Journal of pharmaceutical sciences最新文献

{"title":"Physiologically based pharmacokinetic modeling of tapentadol in children to support pediatric dose selection","authors":"Zilong Wang ,&nbsp;Yujie Yang ,&nbsp;Zhihai Cao ,&nbsp;André Dallmann ,&nbsp;Wei Hu ,&nbsp;Wei Zhang ,&nbsp;Qian Zhang ,&nbsp;Liang Zheng","doi":"10.1016/j.xphs.2025.103830","DOIUrl":"10.1016/j.xphs.2025.103830","url":null,"abstract":"<div><div>Tapentadol, an effective opioid analgesic, is indicated for the treatment of pain that cannot be managed with non-opioid medications. This study employed a physiologically based pharmacokinetic (PBPK) model to characterize the disposition of tapentadol in children across different age groups and to refine pediatric dosing strategies. Initially, an adult PBPK model was developed using the ‘middle-out’ strategy, which was then adjusted by scaling anatomical and physiological parameters to apply it to pediatric populations. The model's precision was confirmed by comparing the simulated plasma concentrations in a virtual population with empirical data. Utilizing this model, we translated dosages from adults to children and assessed weight-adjusted dosages for children aged 2 to 18 years and those under 2 years. The ratios of predicted to observed pharmacokinetic (PK) parameters for adult tapentadol ranged from 0.80 to 1.40 with the pediatric population's predictive mean absolute prediction error (MAPE) being less than 0.45. Based on model validation, we have established the following fixed-dose regimen for tapentadol oral solution for children across various age groups: 2.5 mg for 0–1 month, 3.5 mg for 1–3 months, 5 mg for 3–6 months, 8.5 mg for 6 months to 1 year, 13 mg for 1–2 years, 20 mg for 2–6 years, 35 mg for 6–12 years, and 60 mg for 12–18 years. The results of this study may offer guidance for the clinical investigation of tapentadol in pediatric patients and for developing PBPK models for drugs undergoing multiple metabolic pathways.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 7","pages":"Article 103830"},"PeriodicalIF":3.7,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023476","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":"Relationships between surface tensiometry properties and fluorescence intensity of dark and light exposed monoclonal antibody Nivolumab/Opdivo® by using the contact angle method: A pilot study","authors":"Giorgia Miolo ,&nbsp;Elisabetta De Diana ,&nbsp;Patrizia Polverino de Laureto ,&nbsp;Nicola Realdon ,&nbsp;Sergio Rossi ,&nbsp;Davide Rossi","doi":"10.1016/j.xphs.2025.103823","DOIUrl":"10.1016/j.xphs.2025.103823","url":null,"abstract":"<div><div>Monoclonal antibodies (mAbs) are a class of therapeutic proteins widely used for the treatment of different kinds of cancers and immune-mediated disorders.</div><div>During their real-life, they encounter various stressors, such as light exposure, able to modify their physico-chemical properties both in their formulation and when diluted for patient administration.</div><div>Several biochemical and biophysical analytical approaches are currently used to characterize the physico-chemical properties of mAbs, such as spectroscopic methods (i.e., UV absorption, fluorescence, near and far UV circular dichroism) for conformational studies, size exclusion chromatography, electrophoresis and dynamic light scattering for detecting aggregate formation, LC-MS for their chemical modifications. On these bases, our work is focused on the novel surface tension characterisation of one of these therapeutic mAbs, Nivolumab, in its formulation Opdivo® and after dilution and the relationship with classical fluorescence data. In particular, the mAb has been exposed to two different doses of simulated sunlight and the effect of the light stressor has been compared to the mAb kept in the dark. The application of Solid-like methodology, using the Rossi number as main surface tensiometry parameter, allowed us to demonstrate the close relationship between the physical, i.e., surface tension properties, and physico-chemical fluorescence emission of these big molecules.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 7","pages":"Article 103823"},"PeriodicalIF":3.7,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144022935","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":"Polyphosphate as a novel aggregation suppressor of gamma globulin","authors":"Junpei Kasahara ,&nbsp;Tomohiro Furuki ,&nbsp;Shohei Aikawa ,&nbsp;Hiroshi Ueda ,&nbsp;Kentaro Shiraki","doi":"10.1016/j.xphs.2025.103818","DOIUrl":"10.1016/j.xphs.2025.103818","url":null,"abstract":"<div><div>The aggregation of gamma globulin poses a significant challenge in maintaining the quality of biopharmaceutical products. This study aimed to develop a novel approach to prevent gamma globulin aggregation using polyphosphates (PolyPs), linear polymers comprising 14 to 130 phosphate units. The addition of PolyPs effectively suppressed the formation of subvisible particles (SVPs) in the micrometer-sized fraction of bovine gamma globulin (BGG) during storage at 40 °C, as observed through flow