Journal of Chromatography B最新文献

{"title":"Quantifying the extended energy metabolome of industrially important microorganisms (Saccharomyces cerevisiae) using ultra-performance liquid chromatography with mass spectrometry","authors":"Jordan I. Oliver,&nbsp;Antony N. Davies,&nbsp;Richard Dinsdale","doi":"10.1016/j.jchromb.2024.124342","DOIUrl":"10.1016/j.jchromb.2024.124342","url":null,"abstract":"<div><div>This study has developed a new targeted methodology for the separation, detection, and quantification of metabolites from the wider energy metabolome of industrially important microorganisms such as <em>Saccharomyces cerevisiae</em> in a single analytical sample. This has been achieved using UHPLC-MS technology in HILIC mode. Absolute concentrations of metabolites nicotinamide adenine dinucleotide (NAD), nicotinamide adenine dinucleotide reduced (NADH), nicotinamide adenine dinucleotide phosphate (NADP), nicotinamide adenine dinucleotide phosphate reduced (NADPH), flavin adenine dinucleotide (FAD), adenosine-monophosphate (AMP), adenosine-diphosphate (ADP), and adenosine-triphosphate (ATP) were determined in a single extraction and analytical methodology.</div><div>This study demonstrated the development of a rapid, statistically robust, and reproducible methodology through regression calibrations of standard samples from 0.1 to 100 µMol providing a correlation value of r² = &gt;0.98 for all metabolites. Sample preparation, extraction and analytical methodologies used showed high accuracy, sensitivity, and recovery. With an LOD and LOQ for the targeted analysis of metabolites from the wider energy metabolism in a single sample and analytical run with the lowest LOD of 0.055 nMol (±0.002) and lowest LOQ of 0.167 nMol (±0.006). This method was then applied to <em>Saccharomyces cerevisiae</em> cell culture to evaluate the methodology in industrially used microbial cultures. Results obtained have been statistically determined to be robust and reproducible through recovery analysis using deuterated and isotopically labelled internal standards AMP-¹⁵N, ADP-¹⁵N and ATP-d₁₄.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1248 ","pages":"Article 124342"},"PeriodicalIF":2.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the pharmacological mechanism of fermented Eucommia ulmoides leaf extract in the treatment of cisplatin-induced kidney injury in mice: Integrated traditional pharmacology, metabolomics and network pharmacology","authors":"Kexin Lin ,&nbsp;Lijuan Xiong ,&nbsp;Wen Zhang ,&nbsp;Xuan Chen ,&nbsp;Jieqi Zhu ,&nbsp;Xiaofei Li ,&nbsp;Jianyong Zhang","doi":"10.1016/j.jchromb.2024.124358","DOIUrl":"10.1016/j.jchromb.2024.124358","url":null,"abstract":"<div><div>Cisplatin (CP) is a widely utilized anticancer drug, which also produces significant side effects, notably acute kidney injury (AKI). Fermented <em>Eucommia ulmoides</em> leaf (FEUL), a medicinal and edible Chinese herbal remedy, is known for its renoprotective properties. However, the effect and underlying mechanism of FEUL extract in AKI therapy have remained largely unexplored. This research aimed to elucidate the protective roles of FEUL extract in an AKI mouse model through biochemical assays, histopathological examinations, and investigating the underlying mechanisms based on metabolomics and network pharmacology. The findings demonstrated that pretreatment with orally administered FEUL extract significantly reduced blood urea nitrogen (BUN), and serum creatinine (SCr) levels, and ameliorated CP-induced kidney histopathological injuries. Moreover, FEUL extract attenuated CP-induced endoplasmic reticulum (ER) stress by reducing the protein expressions of PERK, IRE 1α, GRP78, ATF6, ATF4, and CHOP. The metabolomics results indicated that a total of 31 metabolites, involved in taurine and hypotaurine metabolism, lysine degradation, and steroid hormone biosynthesis, were altered after FEUL extract administration. Furthermore, metabolomics integrated with network pharmacology revealed that 8 targets, 4 metabolites, and 3 key pathways including steroid hormone biosynthesis, purine metabolism, and tryptophan metabolism were the main mechanisms of FEUL extract in treating CP-induced AKI. These findings suggested that FEUL extract could offer valuable insights for potential CP-induced AKI treatment strategies.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1248 ","pages":"Article 124358"},"PeriodicalIF":2.