Xenobiotica最新文献_第8页

The metabolism of the orexin-1 selective receptor antagonist nivasorexant. 俄勒欣-1 选择性受体拮抗剂 Nivasorexant 的新陈代谢

IF 1.8 4区医学

Xenobiotica Pub Date : 2024-03-01 DOI: 10.1080/00498254.2024.2319811

Alexander Treiber, Swen Seeland, Belal Haschimi, Aude Weigel, Jodi T Williams, Jerome Gabillet

引用次数: 0

Rehmannioside A inhibits the activity of CYP3A4, 2C9 and 2D6 in vitro 地黄甙 A 在体外可抑制 CYP3A4、2C9 和 2D6 的活性

IF 1.8 4区医学

Xenobiotica Pub Date : 2024-02-22 DOI: 10.1080/00498254.2024.2321969

Congrong Wang, Naixiang Zhou, Mingcui Li, Haixia Chen

引用次数: 0

Indirubin mediates adverse intestinal reactions in guinea pigs by downregulating the expression of AchE through AhR. 靛蓝通过 AhR 下调 AchE 的表达，从而介导豚鼠肠道不良反应。

IF 1.8 4区医学

Xenobiotica Pub Date : 2024-02-01 Epub Date: 2024-01-08 DOI: 10.1080/00498254.2023.2297745

Xiaoting Xu, Reham Taha, Chenghan Chu, Li Xiao, Tao Wang, Xinzhi Wang, Xin Huang, Zhenzhou Jiang, Lixin Sun

{"title":"Indirubin mediates adverse intestinal reactions in guinea pigs by downregulating the expression of AchE through AhR.","authors":"Xiaoting Xu, Reham Taha, Chenghan Chu, Li Xiao, Tao Wang, Xinzhi Wang, Xin Huang, Zhenzhou Jiang, Lixin Sun","doi":"10.1080/00498254.2023.2297745","DOIUrl":"10.1080/00498254.2023.2297745","url":null,"abstract":"Indirubin is the main component of the traditional Chinese medicine Indigo naturalis (IN), a potent agonist of aryl hydrocarbon receptors (AhRs). In China, IN is used to treat psoriasis and ulcerative colitis, and indirubin is used for the treatment of chronic myelogenous leukaemia. However, IN and indirubin have adverse reactions, such as abdominal pain, diarrhoea, and intussusception, and their specific mechanism is unclear.The purpose of our research was to determine the specific mechanism underlying the adverse effects of IN and indirubin. By tracking the modifications in guinea pigs after the intragastric administration of indirubin for 28 days.The results demonstrate that indirubin could accelerate bowel movements and decrease intestinal acetylcholinesterase (AchE) expression. Experiments with NCM460 cells revealed that indirubin significantly reduced the expression of AchE, and the AchE levels were increased after the silencing of AhR and re-exposure to indirubin.This study showed that the inhibition of AchE expression by indirubin plays a key role in the occurrence of adverse reactions to indirubin and that the underlying mechanism is related to AhR-mediated AchE downregulation.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"83-94"},"PeriodicalIF":1.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139075209","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

The effects of genetic polymorphism on toxicity and pharmacokinetics of methotrexate in Egyptian adult patients with leukaemia or lymphoma. 埃及成人白血病或淋巴瘤患者基因多态性对甲氨蝶呤毒性和药代动力学的影响

IF 1.8 4区医学

Xenobiotica Pub Date : 2024-02-01 Epub Date: 2024-03-05 DOI: 10.1080/00498254.2024.2320778

Khloud Shendy, Khaled Abdelkawy, Ahmed Amin Ali, Fathalla Belal, Mostafa Abdelhakiem, Galal Magdy, Nahla Anber, Fawzy Elbarbry

