{"title":"Multiple oxidative modifications on hemoglobin are elevated in breast cancer patients as measured by nanoflow liquid chromatography-tandem mass spectrometry","authors":"Hauh-Jyun Candy Chen , Shun-Xiang Hu , Chi-Wen Tu","doi":"10.1016/j.jpba.2024.116477","DOIUrl":"10.1016/j.jpba.2024.116477","url":null,"abstract":"<div><div>Breast cancer is strongly connected with elevated oxidative stress. Oxidative modifications of hemoglobin can serve as biomarkers for monitoring oxidative stress status in vivo. The structure of hemoglobin modifications derived from malondialdehyde (MDA) in human blood hemoglobin exists as <em>N</em>-propenal and dihydropyridine (DHP). This study reports the simultaneous quantification of eleven modified peptides in hemoglobin derived from MDA and advanced histidine oxidation in 16 breast cancer patients and 16 healthy women using nanoflow liquid chromatography nanoelectrospray ionization tandem mass spectrometry. The results reveal statistically significant increases in the formation of MDA-derived <em>N</em>-propenal and DHP of lysine and advanced oxidation of histidine in hemoglobin of breast cancer patients with the Mann-Whitney <em>U</em>-test <em>p</em> values < 0.0001 and the AUC of ROC between 0.9277 and 1.0. Furthermore, the elevation in modified peptides is significant in patients with early stages of breast cancer. By measuring these oxidative modifications in hemoglobin from a drop of blood, the role of lipid peroxidation and oxidative stress in breast cancer can be assessed using this sensitive assay.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S073170852400517X/pdfft?md5=d683fec4fa7f8248238e51c11f77465c&pid=1-s2.0-S073170852400517X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142316106","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}
Jing Hu , Wenping Zhang , Qiongying Zheng , Wei Liu , Yujie Zhi , Wenhui Jin , Jiayue Lu , Zhen Zhang , Quanlu Dou , Yu Liu , Hang Chen
{"title":"Repeated lyophilization: A neo-method for urine-based reference materials preparation","authors":"Jing Hu , Wenping Zhang , Qiongying Zheng , Wei Liu , Yujie Zhi , Wenhui Jin , Jiayue Lu , Zhen Zhang , Quanlu Dou , Yu Liu , Hang Chen","doi":"10.1016/j.jpba.2024.116481","DOIUrl":"10.1016/j.jpba.2024.116481","url":null,"abstract":"<div><p>In urine drug testing, a cut-off value is often imposed to determine whether the sample is negative or positive. A matrix containing a reference substance helps counteract the adverse effects of the urine matrix across different laboratories to improve the consistency of final results. However, as a biological matrix, urine is prone to corruption and other problems that make it difficult to use as a reference sample. In this study, morphine, nitrazepam, lorazepam, buprenorphine, zolpidem, midazolam, diazepam, and clozapine commonly used in clinical practice were selected as target analytes, and the preparation process was further optimized to repeated lyophilization, in order to obtain more effective, stable, and accurate urine matrix reference materials (mRMs). The appropriate urine density (1.010–1.017 kg/m<sup>3</sup>) for preparing lyophilized samples was investigated through density determination. Conducting repeated lyophilizations resulted in a denser powder with reduced susceptibility to collapse and improved the quality of lyophilized urine samples. Lyophilized urine mRMs could be stored at room temperature for one month or under refrigeration conditions (4 ℃) for six months.</p></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0731708524005235/pdfft?md5=bfbf1bfd321d4d30d64b644e59d390ef&pid=1-s2.0-S0731708524005235-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142240017","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}
Xiaoting Gu , Yutian Cai , Chaoyue Zheng , Liuyao Xie , Linyi Zhang , Bingjie Lu , Shuwen Zhu , Yue Cui , Xiaoyu Ai , Cheng Yang
{"title":"PK-PD relationship of poorly absorbable active ingredients from traditional Chinese medicines explaining by metabolic enzyme of gut microbiota: A case study of Dehydrocorydaline","authors":"Xiaoting Gu , Yutian Cai , Chaoyue Zheng , Liuyao Xie , Linyi Zhang , Bingjie Lu , Shuwen Zhu , Yue Cui , Xiaoyu Ai , Cheng Yang","doi":"10.1016/j.jpba.2024.116478","DOIUrl":"10.1016/j.jpba.2024.116478","url":null,"abstract":"<div><div>Many active ingredients in traditional Chinese medicines generally have the characteristic of poor oral absorption but definite efficacy. It is necessary to establish a comprehensive technical system to explain the “PK-PD relationship” of them. Dehydrocorydaline (DHC), the quality control component in the Chinese patent drug “Kedaling Tablets”, has poor oral absorption but clear efficacy for coronary heart disease. Using DHC as a model drug, the changes in absorption and pharmacological effects of DHC in rats before and after inhibiting nitroreductase (NR) from gut microbiota were studied. The results showed that after inhibiting of NR activity, the plasma