Journal of pharmaceutical and biomedical analysis最新文献

{"title":"A strategy integrated DNA barcoding with metabolomics for screening distinguishable combinatorial chemical quality marker between Pheretima aspergillum and Pheretima vulgaris Chen","authors":"Ye Shang ,&nbsp;Suyi Liu ,&nbsp;Chunxiao Liang ,&nbsp;Tenukeguli Tuliebieke ,&nbsp;Shujing Chen ,&nbsp;Kunze Du ,&nbsp;Xiaoxuan Tian ,&nbsp;Jin Li ,&nbsp;Jun He ,&nbsp;Hua Jin ,&nbsp;Yanxu Chang","doi":"10.1016/j.jpba.2025.116716","DOIUrl":"10.1016/j.jpba.2025.116716","url":null,"abstract":"<div><div><em>Pheretima</em> is an animal-derived traditional Chinese medicines (TCMs). The chemical quality markers of <em>Pheretima</em> used to distinguish different species are still ambiguous. Under this premise, a strategy integrated DNA barcoding with metabolomics is promoted for identifying <em>Pheretima</em> and screening distinguishable combinatorial chemical quality marker (DCQ-marker) between <em>Pheretima aspergillum</em> (<em>P. aspergillum</em>) and <em>Pheretima vulgaris</em> Chen (<em>P. vulgaris</em>). As a result, adenosine, adenine, L-phenylalanine and uridine are successfully selected as DCQ-markers between <em>P. aspergillum</em> and <em>P. vulgaris</em>. This study provides convenient strategy for quickly screening DCQ-marker between <em>P. aspergillum</em> and <em>P. vulgaris</em>. It will be meaningful for further promoting quality control on <em>Pheretima</em> and providing a reference for the quality evaluation of other animal-derived TCMs.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"257 ","pages":"Article 116716"},"PeriodicalIF":3.1,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080264","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":"Monolithic and hierarchically porous biochar/cellulose aerogel as adsorbent for microextraction in packed syringe towards trace sulfonamides in water samples prior to UPLC-MS/MS","authors":"Sai Li,&nbsp;Shuangying Yu,&nbsp;Mengyao Zhang,&nbsp;Zeyi Li,&nbsp;Hui Yu,&nbsp;Zhongfu Xing,&nbsp;Beibei Mao,&nbsp;Pan Zhao","doi":"10.1016/j.jpba.2025.116714","DOIUrl":"10.1016/j.jpba.2025.116714","url":null,"abstract":"<div><div>In this study, biochars with desirable adsorption capacity were prepared by calcination of herbal medicine residue, and the obtained biochars were loaded on cellulose aerogel through a green synthesis method. The monolithic biochar/cellulose aerogel hybrid was packed in the syringe and used as adsorbent for microextraction in packed syringe (MEPS). After introducing cellulose aerogel as the support, the loss of powdered biochars was avoided, and the entire extraction process can be achieved through simple operation of filtration due to the macroporous structure of cellulose aerogel. Coupled with UPLC-MS/MS, the established method was successfully applied to determine trace level of sulfonamides (SAs) in water samples. Extraction parameters such as pH of sample solution, adsorbent type, sample volume, elution solvent type and elution solvent volume were studied. Under the optimized parameters (pH of sample solution:7, adsorbent type: biochar/cellulose aerogel, sample volume: 20 mL, elution solvent: 0.3 mL methanol, the number of aspiration and dispense of sample solution, washing solvent and elution solvent: 3), desirable linearity correlation coefficient (r) in the range of 0.9951–0.9972 was achieved. The limit of detection varied from 0.00407 to 0.0104 ng/mL, and recovery ranging from 65.3 % to 102.4 % was obtained. The proposed method was demonstrated to be sensitive, accurate and easily operative, providing a convenient protocol for sample pretreatment.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"257 ","pages":"Article 116714"},"PeriodicalIF":3.1,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080267","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 amino acids in small volumes of human sweat collected from fingertips of healthy subjects at rest","authors":"Hiroshi Kuroki,&nbsp;Makoto Tsunoda","doi":"10.1016/j.jpba.2025.116718","DOIUrl":"10.1016/j.jpba.2025.116718","url":null,"abstract":"<div><div>Sweat is a body fluid that can be collected noninvasively. Sweat can be utilized as a biofluid for quantification of amino acids for clinical applications, such as disease screening. Amino acids are essential for many biological processes in the human body. Hence, the development of analytical methods for determining the concentrations of amino acids in human sweat can offer valuable insights into the health status of an individual. Sweat analysis can further be utilized as a tool for screening various pathological conditions. In this study, the concentrations of amino acids in small volumes of human sweat collected from fingertips of healthy subjects at rest were investigated. Reliable sweat collection was achieved by optimizing the sample collection procedure. The amino acids in human sweat were derivatized with 4-fluoro-7-nitro-2,1,3-benzoxadiazole, followed by analysis using high-performance liquid chromatography with fluorescence detection. The amino acid concentrations in sweat were quantified. The temporal variability and sex-specific differences in the concentrations of amino acids were evaluated. The results of both intra- and inter-day sweat analyses revealed that except for citrulline and arginine, the concentrations of other amino acids in sweat are relatively stable. This study proposes that the concentrations of amino acids in sweat can be determined with high accuracy, regardless of sweat collection timing. The findings of this study provide useful information that can help develop disease screening methods based on sweat analysis.