Biorheology最新文献

{"title":"In microfluidico: Recreating in vivo hemodynamics using miniaturized devices.","authors":"Shu Zhu, B. A. Herbig, Ruizhi Li, T. Colace, Ryan W. Muthard, K. Neeves, S. Diamond","doi":"10.3233/BIR-15065","DOIUrl":"https://doi.org/10.3233/BIR-15065","url":null,"abstract":"Microfluidic devices create precisely controlled reactive blood flows and typically involve: (i) validated anticoagulation/pharmacology protocols, (ii) defined reactive surfaces, (iii) defined flow-transport regimes, and (iv) optical imaging. An 8-channel device can be run at constant flow rate or constant pressure drop for blood perfusion over a patterned collagen, collagen/kaolin, or collagen/tissue factor (TF) to measure platelet, thrombin, and fibrin dynamics during clot growth. A membrane-flow device delivers a constant flux of platelet agonists or coagulation enzymes into flowing blood. A trifurcated device sheaths a central blood flow on both sides with buffer, an ideal approach for on-chip recalcification of citrated blood or drug delivery. A side-view device allows clotting on a porous collagen/TF plug at constant pressure differential across the developing clot. The core-shell architecture of clots made in mouse models can be replicated in this device using human blood. For pathological flows, a stenosis device achieves shear rates of >100,000 s(-1) to drive plasma von Willebrand factor (VWF) to form thick long fibers on collagen. Similarly, a micropost-impingement device creates extreme elongational and shear flows for VWF fiber formation without collagen. Overall, microfluidics are ideal for studies of clotting, bleeding, fibrin polymerization/fibrinolysis, cell/clot mechanics, adhesion, mechanobiology, and reaction-transport dynamics.","PeriodicalId":9167,"journal":{"name":"Biorheology","volume":"52 5-6 1","pages":"303-18"},"PeriodicalIF":1.1,"publicationDate":"2016-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/BIR-15065","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69792955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Laudatio for Harry Goldsmith.","authors":"S. Chien","doi":"10.3233/BIR-150675","DOIUrl":"https://doi.org/10.3233/BIR-150675","url":null,"abstract":"Professor Harry Goldsmith was born May 11, 1928, in Nurnberg, Germany. His marvelous journey in science started with his undergraduate study at Oxford University, where he received B.A. (Honours) in Chemistry and B.Sc. in Physical Chemistry in 1950 and 1951, respectively. After serving as a Technical Officer at Imperial Chemical Industries Ltd. in Manchester, UK, for six years, and as a Defence Research Board Fellow at Royal Military College of Canada for one year, Harry began his Ph.D. study in Chemistry at McGill University, Montreal, in 1958. Under the advisorship of the late Dr. Stanley G. Mason of the Pulp and Paper Research Institute, Harry completed his outstanding thesis on The Microrheology of Suspensions in 1961. After three years of postdoctoral training in the Department of Chemistry at McGill University, Harry was appointed as an Assistant Professor in the Department of Experimental Medicine in 1964 and was promoted to Associate Professor in 1969. In 1972, he became Full Professor in the Division of Experimental Medicine in the Department of Medicine at McGill, and he was Director of the Division from 1976 to 1995. In addition to his stellar research contributions, Harry played a major leadership role in the education of graduate students and the administration of the Division. Harry Goldsmith made outstanding contributions to the theory and application of rheology. He established the fundamental principle of the rheological behavior of particles in suspension by a combination of ingenious experiments and elegant analysis. The 176-page Chapter on “The Microrheology of Dispersions” by Harry Goldsmith and Stanley Mason in F.R. Eirich’s book in 1967 [1] is a Classic. This marvelous chapter established the fundamental principles of particle motion in laminar and non-uniform flows, with applications to suspension viscosity and blood rheology in large and small vessels, covering the entire field of microrheology, including blood rheology. Having started to work on blood rheology only a few years before, I found this Chapter to be a treasure and read it many times. It gave me tremendous inspiration and had great influence throughout the years on my studies on