department of Microbiology Tokyo Dental College2-1-14 Kanda-Misaki-choChiyoda-kuTokyoJapan Oral Health Science Center Tokyo Dental College2-9-18Kanda-Misaki-choChiyodakuTokyoJapan department of Osteoimmunology Graduate School of Medicine and Faculty of MedicineThe University of Tokyo7-3-1HongoBunkyo-kuTokyoJapan Unit of Prosthodontics Laboratory of Oral-Maxillofacial Biology Faculty of Odonto-StomatologyUniversity of Medicine and Pharmacy at Ho Chi Minh CityHo Chi Minh CityVietnam department of Oral and Maxillofacial surgery Department of Sensory and Motor System MedicineGraduate School of MedicineThe University of TokyoTokyoJapan Division of Rheumatology Department of Internal MedicineKeio University School of MedicineTokyoJapan department of Laboratory animal medicine Research InstituteNational Center for Global Health and MedicineTokyoJapan

The immune-stromal cell interactions play a key role in health and diseases. In periodontitis, the most prevalent infectious disease in humans, immune cells accumulate in the oral mucosa and promote bone destruction by inducing receptor activator of nuclear factor-κB ligand (RANKL) expression in osteogenic cells such as osteoblasts and periodontal ligament cells. However, the detailed mechanism underlying immune–bone cell interactions in periodontitis is not fully understood. Here, we performed single-cell RNAsequencing analysis on mouse periodontal lesions and showed that neutrophil–osteogenic cell crosstalk is involved in periodontitis-induced bone loss. The periodontal lesions displayed marked infiltration of neutrophils, and in silico analyses suggested that the neutrophils interacted with osteogenic cells through cytokine production. Among the cytokines expressed in the periodontal neutrophils, oncostatin M (OSM) potently induced RANKL expression in the primary osteoblasts, and deletion of the OSM receptor in osteogenic cells significantly ameliorated periodontitis-induced bone loss. Epigenomic data analyses identified the OSM-regulated RANKL enhancer region in osteogenic cells, and mice lacking this enhancer showed decreased periodontal bone loss while maintaining physiological bone metabolism. These findings shed light on the role of neutrophils in bone regulation during bacterial infection, highlighting the novel mechanism underlying osteoimmune crosstalk.

关键词： period neutrophil destruction

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Knockdown of neuronal DAF-15/Raptor promotes healthy aging in C.elegans

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Journal of Genetics and Genomics 2024年第5期51卷 507-516页

作者： Xiao Zang Qi Wang Hanxin Zhang Yiyan Zhang Zi Wang Zixing Wu Di Chen Model animal Research Center of Medical School Nanjing UniversityNanjingJiangsu 210061China Zhejiang University-University of Edinburgh Institute School of MedicineZhejiang UniversityHainingZhejiang 314400China department of Colorectal surgery The Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310058China

The highly conserved target of rapamycin(TOR)pathway plays an important role in aging across species.Previous studies have established that inhibition of the TOR complex 1(TORC1)significantly extends lifespan in Caenorhabditis elegans.However,it has not been clear whether TORC1 perturbation affects aging in a spatiotemporal manner.Here,we apply the auxin-inducible degradation tool to knock down endogenous DAF-15,the C.elegans ortholog of regulatory associated protein of TOR(Raptor),to characterize its roles in aging.Global or tissue-specific inhibition of DAF-15 during development results in various growth defects,whereas neuron-specific knockdown of DAF-15 during adulthood significantly extends lifespan and healthspan.The neuronal DAF-15 deficiency-induced longevity requires the intestinal activities of DAF-16/FOXO and PHA-4/FOXA transcription factors,as well as the AAK-2/AMP-activated protein kinaseαcatalytic subunit.Transcriptome profiling reveals that the neuronal DAF-15 knockdown promotes the expression of genes involved in protection.These findings define the tissue-specific roles of TORC1 in healthy aging and highlight the importance of neuronal modulation of aging.

关键词： Aging targetof rapamycin DAF-15 DAF-16 C.elegans

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A rat model of multicompartmental traumatic injury and hemorrhagic shock induces bone marrow dysfunction and profound anemia

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animal Models and Experimental medicine 2024年第3期7卷 367-376页

作者： Lauren S.Kelly Jennifer A.Munley Erick E.Pons Kolenkode B.Kannan Elizabeth M.Whitley Letitia E.Bible Philip A.Efron Alicia M.Mohr department of surgery and Sepsis and Critical Illness Research Center University of Florida College of MedicineGainesvilleFloridaUSA Pathogenesis LLCGainesvilleFloridaUSA

