European Journal of Pharmaceutics and Biopharmaceutics最新文献_第9页

Corrigendum to “pH-Sensitive Tacrolimus loaded nanostructured lipid carriers for the treatment of inflammatory bowel disease” [Eur. J. Pharm. Biopharm. 204 (2024) 114461] 对 "用于治疗炎症性肠病的 pH 值敏感的他克莫司负载纳米结构脂质载体"[Eur. J. Pharm. Biopharm. 204 (2024) 114461]的更正。

IF 4.4 2区医学

European Journal of Pharmaceutics and Biopharmaceutics Pub Date : 2025-01-01 DOI: 10.1016/j.ejpb.2024.114573

Sidra Altaf , Mahira Zeeshan , Hussain Ali , Ahmed Zeb , Iqra Afzal , Ayesha Imran , Danish Mazhar , Salman Khan , Fawad Ali Shah

引用次数: 0

Corrigendum “The chemotherapeutic potential of doxorubicin-loaded PEG-b-PLGA nanopolymersomes in mouse breast cancer model” [Eur. J. Pharm. Biopharm. 94 (2015) 521–531] Corrigendum "The chemotherapeutic potential of doxorubicin-loaded PEG-b-PLGA nanopolymersomes in mouse breast cancer model" [Eur. J. Pharm. Biopharm. 94 (2015) 521-531].

IF 4.4 2区医学

European Journal of Pharmaceutics and Biopharmaceutics Pub Date : 2025-01-01 DOI: 10.1016/j.ejpb.2024.114568

Mona Alibolandi , Fatemeh Sadeghi , Khalil Abnous , Fatemeh Atyabi , Mohammad Ramezani , Farzin Hadizadeh

引用次数: 0

Optimization and evaluation of gastroresistant microparticles designed for siRNA oral delivery siRNA口服给药胃耐药微颗粒的优化与评价。

IF 4.4 2区医学

European Journal of Pharmaceutics and Biopharmaceutics Pub Date : 2025-01-01 DOI: 10.1016/j.ejpb.2024.114588

Thomas Stalder , Nathan Koenig , Raphaël Cornu , Gautier Laurent , Yann Pellequer , Florian Jurin , Brice Moulari , Hélène Martin , Arnaud Beduneau

{"title":"Optimization and evaluation of gastroresistant microparticles designed for siRNA oral delivery","authors":"Thomas Stalder , Nathan Koenig , Raphaël Cornu , Gautier Laurent , Yann Pellequer , Florian Jurin , Brice Moulari , Hélène Martin , Arnaud Beduneau","doi":"10.1016/j.ejpb.2024.114588","DOIUrl":"10.1016/j.ejpb.2024.114588","url":null,"abstract":"<div><div>Oral administration of siRNA is a challenging strategy for the local treatment of intestinal diseases, including cancer and inflammatory bowel disease. Both nucleic acids and delivery systems, especially lipid nanoparticles (LNPs), are sensitive to the acidic pH of the stomach, bile salts and digestive enzymes. The present work focuses on the design and evaluation of gastroresistant alginate microparticles (MPs) prepared with an original process for oral delivery of siRNA. MPs with a mean diameter of less than 200 µm were obtained without extrusion and emulsification methods. Onpattro® marketed pharmaceutical product and TNF-α siRNA-loaded LNPs were successfully microencapsulated with an efficiency of at least 80 %. Gastroresistance properties and intestinal release were demonstrated in simulated gastric and intestinal fluids. After exposure to simulated gastric fluid, MPs in contact with hepatocyte and LPS-activated monocyte-derived macrophage cell lines reduced the expression of transthyretin and TNF-α, demonstrating the preservation of the siRNA activity.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"206 ","pages":"Article 114588"},"PeriodicalIF":4.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754915","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}

引用次数: 0

The effects of ligand distribution and density on the targeting properties of dual-targeting folate/biotin Pluronic F127/Poly (lactic acid) polymersomes 配体分布和密度对双靶向叶酸/生物素Pluronic F127/聚乳酸聚合体靶向性的影响

