Journal of pharmaceutical and biomedical analysis最新文献

{"title":"Comprehensive pharmacokinetic profiling of twelve compounds from Phellinus Igniarius extract in rats by UHPLC-MS/MS.","authors":"Peng Zhao, Caixia Li, Shuting Zhou, Tiantian Wu, Yameng Zhu, Yang Liu, Xiwei Wu, Huizi Ouyang, Haoping Mao, Jun He","doi":"10.1016/j.jpba.2024.116645","DOIUrl":"https://doi.org/10.1016/j.jpba.2024.116645","url":null,"abstract":"<p><p>The medicinal fungus Phellinus Igniarius (P. igniarius) has been demonstrated to possess a variety of pharmacological effects, including anti-oxidant, anti-tumor, blood circulation promotion, anti-diarrheal and sedative properties, etc. In order to gain a deeper understanding of the components in P. igniarius extract and its dynamic process in vivo, an ultra-performance liquid chromatography-triple quadrupole mass spectrometry method was developed and validated for the simultaneous determination of 12 major components (nobiletin tangeretin, narirutin, 3,4-dihydroxybenzaldehyde, hesperidin, hispidin, caffeic acid, hispolon, osmundacetone, amygdalin, salvianolic acid B and protocatechuic acid) of P. igniarius extract in rat plasma. The analyses were conducted using an ACQUITY UPLC BEH C18 column with acetonitrile and 0.1 % formic acid (v/v) in aqueous solution as the mobile phases. The intra-day and inter-day precision was less than 12.61 % for all 12 experiments, with a precision range of -11.28-12.25 %. Extraction recovery exhibited a range of 74.03-114.33 %, while the matrix effect demonstrated a range of 83.95-119.28 %. The stability tests demonstrated that the analytes remained stable, with relative standard deviations below 11.65 %. The pharmacokinetic parameters of the 12 compounds in rat plasma after oral administration of P. igniarius extract were successfully determined by the established UPLC-MS/MS method. The findings presented a pivotal foundation for advancing future research on the in vivo processes and mechanisms underlying the effects of P. igniarius extracts.</p>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"255 ","pages":"116645"},"PeriodicalIF":3.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872383","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":"Dispersive microextraction techniques as efficient strategies for the analysis of saliva: A comprehensive review.","authors":"Andreu L López-Juan, Luis Miguel Moreno-Calleja, Juan L Benedé, Alberto Chisvert","doi":"10.1016/j.jpba.2024.116644","DOIUrl":"https://doi.org/10.1016/j.jpba.2024.116644","url":null,"abstract":"<p><p>This review article brings together two of the current hot-spots in the field of analytical chemistry, and more specifically in the sample preparation stage: the use of dispersive microextraction techniques, and the analysis of saliva. Due to saliva collection is minimally invasive, it is increasingly being considered in bioanalysis. Moreover, bioanalysis is routine and agglutinates a high number of samples demanding for fast results, thus high-throughput assays are highly required. On the other hand, if something characterizes biological matrices, including saliva, is their complex composition. To adapt the matrix to the analytical method to be applied and to avoid as far as possible the matrix effect, an efficient sample preparation stage is required. To this regard dispersive microextraction techniques, as rapid, efficient and sustainable sample preparation approaches, play a crucial role. In the first part of the review, different workflows for the collection and pretreatment will be briefly described, placing special emphasis on advice to follow. Then, a compilation of the different applications of dispersive techniques for the analysis of saliva is presented, in which the trends observed in both specific analytes and microextraction approaches used are discussed.</p>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"255 ","pages":"116644"},"PeriodicalIF":3.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872384","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":"Identification and quality control of isomers in Huo-Xiang-Zheng-Qi Mixture using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry and inductive effects analysis.","authors":"Yourun Chen, Chongyang Wang, Kaiwen Zhang, Meng Zhao, Qing Wang, Yanqing Zhang, Chang-Jiang-Sheng Lai","doi":"10.1016/j.jpba.2024.116646","DOIUrl":"https://doi.org/10.1016/j.jpba.2024.116646","url":null,"abstract":"<p><p>Huo-Xiang-Zheng-Qi Mixture is a renowned traditional Chinese medicine formula used to treat ailments associated with dampness pathogens. This study employed ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry to perform a comprehensive qualitative and quantitative analysis of the chemical compounds in Huo-Xiang-Zheng-Qi Mixture. A total of 155 compounds were identified, including 61 flavonoids and their glycosides, 36 phenylethanoid glycosides, 23 saponins, 14 coumarins, 9 organic acids, 1 amino acid, 2 nucleosides and purines, and 9 additional compounds. For the first time, a practical method based on inductive effects and hydrogen bonding was developed to determine the elution order of PhGs isomers. The relative quantification of 9 isomers and the absolute quantification of 10 compounds in Huo-Xiang-Zheng-Qi Mixture were determined, primarily derived from tangerine peel, licorice and Magnolia officinalis. Notably, 18 β - glycyrrhetinic acid and 9 Phenylethanoid glycosides isomers were quantified for the first time in the Huo-Xiang-Zheng-Qi prescription. These findings were compared with corresponding values in Huo-Xiang-Zheng-Qi oral liquid. The research revealed relatively low levels of 18 β - glycyrrhetinic acid in the mixture and significant differences in the content of four key compounds: magnolol, honokiol, glycyrrhizic acid and hesperidin. This study offers valuable insights into the chemical composition of Huo-Xiang-Zheng-Qi Mixture and provides a foundation for optimizing preparation processes, improving therapeutic efficacy, and establishing quality standards.