XenobioticaPub Date : 2025-03-01Epub Date: 2025-05-10DOI: 10.1080/00498254.2025.2498696
Nattapon Jaisupa, Michael Ashton, Sofia Birgersson
{"title":"Cannabidiol metabolism <i>in vitro</i>: the role of antiseizure medications and CYP2C19 genotypes.","authors":"Nattapon Jaisupa, Michael Ashton, Sofia Birgersson","doi":"10.1080/00498254.2025.2498696","DOIUrl":"10.1080/00498254.2025.2498696","url":null,"abstract":"<p><p>Cannabidiol (CBD) can be used as add-on antiseizure medication. We aimed to investigate CBD depletion kinetics when combined with antiseizure medications, further the effect of intermediate-activity CYP2C19 genotype on CBD metabolism.CBD depletion in pooled human liver microsomes (HLMs) was studied at varying concentrations (400-6000 nM) in the absence and presence of valproic acid, clobazam, stiripentol and topiramate. In addition, CBD metabolism in HLMs from CYP2C19 <i>*1/*2</i> or <i>*1/*4</i> donors was investigated. Incubation samples were analysed for CBD and metabolites 7-OH-CBD and 7-COOH-CBD using LC-MS/MS. CBD <i>in vitro</i> intrinsic clearance (CL<sub>int</sub>) was calculated using estimated V<sub>max</sub> and K<sub>m</sub> values and further extrapolated to <i>in vivo</i> CL<sub>int</sub>.<i>In vitro</i> CL<sub>int</sub> values were reduced by approximately 25-85% in the presence of antiseizure medication(s) with the largest effect observed for the combination of four antiseizure drugs. There was no discernible difference for HLMs with CYP2C19 <i>*1/*2</i> or <i>*1/*4</i> genotype. Increases in CBD depletion half-lives at higher concentrations indicated substrate inhibition and/or metabolic saturation.Projected decreases in CBD CL<sub>int</sub> values when combined with several antiseizure medications suggest a potential for clinically relevant drug-drug interactions. A 1.3- to 4.8-fold increased exposure to unbound systemic CBD concentrations was predicted when combined with these antiseizure medications.</p>","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"246-255"},"PeriodicalIF":1.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026538","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}
XenobioticaPub Date : 2025-03-01Epub Date: 2025-05-19DOI: 10.1080/00498254.2025.2501593
Simon Poulter, Nigel Austin, Stephen P Watson, Sarah J Bucknell, M Alistair O'Brien, Ari Tolonen, Toni Lassila, Lisa A Stott, Andy Mead, Cliona MacSweeney
{"title":"Preclinical pharmacokinetics, metabolism, and disposition of NXE0041178, a novel orally bioavailable agonist of the GPR52 receptor with potential for treatment of schizophrenia and related psychiatric disorders.","authors":"Simon Poulter, Nigel Austin, Stephen P Watson, Sarah J Bucknell, M Alistair O'Brien, Ari Tolonen, Toni Lassila, Lisa A Stott, Andy Mead, Cliona MacSweeney","doi":"10.1080/00498254.2025.2501593","DOIUrl":"10.1080/00498254.2025.2501593","url":null,"abstract":"<p><p>The physico-chemical properties, protein binding, metabolism, permeability, transporter interactions, chemical toxicity, and drug-drug interaction potential of the novel GPR52 agonist NXE0041178 were characterised.NXE0041178 demonstrated high cellular permeability, little interaction with efflux transporters P-gp and BCRP, and extensive brain exposure in rodent, consistent with its intended use in CNS disorders.<i>In vivo</i> pharmacokinetic profiling in mouse, rat and monkey demonstrated that NXE0041178 was well-absorbed, with low clearance, a moderate volume-of-distribution and moderate terminal half-life. Oxidative metabolism was the major elimination pathway, with negligible renal or biliary excretion.NXE0041178 displayed good <i>in vitro</i>-to-<i>in vivo</i> correlation in metabolic clearance in preclinical species and low turnover in human <i>in vitro</i> metabolic systems, suggestive of a human pharmacokinetic profile commensurate with once-daily dosing.Early <i>in vitro</i> metabolite identification studies suggested similar metabolic pathways in human and preclinical species, but a distinct metabolic profile in dog.NXE0041178 caused weak heterotropic catalytic activation of CYP3A4, and weak transcriptional induction of CYP3A4 and CYP2B6. No reactive metabolites of NXE0041178 were detected, and no genotoxicity or clinically relevant inhibition of P450 enzymes were observed.These findings extend our knowledge of the preclinical ADME profile of NXE0041178, supporting its continued development.</p>","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"151-166"},"PeriodicalIF":1.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080807","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}
