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Article ; Online: Screening of Candidate Inflammatory Markers of Epithelial Cells in Hepatocellular Carcinoma Based on Integration Analysis of TCGA/ICGC Databases and Single-cell Sequencing.

Huang, Zupin / Li, Zhuokai / Lv, Xinliang / Tan, Wei

Recent patents on anti-cancer drug discovery

2024

Abstract: Background: Hepatocellular Carcinoma (HCC) is closely linked to inflammatory reactions, with chronic liver diseases acting as major risk factors. In the inflammatory microenvironment, repeated damage and repair of liver cells lead to genetic mutations, ... ...

Abstract	Background: Hepatocellular Carcinoma (HCC) is closely linked to inflammatory reactions, with chronic liver diseases acting as major risk factors. In the inflammatory microenvironment, repeated damage and repair of liver cells lead to genetic mutations, abnormal proliferation, and tumorigenesis. Objective: This study aimed to investigate the expression profile of specific cell clusters under inflammatory stimulation in HCC and identify potential therapeutic drugs. Methods: Comprehensive analysis of HCC transcriptome data and single-cell sequencing data from TCGA, ICGC, and GEO databases was conducted to explore the specific molecular mechanisms of epithelial cells. Virtual screening of natural compounds in the ZINC database and in vitro cell experiments were performed to identify drugs that regulate the expression of inflammatory factors in epithelial cells. Results: Analysis of the single-cell dataset revealed cell clusters closely associated with HCC, notably Epithelial cells, Hepatocytes, MSC, and iPS cells, with Epithelial cells playing a pivotal role in HCC development. Further investigation of TCGA data unveiled 83 differentially expressed genes (DEGs) related to inflammatory responses in HCC. Intersection analysis of DEGs in epithelial cells and HCC DEGs identified 12 common DEGs, including ADRM1, ATP2B1, FZD5, GPC3, KIF1B, KLF6, LY6E, MET, NAMPT, SERPINE1, SPHK1, and SRI. Prognostic analysis revealed that CCL7, GPR132, ITGB8, PTAFR, SELL, and VIP were influential in the survival prognosis of HCC. A prognostic model based on the expression levels of these genes demonstrated an increased risk of HCC associated with higher differential expression of inflammatory response genes. Additionally, molecular dynamics simulations indicated that compounds NADH and Deferoxamine formed stable docking models with the inflammatory protein VIP, suggesting their potential as candidates for targeted therapy. Conclusion: Inflammatory factors CCL7, GPR132, ITGB8, PTAFR, SELL, and VIP influence the inflammatory cascade response in HCC epithelial cells, and their expression correlates with the survival prognosis of HCC patients. Interfering with VIP expression effectively suppresses proliferation, migration, and invasion of HCC cells, as well as inhibiting the occurrence of inflammatory cascade reactions, thus slowing down the progression of hepatocellular carcinoma. Furthermore, compounds NADH and Deferoxamine have the potential to target and bind to the inflammatory protein VIP, highlighting their relevance in potential HCC treatment.
Language	English
Publishing date	2024-01-30
Publishing country	United Arab Emirates
Document type	Journal Article
ZDB-ID	2250820-X
ISSN	2212-3970 ; 1574-8928
ISSN (online)	2212-3970
ISSN	1574-8928
DOI	10.2174/0115748928256530240124093759
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Article: Impact of hepatectomy and postoperative adjuvant transarterial chemoembolization on serum tumor markers and prognosis in intermediate-stage hepatocellular carcinoma.

Hu, Yi-Di / Zhang, Hui / Tan, Wei / Li, Zhuo-Kai

World journal of gastrointestinal surgery

2024 Volume 15, Issue 12, Page(s) 2820–2830

Abstract: Background: Primary hepatocellular carcinoma (HCC) is a common malignant tumour, and its early symptoms are often not obvious, resulting in many patients experiencing middle- to late-stage disease at the time of diagnosis. The optimal time for surgery ... ...

