{"title":"Quantification of Plasma Niraparib Using High-Performance Liquid Chromatography in Patients With Ovarian Cancer","authors":"Yoshito Gando, Makoto Hoshino, Risa Ikuta, Mikio Shirota, Haruko Iwase, Takeo Yasu","doi":"10.1002/bmc.70046","DOIUrl":"https://doi.org/10.1002/bmc.70046","url":null,"abstract":"<div>\u0000 \u0000 <p>Niraparib is a small-molecule inhibitor of poly(adenosine diphosphate [ADP]-ribose) polymerase 1/2, which is used to treat ovarian cancer. Elevated maximum blood concentrations of niraparib and the area under the blood concentration–time curve (AUC) were correlated with body weight up to 77 kg. Lower body weight increases blood niraparib concentrations and the AUC of ovarian cancer in Asian patients. Therefore, therapeutic drug monitoring (TDM) of ovarian cancer drugs may increase niraparib efficacy and minimize adverse events. In this study, we quantified niraparib in human plasma (50 μL) using a simple and specific HPLC–UV method. The analyte was separated on a reversed-phase column with an isocratic mobile phase of 0.5% KH<sub>2</sub>PO<sub>4</sub> (pH 4.5) and acetonitrile (75:25, v/v) at a flow rate of 1.0 mL/min. Calibration curves were linear over 0.25–5 μg/mL (<i>r</i><sup>2</sup> = 0.9998). Intraday and interday precision ranged from 2.25% to 6.29% and 1.73% to 3.20%, respectively, whereas accuracy and recovery ranged from −6.02% to −1.75% and > 93.2%, respectively. We cost-effectively quantified steady-state niraparib concentrations in the plasma of patients with ovarian cancer. Therefore, our method could be applied to the departments of pharmacy and clinical laboratories in general hospitals to facilitate the TDM of niraparib without the need for LC–MS/MS.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 4","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143533292","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":"Exploring the Mechanism of Kai-Xin-San to Improve Cognitive Deficits in AD Rats Induced by D-Gal and Aβ25–35 Based on Multi-Omics and Network Analysis","authors":"Lifen Zhou, Min Zhang, Qin Zheng, Yonggui Song, Zhihong Yan, Huijuan Wang, Yongchang Xiong, Ying Chen, Zhinan Cai, Jinbin Yuan","doi":"10.1002/bmc.70047","DOIUrl":"https://doi.org/10.1002/bmc.70047","url":null,"abstract":"<div>\u0000 \u0000 <p>Alzheimer's disease (<span>AD</span>) is a common neurodegenerative disease for which there are no effective drugs. Kai-Xin-San (KXS), with definite curative effects, is widely used for the prevention and treatment of <span>AD</span> in China. But its mechanism is not yet fully understood. Based on our established rat model and previous pharmacodynamics study, Multi-omics (metabolomics, proteomics) and network analysis were integrated to explore the holistic mechanism of anti-<span>AD</span> effects of KXS. The key pathways were validated with western blot and ELISA methods. Morris water maze and Nissl staining showed that KXS could ameliorate cognitive deficits and pathological morphology of the hippocampus in <span>AD</span> rats. A total of nine metabolites were identified, which were related to pyrimidine metabolism, riboflavin metabolism, tyrosine metabolism, tryptophan metabolism, and glycerophospholipid metabolism. Proteomics results indicated that the improvement of cognitive deficits by KXS was closely related to the regulation of oxidative phosphorylation in mitochondria. Western blotting results showed that KXS significantly inhibited the expression of Mt-nd2 and Ndufb6 in <span>AD</span> rats. Integrated analysis indicated that the anti-<span>AD</span> targets of KXS were interrelated and KXS could exert its anti-<span>AD</span> effect by reducing oxidative stress, neurotoxicity, and inflammation.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 4","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143533299","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":"Integrated Serum Pharmacochemistry and Network Pharmacology Used to Explore Potential Antidepressant Mechanisms of the Kaixin San","authors":"Guoliang Dai, Deming Liu, Youjin Wang, Yanjun Wang, Qian Huang, Wenqing San, Xiaoyong Wang, Wenzheng Ju","doi":"10.1002/bmc.70041","DOIUrl":"https://doi.org/10.1002/bmc.70041","url":null,"abstract":"<div>\u0000 \u0000 <p>Kaixin San (KXS) is a classical prescription for the treatment of depression. However, the mechanism is not clear. In this study, serum pharmacochemistry, mediated by the UHPLC-Orbitrap Exploris 480 mass spectrometer, was used to identify compounds derived from the KXS-medicated serum. These components were used to construct a compound-target network for depression using a network pharmacology approach to predict potential biological targets of KXS. Subsequently, we established a mouse model of CUMS-induced depression and observed the antidepressant effect of KXS. The signalling pathways predicted by the network pharmacology were further validated in animal