European Journal of Pharmaceutical Sciences最新文献

{"title":"Evaluation of the quality of the fixed-dose triple combination dispersible tablet for HIV-positive paediatric population after the continuous direct compression and batch manufacturing techniques","authors":"Eelis Komulainen ,&nbsp;Mpho Kotlolo ,&nbsp;Tuomas Kilpeläinen ,&nbsp;Baatile Komane ,&nbsp;Jarkko Ketolainen ,&nbsp;David R Katerere ,&nbsp;Marko Lehtonen ,&nbsp;Katja Pajula ,&nbsp;Ossi Korhonen","doi":"10.1016/j.ejps.2025.107299","DOIUrl":"10.1016/j.ejps.2025.107299","url":null,"abstract":"<div><h3>Introduction</h3><div>Currently, the paediatric population with positively tested human immunodeficiency virus (HIV) is facing challenges in the administration of off-label and manipulated pharmaceutical products due to the lack of dosage forms specifically designed and authorised for paediatric use. This issue raises concerns regarding medication safety, unavailability of appropriate medications, and improper use of existing treatments. Although paediatric patients prefer liquid and powder formulations, the stability of liquid dosage forms and compatibility of powders with many dietary products remain unresolved.</div></div><div><h3>Aim</h3><div>The aim of this study was to investigate the robustness in the quality and dissolution profiles of fixed-dose dispersible tablets with three different active pharmaceutical ingredients (API) (abacavir sulphate, tenofovir disoproxil fumarate and zidovudine) after utilising continuous direct compression (CDC) and batch manufacturing methods with implemented Design-of-Experiments (DoE).</div></div><div><h3>Methods</h3><div>The powder and tablet properties were evaluated employing quality standards of the European Pharmacopoeia (Ph. Eur.). CDC and batch process methods were used to produce fixed-dose combinations (FDC) of dispersible tablets with the aid of DoE which involved varying mixing speeds and breaking forces.</div></div><div><h3>Results</h3><div>The results indicated that CDC and batch methods could offer similar tablet quality attributes in terms of the physical properties of the tablets and dissolution profiles. The dissolution profiles of 15 min indicated that all six DoE points and the batch of tenofovir disoproxil fumarate met the European Pharmacopoeia standard of greater than 80 % of the drug release for immediate-release dosage forms. For abacavir sulphate the tablets from five out of six DoE points and the batch met the acceptable dissolution criteria. For zidovudine, only two DoE points met the acceptable criteria for the dissolution profile which might be related to the physical properties of the API. Moreover, pre-blending could be used to enhance the flowability of APIs and excipients with poor flowability.</div></div><div><h3>Conclusion</h3><div>FDC dispersible tablets were successfully manufactured with CDC and batch methods. Moreover, the product integrity results were similar for both the production technologies. However, the formulation and pre-blends require further optimization particularly for poorly flowable active pharmaceutical ingredients.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"214 ","pages":"Article 107299"},"PeriodicalIF":4.7,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Excipient variability critically impacts crystallization propensity of spray-dried amorphous solid dispersions.","authors":"Tanaya Singh Bhadoriya, Soumalya Chakraborty, Amit Pariskar, Arvind K Bansal","doi":"10.1016/j.ejps.2025.107294","DOIUrl":"https://doi.org/10.1016/j.ejps.2025.107294","url":null,"abstract":"<p><p>Polymeric amorphous solid dispersions (ASDs) are frequently used to improve solubility and oral bioavailability of poorly water-soluble drugs. The goal of the current investigation was to correlate the variability in the presence of polymeric stabilizer, from different sources and batches, with the stability of the spray-dried ASDs. Polyvinylpyrrolidone-vinyl acetate (PVPVA) and griseofulvin (GSV) were selected as model stabilizer and drug, respectively. Powder X-ray diffraction (pXRD), Differential Scanning Calorimetry (DSC), and Polarized Light Microscopy (PLM) confirmed the amorphous form and phase homogeneity of the spray-dried ASDs. pXRD and modulated DSC were used to determine the functionality (% crystallization) and intermediate functionality (enthalpy relaxation) of PVPVA, respectively, in spray-dried ASDs. The variability in different physicochemical properties of PVPVA, viz. glass transition temperature, viscosity of PVPVA solution in acetone, K-value, residue on ignition, true density, increase in water activity after storage, surface free energy, solvent evaporation kinetics, and diffusion coefficient of GSV in acetone in presence of PVPVA, were measured. Later, these properties were correlated with functionality and intermediate functionality using Pearson's correlation coefficient. Strong correlation (r ≥ 0.6) was observed with solvent evaporation kinetics, diffusion coefficient of GSV in acetone, in presence of PVPVA (indicates interaction of drug with polymer in feed solution of spray drying), K-value (indicates polymer molecular weight and chain length), and increase in water activity after storage (indicates interaction of polymer with water). Functionality-related characteristics (FRCs), and their corresponding functionality-related tests (FRTs), that can affect the functionality of PVPVA, as a stabilizer in GSV-PVPVA spray-dried ASD have been proposed. The learnings of this study will be beneficial to ensure robust performance of spray-dried ASDs containing other poorly soluble drug(s) and water soluble polymer(s). Due attention should be paid to ensure compliance to the proposed FRCs of the stabilizer from different batches and sources, during the manufacturing of spray-dried ASD, to ensure consistent quality and performance.