化学•材料最新文献

{"title":"Iontophoresis-driven alterations in nanoparticle uptake pathway and intracellular trafficking in carcinoma skin cancer cells.","authors":"Gabriela Fávero Galvão, Raquel Petrilli, Vanessa Cristina Arfelli, Andréia Nogueira Carvalho, Yugo Araújo Martins, Roberta Ribeiro Costa Rosales, Leticia Fröhlich Archangelo, Luis Lamberti Pinto daSilva, Renata Fonseca Vianna Lopez","doi":"10.1016/j.colsurfb.2024.114459","DOIUrl":"10.1016/j.colsurfb.2024.114459","url":null,"abstract":"<p><p>Effective treatment of squamous cell carcinoma (SCC) poses challenges due to intrinsic drug resistance and limited drug penetration into tumor cells. Nanoparticle-based drug delivery systems have emerged as a promising approach to enhance therapeutic efficacy; however, they often face hurdles such as inadequate cellular uptake and rapid lysosomal degradation. This study explores the potential of iontophoresis to augment the efficacy of liposome and immunoliposome-based drug delivery systems for SCC treatment. The study assessed iontophoresis effects on SCC cell line (A431) viability, nanoparticle uptake dynamics, and intracellular distribution patterns. Specific inhibitors were employed to delineate cellular internalization pathways, while fluorescence microscopy and immunohistochemistry examined changes in EGFR expression and lysosomal activity. Results demonstrated that iontophoresis significantly increased cellular uptake of liposomes and immunoliposomes, achieving approximately 50 % uptake compared to 10 % with passive treatment. This enhancement correlated with modifications in endocytic pathways, favoring macropinocytosis and caveolin-mediated endocytosis for liposomes, and macropinocytosis and clathrin-mediated pathways for immunoliposomes. Moreover, iontophoresis induced alterations in EGFR distribution and triggered syncytium-like cellular clustering. It also attenuated lysosomal activity, thereby reducing nanoparticle degradation and prolonging intracellular retention of therapeutic agents. These findings underscore the role of iontophoresis in modulating nanoparticle internalization pathways, offering insights that could advance targeted drug delivery strategies and mitigate therapeutic resistance in SCC and other malignancies.</p>","PeriodicalId":279,"journal":{"name":"Colloids and Surfaces B: Biointerfaces","volume":"248 ","pages":"114459"},"PeriodicalIF":5.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875661","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":"Platelet-mimicking nanoparticles loaded with diallyl trisulfide for Mitigating Myocardial Ischemia-Reperfusion Injury in rats.","authors":"Yihan Chen, Ling Lin, Lingling Xu, Qiaofeng Jin, Wenpei Fu, Ying Bai, Tian Huang, Tang Gao, Wenqian Wu, Chunyan Xu, Jing Wang, Li Zhang, Qing Lv, Yali Yang, Mingxing Xie, Xiaoqiu Dong","doi":"10.1016/j.colsurfb.2024.114460","DOIUrl":"10.1016/j.colsurfb.2024.114460","url":null,"abstract":"<p><p>Hydrogen sulfide (H₂S) shows promise in treating myocardial ischemia-reperfusion injury (MIRI), but the challenge of controlled and sustained release hinders its clinical utility. In this study, we developed a platelet membrane-encapsulated mesoporous silica nanoparticle loaded with the H₂S donor diallyl trisulfide (PM-MSN-DATS). PM-MSN-DATS demonstrated optimal encapsulation efficiency and drug-loading content. Comprehensive in vitro and in vivo assessments confirmed the biosafety of PM-MSN-DATS. In vitro, PM-MSN-DATS adhered to inflammation-activated endothelial cells and exhibited targeted accumulation in MIRI rat hearts. In vivo experiments revealed significant reductions in reactive oxygen species (ROS) and myocardial fibrosis area, improving cardiac function. Our findings highlight successfully creating a targeted H₂S delivery system through platelet membrane-coated MSN nanoparticles. This well-designed drug delivery platform holds significant promise for advancing MIRI treatment strategies.</p>","PeriodicalId":279,"journal":{"name":"Colloids and Surfaces B: Biointerfaces","volume":"248 ","pages":"114460"},"PeriodicalIF":5.