Li-Na Zhang, Xiao-Yun Ran, Hong Zhang, Yu Zhao, Qian Zhou, Shan-Yong Chen, Cheng Yang, Xiao-Qi Yu, Kun Li
{"title":"Molecular Engineering of Xanthene Dyes with 3D Multimodal-Imaging Ability to Guide Photothermal Therapy.","authors":"Li-Na Zhang, Xiao-Yun Ran, Hong Zhang, Yu Zhao, Qian Zhou, Shan-Yong Chen, Cheng Yang, Xiao-Qi Yu, Kun Li","doi":"10.1002/adhm.202402295","DOIUrl":"https://doi.org/10.1002/adhm.202402295","url":null,"abstract":"<p><p>Phototheranostics integrates light-based diagnostic techniques with therapeutic interventions, offering a non-invasive, precise, and swift approach for both disease detection and treatment. The efficacy of this approach hinges on the multimodal imaging potential and photothermal conversion efficiency (PCE) of phototheranostic agents (PTAs). Despite the promise, crafting multifunctional phototheranostic organic small molecules brims with challenges. In this research, four innovative xanthene-derived PTAs are synthesized by fine-tuning the donor-π-acceptor (D-π-A) system to strike a balance between radiative and nonradiative decay. The inherent robust photostability and intense fluorescence of the traditional xanthene core are preserved, meanwhile the addition of highly electron-withdrawing groups boosts the non-radiative decay rate to enhance PCE and photoacoustic imaging capabilities. Remarkably, one of the PTAs, DMBA, demonstrates an exceptional absolute fluorescence quantum yield of 2.46% in PBS, and when encapsulated into nanoparticles, it achieves a high PCE of 79.5%. Consequently, DMBA nanoparticles (DMBA-NPs) are effectively employed in fluorescence, 3D photoacoustic, and photothermal imaging-guiding tumor photothermal therapy. This represents the first instance of a multimodal phototheranostic xanthene agent achieving synergistic fluorescence and photoacoustic imaging for diagnostic purposes. Furthermore, this work paves the way for leveraging xanthene fluorophores as versatile tools in the development of multifunctional reagents.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2402295"},"PeriodicalIF":10.0,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542985","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}
Chenyao Nie, Ji Xu, Yuhui Zhao, Ke Nan, Manqi Tan, Zhaobo Liu, Ming Huang, Wenzhi Ren, Bing Wang
{"title":"A Closed-Loop Cascade Strategy for On-Demand Regulation of Uric Acid.","authors":"Chenyao Nie, Ji Xu, Yuhui Zhao, Ke Nan, Manqi Tan, Zhaobo Liu, Ming Huang, Wenzhi Ren, Bing Wang","doi":"10.1002/adhm.202403004","DOIUrl":"https://doi.org/10.1002/adhm.202403004","url":null,"abstract":"<p><p>Despite that the current anti-hyperuricemia drugs can effectively reduce uric acid (UA) levels, imprecise medication dosage or uncontrolled lowering of UA levels may result in undesired effects. To address this issue, a closed-loop cascade strategy based on a biocompatible network composite, NW-FPNP/uricase (UOX), is proposed for on-demand regulation of UA levels. NW-FPNP/UOX is constructed by encapsulation of UOX) as UA-responsive element and FPNP, a nanoparticle of phenylboronic acid modified xanthine oxidase (XOD) inhibitor febuxostat, as H<sub>2</sub>O<sub>2</sub>-sensitive element with AMP/Gd<sup>3+</sup> network. It interrelates the UA metabolization and generation processes into a closed loop of cascade reactions involving UOX-catalyzed UA metabolization and H<sub>2</sub>O<sub>2</sub> generation, H<sub>2</sub>O<sub>2</sub>-triggered febuxostat regeneration and XOD inhibition, and XOD-catalyzed UA generation. Through UA level-dependent auto-adjustment of XOD activity, specially 6% at 600 × 10<sup>-6</sup> m UA compared to 82% at 100 × 10<sup>-6</sup> m, UA levels can be regulated to an appropriate range through dynamically balancing UA metabolization and generation. This biocompatible on-demand UA regulation system prevents the overdose of UA-lowering medications and avoids hypouricemia in hyperuricemia treatment, demonstrating great potential in intelligent UA level management. This work also introduces a new concept of a closed-loop cascade strategy for on-demand regulation of biochemical indicators within specific thresholds.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2403004"},"PeriodicalIF":10.0,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542973","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}
Helena Freire Haddad, Emily F Roe, Vinicius Xie Fu, Elizabeth J Curvino, Joel H Collier
