Inflammation & allergy drug targets最新文献

{"title":"Microbiome Regulation of Autoimmune, Gut and Liver Associated Diseases.","authors":"Bhagirath Singh, Nan Qin, G. Reid","doi":"10.2174/1871528114666160128150747","DOIUrl":"https://doi.org/10.2174/1871528114666160128150747","url":null,"abstract":"Extensive analysis of the complexity and diversity of microbiota using metagenomics in the gut and other body sites has provided evidence that dysbiosis occurs in many disease states. With the application of next generation sequencing technology this research is starting to uncover the impact of microbiota on metabolic, physiological and immunological pathways and elucidate the cellular and molecular mechanisms involved. To highlight these advances we have focused on autoimmunity and gut and liver related diseases and discuss the opportunities and challenges of translating microbiome research towards its application in humans. Towards this goal we discuss the application of fecal microbiome transplantation (FMT) for the treatment of multiple chronic gut associated inflammatory diseases such as Clostridium difficile infection (CDI) and inflammatory bowel disease (IBD). The potential role of human migration across continents and cultures leading to alteration in their microbiome and its implication in health and disease is also discussed.","PeriodicalId":13680,"journal":{"name":"Inflammation & allergy drug targets","volume":"61 1","pages":"84-93"},"PeriodicalIF":0.0,"publicationDate":"2015-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89181908","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":"Design, Synthesis and In Vitro Release Studies of Co-Drugs for Rheumatoid Arthritis.","authors":"Patil Kashmira, S. Dhaneshwar, Chopade Shakuntala, Joshi Poorvashree","doi":"10.2174/1871528114666151201200157","DOIUrl":"https://doi.org/10.2174/1871528114666151201200157","url":null,"abstract":"BACKGROUND\u0000Rheumatoid arthritis (RA) is an autoimmune disease that results in a chronic, systemic inflammation that may affect many tissues and organs, but principally the synovial joints. The tendency for joint destruction is greatest in the early stages of disease hence current trend is to introduce a disease-modifying anti-rheumatic drug (DMARD) immediately after the diagnosis of RA in a step- up approach which is generally followed by its combination with a corticosteroid or NSAID.\u0000\u0000\u0000OBJECTIVE\u0000Hydroxychloroquine (HCQ) is a slow acting DMARD used in the early stage of RA. NSAIDs if given in combination with HCQ would provide immediate symptomatic relief from pain and inflammation even before HCQ starts showing its disease modifying effects. Long half life of HCQ results in its accumulation in the body while frequent intake of NSAIDs results in severe GI side effects. Present project aims at minimizing these shortcomings by designing co-drugs of HCQ and NSAIDs as a potential combination RA therapy.\u0000\u0000\u0000METHOD\u0000Synthesis of two co-drugs was achieved by CDI coupling, followed by their spectral characterization. In vitro release kinetics was studied by HPTLC in aqueous buffers and tissue homogenates of upper GIT.\u0000\u0000\u0000RESULTS\u0000Prodrugs were resistant to hydrolysis in buffers (pH 1.2 and 7.4) and stomach homogenates of Wistar rat but 32- 65% hydrolysis was observed in small intestinal homogenates.\u0000\u0000\u0000CONCLUSION\u0000We propose that the mutual prodrug strategy of a DMARD with NSAID could be useful in initial management of RA wherein NSAIDs would produce their anti-inflammatory effect and simultaneously the process of joint reconstruction by hydroxychloroquine could be initiated.","PeriodicalId":13680,"journal":{"name":"Inflammation & allergy drug targets","volume":"1 1","pages":"47-52"},"PeriodicalIF":0.0,"publicationDate":"2015-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79808455","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":"The ambidextrous cyclooxygenase: an enduring target.","authors":"Mayank Bapna,&nbsp;Lalit Singh Chauhan","doi":"10.2174/1871528114666150401105545","DOIUrl":"https://doi.org/10.2174/1871528114666150401105545","url":null,"abstract":"<p><p>With