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875664","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":"Thioether functionalized degradable poly(amino acids) and its calcium sulfate/calcium hydrogen phosphate composites: Reducing oxidative stress and promoting osteogenesis.","authors":"Wei Zhang, Xiaolu Chen, Hao Deng, Xinyue Yang, Shijie Cai, Hulin Yang, Haohao Ren, Yonggang Yan","doi":"10.1016/j.colsurfb.2024.114485","DOIUrl":"10.1016/j.colsurfb.2024.114485","url":null,"abstract":"<p><p>The imbalance of redox homeostasis, especially the abnormal levels of reactive oxygen species (ROS), is a key obstacle in the bone repair process. Therefore, developing materials capable of scavenging ROS and modulating the microenvironment of bone defects is crucial for promoting bone repair. In this study, to endow poly(amino acids) (PAA) and its composites with anti-oxidative stress properties and enhanced osteogenic differentiation, we designed and prepared a calcium sulfate/calcium hydrogen phosphate/poly(amino acids) (PCDM) composite material with a thioether structure (-S-) in the molecular chain of PAA matrix through situ polymerization and physical blending method. The results showed that the thioether was successfully introduced into the polymer, and the intrinsic viscosities of the poly(amino acids) ranged from 0.27 to 0.73 dL/g. PCDM materials exhibited good mechanical properties, with a compressive strength ranging from 16.28 to 33.83 MPa. The degradation performance results showed that the composite materials had a weight loss of 23.9-35.3 % after four weeks. The antioxidant stress results showed that the PCDM composite materials scavenged 67.6 %-78.3 % of DPPH radicals after 24 h and 61.4 %-93.6 % of ABTS radicals after 4 h, effectively reducing ROS levels in mouse bone mesenchymal stem cells. The cytotoxicity and osteogenic differentiation results showed that the materials had cytocompatibility and could promote alkaline phosphatase secretion and mineralized nodule formation. In conclusion, PCDM materials might broaden the application of poly(amino acids) composites in bone defect repair by regulating the ROS microenvironment and promoting the osteogenic differentiation of stem cells.</p>","PeriodicalId":279,"journal":{"name":"Colloids and Surfaces B: Biointerfaces","volume":"248 ","pages":"114485"},"PeriodicalIF":5.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925852","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":"Computational exploration of the self-aggregation mechanisms of phenol-soluble modulins β1 and β2 in Staphylococcus aureus biofilms.","authors":"Huan Xu, Xiaohan Zhang, Zhongyue Lv, Fengjuan Huang, Yu Zou, Chuang Wang, Feng Ding, Yunxiang Sun","doi":"10.1016/j.colsurfb.2025.114498","DOIUrl":"10.1016/j.colsurfb.2025.114498","url":null,"abstract":"<p><p>The formation of functional bacterial amyloids by phenol-soluble modulins (PSMs) in Staphylococcus aureus is a critical component of biofilm-associated infections, providing robust protective barriers against antimicrobial agents and immune defenses. Clarifying the molecular mechanisms of PSM self-assembly within the biofilm matrix is essential for developing strategies to disrupt biofilm integrity and combat biofilm-related infections. In this study, we analyzed the self-assembly dynamics of PSM-β1 and PSM-β2 by examining their folding and dimerization through long-timescale atomistic discrete molecular dynamics simulations. Our findings revealed that both peptides primarily adopt helical structures as monomers but shift to β-sheets upon dimerization. Monomeric state, PSM-β1 exhibited frequent transitions between helical and β-sheet forms, while PSM-β2 largely retained a helical structure. Upon dimerization, both peptides showed pronounced β-sheet formation around conserved C-terminal residues 21-44. Residues 21-33, largely unstructured as monomers, demonstrated strong tendencies for β-sheet formation and intermolecular interactions, underscoring their central role in the self-assembly of both peptides. Additionally, the PSM-β1 N-terminus formed β-sheets only when interacting with the C-terminus, whereas the PSM-β2 N-terminus remained helical and uninvolved in β-sheet formation. These distinct aggregation behaviors likely contribute to biofilm dynamics, with C-terminal regions facilitating biofilm formation and N-terminal regions influencing stability. Targeting residues 21-33 in PSM-β1 and PSM-β2 offers a promising therapeutic approach for disrupting biofilm integrity. This study advances our understanding of PSM-β1 and PSM-β2 self-assembly and presents new targets for drug design against biofilm-associated diseases.