{"title":"Multi-Target Peptide Nanofiber Immunotherapy Diminishes Complement Anaphylatoxin Activity in Acute Inflammation.","authors":"Helena Freire Haddad, Emily F Roe, Vinicius Xie Fu, Elizabeth J Curvino, Joel H Collier","doi":"10.1002/adhm.202402546","DOIUrl":"https://doi.org/10.1002/adhm.202402546","url":null,"abstract":"<p><p>The anaphylatoxins C3a and C5a are products of the complement cascade that play important and interrelated roles in health and disease. Both are potential targets for anti-inflammatory active immunotherapies in which a patient's own immune system is stimulated to produce therapeutic immune responses against problematic self-molecules. However, the complex and time-dependent interrelations between the two molecules make dual targeting challenging. To investigate a dual-target active immunotherapy against C3a and C5a and to systematically study the effect of varied degrees of responses against both targets, the study employed self-assembled peptide immunogens capable of displaying a broad range of epitope compositions and Design-of-Experiments (DoE) approaches. Peptide nanofibers contained B-cell epitopes of C3a and C5a in defined quantities, and intranasal immunization raised systemic and mucosal immunity against each target. In a lipopolysaccharide-induced model of sepsis, increasing anti-C5a responses are protective, whereas increasing anti-C3a responses are detrimental, and survival rates are negatively correlated with anti-C3a/anti-C5a IgG titer ratio. This work highlights the interplay between the two molecules by making use of a modular, defined, and easily adjusted biomaterial-based active immunotherapy platform.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2402546"},"PeriodicalIF":10.0,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542986","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":"Exos-Loaded Gox-Modified Smart-Response Self-Healing Hydrogel Improves the Microenvironment and Promotes Wound Healing in Diabetic Wounds.","authors":"Pu Yang, Yikun Ju, Naisi Shen, Shuai Zhu, Jiaqian He, Lingxiu Yang, Jiajie Lei, Xiaoli He, Wenjia Shao, Lanjie Lei, Bairong Fang","doi":"10.1002/adhm.202403304","DOIUrl":"https://doi.org/10.1002/adhm.202403304","url":null,"abstract":"<p><p>Wound management has always been a challenge in the clinical treatment of diabetes. In this study, glucose oxidase (GOx) is grafted onto natural pullulan polysaccharides, and oxidization is carried out to form a self-healing hydrogel using carboxymethyl chitosan by means of reversible Schiff base covalent bonding. The smart-response drug release properties of this natural self-healing hydrogel are demonstrated in diabetic wounds by taking advantage of two key factors, namely the pH-responsive nature of Schiff base bonding and the fact that GOx reduces the pH in diabetic wounds. To further enhance the biological functions of the hydrogel dressing, exosomes (Exos) are introduced into the hydrogel system. The GOx present in the hydrogel system improves the high-glucose microenvironment of diabetic wounds, releasing H<sub>2</sub>O<sub>2</sub> to impart antimicrobial effects, and ensuring that the hydrogel realizes a smart-response function. The carboxymethyl chitosan component used to construct the hydrogel plays an effective antibacterial role. Moreover, the Exos loaded into the hydrogel effectively promotes neovascularization of the wound. The Exos also regulates macrophage polarization and reduces the levels of persistent inflammation in diabetic wounds. These results suggest that this smart responsive, multifunctional, and self-healing hydrogel dressing is ideal for the management of diabetic wounds.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2403304"},"PeriodicalIF":10.0,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542974","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}
Chaobo Dai, Zhenghan Shi, Yi Xu, Lingkai Su, Xin Li, Peixue Deng, Hao Wen, Jiahao Wang, Qing Ye, Ray P S Han, Qingjun Liu
{"title":"Wearable Multifunctional Hydrogel for Oral Microenvironment Visualized Sensing Coupled with Sonodynamic Bacterial Elimination and Tooth Whitening.","authors":"Chaobo Dai, Zhenghan Shi, Yi Xu, Lingkai Su, Xin Li, Peixue Deng, Hao Wen, Jiahao Wang, Qing Ye, Ray P S Han, Qingjun Liu","doi":"10.1002/adhm.202401269","DOIUrl":"https://doi.org/10.1002/adhm.202401269","url":null,"abstract":"<p><p>Bacterial-driven dental caries and tooth discoloration are growing concerns as the most common oral health problems. Current diagnostic methods and treatment strategies hardly allow simultaneous early detection and non-invasive treatment of these oral diseases. Herein, a wearable multifunctional double network hydrogel combined with polyaniline and barium titanate (PANI@BTO) nanoparticles is developed for oral microenvironment visualized sensing and sonodynamic therapy. Due to the colorimetric properties of polyaniline, the hydrogel displays a highly sensitive and selective response for visualized sensing of oral acidic microenvironment. Meanwhile, the barium titanate in the hydrogel efficiently generates reactive oxygen species (ROS) under ultrasound irradiation, realizing non-invasive treatment in the oral cavity. Through bacterial elimination experiments and tooth whitening studies, the hydrogel can achieve the dual effect of effectively inhibiting the growth of cariogenic bacteria and degrading tooth surface pigments. Owing to the visualized sensing of the oral acidic microenvironment and efficient sonodynamic therapy function, the proposed hydrogel system offers a solution for the prevention of caries and tooth whitening, which is promising in developing the biomedical system targeting the simultaneous sensing and therapy for oral diseases.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2401269"},"PeriodicalIF":10.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520412","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}
