Toxicology in Vitro最新文献

{"title":"Applicability of the SENS-IS assay to assess skin sensitization of medical devices according the technical specification ISO/TS11796","authors":"Françoise Cottrez ,&nbsp;Elodie Boitel ,&nbsp;Essia Sahli ,&nbsp;Christian Pellevoisin ,&nbsp;Hervé Groux","doi":"10.1016/j.tiv.2025.106032","DOIUrl":"10.1016/j.tiv.2025.106032","url":null,"abstract":"<div><div>Assessing skin sensitization is critical in the development of medical devices, and the SENS-IS assay provides a reliable <em>in vitro</em> alternative to traditional animal models. By utilizing reconstructed human epidermis (RHE), which closely mimics human skin, the assay allows testing with both saline and sesame oil under conditions similar to <em>in vivo</em> models, facilitating a smoother transition to non-animal testing. This study evaluated the efficacy of the SENS-IS assay according to ISO/TS 11796, testing 14 sensitizers and 3 non-sensitizers during the prevalidation phase, as well as the 8 sensitizers and 4 non-sensitizers recommended in an interlaboratory study using MED-2000 silicone extracts spiked with ISO-specified chemicals at LLNA EC3 concentrations.</div><div>The assay successfully identified 20 out of 22 sensitizers tested at EC3 concentrations. Two chemicals, poorly soluble in the vehicles used,—TPO (EC3 = 27) and Isopropyl Myristate (EC3 = 44)—were detected at slightly higher concentrations, with TPO detected at 50 % and Isopropyl Myristate at 75 % of their EC3 values. All 7 non-sensitizers were accurately classified. These results confirm the sensitivity of the SENS-IS assay and underscore its potential for medical device development, advancing the use of non-animal testing methods.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"105 ","pages":"Article 106032"},"PeriodicalIF":2.6,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"6:2 fluorotelomer sulfonate as a safer alternative to PFOS: Comparative cytotoxicity and oxidative stress mechanisms in pancreatic β-cells (INS-1 model)","authors":"Xiao-Min Ren,&nbsp;Jianying Wang,&nbsp;Fenqing Zhao,&nbsp;Pingping Zhang,&nbsp;Zhenghuan Zhang,&nbsp;Zhongneng Yang,&nbsp;Huan He,&nbsp;Zhixiang Xu,&nbsp;Bin Huang,&nbsp;Xuejun Pan","doi":"10.1016/j.tiv.2025.106034","DOIUrl":"10.1016/j.tiv.2025.106034","url":null,"abstract":"<div><div>Previous studies suggest that 6:2 fluorotelomer sulfonate (6:2 FTSA) exhibits lower hepatotoxicity and reduced reproductive and developmental toxicity compared to perfluorooctane sulfonate (PFOS), indicating it may offer a safer alternative. This study aimed to investigate whether 6:2 FTSA is safer than PFOS in terms of its cytotoxic effects on pancreatic β-cells. Using rat insulinoma cells (INS-1) as a model of pancreatic β-cells, we compared the effects of 6:2 FTSA and PFOS in both their acid (6:2 FTSA-H, PFOS-H) and potassium salt forms (6:2 FTSA-K, PFOS-K) on cell viability through Cell Counting Kit-8 (CCK-8) assays, Trypan Blue staining, and apoptosis assays. Results indicated that 6:2 FTSA was less toxic to INS-1 cells than PFOS (6:2 FTSA-H &lt; PFOS-H; 6:2 FTSA-K &lt; PFOS-K), the LOECs of 6:2 FTSA-H, 6:2 FTSA-K, PFOS-H, and PFOS-K were 150 μM, 150 μM, 20 μM, and 10 μM under FBS free conditions, respectively. To further explore whether these compounds induce cell death via oxidative stress, we measured intracellular reactive oxygen species (ROS) levels, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) levels. All four compounds induced oxidative stress in INS-1 cells, with oxidative stress levels corresponding to cytotoxicity, suggesting β-cell death may occur via an oxidative stress mechanism. In conclusion, this study supports the notion that 6:2 FTSA is a safer alternative to PFOS, particularly regarding risks related to pancreatic β-cell cytotoxic effects. While the in vitro experiments in this study provide valuable preliminary information on the compounds' effects on cells and their mechanisms, they cannot fully capture the complexity of the in vivo environment. Therefore, future research should include in vivo experiments to validate the findings from the in vitro studies and comprehensively evaluate the actual effects of the compounds in living organisms.