</p>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":" ","pages":"107294"},"PeriodicalIF":4.7,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Validation of an Optimized and Horizontal Imaged Capillary Isoelectric Focusing Method for mAbs Charge Heterogeneity Analysis.","authors":"Ghizzani Virginia, Gonnella Federico, Gaggioli Andrea, Carocci Alberto, Luciani Francesca, Ascione Alessandro","doi":"10.1016/j.ejps.2025.107297","DOIUrl":"https://doi.org/10.1016/j.ejps.2025.107297","url":null,"abstract":"<p><p>Charge heterogeneity is widely recognized as a Critical Quality Attribute for mAbs, and imaged capillary isoelectric focusing has become the high-throughput gold standard technique for both manufacturers and regulatory agencies. Considering the exponential spread of mAbs across a wide range of medical applications​, the current lack of analytical procedure harmonization renders the feasibility of charge variants evaluation increasingly challenging, particularly in the context of large-scale control activities by supervisory authorities. This issue is highlighted by relevant EDQM's activities within the Biological Standardisation Programme, as well as by a recent publication in Ph. Eur. of a special general chapter on mAbs charge variant analysis by (i)ciEF. To satisfactorily address this urgent demand, the present article describes the development and validation of a mAbs cross-applicable icIEF method fully aligned with the Ph. Eur. Concept. The optimized method provides a further improvement in terms of accuracy, precision and linearity with respect to the general method published in Ph. Eur., as validated according ICH Q2(R2) requirements and elevating the isoelectric point as a valuable identity parameter for mAbs. These results represent a significant advance in the standardization of icIEF technique, thereby streamlining its utilisation in routine quality control activities and reinforcing its relevance in the anti-counterfeiting domain.</p>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":" ","pages":"107297"},"PeriodicalIF":4.7,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Continuous twin-screw wet granulation without adding granulation liquid.","authors":"Dániel Fekete, Richárd Ferdinánd Tóth, Zsombor Kristóf Nagy, Thorsten Cech, Lukas Ries, Edina Szabó","doi":"10.1016/j.ejps.2025.107295","DOIUrl":"https://doi.org/10.1016/j.ejps.2025.107295","url":null,"abstract":"<p><p>Granulation is a major focus of pharmaceutical R&D, as a key step in the development of solid pharmaceuticals. In parallel, the spread of continuous integrated powder-to-tablet production lines is also underway. In this research, a new wet granulation method has been investigated in terms of operation and scalability in a fully continuous powder-to-tablet line. The new wet granulation technique requires no addition of granulation liquid to the powder blend; thus, requires only minimal cooling after granulation, providing a more energy-efficient continuous integrated system for the pharmaceutical industry. This can be achieved by adding an excipient with a monograph and a high daily intake, potassium sodium tartrate tetrahydrate (PST), to the starting powder mixture. PST contains water of crystallization which is released by temperature, forming an in-situ granulation liquid during the process. This wet granulation-based technology produced granules with excellent flowability and immediate-release tablets exceeding 100 N breaking force and 1.5 MPa tensile strength. The continuous setup enabled easy scale-up from 0.5 to 10 kg/h using the same equipment and process parameters.</p>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":" ","pages":"107295"},"PeriodicalIF":4.7,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposing of FDA-approved drugs by targeting SIRT2 to alleviate inflammatory response and kidney injury.","authors":"Hung-Jin Huang, Yen-Chung Lin, Li-Ju Ho, Ruei-Yu Su, Wen-Chih Liu, Hui-Wen Chiu","doi":"10.1016/j.ejps.2025.107296","DOIUrl":"https://doi.org/10.1016/j.ejps.2025.107296","url":null,"abstract":"<p><p>Chronic kidney disease (CKD) involves the gradual loss of kidney function, usually caused by inflammation and fibrosis. The Sirtuin 2 (SIRT2) is predominantly expressed in proximal epithelial tubular cells, and specific inhibition of SIRT2 activity has been shown to alleviate fibrotic kidneys. We focus on targeting SIRT2 