experiments. The results showed that 36 compounds were identified from the KXS-medicated serum. Based on this, 984 genes related to the compounds and 4966 genes related to depression were identified using network pharmacology. Critically, KEGG analysis identified the PI3K/Akt and NF-κB signalling pathways as the main pathways through which KXS exerts its antidepressant effect. KXS significantly alleviated depression-like behaviour and hippocampal histopathological changes in a mouse model of depression. Compared with the model group, the treatment of KXS significantly reduced the expression of protein targets in the PI3K/Akt/NF-κB signalling pathway. All these studies effectively corroborated the predicted results, confirming the feasibility of this integrated strategy.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 4","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143513875","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}
Ying Zhu, Zhaowei Dong, Lu Yang, Qinwan Huang, Jin Wang
{"title":"Mechanism of Bile-Processed Coptidis Rhizoma in the Treatment of Type 2 Diabetes Mellitus in Rats Based on Dissolution Kinetics and Untargeted Metabolomics","authors":"Ying Zhu, Zhaowei Dong, Lu Yang, Qinwan Huang, Jin Wang","doi":"10.1002/bmc.70040","DOIUrl":"https://doi.org/10.1002/bmc.70040","url":null,"abstract":"<div>\u0000 \u0000 <p>Bile-processed Coptidis Rhizoma (BPCR) exhibits stronger efficacy in treating T2DM than Coptidis Rhizoma(CR) alone. However, the synergistic mechanism of its processing remains unknown. This study utilized HPLC to determine the content and dissolution characteristics of alkaloid components in BPCR before and after processing. The results indicated that the diffusion of the alkaloids in BPCR is stronger than that of CR, and their dissolution conforms to the Weibull equation. Additionally, BPCR significantly reduced fasting blood glucose (FBG) and serum insulin (FINS) levels in T2DM rats induced by a high-fat diet (HFD) and streptozotocin (STZ), improved glucose and lipid metabolism, and mitigated liver damage. Serum metabolomics analysis based on UPLC-Q-TOF-MS revealed that BPCR significantly regulates 27 endogenous differential biomarkers. The underlying mechanism may be related to glycerophospholipid metabolism, linoleic acid metabolism, steroid biosynthesis, and arachidonic acid metabolism pathways.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 4","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143513874","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}
Jie Shen, Liye Ge, Guowei Jiang, Yongjun Meng, Weina Ma
{"title":"Pharmacokinetic Study of HRO761 in Rats by Liquid Chromatography Combined With Electrospray Ionization Tandem Mass Spectrometry","authors":"Jie Shen, Liye Ge, Guowei Jiang, Yongjun Meng, Weina Ma","doi":"10.1002/bmc.70033","DOIUrl":"https://doi.org/10.1002/bmc.70033","url":null,"abstract":"<div>\u0000 \u0000 <p>A simple and sensitive liquid chromatography tandem mass spectrometry method was established and validated for determination of HRO761 in rat plasma. After prepared by protein precipitation with acetonitrile, HRO761 and internal standard were separated on a Waters BEH C18 column using acetonitrile containing 0.1% formic acid and 0.1% formic acid in water as mobile phase by gradient elution. The method showed excellent linearity over the range of 5–5000 ng/mL with acceptable intraday and interday precision, accuracy, matrix effect, and recovery. The stability assay indicated that HRO761 was stable during the sample acquisition, preparation, and storage. The method was applied to pharmacokinetic study of HRO761 in rats. The result suggested that after intravenous administration at dose of 1 mg/kg, HRO761 was quickly eliminated from the plasma with the elimination half-life of 1.9 h. After oral administration at doses of 5, 10, and 20 mg/kg, HRO761 was quickly absorbed into plasma and reach the peak concentration (C<sub>max</sub>) of 2598.1–9379.2 ng/mL at 1.0–4.0 h. The exposure increased proportionally with the dose. The oral bioavailability was 79.0%–99.1% over the range of 5–20 mg/kg. This study provides useful information for its further development in clinic.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 4","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481624","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}
Yaozu Xiong, Chu Chen, Xiaohui Deng, Yanmei Hu, Haicui Liu, Li Wan, Leilei Du