Abstract	Background: Primary hepatocellular carcinoma (HCC) is a common malignant tumour, and its early symptoms are often not obvious, resulting in many patients experiencing middle- to late-stage disease at the time of diagnosis. The optimal time for surgery is often missed for these patients, and those who do undergo surgery have unsatisfactory long-term outcomes and a high recurrence rate within five years. Therefore, postoperative follow-up treatments, such as transhepatic arterial chemoembolization (TACE), have become critical to improving survival and reducing recurrence rates. Aim: To validate the prophylactic role of TACE after hepatic resection and to assess its impact on patient prognosis. Methods: This study investigated the efficacy of TACE in patients with intermediate-stage HCC after hepatectomy. When the post-treatment results of the observation group and the control group were compared, it was found that the inclusion of TACE significantly improved the clinical efficacy, reduced the levels of tumour markers and did not aggravate the damage to liver function. Thus, this may be an effective and comprehensive treatment strategy for patients with intermediate-stage HCC that helps to improve their quality of life and survival time. Results: When the baseline data were analysed, no statistical differences were found between the two groups in terms of gender, age, hepatitis B virus, cirrhosis, Child-Pugh grading, number of tumours, maximum tumour diameter and degree of tumour differentiation. The assessment of clinical efficacy showed that the post-treatment overall remission rate of the observation group was significantly higher than that of the control group. In terms of changes in tumour markers, the alpha-fetoprotein and carcinoembryonic antigen levels in the patients in the observation group decreased more significantly after treatment compared with those in the control group. When post-treatment changes in liver function indicators were analysed, no statistical differences were found in the total bilirubin, alanine aminotransferase and aspartate aminotransferase levels between the two groups. Conclusion: In patients with intermediate-stage HCC, post-hepatectomy TACE significantly improved clinical outcomes, reduced tumour-marker levels and may have improved the prognosis by removing residual lesions. Thus, this may be an effective and comprehensive treatment strategy for patients with intermediate-stage HCC.
Language	English
Publishing date	2024-01-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	2573700-4
ISSN	1948-9366
ISSN	1948-9366
DOI	10.4240/wjgs.v15.i12.2820
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Article ; Online: Insufficient stem antetorsion and lower cup abduction is a combined risk factor for posterior hip dislocation in patients undergoing THA for femoral neck fractures: a retrospective analysis.

Li, Zhuokai / Yang, Yang / Guo, Shengyang / Liu, Ju / Zhou, Xiaoxiao / Ji, Houlin

BMC musculoskeletal disorders

2024 Volume 25, Issue 1, Page(s) 103

Abstract: Background: The role of acetabular and femoral component positions with respect to the risk of post-operative instability and dislocation remains debated. In this study, we aimed to identify potential risk factors for early dislocation following primary ...

