Nanomedicine : nanotechnology, biology, and medicine最新文献

{"title":"A combinational chemo-immune therapy using outer membrane vesicles for enhanced cancer therapy by RGD targeting.","authors":"Shuping Li, Xiaodong Gao","doi":"10.2139/ssrn.4156334","DOIUrl":"https://doi.org/10.2139/ssrn.4156334","url":null,"abstract":"Cancer therapies are limited by poor drug penetration that impedes effective tumor treatment. This was overcome in the present study by loading the immune reaction inducing nanocarriers of the bacterial outer membrane vesicles (OMVs) and doxorubicin (DOX) into the natural immunity platform OMV via incubation. Drug accumulation at the tumor site was improved by using the targeting peptide 6-Mal- Arg-Gly-Asp (RGD) on the surface of OMVs to increase internalization via binding to cell surface integrin αvβ3. OMVs stimulate immune responses by reversing the immune-suppressive tumor microenvironment (TME) via decreasing TAM and Treg, increasing CD8+ T and M1, and promoting DC maturation. The combination of DOX and OMVs compensates for the shortcomings of monotherapy (e.g., chemotherapy and immunotherapy) and amplifies the therapeutic efficacy of cancer treatment, while aiding selection of novel nanocarriers and development of effective therapeutic regimens.","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78276023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multifunctional nanoprobe for real-time in vivo monitoring of T cell activation.","authors":"O. Betzer, Yue Gao, Astar Shamul, M. Motiei, T. Sadan, R. Yehuda, Ayelet Atkins, C. Cohen, Mingwu Shen, Xiangyang Shi, R. Popovtzer","doi":"10.2139/ssrn.4094098","DOIUrl":"https://doi.org/10.2139/ssrn.4094098","url":null,"abstract":"Genetically engineered T cells are a powerful new modality for cancer immunotherapy. However, their clinical application for solid tumors is challenging, and crucial knowledge on cell functionality in vivo is lacking. Here, we fabricated a nanoprobe composed of dendrimers incorporating a calcium sensor and gold nanoparticles, for dual-modal monitoring of engineered T cells within a solid tumor. T cells engineered to express a melanoma-specific T-cell receptor and loaded with the nanoprobe were longitudinally monitored within melanoma xenografts in mice. Fluorescent imaging of the nanoprobe's calcium sensor revealed increased intra-tumoral activation of the T cells over time, up to 24 h. Computed tomography imaging of the nanoprobe's gold nanoparticles revealed the cells' intra-tumoral distribution pattern. Quantitative analysis revealed the intra-tumoral T cell quantities. Thus, this nanoprobe reveals intra-tumoral persistence, penetration and functional status of genetically engineered T cells, which can advance T cell-based immunotherapy and promote next-generation live cell imaging.","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76725367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerium dioxide, a Jekyll and Hyde nanomaterial, can increase basal and decrease elevated inflammation and oxidative stress","authors":"Robert A. Yokel PhD ,&nbsp;Marsha L. Ensor MSc ,&nbsp;Hemendra J. Vekaria PhD ,&nbsp;Patrick G. Sullivan PhD ,&nbsp;David J. Feola PharmD, PhD ,&nbsp;Arnold Stromberg PhD ,&nbsp;Michael T. Tseng PhD ,&nbsp;Douglas A. Harrison PhD","doi":"10.1016/j.nano.2022.102565","DOIUrl":"10.1016/j.nano.2022.102565","url":null,"abstract":"<div><p><span>It was hypothesized that the catalyst nanoceria can increase inflammation/oxidative stress from the basal and reduce it from the elevated state. Macrophages clear nanoceria. To test the hypothesis, M0 (non-polarized), M1- (classically activated, pro-inflammatory), and M2-like (alternatively activated, regulatory phenotype) RAW 264.7 macrophages were nanoceria exposed. Inflammatory responses were quantified by IL-1β level, arginase<span> activity, and RT-qPCR and metabolic changes and oxidative stress<span><span> by the mito and glycolysis stress tests (MST and GST). Morphology was determined by light microscopy, macrophage </span>phenotype marker expression, and a novel three-dimensional immunohistochemical method. Nanoceria blocked IL-1β and arginase effects, increased M0 cell </span></span></span>OCR and GST toward the M2 phenotype and altered multiple M1- and M2-like cell endpoints toward the M0 level. M1-like cells had greater volume and less circularity/roundness. M2-like cells had greater volume than M0 macrophages. The results are overall consistent with the hypothesis.