Regulatory Toxicology and Pharmacology最新文献

{"title":"Toxicological evaluation in vitro of novel photosensitizers intended for photodynamic therapy.","authors":"L Svobodova, L Valkova, M Kolarikova, K Kejlova, R Bajgar, K Barton Tomankova, M Rucki, H Bendova, D Jirova, H Kolarova","doi":"10.1016/j.yrtph.2026.106205","DOIUrl":"10.1016/j.yrtph.2026.106205","url":null,"abstract":"<p><p>Three selected photosensitizers (PS) with potential applications in PDT (ZnPcS₂, TMPyP, PPIX) were evaluated for skin irritation, phototoxicity and sensitization using exclusively non-animal test methods. The experimental approach was based on OECD TG with protocol modifications to accommodate the specific requirements of photosensitizers testing. Reconstructed human epidermis (RhE) based assays were performed using adapted protocols derived from OECD TG 439 and OECD TG 498, while skin sensitization was assessed using methods based on OECD TG 442C and OECD TG 442D. TMPyP and PPIX showed no evidence of skin irritation, phototoxicity, early skin inflammation, or skin sensitization under the experimental conditions. In contrast, ZnPcS₂ at higher concentrations (50 and 100 μM) induced a phototoxic response following 18 h exposure of the RhE skin model EpiDerm™ and subsequent red light irradiation (2 × 75 J cm^-2). Importantly, despite its phototoxic activity, ZnPcS₂ did not induce skin irritation, sensitization, or increase of inflammatory biomarkers associated with early skin inflammation. Overall, the investigated photosensitizers were well tolerated in the applied non-animal test systems. These findings demonstrated the suitability of OECD TG-derived methods with protocol adaptations for preclinical safety assessment of PS under conditions relevant to PDT and supported their further development for biomedical applications.</p>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":" ","pages":"106205"},"PeriodicalIF":4.3,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148654264","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}

{"title":"Mutagenicity studies on migrants from food-contact silicone products based on Ames test and chemical analysis.","authors":"Peixue Guo, Zhaoxi Liu, Jin Rong, Xueting Feng, Xiaojie Fan, Di Feng","doi":"10.1016/j.yrtph.2026.106274","DOIUrl":"10.1016/j.yrtph.2026.106274","url":null,"abstract":"<p><p>After simulating food migration using 95% ethanol at 70°C for 2 h on 63 food-contact silicone products, the Ames test was employed to evaluate the mutagenicity of their migrants. Chemical analyses of three positive samples were conducted using gas chromatography-mass spectrometry (GC-MS) and inductively coupled plasma mass spectrometry (ICP-MS). The results indicated that the TA98 strain was more sensitive than the TA97, TA100, and TA102 strains. None of the 30 nipples exhibited mutagenicity against the TA98 strain, whereas 26 of 33 kitchen utensils (79%) tested positive. Migration from a representative sample (K-19, mold) in 95% ethanol demonstrated mutagenicity whether used at room temperature, baked, or frozen, indicating higher mutagenicity when in contact with fatty foods. A total of 22 organic compounds and 14 metal elements were detected in the samples, with migration levels of heavy metals and phthalates below the specific migration limits. The significant difference in results between nipples and kitchenware may be related to differences in their formulations and processing techniques. Further studies are needed to identify the key substances responsible for mutagenicity in these samples and to conduct subsequent risk assessments. Although potentially harmful, these findings do not necessarily indicate a safety risk.</p>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":" ","pages":"106274"},"PeriodicalIF":4.3,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149196210","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}

{"title":"A comprehensive review of regulatory outcomes and timelines of accelerated FDA approvals for non-oncology therapeutics","authors":"Heenam Seo ,&nbsp;Mel Kim ,&nbsp;Eunyoung Kim","doi":"10.1016/j.yrtph.2026.106050","DOIUrl":"10.1016/j.yrtph.2026.106050","url":null,"abstract":"<div><div>Most accelerated approvals for oncology drugs have been granted, few studies have characterized the regulatory outcomes of non-oncology drugs within this framework. To examine regulatory outcome and approval timelines of non-oncology drug indications, a cross-sectional analysis was performed using the Food and Drug Administration's accelerated approval database from 1992 to 2024. Among 328 accelerated approval indications, 98 (30 %) were for non-oncology drugs. Overall, 63/98 (64 %) were converted to full approval with systemic anti-infectives accounting for 50 %. Among the 77 (79 %) original indications, 55 (71 %) were converted to full approval, compared to only 8 (38 %) of the 21 supplemental indications. The median times to accelerated approval and convert to full approval for all non-oncology indications were 7.9 (IQR, 5.9–10.0) and 38.8 (IQR, 22.5–63.9) months, respectively. The median time to accelerated approval was 6.8 (IQR, 5.9–10.0) months for 90 (92 %) chemical drug indications and 8.6 (IQR, 7.9–11.0) for 8 (8 %) biologic drug indications; conversion to full approval took 38.8 (IQR, 22.8–63.8) and 42.6 (IQR, 21.3–100.6) months, respectively. Accelerated approvals for non-oncology biologic drug indications took significantly longer than those for oncology biologic indications (8.6 vs. 6.0 months; <em>p</em> = 0.003). These findings underscore the importance of enhanced regulatory oversight and continued post-marketing evaluation to confirm the clinical benefits of non-oncology drugs approved via the accelerated pathway.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"167 ","pages":"Article 106050"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146097171","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}

