AAPS PharmSciTech最新文献

{"title":"Cyclosporine a Eluting Nano Drug Reservoir Film for the Management of Dry Eye Disease","authors":"Pinal Chaudhari,&nbsp;Vivek M. Ghate,&nbsp;Madhavan Nampoothiri,&nbsp;Shaila A. Lewis","doi":"10.1208/s12249-025-03104-9","DOIUrl":"10.1208/s12249-025-03104-9","url":null,"abstract":"<div><p>Cyclosporine A (CsA) is widely used to treat dry eye disease (DED), and ocular morbidity is on the rise and is a growing concern globally. However, several drug and formulation challenges, such as poor drug solubility, short pre-corneal residence time, and poor patient compliance, have limited the ocular bioavailability of CsA to &lt; 5%. A CsA cyclodextrin-based ternary complex loaded dissolvable nano drug reservoir films were developed to overcome these limitations and efficiently manage DED. Drug-loaded nano-reservoir films were fabricated via lithography using silicone and poly (dimethyl siloxane) (PDMS) molds. Different physicochemical characterizations were performed to confirm the formation of stable CsA-cyclodextrin-based ternary complexes. Formation of nanoreservoirs on the films was confirmed using SEM and AFM. Optimized CsA-complex-loaded nano-reservoir films were evaluated for <i>in vitro</i> drug release, ex vivo corneal permeation, and <i>in vivo</i> precorneal retention. Preclinical efficacy studies were performed to assess the efficacy of CsA-complex-loaded nano-reservoirs in an experimental dry-eye mouse model. Physicochemical characterization confirmed the formation of a stable complex and the improved solubility of CsA. In vitro release and ex vivo permeation studies indicated a controlled drug release and improved permeation, respectively. Furthermore, tear volume measurement and corneal damage assessment using slit-lamp imaging suggested decreased dry eye symptoms, significantly increasing tear volume in the drug-loaded nano-reservoir-treated group. Moreover, histopathological studies corroborated the tear volume and slit-lamp imaging results, with reduced inflammation and neovascularization. The poorly water-soluble drug with cyclodextrin complex incorporated nanoreservoir films presents a potential alternative for managing various ocular diseases.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-025-03104-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143845661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formulation Strategy of BCS-II Drugs by Coupling Mechanistic In-Vitro and Nonclinical In-Vivo Data with PBPK: Fundamentals of Absorption-Dissolution to Parameterization of Modelling and Simulation","authors":"Shriya V A,&nbsp;Usha Y. Nayak,&nbsp;Muddukrishna Badamane Sathyanarayana,&nbsp;Bhim Bahadur Chaudhari,&nbsp;Krishnamurthy Bhat","doi":"10.1208/s12249-025-03093-9","DOIUrl":"10.1208/s12249-025-03093-9","url":null,"abstract":"<div><p>BCS class II candidates pose challenges in drug development due to their low solubility and permeability. Researchers have explored various techniques; co-amorphous and solid dispersion are major approaches to enhance <i>in-vitro</i> drug solubility and dissolution. However, <i>in-vivo</i> oral bioavailability remains challenging. Physiologically based pharmacokinetic (PBPK) modeling with a detailed understanding of drug absorption, distribution, metabolism, and excretion (ADME) using a mechanistic approach is emerging. This review summarizes the fundamentals of the PBPK, dissolution—absorption models, parameterization of oral absorption for BCS class II drugs, and provides information about newly emerging artificial intelligence/machine learning (AI/ML) linked PBPK approaches with their advantages, disadvantages, challenges and areas of further exploration. Additionally, the fully integrated workflow for formulation design for investigational new drugs (INDs) and virtual bioequivalence for generic molecules falling under BCS-II are discussed.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-025-03093-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143845753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sericin from Bombyx Mori as a By-product for DLP 3D Printing in Pharmaceutical and Biomedical Applications","authors":"Éverton da Silva Santos,&nbsp;Denise Tiemi Uchida,&nbsp;Marcos Luciano Bruschi","doi":"10.1208/s12249-025-03108-5","DOIUrl":"10.1208/s12249-025-03108-5","url":null,"abstract":"<div><p>Sericin, a silk-derived protein, has emerged as a potential material for Digital Light Processing (DLP) printing, particularly in uses requiring biocompatibility and sustainability. Sericin is a candidate for developing