Journal of Controlled Release最新文献

{"title":"A safe saponin-based nano-strategy for manganese-mediated STING activation","authors":"Ni Fan, Yunxin Zhang, Ziyu Ge, Yingying Li, Lin Miao, Zhonggao Gao, Gang Hou, Yunfei Li, Yingpeng Li","doi":"10.1016/j.jconrel.2025.114303","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.114303","url":null,"abstract":"The effective delivery of hydrophilic therapeutic agents (e.g., transition metal ions and protein antigens) remains a significant pharmacological hurdle in immunotherapy. Saponin-based delivery platforms demonstrate remarkable potential. Therapeutic modulation of the cGAS–STING pathway using manganese ions (Mn²⁺) holds significant promise for cancer immunotherapy. However, clinical translation faces additional safety challenges beyond delivery issues, since therapeutic doses of Mn²⁺ often induce chronic inflammation and oxidative stress. To address these challenges, we developed a biomimetic nanoparticle, Human serum albumin-Astragaloside IV-MnCl₂ nanoparticles(HSA–A–M NPs), leveraging the dual functionality of the saponin astragaloside IV (AS-IV). AS-IV enhances Mn²⁺ uptake by increasing membrane permeability while suppressing NF-κB-driven inflammation and ROS production, improving safety. The nanoparticle's core, stabilized by HSA, boosts biocompatibility, while surface modifications with chitosan and hyaluronic acid (HA) derivatives (CS-NG@HGS) optimize tumor targeting, yielding the final formulation CS–NG@HGS@HSA–A–M. In vitro and vivo, this platform enhances cGAS–STING-mediated antitumor immunity while minimizing systemic Mn²⁺ toxicity and inflammation. By combining Mn²⁺ delivery with AS-IV's anti-inflammatory effects, it establishes a “controlled-activation” paradigm—potentiating IFN-I production yet curbing excessive immune responses. This dual-action design offers a safer, adaptable framework for metal ion-based combination therapies.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"11 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145260711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting post-extraction complications with functional hydrogels: Mechanistic insights, translational strategies, and clinical prospects","authors":"Hong-Yu Zhang, Zhen-Hao Hu, Chao-Chen Rui, Li-Wen Su, Yu-Jie Xiao, Meng-Di Nie, Huan Su, Yang Wu","doi":"10.1016/j.jconrel.2025.114304","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.114304","url":null,"abstract":"Tooth extraction is a frequently performed dental procedure; however, the complex oral microenvironment can result in post-operative complications such as bleeding, infection, and delayed healing. Effective management of these issues requires a multidisciplinary strategy, with recent advancements in materials science and biotechnology introducing innovative solutions. Among various biomaterials, hydrogels are regarded as particularly suitable for post-extraction sockets due to their exceptional drug delivery capabilities, biocompatibility, and tunable physicochemical properties. This review systematically summarizes the latest progress in hydrogel-based strategies for managing common complications following tooth extraction. It emphasizes the preventative and therapeutic roles of functional hydrogels, details their advantages over traditional approaches, and explores their potential to improve clinical outcomes. Additionally, the unique physical and chemical properties of hydrogels—such as mechanical strength, swelling behavior, degradation rate, and injectability—are discussed, alongside their biological functions, including tissue regeneration, antibacterial activity, and controlled drug release. It concludes by outlining future research directions for functional hydrogels in post-extraction socket management and considers the challenges associated with their clinical transformation.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"37 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145255323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polymeric-lipid nanoparticles that leverage cationic helper lipids and the protein corona for lung-targeted delivery of a novel anti-cancer drug","authors":"Santhni Subramaniam ,&nbsp;Leigh Donnellan ,&nbsp;Anthony Wignall ,&nbsp;Joanna Woodcock ,&nbsp;Carl Coolen ,&nbsp;Stuart Pitson ,&nbsp;Ali Taheri ,&nbsp;Clifford Young ,&nbsp;Peter Hoffmann ,&nbsp;Clive A. Prestidge ,&nbsp;Paul Joyce","doi":"10.1016/j.jconrel.2025.114299","DOIUrl":"10.1016/j.jconrel.2025.114299","url":null,"abstract":"<div><div>Lung cancer remains one of the leading causes of cancer-related mortality worldwide, highlighting the urgent need for more effective therapeutic strategies. Nanomedicine offers a promising avenue to improve treatment outcomes by enabling localised drug delivery within the lungs. Drawing inspiration from the recent success of mRNA lipid nanoparticles, we developed a novel class of polymeric-lipid nanoparticles (P-LNPs) designed to encapsulate RB-012, an anticancer compound that inhibits 14–3-3 protein function but is rapidly cleared from systemic circulation due to its