Lanussy Porfiro de Oliveira, Jerônimo Raimundo de Oliveira Neto, Thiago Sardinha de Oliveira, Lara Marques Naves, Stefanne Madalena Marques, Alessandro Carvalho Cruz, James Oluwagbamigbe Fajemiroye, Gustavo Pedrino, Luciano Morais Lião, Ricardo Menegatti, Luiz Carlos da Cunha
{"title":"Preclinical Pharmacokinetic Assessment of a Promising Vasorelaxant, Analgesic, and Anti-Inflammatory Prototype 5-[1-(4-Fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole (LQFM020) Through Selective Bioanalytical HPLC-PDA-Based Method","authors":"Lanussy Porfiro de Oliveira, Jerônimo Raimundo de Oliveira Neto, Thiago Sardinha de Oliveira, Lara Marques Naves, Stefanne Madalena Marques, Alessandro Carvalho Cruz, James Oluwagbamigbe Fajemiroye, Gustavo Pedrino, Luciano Morais Lião, Ricardo Menegatti, Luiz Carlos da Cunha","doi":"10.1002/bmc.70082","DOIUrl":"https://doi.org/10.1002/bmc.70082","url":null,"abstract":"<p>A simple and selective high-performance liquid chromatography bioanalytical method was developed and validated to determine the pharmacokinetic parameters of 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole (LQFM020) with promising vasorelaxant, anti-inflammatory, and antinociceptive properties while verifying its potential hepatic enzyme induction or inhibition. Chromatographic separation was achieved using a reversed-phase C18 column (ACE, 150 × 4.6 mm, 5 μm) with isocratic elution of a solvent mixture comprising acetonitrile and 0.2% formic acid (30:70, v/v). Detection of LQFM020 and the internal standard, piroxicam, was performed using a photodiode array detector. The method demonstrated excellent linearity (<i>r</i> > 0.998), with precision and accuracy within acceptable limits [intraday precision: 6.1%, interday precision: 9.3%; intraday accuracy: 113.2%, interday accuracy: 107.3%]. Pharmacokinetic studies revealed rapid oral absorption of LQFM020 at doses of 9, 18, and 36 mg/kg, as well as following a single intravenous dose (10 mg/kg). LQFM020 exhibited an absolute bioavailability of 46%, a relatively low apparent volume of distribution, and moderate elimination rates, suggesting extensive plasma protein binding. Additionally, LQFM020 showed no significant effect on the biotransformation of compounds mediated by the cytochrome P450 CYP3A4 enzyme. In conclusion, this new bioanalytical method supports preclinical studies and provides a basis for the utility of LQFM020 as a potential drug candidate.</p>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 5","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bmc.70082","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143809408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Urine Metabolomics Reveals the Intervention Effects and Mechanism of Shenhua Tablets in IgA Nephropathy","authors":"Yuhang Wang, Ping Li, Fengting Yin, Ying Zheng, Huiqiang Liu, Hui Sun, Mengmeng Wang, Chang Liu, Xiangmei Chen, Guangli Yan, Xiaotong Yan, Yu Hu, Shihan Guan, Xijun Wang","doi":"10.1002/bmc.70078","DOIUrl":"https://doi.org/10.1002/bmc.70078","url":null,"abstract":"<div>\u0000 \u0000 <p>Shenhua tablets (SHT), a traditional Chinese medicine (TCM), have shown significant clinical efficacy in treating IgA nephropathy (IgAN), but the underlying mechanisms are not fully understood. This study aims to elucidate the renoprotective effects of SHT on IgAN and explore the potential mechanisms of its action using metabolomics approaches. The renoprotective effects of SHT on IgAN were evaluated in a Thy-1 antibody-induced IgAN rat model. Metabolomics techniques were employed to detect and analyze urine biomarkers of IgAN, and to identify SHT targets and metabolic pathways. SHT significantly reduced the levels of 24-h urine protein (Upro), albumin-to-creatinine ratio (ACR), Interleukin 1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6), alleviated kidney tissue damage, and inhibited mesangial cell proliferation. Seventeen urine metabolites were identified as biomarkers for IgAN, 14 of which were restored by SHT. SHT primarily modulated metabolic pathways, including the tricarboxylic acid (TCA) cycle, glycolysis/gluconeogenesis, pyruvate metabolism, and β-alanine metabolism, upregulating citric acid and succinic acid while downregulating pyruvic acid, L-lactic acid, uracil, and malonic semialdehyde. SHT exerts renoprotective effects in IgAN by modulating key metabolic pathways and normalizing abnormal metabolites levels.