Xenobiotica最新文献_第9页

Physiologically based pharmacokinetic (PBPK) modelling and simulation based integrative approach to assess natural product-drug interactions - effect of glycyrrhetinic acid on quetiapine. 基于生理的药代动力学（PBPK）建模和模拟的综合方法来评估天然产物-药物相互作用-甘草次酸对喹硫平的影响。

IF 1.2 4区医学

Xenobiotica Pub Date : 2026-01-01 Epub Date: 2025-12-28 DOI: 10.1080/00498254.2025.2606996

Falguni P Pankhania, Jagannath Kota, Atish T Paul

{"title":"Physiologically based pharmacokinetic (PBPK) modelling and simulation based integrative approach to assess natural product-drug interactions - effect of glycyrrhetinic acid on quetiapine.","authors":"Falguni P Pankhania, Jagannath Kota, Atish T Paul","doi":"10.1080/00498254.2025.2606996","DOIUrl":"10.1080/00498254.2025.2606996","url":null,"abstract":"Case reports of adverse event and loss of efficacy in individuals are the primary source of natural product drug interactions (NPDIs). Given the fundamental constraints, there is clear need for prospective and systematic study as foolproof methodology to understand NPDIs. Although human trials are confirmatory, an integrative physiologically-based pharmacokinetic (PBPK) modelling approach can be considered, despite challenges associated with NP data availability, variability and complexity.To explore the applicability of this approach, glycyrrhizin (GL) and its active metabolite glycyrrhetinic acid (GA) were identified as an NP with numerous pharmacological benefits and a potential likelihood of concomitant administration with narrow therapeutic antipsychotic drug quetiapine. Numerous serious case reports of quetiapine toxicity in combination with NPs support the proposed hypothesis.Simcyp® simulator was used to develop and validate quetiapine PBPK model followed by its utilisation for the evaluation of NPDI risk. PBPK modelling data indicated ∼ three-fold increase in quetiapine area under the curve (AUC) and peak plasma concentration (Cmax) in the presence of GA, signifying moderate increase in exposure which implies the need for further clinical assessment. This study successfully demonstrated the translation of in vitro information into helpful risk predictions for in vivo NPDIs by PBPK modelling.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"86-97"},"PeriodicalIF":1.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145795068","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}

引用次数: 0

Novel cytochrome P450 2J isoforms in tree shrews are functional drug-metabolising enzymes involved in ebastine and astemizole oxidation. 树鼩中新的细胞色素P450 2J亚型是参与依巴斯汀和阿司咪唑氧化的功能性药物代谢酶。

IF 1.2 4区医学

Xenobiotica Pub Date : 2026-01-01 Epub Date: 2026-01-14 DOI: 10.1080/00498254.2025.2612026

Yasuhiro Uno, Miu Kamizono, Genki Ushirozako, Kyoko Tsukiyama-Kohara, Norie Murayama, Hiroshi Yamazaki

{"title":"Novel cytochrome P450 2J isoforms in tree shrews are functional drug-metabolising enzymes involved in ebastine and astemizole oxidation.","authors":"Yasuhiro Uno, Miu Kamizono, Genki Ushirozako, Kyoko Tsukiyama-Kohara, Norie Murayama, Hiroshi Yamazaki","doi":"10.1080/00498254.2025.2612026","DOIUrl":"10.1080/00498254.2025.2612026","url":null,"abstract":"The cytochromes P450 (P450 or CYP), a family of drug-metabolising enzymes, are important in drug development and drug therapy. In tree shrews, a range of P450s, including CYP1A, CYP2A, CYP2B, CYP2C, CYP2D, CYP2E, CYP3A, CYP4A, and CYP4F, have been identified and analysed. In general tree shrew P450s have enzymatic characteristics similar to those of human P450s.In the present study, the cDNAs of five novel tree shrew P450s homologous to human CYP2J2, namely, CYP2J104, CYP2J105, CYP2J106, CYP2J107, and CYP2J108, were identified. The deduced amino acid sequences (500-502 residues) were highly homologous (79-87%) to human CYP2J2 and were closely related to human CYP2J2 in a phylogenetic tree.All five novel tree shrew CYP2J genes contained nine coding exons and formed a gene cluster at a genomic region corresponding to human CYP2J2. Except for CYP2J104 mRNA, expression of all tree shrew CYP2J2 mRNAs was detected in liver.All five tree shrew CYP2Js metabolised ebastine and astemizole, typical substrates of human CYP2J2, and thus were functional enzymes with characteristics similar to human CYP2J2.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"37-43"},"PeriodicalIF":1.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893353","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}

