International Journal of Pharmaceutics最新文献

{"title":"Gastroretentive fibrous dosage forms for prolonged delivery of sparingly-soluble tyrosine kinase inhibitors. Part 1: Dosage form design, and models of expansion, post-expansion mechanical strength, and drug release","authors":"Aron H. Blaesi ,&nbsp;Nannaji Saka","doi":"10.1016/j.ijpharm.2024.124360","DOIUrl":"10.1016/j.ijpharm.2024.124360","url":null,"abstract":"<div><div>At present, the efficacy and safety of many cancer therapies employing a sparingly-soluble tyrosine kinase inhibitor (TKI) are compromised by excessive fluctuations in the drug concentration in blood. To mitigate this limitation, in this four-part study expandable, gastroretentive fibrous dosage forms that deliver drug into the gastric fluid (and into the blood) at a controlled rate for prolonged time are presented. The dosage form comprises a cross-ply structure of water-absorbing, high-molecular-weight hydroxypropyl methylcellulose (HPMC) based fibers coated with a strengthening, enteric excipient. The intervening spaces between the coated fibers are solid annuli of dispersed drug particles in a low-molecular-weight HPMC-based excipient matrix. The central regions of the annuli are open channels. In this part, models are developed for dosage form expansion, post-expansion mechanical strength, and drug release. The models suggest that upon immersing in a dissolution fluid, the fluid percolates the open channels, diffuses into the annuli and the coated fibers, and the dosage form expands. The expansion rate is inversely proportional, and the post-expansion mechanical strength proportional to the volume fraction of the coating. Drug particles are released from the annuli as the surrounding excipient dissolves. The drug release rate is proportional to the concentration of low-molecular-weight HPMC at the annulus/dissolution fluid interface. The dosage forms can be readily designed for expansion in a few hours, formation of a high-strength viscoelastic mass, and drug release at a constant rate over a day.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"674 ","pages":"Article 124360"},"PeriodicalIF":5.3,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442664","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":"Withdrawal notice to “Impact of various electromagnetic fields on the transdermal permeability of naproxen and the effect of active compound exposure on magnetic field properties” [Int. J. Pharm. 674 (2025) 125475]","authors":"Rafał Rakoczy ,&nbsp;Karolina Zyburtowicz Ćwiartka ,&nbsp;Maciej Konopacki ,&nbsp;Anna Nowak ,&nbsp;Anna Muzykiewicz-Szymańska ,&nbsp;Łukasz Kucharski ,&nbsp;Marian Kordas ,&nbsp;Paula Ossowicz-Rupniewska","doi":"10.1016/j.ijpharm.2025.125564","DOIUrl":"10.1016/j.ijpharm.2025.125564","url":null,"abstract":"","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"674 ","pages":"Article 125564"},"PeriodicalIF":5.3,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795480","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":"Impact of pharmaceutical tablet properties on optical porosimetry performance","authors":"Chi Ki Leung ,&nbsp;Andreas Kottlan ,&nbsp;Rikard Heimsten ,&nbsp;Märta Lewander Xu ,&nbsp;J. Axel Zeitler","doi":"10.1016/j.ijpharm.2025.125567","DOIUrl":"10.1016/j.ijpharm.2025.125567","url":null,"abstract":"<div><div>The porosity of a pharmaceutical tablet influences liquid transport, disintegration and dissolution, rendering its monitoring and control crucial for quality by design. Optical porosimetry, a non-destructive process analytical technology (PAT), combines gas in scattering media absorption spectroscopy (GASMAS), photon time-of-flight spectroscopy (PToFS), tablet thickness measurement and tablet solid refractive index. This article presents a short tutorial on optical porosimetry theory and a performance study of optical porosimetry on pharmaceutical tablets via design of experiments. The investigated tablets share the same formulation, solid refractive index and diameter but differ in porosity (<span><math><mrow><mo>∼</mo><mn>0</mn><mo>.</mo><mn>05</mn></mrow></math></span> and 0.25) and thickness (1, 3 and 5<!--> <!