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"257 ","pages":"Article 116718"},"PeriodicalIF":3.1,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143161413","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":"Molecular mass spectrometric imaging of amino acids in dietary supplement tablets using laser ablation-atmospheric pressure chemical ionization-trapped ion mobility spectrometry-mass spectrometry","authors":"Johannes Schmeinck,&nbsp;Uwe Karst","doi":"10.1016/j.jpba.2025.116719","DOIUrl":"10.1016/j.jpba.2025.116719","url":null,"abstract":"<div><div>A UV laser ablation system coupled to atmospheric pressure chemical ionization-trapped ion mobility spectrometry-mass spectrometry (LA-APCI-TIMS-MS) is presented as a novel mass spectrometry imaging (MSI) tool to investigate the distribution of amino acids and vitamins in dietary supplement tablets. The setup employs a custom-built LA interface for commercially available APCI sources. Average single pulse response (SPR) durations of less than 0.2 s full peak width at 1 % maximum (FW0.01 M) were achieved. Imaging analyses resulted in the detection of 16 amino acids and 10 vitamins, all with unique and complementary distributions that are in most cases heterogeneously distributed over the sample surface. To differentiate between leucine and isoleucine, a second analysis was conducted on the same amino acid tablet with TIMS, showing distinct distributions for the two compounds. These results illustrate the potential of the presented setup to gain insight into the composition and manufacturing conditions of dietary supplements.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"257 ","pages":"Article 116719"},"PeriodicalIF":3.1,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074835","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":"Immunomagnetic bead-based sample preparation method and immunoassay for detecting higenamine in herbal products","authors":"Jinping Qiu,&nbsp;Rui Zhang,&nbsp;Wentao Liu,&nbsp;Yang Lu,&nbsp;Jifeng Liu","doi":"10.1016/j.jpba.2025.116712","DOIUrl":"10.1016/j.jpba.2025.116712","url":null,"abstract":"<div><div>Higenamine (HM), classified as an S3 β2 agonist and prohibited by the World Anti-Doping Agency (WADA), is prevalent in spices and traditional Chinese herbal medicines.Accidental consumption can lead to HM positivity in athletes, necessitating daily monitoring. However, current detection strategies predominantly involve instrumental analysis, with limited development of rapid methodologies incorporating sample preparation for practical, daily applications. In this study, a novel method has been developed for the rapid and quantitative detection of HM in throat lozenges, plant beverages, syrups and grass coral. This innovative approach combines the use of immunomagnetic beads and an indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) to achieve efficient enrichment and detection. In the assay development, a highly sensitive anti-HM monoclonal antibody 1E9 (1E9-mAb) was generated and its binding mechanism to HM was investigated by theoretical simulations. Under optimum conditions, the sensitivity (IC₅₀) and detection limit (IC₁₅) were 0.23 ± 0.02 ng/mL and 0.04 ± 0.01 ng/mL. The detection limits for throat lozenges, plant beverages and syrups were 3, 4, and 2 μg/kg, respectively. The developed assay has been used to detect HM in 28 products on the market. This is the first HM detection method with immunomagnetic beads for sample preparation, and HM was found in grass coral extract and its processed products for the first time. Compared with the previous methods, it provides a more simple and efficient method of detecting trace HM in food and medicines daily.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"257 ","pages":"Article 116712"},"PeriodicalIF":3.1,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074834","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":"Structure elucidation and confirmation of unknown impurities in an animal health product by the strategy of utilizing a variety of advanced analytical techniques","authors":"Jiangtao He,&nbsp;Milan Dissanayake,&nbsp;Jingzhi Tian,&nbsp;Abu Rustum","doi":"10.1016/j.jpba.2025.116713","DOIUrl":"10.1016/j.jpba.2025.116713","url":null,"abstract":"<div><div>During stability test of an animal health finished drug product (liquid transdermal formulation packed in plastic syringe), several unexpected peaks were observed in the HPLC chromatograms. The structure and possible origin of these unknown peaks needed to be determined to ensure the safety and efficacy of the finished drug product. Each unknown peak poses different analytical challenges for full structure elucidation. In this paper, we presented the strategies and experimental results for the identification