引用次数: 0

Practical insights into additional strength biowaivers for oral solid dosage forms: current requirements by major regulatory agencies and path towards harmonization. 对口服固体剂型的额外强度生物豁免的实际见解：主要监管机构的当前要求和协调之路。

IF 1.2 4区医学

Xenobiotica Pub Date : 2026-01-01 Epub Date: 2026-01-11 DOI: 10.1080/00498254.2025.2612031

Chandra Teja Uppuluri, Adithya Karthik Bhattiprolu, Anuj Kumar Saini, Sivacharan Kollipara

{"title":"Practical insights into additional strength biowaivers for oral solid dosage forms: current requirements by major regulatory agencies and path towards harmonization.","authors":"Chandra Teja Uppuluri, Adithya Karthik Bhattiprolu, Anuj Kumar Saini, Sivacharan Kollipara","doi":"10.1080/00498254.2025.2612031","DOIUrl":"10.1080/00498254.2025.2612031","url":null,"abstract":"Additional strength biowaivers offer a strategic advantage in pharmaceutical development by enabling regulatory approval of multiple strengths without separate bioequivalence (BE) studies. This review provides a comprehensive and timely analysis of current regulatory expectations for such waivers across major jurisdictions-USFDA (USA), EMA (Europe), HC (Canada), and ANVISA (Brazil)-for both immediate-release (IR) and modified-release (MR) solid oral dosage forms. The review also explores the evolving harmonisation efforts under the ICH M13A and draft M13B guidelines, highlighting their potential to streamline global submissions and reduce development complexity.Key scientific criteria such as pharmacokinetic linearity, formulation proportionality, and dissolution similarity are critically examined, with emphasis on how agency-specific interpretations influence regulatory outcomes.Several hypothetical case examples are presented to illustrate how regulatory decisions vary based on product-specific nuances and regional requirements. These examples provide practical insights into navigating scenarios, such as deviations in formulation proportionality or dissolution variability, and demonstrate how alternative statistical approaches can support biowaiver eligibility.By bridging current practices with future harmonised standards, this review serves as a valuable and timely resource for pharmaceutical professionals. It empowers developers to align strategies with both existing and emerging guidelines, facilitating efficient, multi-market drug development and regulatory compliance.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"22-36"},"PeriodicalIF":1.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913178","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}

引用次数: 0

α-Hederin inhibits osteosarcoma progression by triggering ferroptosis and disrupting mitochondrial function via PI3K/AKT signalling. α-Hederin通过PI3K/Akt信号通路引发铁下垂和破坏线粒体功能抑制骨肉瘤进展。

IF 1.2 4区医学

Xenobiotica Pub Date : 2026-01-01 Epub Date: 2026-01-11 DOI: 10.1080/00498254.2025.2598384

