Journal of pharmaceutical and biomedical analysis最新文献

{"title":"Evaluation of low volume sampling devices for a pharmacodynamic biomarker analysis: Challenges and solutions","authors":"","doi":"10.1016/j.jpba.2024.116454","DOIUrl":"10.1016/j.jpba.2024.116454","url":null,"abstract":"<div><p>Low volume sampling technologies have gained popularity as they are minimally invasive, reduce patient burden, enhance population diversity, and have the potential to facilitate decentralized clinical trials. Herein, we validated a Gyrolab assay to measure soluble Mucosal Addressin Cell Adhesion Molecule 1 (sMAdCAM-1) in dried blood samples collected using two low volume sampling devices, Mitra and Tasso-M20. This validated assay was implemented in a proof-of-concept study to compare three low volume sampling devices (Mitra, Tasso-M20 and TassoOne Plus) with serum collected via venipuncture from healthy volunteers receiving etrolizumab. We observed significantly higher concentration of sMAdCAM-1 in dried blood samples collected using Mitra and Tasso-M20 compared to serum in some paired samples, which was attributed to interference from the dried blood extraction buffer. To mitigate this interference, samples required substantial dilution into the appropriate buffer, which negatively impacted the detectability of sMAdCAM-1 with the Gyrolab assay. By employing the Quanterix single molecule array (Simoa), known for its superior assay sensitivity, the interference was minimized in the diluted samples. Both liquid blood collected in TassoOne Plus and dried blood collected using Mitra and Tasso-M20 demonstrated great concordance with serum for sMAdCAM-1 measurement. However, a bias was observed in Mitra dried blood samples, presumably due to the different sample collection sites in comparison with venipuncture and Tasso devices. Our study highlights the potential of low volume sampling technologies for biomarker analysis, and underscores the importance of understanding the challenges and limitations of these technologies before integrating them into clinical studies.</p></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142094721","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":"Metabolomics study of Shenling Baizhu Powder in the treatment of multiple organ dysfunction syndrome in the elderly (MODSE) with malnutrition","authors":"","doi":"10.1016/j.jpba.2024.116423","DOIUrl":"10.1016/j.jpba.2024.116423","url":null,"abstract":"<div><p>Malnutrition is an important risk factor for multiple organ dysfunction syndrome in the elderly (MODSE) and seriously affects the occurrence, progression and prognosis of MODSE. Shenling Baizhu Power (SBP), a classic formula from traditional Chinese medicine (TCM), when integrated with enteral nutrition, has been proven to be an effective clinical strategy for treating the patients of MODSE with malnutrition. This study aimed to investigate the metabolic changes during disease occurrence and SBP treatment, and to discover potential metabolic biomarkers for the diagnosis and efficacy evaluation. An untargeted metabolomics strategy based on UHPLC-Q-Orbitrap-HRMS was performed to reveal the differential serum metabolites between MODSE patients with malnutrition (n=59) and healthy controls (n=33), and those between patients treated with enteral nutrition (n=31) and SBP combined with enteral nutrition (n=28). Significantly different metabolites were identified and mapped onto the network of metabolic pathways to explore the metabolic disorders caused by the disease and the metabolic regulatory mechanism of SBP. Additionally, the area under the curve (AUC) of the potential biomarkers was investigated for predicting the disease and the efficacy of SBP. Sixty differential metabolites were identified between the disease and control groups, which were mainly related to amino acid metabolism, energy metabolism and carbohydrate metabolism. In the same way, 50 differential metabolites associated with SBP treatment were identified, which improved metabolic abnormalities in vivo mainly by regulating the above-mentioned metabolic pathways. Finally, 13 differential metabolites in common were selected as the potential biomarkers and the AUC value of each biomarker was within the range of 0.8–1.0, indicating that these biomarkers had high prediction accuracy for the diagnosis and efficacy evaluation of MODSE with malnutrition. This study demonstrates that serum metabolomics approaches based on the UHPLC-Q-Orbitrap-HRMS platform can be applied as a tool to reveal the metabolic changes induced by MODSE with malnutrition and SBP can play an important role in the clinical application.</p></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142087252","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":"Integrating sodium cholate-modified MOF hybrid lipase and solubilization of hydrophobic candidates into a step for liganding fishing lipase inhibitors from Nelumbinis Folium","authors":"","doi":"10.1016/j.jpba.2024.116430","DOIUrl":"10.1016/j.jpba.2024.116430","url":null,"abstract":"<div><p>Enzyme immobilization by metal organic frameworks (MOFs) is an efficient way for screening active constituents in natural products. However, the enzyme’s biocatalysis activity is usually decreased due to unfavorable conformational changes during the immobilization process. In this study, sodium cholate was firstly used as the modifier for zeolitic imidazolate framework-8 (ZIF-8) immobilized lipase to increase both the stability and activity. More importantly, with the help of solubilization of sodium cholate, a total of 3 flavonoids and 6 alkaloids candidate compounds were fished out. Their structures were identified and the enzyme inhibitory activities were verified. In addition, the binding information between the candidate compound and the enzyme was displayed by molecular docking. This study provides valuable information for the improvement of immobilized enzyme activity and functional active ingredients in complicated medicinal plant extracts.