</p>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"255 ","pages":"116646"},"PeriodicalIF":3.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882390","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":"Strategies for automated affinity purification-resin screening for non-traditional biopharmaceuticals in the discovery space.","authors":"Jordan R Cave, Alexey A Makarov, Gregory F Pirrone","doi":"10.1016/j.jpba.2024.116637","DOIUrl":"https://doi.org/10.1016/j.jpba.2024.116637","url":null,"abstract":"<p><p>Biotherapeutics occupy a significant portion of the pharmaceutical pipeline and are projected to continue growing in sales and scope. Further, the field is advancing novel and more complex molecules beyond monoclonal antibodies including multi-target proteins, engineered proteins and bioconjugates. In this aspect, the development of increasingly advanced and challenging therapies necessitates a commiserate degree of innovation to develop automated methods for resin screening, purification, and analytics in the discovery space to quickly identify liabilities and rank candidates with minimal impact on developmental resources. In this work, we introduce an automated resin screening platform tailored to small scale production runs for clone evaluation and process development in the biologics discovery space. The complex characteristics of these novel therapies requires empirical testing of resin to ensure optimal recovery of high-quality material for evaluation to inform on cell line development and future downstream process and analytical method development. This workflow enables the purification of milligrams of protein material for analytical testing and identifies ideal resins to leverage downstream as a candidate quickly progresses. This workflow was validated using a research monoclonal antibody and applied to a novel bispecific fusion protein to evaluate resin performance with respect to recovery, purity and impact on higher-order structure.</p>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"255 ","pages":"116637"},"PeriodicalIF":3.1,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872386","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":"Diazonium-based derivatization for enhanced detection of phosphorylated metabolites by LC-MS in cells.","authors":"Yikang Wang, Feifei Lin, Guozheng Zhu, Xiaoxue Zhou, Youhong Hu, Jia Liu","doi":"10.1016/j.jpba.2024.116642","DOIUrl":"https://doi.org/10.1016/j.jpba.2024.116642","url":null,"abstract":"<p><p>Phosphorylated small molecule metabolites play crucial roles in physiological processes such as glycogen metabolism and inflammation regulation. However, their high polarity, structural similarity, poor chromatographic separation, and weak mass spectrometric signals make their accurate quantification challenging, thereby hindering the study of related metabolic mechanisms and diseases. To address these challenges, we developed a novel derivatization reagent, DMQX (5-diazomethane quinoxaline), and combined it with liquid chromatography-mass spectrometry (LC-MS). This approach achieved baseline separation of five groups of isomers and enabled the quantification of 24 phosphorylated metabolites, providing comprehensive coverage of these metabolites in biological pathways. We applied this method to quantify 21 endogenous phosphorylated metabolites in HepG2 cells with and without vesicular stomatitis virus infection, demonstrating the potential of this analytical approach for advancing the study of metabolic mechanisms through quantitative analysis of phosphorylated metabolites in biological samples.</p>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"255 ","pages":"116642"},"PeriodicalIF":3.1,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864421","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":"Investigation of metabolite profiles of kidney tissues in rats treated with favipiravir drug: An NMR-based metabolomics study.","authors":"Zeynep Rozerin Çevik, Ali Erdoğan, Akın Mumcu, Berat Doğan","doi":"10.1016/j.jpba.2024.116640","DOIUrl":"https://doi.org/10.1016/j.jpba.2024.116640","url":null,"abstract":"<p><p>In response to the urgent need for effective treatments during the rapid spread and high mortality rate of COVID-19, existing drugs were repurposed for potential antiviral effects, including favipiravir, originally designed as an RNA-dependent RNA polymerase inhibitor for influenza. Despite limited antiviral effectiveness against COVID-19, favipiravir has