Baichuan Zhang, Xianwen Yu, Yu Yan, Kang Tang

{"title":"α-Hederin inhibits osteosarcoma progression by triggering ferroptosis and disrupting mitochondrial function via PI3K/AKT signalling.","authors":"Baichuan Zhang, Xianwen Yu, Yu Yan, Kang Tang","doi":"10.1080/00498254.2025.2598384","DOIUrl":"10.1080/00498254.2025.2598384","url":null,"abstract":"Osteosarcoma is the most common primary malignant bone tumour in adolescents, with a poor prognosis and high rates of recurrence and metastasis. Ferroptosis, a form of regulated cell death associated with iron overload and lipid peroxidation, and mitochondrial dysfunction have been recognised as potential therapeutic targets in cancer. α-Hederin, a natural triterpenoid saponin, has shown antitumor effects in several cancers, but its role in osteosarcoma remains unclear. This study aimed to investigate the pharmacological effects and mechanisms of α-hederin on osteosarcoma. We integrated network pharmacology and molecular docking to identify potential targets and pathways, and validated the findings using in vitro experiments in 143B osteosarcoma cells. Network pharmacology analysis revealed 27 overlapping targets between α-hederin and osteosarcoma, with significant enrichment in the PI3K/AKT and ferroptosis pathways. Molecular docking confirmed strong binding affinity between α-hederin and key targets. Functional assays demonstrated that α-hederin inhibited cell proliferation and migration, increased intracellular Fe2+ and lipid reactive oxygen species levels, disrupted mitochondrial membrane potential and ATP production, and downregulated mitochondrial biogenesis proteins. Transmission electron microscopy further revealed typical mitochondrial morphological changes associated with ferroptosis. Western blotting showed decreased expression of GPX4 and SLC7A11, increased ACSL4 levels, and suppressed activation of the PI3K/AKT pathway. Moreover, these effects were partially reversed by the ferroptosis inhibitor Ferrostatin-1. Collectively, these results indicate that α-hederin exerts antitumor effects against osteosarcoma by inducing ferroptosis and impairing mitochondrial function, partly through inhibition of the PI3K/AKT signalling pathway, providing a potential therapeutic strategy for osteosarcoma.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"53-65"},"PeriodicalIF":1.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145669504","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}

引用次数: 0

Green synthesis of Zinc Oxide nanoflowers using camellia sinensis extract and evaluation of their xenobiotic-like cellular, apoptotic, and inflammatory responses in fibroblast cells. 山茶提取物绿色合成氧化锌纳米花及其在成纤维细胞中异种生物样细胞、凋亡和炎症反应的评价。

IF 1.2 4区医学

Xenobiotica Pub Date : 2026-01-01 Epub Date: 2026-01-04 DOI: 10.1080/00498254.2025.2610230

Serap Yesilkir Baydar

{"title":"Green synthesis of Zinc Oxide nanoflowers using camellia sinensis extract and evaluation of their xenobiotic-like cellular, apoptotic, and inflammatory responses in fibroblast cells.","authors":"Serap Yesilkir Baydar","doi":"10.1080/00498254.2025.2610230","DOIUrl":"10.1080/00498254.2025.2610230","url":null,"abstract":"Zinc oxide (ZnO) nanomaterials, acting as engineered xenobiotic-like agents, can induce complex cellular stress and defense responses. This study reports a novel green synthesis of ZnO nanoflowers using Camellia sinensis leaf extract, resulting in a biocompatible nanostructure with a distinctive flower-like morphology.The C. sinensis-mediated synthesis provides a sustainable and reproducible approach for producing stable ZnO nanoflowers. The nanoparticles were thoroughly characterised (hydrodynamic assembly size: 259.3 nm; zeta potential: -32.35 mV; individual nanostructure physical dimensions: ∼38.8 × 138.7 nm), and their biological interactions were evaluated in L929 fibroblasts to assess xenobiotic-like cellular responses.Cytotoxicity was dose- and time-dependent (IC50 = 52.3 µg/mL at 24 h, 14.1 µg/mL at 48 h, and 10.5 µg/mL at 72 h). At a non-toxic IC50 concentration, the nanoflowers induced a transient adaptive stress response, characterised by significant yet reversible upregulation of inflammatory cytokines (IL-1β, IL-10) and key apoptotic regulators (Bax, Bcl-2, and p53).Collectively, this study demonstrates that green-synthesised ZnO nanoflowers trigger moderate, self-resolving apoptotic and inflammatory signalling consistent with a xenobiotic-like adaptive cellular response. These findings highlight the potential of plant-mediated synthesis to engineer ZnO nanostructures with controlled bioactivity, supporting their safer application in biomedical contexts.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"75-85"},"PeriodicalIF":1.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145834732","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}