imaging. Furthermore, PolyPs mitigated the decrease in soluble protein concentration under these conditions. Mass photometry and isothermal titration calorimetry revealed that PolyPs spontaneously form complexes with BGG. The negative zeta potential and positive <em>B₂₂</em> and <em>k_Diff</em> values suggested that the BGG-PolyP complexes were stabilized by electrostatic repulsion. Importantly, far-UV circular dichroism confirmed that the secondary structure of BGG remained unaffected by complexation with PolyPs. Notably, arginine—a commonly used aggregation suppressor—failed to prevent the formation of SVPs in BGG under similar conditions. This study demonstrates the potential of biocompatible and stable PolyPs as a novel additive for inhibiting gamma globulin aggregation, offering a promising alternative to conventional approaches.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 7","pages":"Article 103818"},"PeriodicalIF":3.7,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143946965","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":"Polysorbates and poloxamer rescue filter-induced serotype-dependent loss of AAVs","authors":"Casey Patrick ,&nbsp;Matthew Petroff ,&nbsp;Jefferson Plegaria ,&nbsp;Vladimir Razinkov ,&nbsp;Smrithi Padmakumar ,&nbsp;Krishna M.G. Mallela","doi":"10.1016/j.xphs.2025.103825","DOIUrl":"10.1016/j.xphs.2025.103825","url":null,"abstract":"<div><div>Adeno-associated viruses (AAVs) are the leading viral vector for in-vivo gene therapy, and their use is expected to grow rapidly in the next decade. While AAVs are promising tools for treating many genetic diseases, vectors are vulnerable to adsorptive losses to surfaces due to the low concentrations (10–100 μg/mL) during manufacturing, storage, and administration. Here, we examined the filter-induced loss of two AAV serotypes of Clade E and Clade C as a function of the filter type (materials of composition such as polyvinylidene (PVDF), polyethersulfone (PES), and nylon), pore size (0.22 vs 0.45 μm), pH and ionic strength of the formulation, and hydrophobicity and ionic charge of the AAVs. Our results show that both the AAV serotype and the filter used result in varied amounts of adsorptive losses. Increased hydrophobicity of the AAV or the filter resulted in increased levels of adsorption. Altering formulation pH from 5 - 8 or ionic strength from 50 mM - 180 mM NaCl did not have a significant impact on adsorption loss. Additionally, no change in adsorptive loss was observed with an increase in the filter pore size. Three surfactants (polysorbate 20 (PS20), polysorbate 80 (PS80), and poloxamer 188 (P188)) are observed to rescue the filter-dependent loss of AAVs, but to different minimum concentrations. P188 was found to be the most efficient in the case of nylon filters, whereas PS20 is the most efficient with PES filters. A comparison of empty vs. full capsids shows that empty capsids can be used to optimize formulation parameters for full capsids. This study highlights the importance of surfactants in mitigating filter-dependent surface-induced losses observed during AAV manufacturing processes.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 7","pages":"Article 103825"},"PeriodicalIF":3.7,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144031114","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":"Ex Vivo-In Vitro Protein Adsorption and In Vivo Anti-Inflammatory Effects of Zwitterionized PVA Hydrogel Implants in the New Zealand Albino Rabbit Eye.","authors":"Onyinye Jennifer Uwaezuoke, Lisa Claire du Toit, Pradeep Kumar, Naseer Ally, Yahya Essop Choonara","doi":"10.1016/j.xphs.2025.103822","DOIUrl":"https://doi.org/10.1016/j.xphs.2025.103822","url":null,"abstract":"<p><p>Implantable ocular devices are increasingly used to overcome the drug delivery challenges presented by the physio-anatomical barriers of the eye. Protein adsorption onto the biomaterial occurs within minutes of implantation and is usually the first step in the fouling process that could culminate in implant/device failure, infection, or even death if the infection is not properly managed. The eye can easily be damaged by any inflammatory process due to its immune privilege status, hence, the need for biomaterials that would inherently limit protein adsorption and reduce inflammation. Herein, a super hydrophilic hydrogel ocular device was formulated via facile photo-initiated crosslinking polymerization between polyvinyl alcohol and sulfobetaine methacrylate, 2 polymers that have previously been employed individually, for surface modification of biomaterials towards protein resistance. Protein adsorption onto the hydrogel was studied in vitro and ex vivo using a complex protein solution, and rabbit aqueous and vitreous humour, respectively. In vivo ocular cytocompatibility was studied in New Zealand albino rabbits by subconjunctival implantation over a period of 8 weeks. The concentration of the zwitterionic monomer significantly affected protein adsorption in vitro, and impacted the foreign body response in vivo. In vivo results after 1 week showed a graded acute inflammatory response indicative of tissue repair that resulted in full integration by the 8th week.