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611284","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":"Spectrum-effect relationship between HPLC fingerprints and antioxidant activities of Bletilla striata","authors":"Sha Wen,&nbsp;Yuzhi Luo,&nbsp;Lingyi Liu,&nbsp;Lili Zhou,&nbsp;Lingli Li,&nbsp;Siqi Wang,&nbsp;Huixin Song,&nbsp;Songyuan Xia,&nbsp;Weifeng Li,&nbsp;Xiaofeng Niu","doi":"10.1016/j.jchromb.2024.124351","DOIUrl":"10.1016/j.jchromb.2024.124351","url":null,"abstract":"<div><div><em>Bletilla striata</em> is a perennial herb that was first published in Shennong’s Classic of the Materia Medica, pharmacological studies have shown that it has the activities of promoting wound healing, anti-inflammatory and antioxidant. However, the relationship between the antioxidant activity and the chemical composition of <em>Bletilla striata</em> is still unclear. In this paper, the chemometric method was used to construct the spectral effect relationship between the fingerprints of 20 batches of <em>Bletilla striata</em> extracts from different origins and their in vitro antioxidant activities. The results showed that the chemical composition of the samples from different sources varied significantly, while the samples from Shaanxi and Hubei provinces were of relatively better quality. Among the 10 common peaks, coelonin, gymnoside IX and dactylorhin A were considered to be significantly correlated with the antioxidant activity of <em>Bletilla striata</em>. The results of this study will provide a basis and further insights for the quality evaluation and quality control of <em>Bletilla striata.</em></div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1248 ","pages":"Article 124351"},"PeriodicalIF":2.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638172","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":"Limitations in LC-MS/MS application for adagrasib and pembrolizumab quantification in rat plasma","authors":"Zvonimir Mlinarić","doi":"10.1016/j.jchromb.2024.124354","DOIUrl":"10.1016/j.jchromb.2024.124354","url":null,"abstract":"<div><div>An article by Harsha Shi et al. raises multiple concerns regarding sample preparation, the presence of the analyte in the analyzed solution, authenticity of the MS spectra, administration of drugs and blood collection, choice of internal standard, obtained pharmacokinetic parameters and usage of chromatographic column and solvents. While the research topic is interesting and the development of bioanalytical methods for novel drugs is crucial, this article does not seem to meet the analytical and methodological standards for the reliable determination of adagrasib and pembrolizumab in plasma samples. A detailed explanation is given in the letter.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1248 ","pages":"Article 124354"},"PeriodicalIF":2.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611288","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":"Quantitative analysis of three bioactive components of Biancaea decapetala extracts in rat plasma and RAW264.7 cells using UPLC-MS/MS and its application to comparative pharmacokinetics in normal and diseased states","authors":"Yang Zhou ,&nbsp;Pu Wang ,&nbsp;Zuying Zhou ,&nbsp;Meng Zhou ,&nbsp;Mingyan Chi ,&nbsp;Lin Zheng ,&nbsp;Yong Huang","doi":"10.1016/j.jchromb.2024.124356","DOIUrl":"10.1016/j.jchromb.2024.124356","url":null,"abstract":"<div><div><em>Biancaea decapetala</em> (Roth) O.Deg. (Fabaceae), traditionally utilized by the Hmong for treating rheumatoid arthritis (RA), has its pharmacokinetic behavior under disease conditions largely unexplored. In view of this, a UPLC-MS/MS method was established for the determination of protosappanin B (PTB), protosappanin B-3-<em>O-β-D</em>-glucoside (PTD), and 3-deoxysappanchalcone (3-DSC), key bioactive components of the herb, in rat plasma and RAW264.7 cells to explore the effect of disease state on the pharmacokinetic profiles changes of these three components <em>in vitro</em> and <em>in vivo</em>. These components were detected using multiple reaction monitoring (MRM) process in positive and negative mode. Each calibration curve had a high <em>R</em>² value of &gt; 0.99. The intra- and inter-day precisions of PTD, PTB, 3-DSC were all &lt; 15 %, and accuracy ranged from 85 % to 115 %. The RSD values pertaining to stability, recovery, matrix effect, and stability remained below 15.0 %. It was successfully applied for the investigation of the pharmacokinetics of these three components in rat plasma and RAW264.7 cells after administration of <em>Biancaea decapetala</em> extracts (BDE). In rat pharmacokinetic experiments, significant differences were observed in the AUC_(0-t), MRT_(0-t), and <em>Cl</em>_z/<em>F</em> values of PTD, PTB, 3-DSC between adjuvant-induced arthritis (AA) and normal rats. In cellular pharmacokinetic experiments, comparison with the normal group revealed increased AUC_(0-t) and MRT_(0-t) for these three components in the LPS-induced inflammatory cell model, along with decreased <em>Cl</em>_z/<em>F</em>, which was consistent with <em>in vivo</em> experimental outcomes. These findings suggest an increased absorption rate and a decreased elimination rate of the three components of BDE in AA rats and inflammatory cells, indicating a potential alteration in the rate and extent of drug metabolism. This study provided a theoretical reference for further clarification of its pharmacodynamic basis.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1248 ","pages":"Article 124356"},"PeriodicalIF":2.