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 5","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143793605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Optimizing Mirabegron Stability in Human Plasma: Method Development, Validation Through Integration of Esterase Inhibitors and Stabilizers","authors":"Santosh Tawari, Ujashkumar Shah","doi":"10.1002/bmc.70065","DOIUrl":"https://doi.org/10.1002/bmc.70065","url":null,"abstract":"<div>\u0000 \u0000 <p>The stability of mirabegron in human plasma is addressed in this study. The susceptibility of Mirabegron to enzymatic and oxidative degradation requires the integration of esterase inhibitors and stabilizers into the analytical process. Esterase inhibitors, including sodium fluoride and dichlorvos, as well as stabilizing agents such as malic acid, ascorbic acid, acetic acid, citric acid and sodium bicarbonate were also investigated to mitigate this issue. Samples were prepared through solid-phase extraction (SPE) utilizing Strata-X cartridges. The optimization of chromatographic separation was conducted using a C18 Kromasil column with a solvent mixture consisting of ammonium formate and acetonitrile. Detection employed electrospray ionization (ESI) in positive ionization mode, focusing on MRM transitions of 397.2 → 260.1 for mirabegron and 402.2 → 260.1 for mirabegron D5. The method exhibited an accuracy range of 95.67% to 102.85% and precision of 0.52% to 2.31% for a linearity ranged from 0.100 to 102.496 ng/mL. An advantage of this method is its stability, requiring only a minimal plasma volume of 100 μL, a quick runtime of 3 min, and a high recovery rate of 92.93%, making it highly efficient and reliable for bioequivalence testing, therapeutic monitoring and pharmacokinetic studies.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 5","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Rapid and Sensitive Method for the Determination of Bisoprolol in Human Plasma by Ultra Performance Liquid Chromatography–Tandem Mass Spectrometry","authors":"Yihong Jiang, Yaling Niu, Congchao Ning, Feng Qin, Chengda Yan, Xiumei Lu","doi":"10.1002/bmc.70054","DOIUrl":"https://doi.org/10.1002/bmc.70054","url":null,"abstract":"<div>\u0000 \u0000 <p>A rapid and sensitive ultra-high performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) method for the determination of bisoprolol in human plasma was established and validated. The sample was pretreated by methanol precipitation protein, and the isotope bisoprolol-d<sub>5</sub> was used as the internal standard. The chromatographic column was ACQUITY UPLC BEH-C<sub>18</sub> column (2.1 × 50 mm, 1.7 μm), with methanol and 0.2% formic acid aqueous solution as mobile phase for gradient elution. The electrospray ionization (ESI) source was used in the positive ion mode, and the multiple reaction monitoring (MRM) mode was used. The total running time was only 2.00 min. The correlation coefficient was good (<i>r</i> > 0.99) in the linear range of 0.0200–40.0 ng/mL. The lower limit of quantitation (LLOQ) was 20.0 pg/mL. The intrabatch and interbatch precisions were not more than 8.9% and 9.2%. The intrabatch and interbatch accuracies were −7.9% ~ 6.3% and −6.9% ~ 5.0%. The method was fully validated including whole blood stability and reinjection reproducibility and successfully applied to the pharmacokinetic study of 5-mg bisoprolol in healthy volunteers, which 93.1% incurred samples reanalysis (ISR) met the criteria. Compared with the reported methods, this method had the highest sensitivity and fast analysis speed.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 5","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Simultaneous Determination of 14 Bioactive Components in Fangji Huangqi Tang by UHPLC-QqQ-MS Technique","authors":"Fangfang Xue, Lintong Xie, Xia Zhang, Yifei Gao, Jizhen Guo, Xue Liu, Hui Zhu, Xiao Liu","doi":"10.1002/bmc.70073","DOIUrl":"https://doi.org/10.1002/bmc.70073","url":null,"abstract":"<div>\u0000 \u0000 <p>Fangji Huangqi Tang (FHT) is a traditional prescription frequently utilized in clinical practice, with a wide range of clinical applications and good therapeutic effects. Quality control of FHT is difficult because Chinese medicine compounds usually contain a vast array of components characterized by significant structural diversity. A quick and accurate method to determine the content of active constituents in FHT was essential, by which the purpose of quality control and efficacy assessment could be achieved. A method utilizing UHPLC-QqQ-MS technology in multiple reaction monitoring (MRM) mode was established to quantify 14 bioactive components in FHT simultaneously. These analytes included tetrandrine, fangchinoline, calycosin, calycosin-7-glucoside, medicarpin, formononetin, atractylenolide I, atractylenolide II, atractylenolide III, liquiritigenin, isoliquiritigenin, liquiritin, isoliquiritin, and glycyrrhizic acid. And to our knowledge, the content of calycosin, medicarpin, formononetin, and atractylenolide II in FHT was reported for the first time in this paper. The method was thoroughly validated for stable and reliable application regarding specificity, linearity, precision, stability, repeatability, and accuracy. The established method allowed the simultaneous determination of 14 bioactive components with diverse structures and trace amounts in FHT, ultimately achieving the quality control and assessment of FHT for its safe and appropriate clinical use.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 5","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hengyang Li, Xiaoying Ding, Qi An, Wenjie Li, Long Guo, Yuguang Zheng, Dan Zhang, Weimin Huo