{"title":"Study on Quality Markers of Tibetan Medicine Wuwei Shaji San Based on UHPLC-Q-Exactive Orbitrap-MS and Network Pharmacology Multicomponent Quantification","authors":"Yaozu Xiong, Chu Chen, Xiaohui Deng, Yanmei Hu, Haicui Liu, Li Wan, Leilei Du","doi":"10.1002/bmc.70036","DOIUrl":"https://doi.org/10.1002/bmc.70036","url":null,"abstract":"<div>\u0000 \u0000 <p>The Tibetan medicine Wuwei Shaji powder (WWSJ) has been extensively applied to treating lung diseases such as chronic obstructive pulmonary disease (COPD). However, there are significant limitations in its quality control and evaluation. The purpose of this study was to analyze the overall chemical composition of WWSJ and to predict potential quality markers for WWSJ in the treatment of COPD. Using UHPLC-Q-Exactive Orbitrap-MS, 83 chemical constituents of WWSJ were identified or preliminarily characterized by 14 authentic reference standards, accurate mass counts, and characteristic fragment ions. In addition, serum pharmacology methods were employed to detect 13 blood-migrating components. Further network pharmacological research found that the potential mechanism of WWSJ in the treatment of COPD may be related to the regulation of the immune system and inflammatory response and identified 10 chemicals as key molecules in the treatment of COPD. Finally, the contents of six potential quality markers were determined simultaneously by high-performance liquid chromatography (HPLC). This study lays the foundation for further research on the mechanism of WWSJ in the treatment of COPD.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 4","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481622","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}
Xueqi Yang, Jipeng Song, Huali Lu, Xinyu Gao, Rong Sun, Jiaxin Wang, Zhiyong Li, Guoying Zhang, Pan Zhao, Xin Zhao, Jiangting Liu
{"title":"Process Optimization of Stir-Fried Inonotus hispidus Based on the Box–Behnken Design-Response Surface Method and the Component Variations During the Stir-Frying Process","authors":"Xueqi Yang, Jipeng Song, Huali Lu, Xinyu Gao, Rong Sun, Jiaxin Wang, Zhiyong Li, Guoying Zhang, Pan Zhao, Xin Zhao, Jiangting Liu","doi":"10.1002/bmc.70039","DOIUrl":"https://doi.org/10.1002/bmc.70039","url":null,"abstract":"<div>\u0000 \u0000 <p>The present study was designed to optimize the processing of <i>Inonotus hispidus</i> (<i>I. hispidus</i>) by single-factor studies and response surface methodology (RSM). Stir-frying temperature, stir-frying time, and rotational speed of the stir-frying machine were considered as the variables under investigation, whereas ergosterol, total polysaccharides, alcohol-soluble leachate, appearance, and shape were the parameters being studied. Based on single-factor studies, the optimal stir-frying process parameters for <i>I. hispidus</i> were determined using the subjective evaluation analytic hierarchy process (AHP)–entropy weighting method in conjunction with the Box–Behnken design-response surface method (BBD). Correlation analysis of the indicator components and colorimetric values was conducted using correlation and stepwise regression analysis methods. Compositional changes during processing of the concoction were analyzed using UHPLC-Q-Exactive Orbitrap/MS. The optimal process conditions for stir-frying <i>I. hispidus</i> were a stir-frying temperature of 160°C, a stir-frying time of 9 min, and a rotational speed of the stir-frying machine of 40 r/min. Indicators that have a correlation with colorimetric values include alcohol-soluble leachate, appearance and shape. The composition has changed during the concoction process, particularly the styrylpyrones. The preferred formulation process is stable and feasible, providing a reference for researching the formulation process of <i>I. hispidus</i> and clinical medication.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 4","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481623","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}
Selvakumar Kanthiah, J. Joysa Ruby, Hiriyanna SGB, Valliappan Kannappan
{"title":"Navigating the AQbD Landscape: Enhancing Quality Management in Liquid Chromatography Method Development","authors":"Selvakumar Kanthiah, J. Joysa Ruby, Hiriyanna SGB, Valliappan Kannappan","doi":"10.1002/bmc.70031","DOIUrl":"https://doi.org/10.1002/bmc.70031","url":null,"abstract":"<div>\u0000 \u0000 <p>The implementation of ‘Analytical Quality by Design’ (AQbD) is currently recognised as a methodical and scientific approach to liquid chromatographic (LC) method development. It begins with defining the Analytical Target Profile (ATP), identifying Critical Method Parameters (CMPs) and Critical Quality Attributes (CQAs) or responses. This process also includes risk assessment study by Design of Experiment (DoE) and to optimise LC effectively. The next step is to create an analytical design space and implement a control strategy that will allow for continuous method improvement over the life of the method. Understanding the AQbD principles, methodologies, techniques and applications towards the high-performance liquid chromatography (HPLC) method lifecycle is considered as essential in today's pharmaceutical landscape. As industry demands for quality assurance and regulatory compliance, this review paper briefly discusses the AQbD principles and methodology in HPLC method lifecycle. Also, the paper covers AQbD components such as identification of ATP, CQA, MODR (method operable design region), control strategies and continuous method monitoring. In addition, it also covers regulatory perspectives on AQbD, obstacles and potential outcomes in the development of pharmaceutical analytical methods. These aspects provide valuable insights into the application of AQbD in the field of LC.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 4","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466230","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}