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592621","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":"Quantification of tricyclic glycopeptide in human plasma by UHPLC-MS3 coupled with counter-extraction follow by protein precipitation to enhance sensitivity","authors":"Luyao Yu ,&nbsp;Xiaoqian Chen ,&nbsp;Yingxia Guo ,&nbsp;Jiansong You ,&nbsp;Meiyun Shi ,&nbsp;Yalin Xi ,&nbsp;Lei Yin","doi":"10.1016/j.jchromb.2024.124343","DOIUrl":"10.1016/j.jchromb.2024.124343","url":null,"abstract":"<div><div>An ultra-high performance liquid chromatography tandem mass spectrometry cubed (UHPLC/MS³) assay coupled with protein precipitation and counter-extraction for detection of tricyclic glycopeptide vancomycin in human plasma was established and validated in this study. After protein precipitation and counter-extraction with dichloromethane, chromatographic separation of vancomycin and norvancomycin were performed on a reversed phase column (XBridge Peptide BEH C₁₈ column, 2.1 × 100 mm I.D, 3.5 μm). The transition (parent ions → fragment ions → further fragment ions) at <em>m</em>/<em>z</em> 725.3 → 144.1 → 100.1 was used for quantification of vancomycin. The transition (parent ions → fragment ions) at <em>m</em>/<em>z</em> 718.3 → 144.2 was used for detection of norvancomycin. The linear range of the developed analytical method for quantification of vancomycin was 0.5–100 µg/mL (r = 0.9989). The range of intra- and inter-day precisions of the assay among low, medium and high concentrations is between 1.88 % and 6.33 %. The sensitivity of the analytical method was significantly improved by using MS³ technique as monitoring mode and counter-extraction with dichloromethane followed by protein precipitation as sample processing assay. The developed UHPLC/MS³ assay was successfully applied for clinical therapeutic drug monitoring (TDM) of vancomycin in 45 human plasma samples.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1247 ","pages":"Article 124343"},"PeriodicalIF":2.8,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492172","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":"Preparation of attapulgite nanoparticles modified polypropylene adsorption membrane and its application in small molecular pollutant adsorption","authors":"Shuaibin Wu","doi":"10.1016/j.jchromb.2024.124338","DOIUrl":"10.1016/j.jchromb.2024.124338","url":null,"abstract":"<div><div>In this study, a novel surface covalent reaction method was used to modify attapulgite nanoparticles on the surface of polypropylene adsorption membrane to adsorb various small molecular pollutants for the first time. The surface covalent reaction method has the advantage of step control. Therefore, the uniformity and stability of attapulgite nanoparticles can be ensured, and then could effectively improve the adsorption performance of polypropylene adsorption membrane. On the other hand, compared with various materials modified on the surface of polypropylene adsorption membrane currently, attapulgite nanoparticles has the characteristics of low cost and environmental friendliness, which is more conducive to the large-scale practical application. The polypropylene adsorption membrane modified with attapulgite nanoparticles was characterized by field emission scanning electron microscopy, fourier transform infrared spectrometer and X-ray diffractograph, and it was confirmed that the attapulgite nanoparticles was successfully modified on the surface of the polypropylene adsorption membrane. The experimental results showed that the adsorption capacities of polypropylene adsorption membrane modified with attapulgite nanoparticles could reach 11.53 mg/g, 8.7 mg/g and 5.78 mg/g for cyromazine, malachite green and dagenan respectively within 10 s. In the case of the above three analytes, the minimum detected concentration could reach 0.02 mg/mL, and the relative standard deviation was about 10 %. At the same time, the adsorption performance of polypropylene adsorption membrane modified with attapulgite nanoparticles did not decrease significantly after 50 cycles. A standard recovery of 76.8 % − 89.5 % and a relative standard deviation of 7.2 % − 15.2 % were obtained by using the polypropylene adsorption membrane modified with attapulgite nanoparticles to adsorb cyromazine in cucumber skin samples, indicating that the polypropylene adsorption membrane modified with attapulgite nanoparticles has the ability to treat complex samples.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1247 ","pages":"Article 124338"},"PeriodicalIF":2.8,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441917","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":"Quantification of Epoxyeicosatrienoic acids Enantiomers: The development of reliable and practical liquid chromatography mass Spectrometry assay","authors":"Fadumo A. Isse ,&nbsp;Sara Helal ,&nbsp;Ahmed A. El-Sherbeni ,&nbsp;Dion R Brocks ,&nbsp;Ayman O.S. El-Kadi","doi":"10.1016/j.jchromb.2024.124346","DOIUrl":"10.1016/j.jchromb.2024.124346","url":null,"abstract":"<div><div>Epoxyeicosatrienoic acids (EETs) are increasingly recognized as key metabolites in the arachidonic acid (AA) metabolic pathway. EETs are epoxy derivatives of AA with two