Lymphokine and cytokine research最新文献

{"title":"Estrogen modulates the expression of tumor necrosis factor alpha mRNA in phorbol ester-stimulated human monocytic THP-1 cells.","authors":"G Shanker,&nbsp;M Sorci-Thomas,&nbsp;M R Adams","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Monokines, including tumor necrosis factor alpha (TNF-alpha), have been implicated in the pathogenesis of several pathologic processes, including atherosclerosis. Because estrogen has been found to offer a certain degree of protection against atherosclerotic progression, we examined the effect of estrogen on the expression of TNF-alpha mRNA in a monocyte-macrophage cell line, THP-1. Cells were exposed to 12-O-tetradecanoylphorbol 13-acetate (TPA, 50 ng/ml) for 48 or 96 h to induce differentiation. Some of the cells were treated with lipopolysaccharide (LPS, 10 micrograms/ml) in the last 3 h and/or ethinyl estradiol (estrogen, 10(-9) M) in the last 20 h. Total cellular RNA was isolated and cDNA synthesized and than coamplified using the polymerase chain reaction (PCR) in the presence of two sets (pairs) of 32P-labeled primers, one for TNF-alpha (product size 325 bp) and the second for the internal control, glyceraldehyde 3-phosphate dehydrogenase (G3PDH; 983 bp). The resultant PCR products were separated by agarose gel electrophoresis, and the ratios of radioactivity incorporated into TNF-alpha PCR products to G3PDH products were used to assess the relative changes in the levels of TNF-alpha mRNA abundance in response to various substances. Treatment with TPA for 48 h induced the expression of TNF-alpha mRNA. Treatment of these TPA-stimulated cells with estrogen caused a 62% decrease in TNF-alpha message abundance (p < 0.01). Similar results were obtained with cells stimulated with TPA for 96 h.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":77246,"journal":{"name":"Lymphokine and cytokine research","volume":"13 6","pages":"377-82"},"PeriodicalIF":0.0,"publicationDate":"1994-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18707722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interleukin-7 selectively enhances natural kill cytotoxicity mediated by the CD56bright natural killer subpopulation.","authors":"R Dadmarz,&nbsp;D C Bockstoce,&nbsp;S H Golub","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Both the CD56bright and CD56dim NK cell subpopulation mediate non-major histocompatibility complex-restricted cytolysis of NK-sensitive tumor cell lines, and IL-2-dependent augmentation of cytolysis and proliferation of CD56bright and CD56dim NK cells was recently reported. We investigated the effects of IL-7 and IL-6 on the killing mediated by these cells to determine whether other cytokines besides IL-2 regulate their activity. IL-7 increased the cytotoxicity in only the CD56bright NK cell population. The effect of IL-7 varied from donor to donor but was comparable to that of IL-2. Furthermore, IL-7 was found to induce lymphokine-activated killer (LAK) cell generation primarily in the CD56bright cells. CD56bright NK cells also proliferated in response to IL-7, but only weakly in comparison with IL-2. In contrast to the results with CD56bright NK cells, IL-7 had little effect on the CD56dim subset. However, IL-2 enhanced NK cytotoxicity, induced LAK activity, and caused proliferation of these cells. An anti-IL-2 antibody did not inhibit the IL-7-induced increase in CD56bright cytotoxicity, suggesting that IL-7 acted independently of IL-2. However, the IL-7 effect on CD56bright NK cell cytotoxicity was partially inhibited by anti-CD2, anti-CD11a, and anti-CD18 antibodies and almost completely abrogated by a combination of anti-CD2 and anti-CD11a. These data suggest that cell adhesion molecules (CAM) play a role in the regulation of IL-7-induced CD56bright NK cell cytolysis. In contrast to IL-7-mediated effects, IL-6 alone had no effect on CD56+ NK cell cytotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":77246,"journal":{"name":"Lymphokine and cytokine research","volume":"13 6","pages":"349-57"},"PeriodicalIF":0.0,"publicationDate":"1994-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18541699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of interleukin-2 on bone resorption and natural immunity in osteopetrotic (ia) rats.","authors":"G B Schneider,&nbsp;M Relfson","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Cells of the immune system and the cytokines they produce have been shown to function in the regulation of bone turnover. Incisors absent (ia) osteopetrotic rats demonstrate defects in natural immunity and bone resorption, even though they have excess numbers of both natural killer (NK) cells and osteoclasts. In an attempt to correct these defects, mutant (ia) and normal rats were infused with 3 x 10(4)U recombinant interleukin-2 (rIL-2)/day for 14 days using osmotic minipumps. The effects of IL-2 on natural immune function and bone resorption were evaluated after the infusion period. The percentage of NK cells in the spleen after treatment was quantitated by phenotypic analysis using monoclonal antibodies and flow cytometry. The elevated levels of NK cells normally seen in ia mutants were reduced to normal in the IL-2-infused rats. NK cell activity was evaluated by the 51Cr release assay and found to be enhanced to normal killing levels in the IL-2-treated mutants. The defects in NK function are corrected by IL-2 therapy. Likewise, the bone resorption defect appears to be corrected by the IL-2 infusions. The bone marrow cavity size was significantly increased in the IL-2-treated mutants compared with control mutants. Additionally, the percentage of osteoclasts exhibiting normal morphology was significantly increased in the IL-2-treated mutants. The bone density of the caudal vertebrae, evaluated by gray-scale analysis of x-rays, was found to be reduced in the IL-2-treated mutants. Interleukin-2 corrects both the bone resorption and natural immune defects in the ia mutation.