Zhenguo Lv, Wenhan Lin, Omachi Daniel Ogaji, Yang Liu, Shuting Zhou, Yameng Zhu, Xiwei Wu, Peng Zhao, Tiantian Wu, Caixia Li, Fanjiao Zuo, Huizi Ouyang, Jun He
{"title":"Spectrum-Effect Relationship Between Fingerprints and Anti-Inflammatory and Antitussive Activities of Raw and Processed Mume Fructus Extracts","authors":"Zhenguo Lv, Wenhan Lin, Omachi Daniel Ogaji, Yang Liu, Shuting Zhou, Yameng Zhu, Xiwei Wu, Peng Zhao, Tiantian Wu, Caixia Li, Fanjiao Zuo, Huizi Ouyang, Jun He","doi":"10.1002/bmc.70037","DOIUrl":"https://doi.org/10.1002/bmc.70037","url":null,"abstract":"<div>\u0000 \u0000 <p>Mume Fructus (MF), a representative substance in the field of medicine-food homology, has been extensively utilized in clinical treatments and daily diets for its raw and processed forms. This study aimed to establish the spectrum-effect relationship between ultra–high-performance liquid chromatography coupled with quadrupole tandem time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS) fingerprints and anti-inflammatory and antitussive activities of raw and processed MF extracts. In UHPLC-Q-TOF-MS/MS fingerprints, a total of 21 common peaks were identified. Bioactivity assays demonstrated that the raw and processed MF extracts exhibited varying degrees of anti-inflammatory and antitussive effects. Subsequently, the relevant pharmacologically active ingredients were screened by grey relation analysis and partial least squares regression. The results showed that nine components were associated with anti-inflammatory effects, namely, citric acid, isochlorogenic acid B, isochlorogenic acid A, isochlorogenic acid C, fumaric acid, gallic acid, neochlorogenic acid, chlorogenic acid, and ononin. Additionally, three components were linked to antitussive activity: amygdalin, syringic acid, and succinic acid, respectively. This work developed a model combining UHPLC-Q-TOF-MS/MS fingerprints with anti-inflammatory and antitussive activities to study the spectrum-effect relationship of raw and processed MF extracts. The findings provide a reference for the discovery of bioactive components and contribute to the clinical rationalization of medications.</p>\u0000 </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 4","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143455919","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}
Raja Reddy Kallem, Maisy Yeager, Rosa Chan, Katharine Fletcher, Katie Neal, Nuggehally R. Srinivas
{"title":"A Sensitive and Selective LC–MS/MS-ESI Method for the Quantitation of Metabolites M9, M12, and M20 of Bexicaserin in Human Plasma and Urine Matrices","authors":"Raja Reddy Kallem, Maisy Yeager, Rosa Chan, Katharine Fletcher, Katie Neal, Nuggehally R. Srinivas","doi":"10.1002/bmc.70023","DOIUrl":"https://doi.org/10.1002/bmc.70023","url":null,"abstract":"<p>Bexicaserin is a highly selective 5HT<sub>2c</sub> receptor agonist being developed for the treatment of seizures associated with developmental and epileptic encephalopathies (DEEs). We report an LC–MS/MS method for the quantitative estimation of three pharmacologically inactive metabolites (M9, M12, and M20) of bexicaserin in human plasma/urine. Sample preparation involves the extraction of M9, M12, M20, and internal standards (ISs) from 25-μL plasma and 50-μL urine following protein precipitation. The chromatographic separation of analytes was achieved on a HSS T3-C18 column. The calibration curves ranged from 0.1 to 100 ng/mL for M9, 0.5–500 ng/mL for M12, and 1.0–1000 ng/mL for M20 in plasma and 2.0–2000 ng/mL for M9 and M12 and 10–10,000 ng/mL for M20 in urine. Intraday/interday precision and accuracy, linearity, matrix effect, extraction recovery, carry-over, dilution integrity, stability studies, and incurred sample reanalysis were performed in both plasma and urine. The intraday and interday accuracy and precision for metabolites met the stipulated regulatory guidelines. Stability studies in plasma and urine showed that analytes were stable at bench-top for > 23.5 h and in autosampler for > 69 h. Analytes were stable after five freeze–thaw cycles and > 552 days of long-term storage at −20°C and −80°C.</p>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 4","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bmc.70023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439119","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}