{"title":"The effects of genetic polymorphism on toxicity and pharmacokinetics of methotrexate in Egyptian adult patients with leukaemia or lymphoma.","authors":"Khloud Shendy, Khaled Abdelkawy, Ahmed Amin Ali, Fathalla Belal, Mostafa Abdelhakiem, Galal Magdy, Nahla Anber, Fawzy Elbarbry","doi":"10.1080/00498254.2024.2320778","DOIUrl":"10.1080/00498254.2024.2320778","url":null,"abstract":"Polymorphisms in genes coding folate-metabolising enzymes might alter the pharmacokinetics and sensitivity for methotrexate \"MTX\".The aim of the study aimed to investigate the influence of MTHFR C677T, DHFR19 Ins/del, GGH -401 C > T, and MTR A2756G polymorphisms on MTX toxicity and pharmacokinetics in Egyptian patients with Acute lymphoblastic leukaemia (ALL) or Non-Hodgkin lymphoma (NHL).Fifty adult Egyptian patients with ALL and NHL, treated with high dose MTX, were prospectively enrolled in the study. Clinical and biochemical data was collected objectively from medical records after each cycle of MTX. Plasma concentrations of MTX were measured after 72 h of initiation of infusion. Genotyping was done with a PCR-ARMS and PCR-RFLP assays.The MTHFR C677T T variants significantly increased the risk of leukopoenia, whereas the genotype MTHFR 677 C > T TT significantly associated with lymphocytopenia, thrombocytopenia, and anaemia. The genotype GGH-401 TT was significantly correlated with anaemia. Plasma MTX level was significantly higher in patients with MTR A2756G G variants.MTHFR polymorphism played the main role in MTX toxicities. The pharmacokinetics of MTX was affected by MTR polymorphism. GGH mutation was mainly concerned with anaemia. Pharmacogenetic testing are recommended to optimise MTX therapy.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"95-105"},"PeriodicalIF":1.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139913589","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

High-throughput assay to simultaneously evaluate activation of CYP3A and the direct and time-dependent inhibition of CYP3A, CYP2C9, and CYP2D6 using liquid chromatography-tandem mass spectrometry. 利用液相色谱-串联质谱法进行高通量测定，同时评估 CYP3A 的活化以及对 CYP3A、CYP2C9 和 CYP2D6 的直接和时间依赖性抑制。

IF 1.8 4区医学

Xenobiotica Pub Date : 2024-02-01 DOI: 10.1080/00498254.2024.2308818

Yu Yumoto, Takuro Endo, Hiroshi Harada, Kaoru Kobayashi, Takeshi Nakabayashi, Yoshikazu Abe

{"title":"High-throughput assay to simultaneously evaluate activation of CYP3A and the direct and time-dependent inhibition of CYP3A, CYP2C9, and CYP2D6 using liquid chromatography-tandem mass spectrometry.","authors":"Yu Yumoto, Takuro Endo, Hiroshi Harada, Kaoru Kobayashi, Takeshi Nakabayashi, Yoshikazu Abe","doi":"10.1080/00498254.2024.2308818","DOIUrl":"10.1080/00498254.2024.2308818","url":null,"abstract":"In the early stages of drug discovery, adequate evaluation of the potential drug-drug interactions (DDIs) of drug candidates is important. Several CYP3A activators are known to lead to underestimation of DDIs. These compounds affect midazolam 1'-hydroxylation but not midazolam 4-hydroxylation.We used both metabolic reactions of midazolam to evaluate the activation and inhibition of CYP3A activators simultaneously. For our CYP inhibition assay using cocktail probe substrates, simultaneous liquid chromatography-tandem mass spectrometry monitoring of 1'-hydroxymidazolam and 4-hydroxymidazolam for CYP3A was established in addition to monitoring of 4-hydroxydiclofenac and 1'-hydroxybufuralol for CYP2C9 and CYP2D6.The results of our cocktail inhibition assay were well correlated with those of a single inhibition assay, as were the estimated inhibition parameters for typical CYP3A inhibitors. In our assay, a proprietary compound that activated midazolam 1'-hydroxylation and tended to inhibit 4-hydroxylation was evaluated along with known CYP3A activators. All compounds were well characterised by comparison of the results of midazolam 1'- and 4-hydroxylation.In conclusion, our CYP cocktail inhibition assay can detect CYP3A activation and assess the direct and time-dependent inhibition potentials for CYP3A, CYP2C9, and CYP2D6. This method is expected to be very efficient in the early stages of drug discovery.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"45-56"},"PeriodicalIF":1.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139543142","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