Abstract	Background: The role of acetabular and femoral component positions with respect to the risk of post-operative instability and dislocation remains debated. In this study, we aimed to identify potential risk factors for early dislocation following primary total hip arthroplasty (THA) for displaced intracapsular femoral neck fractures (FNF) using radiological measurements. Methods: We retrospectively analyzed data for patients who underwent cementless primary THA for FNF using a posterolateral approach between January 2018 and December 2021. Follow-up duration, age, sex, affected side, and mean time from THA to dislocation were recorded. Leg-length inequality, abductor lever arm, vertical and horizontal femoral offsets, vertical and horizontal hip centers of rotation, abduction, anteversion of the acetabulum and femoral prosthesis, and combined anteversion were measured. Results: The study sample included 17 men and 34 women, with 21 and 30 patients undergoing left- and right-hip operations, respectively. The mean patient age was 70.18 ± 7.64 years, and the mean follow-up duration was 27.73 ± 13.52 months. The mean time between THA and dislocation was 1.58 ± 0.79 months. Seven patients (13.73%) sustained posterior dislocation of the hip. The abduction angle (36.05 ± 6.82° vs. 45.68 ± 8.78°) (p = 0.008) and anteversion of the femoral prosthesis (8.26 ± 4.47° vs. 19.47 ± 9.01°) (p = 0.002) were significantly lower in the dislocation group than in the control group. There were no significant differences in other parameters. Conclusions: Insufficient stem antetorsion combined with lower abduction angle of the acetabular component were associated with a high risk of dislocation, especially in patients with deep flexion or internal rotation of the flexed hip joint and knees, or in patients with a stiff spine or anterior pelvic tilt, impingement may then occur in the neck of the prosthesis and cup component, ultimately resulting in posterior dislocation. These findings could remind surgeons to avoid simultaneous occurrence of both in THA surgery. These results provide new insight into risk factors for hip dislocation in patients undergoing primary THA for FNF and may aid in reducing the risk of instability and dislocation. Level of evidence: Prospective comparative study Level II.
MeSH term(s)	Male ; Humans ; Female ; Middle Aged ; Aged ; Arthroplasty, Replacement, Hip/adverse effects ; Arthroplasty, Replacement, Hip/methods ; Hip Dislocation/diagnostic imaging ; Hip Dislocation/epidemiology ; Hip Dislocation/etiology ; Retrospective Studies ; Prospective Studies ; Joint Dislocations/surgery ; Femoral Neck Fractures/diagnostic imaging ; Femoral Neck Fractures/surgery ; Femoral Neck Fractures/complications ; Risk Factors ; Hip Prosthesis/adverse effects
Language	English
Publishing date	2024-01-30
Publishing country	England
Document type	Journal Article
ZDB-ID	2041355-5
ISSN	1471-2474 ; 1471-2474
ISSN (online)	1471-2474
ISSN	1471-2474
DOI	10.1186/s12891-024-07199-2
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Article: Long non-coding RNA small nucleolar RNA host gene 1 knockdown suppresses the proliferation, migration and invasion of osteosarcoma cells by regulating microRNA-424-5p/FGF2

Li, Zhuokai / Wang, Xiaohe / Liang, Shuofu

Experimental and therapeutic medicine

2021 Volume 21, Issue 4, Page(s) 325

Abstract: The aim of the present study was to clarify the effect of long non-coding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) on the proliferation, migration and invasion of osteosarcoma (OS) cells and to explore the potential underlying mechanisms. The ...

Abstract	The aim of the present study was to clarify the effect of long non-coding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) on the proliferation, migration and invasion of osteosarcoma (OS) cells and to explore the potential underlying mechanisms. The expression levels of SNHG1, microRNA (miR)-424-5p and fibroblast growth factor 2 (FGF2) in OS tissues and cells were detected using reverse transcription-quantitative polymerase chain reaction. OS cell proliferation, migration and invasion were analysed by MTT, wound healing and Transwell invasion assays, respectively. The targeting relationships between SNHG1 and miR-424-5p, as well as between miR-424-5p and FGF2, were confirmed using RNA-binding protein immunoprecipitation and/or dual-luciferase reporter gene assays. The results demonstrated that the expression levels of SNHG1 and FGF2 were upregulated, whereas the expression of miR-424-5p was downregulated in OS tissues and cells. The silencing of SNHG1 significantly inhibited the proliferation, migration and invasion of OS cells. Additionally, FGF2 was shown to be a target of miR-424-5p, which in turn, was a target of SNHG1. miR-424-5p silencing and FGF2 overexpression both reversed the suppressive effects of SNHG1 knockdown on the proliferation, migration and invasion of OS cells. Thus, the silencing of SNHG1 may inhibit the proliferation, migration and invasion of OS cells by regulating the miR-424-5p/FGF2 axis.
Language	English
Publishing date	2021-02-05
Publishing country	Greece
Document type	Journal Article
ZDB-ID	2683844-8
ISSN	1792-1015 ; 1792-0981
ISSN (online)	1792-1015
ISSN	1792-0981
DOI	10.3892/etm.2021.9756
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Article: miR-221-3p regulates hepatocellular carcinoma cell proliferation, migration and invasion via targeting LIFR.