biorheology. Harry Goldsmith is not only a superb scientist, but also an ingenious designer of instruments for his sophisticated research. For example, his traveling microscopy system allowed the tracking of cells flowing in a tube by the controlled motion of the tube with a velocity that is equal and opposite to that of the cell, thus keeping the cell always in the field of observation for dynamic cinematographic filming and quantitative analysis. He has performed experiments on particles, red blood cells, white blood cells, platelets, and other types of cells. He has the unique capability to apply elegant hydrodynamic theory to analyze such quantitative experiments on individual or groups of cells in terms of their translation, rotation, collision, deformation, adhesion, and aggregat","PeriodicalId":9167,"journal":{"name":"Biorheology","volume":"52 5-6 1","pages":"295-9"},"PeriodicalIF":1.1,"publicationDate":"2016-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/BIR-150675","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69793137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An integrative toy model of cell flattening, spreading, and ruffling.","authors":"M. Herant, M. Dembo","doi":"10.3233/BIR-14042","DOIUrl":"https://doi.org/10.3233/BIR-14042","url":null,"abstract":"BACKGROUND\u0000The processes of cell spreading and crawling are frequently associated with mysterious waves and ruffling cycles of the leading edge.\u0000\u0000\u0000OBJECTIVE\u0000To develop a physical model that can account for these phenomena based on a few simple and plausible rules governing adhesion, contractility, polymerization of cytoskeleton, and membrane tension.\u0000\u0000\u0000METHODS\u0000Extension of a continuum mechanical model of phagocytosis [J Cell Sci. (2006);119(Pt 9):1903-13] adding a simple coupling between membrane curvature and cytoskeletal polymerization.\u0000\u0000\u0000RESULTS\u0000We show that our generalized model has just the right nonlinearity needed for triggering of stochastic/chaotic cycles of ruffling similar to those that are observed in real cells.\u0000\u0000\u0000CONCLUSIONS\u0000The cycles are caused by a branching instability at the leading edge that leads to bifurcations of protrusion into forward moving lamellipodium and upward and rearward folding ruffles. The amplitude of the instability is modulated by the surface tension, with higher tension stabilizing against ruffling (but inhibiting protrusion) and lower tension promoting ruffling and protrusion.","PeriodicalId":9167,"journal":{"name":"Biorheology","volume":"52 5-6 1","pages":"405-14"},"PeriodicalIF":1.1,"publicationDate":"2016-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/BIR-14042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69792009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of L-selectin-dependent hydrodynamic shear thresholding by leukocyte deformability and shear dependent bond number.","authors":"C. D. Paschall, A. Klibanov, M. Lawrence","doi":"10.3233/BIR-15064","DOIUrl":"https://doi.org/10.3233/BIR-15064","url":null,"abstract":"BACKGROUND\u0000During inflammation leukocyte attachment to the blood vessel wall is augmented by capture of near-wall flowing leukocytes by previously adherent leukocytes. Adhesive interactions between flowing and adherent leukocytes are mediated by L-selectin and P-selectin Glycoprotein Ligand-1 (PSGL-1) co-expressed on the leukocyte surface and ultimately regulated by hydrodynamic shear thresholding.\u0000\u0000\u0000OBJECTIVE\u0000We hypothesized that leukocyte deformability is a significant contributory factor in shear thresholding and secondary capture.\u0000\u0000\u0000METHODS\u0000Cytochalasin D (CD) was used to increase neutrophil deformability and fixation was used to reduce deformability. Neutrophil rolling on PSGL-1 coated planar surfaces and collisions with PSGL-1 coated microbeads were analyzed using high-speed videomicroscopy (250 fps).\u0000\u0000\u0000RESULTS\u0000Increased deformability led to an increase in neutrophil rolling flux on PSGL-1 surfaces while fixation led to a decrease in rolling flux. Abrupt drops in flow below the shear threshold resulted in extended release times from the substrate for CD-treated neutrophils, suggesting increased bond number. In a cell-microbead collision assay lower flow rates were correlated with briefer adhesion lifetimes and smaller adhesive contact patches.