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"105 ","pages":"Article 106034"},"PeriodicalIF":2.6,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143464611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A group of novel polyfluoroether substances affects lipid metabolism in human hepatocyte HepaRG cells less than classic perfluoroalkyl compounds","authors":"Faezeh Sadrabadi,&nbsp;Wiebke Alker,&nbsp;Heike Sprenger,&nbsp;Albert Braeuning,&nbsp;Thorsten Buhrke","doi":"10.1016/j.tiv.2025.106024","DOIUrl":"10.1016/j.tiv.2025.106024","url":null,"abstract":"<div><div>Per<em>-</em> and polyfluoroalkyl substances (PFAS) are used for numerous industrial applications including the production of fluorosurfactants. Some prominent PFAS, e.g., perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS), are non-degradable and therefore persist in the environment. They display various toxic properties including dysregulation of hepatic lipid metabolism. At the molecular level, these effects are mainly based on a PFAS-mediated activation of the peroxisome proliferator-activated receptor alpha (PPARα). A group of novel, degradable polyfluoroether compounds has been designed as building blocks for the production of alternative, degradable fluorosurfactants. In the present study, we examined the capacity of four of these novel polyfluoroether compounds to induce PPARα activation, increase intracellular triglyceride accumulation, and produce a cytotoxic response. In contrast to some classic PFAS including PFOA and PFOS, the novel compounds neither activated PPARα in a transactivation assay, nor did they induce expression of selected PPARα-dependent target genes in differentiated HepaRG cells, a model for human hepatocytes. They also did not induce triglyceride accumulation in HepaRG cells. The in vitro data indicate that the polyfluoroether compounds tested in the present study are not PPARα agonists. Since PPARα agonist activity is often associated with toxic responses, it can be assumed that these substances are less toxic than classic PFAS such as PFOA and PFOS, at least with respect to PPARα-dependent toxicity mechanisms.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"105 ","pages":"Article 106024"},"PeriodicalIF":2.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"β-sitosterol protects against ANIT-induced hepatotoxicity and cholestasis via FXR activation","authors":"Yuhui Yan ,&nbsp;Wenyu Wang ,&nbsp;Aiwen Yan ,&nbsp;Haonan Zhu ,&nbsp;Qiang Meng","doi":"10.1016/j.tiv.2025.106020","DOIUrl":"10.1016/j.tiv.2025.106020","url":null,"abstract":"<div><div>Cholestasis, a condition marked by bile acid accumulation in the liver and body systems, leads to liver dysfunction and cirrhosis. Currently, ursodeoxycholic acid (UDCA) and obeticholic acid (OCA) are the only two FDA-approved drugs for Cholestasis. Thus, new therapeutic approaches need to be developed. In this study, we validated the liver-protective properties of β-sitosterol (SIT), a key bioactive element abundant in plants, against hepatic toxicity and cholestasis induced by alpha-naphthylisothiocyanate(ANIT), while elucidating its mechanisms of action both in vivo and in vitro. SIT's FXR activation was confirmed via molecular docking and dual-luciferase assays. In the mechanisms of SIT hepatoprotection, the expression levels of bile salt export pump (Bsep) and multidrug resistance protein2 (Mrp2) which are bile acid efflux transporter, and sulfate transferase 2a1 (Sult2a1) which is a bile acid metabolizing enzyme were all increased by SIT, whereas the expression of uptake transporter sodium taurocholate transporting polypeptide (Ntcp), bile acid synthesis enzyme cholesterol 7α-hydroxylase (Cyp7a1) and oxysterol 12α-hydroxylase (Cyp8b1) was decreased by SIT. In addition, SIT alleviated liver inflammation by suppressing inflammatory factor expression. However, FXR antagonist guggulsterone and FXR siRNA abolished SIT's improvements in liver histology, bile acid transporters, and enzymes. Conclusively, through activating FXR, SIT provides a protective effect against hepatotoxicity and cholestasis. SIT might serve as a new potential therapeutic strategy for the treatment of cholestatic liver diseases.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"104 ","pages":"Article 106020"},"PeriodicalIF":2.6,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the safety of midazolam: A comprehensive analysis of adverse events from FAERS","authors":"Jieyuan Chen ,&nbsp;Zhaojun Wang ,&nbsp;Li Wei ,&nbsp;Songsong Mao","doi":"10.1016/j.tiv.2025.106023","DOIUrl":"10.1016/j.tiv.2025.106023","url":null,"abstract":"<div><div>Midazolam, a potent sedative from the benzodiazepine class, is widely used in anesthesia and intensive care, but it has been linked to severe and life-threatening cardiopulmonary adverse events (AEs). This study investigated real-world AEs associated with midazolam using data from the U.S. Food and Drug Administration (FDA) adverse event reporting system (FAERS) from 2004 to 2024. Disproportionality analysis was performed using four signal detection methods—reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker—to assess midazolam-related AEs. A total of 2952 AE reports were identified, involving seven system organ classes, with 31 specific AEs meeting criteria across all four algorithms. Unexpected AEs not listed in the product label, such as seizure, coma, respiratory failure, anaphylactic shock, and hypothermia, were also observed, with most AEs occurring within the first 10 days of midazolam use. This pharmacovigilance study highlights the need for increased awareness of serious and unexpected AEs, including respiratory failure, anaphylactic shock, hypothermia, and metabolic acidosis, to promote safer use of midazolam in clinical practice.