Expert opinion on drug metabolism & toxicology最新文献_第2页

Using validated model informed precision dosing for dose adjustment: superior evidence needed for efficacy and safety. 使用经过验证的模型进行剂量调整：疗效和安全性需要更好的证据。

Expert opinion on drug metabolism & toxicology Pub Date : 2025-07-01 Epub Date: 2025-05-07 DOI: 10.1080/17425255.2025.2501128

Slobodan M Janković, Nikola Mirković, Dobrivoje Stojadinović, Snežana Lukić

{"title":"Using validated model informed precision dosing for dose adjustment: superior evidence needed for efficacy and safety.","authors":"Slobodan M Janković, Nikola Mirković, Dobrivoje Stojadinović, Snežana Lukić","doi":"10.1080/17425255.2025.2501128","DOIUrl":"10.1080/17425255.2025.2501128","url":null,"abstract":"Introduction: Modelinformed precision dosing (MIPD) allows determining the optimal dosage regimen and its correction based on the target plasma/serum concentrations of the drug. MIPD software must go through a validation and clinical study of its effectiveness and safety before being used in clinical practice.Areas covered: This narrative literature review provides insight into what is known to date about efficacy and safety trials of MIPD concept. Relevant publications were searched for in the PubMed database, without time or language constraints.Expert opinion: The application of MIPD in clinical practice logically and theoretically has great potential to improve the treatment of patients by leading to optimal exposure of target tissues to drugs, while achieving full effect and minimizing toxicity. Greater implementation of MIPD in clinical practice is hindered by the fact that the beneficial effects of MIPD on treatment outcomes and reduction of drug toxicity have been proven through clinical studies only for a small number of drugs. It is necessary to conduct well-designed clinical studies of the effects of MIPD, with sufficient statistical power, to prove the benefits of MIPD administration and to justify the costs of implementation in clinical practice.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"801-810"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Drug-drug interaction between anti-seizure medications in Dravet syndrome and Lennox-Gastaut syndrome. 抗癫痫药物在dravet综合征和lenox -胃综合征中的药物相互作用。

Expert opinion on drug metabolism & toxicology Pub Date : 2025-07-01 Epub Date: 2025-06-07 DOI: 10.1080/17425255.2025.2510302

Roberta Roberti, Antonella Riva, Pasquale Striano, Emilio Russo

{"title":"Drug-drug interaction between anti-seizure medications in Dravet syndrome and Lennox-Gastaut syndrome.","authors":"Roberta Roberti, Antonella Riva, Pasquale Striano, Emilio Russo","doi":"10.1080/17425255.2025.2510302","DOIUrl":"10.1080/17425255.2025.2510302","url":null,"abstract":"Introduction: Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) are rare, severe epileptic encephalopathies requiring complex, individualized treatment due to drug-resistant seizures, non-seizure outcomes, and comorbidities. Polytherapy is an inevitable aspect of managing these conditions, making the management of drug-drug interactions (DDIs) crucial for optimizing efficacy, minimizing toxicity, and addressing broader patient needs.Areas covered: This review discusses current and emerging pharmacological therapies for seizures in DS and LGS. We explore documented and theoretical DDIs between these drugs and other antiseizure medications (ASMs), focusing on pharmacokinetic and pharmacodynamic characteristics. The clinical significance of these DDIs is emphasized, with practical recommendations for their management.Expert opinion: Advances in understanding DDIs are key to optimizing treatment, particularly through the combination of ASMs with distinct mechanisms of action. A rational therapeutic approach should consider not only seizure control but also comorbidities. Understanding metabolic pathways involved in pharmacokinetic interactions is essential for predicting and avoiding adverse effects. Digital tools and decision-support apps can assist clinicians in quickly assessing DDIs and selecting the most effective drug combinations. Ongoing research in pharmacogenetics and personalized medicine holds promise for improving the management of complex conditions like DS and LGS, offering potential for better, individualized therapeutic strategies.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"847-864"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mechanism-based drug safety testing using innovative in vitro liver models: from DILI prediction to idiosyncratic DILI liability assessment. 基于机制的药物安全性测试使用创新的体外肝脏模型：从DILI预测到特异性DILI责任评估。

Expert opinion on drug metabolism & toxicology Pub Date : 2025-07-01 Epub Date: 2025-06-11 DOI: 10.1080/17425255.2025.2516051

