Regulatory Toxicology and Pharmacology最新文献_第7页

An analysis of the use of historical control data in the assessment of regulatory pesticide toxicity studies 分析历史控制数据在农药毒性监管研究评估中的应用。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-10-18 DOI: 10.1016/j.yrtph.2024.105724

Jürg A. Zarn, Sebastian L.B. König, Holly V. Shaw, H. Christoph Geiser

{"title":"An analysis of the use of historical control data in the assessment of regulatory pesticide toxicity studies","authors":"Jürg A. Zarn, Sebastian L.B. König, Holly V. Shaw, H. Christoph Geiser","doi":"10.1016/j.yrtph.2024.105724","DOIUrl":"10.1016/j.yrtph.2024.105724","url":null,"abstract":"<div><div>The concurrent control group is the most important reference for the interpretation of toxicity studies. However, pooled information on control animals from independent studies, <em>i.e.</em>, historical control data (HCD), is also used for the interpretation of results. Currently, an overview on actual HCD use in regulatory toxicology is lacking. Therefore, we evaluated the HCD use of the Joint FAO/WHO Meeting on Pesticide Residues from 2004 to 2021 and compared it with recommendations in regulatory guidelines and in the literature. We found that HCD was used routinely and exclusively to avoid potential false positive decisions regarding the treatment-relatedness of effects, mostly using the HCD range, <em>i.e.,</em> the most extreme values, as a benchmark. HCD were not used to avoid potential false negative decisions or for quality control of the index study. The central assumption of the HCD use, namely that the HCD and control group of the index study follow the same underlying distribution because they are samples of the same data generation process, was not investigated, although numerous factors potentially contribute to effect variation between the different control groups pooled in the HCD. We recommend that the existing guidelines be revised to improve the robustness and transparency of toxicological assessments.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"154 ","pages":"Article 105724"},"PeriodicalIF":3.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473315","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

In vivo micronucleus assay on sodium molybdate in rats and its impact on the overall assessment of the genotoxicity of molybdenum substances 钼酸钠大鼠体内微核试验及其对全面评估钼物质遗传毒性的影响。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-10-11 DOI: 10.1016/j.yrtph.2024.105717

Sue A. Hubbard , Kevin Klipsch , Michael S. Cockburn , Sandra Carey

引用次数: 0

Analysis of implicit and explicit uncertainties in QSAR prediction of chemical toxicity: A case study of neurotoxicity 化学毒性 QSAR 预测中的隐式和显式不确定性分析：神经毒性案例研究。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-10-10 DOI: 10.1016/j.yrtph.2024.105716

Jerry Achar , James W. Firman , Chantelle Tran , Daniella Kim , Mark T.D. Cronin , Gunilla Öberg

{"title":"Analysis of implicit and explicit uncertainties in QSAR prediction of chemical toxicity: A case study of neurotoxicity","authors":"Jerry Achar , James W. Firman , Chantelle Tran , Daniella Kim , Mark T.D. Cronin , Gunilla Öberg","doi":"10.1016/j.yrtph.2024.105716","DOIUrl":"10.1016/j.yrtph.2024.105716","url":null,"abstract":"<div><div>Although uncertainties expressed in texts within QSAR studies can guide quantitative uncertainty estimations, they are often overlooked during uncertainty analysis. Using neurotoxicity as an example, this study developed a method to support analysis of implicitly and explicitly expressed uncertainties in QSAR modeling studies. Text content analysis was employed to identify implicit and explicit uncertainty indicators, whereafter uncertainties within the indicator-containing sentences were identified and systematically categorized according to 20 uncertainty sources. Our results show that implicit uncertainty was more frequent within most uncertainty sources (13/20), while explicit uncertainty was more frequent in only three sources, indicating that uncertainty is predominantly expressed implicitly in the field. The most highly cited sources included Mechanistic plausibility, Model relevance and Model performance, suggesting they constitute sources of most concern. The fact that other sources like Data balance were not mentioned, although it is recognized in the broader QSAR literature as an area of concern, demonstrates that the output from the type of analysis conducted here must be interpreted in the context of the broader QSAR literature before conclusions are drawn. Overall, the method established here can be applied in other QSAR modeling contexts and ultimately guide efforts targeted towards addressing the identified uncertainty sources.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"154 ","pages":"Article 105716"},"PeriodicalIF":3.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406720","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

Selection of solvent and positive control concentration for enhanced Ames test conditions for N-nitrosamine compounds 针对 N-亚硝胺化合物的强化 Ames 试验条件，选择溶剂和阳性对照浓度

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-10-10 DOI: 10.1016/j.yrtph.2024.105711