IF 4.4 2区医学

European Journal of Pharmaceutics and Biopharmaceutics Pub Date : 2024-11-29 DOI: 10.1016/j.ejpb.2024.114598

Qing Xiao Wang, Zi Ling Li, Yan Chun Gong, Xiang Yuan Xiong

{"title":"The effects of ligand distribution and density on the targeting properties of dual-targeting folate/biotin Pluronic F127/Poly (lactic acid) polymersomes","authors":"Qing Xiao Wang, Zi Ling Li, Yan Chun Gong, Xiang Yuan Xiong","doi":"10.1016/j.ejpb.2024.114598","DOIUrl":"10.1016/j.ejpb.2024.114598","url":null,"abstract":"<div><div>Targeted drug delivery systems modified with two or more ligands were expected to have better anti-tumor ability than those with just one ligand due to the complexity and heterogeneity of tumors. Thus, dual-targeting Pluronic/poly (lactic acid) polymersomes containing biotin (BT) and folic acid (FA) ligands (BT/FA-F127-PLA) were designed to study their targeting properties over human ovarian cancer cells (OVCAR-3). Two kinds of dual-ligand targeting polymersomes, BT/FA-F127-PLA and (BT + FA)-F127-PLA, were prepared to study the effect of the dual-ligand distribution on the cell targeting of polymersomes. BT/FA-F127-PLA had two ligands distributed in the same polymersomes whereas (BT + FA)-F127-PLA had two ligands distributed in different polymersomes. The in vitro cytotoxicity and cellular uptake, and in vivo pharmacokinetic behaviors of BT/FA-F127-PLA were superior to those of (BT + FA)-F127-PLA. It suggested that biotin and folate ligands distributed on the same polymersomes could have the targeting effect of synergistic promotion. Further experiments on cell uptake mechanisms of polymersomes showed that the uptake of targeted polymersomes was associated with energy-dependent endocytosis, involving clathrin, caveolin protein, macropinocytosis and ligand receptor-mediated endocytosis. In addition, the effect of different density ratios of dual ligands for BT/FA-F127-PLA was further studied. The results showed that the cellular targeting effect of BT/FA-F127-PLA was the strongest when the molar ratio of biotin to folic acid was 7.5 %: 7.5 %. In conclusion, BT/FA-F127-PLA dual-targeting polymersomes could be good candidates as targeted drug delivery carriers.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"206 ","pages":"Article 114598"},"PeriodicalIF":4.4,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142756974","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}

引用次数: 0

Self-assembled nanovaccine based on apoferritin: Development and vaccine regimen evaluation 基于载铁蛋白的自组装纳米疫苗：开发和疫苗方案评价

IF 4.4 2区医学

European Journal of Pharmaceutics and Biopharmaceutics Pub Date : 2024-11-28 DOI: 10.1016/j.ejpb.2024.114589

Camila Machado França de Almeida , Wendy Martin Rios , Maíra Peres Ferreira Duarte , Izaíra Tincani Brandão , Natalia Floriano Paiva , Fabiana Testa Moura de Carvalho Vicentini

{"title":"Self-assembled nanovaccine based on apoferritin: Development and vaccine regimen evaluation","authors":"Camila Machado França de Almeida , Wendy Martin Rios , Maíra Peres Ferreira Duarte , Izaíra Tincani Brandão , Natalia Floriano Paiva , Fabiana Testa Moura de Carvalho Vicentini","doi":"10.1016/j.ejpb.2024.114589","DOIUrl":"10.1016/j.ejpb.2024.114589","url":null,"abstract":"<div><div>Apoferritin-based systems have been explored last decade for their potential as vaccine delivery for viral diseases. The nanosized properties of an apoferritin-based system could increase immunogenicity, contribute to antigen stability, and reduce the vaccines’ adverse effects. The mutated extracellular portion of the epidermal growth factor receptor (EGFRvIII peptide, PEPvIII) can be applied as a specific tumoral antigen due to rare expression in normal cells. In this context, the present study proposed the development and the immunogenicity evaluation of an apoferritin-based system (AFt) to deliver a peptide vaccine for an antitumoral purpose. We developed a formulation with different PEPvIII:AFt ratios and during the association efficiency analysis, identified the dependence between the AFt concentration and the PEPvIII association percentage in the formulation. Besides, differences in the immune responses against EGFRvIII were observed depending on the PEPvIII concentration due to the different association efficiencies. Finally, the humoral immune response results showed a high antibody production against AFt, which might affect the immunological tolerance. Collectively, this study establishes the PEPvIII:AFt formulation process and highlights the determinant factors for guaranteeing vaccine safety and efficacy.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"206 ","pages":"Article 114589"},"PeriodicalIF":4.4,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142746455","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}