\u0000\u0000\u0000CONCLUSIONS\u0000Leukocyte deformation may control selectin bond number at the flow rates associated with hydrodynamic shear thresholding. Model analysis supported a requirement for both L-selectin catch-slip bond properties and multiple bond formation for shear thresholding.","PeriodicalId":9167,"journal":{"name":"Biorheology","volume":"52 5-6 1","pages":"415-32"},"PeriodicalIF":1.1,"publicationDate":"2016-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/BIR-15064","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69792773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of neutral polymers on the mechanics of red blood cell adhesion onto coated glass surfaces.","authors":"Zhang Zhengwen, H. Meiselman, B. Neu","doi":"10.3233/BIR-15044","DOIUrl":"https://doi.org/10.3233/BIR-15044","url":null,"abstract":"BACKGROUND\u0000Cell-cell and cell-surface adhesion modulated by water-soluble polymers continues to be of current interest, especially since prior reports have indicated a role for depletion-mediated attractive forces.\u0000\u0000\u0000OBJECTIVE\u0000To determine the effects of concentration and molecular mass of the neutral polymer dextran (40 kDa to 28 MDa) on the adhesion of human red blood cells (RBC) to coated glass coverslips.\u0000\u0000\u0000METHODS\u0000Confocal-reflection interference contrast microscopy (C-IRM), in conjunction with phase contrast imaging, was utilized to measure the adhesion dynamics and contact mechanics of RBC during the initial stages of cell contact with several types of substrates.\u0000\u0000\u0000RESULTS\u0000Adhesion is markedly increased in the presence of dextran with a molecular mass ⩾ 70 kDa. This increased adhesiveness is attributed to reduced surface concentration of the large polymers and hence increased attractive forces due to depletion interaction. The equilibrium deformation of adhering RBC was modeled as a truncated sphere and the calculated adhesion energies were in close agreement with theoretical results.\u0000\u0000\u0000CONCLUSIONS\u0000These results clearly demonstrate that polymer depletion can promote RBC adhesion to artificial surfaces and suggest that this phenomenon may play a role in other specific and non-specific cell-cell interactions, such as rouleau formation and RBC-endothelial cell adhesion.","PeriodicalId":9167,"journal":{"name":"Biorheology","volume":"52 5-6 1","pages":"379-89"},"PeriodicalIF":1.1,"publicationDate":"2016-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/BIR-15044","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69792615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of matrix metalloproteases in the kinetics of leukocyte-endothelial adhesion in post-capillary venules.","authors":"H. Lipowsky, A. Lescanic, Rachna Sah","doi":"10.3233/BIR-15063","DOIUrl":"https://doi.org/10.3233/BIR-15063","url":null,"abstract":"BACKGROUND\u0000The endothelial glycocalyx serves as a barrier to leukocyte (WBC)-endothelium (EC) adhesion. Shedding of glycans, by matrix metalloproteases (MMPs) exposes EC integrin receptors to facilitate firm adhesion. However, the effect of shedding on the strength of the adhesive bond remains to be determined.\u0000\u0000\u0000OBJECTIVES\u0000Examine the effect of MMP inhibition on the kinetics of WBC-EC adhesion under normal and inflammatory conditions to delineate differences in the duration and number of adhesive bonds.\u0000\u0000\u0000METHODS\u0000WBC adhesion in post-capillary venules was observed in rat mesentery. Adhesion duration and off-rates (KOFF) were correlated with shear stress during adhesion in response to 1 µM fMLP or 0.5 µM doxycycline (doxy, to inhibit MMP activation).\u0000\u0000\u0000RESULTS\u0000Doxy increased mean adhesion time significantly from 2.5 (control) to 5.6 s, whereas fMLP increased it 8-fold to 20 s, which was not affected by pre-treatment with doxy. Estimates of the number of adhesive bonds (simplified Bell-model) revealed a significantly greater increase with fMLP compared to doxy alone, with no effect on fMLP by pretreatment with doxy. With doxy alone, KOFF was significantly 4-fold greater compared to fMLP, suggesting a much weaker bond.