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"105 ","pages":"Article 106023"},"PeriodicalIF":2.6,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using cimetidine to mitigate cisplatin-induced ototoxicity","authors":"Rahul Sinha ,&nbsp;Si Ja Liu ,&nbsp;Rebekah Lee ,&nbsp;Julia Boyd ,&nbsp;Kyla Geary ,&nbsp;Dianzheng Zhang","doi":"10.1016/j.tiv.2025.106025","DOIUrl":"10.1016/j.tiv.2025.106025","url":null,"abstract":"<div><div>Given the well-established role of organic cation transporter 2 (OCT2) in cisplatin uptake to the inner ear cells, and the fact that cimetidine is an FDA-approved drug with well-established inhibitory activity against OCT2, we hypothesized that inhibiting OCT2-mediated cisplatin uptake with cimetidine could eliminate or alleviate cisplatin-mediated ototoxicity. Our preliminary data showed that cisplatin can reduce the viability of House Ear Institute-Organ of Corti 1 (HEI-OC1) cells in a dose-dependent manner, and cimetidine can effectively counteract this cisplatin-induced toxicity without affecting cisplatin's effect on cancer cells. Therefore, combined application of these drugs could ameliorate cisplatin ototoxicity with minimal impact on their anti-cancer effect.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"104 ","pages":"Article 106025"},"PeriodicalIF":2.6,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143403649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repression of bile salt efflux pump expression by tri-ortho-cresyl phosphate in cultured human hepatic cells","authors":"Valentin Tastet ,&nbsp;Marc Le Vée ,&nbsp;Jennifer Carteret ,&nbsp;David Malnoë ,&nbsp;Arnaud Bruyère ,&nbsp;Olivier Fardel","doi":"10.1016/j.tiv.2025.106021","DOIUrl":"10.1016/j.tiv.2025.106021","url":null,"abstract":"<div><div>Tri-<em>ortho</em>-cresyl phosphate (TOCP) is an environmental toxic pollutant, belonging to the chemical class of organophosphorus flame retardants and repressing hepatic membrane drug transporter expression. The present study investigated whether the liver canalicular bile salt efflux pump (BSEP) may also be targeted by TOCP. TOCP used at a non-cytotoxic concentration of 10 μM for 48 h was demonstrated to decrease BSEP mRNA expression in cultured hepatic HepaRG cells (by a 4.4-fold factor) and primary human hepatocytes (by a 2.5-fold factor). This effect was concentration-dependent (IC₅₀ = 0.8 μM) and was associated with a significant reduction of canalicular taurocholate secretion in HepaRG cells. It was not impaired by TOCP metabolism inhibitors. TOCP also potently antagonized farnesoid-X-receptor (FXR) mediated-BSEP up-regulation. The specific FXR antagonist DY268 decreased constitutive BSEP expression in HepaRG cells, as TOCP, suggesting a major implication of FXR antagonism in TOCP effects towards BSEP. The TOCP-mediated BSEP repression was finally predicted to potentially occur <em>in vivo</em> in response to a neurotoxic dose or to acute or chronic safe doses of TOCP. Taken together, these data demonstrate that the major bile salt transporter BSEP is a target for TOCP, which may support deleterious hepatotoxic effects of this chemical.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"105 ","pages":"Article 106021"},"PeriodicalIF":2.6,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-androgenetic effect of diphlorethohydroxycarmalol on testosterone-induced hair loss by inhibiting 5α-reductase and promoting Wnt/β-catenin signaling pathway in human dermal papilla cells","authors":"Seung Tae Im ,&nbsp;Haeun Mun ,&nbsp;Nalae Kang ,&nbsp;Soo-Jin Heo ,&nbsp;Seung-Hong Lee","doi":"10.1016/j.tiv.2025.106017","DOIUrl":"10.1016/j.tiv.2025.106017","url":null,"abstract":"<div><div>Diphlorethohydroxycarmalol (DPHC), a marine phlorotannin compound derived from the brown alga <em>Ishige okamurae</em>, has been known to have a variety of biological effects. Recently, marine resources have been highlighted by their effects on ameliorating alopecia and related hair loss. Therefore, this study aimed to investigate the potential of DPHC isolated from <em>I. okamurae</em> as a hair loss treatment through examination of its anti-androgenic alopecia effects. Molecular docking analysis predicted that DPHC can be used as a 5α-reductase inhibitor superior to finasteride, which has traditionally been used as an anti-androgenic alopecia agent. In addition, DPHC significantly inhibited 5α-reductase activity in dihydrotestosterone (DHT)-treated human dermal papilla (HDP) cells, and downregulated hair growth inhibitor proteins such as AR, DKK1, TGF-β1, and IL-6. Moreover, DPHC treatment remarkably upregulated both the phosphorylation levels of GSK3β and expression levels of β-catenin in DHT-treated HDP cells, confirming the effects of DPHC on activating the Wnt/β-catenin signaling pathway. Therefore, these findings suggest that DPHC has a significant potential to prevent androgenic alopecia by promoting hair growth and preventing hair loss.