concentration of DHC in rats was decreased, the serum level of total cholesterol, triglyceride and low-density lipoprotein cholesterol were significantly increased. The levels of tumor necrosis factor-α, interleukin-1β, hypersensitive C-reactive protein, intercellular cell adhesion molecule-1 and Monocyte chemoattractant protein-1 were significantly increased, and pathological sections also showed that the efficacy of DHC decreased after inhibiting the activity of NR. We further investigated the drug metabolism of DHC under NR and found that DHC was metabolized into a hydrogenated metabolite, which may have stronger membrane permeability. In summary, NR may mediate the absorption degree and efficacy of DHC in vivo by metabolizing DHC into absorbable metabolite.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0731708524005181/pdfft?md5=122ab13a819259c1b8d3699aebda254b&pid=1-s2.0-S0731708524005181-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289640","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}
Wen Guo , Alexey A. Makarov , Alexei V. Buevich , Yuan Jiang
{"title":"Strategy for improving circular dichroism spectra deconvolution accuracy for macrocyclic peptides in drug discovery","authors":"Wen Guo , Alexey A. Makarov , Alexei V. Buevich , Yuan Jiang","doi":"10.1016/j.jpba.2024.116476","DOIUrl":"10.1016/j.jpba.2024.116476","url":null,"abstract":"<div><p>Peptide therapeutics have emerged as an appealing modality in the pharmaceutical industry. Understanding peptide conformation in solution remains one of the most critical areas for peptide drug development. Circular dichroism (CD) spectroscopy is a useful technique to study the secondary structure of proteins and peptides, but the current approaches are limited to protein-focused models to predict high-order structures of peptides, and the models were built based on X-ray crystallography instead of solution-based technique, as a result, such models may have poor predictions for peptides. In this study, we present a novel CD deconvolution model to determine peptide conformation in solution. To quantitatively obtain secondary structure information using CD, a calibration model is needed beforehand to establish the relationship between each secondary structure feature and the corresponding CD response. A reference set containing the majority of cyclic peptides with known structures from solution-state NMR spectroscopy was used to build the calibration model for CD deconvolution. Improved prediction accuracy on the secondary structure determination for cyclic peptides was achieved by this model compared to the commercial standard model using commercially available platforms. This new CD deconvolution method is crucial for peptide conformational analysis in solution, and has the potential to greatly accelerate peptide drug candidate optimization in the pharmaceutical drug discovery field.</p></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0731708524005168/pdfft?md5=49b4c6dbbe5125b30ea123d1d5ee149a&pid=1-s2.0-S0731708524005168-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142240016","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}
Szymon Kamil Araj , Łukasz Szeleszczuk , Tomasz Gubica , Monika Zielińska-Pisklak , Kostas Bethanis , Elias Christoforides , Marta Katarzyna Dudek , Dariusz Maciej Pisklak
{"title":"Physicochemical and structural analysis of N-phenylacetyl-L-prolylglycine ethyl ester (Noopept) – An active pharmaceutical ingredient with nootropic activity","authors":"Szymon Kamil Araj , Łukasz Szeleszczuk , Tomasz Gubica , Monika Zielińska-Pisklak , Kostas Bethanis , Elias Christoforides , Marta Katarzyna Dudek , Dariusz Maciej Pisklak","doi":"10.1016/j.jpba.2024.116474","DOIUrl":"10.1016/j.jpba.2024.116474","url":null,"abstract":"<div><p><em>N</em>-Phenylacetyl-L-prolylglycine ethyl ester (Noopept, GVS-111, omberacetam) is an orally available active pharmaceutical ingredient (API), with neuroprotective properties and ability to enhance cognitive function. It belongs to nootropic family of drugs and is included in the group of racetams, although its chemical structure is quite different than the other compounds from this group, including the most popular one – piracetam. The mechanism of action of this API is multifaced and is considered to be involving modulation of various neurotransmitter systems within the brain. Despite the significant amount of works devoted to the pharmacodynamics of Noopept, very little is known about its structural and physicochemical properties. Therefore, the aim of current study was to investigate this API in a very thorough way. In this work, the detailed physicochemical analysis of Noopept has been done using TGA/DSC, <sup>1</sup>H and <sup>13</sup>C liquid state NMR, <sup>13</sup>C CP/MAS NMR, SEM, SCXRD, and PXRD. Additionally, quantum chemical DFT computations under periodic boundary conditions, using CASTEP, were conducted to facilitate the analysis of experimental results. Besides, we’ve performed a polymorphism screening of this molecule.</p></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0731708524005144/pdfft?md5=e6277c2787efee3428c14fce11dd379c&pid=1-s2.0-S0731708524005144-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142240015","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}