\u0000\u0000\u0000CONCLUSIONS\u0000Although the increased number of bonds by MMP inhibition with doxy alone and fMLP were similar, the bonds due to doxy appeared weaker as evidenced by their shorter duration, and lesser reduction in KOFF relative to control. Thus doxy limits the availability of integrin binding sites during fMLP stimulated adhesion, but has a pro-adhesive effect due to increased ligands for WBC binding that arises from inhibition of normal sheddase activity on the EC.","PeriodicalId":9167,"journal":{"name":"Biorheology","volume":"52 5-6 1","pages":"433-45"},"PeriodicalIF":1.1,"publicationDate":"2016-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/BIR-15063","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69792511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leukocyte arrest: Biomechanics and molecular mechanisms of β2 integrin activation.","authors":"Zhichao Fan, K. Ley","doi":"10.3233/BIR-15085","DOIUrl":"https://doi.org/10.3233/BIR-15085","url":null,"abstract":"Integrins are a group of heterodimeric transmembrane receptors that play essential roles in cell-cell and cell-matrix interaction. Integrins are important in many physiological processes and diseases. Integrins acquire affinity to their ligand by undergoing molecular conformational changes called activation. Here we review the molecular biomechanics during conformational changes of integrins, integrin functions in leukocyte biorheology (adhesive functions during rolling and arrest) and molecules involved in integrin activation.","PeriodicalId":9167,"journal":{"name":"Biorheology","volume":"52 5-6 1","pages":"353-77"},"PeriodicalIF":1.1,"publicationDate":"2016-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/BIR-15085","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69792808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The autodigestion hypothesis: Proteolytic receptor cleavage in rheological and cardiovascular cell dysfunction1.","authors":"Geert W Schmid-Schönbein","doi":"10.3233/BIR-17131","DOIUrl":"https://doi.org/10.3233/BIR-17131","url":null,"abstract":"<p><p>Transformation of circulating leukocytes from a dormant into an activated state with changing rheological properties leads to a major shift of their behavior in the microcirculation. Low levels of pseudopod formation or expression of adhesion molecules facilitate relatively free passage through microvessels while activated leukocytes with pseudopods and enhanced levels of adhesion membrane proteins become trapped in microvessels, attach to the endothelium and migrate into the tissue. The transformation of leukocytes into an activated state is seen in many diseases. While mechanisms for activation due to infections, tissue trauma, as well as non-physiological biochemical or biophysical exposures are well recognized, the mechanisms for activation in many diseases have not been conclusively liked to these traditional mechanisms and remain unknown. We summarize our recent evidence suggesting a major and surprising role of digestive enzymes in the small intestine as root causes for leukocyte activation and microvascular disturbances. During normal digestion of food digestive enzymes are compartmentalized in the lumen of the intestine by the mucosal epithelial barrier. When permeability of this barrier increases, these powerful degrading enzymes leak into the wall of the intestine and into the systemic circulation. Leakage of digestive enzymes occurs for example in physiological shock and multi-organ failure. Entry of digestive enzymes into the wall of the small intestine leads to degradation of the intestinal tissue in an autodigestion process. The digestive enzymes and tissue/food fragments generate not only activate leukocytes but also cause numerous cell dysfunctions. For example, proteolytic destruction of membrane receptors, plasma proteins and other biomolecules occurs. We conclude that escape of digestive enzymes from the intestinal track serves as a major source of cell dysfunction, morbidity and even mortality, including abnormal leukocyte activation seen in rheological studies.