Journal of Immunotoxicology最新文献

{"title":"IL-2-mediated hepatotoxicity: knowledge gap identification based on the irAOP concept","authors":"Luise A. Roser, Christina Sakellariou, Malin Lindstedt, Vanessa Neuhaus, Susann Dehmel, Charline Sommer, Martin Raasch, Thierry Flandre, Sigrid Roesener, Philip Hewitt, Michael J. Parnham, Katherina Sewald, Susanne Schiffmann","doi":"10.1080/1547691x.2024.2332177","DOIUrl":"https://doi.org/10.1080/1547691x.2024.2332177","url":null,"abstract":"Drug-induced hepatotoxicity constitutes a major reason for non-approval and post-marketing withdrawal of pharmaceuticals. In many cases, preclinical models lack predictive capacity for hepatic dama...","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"107 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140560865","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":"Fine tuning of the innate and adaptive immune responses by Interleukin-2.","authors":"Christina Sakellariou, Luise A Roser, Susanne Schiffmann, Malin Lindstedt","doi":"10.1080/1547691X.2024.2332175","DOIUrl":"10.1080/1547691X.2024.2332175","url":null,"abstract":"<p><p>Novel immunotherapies for cancer and other diseases aim to trigger the immune system to produce durable responses, while overcoming the immunosuppression that may contribute to disease severity, and in parallel considering immunosafety aspects. Interleukin-2 (IL-2) was one of the first cytokines that the FDA approved as a cancer-targeting immunotherapy. However, in the past years, IL-2 immunotherapy is not actively offered to patients, due to limited efficacy, when compared to other novel immunotherapies, and the associated severe adverse events. In order to design improved <i>in vitro</i> and <i>in vivo models</i>, able to predict the efficacy and safety of novel IL-2 alternatives, it is important to delineate the mechanistic immunological events triggered by IL-2. Particularly, in this review we will discuss the effects IL-2 has with the bridging cell type of the innate and adaptive immune responses, dendritic cells. The pathways involved in the regulation of IL-2 by dendritic cells and T-cells in cancer and autoimmune disease will also be explored.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"21 1","pages":"2332175"},"PeriodicalIF":3.3,"publicationDate":"2024-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288306","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":"Effect of epithelial-specific MyD88 signaling pathway on airway inflammatory response to organic dust exposure.","authors":"Amber N Johnson, John Dickinson, Amy Nelson, Rohit Gaurav, Katrina Kudrna, Scott E Evans, Katherine Janike, Todd A Wyatt, Jill A Poole","doi":"10.1080/1547691X.2022.2148782","DOIUrl":"10.1080/1547691X.2022.2148782","url":null,"abstract":"<p><p>The Toll-like receptor (TLR) adaptor protein MyD88 is integral to airway inflammatory response to microbial-enriched organic dust extract (ODE) exposures. ODE-induced airway neutrophil influx and release of pro-inflammatory cytokines was essentially abrogated in global MyD88-deficient mice, yet these mice demonstrate an increase in airway epithelial cell mucin expression. To further elucidate the role of MyD88-dependent responses specific to lung airway epithelial cells in response to ODE <i>in vivo</i>, the surfactant protein C protein (SPC) Cre⁺ embryologic expressing airway epithelial cells floxed for MyD88 to disrupt MyD88 signaling were utilized. The inducible club cell secretory protein (CCSP) Cre⁺, MyD88 floxed, were also developed. Using an established protocol, mice were intranasally instilled with ODE or saline once or daily up to 3 weeks. Mice with MyD88-deficient SPC⁺ lung epithelial cells exhibited decreased neutrophil influx following ODE exposure once and repetitively for 1 week without modulation of classic pro-inflammatory mediators including tumor necrosis factor (TNF)-α, interleukin (IL)-6, and neutrophil chemoattractants. This protective response was lost after 3 weeks of repetitive exposure. ODE-induced Muc5ac mucin expression at 1 week was also reduced in MyD88-deficient SPC⁺ cells. Acute ODE-induced IL-33 was reduced in MyD88-deficient SPC⁺ cells whereas serum IgE levels were increased at one week. In contrast, mice with inducible MyD88-deficient CCSP⁺ airway epithelial cells demonstrated no significant difference in experimental indices following ODE exposure. Collectively, these findings suggest that MyD88-dependent signaling targeted to all airway epithelial cells plays an important role in mediating neutrophil influx and mucin production in response to acute organic dust exposures.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"20 1","pages":"2148782"},"PeriodicalIF":2.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9912912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9294632","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}