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"104 ","pages":"Article 106017"},"PeriodicalIF":2.6,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro human skin absorption of ethyl salicylate, pentyl salicylate, and (Z)-3-hexenyl salicylate from topical formulations: Effects on permeation and distribution","authors":"Kaushal Joshi ,&nbsp;Darren M. Green ,&nbsp;A. Christian Jones ,&nbsp;Sophie E. Davies ,&nbsp;Sophie G. Stocks ,&nbsp;Arianna P. Bartlett ,&nbsp;Anne Marie Api","doi":"10.1016/j.tiv.2025.106019","DOIUrl":"10.1016/j.tiv.2025.106019","url":null,"abstract":"<div><div>In vitro human skin permeation and distribution of the fragrance materials ethyl salicylate (CAS 118–61-6, ES), (Z)-3-hexenyl salicylate (CAS 65405–77-8, HS) and pentyl salicylate (CAS 2050-08-0, PS) from separate 0.5 % (<em>w</em>/w) cream formulations were determined under unoccluded and occluded conditions for 24 h. For PS only, a 0.5 % (<em>w</em>/<em>v</em>) solution in 70/30 (<em>v</em>/v) ethanol/water was also assessed. Consumer relevant finite formulation doses were applied (5 mg/cm² or 5 μl/cm²) with salicylate application of ∼25 μg/cm². Although specifically assessing metabolism was not an aim, the common hydrolysis product salicylic acid (SA) was also quantified and included in overall test compound absorption values.</div><div>For ES, absorbed doses (mean ± standard error, SE) were 12.0 ± 1.0 and 24.7 ± 1.3 % applied dose under unoccluded and occluded conditions, respectively. For HS these values were 7.28 ± 0.52 and 11.1 ± 0.7 % applied dose. For the PS cream, corresponding values were 4.43 ± 0.48 and 7.52 ± 0.63 % applied dose. Whilst for the PS solution values were 8.26 ± 0.31 and 16.1 ± 0.7 % applied dose. The salicylate structure, application vehicle and level of occlusion impacted on the observed skin absorption. Considering salicylates are commonly used fragrance ingredients and have limited skin absorption data, the current research will be helpful in risk assessment to determine systemic exposure that is realistic and fill data gaps.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"104 ","pages":"Article 106019"},"PeriodicalIF":2.6,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictive classification-based read-across for diverse functional vitiligo-linked chemical exposomes (ViCE): A new approach for the assessment of chemical safety for the vitiligo disease in humans","authors":"Shilpayan Ghosh,&nbsp;Sapna Kumari Pandey,&nbsp;Kunal Roy","doi":"10.1016/j.tiv.2025.106018","DOIUrl":"10.1016/j.tiv.2025.106018","url":null,"abstract":"<div><div>We have explored a new approach using a similarity measure-based read-across derived hypothesis to address the precise risk assessment of vitiligo active chemicals. In this analysis, we initially prepared a data set by combining vitiligo active compounds taken from the previous literature with non-vitiligo chemicals, which are non-skin sensitizers reported in another literature. Afterward, we performed the manual curation process to obtain a curated dataset. Furthermore, the optimum similarity measure was identified from a validation set using a pool of 47 descriptors from the analysis of the most discriminating features. The identified optimum similarity measure (i.e., Euclidean distance-based similarity along with seven close source compounds) has been utilized in the read-across derived similarity-based classification studies on close source congeners concerning target compounds. In this study, we identified the positive and negative contributing features toward the assessment of vitiligo potential as well, including the estimation of target chemicals with better accuracy. The applicability domain status of the reported compounds was also studied, and the outliers were identified. As there are no comparative studies in this regard to the best of our knowledge, we can further affirm that it is the first report on the in-silico identification of potential vitiligo-linked chemical exposomes (ViCE) based on the similarity measure of the read-across.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"104 ","pages":"Article 106018"},"PeriodicalIF":2.6,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}