cationic and amphiphilic properties. RB-012 was <em>co</em>-assembled with the anionic polymer polyacrylic acid (PAA) and various combinations of cholesterol, pegylated, and charged helper lipids to form stable P-LNPs that significantly impeded in vitro premature drug release. This approach resulted in &gt;30-fold increase in bioavailability following intravenous administration (2 mg/kg) to Sprague-Dawley rats. Varying the helper lipid composition, through the inclusion of 16–32 mol% of the cationic lipid, DOTAP, yielded a &gt; 50-fold increase in pulmonary drug exposure compared to unformulated RB-012. These biodistribution enhancements were linked to altered protein corona profiles on the nanoparticle surface, with P-LNPs formulated with DOTAP increasing the degree of protein corona adsorption in a concentration-dependent manner, compared to P-LNPs prepared with the anionic helper lipid, DOPE. In vitro and <em>in ovo</em> assays confirmed that the P-LNPs significantly improved the anti-tumour efficacy of RB-012, supporting their potential as a targeted therapeutic platform for lung cancer treatment.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"388 ","pages":"Article 114299"},"PeriodicalIF":11.5,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145254779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radiation-responsive Salmonella mediate therapeutics precise delivery for synergistic tumor radio-immunotherapy.","authors":"Hua Chen,Yinrui Zhu,Wenlong Peng,Yifan Wang,Anqi Dong,Lin Wei,Teng Liu,Lin Hu,Kai Yang","doi":"10.1016/j.jconrel.2025.114292","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.114292","url":null,"abstract":"Direct cytosolic delivery of proteins represents a transformative approach for developing next-generation therapeutic proteins targeting intracellular pathways. Leveraging the unique tumor-targeting capabilities of attenuated Salmonella Typhimurium, including its propensity for tumor-localized colonization and cellular internalization, we have developed a genetically engineered strain regulated by an ionizing radiation-responsive promoter element (rRPE) for precise tumor-specific protein delivery. This innovative rRPE system operates through a radiation-induced molecular cascade: ionizing radiation triggers DNA damage, activating RecA, which subsequently promotes LexA self-hydrolysis, thereby relieving radiation-associated operator gene (rAO) inhibition and enabling PpagC-mediated expression of downstream genes. This radiation-responsive regulatory mechanism allows Salmonella to maintain controlled expression of therapeutic proteins while minimizing premature leakage, with protein production specifically triggered by therapeutic radiation doses. The system demonstrates remarkable therapeutic efficacy through the controlled intracellular release of Shiga toxin's active moiety, STx1A, within bacteria-colonized tumor cells. The intracellularly delivered STx1A effectively disrupts DNA damage repair mechanisms. The synergistic combination of an engineered bacterial system with radiotherapy not only achieves direct tumor growth inhibition but also elicits robust anti-tumor immune responses. Therefore, our investigation establishes a novel paradigm for enhancing radiotherapy efficacy and provides a versatile platform for radio-genetically controlled therapy, potentially revolutionizing the field of bacteria-mediated precision medicine.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"4 1","pages":"114292"},"PeriodicalIF":10.8,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145254820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to ‘Novel design of 3D printed tumbling microrobots for in vivo targeted drug delivery’ [Journal of Controlled Release 386 (2025) 114071]","authors":"Aaron C. Davis ,&nbsp;Siting Zhang ,&nbsp;Adalyn Meeks ,&nbsp;Diya Sakhrani ,&nbsp;Luis Carlos Sanjuan Acosta ,&nbsp;D. Ethan Kelley ,&nbsp;Emma Caldwell ,&nbsp;Luis Solorio ,&nbsp;Craig J. Goergen ,&nbsp;David J. Cappelleri","doi":"10.1016/j.jconrel.2025.114272","DOIUrl":"10.1016/j.jconrel.2025.114272","url":null,"abstract":"","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"388 ","pages":"Article 114272"},"PeriodicalIF":11.5,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145255324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pulmonary inhaled drug delivery systems: From bench to bedside.","authors":"Xiaoke He,Jiahui Zou,Wanting Zhang,Yuhua Ma,Wei He","doi":"10.1016/j.jconrel.2025.114296","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.114296","url":null,"abstract":"Pulmonary inhaled drug delivery systems (PIDDSs) have emerged as a transformative approach to treating respiratory diseases and administering systemic drugs. This delivery platform, encompassing inhalation devices and preparations, has garnered global attention due to its non-invasive nature, rapid absorption rates and avoidance of hepatic first-pass effects. Nevertheless, the performance of PIDDSs is significantly affected by patients' breathing patterns and the aerodynamic properties of preparations. The respiratory system's