Safflower yellow for injection enhances anti-coagulation of warfarin in rats: implications in pharmacodynamics and pharmacokinetics. 注射用红花黄色素可增强华法林对大鼠的抗凝作用：对药效学和药代动力学的影响

IF 1.8 4区医学

Xenobiotica Pub Date : 2024-02-01 Epub Date: 2024-03-13 DOI: 10.1080/00498254.2024.2326987

Yan Liu, Jiahui Sun, Chunjuan Yang, Mengnan Qin, Shiwei Xu, Yue Zhao, Gaofeng Liu

{"title":"Safflower yellow for injection enhances anti-coagulation of warfarin in rats: implications in pharmacodynamics and pharmacokinetics.","authors":"Yan Liu, Jiahui Sun, Chunjuan Yang, Mengnan Qin, Shiwei Xu, Yue Zhao, Gaofeng Liu","doi":"10.1080/00498254.2024.2326987","DOIUrl":"10.1080/00498254.2024.2326987","url":null,"abstract":"This study investigated whether Safflower Yellow for injection (SYI) would affect the anticoagulation of warfarin in rats.Wistar male rats were divided into six groups randomly and administered with SYI (9 mg/kg, intraperitoneal injection) in single-dose and steady-dose warfarin (0.2 mg/kg, oral gavage), respectively. The pharmacodynamic parameters of PT and APTT were measured by a coagulation analyser. R/S-warfarin concentration was measured by UHPLC-MS/MS, and pharmacokinetic parameters calculated using DAS 2.0 software.The single-dose study demonstrated that SYI, alone or co-administered with warfarin, could significantly increase PT, INR, and APTT values (p < 0.01). R-warfarin Cmax, AUC, and t1/2 values increased by 9.25% (p > 0.05), 25.96% (p < 0.01), and 26.17% (p < 0.01), respectively, whereas the CL/F value reduced by 22.22% (p < 0.01) in the presence of SYI. Meanwhile, S-warfarin Cmax, AUC, and t1/2 values increased by 37.41%, 32.11%, and 31.73% (all p < 0.01), respectively, whereas the CL/F value reduced by 33.33% (p < 0.01). The steady-dose study showed that PT, INR, APTT, and the concentrations of R/S-warfarin increased significantly when SYI was co-administered with warfarin (p < 0.01).SYI can enhance warfarin's anticoagulation intensity and decelerate its metabolism in rats.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"75-82"},"PeriodicalIF":1.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140040465","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

Preclinical characterization of the absorption and disposition of the brain penetrant PI3K/mTOR inhibitor paxalisib and prediction of its pharmacokinetics and efficacy in human. 脑穿透性 PI3K/mTOR 抑制剂帕沙利西的吸收和处置的临床前表征及其在人体中的药代动力学和药效预测

IF 1.8 4区医学

Xenobiotica Pub Date : 2024-02-01 Epub Date: 2024-01-15 DOI: 10.1080/00498254.2024.2303586

Laurent Salphati, Jodie Pang, Bruno Alicke, Emile G Plise, Jonathan Cheong, Allan Jaochico, Alan G Olivero, Deepak Sampath, Susan Wong, Xiaolin Zhang