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"103822"},"PeriodicalIF":3.7,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144031710","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":"Pirfenidone encapsulated in succinylated gelatin-coated liposomes exhibits sustained antifibrotic effects in vitro models of renal, pulmonary, and hepatic fibrosis","authors":"Kohei Togami ,&nbsp;Yukimune Kanehira ,&nbsp;Yuki Nakamura ,&nbsp;Hirotsugu Ishii ,&nbsp;Ryota Abe ,&nbsp;Akiyoshi Yamamoto ,&nbsp;Kanako Takehara ,&nbsp;Mio Yasuda ,&nbsp;Hitoshi Tada ,&nbsp;Sumio Chono","doi":"10.1016/j.xphs.2025.103819","DOIUrl":"10.1016/j.xphs.2025.103819","url":null,"abstract":"<div><div>Fibrosis is characterized by excessive extracellular matrix accumulation, leading to organ dysfunction and irreversible damage in advanced stages. Challenges in sustaining drug levels within fibrotic lesions with the currently used antifibrotic therapies, including pirfenidone, often necessitate high drug doses that can cause systemic side effects. Here, we introduce a succinylated gelatin (SG)-coated liposome (SG-lip) system, which enhances pirfenidone retention and enables enzyme-responsive release at sites of fibrosis in an <em>in vitro</em> model. The SG coating, which ensures high collagen-binding affinity, is degraded by matrix metalloproteinases, which are overexpressed in fibrotic tissues, allowing targeted drug release. <em>In vitro</em> experiments using NRK-49F (kidney fibroblasts), WI-38 (lung fibroblasts), and RI-T (hepatic stellate cells) cultured on collagen I gel, SG-lip prolongs drug retention and sustains localized release at sites of fibrosis. In experiments simulating transient drug exposure by washing away the residual pirfenidone after treatment, pirfenidone-loaded SG-lip significantly inhibit fibroblast proliferation, invasion, and myofibroblast differentiation. Our enzyme-triggered drug delivery system enhances the antifibrotic efficacy of pirfenidone, with the potential to reduce systemic exposure and associated side effects. These findings highlight SG-lip as a promising platform for targeted antifibrotic therapy, offering a novel strategy to improve treatment of fibrosis.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 7","pages":"Article 103819"},"PeriodicalIF":3.7,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143943687","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":"Tailored biopolymer capsules for colon-specific drug delivery: A 3D printing perspective","authors":"Jan Muselík ,&nbsp;Alena Komersová ,&nbsp;Jan Elbl ,&nbsp;Roman Svoboda ,&nbsp;Kevin Matzick ,&nbsp;Jana Macháčková ,&nbsp;Marie Nevyhoštěná ,&nbsp;Zuzana Krepelková ,&nbsp;Jaroslav Novotný ,&nbsp;Aleš Franc","doi":"10.1016/j.xphs.2025.103815","DOIUrl":"10.1016/j.xphs.2025.103815","url":null,"abstract":"<div><div>The present study aims to develop capsules employing hot melt extrusion (HME) and fused deposition modeling (FDM) three-dimensional (3D) printing approach. The primary objective was to establish a colon drug delivery system (CDDS) based on multiple release mechanisms. In the study, 3D printed hydroxypropylmethylcellulose (HPMC) based capsules containing polysaccharides (alginate, chitosan pectin from citrus and pectin from apple) were used to provide a time-triggered and microbiota-triggered release mechanism. Thirteen capsule compositions were tested, and physico-chemical properties, disintegration time, dissolution characteristic (lag time) and 50 days accelerated stability were assessed. In addition, an enteric coating by Eudragit S was tested to enhance protection against the gastric environment. Disintegration time of the capsule under <em>in vivo</em> conditions was verified in healthy volunteers by oral administration of the caffeine-loaded capsule and determination of the first-appearance time of caffeine in the saliva. Furthermore, <em>in vivo</em> monitoring of the transition time in piglets was performed by X-ray examination after oral administration of BaSO₄-loaded capsules. Optimal capsule composition was identified as HPMC and pectin from citrus in 80:20 wt% ratio. Printed capsules showed suitable physico-chemical properties, lag time and stability. Minimal drug release in the upper gastrointestinal tract (∼5 %) for the first 8–10 h was ensured by both coated and uncoated capsules. In addition, as demonstrated by the <em>in vivo</em> transition time monitoring assay, with accelerated passage of the capsule through the gastrointestinal tract, degradation is significantly accelerated (∼4 h) by a microbiota-triggered mechanism, effectively targeting the colon. Using 3D printing, a colonic-specific drug delivery system was prepared that could potentially be suitable for treating patients with various intestinal physiological conditions.