XenobioticaPub Date : 2025-03-01Epub Date: 2025-05-22DOI: 10.1080/00498254.2025.2507139
Jianhua Liao, Chunyan Meng, Jun Cheng, Baoqing Liu, Yuzhi Shao
{"title":"HSYA from safflower mitigates oxidative stress, inflammation, and apoptosis in liver ischemia-reperfusion injury.","authors":"Jianhua Liao, Chunyan Meng, Jun Cheng, Baoqing Liu, Yuzhi Shao","doi":"10.1080/00498254.2025.2507139","DOIUrl":"10.1080/00498254.2025.2507139","url":null,"abstract":"<p><p>Liver ischemia-reperfusion injury (IRI) is a common complication during liver transplantation and surgery, characterised by oxidative stress, inflammation, and apoptosis, which contribute to hepatocyte damage and impaired liver function. Safflower, known for its antioxidant and anti-inflammatory properties, has not been fully explored for its potential to alleviate liver IRI.This study aims to investigate the effects of safflower components on oxidative stress and cell apoptosis in liver IRI. A microfluidic liver cell ischemia-reperfusion model was employed to screen safflower components for their protective effects against oxidative stress and apoptosis. The effects of HSYA and other compounds were assessed by measuring cell viability, ROS levels, apoptosis, DNA damage (8-oxo-dG), lipid peroxidation (MDA), and inflammatory cytokine production (TNF-α, IL-1β, IL-6). HSYA exhibited superior protective effects, significantly reducing ROS, apoptosis, DNA damage, and lipid peroxidation. It also decreased pro-inflammatory cytokine levels, underscoring its antioxidant and anti-inflammatory properties.These findings suggest that HSYA effectively mitigates oxidative stress, inflammation, and apoptosis in liver IRI, positioning it as a promising candidate for therapeutic liver protection.</p>","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"239-245"},"PeriodicalIF":1.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102772","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}
XenobioticaPub Date : 2025-03-01Epub Date: 2025-05-22DOI: 10.1080/00498254.2025.2501591
Jianjun Lei, Xuehua Li, Xinpei Wang, Yuwei Xiao, Yang Chi, Qian Sun, He Zhang
{"title":"Research on LCN2 interference to enhance the sensitivity of drug-resistant strains to gemcitabine.","authors":"Jianjun Lei, Xuehua Li, Xinpei Wang, Yuwei Xiao, Yang Chi, Qian Sun, He Zhang","doi":"10.1080/00498254.2025.2501591","DOIUrl":"10.1080/00498254.2025.2501591","url":null,"abstract":"<p><p>The aim of this study was to observe the sensitivity of the resistant strains to gemcitabine by interfering with the LCN2.An AsPC-1 gemcitabine-resistant cell line (GEM-R) was generated. Based on GEM-R, a lentivirus-infected shRNA-transfected LCN2 cell line was established. The proliferation of LCN2-regulated GEM-R cells was evaluated using the CCK-8 test and the mRNA expression of Ki-67. The apoptosis level of each drug-resistant strain was detected by flow cytometry. The expression of Bax, Bcl-2, Akt, E-cadherin and Vimentin were detected by western blotting.A gemcitabine-resistant strain of AsPC-1 was successfully induced and constructed as an shRNA LCN2 strain based on GEM-R. The interference of LCN2 expression enhanced the tumour inhibition and pro-apoptotic level of gemcitabine, increased the Bax/Bcl-2 value, and decreased p-Akt/Akt value. Meanwhile, the expression of E-cadherin was enhanced while the expression of Vimentin was decreased.This study confirmed that LCN2 affects gemcitabine sensitivity by participating in apoptosis and EMT processes, which may provide potential for overcoming gemcitabine resistance.