Drug Metabolism Reviews最新文献_第5页

Antitubercular drugs induced liver injury: an updated insight into molecular mechanisms. 抗结核药物诱导肝损伤:对分子机制的最新见解。

IF 5.9 2区医学

Drug Metabolism Reviews Pub Date : 2023-08-01 DOI: 10.1080/03602532.2023.2215478

Devaraj Ezhilarasan

{"title":"Antitubercular drugs induced liver injury: an updated insight into molecular mechanisms.","authors":"Devaraj Ezhilarasan","doi":"10.1080/03602532.2023.2215478","DOIUrl":"https://doi.org/10.1080/03602532.2023.2215478","url":null,"abstract":"Tuberculosis (TB) remains a major global health burden. Antitubercular drugs (ATDs) such as isoniazid (INH), rifampicin (RIF), pyrazinamide (PZA), and ethambutol are used as first-line therapy in TB patients. Drug-induced liver injury is one of the common side effects that leads to the discontinuation of ATDs in TB patients. Therefore, this review discusses the molecular pathogenesis of ATDs induced liver injury. The biotransformation of INH, RIF, and PZA in the liver liberates several reactive intermediates, leading to peroxidation of the hepatocellular membrane and oxidative stress. INH + RIF administration decreased the expression of bile acid transporters such as the bile salt export pump and multidrug resistance-associated protein 2 and induced liver injury by sirtuin 1 and farnesoid X receptor pathway. INH inhibits the nuclear translocation of Nrf2 by interfering with its nuclear importer, karyopherin β1, thereby inducing apoptosis. INF + RIF treatments alter Bcl-2 and Bax homeostasis, mitochondrial membrane potential, and cytochrome c release, thereby triggering apoptosis. RIF administration enhances the expression of genes involved in fatty acid synthesis and hepatocyte fatty acid uptake (CD36). RIF induces the expression of peroxisome proliferator-activated receptor -γ and its downstream proteins and perilipin-2 by activating the pregnane X receptor in the liver to increase fatty infiltration into the liver. ATDs administration induces oxidative stress, inflammation, apoptosis, cholestasis, and lipid accumulation in the liver. However, ATDs toxic potentials are not elaborately studied at the molecular level in clinical samples. Therefore, future studies are warranted to explore ATDs induced liver injuries at the molecular level in clinical samples whenever possible.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":"55 3","pages":"239-253"},"PeriodicalIF":5.9,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9882324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Bufalin serves as a pharmaceutic that mitigates drug resistance. 蟾毒灵是一种减轻耐药性的药物。

IF 5.9 2区医学

Drug Metabolism Reviews Pub Date : 2023-08-01 DOI: 10.1080/03602532.2023.2206065

Linxuan Miao, Ying Liu, Nasra Mohamoud Ali, Yan Dong, Bin Zhang, Xiaonan Cui

引用次数: 2

Plasma protein-mediated uptake and contradictions to the free drug hypothesis: a critical review. 血浆蛋白介导的摄取和游离药物假说的矛盾:一个重要的回顾。