{"title":"A Strategy Comprehensively and Quickly Identifies the Herbal Composition and Chemical Constituents in Yixishu Lotion by Molecular Networking","authors":"Hengyang Li, Xiaoying Ding, Qi An, Wenjie Li, Long Guo, Yuguang Zheng, Dan Zhang, Weimin Huo","doi":"10.1002/bmc.70069","DOIUrl":"https://doi.org/10.1002/bmc.70069","url":null,"abstract":"<div>\u0000 \u0000 <p>The identification of species is a crucial component of the Chinese patent medicine (CPM) quality evaluation system. Nevertheless, the intricate and varied chemical compositions of different herbs pose a persistent challenge to this study. This study proposes a strategy combining high-resolution mass spectrometry with molecular networking (MN) data processing tools to comprehensively characterize the compounds in Yixishu lotion (YXSL) and identify the species composition. First, the data collected by HPLC-Q-TOF-MS were comprehensively and systematically visualized and analyzed using MN. Second, MN was employed to rapidly classify all compounds based on their similarity in chemical structures, facilitating the swift classification and identification of the main components of different Chinese medicines in compound preparations. Finally, the herbal composition of the compound formulation was determined by combining various compounds with literature. Two hundred twenty compounds and herbal sources of YXSL were preliminarily identified, including 14 matrine alkaloids assigned to SFR, 16 coumarins in CF, 43 isopentenyl flavonoids belonging to EF, 9 benzylisoquinoline alkaloids, 5 protoberberines, 10 tetrahydroprotoberberines and 3 furanoquinoline alkaloids from PCC, 44 phenolic compounds, and 76 other compounds. This study provides a solid foundation for the quality evaluation of YXSL and offers a method for identifying herbal components and compounds in other CPMs.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 5","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Quality by Design Based Chromatography Technique Development and Validation for the Medicine Venetoclax (for Chronic Leukemia), in the Context of Impurities Including Degradation Products","authors":"Rajeshwari Dandabattina, Karuna Sree Merugu, Lova Gani Raju Bandaru, Haridasyam Sharathbabu, Rambabu Gundla, Naresh Kumar Katari","doi":"10.1002/bmc.70072","DOIUrl":"https://doi.org/10.1002/bmc.70072","url":null,"abstract":"<p>The present research study describes the Venetoclax (VEN)-related substances test method using RP-HPLC/DAD techniques. It was developed and validated according to ICH Q14 and Q2(R2) guidelines. The substances were separated using an X-Bridge Phenyl column (150 mm × 4.6 mm, 3.5 μm) and a gradient program. The mobile phase A, consist 0.02 mM Na2HPO4 (pH 8.0) buffer and acetonitrile in an 80:20 v/v ratio. Mobile phase B was prepared using a 75:25 v/v mixture of acetonitrile and a pH 8.0 buffer and well mixed. The flow rate remains constant at 1.0 mL/min, traversing an appropriate gradient program. The VEN and its impurities were detected at 280 nm, with an injection volume of 15 μL and a runtime of 130 min. Moreover, we identified proper degradation impurities and sensitivity of VEN due to forced-degradation study experiments. The linearity and range of the testing procedure were validated by computing <i>r</i><sup>2</sup> values over 0.999. All organic impurities were recovered at a rate of 97.6%–106.0% with a relative standard deviation of 0.11%–4.35%. A robustness test was conducted utilizing the AQbD methodology. The proposed method was stability-indicating in nature and can be used for commercial samples in the pharmaceutical industries.</p>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 5","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bmc.70072","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jingxuan Yang, Yi Wu, Wei Wei, Wenjun Guo, Meng Li, Jiangwei Jia, Yajuan Xu, Yang Wang