</p>","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"230-238"},"PeriodicalIF":1.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000415","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":"LC-MS/MS determination of 27 antipsychotics and metabolites in plasma for medication management monitoring.","authors":"Shanshan Chen, Donghan Wang, Yuanyuan Zhao, Yaqi Sun, Yueyao Luan, Qixuan Sun, Jiaqi Wang, Yuhang Yan, Jing Yu, Chunhua Zhou","doi":"10.1080/00498254.2025.2498702","DOIUrl":"10.1080/00498254.2025.2498702","url":null,"abstract":"<p><p>With the increasing prevalence and escalating complexity of mental disorders, precise medication has become critically important. This necessitates an efficient, accurate, and convenient method for drug concentration monitoring to support laboratory personnel and clinicians. In this study, three liquid chromatography-tandem mass spectrometry methods were developed and validated for simultaneously determining and quantifying 27 antipsychotics and related metabolites in human plasma. The plasma samples were subjected to protein precipitation using methanol, with isotope-labelled internal standards (ISs), followed by separation <i>via</i> isocratic elution on a BEH C18 column. Mass spectrometric analysis was performed using electrospray ionisation in positive ionisation mode with multiple reaction monitoring for quantitative detection. The analytes demonstrated high separation efficiency, with a single sample run time of 3.0 min. The method exhibited a wide linear range with excellent linearity across the concentration range. The intra- and inter-batch precision were ≤10.00%, the accuracy was 88.67-113.29%. Accurate quantification of antipsychotics remained unaffected under various storage conditions: 72 h at room temperature, 7 d at 4 °C refrigeration, and 14 d at -80 °C freezing. This validated methodology has been successfully applied to plasma samples from patients with psychiatric disorders, demonstrating its practical utility for accurate quantification of antipsychotics in large-scale and complex matrices containing multiple analytes.</p>","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"186-199"},"PeriodicalIF":1.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144052551","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}
XenobioticaPub Date : 2025-03-01Epub Date: 2025-05-12DOI: 10.1080/00498254.2025.2498699
Tanvi Kadam, Surendra Agarwal, Saritha Shetty
{"title":"Degradation studies on lurasidone hydrochloride using validated reverse phase HPLC and LC-MS/MS.","authors":"Tanvi Kadam, Surendra Agarwal, Saritha Shetty","doi":"10.1080/00498254.2025.2498699","DOIUrl":"10.1080/00498254.2025.2498699","url":null,"abstract":"<p><p>The research aims to develop and validate a stability-indicating reverse phase high-performance liquid chromatography (RP-HPLC) method for Lurasidone hydrochloride, an antipsychotic drug derived from benzisothiazole derivatives.A Binary Gradient HPLC System with a PDA detector, C18 column (4.6 x 100 mm, 2.5 mm), and a Shimadzu 8040 series triple quadrupole mass analyzer with an electron spray ionizer was used for the LC-MS/MS analysis.The method was linear in the concentration range of 10-50 μg/mL with a correlation coefficient (<i>r</i><sup>2</sup>) of 0.999. The limit of detection (LOD) and limit of quantification (LOQ) were 0.091 μg/mL and 0.275 μg/mL, respectively. Validation included accuracy, percentage recovery, robustness, system suitability, and interday and intraday precision. Forced degradation studies were conducted in acid, alkali, oxidative, neutral, and photolytic conditions after 1, 2, and 6 hours, and in oxidative conditions for 24 hours. Degraded products were evaluated on LC-MS (100 m/z to 550 m/z). Lurasidone was more susceptible to alkali hydrolysis, with fragmentation peaks at 109, 166, 220, and 317 m/z. and possible fragmentation pattern was also evaluated.This method is used for routine quality control analysis as a stability-indicating method of Lurasidone hydrochloride in pharmaceuticals, and the LC-MS data is used for evaluating stability and identifying drug intermediates.