to discover a potent FDA-approved drug as a nephroprotective treatment for patients with CKD. Candidate compounds with high affinity and inhibitory effect for SIRT2 protein were filtered using structure-based virtual screening and quantitative structure-activity relationships (QSARs) prediction mode. The suggested candidate with favorable docking scores and predicted inhibitory activity was further examined for structural stability in 100 ns MD simulations. In addition, trajectories from dynamic simulation revealed that gliquidone remains bound to the target protein's active site in dynamic conditions. Gliquidone exhibited strong binding affinity among the screened drugs toward SIRT2 and maintained stable interactions with key residues in MD trajectories. Experimental validation was performed using a hydrogen peroxide-induced HK-2 cell injury model, followed by western blot analysis of autophagy, NLRP3 inflammasome, and fibrosis-related proteins. The experimental data also confirmed that gliquidone significantly improved HK-2 cell viability under oxidative stress, upregulated autophagy-related proteins (Beclin 1, p62 and LC3-II), suppressed NLRP3 inflammasome activation, and reduced fibrosis-associated factors (collagen type I, CTGF and PAI-1). These findings demonstrate that gliquidone exerts nephroprotective effects by modulating autophagy, inflammation, and fibrotic pathways. Overall, this study provides mechanistic insights supporting gliquidone as a promising repurposed candidate as a possible therapeutic drug for preventing CKD.</p>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":" ","pages":"107296"},"PeriodicalIF":4.7,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in the Pharmaceutical Development of Antibody-Oligonucleotide Conjugates.","authors":"Meng Li, Hongxin An, Jialing Zhang, Weiyu Li, Chuanfei Yu, Lan Wang","doi":"10.1016/j.ejps.2025.107292","DOIUrl":"https://doi.org/10.1016/j.ejps.2025.107292","url":null,"abstract":"<p><p>Antibody-oligonucleotide conjugates (AOCs) are a novel class of therapeutics composed of an antibody, a linker, and an oligonucleotide. AOCs combine the antigen-specific binding capability of an antibody and the gene-regulatory function of an oligonucleotide to achieve targeted and efficient therapeutic intervention across a range of diseases. Although AOCs are in the early stages of development, progress has been steady over the last few decades. The structural complexity and mechanistic diversity of AOCs contribute to manufacturing and quality control challenges, requiring strategies to ensure therapeutic efficacy and minimize off-target toxicity. The design, manufacturing, and quality control of AOCs are essential to ensuring their safety and efficacy. This review summarizes the history and current clinical development of AOCs, focusing on mechanisms of action, molecular design with various linkers, and recent advances in manufacturing processes and quality control. Additionally, the current challenges and future prospects for the development of AOC therapeutics are highlighted.</p>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":" ","pages":"107292"},"PeriodicalIF":4.7,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of hyaluronic acid on the performance of pulmonary surfactant. Towards the production of enhanced clinical surfactant formulations.","authors":"Ainhoa Collada, Amaya Blanco-Rivero, Antonio Cruz, Jesús Pérez-Gil","doi":"10.1016/j.ejps.2025.107298","DOIUrl":"https://doi.org/10.1016/j.ejps.2025.107298","url":null,"abstract":"<p><p>In order to prevent alveolar collapse, the surface tension at the air-liquid interface of alveoli has to be minimized at the end of expiration. Pulmonary surfactant, a lipid-protein complex synthetized and secreted by type II pneumocytes, adsorbs into the alveolar surface to form highly surface-active interfacial films. Lack or inactivation of surfactant is associated with severe respiratory pathologies, some of them treated by supplementation with exogenous surfactant formulations. It has been demonstrated that surfactant is assembled by pneumocytes in a highly packed dehydrated state that unravels once secreted to exhibit optimal interfacial capacities. Once exposed to air and subjected to dynamic breathing, surfactant can be isolated from bronchoalveolar lavages (BAL) in more unpacked and relatively hydrated stages. In this work we have used different biophysical technics, such as surface balances and fluorescence spectroscopy to show how BAL surfactant pre-exposed to certain polymers such as hyaluronic acid (HA) transits to a more stably packed state with improved functional capabilities that approach those of freshly secreted surfactant that had never been exposed to air, such as the surfactant that can be purified from amniotic fluid. These results open new opportunities to develop more efficient therapeutical surfactant preparations to treat respiratory pathologies still unresolved.