{"title":"Preclinical characterization of the absorption and disposition of the brain penetrant PI3K/mTOR inhibitor paxalisib and prediction of its pharmacokinetics and efficacy in human.","authors":"Laurent Salphati, Jodie Pang, Bruno Alicke, Emile G Plise, Jonathan Cheong, Allan Jaochico, Alan G Olivero, Deepak Sampath, Susan Wong, Xiaolin Zhang","doi":"10.1080/00498254.2024.2303586","DOIUrl":"10.1080/00498254.2024.2303586","url":null,"abstract":"Glioblastoma multiforme (GBM) is the most common primary brain tumour in adults. Available treatments have not markedly improved patient survival in the last twenty years. However, genomic investigations have showed that the PI3K pathway is frequently altered in this glioma, making it a potential therapeutic target.Paxalisib is a brain penetrant PI3K/mTOR inhibitor (mouse Kp,uu 0.31) specifically developed for the treatment of GBM. We characterised the preclinical pharmacokinetics and efficacy of paxalisib and predicted its pharmacokinetics and efficacious dose in humans.Plasma protein binding of paxalisib was low, with the fraction unbound ranging from 0.25 to 0.43 across species. The hepatic clearance of paxalisib was predicted to be low in mice, rats, dogs and humans, and high in monkeys, from hepatocytes incubations. The plasma clearance was low in mice, moderate in rats and high in dogs and monkeys. Oral bioavailability ranged from 6% in monkeys to 76% in rats.The parameters estimated from the pharmacokinetic/pharmacodynamic modelling of the efficacy in the subcutaneous U87 xenograft model combined with the human pharmacokinetics profile predicted by PBPK modelling suggested that a dose of 56 mg may be efficacious in humans. Paxalisib is currently tested in Phase III clinical trials.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"64-74"},"PeriodicalIF":1.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139404602","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

Effect of tubeimoside I on the activity of cytochrome P450 enzymes in human liver microsomes. tubeimoside I 对人肝脏微粒体中细胞色素 P450 酶活性的影响。

IF 1.8 4区医学

Xenobiotica Pub Date : 2024-02-01 Epub Date: 2024-01-12 DOI: 10.1080/00498254.2023.2301352

Rui Wang, Kai Zheng, Yunjiao Liu, Shuxia Ji, Yaxin Tang, Jie Wang, Rong Jiang

{"title":"Effect of tubeimoside I on the activity of cytochrome P450 enzymes in human liver microsomes.","authors":"Rui Wang, Kai Zheng, Yunjiao Liu, Shuxia Ji, Yaxin Tang, Jie Wang, Rong Jiang","doi":"10.1080/00498254.2023.2301352","DOIUrl":"10.1080/00498254.2023.2301352","url":null,"abstract":"This study assessed the effect of tubeimoside I on CYP1A2, 2A6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4 to reveal the potential of tubeimoside I to induce drug-drug interaction.The evaluation of cytochromes P450 enzyme (CYP) activity was performed in pooled human liver microsomes with probing substrates of CYP1A2, 2A6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4. Typical inhibitors were employed as positive controls and the effect of 0, 2.5, 5, 10, 25, 50, and 100 μM tubeimoside I was investigated.The activity of CYP2D6, 2E1, and 3A4 was significantly inhibited by tubeimoside I with the IC50 values of 10.34, 11.58, and 9.74 μM, respectively. The inhibition of CYP2D6 and 2E1 was competitive with the Ki value of 5.66 and 5.29 μM, respectively. While the inhibition of CYP3A4 was non-competitive with the Ki value of 4.87 μM. Moreover, the inhibition of CYP3A4 was time-dependent with the KI and Kinact values of 0.635 μM-1 and 0.0373 min-1, respectively.Tubeimoside I served as a competitive inhibitor of CYP2D6 and 2E1 exerting weak inhibition and a non-competitive inhibitor of CYP3A4 exerting moderate inhibition.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"57-63"},"PeriodicalIF":1.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139080953","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

Metabolite characterisation of the peptide-drug conjugate LN005 in liver S9s by UHPLC-Orbitrap-HRMS. 肽-药物偶联物LN005在肝脏S9s代谢产物的UHPLC-Orbitrap-HRMS表征。

IF 1.8 4区医学

Xenobiotica Pub Date : 2024-01-01 Epub Date: 2024-01-08 DOI: 10.1080/00498254.2023.2289635

Yali Yuan, Weiqiang Wang, Jing Luo, Chongzhuang Tang, Yuandong Zheng, Jinghua Yu, Honghong Xu, Mingshe Zhu, Taijun Hang, Hao Wang, Xingxing Diao