complex physiology and inherent delivery barriers also pose substantial challenges to pulmonary drug delivery, including high administration doses, low pulmonary deposition efficiency, inadequate pulmonary retention and poor patient adherence. In recent years, significant efforts have been devoted to improving inhalation devices to minimize the dependence on patients' breathing patterns. Concurrently, researchers have explored how formulation design impacts the safety, delivery dose, pulmonary retention, and sustained/controlled release properties of inhalation preparations. This review provides a comprehensive analysis of the characteristics of PIDDSs, the in-depth mechanisms of pulmonary deposition and clearance, and recent advancements in optimizing inhalation devices and innovating inhalation preparations. Furthermore, we thoroughly discuss the potential advantages of novel inhalation devices and preparations, as well as the emerging fields of inhaled biologics, and propose future technical directions for PIDDS development.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"114 1","pages":"114296"},"PeriodicalIF":10.8,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145254784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomimetic immortalized mesenchymal stem cell-based nanoparticles suppress orthotopic postsurgical glioma via CD73 targeting and chemotherapy","authors":"Yuxuan Zhang ,&nbsp;Yezhong Wang ,&nbsp;Baisheng Li ,&nbsp;Yongquan Han ,&nbsp;Jialin Du ,&nbsp;Yiqing Chen ,&nbsp;Jianbo Ye ,&nbsp;Chuangcai Luo ,&nbsp;Huajian Chen ,&nbsp;Fei Peng ,&nbsp;Yuanyi Xiong ,&nbsp;Jihui Wang ,&nbsp;Yiquan Ke ,&nbsp;Yunxiang Ji","doi":"10.1016/j.jconrel.2025.114297","DOIUrl":"10.1016/j.jconrel.2025.114297","url":null,"abstract":"<div><div>Glioma is highly prone to recurrence post-surgery, and effective postoperative adjuvant therapeutic agents are lacking. Developing drugs that can efficiently cross the blood-brain barrier and target postoperative glioma is crucial for overcoming the challenges associated with the treatment of glioma. Nanomaterials modified with cell membranes have shown promise in crossing the blood-brain barrier for the treatment of glioma, but the origin of the cells as well as their heterogeneity are the current bottlenecks of this strategy. Previously, we demonstrated that immortalized mesenchymal stem cell membranes retain natural tumor-homing capability and offer a stable, scalable, and uniform source for sustained tumor targeting. Here, we proposed the use of immortalized mesenchymal stem cell plasma membranes with tumor-homing properties as carriers to develop biomimetic nanoparticles loaded with shCD73 and doxorubicin, named Lipo-PM@shCD73@DOX. By harnessing the tumor-homing factors, the developed biomimetic nanoparticles effectively crossed the blood-brain barrier and targeted postoperative residual glioma tissues to achieve postoperative gene therapy and chemotherapy for glioma. The present study demonstrates the therapeutic efficacy of biomimetic nanoparticles in delaying glioma progression by inhibiting cellular proliferation and inducing apoptosis. Additionally, we confirmed the <em>in vitro</em> and <em>in vivo</em> biosafety of biomimetic nanoparticles. In conclusion, this study overcame the problems of insufficient cell source and cellular heterogeneity in previous mimetic strategies and developed anti-glioma targeting drug biomimetic nanoparticles that efficiently cross the blood-brain barrier. It constitutes a novel anti-glioma adjuvant that enhances postoperative therapy and delays recurrence.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"388 ","pages":"Article 114297"},"PeriodicalIF":11.5,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145234947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultra-high concentration low-viscosity subcutaneous antibody formulations using ionic liquids","authors":"Anujan Ramesh, Metecan Erdi, Shuyang Zhang, Vineeth Chandran Suja, Samir Mitragotri, Bijay Singh","doi":"10.1016/j.jconrel.2025.114295","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.114295","url":null,"abstract":"Monoclonal antibodies (mAbs) are the single largest class of therapeutics used in various indications including oncology, immunology, and neurology. Given their high prevalence, the development of subcutaneously administrable mAb formulations via conventional needles is an urgent and unmet need. Subcutaneous mAb formulations need to meet several stringent requirements, including high concentrations to enable the delivery of therapeutic doses through small volumes, low viscosity to allow self-administration, and high shelf stability, all of which are inherently linked to protein-protein interactions, which have collectively limited mAb concentrations in current commercial formulations to ~150 mg/ml. Here, we report the use of ionic liquids (ILs) to mitigate protein-protein interactions to formulate antibodies at an ultra-high concentration in excess of 200 mg/ml. In addition to solubilizing antibodies at such high concentrations, IgG-IL formulations maintained a viscosity below the injectable threshold of 20 cP, remained stable at even room temperature and 37 °C, and exhibited improved bioavailability compared to saline formulations upon subcutaneous administration.