</p>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":" ","pages":"107298"},"PeriodicalIF":4.7,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined Experimental and DFT Study of Tamoxifen Adsorption on PEG-Modified Graphene Oxide for Enhanced Drug Delivery.","authors":"Khaled Almansour, Hashem O Alsaab, Mahboubeh Pishnamazi","doi":"10.1016/j.ejps.2025.107293","DOIUrl":"https://doi.org/10.1016/j.ejps.2025.107293","url":null,"abstract":"<p><p>Breast cancer remains a leading cause of cancer-related mortality, with hormone receptor-positive (ER⁺) tumors representing ∼70% of cases. Tamoxifen (TAM), the gold-standard endocrine therapy, suffers from poor solubility (log P ≈ 6.3), low bioavailability (<30%), and acquired resistance. To overcome these limitations, we developed a pH-responsive TAM-loaded graphene oxide-polyethylene glycol (TAM@GO-PEG) nanocomposite through integrated experimental and computational approaches. GO-PEG synthesis yielded a stable nanocarrier with high drug-loading efficiency (DLE ≈ 80%) and pH-dependent charge reversal (+12.6 mV at pH 5.3 vs. +2.1 mV at pH 7.4). In vitro release studies demonstrated tumor-selective kinetics, with 89.3% cumulative release at pH 5.5 versus 61.1% at pH 7.4 over 72 hours. Density functional theory (DFT) simulations revealed that TAM binds primarily via π-π stacking and hydrogen bonding (1.8-2.2 Å), with oxygen-linked GO-O-PEG configurations exhibiting stronger adsorption energy (ΔG = -1.50 eV) than carbon-linked systems (ΔG = -1.30 eV). Electronic structure analysis confirmed enhanced stability (HOMO-LUMO gap = 2.5-3.3 eV) and pH-modulated drug release. Spectroscopic (FTIR, UV-Vis) and microscopic (TEM, XRD) characterization validated nanocomposite formation, while RDG analysis highlighted dominant non-covalent interactions. This study establishes TAM@GO-PEG as a promising nanoplatform for targeted breast cancer therapy, combining high drug loading, pH-triggered release, and tunable electronic properties. The synergy between experimental optimization and DFT modeling provides a robust framework for designing next-generation nanotherapeutics.</p>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":" ","pages":"107293"},"PeriodicalIF":4.7,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug release and pharmacokinetics of intravitreal liposomal injections: a case study with cyclic guanosine monophosphate derivative","authors":"Eetu Valkama ,&nbsp;Amir Sadeghi ,&nbsp;Elisa Toropainen ,&nbsp;Oswaldo Perez ,&nbsp;Nicolaas Schipper ,&nbsp;Marika Ruponen ,&nbsp;Arto Urtti ,&nbsp;Tatu Lajunen","doi":"10.1016/j.ejps.2025.107291","DOIUrl":"10.1016/j.ejps.2025.107291","url":null,"abstract":"<div><div>Retinitis pigmentosa (RP) is an inherited retinal dystrophy that leads to blindness at an early age. Although no effective drug treatment of RP exists, administration of cyclic guanosine monophosphate analogue 8- bromo- β- phenyl- 1, N²- ethenoguanosine- 3′, 5′- cyclic monophosphorothioate, Rp- isomer (CN03) has shown preclinical promise in the treatment of the RP nevertheless, fast drug clearance from vitreous may reduce its clinical applicability. To prolong intravitreal injection intervals of CN03, we investigated CN03 release from liposomes and the pharmacokinetics of intravitreally injected liposomes in rabbits. CN03 was encapsulated into pegylated (5 mol%) liposomes with different phospholipid compositions (18:0 PC, 18:1 PC, and 20:1 PC), achieving varying encapsulation efficiencies of 10.7 ± 1.0%, 84.8 ± 3.4%, and 65.1 ± 2.3%, respectively. The longest release half-life of CN03 was obtained with 20:1 PC liposomes (62.7 ± 4.6 h), whereas 18:1 PC (22.9 ± 2.9 h) and 18:0 PC (2.3 ± 0.6 h) liposomes showed shorter half-lives of release in isolated bovine vitreous humor. Thus, the CN03 release was slowed down by monounsaturated alkyl chains and longer carbon chains of the alkyls in the lipids. The vitreal half-life of CN03 in solution was 4.8 h in rabbit eyes, whereas pegylated 18:1 PC liposomes had a half-life of 6.9 days. A pharmacokinetic simulation model was used to estimate free CN03 concentration in the rabbit and human vitreous humor during drug release from the liposomes<em>.</em> In conclusion, drug loading capacity, CN03 clearance, and vitreal retention of liposomes set limits to the extended injection interval with liposomes. Overall, we present herein a process for in vitro – in vivo extrapolation for intravitreal drug delivery systems.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"214 ","pages":"Article 107291"},"PeriodicalIF":4.7,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction notice to \"Pharmacokinetics of free mycophenolic acid and limited sampling strategy for the estimation of area under the curve in liver transplant patients\" [European Journal of Pharmaceutical Sciences 47 (2012) 636-641].","authors":"Zhidong Gu, Bing Chen, Yanyan Song, Baiyong Shen, Zhecheng Zhu, Weixia Zhang, Junjie Xie, Xiaxing Deng, Chenghong Peng, Qishi Fan, Hao Chen","doi":"10.1016/j.ejps.2025.107278","DOIUrl":"10.1016/j.ejps.2025.107278","url":null,"abstract":"","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":" ","pages":"107278"},"PeriodicalIF":4.7,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145174227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}