Tan, Wei / Li, Zhuokai / Xia, Weifen / Zhu, Jinde / Fan, Rengen

Annals of hepatology

2021 Volume 27 Suppl 1, Page(s) 100567

Abstract: Introduction and objectives: Hepatocellular carcinoma (HCC) is one of the most common and fatal cancers in the world. This study aims to investigate the mechanism by which miR-221-3p regulates HCC cell proliferation, migration and invasion, so as to ... ...

Abstract	Introduction and objectives: Hepatocellular carcinoma (HCC) is one of the most common and fatal cancers in the world. This study aims to investigate the mechanism by which miR-221-3p regulates HCC cell proliferation, migration and invasion, so as to provide a new idea for targeted therapy towards HCC. Materials and methods: Expression quantification data including mature miRNA and mRNA were accessed from TCGA-LIHC dataset, and matched clinical information was obtained as well, which helped identify the miRNA of interest. Thereafter, effect of the miRNA on HCC cell biological functions was assessed with a series of in vitro experiments, such as qRT-PCR, MTT, wound healing assay and Transwell. To gain more insight into the mechanism of the miRNA in HCC, bioinformatics method was conducted to predict downstream target gene. The potential targeting relationship between the miRNA and the predicted mRNA was validated by dual-luciferase reporter assay. Western blot was performed to test protein expression. Results: MiR-221-3p identified by differential expression analysis was found to be significantly elevated in HCC tissue. Overexpressing miR-221-3p noticeably enhanced HCC cell proliferative, migratory and invasive abilities. Leukemia inhibitory factor receptor (LIFR), confirmed as a downstream target of miR-221-3p in HCC by dual-luciferase reporter assay, was poorly expressed in HCC tissue and cells. Additionally, the expression of LIFR was decreased following the targeted binding between miR-221-3p and LIFR 3'-UTR, while increasing the expression of LIFR attenuated the promoting effect of miR-221-3p on HCC cells. Conclusion: MiR-221-3p is an oncogene in HCC cells, and it exerts its role in HCC cell viability and motility via targeting LIFR.
MeSH term(s)	Carcinoma, Hepatocellular/pathology ; Cell Line, Tumor ; Cell Movement/genetics ; Cell Proliferation/genetics ; Humans ; Leukemia Inhibitory Factor Receptor alpha Subunit ; Liver Neoplasms/pathology ; MicroRNAs/metabolism ; Receptors, OSM-LIF
Chemical Substances	LIFR protein, human ; Leukemia Inhibitory Factor Receptor alpha Subunit ; MIRN221 microRNA, human ; MicroRNAs ; Receptors, OSM-LIF
Language	English
Publishing date	2021-10-23
Publishing country	Mexico
Document type	Journal Article
ZDB-ID	2188733-0
ISSN	1665-2681
ISSN	1665-2681
DOI	10.1016/j.aohep.2021.100567
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Article: EMP1 as a Potential Biomarker in Liver Fibrosis: A Bioinformatics Analysis.

Chen, Xuchen / Lv, Xinliang / Han, Manman / Hu, Yexiao / Zheng, Wanqiong / Xue, Haibo / Li, Zhuokai / Li, Kui / Tan, Wei

Gastroenterology research and practice

2023 Volume 2023, Page(s) 2479192

Abstract: Liver fibrosis is a wound-healing response to chronic injury, which may result in cirrhosis and liver failure. Studies have been carried on the mechanisms and pathogenesis of liver fibrosis. However, the potential cell-specific expressed marker genes ... ...

Abstract	Liver fibrosis is a wound-healing response to chronic injury, which may result in cirrhosis and liver failure. Studies have been carried on the mechanisms and pathogenesis of liver fibrosis. However, the potential cell-specific expressed marker genes involved in fibrotic processes remain unknown. In this study, we combined a publicly accessible single-cell transcriptome of human liver with microarray datasets to evaluate the cell-specific expression patterns of differentially expressed genes in the liver. We noticed that
Language	English
Publishing date	2023-03-22
Publishing country	Egypt
Document type	Journal Article
ZDB-ID	2435460-0
ISSN	1687-630X ; 1687-6121
ISSN (online)	1687-630X
ISSN	1687-6121
DOI	10.1155/2023/2479192
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Article: Exosomes Isolated From Bone Marrow Mesenchymal Stem Cells Exert a Protective Effect on Osteoarthritis via lncRNA LYRM4-AS1-GRPR-miR-6515-5p.