Chetan K. Kajavadara, Satyam N. Patel, Rushikesh M. Shukla, Darshan T. Valani, Rajesh J. Patel, Laxit K. Bhatt, Rajesh Sundar, Mukul R. Jain

{"title":"Selection of solvent and positive control concentration for enhanced Ames test conditions for N-nitrosamine compounds","authors":"Chetan K. Kajavadara, Satyam N. Patel, Rushikesh M. Shukla, Darshan T. Valani, Rajesh J. Patel, Laxit K. Bhatt, Rajesh Sundar, Mukul R. Jain","doi":"10.1016/j.yrtph.2024.105711","DOIUrl":"10.1016/j.yrtph.2024.105711","url":null,"abstract":"<div><div>The Ames test is a widely used bacterial mutagenicity assay to evaluate the potential of chemical compounds to induce mutations. In recent years, there has been growing concern regarding the presence of N-nitrosamines in pharmaceuticals, food, and other consumer products. N-Nitrosamines are probable mutagens and carcinogens. To address the reduced sensitivity of the standard Ames test for N-nitrosamines, particularly N-nitrosodimethylamine, the European Medicines Agency (EMA) and United States Food and Drug Administration (FDA) have recently published recommendations for enhanced Ames test (EAT) conditions. However, there is a lack of clear guidance on the selection of N-nitrosamine positive control concentrations, particularly for 1-cyclopentyl-4-nitrosopiperazine, and the amount of solvent to be used in the EAT. This study aims to address the current gap in concentration and volume specifications by providing a comprehensive guide to set up enhanced Ames test conditions specifically for N-nitrosamine compounds using appropriate amounts of solvent, new solvents, and strain-specific positive control concentrations.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"154 ","pages":"Article 105711"},"PeriodicalIF":3.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434368","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

Safety assessment of drug impurities for patient safety: A comprehensive review 针对患者安全的药物杂质安全评估：全面综述。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-10-05 DOI: 10.1016/j.yrtph.2024.105715

Frank Liu

{"title":"Safety assessment of drug impurities for patient safety: A comprehensive review","authors":"Frank Liu","doi":"10.1016/j.yrtph.2024.105715","DOIUrl":"10.1016/j.yrtph.2024.105715","url":null,"abstract":"<div><div>Drug impurities are undesirable but unavoidable chemicals which can occur throughout the drug life cycle. The safety implications of drug impurities can be significant given that they can impact safety, quality, and efficacy of drug products and that certain drug impurities are mutagenic, carcinogenic, or teratogenic. The characteristics of drug impurities could be specific to drug modalities (e.g., small molecules vs. biologics). The commonly encountered drug impurities include elemental impurity, residual solvent, organic impurity, host cell protein and DNA, residual viral vector, extractable and leachable, and particle. They can cause various adverse effects such as immunogenicity, infection, genotoxicity, and carcinogenicity upon significant exposure. Therefore, the effective control of these drug impurities is central for patient safety. Regulations and guidelines are available for drug developers to manage them. Their qualification is obtained based on authoritative qualification thresholds or safety assessment following the classic toxicological risk assessment. The current review focuses on the safety assessment science and methodology used for diverse types of drug impurities. Due to the different nature of diverse drug impurities, their safety assessment represents a significant challenge for drug developers.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"153 ","pages":"Article 105715"},"PeriodicalIF":3.0,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381495","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

Quantitative risk assessments of skin sensitization for 26 allergens in different consumer products in the Saudi market 对沙特市场不同消费品中的 26 种过敏原进行皮肤过敏定量风险评估。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-10-03 DOI: 10.1016/j.yrtph.2024.105714

Adnan S. AL-Mussallam , Rawan S. Alshathri , Bart Desmedt , Fahad S. Aldawsari , Eric Deconinck , Omniyah A. Alharthi , Abdullah T. Bawazir

{"title":"Quantitative risk assessments of skin sensitization for 26 allergens in different consumer products in the Saudi market","authors":"Adnan S. AL-Mussallam , Rawan S. Alshathri , Bart Desmedt , Fahad S. Aldawsari , Eric Deconinck , Omniyah A. Alharthi , Abdullah T. Bawazir","doi":"10.1016/j.yrtph.2024.105714","DOIUrl":"10.1016/j.yrtph.2024.105714","url":null,"abstract":"<div><div>Fragrance chemicals are ubiquitous in cosmetics; however, they have been linked to allergic contact dermatitis. Allergy prevention involves two main strategies. Firstly, consumers are protected by limiting the maximum concentration of fragrance in a given product to avoid inducing allergies. Secondly, consumers who are already sensitized are protected by having the presence of such fragrance communicated to them. In this study, a validated GC-MS method was employed to quantify 26 allergens in 108 products marketed in Saudi Arabia.Additionally, a quantitative risk assessment (QRA) was performed on the studied cosmetics to determine the risk of inducing allergies. The results indicated that most allergens were present at acceptable concentrations, while 19 products carried a risk of inducing allergies. Furthermore, Lilial and Lyral, two prohibited fragrances, were detected in 97 products. It should be emphasized that this is the first study conducted in Saudi Arabia to evaluate the safety of the well-known 26 fragrance allergens. Hence, this study can potentially serve as a regional standard for future research.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"153 ","pages":"Article 105714"},"PeriodicalIF":3.0,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378217","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