-->mm). Critical user-controllable factors impacting the measurement accuracy and precision of the investigated tablets were identified. These are the manufactured tablet thickness, porosity, the user-estimated solid refractive index, and the number of optical porosimetry measurements in decreasing order of significance. A comparison between tablet porosity measured by optical porosimetry and by nominal measurements revealed that optical porosimetry tends to overestimate the porosity of the investigated tablets, particularly at low porosities, and has greater variability. While optical porosimetry poses advantages as a non-destructive and rapid PAT for real-time release testing, users need to be aware of the appropriate range of tablet thickness, porosity and the solid refractive index estimate.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"676 ","pages":"Article 125567"},"PeriodicalIF":5.3,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143852239","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":"Gastroretentive fibrous dosage forms for prolonged delivery of sparingly-soluble tyrosine kinase inhibitors. Part 3: Theoretical models of drug concentration in blood","authors":"Aron H. Blaesi ,&nbsp;Nannaji Saka","doi":"10.1016/j.ijpharm.2024.124362","DOIUrl":"10.1016/j.ijpharm.2024.124362","url":null,"abstract":"<div><div>In this part, drug concentration in blood after ingesting gastroretentive fibrous and immediate-release particulate dosage forms is modeled. The tyrosine kinase inhibitor nilotinib, which is slightly soluble in low-pH gastric fluid but practically insoluble in pH-neutral intestinal fluid is used as drug. The models suggest that upon ingestion, the fibrous dosage form expands, is retained in the stomach for prolonged time, and releases drug into the gastric fluid at a constant rate. The released drug molecules flow into the duodenum with the gastric fluid, and are absorbed by the blood. The drug is eliminated from the blood by the liver at a rate proportional to its concentration. Thus, as the drug concentration in blood increases due to absorption, the elimination rate increases, too, and will eventually be the same as the absorption rate, so that the drug concentration in blood plateaus out. After the gastric residence time, drug absorption stops, and the drug concentration in blood drops to zero. By contrast, after administering the immediate-release particulate dosage form the drug particles are swept out of the stomach rapidly, and drug absorption stops much earlier. The drug concentration in blood rises and falls without attaining steady state. The gastroretentive fibrous dosage forms enable a constant drug concentration in blood for drugs that are insoluble in intestinal fluids.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"674 ","pages":"Article 124362"},"PeriodicalIF":5.3,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141431948","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":"Revolutionizing anticoagulation: Nanoengineered therapies and precision medicine approaches","authors":"Ying Zhang ,&nbsp;Wenqiang Qian ,&nbsp;Weidong Fei ,&nbsp;Yongquan Zheng ,&nbsp;Yao Yao ,&nbsp;Maiqi Kong ,&nbsp;Xiaojun Zhu ,&nbsp;Yujie Peng ,&nbsp;Dan He ,&nbsp;Caihong Zheng","doi":"10.1016/j.ijpharm.2025.125596","DOIUrl":"10.1016/j.ijpharm.2025.125596","url":null,"abstract":"<div><div>With the advancement of therapeutic concepts, early intervention with antithrombotic therapy for patients at potential thrombotic risk is becoming more proactive. Anticoagulant therapy, a critical component of antithrombotic treatment, thus plays a key role in the prevention and treatment of cardiovascular diseases. Unfortunately, existing anticoagulation treatments still face many challenges, including abnormal bleeding, allergic reactions, and drug resistance. To identify novel technologies for addressing these issues and explore the latest research developments in the field of anticoagulation, this paper reviewed the advances of anticoagulant factor-loaded nanoplatforms firstly. These systems can precisely deliver anticoagulant drugs to specific targets, improving drug bioavailability and reducing unnecessary systemic side effects. Subsequently, the paper delved into the development of anticoagulant technologies, including the advancements in biocompatible