</p>","PeriodicalId":77246,"journal":{"name":"Lymphokine and cytokine research","volume":"13 6","pages":"335-41"},"PeriodicalIF":0.0,"publicationDate":"1994-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18705692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of therapy with interleukin-1 receptor antagonist on pulmonary cytokine expression following hemorrhage and resuscitation.","authors":"E Abraham,&nbsp;J Allbee","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Acute lung injury frequently develops following hemorrhage and is characterized by increased proinflammatory cytokine levels and massive neutrophil accumulation in the lung. Blood loss produces rapid increases in IL-1 alpha and IL-1 beta mRNA expression among pulmonary cell populations. To examine the role of IL-1 in producing acute inflammatory lung injury after hemorrhage, we treated mice following hemorrhage and resuscitation with recombinant interleukin-1 receptor antagonist (IL-1Ra), a competitive inhibitor of the actions of IL-1. Therapy with IL-1Ra prevented the posthemorrhage increases in pulmonary TNF-alpha levels normally found after blood loss. Administration of IL-1Ra also diminished the increases in IL-1 beta and IL-6 mRNA levels that occur in the lungs following hemorrhage. However, the amounts of TNF-alpha and IFN-gamma mRNA among intraparenchymal pulmonary mononuclear cells remained elevated after hemorrhage despite therapy with IL-1Ra. These results indicate that therapy with IL-1Ra in the posthemorrhage period is capable of normalizing the expression of some, but not all, of the proinflammatory cytokines whose production among pulmonary cellular populations is increased by blood loss.</p>","PeriodicalId":77246,"journal":{"name":"Lymphokine and cytokine research","volume":"13 6","pages":"343-7"},"PeriodicalIF":0.0,"publicationDate":"1994-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18707719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of epidermal cytokine profiles in sensitization and elicitation phases of allergic contact dermatitis as well as irritant contact dermatitis in mouse skin.","authors":"S Kondo,&nbsp;S Pastore,&nbsp;G M Shivji,&nbsp;R C McKenzie,&nbsp;D N Sauder","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Epidermal cytokines are known to participate in the initiation of immune and inflammatory processes in the skin. In the present study, we examined epidermal cytokine mRNA levels to elucidate the initial molecular events in the sensitization and elicitation phases of allergic contact dermatitis (ACD) as well as in irritant contact dermatitis (ICD). BALB/c mice were sensitized on the dorsal skin with 0.5% dinitrofluorobenzene (DNFB) and challenged with 0.2% DNFB on the ears 6 days later to elicit allergic contact hypersensitivity (ACDe), the elicitation phase. To examine cytokine profiles during the sensitization phase from the same anatomic area, other animals were sensitized on ear instead of dorsal skin. The sensitization phase of ACD (ACDs) was induced by painting the ears of naive mice with 0.5% DNFB. Sodium lauryl sulfate (SLS), utilized as an irritant control, was also applied to the ears of another group of mice to induce ICD. Total RNA was extracted from the epidermis of the treated ears at various time points after each treatment, reverse transcribed to cDNA, and amplified by PCR using radiolabeled cytokine-specific primers. Amplified products were sized by electrophoresis and autoradiography and semiquantitated by densitometry. Autoradiographs were normalized relative to beta-actin signals. ACDs and ACDe showed similar patterns of cytokine mRNA levels; that is, at 6 h after hapten application, interleukin (IL)-1 beta, IL-6, IL-10, and granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA levels were upregulated, and this upregulation was observed until 24 h after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":77246,"journal":{"name":"Lymphokine and cytokine research","volume":"13 6","pages":"367-75"},"PeriodicalIF":0.0,"publicationDate":"1994-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18707721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of protein kinase enzymatic activity in Jurkat T cells during oxidative stress uncoupled from protein tyrosine kinases: role of oxidative changes in protein kinase activation requirements and generation of second messengers.","authors":"R L Whisler,&nbsp;Y G Newhouse,&nbsp;L Beiqing,&nbsp;B K Karanfilov,&nbsp;M A Goyette,&nbsp;K V