{"title":"Exposure to the anti-microbial chemical triclosan disrupts keratinocyte function and skin integrity in a model of reconstructed human epidermis.","authors":"Rachel Baur, Michael Kashon, Ewa Lukomska, Lisa M Weatherly, Hillary L Shane, Stacey E Anderson","doi":"10.1080/1547691X.2022.2148781","DOIUrl":"10.1080/1547691X.2022.2148781","url":null,"abstract":"<p><p>Triclosan is an anti-microbial chemical incorporated into products that are applied to the skin of healthcare workers. Exposure to triclosan has previously been shown to be associated with allergic disease in humans and impact the immune responses in animal models. Additionally, studies have shown that exposure to triclosan dermally activates the NLRP3 inflammasome and disrupts the skin barrier integrity in mice. The skin is the largest organ of the body and plays an important role as a physical barrier and regulator of the immune system. Alterations in the barrier and immune regulatory functions of the skin have been demonstrated to increase the risk of sensitization and development of allergic disease. In this study, the impact of triclosan exposure on the skin barrier and keratinocyte function was investigated using a model of reconstructed human epidermis. The apical surface of reconstructed human epidermis was exposed to triclosan (0.05-0.2%) once for 6, 24, or 48 h or daily for 5 consecutive days. Exposure to triclosan increased epidermal permeability and altered the expression of genes involved in formation of the skin barrier. Additionally, exposure to triclosan altered the expression patterns of several cytokines and growth factors. Together, these results suggest that exposure to triclosan impacts skin barrier integrity and function of human keratinocytes and suggests that these alterations may impact immune regulation.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"20 1","pages":"1-11"},"PeriodicalIF":2.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10364087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10255699","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}

{"title":"Legacy and emerging per- and polyfluoroalkyl substances suppress the neutrophil respiratory burst.","authors":"Drake W Phelps, Anika I Palekar, Haleigh E Conley, Giuliano Ferrero, Jacob H Driggers, Keith E Linder, Seth W Kullman, David M Reif, M Katie Sheats, Jamie C DeWitt, Jeffrey A Yoder","doi":"10.1080/1547691X.2023.2176953","DOIUrl":"10.1080/1547691X.2023.2176953","url":null,"abstract":"<p><p>Per- and polyfluoroalkyl substances (PFASs) are used in a multitude of processes and products, including nonstick coatings, food wrappers, and fire-fighting foams. These chemicals are environmentally-persistent, ubiquitous, and can be detected in the serum of 98% of Americans. Despite evidence that PFASs alter adaptive immunity, few studies have investigated their effects on innate immunity. The report here presents results of studies that investigated the impact of nine environmentally-relevant PFASs [e.g. perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid potassium salt (PFOS-K), perfluorononanoic acid (PFNA), perfluorohexanoic acid (PFHxA), perfluorohexane sulfonic acid (PFHxS), perfluorobutane sulfonic acid (PFBS), ammonium perfluoro(2-methyl-3-oxahexanoate) (GenX), 7H-perfluoro-4-methyl-3,6-dioxa-octane sulfonic acid (Nafion byproduct 2), and perfluoromethoxyacetic acid sodium salt (PFMOAA-Na)] on one component of the innate immune response, the neutrophil respiratory burst. The respiratory burst is a key innate immune process by which microbicidal reactive oxygen species (ROS) are rapidly induced by neutrophils in response to pathogens; defects in the respiratory burst can increase susceptibility to infection. The study here utilized larval zebrafish, a human neutrophil-like cell line, and primary human neutrophils to ascertain whether PFAS exposure inhibits ROS production in the respiratory burst. It was observed that exposure to PFHxA and GenX suppresses the respiratory burst in zebrafish larvae and a human neutrophil-like cell line. GenX also suppressed the respiratory burst in primary human neutrophils. This report is the first to demonstrate that these PFASs suppress neutrophil function and support the utility of employing zebrafish larvae and a human cell line as screening tools to identify chemicals that may suppress human immune function.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"20 1","pages":"2176953"},"PeriodicalIF":2.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10361455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9852039","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}

{"title":"Endoplasmic reticulum stress mediates environmental particle-induced inflammatory response in bronchial epithelium.","authors":"Li Pu, Fen Yi, Wen-Jing Yu, Ya-Jing Li, You-Hui Tu, Ai-Hui Xu, Yong Wang","doi":"10.1080/1547691X.2023.2229428","DOIUrl":"10.1080/1547691X.2023.2229428","url":null,"abstract":"<p><p>While the detailed mechanisms for how particulate matter (PM) causes adverse health effects in the lungs remain largely unknown, endoplasmic reticulum (ER) stress has been implicated in PM-induced lung injury. The present study was undertaken to examine how/if ER stress might regulate PM-induced inflammation, and to begin to define potential underlying molecular mechanisms. Here, ER stress hallmarks were examined in human bronchial epithelial (HBE) cells exposed to