anticoagulant nanomaterials, the application of DNA origami technology, and the progress in external energy-mediated anticoagulation strategies. A common feature of these engineered anticoagulation systems is their ability to modulate the dynamic balance of anticoagulant factors in the body without relying on traditional drugs, enabling more personalized and efficient anticoagulation effects. Finally, the paper examined novel precision anticoagulation strategies that combine biomedical engineering technologies with precision anticoagulation therapy. These strategies can tailor anticoagulation treatments to the specific pathological conditions of individual patients, such as thrombin activity, thereby reducing the risk of excessive anticoagulation. In conclusion, the engineered anticoagulation therapy strategies proposed in this paper represent cutting-edge advancements in anticoagulation medicine, providing more precise and safer solutions for the treatment of thrombotic diseases, and offering important theoretical and practical guidance for future personalized medicine and precision therapies.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"676 ","pages":"Article 125596"},"PeriodicalIF":5.3,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847706","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":"LDLR-targeted orlistat therapeutic nanoparticles: Peptide selection, assembly, characterization, and cell-uptake in breast cancer cell lines","authors":"George Bebawy ,&nbsp;Pamela Collier ,&nbsp;Philip M. Williams ,&nbsp;Jonathan C. Burley ,&nbsp;David Needham","doi":"10.1016/j.ijpharm.2025.125574","DOIUrl":"10.1016/j.ijpharm.2025.125574","url":null,"abstract":"<div><h3>Motivation</h3><div>Many cancers overexpress low-density lipoprotein receptors (LDLR), facilitating cholesterol metabolism for tumour growth. Targeting LDLR offers a promising strategy for selective drug delivery. Orlistat, a fatty acid synthase (FAS) inhibitor, has shown anti-cancer potential, particularly in tumours with high FAS expression. This study introduces an LDLR-Orlistat Targeted Nanoparticles (LDLR-OTNs) to enhance cancer cell uptake via LDLR-mediated endocytosis. The objectives include synthesizing lipid-based orlistat nanoparticles, functionalizing them with an 11-mer LDLR-binding peptide, assessing uptake and cytotoxicity in three LDLR- and FAS-expressing breast cancer cell lines (BT-474, MDA MB 453, MCF-7), and comparing uptake kinetics with non-targeted nanoparticles.</div></div><div><h3>Methods</h3><div>Orlistat nanoparticles (ONs) were synthesised via rapid solvent exchange, producing uncoated ONs, POPC-coated ONs (POPC-ONs), and LDLR-targeted ONs (LDLR-OTNs). Targeting was achieved by conjugating an 11-mer binding peptide (RLTRKRGLKLA) to DSPE-PEG5000 maleimide via click chemistry, confirmed by Ellman’s test. Nanoparticles were characterised using DLS and TEM. Cellular uptake over 24 hours was assessed using fluorescence-labelled POPC-ONs and LDLR-OTNs, and uptake kinetics were analysed. Suramin-blocking studies were used to confirm LDLR-mediated uptake. A 48-hour cytotoxicity assay quantified IC₅₀ values in the aforementioned cell lines.</div></div><div><h3>Results</h3><div>TEM data showed that LDLR-OTNs (33 nm) were smaller than untargeted POPC-ONs (58 nm) and uncoated ONs (67 nm). Ellman’s test confirmed &gt; 99.2% peptide conjugation. Cellular uptake of LDLR-OTNs was rapid, with significant fluorescence by 1 hour and a kinetic plateau at 24–48 hours, with data fitting to a modified exponential model, while that of untargeted POPC-ONs had lower initial uptake, following a logistic model. Suramin blocking reduced LDLR-OTN uptake, confirming receptor-mediated entry. Cytotoxicity assays yielded IC₅₀ values of 23.8 µM (BT-474), 25.8 µM (MDA MB 453), and 8.2 µM (MCF-7), with maximal inhibition at 48 h.</div></div><div><h3>Conclusions</h3><div>LDLR-OTNs demonstrated receptor-mediated uptake and potent cytotoxicity in LDLR- and FAS- overexpressing breast cancer cells. These findings support LDLR-targeted nanoparticles as a promising approach for delivering FAS inhibitors to LDLR-rich tumours, meriting further investigation in targeted cancer therapy development.