durable and precise 3D-printed structures due to its natural origin and intrinsic properties like film-forming ability and cross-linking potential. Its biocompatibility makes it suitable for medical applications, such as targeted delivery of anticancer drugs or creation of therapeutic supports directly on affected skin, orthodontic and cosmetic biomaterials, disease modulation, wound healing, antioxidant and antimicrobial applications, and regenerative medicine. Additionally, sericin can strengthen and stabilize printed structures while maintaining environmental integrity, aligning with the growing demand for eco-friendly materials in advanced manufacturing. However, formulating sericin-based resins for DLP printing presents challenges, including optimizing cross-linking and curing processes for obtaining desired properties of material. Overcoming these challenges could unlock the full potential of sericin in diverse fields, such as tissue engineering, where biocompatibility and precise structural integrity are critical. This review investigates the potential of sericin-based resins for 3D printing, emphasizing the protein’s compatibility with photopolymerizable systems and its capacity to improve the overall performance of DLP-printed materials. Further research is essential to refine sericin-based formulations, enabling their broader application in 3D printing technologies. By examining the unique characteristics of sericin, including its origins and material properties, this review underscores the protein's potential to drive innovation in sustainable manufacturing. Ultimately, sericin offers a viable alternative to synthetic resins and holds promise for advancing both biomedical and environmental applications through innovative 3D printing technologies.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143845663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Nanoparticle Formulations for Intracellular Delivery in Colorectal Cancer Therapy","authors":"Burcu Uner,&nbsp;Erdogan Oguzhan Akyildiz,&nbsp;Kubra Kolci,&nbsp;Rengin Reis","doi":"10.1208/s12249-025-03092-w","DOIUrl":"10.1208/s12249-025-03092-w","url":null,"abstract":"","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143818158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Finite Dose In Vitro Permeation Testing: Significance of Occluding the Donor compartment, a Case study","authors":"Prajwal N. Murthy,&nbsp;Mohammad Moinul Hossain,&nbsp;Santanu Kundu,&nbsp;Srinath Rangappa,&nbsp;Shivakumar H. N.","doi":"10.1208/s12249-025-03091-x","DOIUrl":"10.1208/s12249-025-03091-x","url":null,"abstract":"<div><p>The evaporation of the solvent induces significant changes in formulation, directly impacting its performance. The performance of topical products is determined by the interplay between their inherent quality attributes and the transformations that occur due to solvent evaporation when applied to the skin in clinically relevant doses. To accurately assess, <i>in vivo</i> performance, it is advisable to apply smaller doses to the skin and keep the donor compartment open to enable evaporation of solvents while carrying out <i>in vitro</i> permeation tests. This manuscript highlights the critical role of solvent evaporation in differentiating the performance of two compositionally distinct products. One gel formulation contained alcohol, while the other did not. Although both exhibited similar quality attributes, their drying profiles varied significantly. Permeation studies conducted with closed donor compartments (Evaporation-disabled (ED)) failed to reveal these differences. However, when the donor compartments were exposed to the atmosphere to allow evaporation (Evaporation-enabled (EN)), the performance differences between the two products became evident.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Foam-Based Drug Delivery Systems for Skin Disorders: A Comprehensive Review","authors":"Syrsulu Myrzagulova,&nbsp;Zhexenova Azhar N,&nbsp;Mohit Kumar,&nbsp;Devesh Kumar,&nbsp;Akshay Kumar","doi":"10.1208/s12249-025-03098-4","DOIUrl":"10.1208/s12249-025-03098-4","url":null,"abstract":"<div><p>Foam-based drug delivery systems signify a significant innovation in dermatology, facilitating improved drug penetration and administration via a gas-liquid dispersion matrix. These formulations have shown considerable promise in the medical, cosmetic, and pharmaceutical fields. Recent improvements in topical foams have resulted in their extensive utilization in dermatological therapies, with a growing emphasis on categorization techniques grounded