Juliusz Kruszelnicki, Amanda M. Lietz, Guy Parsey, Soheila Mohades, Mark J. Kushner
{"title":"Consequences Of Environmental Factors In Plasma Treatment Of Liquids, Tissues And Materials","authors":"Juliusz Kruszelnicki, Amanda M. Lietz, Guy Parsey, Soheila Mohades, Mark J. Kushner","doi":"10.1016/j.cpme.2017.12.003","DOIUrl":"10.1016/j.cpme.2017.12.003","url":null,"abstract":"<div><p><span>The approved use of atmospheric pressure plasma sources in treatment of biological materials has as one consideration the ability to reproduce the procedure. In this context, the environment in which the plasma source is operated is a factor. Environment is used here in the most general way to refer to all components surrounding or interacting with the plasma source that may affect the </span><em>dose</em> delivered to the biological material. These components may include the physical electrical layout of the procedure (e.g., location of electrical ground planes, permittivity of the material being treated), pulse-power protocol, humidity or aerosol content of the surrounding air, alignment of the plasma source, porosity of the material being treated, or depth of the well-plate for <em>in-vitro</em><span><span> studies. In this paper, results from computational investigations will be discussed that address the consequences of environmental factors in consistency of treatment of biological materials by plasma jets and </span>dielectric barrier discharges. The computational platforms used in this investigation are </span><em>nonPDPSIM,</em><span> a 2-dimensional plasma hydrodynamics model and </span><em>Global_Kin</em>, a 0-dimensional plasma kinetics model. Emphasis will be on plasma activation of liquids, aerosols or liquid covered materials, and treatment of non-planar or porous materials, including the physical layout of <em>in-vitro</em> studies.</p></div>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77908765","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":"Interaction Between Cap- Derived Singlet Oxygen And Tumor Cell Protective Catalase: Update And Chances","authors":"Georg Bauer","doi":"10.1016/j.cpme.2017.12.028","DOIUrl":"10.1016/j.cpme.2017.12.028","url":null,"abstract":"<div><p><span><span>Transformation of cells from various tissues requires NADPH oxidase-dependent generation of extracellular superoxide anions. These drive the proliferation, but also cause the elimination of malignant cells through the HOCl and the NO/peroxynitrite signaling pathways. These intercellular signaling pathways induce </span>apoptosis<span><span> selectively in malignant cells, due to site-specific concerted interaction of defined reactive oxygen and nitrogen species (ROS/RNS). Tumor progression requires the expression of membrane-associated catalase. This enzyme interferes with HOCl signaling through decomposition of H2O2, and with NO/peroxynitrite signaling through </span>oxidation of NO and decomposition of </span></span>peroxynitrite. Membrane-associated catalase has been found on all lines of bona fide tumor cells and represents a promising target for novel antitumor strategies. Inactivation of tumor cell-specific membrane-associated catalase reactivates intercellular ROS/RNS-dependent apoptosis-inducing signaling and leads to autocrine apoptotic selfdestruction of tumor cells.</p><p><span><span>Model experiments with defined ROS and RNS led to the conclusion that CAP-derived singlet oxygen might lead to site-specific inactivation of catalase, followed by tumor cell-specific generation of secondary singlet oxygen and further inactivation of catalase. This then allows for subsequent reactivation of intercellular ROS/RNS-dependent apoptosis-inducing signaling [1]. Only on the first sight, this model seemed a) to be in contradiction to the model on the dependence of CAP action from aquaporins [2] and b) to be independent of subsequent </span>immunogenic cell death<span> and activation of a cytotoxic T cell response [3, 4]. The analysis of existing experimental data from several groups and the alignment of site-specific mechanisms, defined by chemical biology and </span></span>cell biology, allowed to establish an updated and comprehensive model [5] that includes the concepts from references [1-4] in a rational way. This model shows several biochemical amplification loops related to the generation of secondary singlet oxygen, a positive feed-back of HOCl signaling on immunogenic modulation, as well as a feedback loop from activated T cells to catalase inactivation and reactivation of intercellular ROS/RNS signaling. Thereby HOCl seems to play a role as mediator for apoptosis induction and enhancer of immunogenic stimulation.