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"676 ","pages":"Article 125574"},"PeriodicalIF":5.3,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143842984","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":"A universal digital control concept for end-to-end manufacturing","authors":"L. Kuchler ,&nbsp;A. Azimi ,&nbsp;H. Damiri ,&nbsp;S. Martinuzzi ,&nbsp;M. Steinberger ,&nbsp;J. Rehrl ,&nbsp;J. Poms ,&nbsp;M. Kureck ,&nbsp;D. Kirschneck ,&nbsp;M. Horn ,&nbsp;J. Khinast ,&nbsp;S. Sacher","doi":"10.1016/j.ijpharm.2025.125599","DOIUrl":"10.1016/j.ijpharm.2025.125599","url":null,"abstract":"<div><div>With the implementation of advanced manufacturing concepts (e.g., continuous operation, integration of different process routes and modular manufacturing), control of the process and the related product quality becomes more complex. Unlike traditional in-process controls and end-product testing, modern high-speed manufacturing does not allow for delays due to measurements between unit operations and requires real-time information about the material state and associated control actions. This study presents a universally applicable control concept, which offers the highest level of control together with flexibility for processing, equipment and automation. The concept can deal with a combination of batch and continuously operated process steps, manual and automated operation, different scales of equipment, and digital and manual data acquisition. It was demonstrated using a compact end-to-end manufacturing line for tablets, which included the active pharmaceutical ingredient (API) synthesis, crystallization, filtration and washing, as well as the formulation part. A suspension of API was directly fed into hot melt extrusion (HME), which was combined with direct compaction (DC). The control strategy was based on data not only from classical process analytical technology (PAT) sensors, but also from the equipment and soft sensors (e.g., the content was monitored and controlled using the soft sensors and the feeder data). The process and quality information were fed into a digital twin of the entire process, which executed the model-based control strategy.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"676 ","pages":"Article 125599"},"PeriodicalIF":5.3,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143877314","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":"Self-Assembling protein nanoparticle platform for multivalent antigen delivery in vaccine development","authors":"Hao Wu ,&nbsp;Ruiqi Weng ,&nbsp;Jiaxuan Li ,&nbsp;Zhiwei Huang ,&nbsp;Xiaotian Tie ,&nbsp;Jianhua Li ,&nbsp;Keda Chen","doi":"10.1016/j.ijpharm.2025.125597","DOIUrl":"10.1016/j.ijpharm.2025.125597","url":null,"abstract":"<div><div>Nanoparticle vaccines can efficiently and repeatedly display multivalent antigens, thereby improving the targeted delivery of antigens and inducing more durable immune responses, making them an important representative of novel vaccines. The global COVID-19 pandemic has accelerated the development of nanoparticle vaccines, offering a promising solution for the prevention and control of infectious diseases. Currently, the development of nanoparticle vaccines involves the use of various types of nanoparticles, including liposomes, polymers, inorganic materials, and emulsions. Protein nanoparticles candidate vaccines are attracting increasing attention because of their unique antigen presentation methods and self-assembly characteristics during their development, leading to a broad consensus on their promising future. Naturally self-assembling protein nanoparticles, such as ferritin, enhance antigen presentation, which aids in the activation of both humoral and cellular immune responses. This has led to significant advancements in the study of hepatitis B virus. Meanwhile, some synthetically engineered protein nanoparticles, such as mi3, and I53-50, can induce higher antibody titers through chemical conjugation with the SpyTag-SpyCatcher system, thereby providing better immunoprotection and showing promising prospects in the prevention of H1N1 and H3N2 influenza virus infections. This article reviews the unique advantages of protein nanoparticles as antigen delivery platforms, progress made in immunological design mechanisms, advances in the application of related adjuvants in preclinical and clinical trials, and the performance of commonly used computationally designed protein nanoparticles in preclinical trials, with a particular emphasis on the progress in the application of cationic nanoparticle vaccines. The aim is to provide future researchers with effective adjuvant strategies and high-quality selections for computationally designed protein nanoparticles, thereby promoting the clinical trial process of protein nanoparticles vaccines.