</p>","PeriodicalId":279,"journal":{"name":"Colloids and Surfaces B: Biointerfaces","volume":"248 ","pages":"114498"},"PeriodicalIF":5.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942104","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":"Stimuli-responsive dual-drug loaded microspheres with differential drug release for antibacterial and wound repair promotion.","authors":"Yating Wu, Guihua Wei, Xin Cao, Ran Wang, Xue Gou","doi":"10.1016/j.colsurfb.2024.114455","DOIUrl":"10.1016/j.colsurfb.2024.114455","url":null,"abstract":"<p><p>The healing of infected wounds is a complex and dynamic process requiring tailored treatment strategies that address both antimicrobial and reparative needs. Despite the development of numerous drugs, few approaches have been devised to optimize the timing of drug release for targeting distinct phases of infection control and tissue repair, limiting the overall treatment efficacy. Here, a stimuli-responsive microsphere encapsulating dual drugs was developed to facilitate differential drug release during distinct phases of antibacterial and repair promotion, thereby synergistically enhancing wound healing. Specifically, zeolite imidazolate backbone in poly (lactic-co-glycolic acid) (PLGA) microsphere was employed for the encapsulation of ciprofloxacin (CIP), responding to acidic environment of bacteria and releasing antibiotic for antibacterial therapy. Meanwhile, curcumin (CUR) encapsulated in PLGA exhibited a gradual release profile, contributing to synergistic antibacterial effects. During the tissue repair phase, near-infrared light stimulation of Fe₃O₄ embedded in PLGA generated heat, elevating the temperature to the glass transition point of PLGA, which significantly enhanced the release of CUR thereby promoting tissue repair. In vitro experiments demonstrated that the release of CIP and CUR achieved significant antibacterial effects in the early stages of treatment. Additionally, CUR could effectively enhance fibroblast migration and proliferation. In vivo studies using a mouse abscess model revealed that the microspheres exhibited remarkable antibacterial and wound-healing capabilities, effectively enhancing the re-epithelialization of wound tissue and reducing the infiltration of inflammatory cells. This study provides novel strategies for constructing drug delivery systems that match dynamic stages of wound healing, offering improved therapeutic outcomes for infected wounds.</p>","PeriodicalId":279,"journal":{"name":"Colloids and Surfaces B: Biointerfaces","volume":"248 ","pages":"114455"},"PeriodicalIF":5.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862588","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":"Corrigendum to \"Preparation of antibacterial hydrogel from poly(aspartic hydrazide) and quaternized N-[3-(dimethylamino) propyl] methylacrylamide copolymer with antioxidant and hemostatic effects for wound repairing\" [Colloids Surf. B Biointerfaces 238 (2024) 113881].","authors":"Yu Zhang, Junling Wang, Zhe Cui, Shuai Guo, Yong Wang, Wenjuan Li, Chengyan Zhou, Mingtao Run, Jianglei Qin","doi":"10.1016/j.colsurfb.2024.114463","DOIUrl":"10.1016/j.colsurfb.2024.114463","url":null,"abstract":"","PeriodicalId":279,"journal":{"name":"Colloids and Surfaces B: Biointerfaces","volume":"248 ","pages":"114463"},"PeriodicalIF":5.