引用次数: 0

Design, fabrication, and evaluation of antimicrobial sponge microneedles for the transdermal delivery of insulin 用于胰岛素透皮给药的抗菌海绵微针的设计、制造和评价

IF 4.4 2区医学

European Journal of Pharmaceutics and Biopharmaceutics Pub Date : 2024-11-28 DOI: 10.1016/j.ejpb.2024.114586

Xinyi Zhang , Yuelian Zhang , Huishan Zheng , Xue Yang , Shiqi Zou , Jianmin Chen

{"title":"Design, fabrication, and evaluation of antimicrobial sponge microneedles for the transdermal delivery of insulin","authors":"Xinyi Zhang , Yuelian Zhang , Huishan Zheng , Xue Yang , Shiqi Zou , Jianmin Chen","doi":"10.1016/j.ejpb.2024.114586","DOIUrl":"10.1016/j.ejpb.2024.114586","url":null,"abstract":"<div><div>Transdermal drug delivery systems hold promise, but their effectiveness is often constrained by the skin’s barrier. Microneedles (MNs) improve drug permeability by creating micro-channels in the skin, yet they continue to face challenges such as infection risks and safety concerns. To overcome these challenges, a novel antimicrobial sponge MNs (ASMNs@PVP-INS) modified with polyvinylpyrrolidone (PVP) for insulin (INS) delivery was designed. Mechanical testing demonstrated that these MNs possess excellent mechanical strength, capable of withstanding at least 0.11 N per needle without rupture. In vitro drug penetration tests revealed that the MNs consistently released over 75 % of INS within a 6 h. In an animal model, ASMNs@PVP-INS reduced initial blood glucose levels from 22.4 to 5.72 mmol/L, effectively maintaining glucose control for more than 6 h without inducing hypoglycemia. Additionally, agar diffusion assays indicated that INS loading did not compromise the antimicrobial properties of antimicrobial sponge MNs (ASMNs). Skin irritation tests showed that ASMNs@PVP-INS exhibited mild irritation (PII < 0.6), with skin damage fully recovering within 8 h. Safety assessments indicated no significant toxicity to mice, with biochemical markers remaining within normal ranges, thereby confirming their good biocompatibility. In conclusion, ASMNs@PVP-INS hold promise as a novel drug delivery vehicle.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"206 ","pages":"Article 114586"},"PeriodicalIF":4.4,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142746456","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}

引用次数: 0

Preparation and characterization of the ground mixture of rebamipide commercial tablets and Hydroxypropyl Cellulose-SSL by ball-milling: Application to the dispersoid of mouthwash suspension 球磨法制备利巴米胺市售片与羟丙基纤维素- ssl混料及其在漱口水混悬液中的应用

IF 4.4 2区医学

European Journal of Pharmaceutics and Biopharmaceutics Pub Date : 2024-11-27 DOI: 10.1016/j.ejpb.2024.114584