Wang, Xiuhui / Li, Zhuokai / Cui, Yin / Cui, Xu / Chen, Cheng / Wang, Zhe

Frontiers in cell and developmental biology

2021 Volume 9, Page(s) 644380

Abstract: Objectives: The aim of this study was to investigate the effects of exosomes isolated from human bone marrow mesenchymal stem cells (BMSCs) on osteoarthritis (OA) and a competitive endogenous RNA (ceRNA) network.: Methods: Exosomes were isolated from ...

Abstract	Objectives: The aim of this study was to investigate the effects of exosomes isolated from human bone marrow mesenchymal stem cells (BMSCs) on osteoarthritis (OA) and a competitive endogenous RNA (ceRNA) network. Methods: Exosomes were isolated from human BMSCs and characterized by transmission electron microscopy (TEM), Nanosight (NTA), and western blotting. Chondrocytes were treated with interleukin-1β (IL-1β) and then transfected with exosomes. Cell viability and apoptosis were determined using Cell Counting Kit-8 (CCK-8) and flow cytometry, respectively. Cells with IL-1β and exosomes were sequenced, and differentially expressed lncRNAs (DE-lncRNAs) and miRNAs (DE-miRNAs) were identified. Thereafter, a ceRNA network (LYRM4-AS1-GRPR-miR-6515-5p) was chosen for further validation. Results: TEM, NTA, and western blotting showed that exosomes were successfully isolated, and PKH67 staining showed that exosomes could be taken up by IL-1β-induced chondrocytes. Compared with the control group, IL-1β significantly decreased cell viability and promoted apoptosis ( Conclusion: Exosomes may alleviate OA inflammation by regulating the LYRM4-AS1/GRPR/miR-6515-5p signaling pathway.
Language	English
Publishing date	2021-05-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2021.644380
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Article ; Online: Baicalein ameliorates osteoporosis via AKT/FOXO1 signaling.

Cai, Pan / Lu, Yan / Yin, Zhifeng / Wang, Xiuhui / Zhou, Xiaoxiao / Li, Zhuokai

Aging

2021 Volume 13, Issue 13, Page(s) 17370–17379

Abstract: In this study, we used bioinformatics and ... ...

Abstract	In this study, we used bioinformatics and an
MeSH term(s)	3T3 Cells ; Animals ; Bone Density Conservation Agents/pharmacology ; Bone and Bones/drug effects ; Bone and Bones/metabolism ; Calcification, Physiologic/drug effects ; Calcification, Physiologic/genetics ; Cyclin D1/genetics ; Databases, Factual ; Extracellular Matrix/metabolism ; Flavanones/pharmacology ; Forkhead Box Protein O1/drug effects ; Forkhead Box Protein O1/genetics ; Glucocorticoids ; Humans ; Mice ; Osteoporosis/chemically induced ; Osteoporosis/drug therapy ; PTEN Phosphohydrolase/genetics ; Proto-Oncogene Proteins c-akt/drug effects ; Proto-Oncogene Proteins c-akt/genetics ; Signal Transduction/drug effects ; TOR Serine-Threonine Kinases/genetics
Chemical Substances	Bone Density Conservation Agents ; CCND1 protein, human ; FOXO1 protein, human ; Flavanones ; Forkhead Box Protein O1 ; Glucocorticoids ; Cyclin D1 (136601-57-5) ; baicalein (49QAH60606) ; MTOR protein, human (EC 2.7.1.1) ; TOR Serine-Threonine Kinases (EC 2.7.1.1) ; AKT1 protein, human (EC 2.7.11.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; PTEN Phosphohydrolase (EC 3.1.3.67) ; PTEN protein, human (EC 3.1.3.67)
Language	English
Publishing date	2021-07-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1945-4589
ISSN (online)	1945-4589
DOI	10.18632/aging.203227
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Article ; Online: Trophinin Is an Important Biomarker and Prognostic Factor in Osteosarcoma: Data Mining from Oncomine and the Cancer Genome Atlas Databases.