in formulation composition and the creation of novel methodologies for assessing essential physicochemical factors. Foam formulations comprising calcipotriol and betamethasone demonstrate 30% enhanced therapeutic effectiveness in the treatment of psoriasis compared to traditional topical therapies. The low-density, aerated structure of foams promotes improved skin covering and hydration, which is especially advantageous for disorders like eczema. Moreover, novel advances such as propellant-free foams and the incorporation of nanotechnology have broadened the use of foam-based delivery methods in targeted drug administration and customized medicine. Ongoing research into new biomaterials and refined formulation procedures seeks to overcome these constraints, ensuring that foam-based systems emerge as a breakthrough method in dermatological care. These systems promise to enhance clinical results and overall patient quality of life by increasing medication bioavailability, patient adherence, and therapeutic effectiveness.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Gene Therapy: Towards a New Era of Medicine","authors":"Mokshit Bhagat,&nbsp;Raj Kamal,&nbsp;Jyoti Sharma,&nbsp;Kirandeep Kaur,&nbsp;Amit Sharma,&nbsp;Thakur Gurjeet Singh,&nbsp;Rohit Bhatia,&nbsp;Ankit Awasthi","doi":"10.1208/s12249-025-03096-6","DOIUrl":"10.1208/s12249-025-03096-6","url":null,"abstract":"","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143769722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"QbD-Based Development of Fluocinolone Nanocomposite Transdermal Gel: Optimization, Characterization, and Enhanced Anti-hyperpigmentation Efficacy Assessment","authors":"Priyanka Rathore,&nbsp;Rishikesh Gupta,&nbsp;Prem Prakash Singh,&nbsp;Anshu Awasthi,&nbsp;Ankita Kishore,&nbsp;Kuldeep K. Bansal,&nbsp;Alok Kumar Mahor","doi":"10.1208/s12249-025-03094-8","DOIUrl":"10.1208/s12249-025-03094-8","url":null,"abstract":"<div><p>The current study presents a comprehensive pharmaceutical engineering approach to developing an advanced transdermal drug delivery system for addressing skin hyperpigmentation through innovative nanocomposite gel formulation. Utilizing a systematic Quality-by-Design (QbD) methodology with Box-Behnken design, we developed a novel fluocinolone-loaded chitosan-graphene oxide nanocomposite (FCGN1) aimed at optimizing pharmaceutical performance and therapeutic efficacy. The nanocomposite formulation demonstrated critical pharmaceutical quality attributes: a precisely controlled nanoscale particle size of 144.78 ± 0.15 nm, stable zeta potential of -17.93 ± 3.75 mV, and high drug entrapment efficiency of 81.3 ± 3.64%. The optimized gel formulation (FNTG3) exhibited superior transdermal delivery characteristics, achieving approximately 70% permeation within 15 h and a significant flux rate of 190 µg/cm², which substantially outperforms current market alternatives. The comprehensive pharmaceutical evaluation included rigorous stability studies over 45 days, confirming consistent physical stability and sustained drug permeation. <i>In vivo</i> assessments using a UVB-induced hyperpigmentation rat model validated the formulation's dermal tolerability and depigmentation potential, demonstrating comparable or superior performance to commercial hydroquinone treatments. Histopathological analyses revealed pronounced depigmentation effects, attributable to the synergistic design of the nanocomposite system. The strategic integration of fluocinolone, chitosan, and graphene oxide facilitated enhanced drug release kinetics and improved skin penetration, highlighting the potential of rational pharmaceutical design in developing advanced topical delivery systems. This research provides a robust framework for developing sophisticated pharmaceutical dosage forms with enhanced therapeutic performance, offering significant insights into nanoscale drug delivery technologies for dermatological applications. The findings underscore the importance of systematic optimization and multifunctional component design in creating innovative pharmaceutical formulations.