Hackshaw","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Prior studies have suggested that intracellular phosphorylation events and cellular redox mechanisms may interact in regulating a variety of cellular functions, including the transcriptional activation of gene expression. Increased activity of transcriptional factors NF kappa B and AP1 has been described in cells exposed to oxidative stress and following the direct stimulation of protein kinase C (PKC) by phorbol diesters. However, the mechanisms that may contribute to redox regulation of PKC are unknown. We studied the expression of PKC activity and several second messengers in human Jurkat T cells exposed to oxidative stress in the form of H2O2. Micromolar concentrations of H2O2 rapidly induced increased cytosolic PKC enzymatic activity in Jurkat T cells that was associated with a marked arrest of cellular proliferation. The increase in cytosolic PKC activity in cells treated with H2O2 was accompanied by elevations in intracellular free calcium ([Ca2+]i), generation of inositol phosphates, and release of arachidonic acid. Functional studies showed that H2O2 enhancement of cytosolic PKC activity required phospholipase C activity but was not primarily mediated by arachidonic acid. The response of PKC to oxidative stress displayed a lack of Ca2+ dependence and was uncoupled from the activity of protein tyrosine kinases (PTK). Furthermore, the reduced activation requirements of PKC from cells treated with H2O2 were associated with shifts in elution profiles of PKC enzymatic activity after Mono-Q chromatography. These shifts appeared to represent intrinsic changes in the conformation of PKC induced by oxidative stress because western blotting failed to reveal any PKC cleavage products or reductions in native PKC alpha or beta. These findings indicate that oxidative regulation of intracellular events can intersect phosphorylation events mediated by PKC through the release of second messengers as well as direct changes in PKC activation requirements. Moreover, redox regulation of PKC is distinct from T cell receptor signaling in that the activity of PKC is uncoupled from the regulatory influences of PTK.</p>","PeriodicalId":77246,"journal":{"name":"Lymphokine and cytokine research","volume":"13 6","pages":"399-410"},"PeriodicalIF":0.0,"publicationDate":"1994-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18707724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD4+ T lymphocyte depletion attenuates lipopolysaccharide-induced tumor necrosis factor secretion by alveolar macrophages in the mouse.","authors":"N B D'Souza,&nbsp;F J Mandujano,&nbsp;S Nelson,&nbsp;W R Summer,&nbsp;J E Shellito","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Mechanisms underlying the control of cytokine secretion by alveolar macrophages are not fully understood. We hypothesized that T lymphocytes or their products modulate the capacity of alveolar macrophages to release cytokines in response to an exogenous stimulus. In this study, we investigated the role of lymphocytes expressing surface CD4 (CD4+) antigen in the regulation of tumor necrosis factor alpha (TNF-alpha) secretion by alveolar macrophages. Specific pathogen-free male BALB/c mice were injected intraperitoneally with 0.3 mg monoclonal anti-CD4 antibody or phosphate-buffered saline. Depletion of CD4+ splenic lymphocytes was confirmed 6 days later by flow cytometry. On day 6, mice were challenged intratracheally with E. coli lipopolysaccharide (LPS, 1-100 micrograms/100 g BW) or phosphate-buffered saline. The lungs were lavaged 3 h later and the bronchoalveolar lavage fluid assessed for TNF activity and cell recovery (total and differential). No TNF was detected in the lavage fluid of animals pretreated with antibody or phosphate-buffered saline and given phosphate-buffered saline intratracheally. However, the saline-treated mice challenged with LPS (100 micrograms/100 g BW) released 3.76 +/- 0.18 ng TNF/ml bronchoalveolar lavage fluid. In contrast, mice depleted of CD4+ T lymphocytes released almost 50% less TNF (1.94 +/- 0.23 ng TNF/ml lavage fluid, p < 0.001) in response to the same dose of LPS.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":77246,"journal":{"name":"Lymphokine and cytokine research","volume":"13 6","pages":"359-66"},"PeriodicalIF":0.0,"publicationDate":"1994-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18707720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alterations in L-selectin expression and elastase activity in neutrophils from patients receiving granulocyte colony-stimulating factor alone or in conjunction with high-dose chemotherapy with autologous bone marrow transplantation.","authors":"K M Rao,&nbsp;M S Currie,&nbsp;H J Cohen,&nbsp;W P Peters","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We determined L-selectin expression and elastase levels in neutrophils obtained from patients receiving granulocyte colony-stimulating factor (G-CSF) either alone (given for increasing peripheral progenitor cells for harvest) or in combination with high-dose chemotherapy with autologous bone transplantation support (BMT). Administration of G-CSF alone for 3-5 days produced a decrease in L-selectin expression in neutrophils (25 +/- 4 versus 7 +/- 