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89820938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlative imaging to resolve molecular structures in individual cells: Substrate validation study for super-resolution infrared microspectroscopy","authors":"Agnes Paulus PhD ,&nbsp;Sahana Yogarasa BSc ,&nbsp;Mustafa Kansiz PhD ,&nbsp;Isak Martinsson PhD ,&nbsp;Gunnar K. Gouras MD, PhD, Professor ,&nbsp;Tomas Deierborg PhD, Professor ,&nbsp;Anders Engdahl PhD ,&nbsp;Ferenc Borondics PhD ,&nbsp;Oxana Klementieva PhD","doi":"10.1016/j.nano.2022.102563","DOIUrl":"10.1016/j.nano.2022.102563","url":null,"abstract":"<div><p>Light microscopy has been a favorite tool of biological studies for almost a century, recently producing detailed images with exquisite molecular specificity achieving spatial resolution at nanoscale. However, light microscopy is insufficient to provide chemical information as a standalone technique. An increasing amount of evidence demonstrates that optical photothermal infrared microspectroscopy (O-PTIR) is a valuable imaging tool that can extract chemical information to locate molecular structures at submicron resolution. To further investigate the applicability of sub-micron infrared microspectroscopy for biomedical applications, we analyzed the contribution of substrate chemistry to the infrared spectra acquired from individual neurons grown on various imaging substrates. To provide an example of correlative immunofluorescence/O-PTIR imaging, we used immunofluorescence to locate specific organelles for O-PTIR measurement, thus capturing molecular structures at the sub-cellular level directly in cells, which is not possible using traditional infrared microspectroscopy or immunofluorescence microscopy alone.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1549963422000491/pdfft?md5=499ad7157db3fdf1f38c08c7381b93ee&pid=1-s2.0-S1549963422000491-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89941863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fabrication of tumor targeting rare-earth nanocrystals for real-time NIR-IIb fluorescence imaging-guided breast cancer precise surgery","authors":"Kang-Liang Lou BA ,&nbsp;Pei-Yuan Wang PhD ,&nbsp;Rui-Qin Yang MA ,&nbsp;Yi-Yang Gao MA ,&nbsp;Hai-Na Tian MA ,&nbsp;Yong-Ying Dang BA ,&nbsp;Yang Li PhD ,&nbsp;Wen-He Huang BA ,&nbsp;Min Chen PhD ,&nbsp;Xiao-Long Liu PhD ,&nbsp;Guo-Jun Zhang MD, PhD","doi":"10.1016/j.nano.2022.102555","DOIUrl":"10.1016/j.nano.2022.102555","url":null,"abstract":"<div><p>The near-infrared fluorescence imaging has been integrated into the operating room to guide tumor resection, potentially reducing the positive margin rates in breast-conserving surgery (BCS). Relative to the widely used first near-infrared fluorescence imaging, imaging in the second near-infrared (NIR-II) region possesses higher contrast and deeper tissue penetration, particularly in the NIR-IIb window, offering many new opportunities for imaging-guided BCS. Here, we fabricated the c(RGDfC) functionalized erbium-based rare-earth nanoparticles (ErNPs@cRGD) with superior optical property in NIR-IIb region. Owing to deeper tissue penetration and efficient tumor targeting, ErNPs@cRGD-based NIR-IIb fluorescence imaging achieved enhanced signal-to-background ratios in tumor visualization, which was able to guide more complete tumor resection, identify multiple microtumors and distinguish malignant lesions from normal tissues in various mice models. Based on these, this NIR-IIb imaging strategy for surgical navigation can significantly reduce positive margin rates and improve prognosis, laying a foundation for the clinical resection of breast cancer.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1549963422000417/pdfft?md5=81ef097029e6a6ef09f343de638ea89b&pid=1-s2.0-S1549963422000417-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88852211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antioxidant enzymes immobilized on gold and silver nanoparticles enhance DNA repairing systems of rat skin after exposure to ultraviolet radiation","authors":"Agnieszka M. Pudlarz Dr ,&nbsp;Katarzyna Ranoszek-Soliwoda Dr hab. ,&nbsp;Michał S. Karbownik Dr ,&nbsp;Ewa Czechowska Dr ,&nbsp;Emilia Tomaszewska Dr ,&nbsp;Grzegorz Celichowski Prof. ,&nbsp;Jarosław Grobelny Prof. ,&nbsp;Ewa Chabielska Prof. ,&nbsp;Anna Gromotowicz-Popławska Dr hab. ,&nbsp;Janusz Szemraj