</p></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142077508","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":"Metabolic signatures of metabolites of the purine degradation pathway in human plasma using HILIC UHPLC–HRMS","authors":"","doi":"10.1016/j.jpba.2024.116451","DOIUrl":"10.1016/j.jpba.2024.116451","url":null,"abstract":"<div><p>The metabolic disorders in the purine degradation pathway have proven to be closely associated with several human diseases. However, the etiology is not yet fully understood. Profile assay of purine intermediates and uric acid involved in the metabolic pathway can provide additional insight into the nature and severity of related diseases. Purine metabolites are endogenous chemicals with high hydrophilicity, polarity, and similar structures, thus there is a great need for a specific method to quantify them directly in biological fluids with a short running time. Herein, eight purine degradation pathway metabolites, including xanthine, hypoxanthine, guanine, xanthosine, inosine, guanosine, adenosine and uric acid, in human plasma were quantitatively measured using hydrophilic interaction chromatography-tandem high-resolution mass spectrometry (HILIC-HRMS) in a short running time of 10 min. The method was systematically validated for specificity, linearity of the calibration curve, the limit of detection, the limit of quantification, the lower limit of quantification, precision, accuracy, extraction recovery, matrix effect, and stability. The results showed that the method was linear (<em>R</em>² &gt; 0.99), accurate (the intra- and inter-day recoveries of all analytes ranged from 90.0 % to 110.0 %), and precise (the intra- and inter-day precisions were less than 6.7 % and 8.9 %, respectively) with the lower limits of quantification ranging from 3 to 10,000 ng/mL. The extraction recoveries and matrix effects were repeatable and stable. All the analytes were stable in the autosampler and could be subject to three freeze-thaw cycles. The developed method was ultimately applied to 100 plasma specimens from healthy individuals. The results showed that the concentrations of different purine metabolites varied dramatically in plasma specimens. Diet and body mass index (BMI) were the most significant factors determining purine levels, followed by drinking and sex. Age, smoking and bedtime showed a very weak correlation with purine metabolism. The findings of the present work reveal the characteristics of purine metabolism in human plasma under non-pathological conditions. The results also highlight the factors that can cause changes in purine metabolism, which are useful in developing effective treatment strategies for metabolic disorders of purines, particularly for those caused by lifestyle factors.</p></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142095230","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":"Dynamic changes in pyroptosis following spinal cord injury and the identification of crucial molecular signatures through machine learning and single-cell sequencing","authors":"","doi":"10.1016/j.jpba.2024.116449","DOIUrl":"10.1016/j.jpba.2024.116449","url":null,"abstract":"<div><p>The pathological cascade of spinal cord injury (SCI) is highly intricate. The onset of neuroinflammation can exacerbate the extent of damage. Pyroptosis is a form of inflammation-linked programmed cell death (PCD), the inhibition of pyroptosis can partially mitigate neuroinflammation. It is imperative to delineate the principal cell types susceptible to pyroptosis and concomitantly identify key genes associated with this process. We initially defined the pyroptosis-related genes (PRGs) and analyzed their expression at different time points post SCI. The results demonstrate a substantial upregulation of differentially expressed genes (DEGs) related to pyroptosis on the 7 days post-injury (dpi), these DEGs in the 7 dpi are closely related to the inflammatory response. Subsequently, immune infiltration analysis revealed a predominant presence of inflammatory microglia. Through correlation analysis, we postulated that pyroptosis primarily manifested within the inflammatory microglia. Employing machine learning algorithms, we identified four pyroptosis-related molecular signatures, which were experimentally validated using BV2 cells and spinal cord tissue samples. The robustness of the identified molecular signatures was further confirmed through single-cell sequencing data analysis. Overall, our study elucidates the temporal dynamics of pyroptosis and identifies key molecular signatures following SCI. These findings can provide novel evidence for therapeutic interventions in SCI.