{"title":"Lack of significant risk from everyday dietary nickel: Rethinking the application of oral toxicity reference values","authors":"Michael D. Dutton ,&nbsp;Chris Bacigalupo","doi":"10.1016/j.yrtph.2026.106055","DOIUrl":"10.1016/j.yrtph.2026.106055","url":null,"abstract":"<div><div>Toxicity reference value (TRV) is a general term for an exposure limit below which health impairment is not expected. TRVs are used to develop environmental quality standards and for other risk-based activities. Nickel (Ni) TRVs developed by several influential regulatory agencies have used toxicity data from rats orally exposed to nickel sulfate hexahydrate (NSHH). These TRVs converted doses from an NSHH-basis to an ‘as-nickel’ basis, under the belief that controls received no Ni, which is not the case. The extrapolation from a point-of-departure to a human-relevant limit has resulted in TRVs that are, in some instances, less than the estimated normal daily dietary nickel intake observed in certain human life stages. As a result, Ni that is present naturally in food has been incorrectly believed to be contributing to human health risk. The now common risk assessment practice of applying these Ni TRVs on an ‘inclusive of baseline diet’ basis, contrasts with the Institute of Medicine (IOM) perspective that there is no evidence of adverse effects associated with a normal diet: rather, human health risk is associated with excess nickel intake as soluble nickel salts. TRVs based on soluble Ni salts are to be distinguished from the normal Ni-containing diet.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"167 ","pages":"Article 106055"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146166492","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}

{"title":"Derivation of a Point of Departure using NAMs for application in Quantitative Risk Assessment of fragrance materials","authors":"Andreas Natsch ,&nbsp;Peter Griem ,&nbsp;Amaia Irizar ,&nbsp;James Bridges ,&nbsp;Matthias Vey ,&nbsp;Isabelle Lee ,&nbsp;Anne Marie Api ,&nbsp;Petra Kern ,&nbsp;Ian Kimber","doi":"10.1016/j.yrtph.2026.106052","DOIUrl":"10.1016/j.yrtph.2026.106052","url":null,"abstract":"<div><div>Skin sensitization is a key endpoint for the safety assessment of topical consumer products. Ingredients with the potential to act as skin sensitizers differ markedly in their threshold for induction but can be used safely if their potency is characterized and exposure remains within an appropriate margin of safety. To this end, the fragrance industry co-developed Quantitative Risk Assessment (QRA) which starts with the No-Expected-Sensitization-Induction-Level (NESIL). Historically, QRA relies on a weight of evidence approach based on animal data, human confirmatory tests and read across. To allow an approach based solely on New Approach Methodologies (NAMs), the International Dialogue for the Evaluation of Allergens (IDEA) initiative, developed an extended Reference Chemical Potency List (RCPL) integrating human and animal data to derive potency values (PV). Here, we use PVs to evaluate the suitability of quantitative NAMs, including Defined Approaches (DAs), to derive a Point-of-Departure (NAM-PoD) for skin sensitization potency assessment. Evaluation of NAM-PoD derived by SARA-ICE DA, Regression DA and GARDskin dose-response assay (GSDR), indicates that the sensitization potency of fragrance chemicals can be reliably predicted using each approach. Through comparison of NAM-PoDs with <em>in vivo</em> human sensitization thresholds, NAM-specific adjustment factors were derived to convert NAM-PoDs into NAM-NESILs for QRA.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"167 ","pages":"Article 106052"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146119968","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}