IF 5.9 2区医学

Drug Metabolism Reviews Pub Date : 2023-08-01 DOI: 10.1080/03602532.2023.2195133

Julia Annette Schulz, David M Stresser, John Cory Kalvass

{"title":"Plasma protein-mediated uptake and contradictions to the free drug hypothesis: a critical review.","authors":"Julia Annette Schulz, David M Stresser, John Cory Kalvass","doi":"10.1080/03602532.2023.2195133","DOIUrl":"https://doi.org/10.1080/03602532.2023.2195133","url":null,"abstract":"According to the free drug hypothesis (FDH), only free, unbound drug is available to interact with biological targets. This hypothesis is the fundamental principle that continues to explain the vast majority of all pharmacokinetic and pharmacodynamic processes. Under the FDH, the free drug concentration at the target site is considered the driver of pharmacodynamic activity and pharmacokinetic processes. However, deviations from the FDH are observed in hepatic uptake and clearance predictions, where observed unbound intrinsic hepatic clearance (CLint,u) is larger than expected. Such deviations are commonly observed when plasma proteins are present and form the basis of the so-called plasma protein-mediated uptake effect (PMUE). This review will discuss the basis of plasma protein binding as it pertains to hepatic clearance based on the FDH, as well as several hypotheses that may explain the underlying mechanisms of PMUE. Notably, some, but not all, potential mechanisms remained aligned with the FDH. Finally, we will outline possible experimental strategies to elucidate PMUE mechanisms. Understanding the mechanisms of PMUE and its potential contribution to clearance underprediction is vital to improving the drug development process.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":"55 3","pages":"205-238"},"PeriodicalIF":5.9,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10249197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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: 2

The alteration of drug metabolism enzymes and pharmacokinetic parameters in nonalcoholic fatty liver disease: current animal models and clinical practice. 非酒精性脂肪性肝病中药物代谢酶和药代动力学参数的改变:目前的动物模型和临床实践

IF 5.9 2区医学

Drug Metabolism Reviews Pub Date : 2023-08-01 DOI: 10.1080/03602532.2023.2202359

Yan Zhu, Li Chen, Yuqi He, Lin Qin, Daopeng Tan, Zhaojun Bai, Yu Song, Yuhe Wang

{"title":"The alteration of drug metabolism enzymes and pharmacokinetic parameters in nonalcoholic fatty liver disease: current animal models and clinical practice.","authors":"Yan Zhu, Li Chen, Yuqi He, Lin Qin, Daopeng Tan, Zhaojun Bai, Yu Song, Yuhe Wang","doi":"10.1080/03602532.2023.2202359","DOIUrl":"https://doi.org/10.1080/03602532.2023.2202359","url":null,"abstract":"Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease. The whole concept of NAFLD has now moved into metabolic dysfunction-associated fatty liver disease (MAFLD) to emphasize the strong metabolic derangement as the basis of the disease. Several studies have suggested that hepatic gene expression was altered in NAFLD and NAFLD-related metabolic comorbidities, particularly mRNA and protein expression of phase I and II drug metabolism enzymes (DMEs). NAFLD may affect the pharmacokinetic parameters. However, there were a limited number of pharmacokinetic studies on NAFLD at present. Determining the pharmacokinetic variation in patients with NAFLD remains challenging. Common modalities for modeling NAFLD included: dietary induction, chemical induction, or genetic models. The altered expression of DMEs has been found in rodent and human samples with NAFLD and NAFLD-related metabolic comorbidities. We summarized the pharmacokinetic changes of clozapine (CYP1A2 substrate), caffeine (CYP1A2 substrate), omeprazole (Cyp2c29/CYP2C19 substrate), chlorzoxazone (CYP2E1 substrate), midazolam (Cyp3a11/CYP3A4 substrate) in NAFLD. These results led us to wonder whether current drug dosage recommendations may need to be reevaluated. More objective and rigorous studies are required to confirm these pharmacokinetic changes. We have also summarized the substrates of the DMEs aforementioned. In conclusion, DMEs play an important role in the metabolism of drugs. We hope that future investigations should focus on the effect and alteration of DMEs and pharmacokinetic parameters in this special patient population with NAFLD.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":"55 3","pages":"163-180"},"PeriodicalIF":5.9,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9881794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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: 1

Physiological and pathophysiological roles of hepoxilins and their analogs. 血红素及其类似物的生理和病理生理作用。