Background:Severe trauma is associated with systemic inflammation and organ dysfunction.Preclinical rodent trauma models are the mainstay of postinjury research but have been criticized for not fully replicating severe human trauma.The aim of this study was to create a rat model of multicompartmental injury which recreates profound traumatic injury.Methods:Male Sprague-Dawley rats were subjected to unilateral lung contusion and hemorrhagic shock(LCHS),multicompartmental polytrauma(PT)(unilateral lung contusion,hemorrhagic shock,cecectomy,bifemoral pseudofracture),or na?ve controls.Weight,plasma toll-l ike receptor 4(TLR4),hemoglobin,spleen to body weight ratio,bone marrow(BM)erythroid progenitor(CFU-GEMM,BFU-E,and CFU-E)growth,plasma granulocyte colony-stimulating factor(G-CSF)and right lung histologic injury were assessed on day 7,with significance defined as p values<0.05(*).Results:Polytrauma resulted in markedly more profound inhibition of weight gain compared to LCHS(p=0.0002)along with elevated plasma TLR4(p<0.0001),lower hemoglobin(p<0.0001),and enlarged spleen to body weight ratios(p=0.004).Both LCHS and PT demonstrated suppression of CFU-E and BFU-E growth compared to na?ve(p<0.03,p<0.01).Plasma G-CSF was elevated in PT compared to both na?ve and LCHS(p<0.0001,p=0.02).LCHS and PT demonstrated significant histologic right lung injury with poor alveolar wall integrity and interstitial edema.Conclusions:Multicompartmental injury as described here establishes a reproducible model of multicompartmental injury with worsened anemia,splenic tissue enlargement,weight loss,and increased inflammatory activity compared to a less severe model.This may serve as a more effective model to recreate profound traumatic injury to replicate the human inflammatory response postinjury.

关键词： anemia i nflammation polytrauma pseudofracture shock

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The efficacy of vitamin E in preventing arthrofibrosis after joint replacement

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animal Models and Experimental medicine 2024年第2期7卷 145-155页

作者： Yingfang Fan Jean Yuh Sashank Lekkala Mehmet D.Asik Andrew Thomson Madeline McCanne Mark A.Randolph Antonia F.Chen Ebru Oral Harris Orthopaedic Laboratory Department of Orthopaedic SurgeryMassachusetts General HospitalBostonMassachusettsUSA department of Orthopaedic surgery Harvard Medical SchoolBostonMassachusettsUSA department of surgery Harvard Medical SchoolBostonMassachusettsUSA department of Orthopaedic surgery Brigham and Women's HospitalBostonMassachusettsUSA

Background:Arthrofibrosis is a joint disorder characterized by excessive scar formation in the joint tissues.Vitamin E is an antioxidant with potential anti-fibroblastic effect.The aim of this study was to establish an arthrofibrosis rat model after joint replacement and assess the effects of vitamin E supplementation on joint fibrosis.Methods:We simulated knee replacement in 16 male Sprague–Dawley rats.We immobilized the surgical leg with a suture in full flexion.The control groups were killed at 2 and 12 weeks(n=5 per group),and the test group was supplemented daily with vitamin E(0.2 mg/mL)in their drinking water for 12 weeks(n=6).We performed histological staining to investigate the presence and severity of arthrofibrosis.Immunofluorescent staining andα2-macroglobulin(α2M)enzyme-linked immunosorbent assay(ELISA)were used to assess local and systemic inflammation.Static weight bearing(total internal reflection)and range of motion(ROM)were collected for functional assessment.Results:The ROM and weight-bearing symmetry decreased after the procedure and recovered slowly with still significant deficit at the end of the study for both groups.Histological analysis confirmed fibrosis in both lateral and posterior periarticular tissue.Vitamin E supplementation showed a moderate anti-inflammatory effect on the local and systemic levels.The vitamin E group exhibited significant improvement in ROM and weight-bearing symmetry at day 84 compared to the control group.Conclusions:This model is viable for simulating arthrofibrosis after joint replacement.Vitamin E may benefit postsurgical arthrofibrosis,and further studies are needed for dosing requirements.

关键词： arthrofibrosis range of motion total knee arthroplasty vitamin E

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Preliminary exploration of animal models of congenital choledochal cysts

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World Journal of Gastroenterology 2024年第10期30卷 1420-1430页

作者： Shu-Hao Zhang Yue-Bin Zhang Duo-Te Cai Tao Pan Ken Chen Yi Jin Wen-Juan Luo Zong-Wei Huang Qing-Jiang Chen Zhi-Gang Gao department of General surgery Children’s HospitalZhejiang University School of MedicineHangzhou 310000Zhejiang ProvinceChina

BACKGROUND Various animal models have been used to explore the pathogenesis of choledochal cysts(CCs),but with little convincing results.Current surgical techniques can achieve satisfactory outcomes for treatment of CCs.Consequently,recent studies have focused more on clinical issues rather than basic research.Therefore,we need appropriate animal models to further basic research.AIM To establish an appropriate animal model that may contribute to the investigation of the pathogenesis of CCs.METHODS Eighty-four specific pathogen-free female Sprague-Dawley rats were randomly allocated to a surgical group,sham surgical group,or control group.A rat model of CC was established by partial ligation of the bile duct.The reliability of the model was confirmed by measurements of serum biochemical indices,morpho-logy of common bile ducts of the rats as well as molecular biology experiments in rat and human tissues.RESULTS Dilation classified as mild(diameter,≥1 mm tosurgery,while direct bilirubin,total bilirubin,and gamma-glutamyltransferase were further increased 14 d after surgery.Most of the biochemical indices gradually decreased to normal ranges 28 d after surgery.The protein expression trend of signal transducer and activator of transcription 3 in rat model was consistent with the human CC tissues.CONCLUSION The model of partial ligation of the bile duct of juvenile rats could morphologically simulate the cystic or fusiform CC,which may contribute to investigating the pathogenesis of CC.

关键词： Choledochal cyst animal model Partial ligation Cystic and fusiform dilation Juvenile rats

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