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"79 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145234951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innate immune mechanisms underlying the efficacy of a next-generation nanoparticle-based vaccine against opioid use disorders","authors":"Fatima A. Hamid, Kobra Rostamizadeh, Nicholas Skiados, Nguyet-Minh Nguyen Le, Debra L. Walter, Bryan Hannon, Courtney Marecki, Yuanzhi Bian, Diego Luengas, Chenming Zhang, Marco Pravetoni","doi":"10.1016/j.jconrel.2025.114294","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.114294","url":null,"abstract":"Since 1999, the opioid use disorder (OUD) and overdose epidemic has claimed millions of lives with ~3 million people currently diagnosed with OUD and ~ 100,000 fatal overdoses occurring annually. Curbing this public health crisis requires accelerating the translation of innovative, effective, and safe treatments. Our team is advancing vaccines against a variety of opioids as a preventative and therapeutic strategy against OUD and overdose. Previously, we reported that a hybrid lipid-polymer nanoparticle (HLPNP)-based vaccine targeting oxycodone demonstrated superior immunogenicity and efficacy in mice compared to an equivalent conjugate vaccine formulated in aluminum salts. Here, we extended our investigation of the HLPNP-based oxycodone vaccine to rats and applied the HLPNP platform to a lead vaccine targeting fentanyl and its analogs. Additionally, this study tested whether HLPNP offer a suitable delivery system for vaccines adjuvanted with the toll-like receptor 7 and 8 (TLR7/8) agonist R848. This study assessed vaccine efficacy in blocking opioid-induced antinociception, respiratory/cardiovascular depression, and drug distribution to the brain. Innate immune responses to the anti-oxycodone nanovaccines were tested in murine macrophage and dendritic cell (DC) lines using cellular activation co-stimulatory/maturation markers. Cytokine profiles and immune cell activation in response to anti-fentanyl nanovaccines were assessed in human whole blood using multiplex cytokine assays paired with flow cytometry. Results demonstrate that HLPNP-formulated oxycodone vaccines exhibit improved efficacy in rats and superior activation of macrophage and DC compared to aluminum formulated conjugate vaccines. While the HLPNP-based fentanyl vaccine showed diminished efficacy relative to the unformulated vaccine in rats, adding R848 to the HLPNP formulation rescued its efficacy. These comprehensive immune profiling advance our understanding of OUD vaccines, providing a rational blueprint for next-generation vaccine design.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"108 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145234946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Control of pharmacokinetics of radioimmunoconjugates using chelating agents containing poly(ethylene glycol)","authors":"Kazuma Nakashima,&nbsp;Hiroki Jinda,&nbsp;Hiroki Shimohara,&nbsp;Hiroyuki Watanabe,&nbsp;Masahiro Ono","doi":"10.1016/j.jconrel.2025.114293","DOIUrl":"10.1016/j.jconrel.2025.114293","url":null,"abstract":"<div><div>Radioimmunoconjugates (RICs) composed of a monoclonal antibody (mAb) and radioisotope (RI) offer an attractive modality in oncology; however, their low tumor/blood ratio has limited their utility. To establish a novel strategy to improve the tumor/blood ratio without compromising the tumor accumulation of RICs, we developed novel DOTA-based chelating agents containing maleimide and discrete poly(ethylene glycol) (dPEG) scaffolds to synthesize RICs degrading into residualizing radiometabolites with high molecular weight in tumor cells: Mal-DOTA-PEG24 and Mal-DOTA-PEG48 modified by one dPEG scaffold, and Mal-DOTA-(PEG48)₃ modified by three dPEG scaffolds. Trastuzumab-based RICs with Mal-DOTA-PEG24, Mal-DOTA-PEG48, or Mal-DOTA-(PEG48)₃ showed different radioactivity distribution on human epidermal growth factor receptor 2 (HER2)/<em>neu</em>-expressing SK-OV-3 cells; RICs containing a PEGylated chelating agent of higher molecular weight exhibited higher-level retention of radiometabolites in cells after their internalization but increased dissociation from cell surfaces. An RIC containing one dPEG48 scaffold showed the highest tumor accumulation of radioactivity <em>in vivo</em> with a favorable tumor/blood ratio among PEGylated RICs, indicating that the optimized PEGylation of chelating agents markedly contributes to controlling the pharmacokinetics of RICs. These findings suggest the promising property of Mal-DOTA-PEG48 as a radiosynthetic platform to develop RICs with favorable pharmacokinetics.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"388 ","pages":"Article 114293"},"PeriodicalIF":11.5,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145229301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}