IF 5.9 2区医学

Drug Metabolism Reviews Pub Date : 2023-08-01 DOI: 10.1080/03602532.2023.2219035

Sara A Helal, Fadumo Ahmed Isse, Samar H Gerges, Ayman O S El-Kadi

{"title":"Physiological and pathophysiological roles of hepoxilins and their analogs.","authors":"Sara A Helal, Fadumo Ahmed Isse, Samar H Gerges, Ayman O S El-Kadi","doi":"10.1080/03602532.2023.2219035","DOIUrl":"https://doi.org/10.1080/03602532.2023.2219035","url":null,"abstract":"The metabolism of arachidonic acid (AA) occurs via different pathways leading to the production of a great number of metabolites with a wide range of biological effects. Hepoxilins (HXs) are physiologically active AA metabolites produced through the lipoxygenase pathway. Since their discovery, several researchers have investigated their biological effects. They were proven to have pro-inflammatory, anti-apoptotic, and skin-protective effects. HXs also contribute to the processes of neutrophil activation and migration and inflammatory hyperalgesia. The major limitation to their effects is that they are highly labile and are metabolized into less active compounds which led to the synthesis of stable HXs analogs called proprietary bioactive therapeutics (PBTs). Although PBTs were synthesized to further study the effect of HXs, they showed different effects than natural HXs under some conditions. PBTs were proven to have anti-inflammatory and anti-cancer effects and were found to be potent antagonists of the thromboxane receptor. In this review article, we aimed to provide an overview of some physiological and pathophysiological effects of hepoxilins and their analogs on the skin, platelet, blood vessel, neutrophil, and cell survival.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":"55 3","pages":"254-266"},"PeriodicalIF":5.9,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10274610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Relationship between blood-brain barrier changes and drug metabolism under high-altitude hypoxia: obstacle or opportunity for drug transport? 高原缺氧条件下血脑屏障变化与药物代谢的关系:药物转运的障碍还是机遇?

IF 5.9 2区医学

Drug Metabolism Reviews Pub Date : 2023-02-01 DOI: 10.1080/03602532.2023.2180028

Guiqin Liu, Xue Bai, Jianxin Yang, Yabin Duan, Junbo Zhu, Li Xiangyang

{"title":"Relationship between blood-brain barrier changes and drug metabolism under high-altitude hypoxia: obstacle or opportunity for drug transport?","authors":"Guiqin Liu, Xue Bai, Jianxin Yang, Yabin Duan, Junbo Zhu, Li Xiangyang","doi":"10.1080/03602532.2023.2180028","DOIUrl":"https://doi.org/10.1080/03602532.2023.2180028","url":null,"abstract":"The blood-brain barrier is essential for maintaining the stability of the central nervous system and is also crucial for regulating drug metabolism, changes of blood-brain barrier's structure and function can influence how drugs are delivered to the brain. In high-altitude hypoxia, the central nervous system's function is drastically altered, which can cause disease and modify the metabolism of drugs in vivo. Changes in the structure and function of the blood-brain barrier and the transport of the drug across the blood-brain barrier under high-altitude hypoxia, are regulated by changes in brain microvascular endothelial cells, astrocytes, and pericytes, either regulated by drug metabolism factors such as drug transporters and drug-metabolizing enzymes. This article aims to review the effects of high-altitude hypoxia on the structure and function of the blood-brain barrier as well as the effects of changes in the blood-brain barrier on drug metabolism. We also hypothesized and explore the regulation and potential mechanisms of the blood-brain barrier and associated pathways, such as transcription factors, inflammatory factors, and nuclear receptors, in regulating drug transport under high-altitude hypoxia.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":"55 1-2","pages":"107-125"},"PeriodicalIF":5.9,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9501098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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: 1

Effects of intestinal flora on pharmacokinetics and pharmacodynamics of drugs. 肠道菌群对药物药代动力学和药效学的影响。

IF 5.9 2区医学

Drug Metabolism Reviews Pub Date : 2023-02-01 DOI: 10.1080/03602532.2023.2186313

Amina Džidić-Krivić, Jasna Kusturica, Emina Karahmet Sher, Nejra Selak, Nejra Osmančević, Esma Karahmet Farhat, Farooq Sher