</p><p><span>The detailed biochemical analysis<span> of generation of secondary singlet oxygen by tumor cells after initial interaction with exogenous singlet oxygen allowed to predict that an increase in the concentrations of tumor cell-derived extracellular superoxide anions and/or nitric oxide should cause a substantial synergistic effect with exogenous singlet oxygen. Therefore, a hybrid molecule, consisting of a plant-derived NOX stimulator and a plant-derived inhibitor of NO </span></span>dioxygenase<span>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76453757","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":"Immunogenic Cell Death In Murine Colon-Carcinoma Cells Following Exposure To Cold Physical Plasma-Treated Saline Solution","authors":"Eric Freund , Christine Hackbarth , Lars-Ivo Partecke , Sander Bekeschus","doi":"10.1016/j.cpme.2017.12.030","DOIUrl":"10.1016/j.cpme.2017.12.030","url":null,"abstract":"<div><p>Diffuse peritoneal metastasis of gastrointestinal tumors is a life-threatening complication in end-stage tumor patients. Standard of care is hyperthermic intraperitoneal chemotherapy (HIPEC) and/or radiation therapy, both associated with significant side effects [1]. Previous studies have suggested that cold physical plasma may present a new anti-tumor tool with few to none side effects [2]. Moreover, plasma-induced reactive species can be transferred to cell culture medium where they react to more stable entities. We were able to demonstrate that phosphate-buffered saline (PBS) treated with cold physical plasma has toxic effects on mouse carcinoma cells cultured in 2D. We observed a reduced metabolic activities and apoptotic cell death. Morphological alterations, such as spiking of nuclei and changes in the shape of cytofilaments were also visible. Accordingly, treatment increased cell stiffness and reduced cell motility. Cancer cells are able to develop several mechanisms to subvert and avoid immune response. Danger associated molecular patterns (DAMPs) are linked to an immunogenic cell death (ICD) [3]. We observed an upregulation of DAMPs on the cell surface as well as increased concentrations in the cell’s liquid surroundings following incubation with plasma-treated saline. The activation of the immune system for cancer therapy is a promising approach. Animal experiments will show whether plasma-treated saline solution is effective in vivo and could be in principle considered for medical application.</p></div>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78948846","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":"Immune modulatory properties of radiotherapy","authors":"Udo S. Gaipl","doi":"10.1016/j.cpme.2017.12.020","DOIUrl":"10.1016/j.cpme.2017.12.020","url":null,"abstract":"<div><p><span><span>Radiotherapy (RT) is a common treatment for cancer and about 60% of all cancer patients will receive it during their course of illness. RT primarily aims to achieve local tumor control. The induction of DNA damage by </span>reactive oxygen species<span><span> (ROS), tumor cell death and the modulation of the </span>tumor microenvironment are the main effects of ionizing irradiation to reduce tumor masses, but also to modulate the immune system. RT might thereby act as an </span></span><em>in situ</em> cancer vaccine under certain microenvironmental conditions. However, RT also fosters the upregulation of immune suppressive molecules such as immune checkpoint molecules.</p><p><span><span>The presentation will focus on how local irradiation changes the tumor cell phenotype and the tumor microenvironment and consecutively does impact on local and systemic changes in immune cell compositions. In particular the impact of ROS, danger signals and cytokines on it will be outlined. The dynamics of immune changes, the </span>radiosensitivity of distinct immune cells as well as biological basis for reasonable combination of RT with </span>immune stimulation<span> will be discussed in detail, as well as how radiation-induced immune suppression can be overcome. Based on the pre-clinical knowledge, innovative clinical study concepts of radio-immune treatments will be presented.</span></p></div>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77869931","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":"Flexible Electronics Technologies for the Fabrication of Surface Dielectric Barrier Discharge Devices","authors":"Do-Geun Kim, Sunghoon Jung, Seunghun Lee","doi":"10.1016/j.cpme.2017.12.008","DOIUrl":"10.1016/j.cpme.2017.12.008","url":null,"abstract":"<div><p><span>Flexible electronics have been extensively studied for the development of flexible displays and semiconductor devices. Heterojunction<span> and patterning techniques between metal and polymer have been studied to realize complicated electrode wiring.[1] Flexible electronics technologies can also be used to fabricate devices for surface dielectric<span> barrier discharge (SDBD). Recently, SDBD were developed as a flexible device based on polymer dielectric substrates.[2] The flexible devices using polymer dielectrics have technical issues such as bonding between metal electrodes and polymer substrates, patterning of metal electrodes, and suppression of polymer deformation by plasma generated radicals. In this presentation, we report the result of SDBD device fabricated by printed electronics technologies. For example, the SDBD devices based on the polyimide substrate with the patterned electrode by printing method showed stable discharge characteristics with a dielectric thickness of 100 micrometers or less, a sinusoidal frequency of 5-10 kHz, and a discharge voltage of 2 kV.</span></span></span><span><figure><span><img><ol><li><span>Download : <span>Download high-res image (222KB)</span></span></li><li><span>Download : <span>Download full-size image</span></span></li></ol></span></figure></span></p><p>Figure 1. SDBD device fabricated on polyimide substrates (left), and discharge image (right)</p></div>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74176357","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}
Paul Maguire, Harold McQuaid, David Rutherford, Davide Mariotti