the discovery of COX, pain has not been treated in a relentless manner. Numbers of drugs with fewer side effects were discovered and are used successfully for treatment of pain. With new research coming into being since the discovery of COX, it was established that COX can be targeted not only for treatment of pain but for curing various diseases like cancer, Alzheimer's, Parkinson's disease, Glaucoma etc. With the sighting of COX-3, another isoform of COX, new diseases are being targeted for better treatment. </p>","PeriodicalId":13680,"journal":{"name":"Inflammation & allergy drug targets","volume":"13 6","pages":"387-92"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33057779","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":"A systematic review of drugs in late-stage development for the treatment of multiple sclerosis: a focus on oral synthetic drugs.","authors":"Malihe Safavi,&nbsp;Shekoufeh Nikfar,&nbsp;Mohammad Abdollahi","doi":"10.2174/1871528114666150529102613","DOIUrl":"https://doi.org/10.2174/1871528114666150529102613","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a heterogeneous, chronic, debilitating immune-mediated disease of the central nervous system (CNS). There are four types of MS according to their relapsing or progressive pattern that include relapsing-remitting (RRMS), secondary progressive (SPMS), primary progressive (PPMS), and progressive relapsing (PRMS). There is no definite cure for MS, thus medications typically focus on slowing the progression of the disease, managing symptoms and improving the quality of life. There is no specific medication for the management of PPMS and thus these patients are often neglected. New medicines in this phase of the disease are needed. On the other hand injectable immunomodulatory medicines, which dominated the MS market for over the past two decades, raise the issues of adherence and tolerance while oral therapies do offer a step forward in convenience. This systematic review article discusses the emerging synthetic small molecule that administered orally for MS treatment. We searched PubMed, Web of Science and Google Scholar to summaries the present knowledge on mechanism of action, and completed and current clinical trial of laquinimod, masitinib and siponimod. Data were collected from 1985 to January 2015. The development of effective medicines for MS is critically dependent upon understanding the biological basis of this complex multifactorial disease. The current pharmacotherapeuetic options for its treatment are mainly immunomodulators which were developed on the basis that MS is an autoimmune disease. The new synthetic small molecule agents such as laquinimod, masitinib and siponimod with different mechanism of actions can be administered orally rather than by injection. </p>","PeriodicalId":13680,"journal":{"name":"Inflammation & allergy drug targets","volume":"13 6","pages":"351-66"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33340747","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":"Cardiovascular Magnetic Resonance Imaging clarifies cardiac pathophysiology in early, asymptomatic diffuse systemic sclerosis.","authors":"Sophie I Mavrogeni,&nbsp;Konstantinos Bratis,&nbsp;Georgia Karabela,&nbsp;George Spiliotis,&nbsp;Kees van Wijk,&nbsp;David Hautemann,&nbsp;Johan H C Reiber,&nbsp;Loukia Koutsogeorgopoulou,&nbsp;George Markousis-Mavrogenis,&nbsp;Genovefa Kolovou,&nbsp;Efthymios Stavropoulos","doi":"10.2174/1871528114666150916112551","DOIUrl":"https://doi.org/10.2174/1871528114666150916112551","url":null,"abstract":"<p><strong>Background: </strong>Myopericardial inflammation, perfusion's defects and fibrosis are major causes of cardiac disease in scleroderma (SSc). We hypothesized that using inflammation and stress perfusion-fibrosis cardiovascular magnetic resonance (CMR), we can identify the pathophysiology of heart disease in asymptomatic diffuse SSc.