{"title":"Effects of intestinal flora on pharmacokinetics and pharmacodynamics of drugs.","authors":"Amina Džidić-Krivić, Jasna Kusturica, Emina Karahmet Sher, Nejra Selak, Nejra Osmančević, Esma Karahmet Farhat, Farooq Sher","doi":"10.1080/03602532.2023.2186313","DOIUrl":"https://doi.org/10.1080/03602532.2023.2186313","url":null,"abstract":"Gut microbiota is known as unique collection of microorganisms (including bacteria, archaea, eukaryotes and viruses) that exist in a complex environment of the gut. Recently, this has become one of the most popular areas of research in medicine because this plays not only an important role in disease development, but gut microbiota also influences drug pharmacokinetics. These alterations in drug pharmacokinetic pathways and drug concentration in plasma and blood often lead to an increase in the incidence of toxicological events in patients. This review aims to present current knowledge of the most commonly used drugs in clinical practice and their dynamic interplay with the host's gut microbiota as well as the mechanisms underlying these metabolic processes and the consequent effect on their therapeutic efficacy and safety. These new findings set a foundation for the development of personalized treatments specific to each metabolism, maximizing drugs' therapeutic effects and minimizing the side effects because they are one of the major limiting factors in treating patients.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":"55 1-2","pages":"126-139"},"PeriodicalIF":5.9,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9501564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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: 9

Metabolic activation of tyrosine kinase inhibitors: recent advance and further clinical practice. 酪氨酸激酶抑制剂的代谢激活：最新进展和进一步临床实践。

IF 5.9 2区医学

Drug Metabolism Reviews Pub Date : 2023-02-01 Epub Date: 2022-12-01 DOI: 10.1080/03602532.2022.2149775

Miao Yan, Wenqun Li, Wen-Bo Li, Qi Huang, Jing Li, Hua-Lin Cai, Hui Gong, Bi-Kui Zhang, Yi-Kun Wang

{"title":"Metabolic activation of tyrosine kinase inhibitors: recent advance and further clinical practice.","authors":"Miao Yan, Wenqun Li, Wen-Bo Li, Qi Huang, Jing Li, Hua-Lin Cai, Hui Gong, Bi-Kui Zhang, Yi-Kun Wang","doi":"10.1080/03602532.2022.2149775","DOIUrl":"10.1080/03602532.2022.2149775","url":null,"abstract":"At present, receptor tyrosine kinase signaling-related pathways have been successfully mediated to inhibit tumor proliferation and promote anti-angiogenesis effects for cancer therapy. Tyrosine kinase inhibitors (TKIs), a group of novel chemotherapeutic agents, have been applied to treat diverse malignant tumors effectively. However, the latent toxic and side effects of TKIs, such as hepatotoxicity and cardiotoxicity, limit their use in clinical practice. Metabolic activation has the potential to lead to toxic effects. Numerous TKIs have been demonstrated to be transformed into chemically reactive/potentially toxic metabolites following cytochrome P450-catalyzed activation, which causes severe adverse reactions, including hepatotoxicity, cardiotoxicity, skin toxicity, immune injury, mitochondria injury, and cytochrome P450 inactivation. However, the precise mechanisms of how these chemically reactive/potentially toxic species induce toxicity remain poorly understood. In addition, we present our viewpoints that regulating the production of reactive metabolites may decrease the toxicity of TKIs. Exploring this topic will improve understanding of metabolic activation and its underlying mechanisms, promoting the rational use of TKIs. This review summarizes the updated evidence concerning the reactive metabolites of TKIs and the associated toxicities. This paper provides novel insight into the safe use of TKIs and the prevention and treatment of multiple TKIs adverse effects in clinical practice.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":"55 1-2","pages":"94-106"},"PeriodicalIF":5.9,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10183671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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: 1

3D self-assembled nanocarriers for drug delivery. 用于药物递送的三维自组装纳米载体。

IF 5.9 2区医学

Drug Metabolism Reviews Pub Date : 2023-02-01 DOI: 10.1080/03602532.2023.2172182

Hossein Karballaei Mirzahosseini, Mojgan Sheikhi, Farhad Najmeddin, Mehrnoosh Shirangi, Mojtaba Mojtahedzadeh