PM. To confirm roles of certain pathways, siRNA targeting ER stress genes and an ER stress inhibitor were employed. Expression of select inflammatory cytokines and related signaling pathway components by the cells were assessed as well. The results showed that PM exposure induced elevations in two ER stress hallmarks, i.e. GRP78 and IRE1α, in time-and/or dose-related manners in the HBE cells. Inhibition of ER stress by siRNA for GRP78 or IRE1α significantly alleviated the PM-induced effects. Further, ER stress appeared to regulate PM-induced inflammation - likely through downstream autophagy and NF-κB pathways - as implied by studies showing that inhibition of ER stress by siRNA of GRP78 or IRE1α caused significant amelioration of PM-induced autophagy and subsequent activation of NF-κB pathways. Moreover, the ER stress inhibitor 4-PBA were used to confirm the protective effects against PM-induced outcomes. Together, the results suggest ER stress plays a deleterious role in PM-induced airway inflammation, possibly through activation of autophagy and NF-κB signaling. Accordingly, protocols/treatments that could lead to inhibited ER stress could potentially be effective for treatment of PM-related airway disorders.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"20 1","pages":"2229428"},"PeriodicalIF":3.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10183595","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":"Examining the role of nickel and NiTi nanoparticles promoting inflammation and angiogenesis.","authors":"Anup K Srivastava,&nbsp;Dustin M Snapper,&nbsp;Jiwen Zheng,&nbsp;Banu S Yildrim,&nbsp;Sandeep Srivastava,&nbsp;Steven C Wood","doi":"10.1080/1547691X.2022.2080307","DOIUrl":"https://doi.org/10.1080/1547691X.2022.2080307","url":null,"abstract":"<p><p>Nickel titanium (NiTi, or Nitinol) alloy is used in several biomedical applications, including cardiac, peripheral vascular, and fallopian tube stents. There are significant biocompatibility issues of metallic implants to nickel ions and nano-/micro-sized alloy particles. Our laboratories have recently shown that microscale CoCr wear particles from metal-on-metal hips crosslink with the innate immune signaling Toll-like receptor 4 (TLR4), prompting downstream signaling that results in interleukin <i>(IL)-1β</i> and <i>IL-8</i> gene expression. <i>In vivo,</i> NiTi alloy can also generate wear particles on the nanoscale (NP) that have thus far not been studied for their potential to induce inflammation and angiogenesis that can, in turn, contribute to implant (e.g. stent) failure. Earlier studies by others demonstrated that nickel could induce contact hypersensitivity by crosslinking the human, but not the mouse, TLR4. In the present work, it is demonstrated that NiCl₂ ions and NiTi nanoparticles induce pro-inflammatory and pro-angiogenic cytokine/chemokine expression in human endothelial and monocyte cell lines <i>in vitro.</i> These observations prompt concerns about potential mechanisms for stent failure. The data here showed a direct correlation between intracellular uptake of Ni²⁺ and generation of reactive oxygen species. To determine a role for nickel and NiTi nanoparticles in inducing angiogenesis <i>in vivo</i>, 1-cm silicone angioreactors were implanted subcutaneously into athymic (T-cell-deficient) nude mice. The angioreactors contained Matrigel (a gelatinous protein mixture that resembles extracellular matrix) in addition to one of the following: PBS (negative control), VEGF/FGF-2 (positive control), NiCl_2, or NiTi NP. The implantation of angioreactors represents a potential tool for quantification of angiogenic potentials of medical device-derived particles and ions <i>in vivo</i>. By this approach, NiTi NP were found to be markedly angiogenic, while Ni²⁺ was less-so. The angioreactors may provide a powerful tool to examine if debris shed from medical devices may promote untoward biological effects.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"19 1","pages":"61-73"},"PeriodicalIF":3.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10765802","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":"Adaptation of an ELISA assay for detection of IgG_2a responses against therapeutic monoclonal antibodies in a mouse immunization model.","authors":"Shraddha S Rane,&nbsp;Rebecca J Dearman,&nbsp;Ian Kimber,&nbsp;Jeremy P Derrick","doi":"10.1080/1547691X.2021.2020937","DOIUrl":"https://doi.org/10.1080/1547691X.2021.2020937","url":null,"abstract":"<p><p>Biotherapeutic monoclonal antibodies (mAb) play important roles in clinical medicine but their potential to elicit immune responses in patients remains a major issue. In a study designed to investigate the effect of aggregation on immunogenic responses, mice were immunized with two monoclonal antibodies (mAb1 and mAb2). Serum levels of total IgG, IgG₁, and IgG_2a were measured by ELISA. An anti-mouse IgG_2a monoclonal detection antibody cross-reacted with mAb2 but not mAb1, leading to high background when the ELISA plate was coated with mAb2. The problem was solved by use of a goat anti-mouse IgG_2a polyclonal antibody that demonstrated the required specificity. IgG_2a responses were similar for monomer- or aggregate-coated ELISA plates. The results demonstrate the importance of assessment of the specificity of individual reagents when measuring antibody responses against therapeutic antibodies by ELISA.