Prof.","doi":"10.1016/j.nano.2022.102558","DOIUrl":"10.1016/j.nano.2022.102558","url":null,"abstract":"<div><p>The aim of the study was to investigate in vivo whether the application of immobilized superoxide dismutase (SOD) and catalase (CAT) could enhance DNA repairing systems and reduce level of CPD (cyclobutane pyrimidine dimers) and 6-4PP ((6-4) pyrimidine-pyrimidone photoproducts), and whether the immobilization on gold (AuNPs) and silver (AgNPs) nanoparticles affects the outcome. The study presents secondary analysis of our previous research. Three-day application of SOD and CAT in all forms of solution decreased the levels of CPD and 6-4PP boosted by UV irradiation. The mRNA expression level of the nucleotide excision repair (NER) system genes (XPA, XPC, ERCC1, ERCC2, ERCC3, LIG1) increased after application of immobilized and free enzymes. Increased by UV irradiation, p53 mRNA expression level normalized with the enzyme application. In conclusion, application of free and immobilized antioxidant enzymes accelerates removal of harmful effects of UV radiation in the rat skin by increasing expression level of NER genes.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1549963422000442/pdfft?md5=b1db84c04f1707da7f7dabd51938e8cf&pid=1-s2.0-S1549963422000442-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77253930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A nanotherapy responsive to the inflammatory microenvironment for the dual-targeted treatment of atherosclerosis","authors":"Ge Li PhD ,&nbsp;Fei Xu PhD ,&nbsp;Bo Yang MSc ,&nbsp;Xinyue Lu MSc ,&nbsp;Xiangyu Li PhD ,&nbsp;Yanfei Qi PhD ,&nbsp;Lesheng Teng PhD ,&nbsp;Youxin Li PhD ,&nbsp;Fengying Sun PhD ,&nbsp;Wenhua Liu PhD","doi":"10.1016/j.nano.2022.102557","DOIUrl":"10.1016/j.nano.2022.102557","url":null,"abstract":"<div><p>Atherosclerosis remains the main cause of death and disability, as well as a leading cause of coronary arterial disease. Inflammation is one of the pathogenic factors of arteriosclerosis; however, the current treatments based on lowering the level of inflammation in the plaque tissue of patients with atherosclerosis are not clinically used. Herein, we hypothesize that α_vβ₃ receptor affinity and low pH sensitivity may be regarded as a valid therapeutic strategy for targeting sites of atherosclerosis according to the microenvironments of inflammation. To prove this tentative hypothesis, an acid-labile material polyketal named PK3 was synthesized, and the cRGDfc peptide was used to modify nanoparticles composed of poly(lactide-co-glycolide) (PLGA), lecithin, and PK3, loaded with the anti-atherosclerotic drug rapamycin (RAP). The nanoparticles were prepared using an O/W method and then characterized, which showed an appropriate particle size and fulfilling responsive behaviors. In vitro release studies and stability tests showed that these nanoparticles can be effectively internalized by human umbilical vein endothelial cells (HUVEC), and also show a good in vitro anti-inflammatory effect. After intravenous (i.v.) injection, RGD targeted by pH-responsive nanotherapy (RAP-Nps-RGD) may be accumulated at the plaque site in ApoE^−/− mice with atherosclerosis and can effectively attenuate plaque progression compared to other formulations. Moreover, its good safety profile and biocompatibility have been revealed in both in vitro and in vivo estimations. Accordingly, the prospect of nanoparticles responsive to the inflammatory microenvironment for preventing atherosclerotic through inflammation modulation provides great feasibility for the administration of alternate drug molecules to inflamed sites to slow down the process of arteriosclerosis.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77669667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microfluidic-driven mixing of high molecular weight polymeric complexes for precise nanoparticle downsizing","authors":"Sara Gimondi MSc,&nbsp;Rui L. Reis PhD,&nbsp;Helena Ferreira PhD,&nbsp;Nuno M. Neves PhD","doi":"10.1016/j.nano.2022.102560","DOIUrl":"10.1016/j.nano.2022.102560","url":null,"abstract":"<div><p><span><span><span><span>Chitosan (CHIT) and hyaluronic acid (HA) are two </span>polysaccharides (PSs) with high value in several </span>biomedical applications<span>. In this study, we present a microfluidic method to synthetize CHIT-HA NPs to overcome the disadvantages of the dropwise approach generally used for nanoprecipitation of </span></span>polyelectrolyte complexes<span>. The proposed microfluidic approach enables to generate monodisperse suspensions of NPs with ≈100 nm of size compared to the dropwise method that generated ≈2 times bigger NPs. Finally, we evaluated the potential of obtained NPs in an inflammatory scenario. The treatment with NPs led to the reduction of the main inflammatory molecules produced by macrophages (PGE</span></span>₂, IL-6, IL-8, MCAF and TNF-α) and fibroblasts (IL-1 α, PGE₂<span><span>, TNF-α) stimulated with lipopolysaccharide or conditioned medium, respectively. This study demonstrates that our approach can be used to enhance the synthesis of </span>nanocarriers<span> based on bioactive macromolecules.