Mapping new psychoactive substances: Leveraging GIS technology for advanced global surveillance and policy support 绘制新型精神活性物质地图：利用 GIS 技术进行先进的全球监控和政策支持。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-10-02 DOI: 10.1016/j.yrtph.2024.105713

Ting-Jung Ku , Tien-Chueh Kuo , Olivia A. Lin , Yufeng Jane Tseng

{"title":"Mapping new psychoactive substances: Leveraging GIS technology for advanced global surveillance and policy support","authors":"Ting-Jung Ku , Tien-Chueh Kuo , Olivia A. Lin , Yufeng Jane Tseng","doi":"10.1016/j.yrtph.2024.105713","DOIUrl":"10.1016/j.yrtph.2024.105713","url":null,"abstract":"<div><div>The escalating challenge of New Psychoactive Substances (NPS) necessitates enhanced global monitoring and analysis capabilities. This study introduces an advanced interactive visualization tool that employs Geographic Information System (GIS) technologies to improve the functionality of the UNODC's Early Warning Advisory. The tool enables dynamic observation and analysis of NPS's geographical and temporal distribution, thereby facilitating a comprehensive understanding of their public health impacts. By incorporating detailed choropleth maps and annual and cumulative bar charts, the tool allows policymakers and researchers to visually track and analyze trends in NPS usage and control efforts across different regions. The results demonstrate the tool's effectiveness in providing actionable insights, which support the strategic development of public health policies and interventions to curb the global rise in NPS usage. This initiative illustrates the essential role of digital tools in enhancing public health strategies and responses to emerging drug trends. This rising challenge underscores the urgent need for innovative solutions in monitoring drug trends, a theme explored in this paper. The web tool is available at <span><span>https://nps-vis.cmdm.tw</span><svg><path></path></svg></span>, and the code is available at <span><span>https://github.com/CMDM-Lab/nps-vis</span><svg><path></path></svg></span>.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"153 ","pages":"Article 105713"},"PeriodicalIF":3.0,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375878","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

Optimizing the detection of N-nitrosamine mutagenicity in the Ames test 优化艾姆斯试验中 N-亚硝胺致突变性的检测。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-09-28 DOI: 10.1016/j.yrtph.2024.105709

Robert H. Heflich , Michelle E. Bishop , Roberta A. Mittelstaedt , Jian Yan , Sharon K. Guerrero , Audrey M. Sims , Kamela Mitchell , Nyosha Moore , Xilin Li , Nan Mei , Rosalie K. Elespuru , Sruthi T. King , David A. Keire , Naomi L. Kruhlak , Robert T. Dorsam , Andre S. Raw , Karen L. Davis Bruno , Timothy J. McGovern , Aisar H. Atrakchi

{"title":"Optimizing the detection of N-nitrosamine mutagenicity in the Ames test","authors":"Robert H. Heflich , Michelle E. Bishop , Roberta A. Mittelstaedt , Jian Yan , Sharon K. Guerrero , Audrey M. Sims , Kamela Mitchell , Nyosha Moore , Xilin Li , Nan Mei , Rosalie K. Elespuru , Sruthi T. King , David A. Keire , Naomi L. Kruhlak , Robert T. Dorsam , Andre S. Raw , Karen L. Davis Bruno , Timothy J. McGovern , Aisar H. Atrakchi","doi":"10.1016/j.yrtph.2024.105709","DOIUrl":"10.1016/j.yrtph.2024.105709","url":null,"abstract":"<div><div>Accurately determining the mutagenicity of small-molecule <em>N</em>-nitrosamine drug impurities and nitrosamine drug substance-related impurities (NDSRIs) is critical to identifying mutagenic and cancer hazards. In the current study we have evaluated several approaches for enhancing assay sensitivity for evaluating the mutagenicity of <em>N</em>-nitrosamines in the bacterial reverse mutagenicity (Ames) test. Preincubation assays were conducted using five activation conditions: no exogenous metabolic activation and metabolic activation mixes employing both 10% and 30% liver S9 from hamsters and rats pretreated with inducers of enzymatic activity. In addition, preincubations were conducted for both 60 min and 30 min. These test variables were evaluated by testing 12 small-molecule <em>N</em>-nitrosamines and 17 NDSRIs for mutagenicity in <em>Salmonella typhimurium</em> tester strains TA98, TA100, TA1535, and TA1537, and <em>Escherichia coli</em> strain WP2 uvrA (pKM101). Eighteen of the 29 <em>N</em>-nitrosamine test substances tested positive under one or more of the testing conditions and all 18 positives could be detected by using tester strains TA1535 and WP2 uvrA (pKM101), preincubations of 30 min, and S9 mixes containing 30% hamster liver S9. In general, the conditions under which NDSRIs were mutagenic were similar to those found for small-molecule <em>N</em>-nitrosamines.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"153 ","pages":"Article 105709"},"PeriodicalIF":3.0,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352730","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