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142870770","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":"pH/H₂O₂ dual-responsive macrophage-targeted chitosaccharides nanoparticles to combat intracellular bacterial infection.","authors":"Xiaomei Dai, Yu Li, Yongjie Zhang, Yuqin Zou, Siyuan Yuan, Feng Gao","doi":"10.1016/j.colsurfb.2024.114465","DOIUrl":"10.1016/j.colsurfb.2024.114465","url":null,"abstract":"<p><p>Antibiotic resistance combined with bacteria internalization result in recurrent infections that seriously threaten human health. To overcome these problems, a pH/H₂O₂ dual-responsive nanoparticle (COSBN@CFS@PS) that can target macrophages, exhibiting synergistic antibiotic and β-lactamase inhibitor activity, is reported. Chitosaccharides (COS) is covalently bound with benzenboronic acid pinacol ester and assemble with cefoxitin sodium salt (CFS) to form COSBN@CFS nanoparticles. Then, COSBN@CFS was encapsulated with phosphatidylserine (PS), which aimed to targeted uptake by macrophages. After the uptake, the pH/H₂O₂ dual-responsive nanoparticle could effectively inhibit β-lactamase activity by release boronic acid (β-lactamase inhibitor), and then reinforced the antibacterial activity of CFS. Meanwhile, the resultant nanoparticles could significantly inhibit the growth of CFS-resistant bacteria. Furthermore, these nanoparticles could eliminate intracellular bacteria in vivo through the synergistic activities of antibiotic and β-lactamase inhibitor. The excellent biocompatibility and outstanding bactericidal activity promise COSBN@CFS@PS have great potential for diverse intracellular bacterial infection therapy.</p>","PeriodicalId":279,"journal":{"name":"Colloids and Surfaces B: Biointerfaces","volume":"248 ","pages":"114465"},"PeriodicalIF":5.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875663","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":"Construction of a high-capacity drug microcarrier using diatom frustules.","authors":"Houjie Wang, Runyu You, Yangqi Jin, Guangning Wang, Feng Li, Yahui Gao, Changping Chen, Nengming Xiao, Junrong Liang","doi":"10.1016/j.colsurfb.2024.114481","DOIUrl":"10.1016/j.colsurfb.2024.114481","url":null,"abstract":"<p><p>The drug loading capacity is a critical performance metric for drug delivery systems. A high capacity ensures efficient drug delivery to target sites at lower doses, reducing the amount of carrier material needed and lessening patient burden. However, improving drug loading capacity in diatom frustule-based systems remains a challenge. In this study, we explored effective strategies for developing a microcarrier with a high drug loading efficiency using diatom frustules (DF) derived from Thalassiosira weissflogii. We found that combining an evaporative loading method with a chitosan (Chi) coating was particularly effective for enhancing the drug loading capacity of indomethacin (IND), a hydrophobic model drug. Further optimization of the indomethacin-to-APTES-modified frustule (DF-NH₂) ratio to 2:1, along with adjusting the medium pH to 5, further improved drug loading efficiency. Additionally, the chitosan coating on the drug-loaded frustules not only enabled sustained drug release but also enhanced the biocompatibility of the carriers. The resulting DF-NH₂/IND@Chi microcarrier demonstrated a drug loading efficiency of 58.78 ± 1.92 % for IND, with a pH-dependent controlled release profile. This performance significantly outperforms previous reports, which typically report loading efficiencies between 10 % and 35 %, with few exceeding 40 %. In vitro cytotoxicity tests also revealed significant activity against colon cancer cells, highlighting the potential therapeutic benefits of this system. This study provides a systematic approach to creating high-capacity drug microcarriers using diatom frustules, offering promising prospects for future drug delivery applications.</p>","PeriodicalId":279,"journal":{"name":"Colloids and Surfaces B: Biointerfaces","volume":"248 ","pages":"114481"},"PeriodicalIF":5.