{"title":"Study on Cold and Hot Properties of Chinese Materia Medica Using Liquid Chromatography-Mass Spectrometry-Based Metabolomics Combined With Network Pharmacology Analysis","authors":"Jingxuan Yang, Yi Wu, Wei Wei, Wenjun Guo, Meng Li, Jiangwei Jia, Yajuan Xu, Yang Wang","doi":"10.1002/bmc.70070","DOIUrl":"https://doi.org/10.1002/bmc.70070","url":null,"abstract":"<div>\u0000 \u0000 <p>The cold/hot properties of Chinese materia medica (CMM) are the core theory of traditional Chinese medicine (TCM). This study aims to investigate the cold/hot properties of CMM and find the possible mechanisms related to CMM properties using liquid chromatography-mass spectrometry (LC-MS)-based metabolomics combined with network pharmacology analysis. Typical cold and hot CMMs were given to mice by intragastric administration. The metabolomics analyses showed that cold/hot CMMs induced metabolome changes by modulating arginine and proline metabolism, tricarboxylic acid cycle, fatty acid metabolism, etc. The joint analysis of metabolomics and network pharmacology suggested that cold and hot CMMs could modulate the expression of IL-6, IL-1β, TNF, and CASPS and influence metabolic changes, thereby exhibiting their cold/hot properties. The validation study showed that the serum levels of IL-6 and IL-1β were regulated by CMM administration. Molecular docking analysis suggested that the active compound of CMM had good binding energy with target proteins. This study conducted a primary investigation to explore the CMM property from the perspective of metabolomics, which is expected to provide some research data related to the body metabolism for the scientific connotation of the cold/hot properties of CMM.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 5","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Metabolomics Based Exploration of the Mechanism of Action of Tripterygium Glycosides in Diabetic Kidney Disease","authors":"Li Long, Jianfeng Yu, Jingsong Jin, Jibo Zhang","doi":"10.1002/bmc.70071","DOIUrl":"https://doi.org/10.1002/bmc.70071","url":null,"abstract":"<div>\u0000 \u0000 <p><i>Tripterygium</i> glycosides (TGs), the primary active components of <i>Tripterygium wilfordii</i>, have demonstrated therapeutic efficacy in treating diabetic kidney disease (DKD). However, the precise mechanisms underlying their action remain elusive, limiting the full realization of their medicinal potential. This study employed serum metabolomics based on liquid chromatography–mass spectrometry (LC-MS) analysis to elucidate the mechanisms by which TGs combat DKD. We evaluated the protective effects of TGs on DKD following treatment. Serum samples were collected before and after treatment, and their metabolic profiles were analyzed using LC-MS. Our metabolomics analysis revealed that TGs significantly modulated the hedgehog signaling pathway, a key metabolic pathway implicated in DKD pathogenesis. This study represents the first comprehensive investigation of the metabolic pathways regulated by TGs in the context of DKD using a metabolomics approach. Our findings provide a robust theoretical foundation for the more effective utilization and potential combination therapies involving TGs in the management of DKD. These insights pave the way for further research and development of targeted therapeutic strategies for this challenging condition.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 5","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Preclinical Concomitant Toxicokinetic Study of Schisandrin B by HPLC–MS/MS","authors":"Sanwen Li, Qing Shao, Hongqun Qiao","doi":"10.1002/bmc.70068","DOIUrl":"https://doi.org/10.1002/bmc.70068","url":null,"abstract":"<div>\u0000 \u0000 <p>Schisandrin B (Sch B), a natural lignan extracted from schisandra chinesis, has exhibited various pharmacological activities including anticancer effects. However, studies on the preclinical toxicokinetic profile of Sch B have not been publicly reported. This study aimed to investigate the preclinical concomitant toxicokinetics of multiple administration of Sch B. Sch B was administered orally to rats and dogs at 150, 300, and 600 mg/kg/day and 50, 100, and 200 mg/kg/day, respectively, for 26 weeks. Plasma concentrations of Sch B were determined by a validated HPLC–MS/MS method. According to the toxicokinetic results, significant gender differences were observed in the rats, and females had higher exposures than males for each dosing group. Toxicokinetic analysis demonstrated a notable accumulation in the plasma of dogs during the repeated administration of Sch B, and the degree of accumulation increased with the increase of the dose. The findings of this study indicated that there were differences in the concomitant toxicokinetics of Sch B between rats and dogs. These results can inform clinical studies and provide valuable insights for future human Sch B risk assessments.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 5","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}