of these unexpected peaks using a combination of different advanced analytical techniques, namely HPLC/PDA, High Resolution MS and MS2, and headspace GC/MS. The orthogonal information provided by UV spectra, HRMS data, elemental composition, and MS2 fragmentation of these unknown peaks were used to propose the most probable structures for these unknown peaks. The proposed structures of these unknown peaks were fully confirmed by reference materials. The origins of these compounds were identified through an extraction study of the primary packaging materials. Hence, the unknown peaks were confirmed as leachable compounds from the primary packaging materials. Successful identification of these compounds enables quantification and toxicological evaluation. Additionally, the identification of these leachable compounds can be used to improve the primary package production process. By minimizing or eliminating the use of these compounds in the package production process, the risk of these compounds migrating into final finished drug product will be minimized in the future.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"257 ","pages":"Article 116713"},"PeriodicalIF":3.1,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074837","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":"Trametes robiniophila Murr. extract alleviates influenza-induced lung injury by regulating gut microbiota and metabolites","authors":"Jiyuan Cao ,&nbsp;Yu Zhang ,&nbsp;Yingnan Jiang ,&nbsp;Guangyao Li ,&nbsp;Guoying Zhang ,&nbsp;Jianya Ling","doi":"10.1016/j.jpba.2025.116700","DOIUrl":"10.1016/j.jpba.2025.116700","url":null,"abstract":"<div><div><em>Trametes robiniophila</em> Murr. (Huaier) is a traditional medicinal fungus known for its pharmacological properties, including heat-clearing, detoxifying, anti-inflammatory, and antitumor effects. Our previous research has demonstrated its antiviral activity, but the exact therapeutic mechanisms remain unclear. This study aims to explore the mechanisms of 50 % methanol extract of Huaier (HME) in treating influenza using 16S rRNA high-throughput sequencing and metabolomics techniques. The results showed that the HME significantly reduced the lung index and viral load in the lungs of influenza-infected mice, alleviated pathological damage in lung tissues, and downregulated the expression levels of inflammatory cytokines Interleukin-6 (IL-6), Tumor Necrosis Factor-<em>α</em> (TNF-<em>α</em>) and Interferon-<em>γ</em> (IFN-<em>γ</em>) in lung tissues. Furthermore, the HME enhanced the diversity of gut microbiota in infected mice, significantly increasing the relative abundance of beneficial bacteria, such as <em>Alistipes</em> and <em>Alloprevotella</em>. Through non-targeted metabolomic analysis of mouse feces, 45 potential biomarkers were identified. Meanwhile, the low-dose of HME was able to restore the disrupted metabolic levels. Analysis of gut microbiota and biomarker pathways revealed that HME primarily affects nicotinate and nicotinamide metabolism, which may be the key mechanism for its intervention in influenza. In addition, Spearman correlation analysis showed that most biomarkers were significantly associated with pharmacodynamics and the <em>Alloprevotella</em>.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"257 ","pages":"Article 116700"},"PeriodicalIF":3.1,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066303","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 validated single-step saliva and serum sample extraction LC-MS/MS method for the analysis of nicotine, cotinine and 3’-hydroxycotinine for clinical vaping studies","authors":"Vera van der Velpen ,&nbsp;Evangelia Liakoni ,&nbsp;Mats B. Hirt ,&nbsp;Celina M. Vonwyl ,&nbsp;Samuel E. Christen ,&nbsp;Urs Duthaler ,&nbsp;Peyton Jacob ,&nbsp;Manuel Haschke","doi":"10.1016/j.jpba.2025.116703","DOIUrl":"10.1016/j.jpba.2025.116703","url":null,"abstract":"<div><h3>Introduction</h3><div>Quantifying low nicotine and metabolite concentrations in biofluids is challenging due environmental nicotine contamination. However, accurate quantification of low concentrations is crucial for studies on electronic nicotine delivery systems (ENDS) using e-liquids with varying nicotine content.</div></div><div><h3>Methods</h3><div>We developed an LC-MS/MS method to quantify nicotine, cotinine, and 3’-hydroxycotinine (3-OH-cotinine) in serum and saliva for pharmacokinetic (PK) analyses and large studies.</div></div><div><h3>Results</h3><div>For reliable chromatography and to limit bench work, C18 chromatography was used with single-step extraction using methanol and 0.1 M ZnSO₄ (4:1, v/v) in serum and 80 % methanol in saliva. Environmental nicotine contamination was addressed through implementation of a C18 delay column, which separated the environmentally abundant nicotine present in the mobile phases from sample nicotine peaks. Total run-time was 6 min and lower limits of quantification were 0.5, 0.25 and 0.5 ng/ml for nicotine, cotinine and 3-OH-cotinine, respectively, in serum and 3, 1 and 2 ng/ml in saliva. The standard curves in both biofluids ranged up to 1000 ng/ml with R-values &gt; 0.995. The within- and between-run accuracy ranged from 97.1 % to 106.9 % with a precision of ≤ 10.8 %. Cross-validation of serum samples with another laboratory showed good agreement with a bias of 0.56, −3.0 and −6.5 ng/ml for nicotine, cotinine and 3-OH-cotinine, respectively.