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143761754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of Curcumin-β-Cyclodextrin Complex Release in Injectable Hyaluronic Acid/Quince Seed Gum Hydrogel","authors":"Serdar Kolay,&nbsp;Nilhan Kayaman Apohan,&nbsp;Erdinç Babuç,&nbsp;Gökay Gün","doi":"10.1208/s12249-025-03095-7","DOIUrl":"10.1208/s12249-025-03095-7","url":null,"abstract":"<div><p>Injectable hydrogels play a crucial role in various biomedical applications, serving as fillers in tissue engineering, facilitating cell repair, and contributing to the development of drug delivery systems. This study aims to investigate the release of dissolved curcumin from a new injectable hyaluronic acid/quince seed gum (HA/QSG) hydrogel. Curcumin possesses numerous biological activities, including anti-cancer, antioxidant, antimicrobial, and anti-inflammatory properties. However, due to its very low water solubility, its bioavailability is poor. To address this, curcumin was encapsulated in three inclusion complexes: Cur 1:2 β-CD, Cur 1:4 β-CD, and Cur 1:6 β-CD. These Cur-β-CD inclusion complexes were lyophilized and converted into a water-soluble form. The curcumin, bisdemethoxycurcumin, and desmethoxycurcumin content of the obtained lyophilized Cur-β-CD complexes were analyzed using the HPLC method. HA-QSG hydrogels were loaded with Cur 1:2 β-CD inclusion complex in compositions of 0.75% (w/w), 0.50% (w/w), and 0.25% (w/w). The dissolution profiles of the HA-QSG hydrogels were examined in a pH 6.8 phosphate buffer medium, used as the swelling medium in intra-articular hydrogels. The initial burst of the 0.75% (w/w) hydrogel reached 9% release within the first 15 min, whereas the 0.25% (w/w) hydrogel exhibited only 6% release during the same period. The 0.75%(w/w) and 0.50% (w/w) hydrogels displayed very similar dissolution profiles, with a slightly faster release in the early stages of dissolutions, compared to the 0.25%(w/w) Cur β-CD-HA-QSG hydrogel. The 0.25%(w/w) Cur β-CD-HA-QSG hydrogel demonstrated a relatively slower release rate particularly during the initial stage of dissolution period. However, all three formulations reached approximately 98% release within 24 h. While the 0.75%(w/w) and 0.50%(w/w) curcumin-loaded HA-QSG hydrogels, with their rapid initial release, may be suited for intra-articular applications requiring quick drug availability, the 0.25%(w/w) curcumin-loaded HA-QSG hydrogel, with its slower release, may be more beneficial for sustained intra-articular delivery.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-025-03095-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biogenic Amino Acid Cross-Linked Hyaluronic Acid Nanoparticles Containing Dexamethasone for the Treatment of Dry Eye Syndrome","authors":"Ajit Mishra,&nbsp;Jitu Halder,&nbsp;Ivy Saha,&nbsp;Vineet Kumar Rai,&nbsp;Ritu Mahanty,&nbsp;Deepak Pradhan,&nbsp;Priyanka Dash,&nbsp;Chandan Das,&nbsp;Tushar Kanti Rajwar,&nbsp;Bibhanwita Satpathy,&nbsp;Salim Manoharadas,&nbsp;Muralidhar Tata,&nbsp;Amit Goyal,&nbsp;Biswakanth Kar,&nbsp;Goutam Ghosh,&nbsp;Goutam Rath","doi":"10.1208/s12249-025-03090-y","DOIUrl":"10.1208/s12249-025-03090-y","url":null,"abstract":"<div><p>Ocular barriers, poor retention time, and frequent ocular discharge suppress the activity of Dexamethasone. Arginine (Arg) and hyaluronic acid (HA) are crucial for maintaining ocular health because of their unique biological benefits. In this study, we investigated the cationic properties of arginine to develop dexamethasone-loaded HA nanoparticles (ADHA NPs) and evaluated their therapeutic potential in alleviating dry eye syndrome using various reported <i>in-vitro</i> and <i>in-vivo</i> techniques. The ionic cross-linking method was used to prepare ADHA NPs. The ADHA NPs exhibited nearly 94.99 ± 4.16% drug release at the end of 6 h and followed the Korsemeyar-Peppas kinetic model (R² = 0.9811). Moreover, the developed formulation exhibited a higher water retention capacity, i.e., 86.89 ± 1.41%, and revealed enhanced mucoadhesion characteristics. ADHA NPs also exhibited significant anti-inflammatory effects (<i>p</i> &lt; 0.001) compared to dexamethasone in LPS-induced RAW 264.7 cell lines against proinflammatory cytokines IL-1 β, NO and TNF-α. Furthermore, cell line studies in HCECs (human corneal epithelial cells) showed cytocompatibility and a dose-dependent uptake of ADHA NPs. ADHA NPs also maintained the cell integrity against 0.005% benzalkonium chloride (BAC) induced dry eye model on HCECs. Further, the Schirmer tear test showed twofold enhanced tear production in the developed formulation, and ADHA NPs seem to maintain the uniform structure of the tear. <i>In vivo,</i> drug retention studies ensured the good retention properties of ADHA NPs up to 12 h. In conclusion, ADHA NPs, because of their anti-inflammatory, mucoadhesiveness, modified drug release capacity, and higher drug retention properties, could serve as a potential therapeutic alternative for treating dry eye conditions.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}