1, mean +/- SEM; mean channel fluorescence, n = 10) with no effect on neutrophil elastase activity (3.1 +/- 0.3 versus 3.4 +/- 0.6; micrograms elastase/million cells; n = 9). In contrast, in patients in the BMT group the L-selectin expression was increased (26 +/- 2 versus 38 +/- 3; n = 20) and elastase activity was markedly decreased (2.9 +/- 0.2 versus 1.4 +/- 0.2, n = 12) compared with values before BMT. The changes in L-selectin expression correlated with the ability of neutrophils to adhere to human umbilical vein endothelial cells. The decrease in the neutrophil elastase activity was not associated with an increase in the plasma elastase/alpha 1-antitrypsin complex levels, indicating that the decrease in the neutrophil elastase activity is not caused by activation of neutrophils and release of the enzyme into the plasma. Administration of G-CSF alone did not cause a decrease in the neutrophil elastase activity but increased plasma elastase/alpha 1-antitrypsin complex levels. There was no change in CR3 expression on neutrophils under any of these conditions. These observations suggest that the changes seen in neutrophils during BMT are influenced by various factors associated with BMT other than the administered cytokine alone.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":77246,"journal":{"name":"Lymphokine and cytokine research","volume":"13 6","pages":"383-90"},"PeriodicalIF":0.0,"publicationDate":"1994-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18541701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Variation in the expression of human immunodeficiency virus RNA and cytokine mRNA in rectal mucosa during the progression of infection.","authors":"S Reka,&nbsp;M L Garro,&nbsp;D P Kotler","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Previous studies demonstrated that mucosal HIV p24 antigen content varied during the progression of HIV infection. In this study, expression of HIV RNA and mRNA of selected cytokines was examined in rectal mucosa from HIV-infected individuals. Rectal biopsies from 27 subjects were studied: 7 with CD4 counts > 500/mm3 (early), 11 with CD4 < 500 (intermediate), and 9 with AIDS (late), plus 4 HIV-seronegative controls. RNA in situ hybridization was performed using 35S-labeled riboprobes of HIV, TNF-alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-10, INF-alpha, IFN-gamma, and TGF-beta. HIV RNA was detected more frequently in the intermediate group than in the other groups (p < 0.005). Cytokine mRNA expression also varied during disease progression. The expression of IFN-alpha, IFN-gamma, and TGF-beta mRNA was most prevalent early in the disease; peak expression of IL-4, IL-5, IL-6, and IL-10 was seen during the intermediate stage, and peak expression of TNF-alpha and IL-1 beta mRNA were seen in AIDS patients. HIV RNA and cytokine mRNA expression vary during HIV disease progression. HIV RNA expression is greatest in the intermediate stage of the disease. The pattern of cytokine mRNA expression suggests predominant cell-mediated immunity under basal conditions and early in the disease, generalized cytokine activation in its middle phase, and proinflammatory cytokine activation in AIDS patients. Cytokine modulation of HIV expression in rectal mucosa in vivo may occur and have pathogenic importance.</p>","PeriodicalId":77246,"journal":{"name":"Lymphokine and cytokine research","volume":"13 6","pages":"391-8"},"PeriodicalIF":0.0,"publicationDate":"1994-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18707723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Coexpression of the human TNF receptors TR60 and TR80 in insect cells: analysis of receptor complex formation.","authors":"D Moosmayer,&nbsp;A Dinkel,&nbsp;E Gerlach,&nbsp;B Hessabi,&nbsp;M Grell,&nbsp;K Pfizenmaier,&nbsp;P Scheurich","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>For investigation of a possible physical interaction between the two human tumor necrosis factor receptors, TR60 (type I) and TR80 (type II), the baculovirus expression system was used. Each of the receptors was expressed as a membrane-integrated protein in insect cells, able to specifically bind the two ligands, tumor necrosis factor (TNF) and lymphotoxin (LT alpha). Typically, about 150,000 membrane receptors per cell could be detected 40 h after infection, exerting high affinity ligand binding capacity with Kd values virtually identical to that of human cell lines. The baculovirus system allowed coexpression of both TNF membrane receptors at very high and about equal numbers to investigate the existence of heteromultimeric receptor complexes, either formed spontaneously or ligand induced. Neither saturation binding studies nor immunoprecipitation experiments gave an indication for the existence of TNF receptor heteromers. These data are in accordance with the current view of TNF signaling, in which homonultimerization, rather than heteromer formation of TNF receptors is the initial activating event.</p>","PeriodicalId":77246,"journal":{"name":"Lymphokine and cytokine research","volume":"13 5","pages":"295-301"},"PeriodicalIF":0.0,"publicationDate":"1994-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18857502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}