</p><p><strong>Patients-methods: </strong>46 recently diagnosed, asymptomatic patients with diffuse SSc had a CMR examination using a 1.5T system. ECG gated breath hold cine and short tau inversion recovery (STIR) T2 images were initially acquired. If T2 ratio<2 a stress perfusion-fibrosis protocol was applied. If T2>2 a myocarditis protocol including early (EGE) and late (LGE) gadolinium imaging was applied. SSc patients' results were compared with age and sex-matched controls and patients with coronary artery disease (CAD).</p><p><strong>Results: </strong>In 2/46 SSc with T2 ratio>2, the myocarditis protocol was positive for acute myocardial inflammation, who developed clinical signs of acute myocarditis shortly after the CMR evaluation. In the rest 44/46 with T2 ratio<2 the stress perfusion-fibrosis CMR identified a significant reduction in Myocardial Perfusion Reserve Index (MPRI) compared with matched controls (0.6±0.4 vs 3.2±0.8, p<0.001), but not with CAD (0.6±0.4 vs 0.86±0.46, p=NS) and correlated only with the presence of digital ulcers (p<0.05). The scar was diffused and greater compared to controls, but did not differ from that assessed in CAD. Two years follow up, available in 11/44 SSc, showed further asymptomatic MPRI deterioration in all and diffuse subendocardial LGE in 8/11, without any change in LV, RV volumes and ejection fractions.</p><p><strong>Conclusion: </strong>CMR may reveal severe cardiac involvement in early, asymptomatic diffuse SSc with normal routine cardiac evaluation, presenting either as myocardial inflammation or as severe reduction of MPRI and diffuse fibrosis with further deterioration in the long term follow up.</p>","PeriodicalId":13680,"journal":{"name":"Inflammation & allergy drug targets","volume":"14 1","pages":"29-36"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1871528114666150916112551","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34006443","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":"Suramin attenuated inflammation and reversed skin tissue damage in experimentally induced atopic dermatitis in mice.","authors":"Abdullah Alyoussef","doi":"10.2174/1871528114666150529100957","DOIUrl":"https://doi.org/10.2174/1871528114666150529100957","url":null,"abstract":"<p><p>Atopic dermatitis (AD) is a skin disease that is characterized by inflammation. Skin barrier dysfunction is commonly seen in AD leading to commonly seen infectious lesions in the skin of AD. Most people develop the skin inflammation condition first, before any skin lesions become visible. Suramin is potent competitive inhibitor of reverse transcriptase and blocks the infectivity and cytopathic effects. Therefore, the following study was performed to illustrate if suramin could produce protection against AD in-vivo. AD like symptoms were introduced in mice by epicutaneous application of DNCB on shaved dorsal skin and ears. 20 mg/kg suramin was taken by intra-peritoneal injection twice weekly for 3 weeks to assess their anti-pruritic effects. Serum levels of inflammatory cytokine, interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-αwere assessed by using ELISA kits. We found that suramin alleviated DNCB-induced AD-like symptoms as quantified by skin lesion, dermatitis score, ear thickness and scratching behavior. Levels of reactive oxygen species in the suramin group were significantly inhibited as compared with that in the DNCB group. In parallel, suramin blocked DNCB-induced elevation in serum TNF-α, IL-1β, IL-6 and IgE. The collective results indicate that suramin suppresses DNCB-induced AD in mice via reduction of inflammatory mediators. </p>","PeriodicalId":13680,"journal":{"name":"Inflammation & allergy drug targets","volume":"13 6","pages":"406-10"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33340748","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":"Investigation of 5-HT2A gene expression in PBMCs of patients with allergic asthma.","authors":"Ghasem Ahangari,&nbsp;Somayeh Emadi Koochak,&nbsp;Leila Mohammadi Amirabad,&nbsp;Gholamreza Derkhshan Deilami","doi":"10.2174/1871528114666150803152433","DOIUrl":"https://doi.org/10.2174/1871528114666150803152433","url":null,"abstract":"<p><strong>Background: </strong>Asthma is an inflammatory airway disorder in which different immune cells in the blood and lungs play a fundamental role. In asthma condition, the airway inflammation accompanied by bronchial smooth muscle spasm cause airway obstruction. A study showed that high concentration of blood serotonin is associated with the intensity and exacerbation of asthma disease. Other studies showed that a subtype of serotonin receptor called 5-Hydroxytriptamine 2A receptor (5- HT2A) can enhance T-cell blastogenesis and production of pro-inflammatory cytokines such as IFNγ.