been reported to cause several adverse drug events (ADEs) in the body. Recent studies have shown that favipiravir can damage various tissues in rats. However, a detailed analysis of its effects on the metabolomics profile of tissues using high-resolution spectroscopic technologies has not yet been conducted. In this study, it was aimed to analyze the metabolomic changes in rat kidney tissues induced by favipiravir, using high-resolution nuclear magnetic resonance (NMR) spectroscopy. Sixty male Wistar Albino rats were randomly divided into three groups: control, low-dose favipiravir (200 mg/kg), and high-dose favipiravir (300 mg/kg), with 20 rats per group. Each group received its respective treatment via oral gavage. After the treatment period, kidney tissue samples were collected and subjected to ¹H NMR analysis. Bioinformatics analysis of the obtained ¹H NMR spectra suggests that favipiravir induces dose-dependent metabolic changes in kidney tissue, with higher doses causing more profound disruptions in several pathways.</p>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"255 ","pages":"116640"},"PeriodicalIF":3.1,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872385","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":"Plasma metabolomic signatures after oral administration of ritonavir in COVID-19 treatment via chemometrics-assisted UPLC/Q-TOF/MS/MS.","authors":"Fatma Demirkaya Miloglu, Burak Bayrak, Busra Yuksel, Sema Nur Demir, Gulsah Gundogdu, Yucel Kadioglu, A M Abd El-Aty","doi":"10.1016/j.jpba.2024.116638","DOIUrl":"https://doi.org/10.1016/j.jpba.2024.116638","url":null,"abstract":"<p><p>Understanding the pharmacodynamics of ritonavir through metabolomics offers insights into its side effects and helps in the development of safer therapies. This study aimed to investigate the effects of ritonavir treatment on the metabolic profiles of rabbits via a metabolomics approach, with the objective of elucidating its impact on various biochemical pathways and identifying relevant biomarkers. The rabbits were divided into control and ritonavir-treated groups, and their plasma samples were analyzed via ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF/MS/MS). Metabolites were identified on the basis of the masscharge ratio (m/z) and validated via XCMS software. Metabolites with a fold change ≥ 1.5 and P ≤ 0.01 were analyzed via principal component analysis (PCA) and orthogonal partial least squares discrimination analysis (OPLS-DA) to distinguish between the groups. MetaboAnalyst 6.0 was used for pathway analysis to identify metabolic pathways affected by ritonavir. The PCA and OPLS-DA models revealed clear separation between the control and ritonavir-treated groups, with high R² and Q² values indicating robust model performance. Pathway analysis revealed that ritonavir treatment significantly affected several metabolic pathways, including those related to ether lipid, phenylalanine, sphingolipid, and glycerophospholipid metabolism. Particularly significant changes were observed in metabolites related to lipid metabolism, oxidative stress responses and cellular signaling. Ritonavir significantly impacts metabolic pathways, particularly those involved in lipid metabolism, and oxidative stress responses, which may influence immune responses and drug interactions. This study also highlights the potential of integrating metabolomics with personalized medicine approaches to optimize ritonavir treatment strategies and reduce adverse effects. These findings indicate that ritonavir significantly influences cellular homeostasis and metabolic processes in addition to its antiviral properties. This highlights the necessity of comprehending the metabolic effects of ritonavir to enhance its clinical application, especially in the management of COVID-19. Further research is warranted to explore these alterations and their implications for therapeutic strategies.</p>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"255 ","pages":"116638"},"PeriodicalIF":3.1,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864591","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":"First separation of commendamide enantiomers.","authors":"Saba Jorbenadze, Giorgia Sprega, Aluda Chelidze, Barbara Sechi, Roberto Dallocchio, Bezhan Chankvetadze, Vincenzo Di Marzo, Rosaria Villano, Paola Peluso","doi":"10.1016/j.jpba.2024.116643","DOIUrl":"https://doi.org/10.1016/j.jpba.2024.116643","url":null,"abstract":"<p><p>N-(3-hydroxyacyl)glycines are compounds of remarkable interest due to their biogenic origin and bioactivity and as precursors of the corresponding 3-acyloxy derivatives which represent an important class of bioactive products of bacterial origin. Commendamide [N-(3-hydroxypalmitoyl)glycine] (1) is a gut microbiota-derived bioactive metabolite that is structurally like endogenous long-chain N-acyl-amino acids belonging to the endocannabinoidome, a complex lipid signaling system involved in several aspects of mammalian physiology and pathology. Thanks to this structural similarity, this compound and its analogues, like the N-(3-hydroxymyristoyl)glycine 2, exert a remarkable bioactivity in mammals, for instance, through activation of G-protein-coupled receptors (GPCRs). N-(3-Hydroxyacyl)glycines are chiral