Zhen Ding, Xingfu Bao, Tianyan Chen, Jinming Zhang, Chengjing Xu, Nan Tang, Min Hu, Zhen Liu
{"title":"Biocompatible Metal-Organic Framework-Based Fabric Composite as an Efficient Personal Protective Equipment for Particulate Matter-Induced Pulmonary Injury.","authors":"Zhen Ding, Xingfu Bao, Tianyan Chen, Jinming Zhang, Chengjing Xu, Nan Tang, Min Hu, Zhen Liu","doi":"10.1002/adhm.202403061","DOIUrl":"https://doi.org/10.1002/adhm.202403061","url":null,"abstract":"<p><p>Efficient personal protection has emerged as a crucial approach for reducing pulmonary injury induced by particulate matter (PM). However, current personal protective equipments usually lack essential biosafety concerns and fail to own adsorbing/antioxidant/antibacterial function together, making it a challenge to develop an integrated platform with the above characteristics. Herein, a facile oxygen-free hydrothermal strategy is proposed to synthesize new copper-based metal-organic frameworks, Cu-HHTPs, (HHTP: 2,3,6,7,10,11-hexahydroxytriphenylene), with great adsorbing/antioxidant/antibacterial activity and high biosafety. The Cu-HHTPs can serve as an efficient additive incorporated with various fabrics including cellulose acetate (CA) membrane to achieve novel fabric composites, such as CA@Cu-HHTPs, with ideal scavenging outcome for the main components of PM. Evidenced by the animal experiments, CA@Cu-HHTPs can highly mitigate PM-induced adverse effects via adsorbing PM, scavenging ROS, and killing bacteria, leading to a significant reduction in lung permeability, inflammation and oxidative stress, and pulmonary infection. Last but not least, a two-week exposure of CA@Cu-HHTPs exhibits no obvious damage toward the animals by examining their long-term toxicity. Collectively, this study not only highlights the potential of Cu-HHTPs as attractive additives for the preparation of fabric composites, but also lays out a new concept toward the development of new-generation multifunctional personal protective equipment against PM.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2403061"},"PeriodicalIF":10.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520408","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}
Yunan Peng, Yixuan Shang, Junyi Che, Yunru Yu, Yuanjin Zhao, Xiaoping Gu
{"title":"Multifunctional Analgesic Sutures from Microfluidic Spinning Technology.","authors":"Yunan Peng, Yixuan Shang, Junyi Che, Yunru Yu, Yuanjin Zhao, Xiaoping Gu","doi":"10.1002/adhm.202402420","DOIUrl":"https://doi.org/10.1002/adhm.202402420","url":null,"abstract":"<p><p>Sutures are the most commonly used wound repair method after surgery. However, addressing delayed recovery and pain management remains a significant challenge. Here, microfibers are developed from microfluidic spinning with long-lasting analgesia capabilities for sutures. By using a solvent extraction manner, the polycaprolactone (PCL) microfibers encapsulated with ropivacaine (ROP), a well-known analgesic, can be continuously obtained from microfluidics. The intrinsic property of PCL and the advantage of microfluidic spinning technique impart the microfiber with highly controlled morphologies, mechanical strengths, as well as drug release. After exploring their biocompatibility both at in vitro and in vivo levels, the microfibers are directly applied to wound suture. The results demonstrate the lasting analgesic effect of the microfiber on mice with incision pain, highlighting its potential as promising suture for post-surgery treatments. It is anticipated that the multifunctional analgesic sutures produced through microfluidic spinning will pave the way for utilizing fibers as effective sutures in clinical incision wound treatment.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2402420"},"PeriodicalIF":10.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520411","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}
Andrew House, Anjeli Santillan, Evan Correa, Victoria Youssef, Murat Guvendiren