{"title":"Metabolite characterisation of the peptide-drug conjugate LN005 in liver S9s by UHPLC-Orbitrap-HRMS.","authors":"Yali Yuan, Weiqiang Wang, Jing Luo, Chongzhuang Tang, Yuandong Zheng, Jinghua Yu, Honghong Xu, Mingshe Zhu, Taijun Hang, Hao Wang, Xingxing Diao","doi":"10.1080/00498254.2023.2289635","DOIUrl":"10.1080/00498254.2023.2289635","url":null,"abstract":"LN005 is a peptide-drug conjugate (PDC) targeting glucose-regulated protein 78 (GRP78) to treat several types of cancer, such as breast, colon, and prostate cancer.As a new drug modality, understanding its metabolism and elimination pathways will help us to have a whole picture of it. Currently, there are no metabolic studies on LN005; therefore, this study aimed to investigate the metabolism of LN005, clarify its metabolic profile in the liver S9s of different species, and identify the major metabolic pathways and differences between species.The incubation samples were measured by ultra-high performance liquid chromatography combined with orbitrap tandem mass spectrometry (UHPLC-Orbitrap-HRMS).The results showed that LN005 was metabolised by liver S9s, and four metabolites were identified. The main metabolic pathway of LN005 in liver S9s was oxidative deamination to ketone or hydrolysis. Similar metabolic profiles were observed in mouse, rat, dog, monkey, and human liver S9s, indicating no differences between these four animal species and humans.This study provides information for the structural modification and optimisation of LN005 and affords a reference for subsequent animal experiments and human metabolism of other PDCs.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-9"},"PeriodicalIF":1.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138478643","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

Dose proportionality and bioavailability of quinoxaline-based JNK inhibitor after single oral and intravenous administration in rats. 基于喹喔啉的 JNK 抑制剂在大鼠口服和静脉注射后的剂量比例和生物利用度

IF 1.8 4区医学

Xenobiotica Pub Date : 2024-01-01 Epub Date: 2024-01-02 DOI: 10.1080/00498254.2023.2299686

Galina A Frelikh, Elena A Yanovskaya, Alexander P Lakeev, Galina A Chernysheva, Vera I Smolyakova, Anastasia R Kovrizhina

{"title":"Dose proportionality and bioavailability of quinoxaline-based JNK inhibitor after single oral and intravenous administration in rats.","authors":"Galina A Frelikh, Elena A Yanovskaya, Alexander P Lakeev, Galina A Chernysheva, Vera I Smolyakova, Anastasia R Kovrizhina","doi":"10.1080/00498254.2023.2299686","DOIUrl":"10.1080/00498254.2023.2299686","url":null,"abstract":"The dose proportionality and bioavailability of the potential anti-inflammatory and neuroprotective JNK inhibitor 11H-indeno[1,2-b]quinoxalin-11-one oxime (IQ-1) were evaluated by comparing pharmacokinetic parameters after single oral (25, 50 and 100 mg/kg) and intravenous (1 mg/kg) IQ-1 administration in rats.IQ-1 and its major metabolite ketone 11H-indeno[1,2-b]quinoxalin-11-one (IQ-18) were isolated from plasma samples by liquid-liquid extraction. IQ-1 (E-isomer) and IQ-18 were simultaneously quantified in plasma by the validated method of liquid chromatography with triple quadrupole mass spectrometry (HPLC-MS/MS).The absolute bioavailability of IQ-1 was < 1.5%. Cmax values were 24.72 ± 4.30, 25.66 ± 7.11 and 37.61 ± 3.53 ng/mL after single oral administration of IQ-1 at doses of 25, 50 and 100 mg/kg, respectively. IQ-1 exhibited dose proportionality at 50-100 mg/kg dose levels, whereas its pharmacokinetics was not dose proportional over the range of 25-50 mg/kg. IQ-18 demonstrated the invariance of the dose-normalized Cmax.In this study we systematically elucidated the absorption characteristics of IQ-1 in rat gastrointestinal tract and provided better understanding of IQ-1 pharmacology for the future development of a new formulations and therapeutic optimisation.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"18-25"},"PeriodicalIF":1.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139049415","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