Senri Mizobuchi , Kaoru Hirose , Naoko Ishii , Yayoi Kawano , Takehisa Hanawa

{"title":"Preparation and characterization of the ground mixture of rebamipide commercial tablets and Hydroxypropyl Cellulose-SSL by ball-milling: Application to the dispersoid of mouthwash suspension","authors":"Senri Mizobuchi , Kaoru Hirose , Naoko Ishii , Yayoi Kawano , Takehisa Hanawa","doi":"10.1016/j.ejpb.2024.114584","DOIUrl":"10.1016/j.ejpb.2024.114584","url":null,"abstract":"<div><div>In the present study, to prepare dispersoids with high dispersion stability that can be used as mouthwash, ground mixtures of commercial rebamipide (RB) tablets and hydroxypropyl cellulose (HPC-SSL) samples were prepared by dry milling. The physicochemical properties of the ground mixture of HPC-SSL and the powder obtained from the preliminary ground RB tablets were then compared. The dispersoids’ physicochemical properties, dispersion stability, retention, and diffusiveness to the mucosal surfaces were evaluated <em>in vitro</em>. By co-grinding with HPC-SSL, RB transformed into fine particles around 303.6 – 361.5 nm that tended to prevent particle agglomeration in solution over time. The sample microparticles formed with HPC-SSL also avoided agglomeration on the mucosal surface for 24 h, improving oral retention. Furthermore, the ground mixture of HPC-SSL and the powder obtained from the preliminary ground RB tablets dispersed and permeated the mucus gel layer on the mucosal surface (24.2 %) but not the mucosal cells, indicating that RB remained on the mucosal surface. These results suggest that ground mixtures of commercial rebamipide (RB) tablets and hydroxypropyl cellulose (HPC-SSL) samples can be applied as a powdered suspension preparation because they showed high dispersion stability and oral mucosal retention.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"206 ","pages":"Article 114584"},"PeriodicalIF":4.4,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142746457","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}

引用次数: 0

Numerical modeling and simulation for microneedles drug delivery: A novel comprehensive swelling-obstruction-mechanics model 微针给药的数值建模与仿真：新型膨胀-阻塞-力学综合模型

IF 4.4 2区医学

European Journal of Pharmaceutics and Biopharmaceutics Pub Date : 2024-11-26 DOI: 10.1016/j.ejpb.2024.114583

Peijing Yang , Qinghua Song , Lujie Zhang , Zhanqiang Liu , Haifeng Ma

{"title":"Numerical modeling and simulation for microneedles drug delivery: A novel comprehensive swelling-obstruction-mechanics model","authors":"Peijing Yang , Qinghua Song , Lujie Zhang , Zhanqiang Liu , Haifeng Ma","doi":"10.1016/j.ejpb.2024.114583","DOIUrl":"10.1016/j.ejpb.2024.114583","url":null,"abstract":"<div><div>Hydrogel microneedles have attracted significant attention in drug delivery due to their non-invasiveness and efficient administration. However, a thorough understanding of the drug transport mechanism is essential to achieve controlled drug delivery and geometry optimization of microneedles. In this study, a new swelling-obstruction-mechanics model is presented to describe the swelling and drug release behavior of hydrogel microneedles. The model integrates the swelling kinetics, the obstruction scaling of drug molecules, and the mechanical properties of hydrogel and skin and reveals the effects of swelling of the microneedle matrix and drug molecules on drug release. Subsequently, numerical simulations were conducted using the model, which enabled the optimization of hydrogel microneedle design parameters by adjusting the input variables. The results show that the geometric parameters of microneedles, especially the cross-sectional shape, have a significant effect on the drug release performance. Nevertheless, the parameters affect each other and need to be considered in the selection of a variety of factors. Additionally, penetration depth significantly affects drug release efficiency, highlighting the need for auxiliary application devices. In summary, the model advances both theoretical understanding and practical design of hydrogel microneedles, identifying key factors in drug release and optimizing their efficiency and reliability for clinical applications.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"206 ","pages":"Article 114583"},"PeriodicalIF":4.4,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738866","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}

引用次数: 0

A multifaceted approach to understanding protein-buffer interactions in biopharmaceuticals 从多方面了解生物制药中蛋白质与缓冲剂的相互作用。

IF 4.4 2区医学

European Journal of Pharmaceutics and Biopharmaceutics Pub Date : 2024-11-19 DOI: 10.1016/j.ejpb.2024.114582

Blaž Lebar , Maria Orehova , Boštjan Japelj , Ernest Šprager , Rok Podlipec , Tilen Knaflič , Iztok Urbančič , Benjamin Knez , Mitja Zidar , Jure Cerar , Janez Mravljak , Aleš Žula , Denis Arčon , Janez Plavec , Stane Pajk