</p></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0731708524004898/pdfft?md5=74594663da2104714edcdc680190b652&pid=1-s2.0-S0731708524004898-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142095229","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":"Distinct chemical degradation pathways of AAV1 and AAV8 under thermal stress conditions revealed by analytical anion exchange chromatography and LC-MS-based peptide mapping","authors":"","doi":"10.1016/j.jpba.2024.116452","DOIUrl":"10.1016/j.jpba.2024.116452","url":null,"abstract":"<div><p>Adeno-associated virus (AAV)-based gene therapy is experiencing a rapid growth in the field of medicine and holds great promise in combating a wide range of human diseases. For successful development of AAV-based products, comprehensive thermal stability studies are often required to establish storage conditions and shelf life. However, as a relatively new modality, limited studies have been reported to elucidate the chemical degradation pathways of AAV products under thermal stress conditions. In this study, we first presented an intriguing difference in charge profile shift between thermally stressed AAV8 and AAV1 capsids when analyzed by anion exchange chromatography. Subsequently, a novel and robust peptide mapping protocol was developed and applied to elucidate the underlying chemical degradation pathways of thermally stressed AAV8 and AAV1. Compared to the conventional therapeutic proteins, the unique structure of AAV capsids also led to some key differences in how modifications at specific sites may impact the overall charge properties. Finally, despite the high sequency identity, the analysis revealed that the opposite charge profile shifts between thermally stressed AAV8 and AAV1 could be mainly attributed to a single modification unique to each serotype.</p></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0731708524004928/pdfft?md5=54753f221f2d67530f2c1b6c4cc7d0bd&pid=1-s2.0-S0731708524004928-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142094629","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":"Detection of N-desethyl etonitazene in a drug checking sample: Chemical analysis and pharmacological characterization of a recent member of the 2-benzylbenzimidazole “nitazene” class","authors":"","doi":"10.1016/j.jpba.2024.116453","DOIUrl":"10.1016/j.jpba.2024.116453","url":null,"abstract":"<div><p>The emergence of 2-benzylbenzimidazole “nitazene” opioids is stirring up the recreational synthetic opioid market. Many nitazene analogues act as potent agonists at the µ‑opioid receptor (MOR), as demonstrated in various <em>in vitro</em> and <em>in vivo</em> studies. Severe intoxication and overdose deaths associated with nitazene analogues are increasingly being reported. Nitazene opioids are classified as a public health threat, stressing the need for close monitoring of new developments on the recreational drug market. This study reports on the detection of <em>N</em>-desethyl etonitazene in a sample handed in by a recreational drug user at a Swiss drug checking service in August 2023. The person bought the sample through an internet source where it was stated to contain isotonitazene. Chemical analyses were conducted to characterize the sample, <em>i.e.</em> nuclear magnetic resonance (NMR), capillary electrophoresis (CE), and high-resolution mass spectrometry (HRMS). The sample was additionally investigated using two different <em>in vitro</em> MOR activation assays. NMR and high-performance liquid chromatography (HPLC) coupled to HRMS confirmed the presence of <em>N</em>-desethyl etonitazene at a high purity and in the absence of isotonitazene and etonitazene. <em>N</em>-Desethyl nitazene analogues have been detected before as metabolites of isotonitazene and etonitazene. However, as first seen with <em>N</em>-desethyl isotonitazene, they are now emerging as standalone drugs. The applied bioassays demonstrated increased efficacy and approximately 6–9-fold higher potency of <em>N</em>-desethyl etonitazene at MOR compared to fentanyl. <em>N</em>-Desethyl etonitazene showed EC₅₀ values of 3.35 nM and 0.500 nM in the β-arrestin 2 recruitment and Aequoscreen® assays, respectively. The opioid activity present in the collected sample was additionally evaluated using the bioassays and showed good overlap with the reference standard, in line with the analytical purity assessment. This demonstrates the potential of these bioassays to provide a rapid opioid activity assessment of authentic samples. The emergence of other <em>N</em>-desethyl nitazene analogues must be considered during forensic and clinical toxicology casework, to avoid misclassification of intake of such analogues as metabolites. Finally, drug checking services enable the close monitoring of market developments and trends and are of great value for early warning and harm reduction purposes.