{"title":"Atmospheric microplastics: A review of pollution characteristics, human exposure pathways, and emerging health risks","authors":"MohammadAmin Azizi ,&nbsp;Zahra Khashi ,&nbsp;Razieh Ashoori ,&nbsp;Farzaneh Rostami ,&nbsp;Abooalfazl Azhdarpoor","doi":"10.1016/j.yrtph.2026.106053","DOIUrl":"10.1016/j.yrtph.2026.106053","url":null,"abstract":"<div><div>Microplastics (MPs) pollution is a growing environmental issue due to excessive plastic use and improper waste disposal. While early studies focused on MPs in aquatic and terrestrial ecosystems, recent research has expanded to include air quality. This comprehensive narrative review examines MP concentrations in both indoor and outdoor air, highlighting that poorly ventilated indoor spaces have the highest levels of MPs, while good ventilation helps reduce pollution. Factors such as humidity and precipitation decrease MP concentrations through particle deposition, while temperature, wind, and environmental conditions influence their dispersion and persistence. Effective management of environmental conditions and ventilation design is essential to reduce human exposure to MPs. MPs in indoor and outdoor environments show distinct characteristics. Indoor MPs are mostly small (&lt;30 μm), transparent or black, and mainly appear as fibers, originating from textiles, carpets, and furniture. Outdoor MPs are more diverse, often found as fragments and composed of polymers like polystyrene (PS), polyethylene (PE), and polyethylene terephthalate (PET). Human exposure to MPs occurs primarily through inhalation and ingestion, with indoor environments posing higher risks due to particle accumulation and prolonged human presence. Fine MPs (&lt;10 μm, especially ≤2.5 μm) can penetrate deep into the lungs, causing inflammation, oxidative stress, and systemic toxicity. Ingestion through dust is particularly concerning for infants and toddlers. Despite increasing evidence of health risks, the lack of standardized methods and regulatory limits highlights the urgent need for harmonized exposure assessment and targeted public health interventions. By synthesizing existing literature, this review provides a qualitative assessment of the current state of knowledge, identifies key research gaps, and discusses implications for future policy and exposure mitigation strategies.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"167 ","pages":"Article 106053"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146119951","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}

{"title":"Occurrence and dietary risk assessment of pesticide residues in bananas and kiwifruits from Turkey","authors":"Fatma Oznur Afacan ,&nbsp;Nimo Hussain Yussuf ,&nbsp;Tuba Buyuksirit-Bedir ,&nbsp;Cagla Kayisoglu ,&nbsp;Eylem Odabas ,&nbsp;Ozgur Golge ,&nbsp;Bulent Kabak","doi":"10.1016/j.yrtph.2026.106037","DOIUrl":"10.1016/j.yrtph.2026.106037","url":null,"abstract":"<div><div>This study assessed the occurrence and dietary risk of pesticide residues in bananas and kiwifruits marketed in Turkey. A total of 50 banana and 50 kiwifruit samples were analyzed for 235 pesticide residues using LC-MS/MS. The analytical method exhibited satisfactory recoveries, acceptable precision, and adequate sensitivity, in full compliance with the European SANTE/11312/2021 Guidelines. Pesticide residues were detected in 82 % of banana and 46 % of kiwifruit samples, with 28 % and 30 % of samples exceeding the EU maximum residue levels (MRLs), respectively. Triadimefon and fenarimol were the most frequently detected compounds in bananas, while acetamiprid and cycloate were the predominant residues in kiwifruits. Chronic dietary exposure assessment, conducted using both deterministic and probabilistic (Monte Carlo simulation) approaches, indicated that chronic hazard indices (<em>HIc</em>) remained well below the threshold value of 1 for both adults and children. Probabilistic modeling revealed right-skewed exposure distributions, with 95th percentile <em>HIc</em> values of 0.0068 and 0.0094 for adults and children, respectively, for bananas, and 0.0013 and 0.0033 for kiwifruit, thereby confirming negligible chronic health risks even under high-exposure scenarios. Acute hazard quotients (<em>HQa</em>) were generally below 1 for adults, whereas a potential acute risk (<em>HQa</em> &gt; 1) was identified for children in a single kiwifruit sample due to indoxacarb, indicating that acute concerns may arise for vulnerable populations under worst-case exposure conditions.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"167 ","pages":"Article 106037"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146039875","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}

{"title":"Analysis of two guideline-compliant developmental neurotoxicity studies with imidacloprid to assist the interpretation of findings that impact global registrations","authors":"L.P. Sheets ,&nbsp;M. Patel ,&nbsp;L. Zorrilla ,&nbsp;K. Bothe","doi":"10.1016/j.yrtph.2026.106040","DOIUrl":"10.1016/j.yrtph.2026.106040","url":null,"abstract":"<div><div>Imidacloprid is a neonicotinoid insecticide that was first registered in the early 1990's, with global registrations that include agricultural, residential and veterinary uses. In 2001, Bayer reported a developmental neurotoxicity (DNT) study with imidacloprid that complied with U.S. EPA and OECD guidelines to support global registrations. The report concluded that there were slight effects in the offspring at the highest dietary level related to general or acute (neuro)-toxicity and no evidence of DNT at any dose; however, the European Food Safety Authority (EFSA) questioned certain findings at the high dose and whether the study established a clear NOAEL. More recently, the Jai Research Foundation (JRF) independently conducted a guideline-compliant DNT study with imidacloprid for other registrants, with elements incorporated into the study design to facilitate comparison with the Bayer study that could address these issues. This paper examines the findings from both studies, in the context of an updated literature review, to address regulatory uncertainty and persistent claims from non-governmental organizations that imidacloprid is a developmental neurotoxicant. The present analysis supports the interpretation that differences in brain measurements at the high dose in the Bayer study were incidental and unrelated to treatment and that imidacloprid is not a developmental neurotoxicant.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"167 ","pages":"Article 106040"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146086903","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}