Sibel Bahtiri, Tessa M S Hagens, Bob van de Water, Marije Niemeijer

{"title":"Mechanism-based drug safety testing using innovative in vitro liver models: from DILI prediction to idiosyncratic DILI liability assessment.","authors":"Sibel Bahtiri, Tessa M S Hagens, Bob van de Water, Marije Niemeijer","doi":"10.1080/17425255.2025.2516051","DOIUrl":"10.1080/17425255.2025.2516051","url":null,"abstract":"Introduction: Idiosyncratic drug-induced liver injury (iDILI) remains unpredictable. As adverse responses arise in a small fraction of patients, drugs often fail in later drug development stages or post-approval, thereby tremendously increasing costs and putting patients at risk, highlighting the need for accurate early identification of iDILI liabilities.Covered areas: Using articles from the last 5 years (PubMed), iDILI risk factors are described, in vitro liver models and mechanism-based readout strategies are evaluated on their potential to enable iDILI liability assessment.Expert opinion: Various in vitro liver models are established for disease modeling and DILI prediction. Drawbacks for each of these seem inevitable, making the evaluation of their application domain and iDILI liability assessment potential crucial. A tiered approach could be considered, whereby compounds are initially screened and flagged using simple fit-for-purpose models for DILI prediction, followed by multicellular liver models that integrate the current knowledge of iDILI onset in combination with mechanistic readouts. Multiplexing models within an integrated mechanism-based testing strategy could improve the safety assessment accuracy. Defined in vitro models should integrate critical hepatocyte intrinsic risk factors as well as adaptive immune system components to refine iDILI liability assessment.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"769-787"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Interactions between phytotherapeutics and chemotherapeutics: the current evidence. 植物疗法和化学疗法之间的相互作用：目前的证据。

Expert opinion on drug metabolism & toxicology Pub Date : 2025-07-01 Epub Date: 2025-06-10 DOI: 10.1080/17425255.2025.2517733

Sarah Allegra, Francesco Chiara, Giuliana Abbadessa, Asia Di Pietro, Maura Caudana, Silvia De Francia

{"title":"Interactions between phytotherapeutics and chemotherapeutics: the current evidence.","authors":"Sarah Allegra, Francesco Chiara, Giuliana Abbadessa, Asia Di Pietro, Maura Caudana, Silvia De Francia","doi":"10.1080/17425255.2025.2517733","DOIUrl":"10.1080/17425255.2025.2517733","url":null,"abstract":"Introduction: The historical context of phytotherapy affects its potential as therapeutic products, and bioactive metabolites are crucial to the pharmacological effects, safety and effectiveness of alternative medicines.Areas covered: Phytotherapy is of great interest to cancer patients. Therefore, the purpose of this study was to gather publications about the interactions between chemotherapy and phytotherapeutics, medicinal plants, and similar formulations. To find publications published between January 2015 and January 2025, a MEDLINE PubMed search was conducted.Expert opinion: Several scientists and medical specialists have been looking into the potential of natural items to heal microbial cancer and chemotherapy-related adverse effects. The main factor influencing phytochemicals anticancer effectiveness is their ability to target a variety of pathways, including antimutagenic, antioxidant, and antiproliferative qualities. They can also regulate the host immune response to cancer by improving the surveillance of lymphocytes in cancer cells and lowering the inflammatory milieu. Because carcinogenesis is complex and involves a wide range of factors and signaling cascades, phytochemicals that target several targets may be useful anticancer drugs.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"831-845"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development and hepatotoxicity of rifamycin derivatives. 利福霉素衍生物的发展和肝毒性。

Expert opinion on drug metabolism & toxicology Pub Date : 2025-06-29 DOI: 10.1080/17425255.2025.2525451

Jiaojiao Zhang, Joshua Mattila, Peter Wipf, Xiaochao Ma

引用次数: 0

Transforming IBD care: the future of personalized therapy through multi-omics and pharmacogenomics. 改变IBD治疗：通过多组学和药物基因组学实现个性化治疗的未来。

Expert opinion on drug metabolism & toxicology Pub Date : 2025-06-26 DOI: 10.1080/17425255.2025.2521048