{"title":"3D self-assembled nanocarriers for drug delivery.","authors":"Hossein Karballaei Mirzahosseini, Mojgan Sheikhi, Farhad Najmeddin, Mehrnoosh Shirangi, Mojtaba Mojtahedzadeh","doi":"10.1080/03602532.2023.2172182","DOIUrl":"https://doi.org/10.1080/03602532.2023.2172182","url":null,"abstract":"There are many benefits to drug delivery from drug-carrier nanostructure systems. It might be developed to carefully control drug release rates or to deliver a precise amount of a therapeutic substance to particular body areas. Self-assembling is the process by which molecules and nanoparticles spontaneously organize into organized clusters. For instance, proteins and peptides can interact with one another to create highly organized supramolecular structures with various properties, such as helical ribbons and fibrous scaffolds. Another advantage of self-assembly is that it may be effective with a variety of materials, including metals, oxides, inorganic salts, polymers, semiconductors, and even organic semiconductors. Fullerene, graphene, and carbon nanotubes (CNTs), three of the most fundamental classes of three-dimensionally self-assembling nanostructured carbon-based materials, are essential for the development of modern nanotechnologies. Self-assembled nanomaterials are used in a variety of fields, including nanotechnology, imaging, and biosensors. This review study begins with a summary of various major 3D nanomaterials, including graphene oxide, CNTs, and nanodiamond, as well as 3D self-assembled polyfunctionalized nanostructures and adaptable nanocarriers for drug delivery.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":"55 1-2","pages":"140-162"},"PeriodicalIF":5.9,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10182021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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: 2

Effect of inflammation on cytochrome P450-mediated arachidonic acid metabolism and the consequences on cardiac hypertrophy. 炎症对细胞色素p450介导的花生四烯酸代谢的影响及其对心肌肥厚的影响。

IF 5.9 2区医学

Drug Metabolism Reviews Pub Date : 2023-02-01 DOI: 10.1080/03602532.2022.2162075

Mohammed A W ElKhatib, Fadumo Ahmed Isse, Ayman O S El-Kadi

{"title":"Effect of inflammation on cytochrome P450-mediated arachidonic acid metabolism and the consequences on cardiac hypertrophy.","authors":"Mohammed A W ElKhatib, Fadumo Ahmed Isse, Ayman O S El-Kadi","doi":"10.1080/03602532.2022.2162075","DOIUrl":"https://doi.org/10.1080/03602532.2022.2162075","url":null,"abstract":"The incidence of heart failure (HF) is generally preceded by cardiac hypertrophy (CH), which is the enlargement of cardiac myocytes in response to stress. During CH, the metabolism of arachidonic acid (AA), which is present in the cell membrane phospholipids, is modulated. Metabolism of AA gives rise to hydroxyeicosatetraenoic acids (HETEs) and epoxyeicosatrienoic acids (EETs) via cytochrome P450 (CYP) ω-hydroxylases and CYP epoxygenases, respectively. A plethora of studies demonstrated the involvement of CYP-mediated AA metabolites in the pathogenesis of CH. Also, inflammation is known to be a characteristic hallmark of CH. In this review, our aim is to highlight the impact of inflammation on CYP-derived AA metabolites and CH. Inflammation is shown to modulate the expression of various CYP ω-hydroxylases and CYP epoxygenases and their respective metabolites in the heart. In general, HETEs such as 20-HETE and mid-chain HETEs are pro-inflammatory, while EETs are characterized by their anti-inflammatory and cardioprotective properties. Several mechanisms are implicated in inflammation-induced CH, including the modulation of NF-κB and MAPK. This review demonstrated the inflammatory modulation of cardiac CYPs and their metabolites in the context of CH and the anti-inflammatory strategies that can be employed in the treatment of CH and HF.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":"55 1-2","pages":"50-74"},"PeriodicalIF":5.9,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9553624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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: 4