{"title":"Physicochemical and radon analysis of commercial non-alcoholic carbonated beverages in Iraqi Kurdistan","authors":"Alla Ahmed Muhamad Amin ,&nbsp;Hiwa Mohammad Qadr","doi":"10.1016/j.yrtph.2026.106054","DOIUrl":"10.1016/j.yrtph.2026.106054","url":null,"abstract":"<div><div>Naturally occurring radioactive materials, particularly radon (²²²Rn) gas, can accumulate in carbonated beverages through source water and carbonation processes, potentially exposing consumers through ingestion and inhalation pathways. This investigation measured ²²²Rn activity concentrations and physicochemical parameters in 25 commercially available non-alcoholic carbonated beverages from Iraqi Kurdistan and evaluated associated radiological health risks. ²²²Rn concentrations ranged between 20.4 and 48.5 mBq/L, averaging 34.0 mBq/L. All measurements remained considerably below drinking water reference limits established by USEPA (11,100 mBq/L), WHO (100,000 mBq/L), and UNSCEAR (40,000 mBq/L). Physicochemical analysis revealed pH values of 2.2–4.5, electrical conductivity of 603–2622 μS/cm, total dissolved solids of 515–2250 mg/L, and Brix values of 0.4–12.3%. Calculated annual effective doses for adults, considering both ingestion and inhalation routes, stayed well beneath the WHO reference level of 100 μSv/y. Excess lifetime cancer risk values were approximately three orders of magnitude lower than USEPA's acceptable threshold. Statistical analysis showed no significant correlations between ²²²Rn concentrations and physicochemical properties. These non-alcoholic carbonated beverages present negligible radiological health risks to consumers. However, periodic monitoring of ²²²Rn concentrations in commercial beverages and continued surveillance of source water quality remain recommended to ensure ongoing compliance with safety standards and maintain public health protection.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"167 ","pages":"Article 106054"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142439","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}

{"title":"Nitrosamine drug substance-related impurities cause DNA methylation adducts in vitro and in primary hepatocytes upon Cytochrome P450-dependend metabolic activation","authors":"Matthias Vogel ,&nbsp;Max J. Carlsson ,&nbsp;Claudia Skowron ,&nbsp;Christina Felske ,&nbsp;Rhys Whomsley ,&nbsp;Jörg Fahrer","doi":"10.1016/j.yrtph.2026.106036","DOIUrl":"10.1016/j.yrtph.2026.106036","url":null,"abstract":"<div><div><em>N</em>-nitrosamines are DNA alkylating agents found in food, cosmetics, tobacco products and, more recently, drugs. Following Cytochrome P450 (CYP)-mediated metabolic activation, these compounds cause DNA damage and mutations. Unlike well-characterized compounds like <em>N</em>-nitrosodimethylamine (NDMA), data on the genotoxicity of nitrosamine drug substance-related impurities (NDSRIs) remain limited. Given their regulatory relevance, this study assessed the genotoxic potential of three NDSRIs —<em>N</em>-nitrosobetahistine (NBH), <em>N</em>-nitrosofluoxetine (NFluo), and <em>N</em>-nitrosonortriptyline (NNT) —compared to NDMA. The NDSRIs demonstrated distinct DNA methylating potential, confirmed by elevated levels of <em>N</em>7-methyl-deoxyguanosine (<em>N7</em>-MedG) and <em>O</em>⁶-methyl-deoxyguanosine (<em>O</em>⁶-MedG) in a DNA alkylation assay with metabolic activation. Recombinant CYP isoforms contributed differentially to the bioactivation of each NDSRI, highlighting enzyme-specific pathways of toxification. Subsequently, we demonstrated that all NDSRIs cause DNA methylation adducts (<em>N</em>7-MedG &gt; <em>O</em>⁶-MedG) in primary rat hepatocytes, with generally higher levels than those caused by NDMA. Consistently, the NDSRIs generated more DNA strand breaks than NDMA, which followed the DNA adduct kinetics. Furthermore, all NDSRIs showed cytotoxicity after 24 h, whereas no cytotoxic effect was observed for NDMA. Taken together, our study provided evidence that the three NDSRIs are genotoxic in primary rat hepatocytes, which warrants further investigation with regard to their mutagenic potential.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"167 ","pages":"Article 106036"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146030510","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}