引用次数: 0

Mass balance and metabolite profiling of ¹⁴C-Zalunfiban in humans following single-dose subcutaneous administration. 单次皮下给药后14c -扎伦非班在人体内的质量平衡和代谢物分析。

IF 1.5 4区医学

Xenobiotica Pub Date : 2026-01-01 Epub Date: 2025-12-15 DOI: 10.1080/00498254.2025.2597225

Robert B MacArthur, Sem A O F Rikken, Spandana R Vootukuri, Barry S Coller, C Michael Gibson, Christopher B Granger, G Montalescot, Jurriën M Ten Berg, Murray P Ducharme, Arnoud W J van 't Hof

{"title":"Mass balance and metabolite profiling of 14C-Zalunfiban in humans following single-dose subcutaneous administration.","authors":"Robert B MacArthur, Sem A O F Rikken, Spandana R Vootukuri, Barry S Coller, C Michael Gibson, Christopher B Granger, G Montalescot, Jurriën M Ten Berg, Murray P Ducharme, Arnoud W J van 't Hof","doi":"10.1080/00498254.2025.2597225","DOIUrl":"10.1080/00498254.2025.2597225","url":null,"abstract":"The human metabolic and excretion profile of zalunfiban, a novel glycoprotein IIb/IIIa inhibitor, was studied in a phase 1 clinical trial.14C-zalunfiban was administered subcutaneously as a single fixed dose (9.5 mg with 5 μCi total radioactivity).Zalunfiban whole blood concentrations were measured using liquid chromatography-mass spectrometry. 14C-zalunfiban and metabolites were measured using liquid scintillation counting and accelerator mass spectrometry in whole blood, urine, and faeces. Eight participants were enrolled. Zalunfiban was well-tolerated.Following injection zalunfiban was detectable within 5 minutes and the last measurable concentration was observed within 4 hours. The median Tmax was 0.25 hours and mean half-life was 0.96 hours. Zalunfiban accounted for 35.6% of total whole blood radioactivity AUC at 4 hours. The single major identified metabolite was des-gly-zalunfiban (M1), which has <1% of zalunfiban's antiplatelet activity. M1 was the primary urinary metabolite (52.98% of dose) with minor amounts of zalunfiban (1.31%) detected. M1 was also the major metabolite in faeces (2.87%). Total dose recovery reached >90% by 240 hours.Zalunfiban is rapidly metabolised to the nearly inactive M1 metabolite, which is excreted primarily in urine. Renal impairment, therefore, is unlikely to significantly prolong zalunfiban effects and dose adjustment in patients with reduced renal function may not be required.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-10"},"PeriodicalIF":1.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145655673","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}

引用次数: 0

Methyl mercury pharmacokinetics in man: a five-compartment hybrid model. 甲基汞在人体内的药代动力学：一个5室混合模型。

IF 1.2 4区医学

Xenobiotica Pub Date : 2026-01-01 Epub Date: 2025-12-21 DOI: 10.1080/00498254.2025.2598387

Fred Farris, Ayda Awaness, Arman Kiledjian, Janna Mozannar, Michael Chuvanjyan, Joe Su

引用次数: 0

l-Arginine combined with 5-fluorouracil inhibits EMT by regulating iNOS expression in hepatocellular carcinoma. l -精氨酸联合5-氟尿嘧啶通过调节肝细胞癌中iNOS的表达抑制EMT。

IF 1.2 4区医学

Xenobiotica Pub Date : 2026-01-01 Epub Date: 2025-12-15 DOI: 10.1080/00498254.2025.2599958

Han Wang, Yao Lu, Sisi Cheng, Yining Zhang, Yiying Li, Qingzan Zhao, Ling Liu

引用次数: 0

Unravelling the toxic potential of imidacloprid and chlorothalonil in thyroid, liver, and kidney of rats: a combined experimental and computational investigations. 揭示吡虫啉和百菌清对大鼠甲状腺、肝脏和肾脏的潜在毒性：一项结合实验和计算的研究。

IF 1.2 4区医学

Xenobiotica Pub Date : 2025-10-01 Epub Date: 2025-12-10 DOI: 10.1080/00498254.2025.2592099