</div></div><div><h3>Conclusions</h3><div>The integration of a delay column into the LC-MS/MS method mitigated the interference from environmental nicotine and facilitated the quantification of very low nicotine concentrations and two of its major metabolites in saliva and serum. C18 chromatography and single-step sample extraction make the method stable and suitable for large sample loads.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"258 ","pages":"Article 116703"},"PeriodicalIF":3.1,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143289643","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":"Mimicking the reactivity of drug metabolites: Biomolecule conjugation of an electrochemically-generated, reactive oxidation product of the antibiotic minocycline","authors":"Erik Niehaves,&nbsp;Uwe Karst","doi":"10.1016/j.jpba.2025.116710","DOIUrl":"10.1016/j.jpba.2025.116710","url":null,"abstract":"<div><div>Minocycline is an antibiotic of the tetracycline family which is widely used to treat a range of medical conditions. Although it has been in use for more than 50 years, little information is available on its metabolism in the human body. In this study, we simulate the biotransformation of minocycline by means of electrochemistry coupled to mass spectrometry. This analytical technique has already been used successfully in several cases to imitate enzyme-catalyzed reactions. Using this approach, we could show the generation of multiple electrochemical oxidation products which were characterized by tandem mass spectrometry. A <em>N</em>-dealkylated product was found to correspond to a literature-known <em>in vivo</em> metabolite. Two further oxidation products were detected, one of which exhibiting a reactive quinone moiety formed through electrochemical oxidation. The reactivity of this transformation product was assessed by conjugation reactions with glutathione, human hemoglobin and human serum albumin as model biomolecules. For all three peptides, conjugation reactions took place within minutes, corresponding to the number of free cysteine residues in the respective molecule, which are particularly susceptible to electrophiles like quinones. For glutathione, serum albumin and α-hemoglobin, a single conjugation of the reactive transformation product took place, whereas a twofold conjugation was detected for β-hemoglobin. This project showcases the capability of the purely instrumental approach to simulate the metabolism of xenobiotics without an interfering matrix to screen for reactive transformation products and to assess the reactivity of these products with regard to biomolecules.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"257 ","pages":"Article 116710"},"PeriodicalIF":3.1,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066300","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":"Confined CHA-HCR system for sensitive and specific detection of ANXA2 mRNA in adenomyosis tissues","authors":"Guan Lin ,&nbsp;Zhenna Wang ,&nbsp;Qiulei Li ,&nbsp;Jinna Zhang ,&nbsp;Sang Guo ,&nbsp;Huo Xu ,&nbsp;Shunhe Lin ,&nbsp;Xi Xie","doi":"10.1016/j.jpba.2025.116708","DOIUrl":"10.1016/j.jpba.2025.116708","url":null,"abstract":"<div><div>Isothermal, enzyme-free amplification techniques, such as the hybridization chain reaction (HCR) and catalytic hairpin assembly (CHA), have gained significant attention for mRNA analysis. Despite their potential, these methods still face challenges, including false positives and low amplification efficiency. To overcome these limitations, we have developed a confined catalytic hairpin assembly and hybridization chain reaction (CHA-HCR) system that utilizes cholesterol-modified hairpin probes to enhance the sensitivity and specificity of mRNA detection. This system integrates cholesterol-modified hairpin probes (CHA probes) with hybridization chain reaction probes (HCR probes), leveraging hydrophobicity-mediated assembly to create a robust biosensing platform. The CHA-HCR system initiates a complex formation with the target mRNA, triggering a cascade of hybridization events that amplify the fluorescence signal. Employing ANXA2 mRNA as a model system, our results reveal that the CHA-HCR system achieves a detection limit (LOD) of 8.7 pM and offers high selectivity, effectively distinguishing ANXA2 mRNA from similar RNAs with single-base mismatches. Additionally, the CHA-HCR probes demonstrate stable detection performance in complex environments and exhibit excellent sensing capabilities in clinical tissue samples, successfully differentiating ANXA2 mRNA expression between leiomyoma and adenomyosis patient tissues. This study introduces a promising approach for the early diagnosis and monitoring of diseases associated with mRNA, potentially contributing to improved clinical outcomes and personalized treatment strategies.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"257 ","pages":"Article 116708"},"PeriodicalIF":3.1,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066257","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}