</p><p><strong>Objective: </strong>The objective of this study was to assess the level of 5-HT2A in peripheral blood mononuclear cells (PBMCs) of asthmatic patients.</p><p><strong>Methods: </strong>PBMCs were extracted from blood of 30 patients with asthma and 30 normal people. After synthesizing cDNAs from total mRNAs, real-time PCR was performed to amplify 5-HT2A and β-actin (as an internal control). The expression ratios were analyzed in patients with asthma in comparison with normal group.</p><p><strong>Results: </strong>The results indicated that gene expression is significantly increased in peripheral blood mononuclear cells (PBMCs) of asthma patients in comparison with normal group (P = 0.003).</p><p><strong>Conclusion: </strong>The results of this study can suggest designing a protocol by using of the 5-HT2A receptor expression in PBMCs as a biomarker of asthma, but this requires further studies on a larger number of patients. In addition, the potential role of this receptor in bronchoconstriction can lead us to use its antagonists as a new treatment in asthma.</p>","PeriodicalId":13680,"journal":{"name":"Inflammation & allergy drug targets","volume":"14 1","pages":"60-4"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1871528114666150803152433","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33888254","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":"7-prenyloxi-6-methoxycoumarin from Polygala sabulosa A.W. Bennett Regulates p38 MAPK and NF-kB Pathways Inhibiting the Inflammation Induced by Carrageenan in the Mouse Model of Pleurisy.","authors":"Marcus Vinicius Pereira Dos Santos Nascimento,&nbsp;Fábio Arruda-Silva,&nbsp;Ana Beatriz G Luz,&nbsp;Dalila Venzke,&nbsp;Gustavo S Queiroz,&nbsp;Beatriz G Mendes,&nbsp;Eduardo R Fernandes-Ribeiro,&nbsp;Tânia S Fröde,&nbsp;Moacir G Pizzolatti,&nbsp;Eduardo M Dalmarco","doi":"10.2174/1871528114666151005125120","DOIUrl":"https://doi.org/10.2174/1871528114666151005125120","url":null,"abstract":"<p><strong>Context: </strong>Polygala sabulosa, popularly known as \"timutu-pinheirinho,\" has been used in Brazilian folk medicine for the treatment of bowel and kidney disorders and as an expectorant.</p><p><strong>Objective: </strong>Evaluate the anti-inflammatory effects of the crude extract (CE), acetonic fraction (Ac), and the main compound, 7-prenyloxi-6-methoxycoumarin (PC) on a mouse model of carrageenan-induced pleurisy.</p><p><strong>Materials and methods: </strong>A mouse model of carrageenan-induced pleurisy was used to investigate the effects of P. sabulosa CE, Ac and PC on leukocyte migration, exudate formation, activities of myeloperoxidase (MPO), and adenosine-deaminase (ADA), levels of tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β) and nitric oxide (NO). In addition, the effect of the plant material on lung histology was also evaluated. The effects of PC on the TNF-α, IL-1β and NO synthase 2 (NOS2) mRNA expression, were also investigated. Finally, the effect of PC on the nuclear factor-kappa B (NF-κB) and p38 mitogen-activated protein kinase (p38 MAPK) was also evaluated.</p><p><strong>Results: </strong>CE, Ac and PC reduced inflammation in the pleural cavity and lungs. This effect was evidenced by reduction on all inflammatory parameters evaluated; the exception being the inability of the CE to inhibit exudate formation. In isolation, PC showed reduction on mRNA levels of TNF-α, IL-1β and NOS2, and on activation of the NF-κB and p38 MAPK pathways.</p><p><strong>Conclusion: </strong>The presented results show that P. sabulosa has significant anti-inflammatory activity, as does its main compound, PC. Moreover, the results suggest that PC exerts its effects mainly by inhibited the NF-κB and p38 MAPK pathways.