Cai, Pan / Lu, Yan / Yin, Zhifeng / Wang, Xiuhui / Zhou, Xiaoxiao / Li, Zhuokai

publication RETRACTED

BioMed research international

2021 Volume 2021, Page(s) 6885897

Abstract: Osteosarcoma (OS) is a type of bone malignancy with a high rate of treatment failure. To date, few evident biomarkers for the prognostic significance of OS have been established. Oncomine was used to integrate RNA and DNA-seq data from the Gene ... ...

Abstract	Osteosarcoma (OS) is a type of bone malignancy with a high rate of treatment failure. To date, few evident biomarkers for the prognostic significance of OS have been established. Oncomine was used to integrate RNA and DNA-seq data from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and the published literature. The correlation of the gene Trophinin (TRO) and different types of cancers was generated using the Cancer Cell Line Encyclopedia (CCLE) online tool. Prognostic values of featured Melanoma Antigen Gene (MAGE) members were further assessed by establishing the overall survival using the Kaplan-Meier plotter. Moreover, the online tool, Database for Annotation, Visualization and Integrated Discovery version (DAVID), was used to understand the biological meaning list of the genes. MAGEB10, MAGED2, TRO, MAGEH1, MAGEB18, MAGEB6, MAGEB4, MAGEB1, MAGED4B, MAGED1, MAGEB2, and MAGEB3 were significantly overexpressed in sarcoma. TRO was further demonstrated to be distinctively upregulated in osteosarcoma cell lines and associated with shorter overall survival. TRO may play an important role in the development of OS and may be a promising potential biomarker and prognostic factor.
MeSH term(s)	Biomarkers, Tumor/metabolism ; Bone Neoplasms/diagnosis ; Bone Neoplasms/genetics ; Bone Neoplasms/metabolism ; Cell Adhesion Molecules/metabolism ; Cell Line, Tumor ; Data Mining ; Databases, Genetic ; Gene Ontology ; Genome, Human ; Humans ; Kaplan-Meier Estimate ; Neoplasm Proteins/genetics ; Neoplasm Proteins/metabolism ; Osteosarcoma/diagnosis ; Osteosarcoma/genetics ; Osteosarcoma/metabolism ; Prognosis
Chemical Substances	Biomarkers, Tumor ; Cell Adhesion Molecules ; Neoplasm Proteins ; TRO protein, human
Language	English
Publishing date	2021-07-06
Publishing country	United States
Document type	Journal Article ; Retracted Publication
ZDB-ID	2698540-8
ISSN	2314-6141 ; 2314-6133
ISSN (online)	2314-6141
ISSN	2314-6133
DOI	10.1155/2021/6885897
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Article ; Online: Letter by Fadahunsi et al Regarding Article, "Clinical and Echocardiographic Outcomes Following Permanent Pacemaker Implantation After Transcatheter Aortic Valve Replacement Meta-Analysis and Meta-Regression".

Fadahunsi, Opeyemi / Li, Zhuokai / Donato, Anthony

Circulation. Cardiovascular interventions

2018 Volume 10, Issue 11

MeSH term(s)	Aortic Valve ; Echocardiography ; Heart Valve Prosthesis ; Pacemaker, Artificial ; Transcatheter Aortic Valve Replacement
Language	English
Publishing date	2018-01-11
Publishing country	United States
Document type	Letter ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	2450797-0
ISSN	1941-7632 ; 1941-7640
ISSN (online)	1941-7632
ISSN	1941-7640
DOI	10.1161/CIRCINTERVENTIONS.117.005820
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