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 7","pages":"Article 103815"},"PeriodicalIF":3.7,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972737","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":"Comparative evaluation of chelators in the context of analysis of antibody oxidative stability","authors":"Poulami Majumder,&nbsp;Sara M. Eslami,&nbsp;Allison L. Dill","doi":"10.1016/j.xphs.2025.103820","DOIUrl":"10.1016/j.xphs.2025.103820","url":null,"abstract":"<div><div>Oxidation is a critical post-translational modification for antibodies that naturally possess many solvent-exposed amino acid residues. Presence of oxidized methionine and tryptophan residues may potentially impact safety, efficacy, clearance, and immunogenicity of antibodies, emphasizing the importance of including oxidation assays as a part of the antibody control strategy. Sub-unit Reversed Phase HPLC is a commonly employed method to measure oxidation, wherein enzymatic digestion of antibodies followed by disulfide reduction is essential for sample preparation. Peaks resulting from intact sub-units i.e. light chain (LC), single-chain crystallizable fragment (Fc), and N-terminal half of heavy chain (Fd) and additional peaks arising due to subunit oxidation can be easily resolved to quantify oxidative degradation. Our data suggest that the performance of the method can be compromised due to sample oxidation during the analysis window imposing restrictions on sample throughput and increasing method variability. Drug substance batches of six monoclonal antibodies with variable subclasses and isoelectric points showed an increase of 5-50% in subunit oxidation levels when tested over 48 hours. With an aim to minimize oxidation during analysis we modified the sample preparation technique using a variety of metal chelators including Ethylenediaminetetraacetic acid (EDTA), Ethylene Glycol-bis (β-aminoethyl ether)-N,N,N′,N′-Tetraacetic Acid (EGTA), Diethylene Triamine Pentaacetic Acid (DTPA), Nitrilotriacetic acid (NTA) and Hydroxyethyl Ethylenediamine Triacetic Acid (HEDTA). EGTA showed the most prevalent stabilizing influence on subunit oxidation for all drug substance batches screened. Overall, our results demonstrate that careful optimization of sample preparation during oxidation analysis can increase sample throughput significantly and highlight the feasibility of using EGTA as a more suitable alternative to EDTA, the most employed trace-metal chelator in the biopharmaceutical space.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 7","pages":"Article 103820"},"PeriodicalIF":3.7,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143943686","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":"3D printing for personalized formulations: individual dosing strategies for propranolol hydrochloride tablets","authors":"Yingjun Xiao ,&nbsp;Xiaolu Han ,&nbsp;Yunqi Bi ,&nbsp;Xiaoxuan Hong ,&nbsp;Xianfu Li ,&nbsp;Nan Liu ,&nbsp;Shanshan Yang ,&nbsp;Hui Zhang ,&nbsp;Zengming Wang ,&nbsp;Aiping Zheng","doi":"10.1016/j.xphs.2025.103816","DOIUrl":"10.1016/j.xphs.2025.103816","url":null,"abstract":"<div><div>3D printing technology is characterized by highly personalized, small batch production, and excellent reproducibility. These features enable it to address the limitations of traditional dose-dividing methods currently employed in medical institutions, thereby fulfilling the diverse dosing requirements of patients. In this study, we developed two individual dosing strategies for formulating 3D printing pharmaceutical formulations (3DPF) and 3D printing divided-dose tablets (3DPDT). Specifically, 3DPF were prepared using a gel ink containing propranolol hydrochloride as the active pharmaceutical ingredient, while 3DPDT were fabricated using a paste ink incorporating powdered commercial tablets. We investigated the rheological properties of the gel and paste ink, and assessed the mechanical properties, assay, and dissolution profile of tablets. The results indicate that the appearance, mechanical properties, drug content, content uniformity and drug dissolution rate of 3DPF and 3DPDT meet the United States Pharmacopoeia-National Formulary 2024 (USP-NF 2024) requirements. These strategies demonstrate highly reproducible and high-quality tablet preparation capabilities, which are applicable in drug development and pharmacy services. Furthermore, these approaches effectively resolve the issue of fixed dosages in commercially available drugs failing to meet the personalized medication needs of special populations. They provide a novel and promotable individual dosing solution tailored to the medication requirements of various patient groups.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 7","pages":"Article 103816"},"PeriodicalIF":3.7,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972670","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":"A cluster of articles in memory of Rodolfo Pinal, Ph.D.","authors":"Hwee Jing Ong, Fernando Alvarez-Nunez, Teresa Carvajal, Samuel H Yalkowsky","doi":"10.1016/j.xphs.2025.103821","DOIUrl":"10.1016/j.xphs.2025.103821","url":null,"abstract":"","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"103821"},"PeriodicalIF":3.7,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998296","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}