chiral centers formed by cytochrome P450 (CYP) enzymes. EETs have reported biological activities as racemates; however, knowledge on specific optical isomers of EET is lacking. A main reason is the absence of practical assay to quantify EETs isomers associated with specific pathological conditions and enzymes. The reported underivatized chiral LC-MS/MS assays utilize different mobile phases and flow rates or required long run times to achieve separation of EET stereoisomers. Others incorporated a derivatization step before the separation of EETs in their assays. Therefore, the objective of this study was to develop and validate a stereoselective assay for the simultaneous quantitation of underivatized EET enantiomers using Liquid Chromatography Mass Spectrometry (LC-MS/MS) with an optimum baseline separation using binary mobile phase and gradient elution. Herein, we report the development and validation of an LC-MS/MS assay, and its application to quantify the formation of EET enantiomers mediated by human liver microsomes. Assay linearity extends over 10–600 ng/mL with r² &gt; 0.99 for all EETs enantiomers. The inter-run accuracy was within ± 15 %, and precision was ≤ 15 %, and &lt; 20 % for the LLOQ. The matrix effect for the current assay was within ≤ ±20 %, and the mean recovery for quantitative methods was 70–125 %. The assay proved to be reliable and practical for chiral analysis.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1247 ","pages":"Article 124346"},"PeriodicalIF":2.8,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Facile preparation of titanium functionalized cross-linked chitosan polymer for phosphoproteome analysis in serum","authors":"Xiuqin Sheng,&nbsp;Yimin Guo,&nbsp;Chuan-Fan Ding,&nbsp;Yinghua Yan","doi":"10.1016/j.jchromb.2024.124347","DOIUrl":"10.1016/j.jchromb.2024.124347","url":null,"abstract":"<div><div>Efficient phosphopeptide enrichment is extremely important for proteomics research. In this work, chitosan (CTs), 2,3-dihydroxyterephthalaldehyde (2,3-DHA), and carbohydrazide (CHZ) are polymerized to generate the polymer (DHA-CTs-CHZ), and then the polymer (DHA-CTs-CHZ) is coupled with a significant number of titanium ions to enrich phosphopeptides. The material exhibits high selectivity (5000:1 M ratio of BSA to β-casein), sensitivity (0.001 fmol/μL), loading (83.3 μg/mg), recovery (98.6 ± 1.2 %), and effective size exclusion for phosphopeptide enrichment. In addition, 46 phosphopeptides and 31 phosphorylated sites associated with 27 phosphorylated proteins were successfully captured from the serum of normal subjects, while 47 phosphopeptides and 35 phosphorylated sites associated with 30 phosphorylated proteins were successfully captured from Alzheimer’s disease (AD) patients’ serum.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1247 ","pages":"Article 124347"},"PeriodicalIF":2.8,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520583","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":"Pharmacokinetic and tissue distribution study of pectolinarigenin in rats using UPLC-MS/MS","authors":"Yingying Pan ,&nbsp;Zihan Tan ,&nbsp;Ping Liu ,&nbsp;Aixia Yang ,&nbsp;Lin-Lin Chen","doi":"10.1016/j.jchromb.2024.124344","DOIUrl":"10.1016/j.jchromb.2024.124344","url":null,"abstract":"<div><div>Pectolinarigenin (PEC), a natural flavonoid isolated from <em>Cirsium japonicum</em>, exhibits promising therapeutic potential for multiple cancers. In present study, a simple and sensitive UPLC-MS/MS method was established for the quantification of PEC in rat plasma and tissues. The assay procedure involved a one-step protein precipitation with tadalafil as the internal standard, and separation on a Welch Xtimate UHPLC C₁₈ column by gradient elution of acetonitrile/aqueous formic acid (0.1 %, v/v) at a flow rate of 0.2 m L·min⁻¹. The detection was conducted using multiple-reaction monitoring via an electrospray ionization source in positive ionization mode. The established method was proved to be highly sensitive with a good linearity (R² &gt; 0.99) in respective concentration range (0.1–100 ng·mL⁻¹ in plasma and 1–10,000 ng·mL⁻¹ in tissues) and acceptable extraction recovery (≥71.17 %), matrix effect and stability, which was applied to study the pharmacokinetics and tissue distribution of PEC after intravenous (100 μg·kg⁻¹) and oral administration (10, 20 and 40 mg·kg⁻¹). PEC was promptly absorbed (<em>T</em>_max ≤ 0.222 h) and maintained at a low level with slow elimination (<em>t</em>_{1/2 z} ≥ 14.47 h) in rats after oral administration, resulting in extremely low bioavailability (0.56–0.68 %). However, PEC is widely distributed in rat tissues with high exposure in GI tract, liver and kidney. The bioavailability and tissue affinity were firstly revealed, which would guide directions for further development of PEC as an anti-tumor drug candidate.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1247 ","pages":"Article 124344"},"PeriodicalIF":2.8,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520584","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}