</p>","PeriodicalId":13680,"journal":{"name":"Inflammation & allergy drug targets","volume":"14 1","pages":"37-46"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1871528114666151005125120","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34060965","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":"Cardiovascular involvement in pediatric systemic autoimmune diseases: the emerging role of noninvasive cardiovascular imaging.","authors":"Sophie Mavrogeni,&nbsp;George Servos,&nbsp;Roubini Smerla,&nbsp;George Markousis-Mavrogenis,&nbsp;Georgia Grigoriadou,&nbsp;Genovefa Kolovou,&nbsp;George Papadopoulos","doi":"10.2174/1871528114999150317150050","DOIUrl":"https://doi.org/10.2174/1871528114999150317150050","url":null,"abstract":"<p><p>Cardiac involvement in pediatric systemic autoimmune diseases has a wide spectrum of presentation ranging from asymptomatic to severe clinically overt involvement. Coronary artery disease, pericardial, myocardial, valvular and rythm disturbances are the most common causes of heart lesion in pediatric systemic autoimmune diseases and cannot be explained only by the traditional cardiovascular risk factors. Therefore, chronic inflammation has been considered as an additive causative factor of cardiac disease in these patients. Rheumatic fever, juvenile idiopathic arthritis, systemic lupus erythematosus, ankylosing spondylitis/spondyloarthritides, juvenile scleroderma, juvenile dermatomyositis/polymyositis, Kawasaki disease and other autoimmune vasculitides are the commonest pediatric systemic autoimmune diseases with heart involvement. Noninvasive cardiovascular imaging is an absolutely necessary adjunct to the clinical evaluation of these patients. Echocardiography is the cornerstone of this assessment, due to excellent acoustic window in children, lack of radiation, low cost and high availability. However, it can not detect disease acuity and pathophysiologic background of cardiac lesions. Recently, the development of cardiovascular magnetic resonance imaging holds the promise for early detection of subclinical heart disease and detailed serial evaluation of myocardium (function, inflammation, stress perfusion-fibrosis) and coronary arteries (assessment of ectasia and aneurysms). </p>. </p>","PeriodicalId":13680,"journal":{"name":"Inflammation & allergy drug targets","volume":"13 6","pages":"371-81"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33137386","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":"Mechanistic overview of immune modulatory effects of environmental toxicants.","authors":"Haji Bahadar,&nbsp;Mohammad Abdollahi,&nbsp;Faheem Maqbool,&nbsp;Maryam Baeeri,&nbsp;Kamal Niaz","doi":"10.2174/1871528114666150529103003","DOIUrl":"https://doi.org/10.2174/1871528114666150529103003","url":null,"abstract":"<p><p>The immune system is an integrated organization, comprising of specific organs, cells and molecules playing a crucial role in the maintenance of health. The purpose of this paper is to give a mechanistic overview of toxic effects of various chemicals and pharmacological agents, and their interaction with the various components of the immune system that leads to modulation of the immune responses. Studies suggest that many chemical agents present in the environment like; heavy metals, agrochemicals, and various types of hydrocarbons possess immune toxicity and cause either structural, functional or compositional changes in various components of the immune system that alters immune response. There is present a complex bidirectional relationship between central nervous system (CNS) and the immune system. And receptors for neuropeptides, neurotransmitters, and hormones are located on lymphoid organs. Therefore, we are of the opinion that Endocrine Disrupting Chemicals (EDCs) present in our environment may be indirectly involved in causing immune toxicity via neuroendocrine channels, and vice versa many neurological disorders may be associated with environmental pollutants utilizing immuno-neuroendocrine pathways. </p>","PeriodicalId":13680,"journal":{"name":"Inflammation & allergy drug targets","volume":"13 6","pages":"382-6"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33340746","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}