{"title":"Investigating Electron And Radical Interactions With Biomolecules And Cells Using A Droplet In Plasma Laboratory","authors":"Paul Maguire, Harold McQuaid, David Rutherford, Davide Mariotti","doi":"10.1016/j.cpme.2017.12.050","DOIUrl":"10.1016/j.cpme.2017.12.050","url":null,"abstract":"<div><p><span>Plasmas-liquid interactions are a valuable source of radical species for plasma medicine including cancer treatment and antimicrobial applications. However untangling the complex interplay between species and biology over very short timescales and distances is proving extremely challenging. Radiolysis induced damage to DNA is considered to be significantly affected by low energy secondary species such as OH radicals but also via direct interaction with low energy solvated electrons (LEE). Pt adducts and the presence of Au </span>nanoparticles are also known to enhance the LEE effectiveness. However direct investigation of LEE and radical interactions with biomolecules e.g. DNA in a liquid environment at atmospheric pressure or in a living cell present very significant experimental challenges. LEE sources have been proposed such as 2D radioactive layers and UV-induced emission from metals. In this work we look at the potential of a living laboratory based on small liquid droplets containing biomolecules or cells passed through a plasma and exposed to a high flux of electrons and selectable radicals. We also consider the potential of using droplets to deliver plasma-activated media near instantaneously downstream.</p><p>Transport of micron-sized liquid droplets through a low temperature non-equilibrium RF plasma [1] at atmospheric pressure has demonstrated a number of remarkable and unexpected effects. The microdroplet system allows for a controlled (air-free) gas ambient environment, a large surface area to volume ratio, very small reaction volume and low droplet temperature. In addition, flow induced convection in the liquid can be minimised. After a very short plasma exposure time, ~120°μ s, there is evidence that chemical reactions induced by the plasma and gas flux proceed at a rate that is significantly faster that observed in plasma – bulk liquid studies and many orders of magnitude faster than in standard bulk chemistry [2]. The high chemical reactivity is thought to depend not only on the picolitre droplet volume, as in microreaction chemistry, but also on the high level of surface charge due to net electron bombardment in the plasma and the high flux of low energy electrons which arrive at the charged droplet with almost zero net energy. We have observed very rapid electron reduction of metal (Au) salts to form Au nanoparticles at rates that are much greater than observed with gamma radiolysis or high energy electron beams. This points to the possible effectiveness of plasma-generated Ultra-Low Energy Electrons (ULEE) in reduction reactions that may prove valuable for electron – biomolecule studies. We have also observed H<sub>2</sub>O<sub>2</sub> and OH in the liquid most likely due to generation of these species in the plasma phase, which contains only He and H<sub>2</sub>O vapour. We have used droplets as carriers for single bacteria cells, which are then exposed to plasma species (electrons, OH and H<sub>2</sub>O<sub>2</","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76258351","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}
Philipp Jansen , Dirk Schadendorf , Sander Bekeschus , Joachim Klode , Ingo Stoffels
{"title":"Laser-Assisted Delivery Of Cold Atmospheric Plasma In Unresectable Cutaneous Metastasis In Melanoma Patients","authors":"Philipp Jansen , Dirk Schadendorf , Sander Bekeschus , Joachim Klode , Ingo Stoffels","doi":"10.1016/j.cpme.2017.12.071","DOIUrl":"10.1016/j.cpme.2017.12.071","url":null,"abstract":"<div><p>According to the World Health Organization, the incidence of melanoma<span><span> is increasing faster than that of any other major cancer in the world. Melanoma is the fifth most common cancer in the United States, posing a substantial health and economic burden. Treatment of early and multiple cutaneous unresectable </span>metastasis in melanoma patients is a major therapeutic problem.</span></p><p><span>Cold atmospheric plasma (CAP) contains electrons, charged particles, radicals, various excited molecules, UV photons, and transient electric fields. These various compositional elements have the potential either to enhance cellular activity, or to disrupt it. In particular, based on this unique composition, CAP could offer a minimally-invasive surgical approach allowing for specific cancer cell<span><span> or tumor tissue removal without influencing healthy cells. Topical application of treatment agents is a basic principle of dermatological therapy. However, the effective barrier function of the skin significantly impairs the bioavailability of most </span>topical drugs. Fractional ablative lasers represent an innovative strategy to overcome the epidermal barrier in a standardized, contact-free manner. The bioavailability of topical agents can be significantly enhanced using laser-assisted delivery. Ablative fractional laser resurfacing creates vertical channels that might assist the delivery of topically applied cold plasma into </span></span>cutaneous melanoma metastasis.</p><p>For lesions refractory to elective treatments, the laser-assisted drug delivery technique combined with cold atmospheric plasma may present a new potential option.</p><p>We report on a pilot study showing a proof of concept for enhancing topical cold atmospheric plasma permeation into depth by ablative fractional laser technique.</p></div>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.071","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84584794","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}