Orwa Siddig , Keran Chen , Xinrui Wu , Mohammed Ismail , Min Song , Tai-jun Hang
{"title":"Pharmacovigilance of drug-drug interactions: A pharmacokinetic study on the combined oral administration of lurasidone and clozapine in rats by using LC-MS/MS","authors":"Orwa Siddig , Keran Chen , Xinrui Wu , Mohammed Ismail , Min Song , Tai-jun Hang","doi":"10.1016/j.jpba.2024.116473","DOIUrl":"10.1016/j.jpba.2024.116473","url":null,"abstract":"<div><p>In recent years, the expanding array of psychotropic medications has led to an increase in drug-drug interactions, particularly with combinations of different antipsychotics or psychotropic medications in clinical practice. However, the potential pharmacokinetic interactions between Lurasidone and Clozapine have not been extensively studied. Thus, this study aims to investigate these potential interactions by analyzing their pharmacokinetics in rat plasma after single oral administrations using developed LC-MS/MS methods. The study revealed notable changes in Lurasidone's pharmacokinetic parameters between single and combination administrations. Specifically, there were significant reductions in t<sub>1/2</sub> and V<sub>d</sub> by 3.3 and 1.5-fold (p < 0.05) respectively, while C<sub>max</sub> and AUC<sub>0-t</sub> proved a significant increase by 1.8 and 1.6-fold (p < 0.05) respectively following the combination administration. Furthermore, separate co-administration markedly decreased Clozapine's C<sub>max</sub> and AUC 0-t by 1.6 and 1.3-fold (p < 0.05) respectively, after the combination administration. Moreover, the AUC ratio for Lurasidone was 0.2, indicating a diminished therapeutic effect, whereas the AUC ratio for Clozapine suggested an elevated risk of adverse effects. These findings confirm the presence of drug-drug interactions between Lurasidone and Clozapine, suggesting potential implications for treatment efficacy. Recommendations for future clinical research include conducting pharmacodynamic studies to evaluate the impact of Lurasidone and Clozapine combination therapy. This underscores the importance of thoroughly assessing these interactions for clinical relevance and provides a scientific foundation for future evaluations of this drug combination.</p></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0731708524005132/pdfft?md5=8dea8bebbe5ff3892a28511ed8f1fdcf&pid=1-s2.0-S0731708524005132-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142240018","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}
Wen Zhang , Shuhui Cai , Wenhao Luan , Menglei Ding , Liuqing Di
{"title":"Integrated serum pharmacochemistry, network pharmacology and experimental verification to explore the mechanism of Aconiti Lateralis Radix Praeparata in treatment of lung cancer","authors":"Wen Zhang , Shuhui Cai , Wenhao Luan , Menglei Ding , Liuqing Di","doi":"10.1016/j.jpba.2024.116472","DOIUrl":"10.1016/j.jpba.2024.116472","url":null,"abstract":"<div><p>Aconiti Lateralis Radix Praeparata <strong>(</strong><em>Fuzi</em>) is a traditional Chinese medicine (TCM) widely used in treating cancer. Our formerly investigations confirmed the anti-lung cancer efficacy of <em>Fuzi</em>, but systematic analysis of the ingredients of <em>Fuzi</em> absorbed into serum and the corresponding molecular mechanism in treating lung cancer remained unknown. In this work, UPLC-Q-TOF-MS was applied to detect the ingredients of <em>Fuzi</em> in rat serum. Next, the possible targets and key pathways of the components absorbed into serum of <em>Fuzi</em> were predicted by network pharmacology. Then, the binding activity of components and potential targets were performed by molecular docking. Afterwards, the proliferation, mitochondrial membrane potential (MMP), apoptosis and reactive oxygen species (ROS) of lung cancer cells after treatment with <em>Fuzi</em>-containing serum were determined by MTT assay, JC-1 fluorescent probe, Annexin V-FITC/PI double staining and DCFH-DA respectively. Finally, the predicted target was further validated with qRT-PCR. In total, identification of 20 components of <em>Fuzi</em> derived from rat serum were achieved. The prediction of network pharmacology indicated that these compounds might exert their therapeutic effects by modulating mTOR. The findings from molecular docking proved that fuziline, songorine, napelline and hypaconitine exhibited binding potential with the mTOR. Cancer cell experiments revealed that the <em>Fuzi</em>-containing serum inhibited cell proliferation, induced apoptosis, reduced MMP and increased ROS. Additionally, <em>Fuzi</em>-containing serum significantly reduced the mRNA expression of mTOR. This study revealed that fuziline, songorine, napelline and hypaconitine were the main ingredients of <em>Fuzi</em> absorbed into serum. Furthermore, <em>Fuzi</em>-containing serum demonstrated inhibitory effects on the proliferation of lung cancer cells and induced the apoptosis. Combined with the results of network pharmacology, molecular docking and biological verification, <em>Fuzi</em>-containing serum might exert its anti-lung cancer effect by inhibiting mTOR. This study would provide a deeper understanding of <em>Fuzi</em> in treating lung cancer and offer a scientific reference for its clinical utilization.