</p>","PeriodicalId":9167,"journal":{"name":"Biorheology","volume":"53 5-6","pages":"179-191"},"PeriodicalIF":1.1,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/BIR-17131","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34791298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The expression dynamics of mechanosensitive genes in extra-embryonic vasculature after heart starts to beat in chick embryo.","authors":"Saranya Rajendran, L. Sundaresan, K. Rajendran, Monica Selvaraj, Ravi Gupta, S. Chatterjee","doi":"10.3233/BIR-15075","DOIUrl":"https://doi.org/10.3233/BIR-15075","url":null,"abstract":"BACKGROUND Fluid flow plays an important role in vascular development. However, the detailed mechanisms, particularly the link between flow and modulation of gene expression during vascular development, remain unexplored. In chick embryo, the key events of vascular development from initiation of heart beat to establishment of effective blood flow occur between the stages HH10 and HH13. Therefore, we propose a novel in vivo model to study the flow experienced by developing endothelium. OBJECTIVE Using this model, we aimed to capture the transcriptome dynamics of the pre- and post-flow conditions. METHODS RNA was isolated from extra embryonic area vasculosa (EE-AV) pooled from three chick embryos between HH10-HH13 and RNA sequencing was performed. RESULTS The whole transcriptome sequencing of chick identified up-regulation of some of the previously well-known mechanosensitive genes including NFR2, HAND1, CTGF and KDR. GO analyses of the up-regulated genes revealed enrichment of several biological processes including heart development, extracellular matrix organization, cell-matrix adhesion, cell migration, blood vessel development, patterning of blood vessels, collagen fibril organization. Genes encoding for gap junctions proteins which are involved in vascular remodeling and arterial-venous differentiation, and genes involved in cell-cell adhesion, and ECM interactions were significantly up-regulated. Validation of selected genes through semi quantitative PCR was performed. CONCLUSION The study indicates that shear stress plays a major role in development. Through appropriate validation, this platform can serve as an in vivo model to study conditions of disturbed flow in pathology as well as normal flow during development.","PeriodicalId":9167,"journal":{"name":"Biorheology","volume":"53 1 1","pages":"33-47"},"PeriodicalIF":1.1,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/BIR-15075","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69792719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effects of drag-reducing polymers in a rat model of monocrotaline-induced pulmonary hypertension.","authors":"Yali Wang, F. Hu, Xiaoyan Mu, Feng Wu, Dechun Yang, Guixiang Zheng, Xiaoning Sun, Kaizheng Gong, Zhen-gang Zhang","doi":"10.3233/BIR-15062","DOIUrl":"https://doi.org/10.3233/BIR-15062","url":null,"abstract":"OBJECTIVES Drag-reducing polymers (DRPs) are blood-soluble macromolecules which may increase blood flow and reduce vascular resistance. The purpose of the present study was to observe the effect of DRPs on monocrotaline-induced pulmonary hypertension (PH) in the rat model. METHODS A total of 64 male Wistar rats were randomly divided into four groups: Group I (pulmonary hypertension model + DRP treatment); Group II (pulmonary hypertension model + saline treatment); Group III (control + DRP treatment); Group IV (control + saline treatment). After five weeks, comparisons were made of the following indices: survival rate, body weight, blood pressure, right ventricular systolic pressure, right ventricular hypertrophy, wall thickness of pulmonary arteries, the internal diameter of small pulmonary arteries, plasma IL-1β and IL-6. RESULTS The survival rate after 5 weeks varied significantly across all groups (P=0.013), but the survival rates of Groups I and II were not statistically significantly different. Administration of DRP (intravenous injection twice weekly) attenuated the PH-induced increase in right ventricular systolic pressure and suppressed the increases in right ventricular (RV) weight and the ratio of right ventricular weight to left ventricle plus septum weight (RV/LV + S). DRP treatment also significantly decreased the wall thickness of pulmonary arteries, augmented the internal diameter of small pulmonary arteries, and suppressed increases in the plasma levels of IL-1β and IL-6. CONCLUSIONS DRP treatment with intravenous injection effectively inhibited the development of monocrotaline-induced pulmonary hypertension in the rat model. DRPs may have potential application for the treatment of pulmonary hypertension.","PeriodicalId":9167,"journal":{"name":"Biorheology","volume":"53 1 1","pages":"13-22"},"PeriodicalIF":1.1,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/BIR-15062","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69792395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}