Rethinking the necessity of long-term toxicity studies for biotherapeutics using weight of evidence assessment 利用证据权重评估重新思考生物治疗药物长期毒性研究的必要性。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-09-26 DOI: 10.1016/j.yrtph.2024.105710

Payal Rana , Brett Hollingshead , Raja Mangipudy

{"title":"Rethinking the necessity of long-term toxicity studies for biotherapeutics using weight of evidence assessment","authors":"Payal Rana , Brett Hollingshead , Raja Mangipudy","doi":"10.1016/j.yrtph.2024.105710","DOIUrl":"10.1016/j.yrtph.2024.105710","url":null,"abstract":"<div><div>The registration of biotherapeutics for chronic indications requires 6-month toxicity studies. However, extensive experience has shown that the non-clinical safety profiles of biotherapeutics are generally predictable. This suggests that conducting multiple studies, especially a 6-month study may not be necessary. In a meta-analysis of biologics developed for non-oncology indications over last 25 years at Pfizer, we compared organ system findings between short-term (1–3 month) and long-term (6-month) animal studies. Our goal was to determine if there were differences in the safety profiles between the two study durations and their relevance to human risk assessment. Our analysis revealed that most clinically relevant toxicities could be detected in shorter-term studies (87%; 26/30 programs). This suggests either an undifferentiated safety profile between short-and long-term studies, or anticipated toxicities based on the modality, such as immunogenicity or exaggerated pharmacology. However, for 4 out of 30 programs (13%), long-term studies did identify either potential new toxicities or more severe manifestation of exaggerated pharmacology, leading to modifications in clinical trial designs and human risk assessment. Our experience suggests that 3-month toxicity studies may be sufficient to support late-stage clinical development for a majority of standard biotherapeutic programs. This pragmatic and science-based approach aligns with the goal of advancing 3R's initiatives in nonclinical safety assessment.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"153 ","pages":"Article 105710"},"PeriodicalIF":3.0,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352732","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

Re-evaluation of the reduced heart weights in male rats in a 28-day oral repeated-dose toxicity study of tetramethylammonium hydroxide 重新评估四甲基氢氧化铵 28 天口服重复剂量毒性研究中雄性大鼠心脏重量减少的情况。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-09-26 DOI: 10.1016/j.yrtph.2024.105712

Akira Kawashima, Kaoru Inoue

{"title":"Re-evaluation of the reduced heart weights in male rats in a 28-day oral repeated-dose toxicity study of tetramethylammonium hydroxide","authors":"Akira Kawashima, Kaoru Inoue","doi":"10.1016/j.yrtph.2024.105712","DOIUrl":"10.1016/j.yrtph.2024.105712","url":null,"abstract":"<div><div>We recently conducted a detailed hazard assessment of tetramethylammonium hydroxide (TMAH), a priority chemical substance under the Japan Chemical Substances Control Law. During this assessment, there was debate regarding the reduced heart weight observed in the treated male groups in the 28-day rat oral repeated-dose toxicity study. This finding was not observed in females in this study and in both sexes of oral toxicity studies for tetramethylammonium chloride (TMAC) or tetramethylammonium hydrogen phthalate (TMAHP). Unpublished individual data from the oral TMAH developmental and reproductive toxicity (DART) screening study were also obtained; no effect on heart weight was observed. In addition, background data on rat heart weight from six 28-day oral toxicity studies conducted in the same facility, year, strain, age, and breeder as the TMAH study were obtained from the Japan Existing Chemical Substances Database (JECDB). These investigations suggest that the statistically significant lower heart weight in the treated males in the 28-day toxicity study is likely caused by an incidental skewing of individuals with heavier heart weights toward control male groups and is not due to TMAH treatment. Thus, it is worthwhile to include as much relevant data as possible to confirm or refute unexpected findings in toxicity studies.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"153 ","pages":"Article 105712"},"PeriodicalIF":3.0,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352731","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