{"title":"A multifaceted approach to understanding protein-buffer interactions in biopharmaceuticals","authors":"Blaž Lebar , Maria Orehova , Boštjan Japelj , Ernest Šprager , Rok Podlipec , Tilen Knaflič , Iztok Urbančič , Benjamin Knez , Mitja Zidar , Jure Cerar , Janez Mravljak , Aleš Žula , Denis Arčon , Janez Plavec , Stane Pajk","doi":"10.1016/j.ejpb.2024.114582","DOIUrl":"10.1016/j.ejpb.2024.114582","url":null,"abstract":"<div><div>The excipient selection process plays a crucial role in biopharmaceutical formulation development to ensure the long-term stability of the drug product. Though there are numerous options approved by regulatory authorities, only a subset is commonly utilized. Previous research has proposed various stabilization mechanisms, including protein-excipient interactions. However, identifying these interactions remains challenging due to their weak and transient nature. In this study, we present a comprehensive approach to identify such interactions. Using the <span><math><mrow><msup><mrow><mspace></mspace></mrow><mn>1</mn></msup><mi>H</mi></mrow></math></span> <span><math><msub><mi>T</mi><mn>2</mn></msub></math></span> CPMG (Carr-Purcel-Meiboom-Gill) filter experiment we identified interactions of rituximab with certain buffers and amino acids, shedding light on its Fc fragment instability that manifested during the enzymatic cleavage of the antibody. Moreover, chemometric analyses of 2D NMR fingerprints revealed interactions of selected excipients with antibody fragments. Furthermore, molecular dynamics simulations revealed potential interacting hotspots without NMR spectra assignment. Our results highlight the importance of an orthogonal methods approach to uncovering these critical interactions, advancing our understanding of excipient stabilization mechanisms and rational formulation design in biopharmaceutics.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"206 ","pages":"Article 114582"},"PeriodicalIF":4.4,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686342","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}

引用次数: 0

Continuous twin-screw melt granulation of drug-loaded electrospun fibers 载药电纺纤维的连续双螺杆熔融造粒。

IF 4.4 2区医学

European Journal of Pharmaceutics and Biopharmaceutics Pub Date : 2024-11-17 DOI: 10.1016/j.ejpb.2024.114580

Petra Záhonyi, Áron Gábor Müncz, Anna Péter-Haraszti, Zsombor Kristóf Nagy, István Csontos, György Marosi, Edina Szabó

{"title":"Continuous twin-screw melt granulation of drug-loaded electrospun fibers","authors":"Petra Záhonyi, Áron Gábor Müncz, Anna Péter-Haraszti, Zsombor Kristóf Nagy, István Csontos, György Marosi, Edina Szabó","doi":"10.1016/j.ejpb.2024.114580","DOIUrl":"10.1016/j.ejpb.2024.114580","url":null,"abstract":"<div><div>Electrospinning (ES) is a promising continuous formulation strategy to produce amorphous solid dispersions (ASDs) and thereby improve the dissolution of poorly water-soluble drugs. However, processing the electrospun material into solid dosage forms (e.g. tablets) is challenging due to the poor flow properties. In this research, continuous twin-screw melt granulation was applied to improve the flowability of the fibers and therefore ease the further processing steps. During this work, two ASD compositions were investigated: one containing 60 % poly-vinylpyrrolidone-vinyl acetate 6:4 copolymer and 40 % itraconazole (ITR), and another one containing hydroxypropyl methylcellulose (HPMC) and ITR in the same ratio. Both fiber compositions were granulated with polyethene glycol as the binder material, while the effects of the process parameters were examined. The application of higher granulation temperature and screw configurations with increased shear forces compromised the fibrous structure, induced crystallization of the ASD, and decreased the dissolution. However, the stability of the ITR-HPMC fibers proved to be higher as their granulation at 60 °C led to granules with adequate flow properties and dissolution. Moreover, tablets with fewer excipients were pressed from them, resulting in a 34 % reduction in weight. Consequently, this process can complement ES technology and facilitate its industrial implementation.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"206 ","pages":"Article 114580"},"PeriodicalIF":4.4,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675569","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}

引用次数: 0