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":" ","pages":"1-7"},"PeriodicalIF":3.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39948188","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":"Mitochondrial disruption in isolated human monocytes: an underlying mechanism for cadmium-induced immunotoxicity.","authors":"Ulfat M Omar,&nbsp;Ekramy M Elmorsy,&nbsp;Ayat B Al-Ghafari","doi":"10.1080/1547691X.2022.2113840","DOIUrl":"https://doi.org/10.1080/1547691X.2022.2113840","url":null,"abstract":"<p><p>Cadmium (Cd) is an immunotoxic metal frequently found in the environment. The <i>in vitro</i> study undertaken here evaluated the immunotoxic effects of Cd in isolated human peripheral blood monocytes (hPBM). The results of the studies of exposures to varying doses of Cd (0, 0.1, 1, 10, and 100 µM, as cadmium dichloride [CdCl₂]) for 3, 6, 12, 24, 48, and 72 hr showed the test agent was cytotoxic to the cells in time- and concentration-related manners. Thereafter, using only those doses found to not cause extreme cell lethality a 48-hr period, the impact of 0.1 or 1 µM CdCl₂ on the cells was evaluated. Functionally, CdCl₂ treatment led to time- and concentration-related decreases in hPBM phagocytic activities as well as in the ability of the cells to form/release cytokines (including tumor necrosis factor [TNF]-α and interleukin [IL]-6 and -8). The CdCl₂ also led to significantly decreased ATP production (in part, via inhibition of mitochondrial complexes I and III) as well as in mitochondrial membrane potentials (MMP) and oxygen consumption rates (OCR; associated with parallel increases in cell lactate production) in the cells. In addition, CdCl₂ treatment resulted in significant increases in mitochondrial membrane fluidity (MMF) and cell unsaturated fatty acid content. Based on the results here, one might conclude that some of the effects that arose during the CdCl₂-induced dysfunction of the isolated hPBM (i.e. changes phagocytic activity, cytokine formation/secretion) could have evolved secondary to CdCl₂-induced disruptions of hPBM cell bioenergetics - an effect that itself was a culmination of an overall toxicity from CdCl₂ upon the mitochondria within these cells.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"19 1","pages":"81-92"},"PeriodicalIF":3.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10415820","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":"Long non-coding RNA PMS2L2 is down-regulated in osteoarthritis and inhibits chondrocyte proliferation by up-regulating miR-34a.","authors":"Fei Yang,&nbsp;Min Zhao,&nbsp;Qinghua Sang,&nbsp;Changhong Yan,&nbsp;Zhenjun Wang","doi":"10.1080/1547691X.2022.2049664","DOIUrl":"https://doi.org/10.1080/1547691X.2022.2049664","url":null,"abstract":"<p><p>Long non-coding RNA (lncRNA) PMS2L2 has been reported to participate in endotoxin-induced inflammatory responses. As these types of responses can promote osteoarthritis (OA), it was of interest to ascertain if PMS2L2 may be involved in OA. To explore any potential participation of PMS2L2 in OA, synovial fluid was extracted from both OA patients and healthy controls (<i>n</i> = 62 each) and PMS2L2 expression of each sample determined by RT-qPCR. In addition, as miR-34a has a potential binding site on PMS2L2, hypothetical interactions between PMS2L2 and miR-34a in chondrocytes were analyzed by performing over-expression experiments. Furthermore, the role of PMS2L2 and miR-34a in the regulation of chondrocyte proliferation was analyzed using CCK-8 and BrdU assays. The results showed that PMS2L2 expression in OA patient synovial fluid was lower compared to that in control group fluid, and the extent of this reduction was related to disease stage. In <i>in vitro</i> studies, it was seen that endotoxin treatment of chondrocytes led to decreased PMS2L2 expression. It was found that PMS2L2 over-expression caused increased miR-34a expression in OA patient chondrocytes but not in cells from healthy controls. In contrast, miR-34a over-expression in either cell population did not affect PMS2L2 expression. Lastly, over-expression of both PMS2L2 and miR-34a led to inhibited chondrocyte proliferation. Of note, a combined over-expression of PMS2L2 and miR-34a resulted in stronger effects on proliferation compared to that from either single over-expression. Based on the findings that PMS2L2 is down-regulated during ongoing states of OA, and that changes in PMS2L2 expression can lead to increases in chondrocyte expression of miR-34a - resulting in inhibition of chondrocyte proliferation in OA. From these findings, one may conclude that finding means to regulate PMS2L2 could be a promising new target in the development of regimens for the treatment of OA.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"19 1","pages":"74-80"},"PeriodicalIF":3.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10765808","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}