</p></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0731708524005120/pdfft?md5=db7010e1a3d18a816a88e3d9bb0be44d&pid=1-s2.0-S0731708524005120-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142232815","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}
Julie Horne , Pierre Beckers , Pierre-Yves Sacré , Pierre Francotte , Eric Caudron , Philippe Hubert , Cédric Hubert , Charlotte De Bleye , Eric Ziemons
{"title":"Surface enhanced transmission Raman spectroscopy: Quantitative performances for impurity analysis in complex matrices","authors":"Julie Horne , Pierre Beckers , Pierre-Yves Sacré , Pierre Francotte , Eric Caudron , Philippe Hubert , Cédric Hubert , Charlotte De Bleye , Eric Ziemons","doi":"10.1016/j.jpba.2024.116469","DOIUrl":"10.1016/j.jpba.2024.116469","url":null,"abstract":"<div><p>A transmission detection mode was investigated with SERS analyses (SETRS). A comparison between backscattering and transmission detection modes was conducted to demonstrate the feasibility of performing SETRS analyses. The impact of various parameters on the SERS signal intensity such as sample volume, lens collection optic, laser beam size and laser power were then examined. The analytical performances of SETRS were further evaluated through the quantification of an impurity (4-aminophenol) ranging from 3 to 20 µg/mL in a commercial pharmaceutical product using a total error risk-based approach. To account for expected variability of routine analysis, 9 batches of silver nanoparticles suspensions were used and experiments were performed over 5 different days and by 2 operators. Univariate spectral analysis based on a quadratic regression was compared to a multivariate approach using a partial least square regression. The presented results demonstrated that SETRS can be used to determine an impurity in a complex matrix opening new perspectives for quantitative applications.</p></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0731708524005090/pdfft?md5=056e69eef170a95924529297fe6219f2&pid=1-s2.0-S0731708524005090-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142168121","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}
Ayinazhaer Aihemaiti , Yuqing Liu , Peichen Zou , Hongyu Liu , Liang Zhu , Yabin Tang
{"title":"Simultaneous determination of canonical purine metabolism using a newly developed HILIC-MS/MS in cultured cells","authors":"Ayinazhaer Aihemaiti , Yuqing Liu , Peichen Zou , Hongyu Liu , Liang Zhu , Yabin Tang","doi":"10.1016/j.jpba.2024.116468","DOIUrl":"10.1016/j.jpba.2024.116468","url":null,"abstract":"<div><p>Purine metabolism acts as the core role in human metabolic network. It offers purine metabolites as raw material for building blocks in cell survival and proliferation. Purine metabolites are the most abundant metabolic substrates in organisms. There are few reports to simultaneously quantify canonical purine metabolism in cells. A novel hydrophilic interaction liquid chromatography coupled with mass spectrometry (HILIC-MS/MS) method was developed to simultaneously determine purines profile in biological samples. Chromatographic separation was achieved using a HILIC (Waters Xbridge™ Amide) column. Different optimizing chromatographic conditions and mass spectrometric parameters were tested in order to provide the best separation and the lowest limit of quantification (LLOQ) values for targeted metabolites. The validation was evaluated according to the Food and Drug Administration guidelines. The limit of determination (LOD) and the LOQ values were in the range of 0.02–8.33 ng mL<sup>−1</sup> and 0.1–24.5 ng mL<sup>−1</sup>, respectively. All calibration curves displayed good linear relationship of with excellent correlation coefficient (r) ranging from 0.9943 to 0.9999. Both intra-day and inter-day variability were below 15 %, respectively. Trueness, expressed as relative error, was always within ±15 %. In addition, no derivatization procedure and ion-pair reagents are in need. The innovated approach demonstrates high sensitivity, strong specificity, and good repeatability, making it suitable for absolute quantitative studies of canonical purine metabolism in cultured cells.</p></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0731708524005089/pdfft?md5=f5a483020bafc3a0bd7114fe3e6ffb33&pid=1-s2.0-S0731708524005089-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142230631","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}