</p></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S073170852400493X/pdfft?md5=6eef866d134e39005f710f261dc4252c&pid=1-s2.0-S073170852400493X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142094723","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":"Application of microdialysis combined with lipidomics to analyze fatty acid metabolic changes in the disease process of rheumatoid arthritis","authors":"","doi":"10.1016/j.jpba.2024.116448","DOIUrl":"10.1016/j.jpba.2024.116448","url":null,"abstract":"<div><p>Rheumatoid arthritis (RA) is a metabolically active disease, with shifts in fatty acid metabolism during disease progression profoundly affecting the systemic inflammatory response. Altered fatty acid biomarker metabolism may be a key target for the treatment of RA. To investigate the changes of fatty acid metabolism in RA, collagen-induced arthritis (CIA) model was established. Microdialysis sampling was utilized to overcome the characteristic of occlusive joint cavity <em>in vivo</em> synovial fluid (SF) sampling. Lipidomic methods were established with the UHPLC-Orbitrap Exploris120 platform, and lipid measurements were performed on serum and SF samples. Then, multivariate statistical analyses were performed to detect changes in lipid metabolites induced by CIA. Consequently, a total of 22 potential biomarkers associated with differential fatty acids were screened and identified in serum, and 13 were identified in SF. Notably, alterations were observed in metabolites such as Hexadecanoic acid, Octadecanoic acid, Arachidonic acid, (+/-)11,12-EpETrE, DHA, DPA, Myristic acid, Suberic acid, and others. This study explored a new mechanism of the RA disease process from the perspective of fatty acid metabolism. It provided a new strategy for experimental research on determining the optimal time for establishing CIA model and screening clinical diagnostic biomarkers.</p></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142094628","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":"Study on the chemical composition of Gegen-Tianma decoction and its absorbed constituents in rat plasma, brain based on UPLC-Q-TOF-MS and DESI-MSI","authors":"","doi":"10.1016/j.jpba.2024.116446","DOIUrl":"10.1016/j.jpba.2024.116446","url":null,"abstract":"<div><p>In traditional Chinese medicinal practices, Gegen (GG) and Tianma (TM) are widely utilized for headache relief, but their material basis has not been comprehensively characterized. This research utilized ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF-MS) for precise determination of Gegen-Tianma's (GGTM) material composition, and employed desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) to pinpoint the brain-absorbed components and various metabolites post oral administration to rats. A total of 80 chemical constituents were identified from GGTM, 11 prototypes and 18 metabolites were identified from plasma. The brain tissue was identified in total 4 prototypes and 5 metabolites, these constituents were basically located in the prefrontal cortex and thalamus. The absorption patterns of components in the rat brain aligned with the varied distribution of metabolites within the brain. This study provides a solid theoretical basis for in-depth exploration of potential drug targets and elucidation of the specific mechanism of action of GGTM in the treatment of migraine.</p></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142084143","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":"In-depth phytochemical profiling of Roscoea purpurea (Kakoli): Comparative UHPLC-MS/QToF and GC-MS/MS analysis of supercritical CO2 fluid - and conventional solvent - based extractive processes","authors":"","doi":"10.1016/j.jpba.2024.116444","DOIUrl":"10.1016/j.jpba.2024.116444","url":null,"abstract":"<div><p>The remarkable biodiversity of medicinal plants worldwide highlights their significance in traditional and alternative medicine. Astavarga, a group of eight medicinal herbs from the Himalayan region of India, including <em>Roscoea purpurea</em> (commonly known as Kakoli), is esteemed in Ayurveda for its health-promoting and rejuvenating properties. In this comprehensive study, we aimed to develop and optimise robust UHPLC-MS/QToF (Ultra-high-performance liquid chromatography-mass spectrometry coupled with quadrupole time of flight) and GC-MS/MS (Gas chromatography-tandem mass spectrometry) methods to identify the phytochemicals in <em>R. purpurea</em> root hydromethanolic extract and essential oil. We also conducted a comparative assessment of supercritical fluid extraction and conventional solvent extraction methods for the first time in <em>R. purpurea</em> root, highlighting their relevance to the medicinal field. Using the UHPLC/MS-QToF method, we identified a total of fifty-six phytometabolites, while sixteen volatile constituents were discerned within the essential oil of <em>R. purpurea</em> by GC-MS/MS method. Among the volatile constituents, <em>β</em>-eudesmol (40.84 %), guaiac acetate (10.55 %), and <em>γ</em>-eudesmol (10.31 %) were emerged as the principal components. Our findings were further compared with the volatile constituents extracted via supercritical fluid extraction and conventional solvent extraction methods. Notably, our research unveiled the presence of a carotenoid metabolite, 15-methyl retinol, for the first time. Furthermore, our fatty acid analysis of the supercritical fluid extract revealed elevated levels of unsaturated fatty acids, particularly oleic and linoleic acids. The methods were validated in terms of system specificity also. The discovery of these well-recognised therapeutically active components in <em>R. purpurea</em> significantly enhances its potential, highlighting its unique profile among medicinal plants in the Himalayan region and its suitability for traditional Ayurveda.</p></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142083246","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}