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"676 ","pages":"Article 125597"},"PeriodicalIF":5.3,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143856124","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":"Acidification of phosphate buffered saline","authors":"Lukáš Veselý ,&nbsp;Behera Susrisweta ,&nbsp;Radim Štůsek ,&nbsp;David Mužík ,&nbsp;Dominik Heger","doi":"10.1016/j.ijpharm.2025.125593","DOIUrl":"10.1016/j.ijpharm.2025.125593","url":null,"abstract":"<div><div>It has been demonstrated that freezing-induced acidity changes have an impact on the structural integrity, degree of aggregation, and chemical stability of frozen food and pharmaceutical products. The stability of the compounds in solutions is maintained by the presence of buffers. However, many buffers are unsuitable for applications involving freezing as this process substantially alters the acidity. In this study, we determine the effect of initial pH, concentration, and cooling rate on the freezing-induced change in acidity of phosphate buffered saline (PBS) in the frozen state via UV–VIS spectroscopy. Furthermore, we examine the impact of individual salts present in PBS and discuss the mechanisms affecting the resulting acidity that we approximate via Hammett acidity function (<em>H</em>_2–).</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"676 ","pages":"Article 125593"},"PeriodicalIF":5.3,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143858830","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":"Chitosan-aloe vera scaffolds with tuned extracellular vesicles and histatin-5 display osteogenic and anti-biofilm activities","authors":"Patricia García-García ,&nbsp;Carmen Évora ,&nbsp;Araceli Delgado ,&nbsp;Patricia Diaz-Rodriguez","doi":"10.1016/j.ijpharm.2025.125592","DOIUrl":"10.1016/j.ijpharm.2025.125592","url":null,"abstract":"<div><div>The use of extracellular vesicles (EVs) has garnered significant attention as an alternative to cell-based therapies due to their stability and biocompatibility. In this study, we stimulated mesenchymal stem cells (MSCs) with therapeutic agents affecting the bone regenerative cascade, including bone morphogenetic protein 2 (BMP-2), stromal-derived factor (SDF-1), interleukin 4 (IL-4), alendronate (ALD) and osteogenic differentiation media to obtain osteogenic EVs. The tuned EVs were tested on MSCs and fibroblasts, selecting EVs-BMP-2 as suitable systems. Chitosan-aloe vera (AV) scaffolds were designed to allow for the loading and release of these EVs while leveraging the antibacterial and anti-inflammatory properties of AV. To enhance the dual effect on regeneration and antibacterial activity, poly(lactic-co-glycolic acid) (PLGA) microspheres encapsulating Histatin 5 (Hist-5) were incorporated to the scaffolds. Hist-5 encapsulation was successful, and effectively prevented <em>Staphylococcus aureus</em> biofilm formation on the scaffolds surface. The optimized chitosan-AV scaffolds loaded with EVs-BMP-2 promoted MSCs adhesion and proliferation and exhibited a 2-fold increase in osteogenic differentiation compared to chitosan scaffolds. This study demonstrates the successful combination of bioengineered EVs and Hist-5-loaded microspheres within a chitosan-AV scaffold, providing a promising dual approach for enhancing bone regeneration while reducing the risk of infection. These systems show potential as effective implants for bone fractures, offering both antibacterial and regenerative capabilities.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"676 ","pages":"Article 125592"},"PeriodicalIF":5.3,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143838142","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}