Dominika Sersenová , Helena Gbelcová , Adam Polakovič , Vanda Repiská , Zdenko Machala
{"title":"Effect Of Plasma Pen Treatment And Plasma Activated Medium (PAM) On Cancer And Normal Cells","authors":"Dominika Sersenová , Helena Gbelcová , Adam Polakovič , Vanda Repiská , Zdenko Machala","doi":"10.1016/j.cpme.2017.12.038","DOIUrl":"10.1016/j.cpme.2017.12.038","url":null,"abstract":"<div><p>Non-thermal atmospheric pressure plasma has recently found an ever growing use in medicine; including development of new cancer treatments. The most significant factor, produced by plasma that influence cancer cells<span> are reactive oxygen and nitrogen species (RONS). RONS react with the surrounding air, cellular aqueous media and with cells themselves; however, the exact mechanism of their interaction with the cells is not yet fully understood. Some of the studies suggest that plasma is able to induce apoptosis in cancer cells and has a potential to selectively kill cancer cells without causing a major destruction of normal cells [1]. Plasma can be applied both directly on cell or tissues or indirectly – by plasma-activated medium (PAM). It is a cellular medium, which was treated by plasma and then applied onto the cells, so the cells interact only with RONS produced in PAM [2].</span></p><p>The aim of this study was to test <em>in vitro</em><span> the effect of plasma on cancer cells A375 (human melanoma<span><span> epithelial cells) and normal cells HEK293T (human embryonic kidney cells). As a medium we used DMEM with 10% FBS. The first part focuses on direct treatment of cells by our design of air corona plasma pen [3,4]. In the second part, we evaluated the effect of PAM on the cells. We used discharges generated in atmospheric air, unlike the majority of plasma jets used for biomedical application that use </span>rare gases<span> (He, Ar). Cell viability was measured using the MTT test.</span></span></span></p><p>In the first setup, cells were treated with the corona plasma multipen. The cells were placed in 96-well plate with 100μl of medium and the corona discharge operated in between the 8 pen needles and steel wire above the medium surface. Medium temperature did not exceed 34°C. The cell viability was measured after 24-hour incubation and it was evaluated in dependence on time of plasma treatment. Viability of both types of cells decreased with the time of plasma treatment with no selectivity on cancer cells. After 5 minutes of plasma treatment almost all cells were dead (> 95 %).</p><p>In the second setup, the effect of PAM on cells was tested in various experimental setups aiming to find the most effective way of PAM production. We used transient spark or streamer corona discharges with different parameters in combination with electro-spraying of the used medium. The discharges were operated in between the high voltage needle and a grounded mesh. The cells viability was evaluated after 24- and 48-hour incubation. We investigated the cell viability dependence on time of plasma treatment, on the used discharge regime, treatment before and after FBS was added, and on the amount of PAM added to the cells.</p><p>To conclude, cold plasma has the potential to be used in cancer treatment, because it can be used on live cells and tissues. The use of direct plasma is more technically demanding and still possible mainly in surface ","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73527791","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":"Controlling of apoptosis and proliferation of HepG2 cancer cells by treatment of plasma jet and N-acetylcysteine combination","authors":"Zilan Xiong , Shasha Zhao","doi":"10.1016/j.cpme.2017.12.019","DOIUrl":"10.1016/j.cpme.2017.12.019","url":null,"abstract":"<div><p>It is well known that atmospheric pressure plasma could induce apoptosis of cancer cells. [1][2] However, the interaction and mechanism between plasma and cancer cells has not been fully understood yet. [3] Here, we report the controlment of apoptosis and proliferation of human hepatocellular carcinoma cell (HepG2) by combined treatment of He/O<sub>2</sub> plasma jet and N-acetylcysteine (NAC, free radical scavenger). It is found that the fate of HepG2 cells could be controlled by plasma treatment time together with NAC pretreatment. Pure plasma treatment could induce apoptosis of HepG2 cells. However, on one hand, 15s plasma with NAC pre-treatment could enhance proliferation of HepG2 cell as a function of NAC concentration. On the other hand, NAC-pretreatment could markedly compromise apoptosis effect by long time plasma treatment (e.g. >240s) without proliferation observed. The NAC and 15s plasma treatment accelerates the G1 to S phase transition of HepG2 cells causing proliferation while long time plasma treatment arrests the cell cycle at the G2/M phase inducing apoptosis.</p></div>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86863840","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}