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913222","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":"Investigation of bacterial nanocellulose/calcium phosphates-based composite containing cerium for bone repair.","authors":"Ricardo Barbosa Sousa, Alessandra Cristina Dametto, Gabriela Fontana de Mesquita, Pedro Henrique Ricardo, Júlia Venturini Helaehil, Santiago Medina-Carrasco, Josy Anteveli Osajima Furtini, Guilherme Ferreira Caetano, Hernane S Barud, Edson C Silva-Filho","doi":"10.1016/j.colsurfb.2024.114476","DOIUrl":"10.1016/j.colsurfb.2024.114476","url":null,"abstract":"<p><p>Bacterial nanocellulose (BNC) has attracted considerable attention in the field of biomedical engineering due to its potential for use in bone regeneration applications. The present study investigates the in vitro and in vivo efficacy of bacterial nanocellulose (BNC) combined with calcium and cerium ions (BNC-Ce:CaP) in bone regeneration applications. XRD analysis confirmed the presence of monetite and hydroxyapatite phases in BNC-CaP, while BNC-Ce:CaP revealed an additional brushite phase. Based on XPS analysis, cerium (III) is found in BNC-Ce:CaP at a concentration of 4.14 % (mol/mol). BNC revealed ultrafine 3D nanofibers with diameters ranging from 20.8 to 53.0 nm, while BNC-Ce:CaP composite, containing cerium, exhibited urchin-like structures with diameters around 1 µm and BNC-CaP composite presented phosphates covering the fiber surfaces, leading to significant thickness increases and pleat formation (70-180 nm). The composite materials demonstrated insignificant cytotoxicity. The results performed by histomorphometric analysis demonstrated that the BNC-Ce:CaP composites showed superior mineralized tissue formation after 60 days. Gene expression revealed a reduction in the inflammatory response and an increase in the expression of osteogenic markers, such as Bmp-2 and Osterix, in addition to an increase in the expression of angiogenic genes, such as Vegf. These findings highlight the potential of BNC-Ce:CaP composites as effective barriers to promote bone regeneration.</p>","PeriodicalId":279,"journal":{"name":"Colloids and Surfaces B: Biointerfaces","volume":"248 ","pages":"114476"},"PeriodicalIF":5.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925851","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":"Anticancer therapeutic effect of magnetic guided cobalt ferrite/doxorubicin-loaded ROS-responsive bilirubin nanoparticles in a colon cancer model.","authors":"Hyo Kang, Reju George Thomas, Subin Kim, Jae Kyun Ju, Yong Yeon Jeong","doi":"10.1016/j.colsurfb.2024.114487","DOIUrl":"10.1016/j.colsurfb.2024.114487","url":null,"abstract":"<p><strong>Purpose: </strong>The aim of this study is to synthesize the cobalt iron oxide (CoFe) and doxorubicin (Dox)-loaded chitosan bilirubin (ChiBil) nanoparticles and to investigate the anticancer therapeutic effect of the synthesized nanoparticles under magnetic guidance in a colon cancer.</p><p><strong>Materials and methods: </strong>ChiBil-CoFe-Dox nanoparticles were synthesized by conjugating CoFe and Dox and then loaded onto ChiBil nanoparticles. Synthesis were characterized using thermogravimetric (TGA) analysis, inductive coupled plasma (ICP) analysis, dynamic light scattering (DLS), zeta potential and field emission-transmission electron microscopy (FE-TEM). Cellular uptake and cytotoxicity studies were conducted in vitro. Biodistribution and tumor inhibition study was done in vivo CT-26 colon cancer model.</p><p><strong>Results: </strong>The ChiBil-CoFe-Dox nanoparticles were successfully synthesized in this study. The in vitro cytotoxicity study showed that the ChiBil-CoFe-Dox nanoparticle had a toxic effect on cancer cells. The accumulation of ChiBil-CoFe-Dox nanoparticles was enhanced under magnetic guidance, as observed by in vivo. Tumor inhibition study showed that the ChiBil-CoFe-Dox nanoparticle effectively reduced tumor size in vivo mice colon cancer model, especially when combined with magnetic guidance.</p><p><strong>Conclusion: </strong>This study showed that ChiBil-CoFe-Dox nanoparticle was successfully synthesized and effectively reduced tumor size, especially when combined with magnetic guidance. The in vitro and in vivo results suggested that the ROS stimuli responsive ChiBil-CoFe-Dox nanoparticles may be a potent therapeutic option for treating colon cancer.</p>","PeriodicalId":279,"journal":{"name":"Colloids and Surfaces B: Biointerfaces","volume":"248 ","pages":"114487"},"PeriodicalIF":5.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930217","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}