Niloofar Khoshnam Rad, Ghazal Roostaei, Shekoufeh Nikfar, Mohammad Abdollahi

{"title":"Transforming IBD care: the future of personalized therapy through multi-omics and pharmacogenomics.","authors":"Niloofar Khoshnam Rad, Ghazal Roostaei, Shekoufeh Nikfar, Mohammad Abdollahi","doi":"10.1080/17425255.2025.2521048","DOIUrl":"10.1080/17425255.2025.2521048","url":null,"abstract":"Introduction: Inflammatory bowel disease (IBD) treatment remains challenging, with many patients experiencing suboptimal responses despite advances in therapies. This necessitates more precise and personalized approaches.Areas covered: A literature search was conducted using Embase, Scopus, and PubMed (January 2000-March 2024) with keywords such as 'inflammatory bowel disease,' 'pharmacogenomics,' 'multi-omics,' and 'multi-omics.' This review discusses (1) key pharmacogenomic markers influencing drug metabolism, efficacy, and toxicity; (2) the role of multi-omics (genomics, proteomics, metabolomics) in elucidating IBD pathogenesis and predicting therapeutic outcomes; and (3) emerging technologies such as AI-driven predictive models and organoids. Challenges in translating these tools into clinical practice - including cost, data standardization, and workflow integration - are critically examined.Expert opinion: Integrating pharmacogenomics with multi-omics holds transformative potential for IBD care. While TPMT genotyping exemplifies current clinical utility, future frameworks will require harmonized multi-omic data to guide therapy selection. Key barriers include high costs of omics profiling, interpretative complexity, and clinician training gaps. Collaborative efforts among researchers, clinicians, and policymakers are essential to validate biomarkers, standardize methodologies, and implement cost-effective assays. Prioritizing real-world studies and AI-powered decision-support tools will accelerate the shift from trial-and-error to personalized IBD management.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"1-17"},"PeriodicalIF":0.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144487492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pharmacokinetic evaluation of concizumab for the treatment of hemophilia. 康珠单抗治疗血友病的药代动力学评价。

Expert opinion on drug metabolism & toxicology Pub Date : 2025-06-25 DOI: 10.1080/17425255.2025.2524873

Johnny Mahlangu

{"title":"Pharmacokinetic evaluation of concizumab for the treatment of hemophilia.","authors":"Johnny Mahlangu","doi":"10.1080/17425255.2025.2524873","DOIUrl":"10.1080/17425255.2025.2524873","url":null,"abstract":"Introduction: Replacement therapy is the global standard of care in hemophilia. However, several unmet needs have favored the development of non-factor therapies. Concizumab, an anti-tissue factor pathway inhibitor (anti-TFPI) administered daily, restores thrombin generation in all hemophilia subtypes.Areas covered: The pharmacokinetic profile of concizumab from several clinical trials demonstrates target-mediated drug disposition (TMDD) and a consistent exposure-response profile when given daily. Concizumab has an acceptable safe profile and efficacy in hemophilia A or B with and without inhibitors.Expert opinion: Despite the availability of diverse therapies for hemophilia management, unmet needs remain, including limited prophylaxis for hemophilia B inhibitor patients. Concizumab was developed to address this gap. Its target-mediated drug deposition results in a nonlinear pharmacokinetic profile and a need for a daily injection schedule, which ensures a stable, consistent, and sustained pharmacokinetic profile. While the daily injection may seem demanding, it does not compromise the optimal benefits of concizumab prophylaxis. Moreover, the acceptable safe profile and efficacy of concizumab in bleed prevention in hemophilia A or B with and without inhibitors provide reassurance that it may be a therapeutic option in managing all hemophilia patients.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144369878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chitosan-functionalized bentonite nanostructure as a promising compound to reduce the toxicity of aflatoxin B1: an in vitro and in vivo study. 壳聚糖功能化膨润土纳米结构作为降低黄曲霉毒素B1毒性的有前景的化合物：体外和体内研究。

Expert opinion on drug metabolism & toxicology Pub Date : 2025-06-24 DOI: 10.1080/17425255.2025.2522797

Behnam Ghorbani-Nejad, Mehdi Ranjbar, Motahareh Soltani, Ali Dini, Somayyeh Karami-Mohajeri, Mahdiyeh Lashkarizadeh, Mohammad Moradi Ghahderijani, Ali Mandegary, Mahmoud Reza Heidari, Payam Khazaeli, Iman Zangiabadi

{"title":"Chitosan-functionalized bentonite nanostructure as a promising compound to reduce the toxicity of aflatoxin B1: an in vitro and in vivo study.","authors":"Behnam Ghorbani-Nejad, Mehdi Ranjbar, Motahareh Soltani, Ali Dini, Somayyeh Karami-Mohajeri, Mahdiyeh Lashkarizadeh, Mohammad Moradi Ghahderijani, Ali Mandegary, Mahmoud Reza Heidari, Payam Khazaeli, Iman Zangiabadi","doi":"10.1080/17425255.2025.2522797","DOIUrl":"10.1080/17425255.2025.2522797","url":null,"abstract":"Introduction: This study aimed to evaluate the detoxification potential of chitosan-functionalized bentonite nanostructures (BT-CTS) against Aflatoxin B1 (AFB1), a hepatotoxic mycotoxin, using both in vitro and in vivo models. The experimental design included synthesis, characterization, and biological evaluation.Methods: BT-CTS was synthesized through co-sedimentation and characterized using SEM, FTIR, BET, and dynamic light scattering. In vitro cytotoxicity, reactive oxygen species (ROS) generation, and antioxidant status were assessed in HepG2 cells. In vivo, rats were administered AFB1 (12.5 µg/kg/day) with or without BT-CTS (5 g/kg). Oxidative stress markers, serum biochemistry, liver histology, and total antioxidant capacity (TAC) were evaluated.Results: BT-CTS exhibited a mean particle size of 98 nm and demonstrated a robust porous structure. The IC50 for BT-CTS on HepG2 cells was 5.10 mg/mL. BT-CTS reduced AFB1-induced cytotoxicity and ROS levels in vitro. In vivo, BT-CTS mitigated oxidative stress (lower protein carbonyls and lipid peroxidation), improved TAC, and preserved liver function and histological integrity.Conclusions: BT-CTS effectively counteracts AFB1-induced toxicity, demonstrating strong potential as a detoxifying agent. However, further studies are needed to confirm its long-term safety and efficacy across various biological systems.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"1-14"},"PeriodicalIF":0.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144334727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Adverse events of cephalosporins in the pediatric population: a comprehensive review. 头孢菌素在儿科人群中的不良事件：一项综合综述。