Samia Belahcene, Widad Kebsa, Gagandeep Singh, Essaid Leghouchi

{"title":"Unravelling the toxic potential of imidacloprid and chlorothalonil in thyroid, liver, and kidney of rats: a combined experimental and computational investigations.","authors":"Samia Belahcene, Widad Kebsa, Gagandeep Singh, Essaid Leghouchi","doi":"10.1080/00498254.2025.2592099","DOIUrl":"10.1080/00498254.2025.2592099","url":null,"abstract":"This investigation was planned to evaluate the mechanistic interactions of Imidacloprid (IM) and Chlorothalonil (CL), inducing toxicity after 28 days of oral administration. Male Wistar rats were divided into a control (CR) and three treatment groups, receiving IM (45 mg/kg), CL (300 mg/kg), and mixture of IM+CL.IM and CL,individually or in combination induced a hypothyroidstate with a sharp decline in insulin levels. Additionally, high plasma alanine transferase (ALT/SGPT) and aspartate transferase (AST/SGOT) levels, as well as alkaline phosphatase (Alk-P) and creatinine were recorded in all treated groups. Both IM and CL significantly compromised the antioxidant defense system by increasing the MDA level, and inhibiting the activity of CAT and SOD.A significant binding affinity of IM and CL to enzymes integral to the blood transport and receptor binding of THs like MCT8 and TSHR was observed. The MD simulations revealed the strong and stable interactions between IM, CL, MCT8, and TSH-R. MMGBSA energies showed that both pesticides compete with hormones at active sites, indicating their potential to modulate key enzymes involved in thyroid hormone transport and action.Therefore, it is anticipated that these resultswill provide beneficial knowledge for future therapeutic endeavors.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"763-779"},"PeriodicalIF":1.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145565448","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}

引用次数: 0

Silver diamine fluoride, a caries restorative agent, induces cytotoxicity in primary human gingival fibroblasts. 氟化二胺银是一种龋修复剂，可诱导原代人牙龈成纤维细胞的细胞毒性。

IF 1.2 4区医学

Xenobiotica Pub Date : 2025-10-01 Epub Date: 2025-11-18 DOI: 10.1080/00498254.2025.2590033

George Mathew Mebin, Perumal Elumalai, Subramanian Raghunandhakumar, Devaraj Ezhilarasan

{"title":"Silver diamine fluoride, a caries restorative agent, induces cytotoxicity in primary human gingival fibroblasts.","authors":"George Mathew Mebin, Perumal Elumalai, Subramanian Raghunandhakumar, Devaraj Ezhilarasan","doi":"10.1080/00498254.2025.2590033","DOIUrl":"10.1080/00498254.2025.2590033","url":null,"abstract":"Silver diamine fluoride (SDF) is commonly used in clinical settings to manage dental caries in young children. A major drawback of SDF is its tendency to darken carious lesions, turning them brown or black, which has drawn criticism. This study investigates the cytotoxic effects of SDF on human gingival fibroblasts (hGF).hGF cells were exposed to varying concentrations of SDF (0.0001%, 0.001%, and 0.005%) for a 24-hour period. We analysed cytotoxicity, the potential for reactive oxygen species (ROS) production, mitochondrial function, morphological indicators of apoptosis, and key molecular markers of apoptosis.The findings revealed that SDF exposure led to significant, dose-dependent cytotoxicity and ROS generation in hGF. Morphological changes consistent with apoptosis were observed. Furthermore, SDF disrupted the balance of Bax and Bcl-2 proteins and reduced the expression of proliferating cell nuclear antigen in these cells. In animal studies, single SDF application for 3 h resulted in mild structural alterations of gingival tissue and basilar hyperplasia in rats.Overall, the findings demonstrate that SDF exhibits cytotoxicity towards hGF, primarily through intracellular ROS production and subsequent apoptosis. Additionally, the in vivo experiments validate the mild toxic effects of SDF on rat gingival tissues. Developing controlled drug delivery approaches could help mitigate SDF's toxicity in clinical applications.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"753-762"},"PeriodicalIF":1.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145514373","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}

引用次数: 0