{"title":"Cellular Alignment and Matrix Stiffening Induced Changes in Human Induced Pluripotent Stem Cell Derived Cardiomyocytes.","authors":"Andrew House, Anjeli Santillan, Evan Correa, Victoria Youssef, Murat Guvendiren","doi":"10.1002/adhm.202402228","DOIUrl":"https://doi.org/10.1002/adhm.202402228","url":null,"abstract":"<p><p>Biological processes are inherently dynamic, necessitating biomaterial platforms capable of spatiotemporal control over cellular organization and matrix stiffness for accurate study of tissue development, wound healing, and disease. However, most in vitro platforms remain static. In this study, a dynamic biomaterial platform comprising a stiffening hydrogel is introduced and achieved through a stepwise approach of addition followed by light-mediated crosslinking, integrated with an elastomeric substrate featuring strain-responsive lamellar surface patterns. Employing this platform, the response of human induced pluripotent stem cell-derived cardiomyocytes (hIPSC-CMs) is investigated to dynamic stiffening from healthy to fibrotic tissue stiffness. The results demonstrate that culturing hIPSC-CMs on physiologically relevant healthy stiffness significantly enhances their function, as evidenced by increased sarcomere fraction, wider sarcomere width, significantly higher connexin-43 content, and elevated cell beating frequency compared to cells cultured on fibrotic matrix. Conversely, dynamic matrix stiffening negatively impacts hIPSC-CM function, with earlier stiffening events exerting a more pronounced hindering effect. These findings provide valuable insights into material-based approaches for addressing existing challenges in hIPSC-CM maturation and have broader implications across various tissue models, including muscle, tendon, nerve, and cornea, where both cellular alignment and matrix stiffening play pivotal roles in tissue development and regeneration.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2402228"},"PeriodicalIF":10.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520409","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}
Melissa A. Cadena, Anson Sing, Kylie Taylor, Linqi Jin, Liqun Ning, Mehdi Salar Amoli, Yamini Singh, Samantha N. Lanjewar, Martin L. Tomov, Vahid Serpooshan, Steven A. Sloan
{"title":"A 3D Bioprinted Cortical Organoid Platform for Modeling Human Brain Development (Adv. Healthcare Mater. 27/2024)","authors":"Melissa A. Cadena, Anson Sing, Kylie Taylor, Linqi Jin, Liqun Ning, Mehdi Salar Amoli, Yamini Singh, Samantha N. Lanjewar, Martin L. Tomov, Vahid Serpooshan, Steven A. Sloan","doi":"10.1002/adhm.202470173","DOIUrl":"https://doi.org/10.1002/adhm.202470173","url":null,"abstract":"<p><b>3D Bioprinting</b></p><p>The cover of the article 2401603 by Vahid Serpooshan, Steven A. Sloan, and co-workers conceptualizes the attraction of endothelial roads towards a spherical city, where new vascularization invites life and greenery that is otherwise lacking. This work utilizes 3D bioprinting of gelatin methacrylate scaffolds to support the growth and differentiation of human brain organoids. The custom and tunable architecture of bioprinted scaffolds allows for intricate features like the introduction of endothelialized channels that migrate towards and infiltrate embedded organoids. Cover art by Flyazure.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":"13 27","pages":""},"PeriodicalIF":10.0,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adhm.202470173","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142541013","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}
Wonwoo Jeong, Jeonghyun Son, Jeonghan Choi, Jonghyeuk Han, Seunggyu Jeon, Min Kyeong Kim, Won Ha, Hyun-Wook Kang
{"title":"Clinically Relevant and Precisely Printable Live Adipose Tissue-Based Bio-Ink for Volumetric Soft Tissue Reconstruction.","authors":"Wonwoo Jeong, Jeonghyun Son, Jeonghan Choi, Jonghyeuk Han, Seunggyu Jeon, Min Kyeong Kim, Won Ha, Hyun-Wook Kang","doi":"10.1002/adhm.202402680","DOIUrl":"https://doi.org/10.1002/adhm.202402680","url":null,"abstract":"<p><p>Autologous fat is widely used in soft tissue reconstruction; however, significant volume reduction owing to necrosis and degradation of the transplanted adipose tissue (AT) remains a major challenge. To address this issue, a novel live AT micro-fragment-based bio-ink (ATmf bio-ink) compatible with precision 3D printing, is developed. Live AT micro-fragments of ≈280 µm in size are prepared using a custom tissue micronizer and they are incorporated into a fibrinogen/gelatin mixture to create the ATmf bio-ink. AT micro-fragments exhibit high viability and preserve the heterogeneous cell population and extracellular matrix of the native AT. The developed bio-ink enables precise micropatterning and provides an excellent adipo-inductive microenvironment. AT grafts produced by co-printing the bio-ink with polycaprolactone demonstrate a 500% improvement in volume retention and a 300% increase in blood vessel infiltration in vivo compared with conventional microfat grafts. In vivo engraftment of AT grafts is further enhanced by using a stem cell-laden ATmf bio-ink. Last, it is successfully demonstrated that the bio-ink is enabled for the creation of clinically relevant and patient-specific AT grafts for patients undergoing partial mastectomy. This novel ATmf bio-ink for volumetric soft tissue reconstruction offers a pioneering solution for addressing the limitations of existing clinical techniques.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2402680"},"PeriodicalIF":10.0,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520410","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}