</span></span></p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81154106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diversifying the skin cancer-fighting worthwhile frontiers: How relevant are the itraconazole/ascorbyl palmitate nanovectors?","authors":"Caroline Lamie Bsc ,&nbsp;Enas Elmowafy PhD ,&nbsp;Dalia A. Attia PhD ,&nbsp;Mohamed M. Elmazar PhD ,&nbsp;Nahed D. Mortada PhD","doi":"10.1016/j.nano.2022.102561","DOIUrl":"10.1016/j.nano.2022.102561","url":null,"abstract":"<div><p>Fighting malignant neoplasms <em>via</em><span><span> repurposing existing </span>drugs<span> could be a welcome move for prosperous cancer remediations. In the current work, nanovehiculation and optimization of the repositioned itraconazole<span> (ITZ) utilizing ascorbyl palmitate (AP) aspasomes would be an auspicious approach. Further, the optimized aspasomes were incorporated in a cream and tracked for skin deposition. The </span></span></span><em>in vivo</em><span> efficacy of aspasomal cream on mice subcutaneous Ehrlich carcinoma<span><span> model was also assessed. The optimized aspasomes revealed nano size (67.83 ± 6.16 nm), negative charge (-79.40 ± 2.23 mV), &gt; 95% ITZ entrapment and high colloidal stability. AP yielded substantial antioxidant capacity and pushed the ITZ cytotoxicity forward against </span>A431 cells (IC</span></span>₅₀<span> = 5.3±0.27 μg/mL). An appealing privilege was the aspasomal cream that corroborated spreadability, contemplated skin permeation and potentiated </span><em>in vivo</em><span><span> anticancer<span> competence, reflected in 62.68% reduction in the tumor weight. Such synergistic tumor probes set the foundation for futuristic clinical translation and </span></span>commercialization.</span></p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76197085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA-gold nanoprobe-based integrated biosensing technology for non-invasive liquid biopsy of serum miRNA: A new frontier in prostate cancer diagnosis","authors":"Prakash Kshirsagar Ph.D. ,&nbsp;Parthasarathy Seshacharyulu Ph.D. ,&nbsp;Sakthivel Muniyan Ph.D. ,&nbsp;Satyanarayan Rachagani Ph.D. ,&nbsp;Lynette M. Smith Ph.D. ,&nbsp;Christopher Thompson Ph.D. ,&nbsp;Ashu Shah Ph.D. ,&nbsp;Kavita Mallya MS ,&nbsp;Sushil Kumar Ph.D. ,&nbsp;Maneesh Jain Ph.D. ,&nbsp;Surinder K. Batra Ph.D.","doi":"10.1016/j.nano.2022.102566","DOIUrl":"10.1016/j.nano.2022.102566","url":null,"abstract":"<div><p><span><span>The low specificity of prostate-specific antigen contributes to overdiagnosis and ov ertreatment of </span>prostate cancer<span><span> (PCa) patients. Hence, there is an urgent need for inclusive diagnostic platforms that could improve the diagnostic accuracy of PCa. Dysregulated </span>miRNAs<span> are closely associated with the progression and recurrence and have emerged as promising diagnostic and prognostic biomarkers for PCa. Nevertheless, simple, rapid, and ultrasensitive quantification of serum miRNAs is highly challenging. This study designed, synthesized, and demonstrated the practicability of DNA-linked gold nanoprobes (DNA-AuNPs) for the single-step quantification of miR-21/miR-141/miR-375. In preclinical study, the assay differented PCa Pten conditional knockout (Pten</span></span></span>^cKO) mice compared to their age-matched Pten wild-type (Pten^WT<span>) control mice. In human sera, receiver operating characteristic (ROC) curve-based correlation analyses revealed clear discrimination between PCa patients from normal healthy controls using training and validation sets. Overall, we established integrated nano-biosensing technology for the PCR-free, non-invasive liquid biopsies of multiple miRNAs for PCa diagnosis.</span></p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9721761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}