</p>","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"200-208"},"PeriodicalIF":1.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144012958","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":"Pharmacokinetics and tissue distribution of intranasal administration of rapamycin in rats.","authors":"Anqi Yang, Zhe Hu, Chengyu Hu, Jiayi Liu, Jianchen Fan, Lifen Gong, Liqun Jiang, Xin Huang, Yicheng Xie, Jia Liu","doi":"10.1080/00498254.2025.2498009","DOIUrl":"10.1080/00498254.2025.2498009","url":null,"abstract":"<p><p>Rapamycin has been shown to be effective in the treatment of a variety of neurological disorders, including epilepsy. Intranasal drug administration is a novel mode of drug delivery that bypasses the blood-brain barrier and numerous biological effects thereby entering the central nervous system directly. Thus, the objective of this study was to investigate the brain entrance efficacy of rapamycin following intranasal administration of rapamycin.First, we found that acute high-dose administration with a total dose of 0.326 mg of rapamycin in a novel dosage form produced few side effects on body weight, various organs, and nasal mucosa in rats. Then, we examined the distribution of drug concentrations in the brain, nasal mucosa, and blood using the above dosage form administered intranasally to rats at 0.04 mg/kg. We found that intranasal administration was significantly more efficacious than oral administration for rapamycin brain delivery. We also discovered gender differences in drug absorption following intranasal administration of rapamycin, wherein rapamycin exhibited faster systemic absorption in female rats compared to males. Our study demonstrated that intranasal administration of rapamycin is highly effective and low toxic, which may provide a new delivery option for rapamycin therapy in brain diseases.</p>","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"176-185"},"PeriodicalIF":1.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144012979","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":"Nrf2 signaling pathway studies in <i>Drosophila melanogaster</i>: parallel roles in human health and insect environmental responses.","authors":"Jingyi Li, Shushen Sun, Ying Li, Mengzhe Tian, Xinyi Li, Suxia Ren, Zengyi Huang, Yiwen Wang, Shaoshan Du","doi":"10.1080/00498254.2025.2465239","DOIUrl":"10.1080/00498254.2025.2465239","url":null,"abstract":"<p><p>The Nrf2 signalling pathway is crucial for cellular defense against oxidative stress and xenobiotic toxicity, highlighting its importance in both human health and environmental responses.This review focuses on the dual role of <i>Drosophila melanogaster</i> in Nrf2 research: we utilised the PubMed database to collect and summarised research articles on fruit fly Nrf2 studies published in the past decade, using keywords such as 'Nrf2', 'CncC', and '<i>Drosophila</i>'.We found that <i>Drosophila melanogaster</i>, as a classical model organism for studying human diseases such as neurodegenerative disorders, cancers, and diabetes, and as an insect model for investigating xenobiotic responses and pesticide resistance, is particularly well-suited for exploring the diverse and complex functions of Nrf2 pathway.Additionally, Natural products such as curcumin and quercetin can modulate Nrf2 activity for cytoprotection. Utilising <i>D. melanogaster</i>'s genetic tools and short life cycles, researchers can discover new therapeutics and study their mechanisms.This twofold exploration not only advances our understanding of Nrf2 in human health but also provides insights into pest control strategies through enhanced insect resistance mechanisms. Continued research in this area is essential for developing innovative treatments and effective pest management approaches.</p>","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"85-98"},"PeriodicalIF":1.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392111","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}