and the availability of their pure enantiomers may bring light to possible enantioselective pathways within the biological processes which these compounds are involved in. A sustainable synthesis of rac-1 and its analogues was recently reported, but asymmetric synthesis and enantioseparation methods to access their pure or enriched enantiomers were not reported so far. In this paper, we report the first direct separation of commendamide enantiomers by using enantioselective high-performance liquid chromatography (HPLC) with polysaccharide-based chiral columns, aqueous-organic mixtures as mobile phases and either electrospray ionization mass spectrometry (ESI-MS) or UV detection. Optimal enantioseparation was obtained by using an amylose tris(3,5-dimethylphenylcarbamate)-based chiral column and acetonitrile/water 60:40 (v/v) (0.1 % acetic acid) as mobile phase. By adopting the same method, the enantioseparation of the analogue 2 was also performed. The molecular bases of the higher retention and selectivity observed for the N-(3-hydroxyacyl)glycine 1 compared to the analogue 2 were explored by computational analysis.</p>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"255 ","pages":"116643"},"PeriodicalIF":3.1,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864590","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":"Plasma bile acid profile analysis by liquid chromatography-tandem mass spectrometry and its application in healthy subjects and IBD patients.","authors":"Xuepeng Gong, Dong Liu, Lu Liu, Guangjie Yang, Yongfang Lei, NingHong Li, Yufei Chen, Hengyi Yu, Xiping Li, Dong Xiang","doi":"10.1016/j.jpba.2024.116639","DOIUrl":"https://doi.org/10.1016/j.jpba.2024.116639","url":null,"abstract":"<p><p>Bile acids (BAs), not only promote the absorption of fat-soluble nutrients and regulate the metabolism of multiple substances but also have a potential role as diagnostic and prognostic indicators in a variety of diseases such as cholestasis, hepatocellular carcinoma, and diabetes mellitus. Here, a rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous quantification of 50 BAs was developed and validated. Sample preparation included internal standard spiking, followed by protein precipitation, centrifugation, solvent evaporation, and reconstitution. Baseline separation of all isobaric BA species was achieved on an Ultimate XS-C18 column (5 μm, 150 mm × 4.6 mm). The method showed good linearity with high regression coefficients (>0.990) with acceptable accuracy and precision for intra-day and inter-day analyses and achieved good recovery rates for representative analytes. No apparent carryover or matrix effect was observed. The analytical method was successfully applied to the determination of the plasma BA profile in healthy subjects and patients with inflammatory bowel disease (IBD). The routine instrumentation, low sample volume, simple pretreatment, wide range of BAs, and good separation make this LC-MS/MS method suitable for use as a BA profile assay in clinical and basic research studies. This method could be poised to identify possible BA biomarkers for non-invasive early diagnosis and therapeutic evaluation of IBD.</p>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"255 ","pages":"116639"},"PeriodicalIF":3.1,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877470","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":"Evaluation study of congelex laxative granules based on HPLC fingerprint, multi-component content determination, and chemometrics.","authors":"Chengjialu Qian, Shizhao Wang, Hongyan Chen","doi":"10.1016/j.jpba.2024.116636","DOIUrl":"https://doi.org/10.1016/j.jpba.2024.116636","url":null,"abstract":"<p><p>Congelex Laxative Granules is an in-house preparation of Hebei Provincial Hospital of Traditional Chinese Medicine. This study aims to establish the HPLC fingerprint of Congelex Laxative Granules and evaluate its quality using chemometric methods. The Agilent Eclipse Plus C18 column and a methanol-water gradient elution system were employed, with detection at 224 nm. The High-performance liquid chromatography (HPLC) analysis of 20 batches of samples successfully established a fingerprint with 17 common peaks and a similarity exceeding 0.95. Seven main active components, including salidroside, echinacoside, acteoside, specnuezhenide, wedelolactone, aurantio-obtusin, and chrysophanol, were quantitatively analyzed. Hierarchical Cluster Analysis (HCA), principal component analysis (PCA), and orthogonal partial least squares-discriminant analysis (OPLS-DA) were used to comprehensively evaluate sample quality. Results indicated that the 20 batches could be divided into two categories, with consistent results from PCA and HCA. The OPLS-DA model was stable and reliable, identifying salidroside, acteoside, and chrysophanol as key differential markers. The conclusion shows that the established fingerprint and content determination method provide an accurate and reliable tool for the quality control and comprehensive evaluation of Congelex Laxative Granules.</p>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"255 ","pages":"116636"},"PeriodicalIF":3.1,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877464","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}