Expert opinion on drug metabolism & toxicology Pub Date : 2025-06-24 DOI: 10.1080/17425255.2025.2523511

Stef Schouwenburg, Merel Noomen, Enno D Wildschut, Matthijs de Hoog, Birgit C P Koch, Alan Abdulla

{"title":"Adverse events of cephalosporins in the pediatric population: a comprehensive review.","authors":"Stef Schouwenburg, Merel Noomen, Enno D Wildschut, Matthijs de Hoog, Birgit C P Koch, Alan Abdulla","doi":"10.1080/17425255.2025.2523511","DOIUrl":"10.1080/17425255.2025.2523511","url":null,"abstract":"Background: Cephalosporins are the second most prescribed antibiotics worldwide and are applied for a wide range of infective indications. However, there is limited information about the toxicity profile of cephalosporins in pediatrics. Consequently, the aim of this narrative review is to provide a complete overview of the toxicity associated with cephalosporin treatment in children.Areas covered: Adverse events (AEs) and toxicity of cephalosporin antibiotics in pediatrics are reviewed.Expert opinion/commentary: Overall, 35 studies concerning AEs in cephalosporins were identified. Most AEs were reported in the system organ classes (SOC) gastrointestinal (GI), infections and infestations, and skin and subcutaneous. For oral administration, the most common AE of the GI SOC were diarrhea with an incidence rate varying between from 0.6% to 15.2%, for which cefdinir was the most reported cephalosporin with AE. Observed incidence rates for a diverse spectrum of SOC and AEs varied widely due to heterogeneity in study populations and lack of AE reporting criteria. This narrative review provides a complete overview of reported AEs in literature caused by cephalosporins in pediatrics. In the future, cephalosporin therapeutic drug monitoring might provide insights into toxicity threshold concentrations.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144334726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evaluating the drug interactions in kratom usage: clinical application. 评价克拉通用药中的药物相互作用：临床应用。

Expert opinion on drug metabolism & toxicology Pub Date : 2025-06-22 DOI: 10.1080/17425255.2025.2521045

Leena R Dhoble, Abhishek Gour, Christopher R McCurdy, Abhisheak Sharma

{"title":"Evaluating the drug interactions in kratom usage: clinical application.","authors":"Leena R Dhoble, Abhishek Gour, Christopher R McCurdy, Abhisheak Sharma","doi":"10.1080/17425255.2025.2521045","DOIUrl":"10.1080/17425255.2025.2521045","url":null,"abstract":"Introduction: Mitragyna speciosa (Korth.) Havil. (Rubiaceae), commonly known as kratom, is a tropical tree native to Southeast Asia, traditionally used for its diverse ethnopharmacological activities, including analgesic and anxiolytic effects. Kratom's unique pharmacological profile allows it to function as a stimulant at low doses and produces opioid-like effects at high doses, making it a potential alternative for pain management and mitigation of opioid use disorder.Areas covered: Google Scholar and PubMed, along with FAERS database, were systematically searched to evaluate the clinical applications of kratom by examining its drug interactions, which can significantly impact the pharmacokinetics and pharmacodynamics of concomitant medications. By examining current evidence, this review aims to highlight the importance of establishing safe clinical practices and protocols for healthcare providers and patients.Expert opinion: Evaluating drug interactions in kratom usage is clinically imperative because kratom's bioactive alkaloids can interact with the pharmacokinetic and pharmacodynamic processes of concurrent medications, potentially resulting in adverse effects or compromised therapeutic outcomes. This review presents an expert opinion on the clinical relevance of kratom's interactions with drugs, aiming to inform clinical practice, highlight ethical and regulatory considerations, and propose future research directions to improve the understanding of kratom's pharmacological profile and enhance user safety.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"1-11"},"PeriodicalIF":0.0,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144304092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0