XenobioticaPub Date : 2025-02-01Epub Date: 2025-04-13DOI: 10.1080/00498254.2025.2478928
Abdul Ahad, Mohammad Raish, Yousef A Bin Jardan, Abdullah M Al-Mohizea, Fahad I Al-Jenoobi
{"title":"Development of eugenol-fortified fisetin-loaded nano-invasomes gel.","authors":"Abdul Ahad, Mohammad Raish, Yousef A Bin Jardan, Abdullah M Al-Mohizea, Fahad I Al-Jenoobi","doi":"10.1080/00498254.2025.2478928","DOIUrl":"10.1080/00498254.2025.2478928","url":null,"abstract":"<p><p>The goal of current investigation was to develop eugenol-fortified fisetin nano-invasomes. Fisetin-loaded invasomes were prepared using thin film hydration procedure and evaluated for various parameters. Additionally, the optimised fisetin invasomes formulation (F5) was converted to fisetin invasomes gel using Carbopol<sup>®</sup> as gelling agent and evaluated for pH, spreadability, homogeneity, drug content, <i>in vitro</i> fisetin release, antioxidant activity and stability study.Prepared optimised fisetin invasomes formulation (F5) demonstrated vesicles size, PDI, zeta potential and entrapment efficiency of 153.85 ± 14.32 nm, 0.208 ± 0.042, -12.67 ± 1.08 mV and 72.10 ± 6.36%. The TEM image indicated that the prepared invasomes vesicles are intact, spherical and found in the range of nanosized scale. Prepared fisetin invasomes gel showed better spreadability and <i>in vitro</i> fisetin released in contrast to fisetin control gel. Substantial improvement in the DPPH radical scavenging activity of fisetin invasomes gel 44.70% (3.1 µM) and 83.94% (50 µM), was noted as compared to the control gel at 39.47% (3.1 µM) and 79.10% at (50 µM). The prepared fisetin invasomes gel formulation was found stable at 4 °C.Based on the results, prepared invasomes gel formulation was found as a viable method for better delivery of bioactive compound(s) including fisetin.</p>","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"140-149"},"PeriodicalIF":1.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617334","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}
XenobioticaPub Date : 2025-02-01Epub Date: 2025-05-04DOI: 10.1080/00498254.2025.2497050
Yifei Long, Xueying Li, Yue Liu, Mi Zhang, Fumin Feng
{"title":"Inhibition of YAP can down-regulate NLRP3 inflammasome and improve anti-tuberculosis drug-induced liver injury.","authors":"Yifei Long, Xueying Li, Yue Liu, Mi Zhang, Fumin Feng","doi":"10.1080/00498254.2025.2497050","DOIUrl":"10.1080/00498254.2025.2497050","url":null,"abstract":"<p><p>Yes-associated protein (YAP) is a core effector molecule in the Hippo signalling pathway, but its role in antituberculosis drug-induced liver injury (ADLI) is unclear. We aimed to explore the regulatory effects of YAP on the NLRP3 inflammasome in ADLI and its potential hepatoprotective effects.An ADLI animal model was established. Various indicators of experimental animals were detected at 0, 7, 14, and 21 days. On day 7, HE staining observed liver tissue, and liver index, ALT, and AST levels confirmed the ADLI model. YAP's mRNA and protein levels were examined, YAP inhibitor effects were observed, and NLRP3 inflammasome, inflammation, and oxidative stress indicators were analysed.It was found that the mRNA and protein levels of YAP increased during ADLI and then decreased due to the action of YAP inhibitors. YAP caused an elevation in NLRP3 inflammasome indicators, as well as increased expression of inflammation and oxidative stress. After feeding with YAP inhibitors, these indicators were reduced.The results suggest that targeting YAP may be a novel therapeutic strategy for alleviating antituberculosis drug-induced liver injury.</p>","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"131-139"},"PeriodicalIF":1.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144018497","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}