International immunopharmacology最新文献

{"title":"Epiberberine ameliorates MNNG-induced chronic atrophic gastritis by acting on the EGFR-IL33 axis.","authors":"Juan Li, Xiantao Chen, Changxia Mao, Mengyuan Xiong, Zhengcai Ma, Jianyu Zhu, Xuegang Li, Wanqun Chen, Hang Ma, Xiaoli Ye","doi":"10.1016/j.intimp.2024.113718","DOIUrl":"10.1016/j.intimp.2024.113718","url":null,"abstract":"<p><p>Chronic atrophic gastritis (CAG) is a prevalent form of chronic gastritis that presents with chronic inflammation of the gastric mucosa, localised gastric mucosal glandular atrophy and intestinal metaplasia. Despite the existence of diagnostic criteria, effective therapeutic strategies for this condition remain to be developed. The objective of this study was to examine the potential therapeutic benefits of epiberberine in mitigating MNNG-induced CAG and to elucidate the underlying mechanisms. MNNG was employed to establish a CAG mouse model and a GES-1 cell model, and EPI was observed to be efficacious in ameliorating the gastric mucosal injury and inflammatory infiltration induced by MNNG in the CAG model mice, a finding that was subsequently validated in the GES-1 model cells. Bioinformatics analysis indicated that EPI may exert a direct effect on EGFR, thereby regulating the expression of IL-33 and thereby achieving the therapeutic effect of CAG. This hypothesis was also validated by molecular docking prediction, CETSA, and overexpression of EGFR in GES-1 model cells, using EGFR agonists and inhibitors to further demonstrate that EPI may act as an antagonist supplement to EGFR for the treatment of CAG.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"145 ","pages":"113718"},"PeriodicalIF":4.8,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mollugin inhibits IL-1β production by reducing zinc finger protein 91-regulated Pro-IL-1β ubiquitination and inflammasome activity.","authors":"Lei Song, Yi Tai, Jia Xuan Li, Shen Cao, Jing Han, Xin Zhe Liu, Sheng Cao, Ming Yue Li, Hong Xiang Zuo, Yue Xing, Juan Ma, Xuejun Jin","doi":"10.1016/j.intimp.2024.113757","DOIUrl":"10.1016/j.intimp.2024.113757","url":null,"abstract":"<p><strong>Background: </strong>Rubia cordifolia L. has been formally included in the Chinese Pharmacopoeia and utilized for centuries as a traditional Chinese medicine. Mollugin, a quinone compound, is a major active compound extracted from Rubia cordifolia L. Mollugin was reported has multiple pharmacological activity, including anti-inflammatory, anti-tumor effects. However, the anti-inflammatory mechanism is not yet clear. In this study, we explored the anti-inflammatory activity and potential mechanism of mollugin in vitro and in vivo.</p><p><strong>Materials and methods: </strong>We explored the mechanisms that mollugin suppressed IL-1β expression through ZFP91 using various assays, including western blot, immunofluorescence, immunoprecipitation, MTT, RT-PCR, and ELISA assays in vitro. In vivo, oral administration of DSS induced colitis in mice and intraperitoneal injection of alum induced peritonitis in mice.</p><p><strong>Results: </strong>First, the results demonstrated that mollugin dramatically suppressed IL-1β secretion through reducing ZFP91 in macrophages. Crucially, we proved that mollugin inhibited K63-linked Pro-IL-1β ubiquitination through ZFP91 and limitated Pro-IL-1β cleavage efficacy. In addition, ZFP91-mediated Caspase-8 inflammasome component expression was inhibited by mollugin. Furthermore, mollugin inhibited the assembly of the Caspase-8 inflammasome complex by downregulating ZFP91. In vivo studies further revealed that mollugin improved DSS-induced colitis and alum-induced peritonitis in mice by reducing ZFP91. Notely, mollugin significantly altered the abundance of gut flora in DSS-induced colitis mice, which in turn ameliorated the colitis.</p><p><strong>Conclusion: </strong>We present a novel finding that mollugin inhibition of ZFP91 is a crucial regulatory step, preventing undue inflammatory responses and thereby maintaining immune homeostasis. The current study offers new insight into the development of anti-inflammatory therapeutics targeting ZFP91.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"145 ","pages":"113757"},"PeriodicalIF":4.8,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ALKBH5 promotes malignant proliferation of renal clear cell carcinoma by activating the MAPK pathway through binding to HNRNPDL.","authors":"Wei Song, Houliang Zhang, Jinliang Ni, Huiqing Hu, Weipu Mao, Keyi Wang, Bo Peng","doi":"10.1016/j.intimp.2024.113776","DOIUrl":"10.1016/j.intimp.2024.113776","url":null,"abstract":"<p><p>It is well established that ALKBH5 plays a crucial role in the malignant progression of various types of tumors. However, its role in clear cell renal cell carcinoma (ccRCC) and the underlying regulatory mechanisms remain unclear. In this study, we employed a range of techniques, including protein blotting, real-time quantitative PCR, silver staining, mass spectrometry, co-immunoprecipitation (Co-IP), GST-pull down, and immunofluorescence, to investigate the functions of ALKBH5 in ccRCC and elucidate the specific mechanisms involved. Our results demonstrated that ALKBH5 expression was significantly upregulated in ccRCC. In vitro experiments revealed that ALKBH5 promoted tumor proliferation, invasion, migration, and stemness. In vivo, ALKBH5 was shown to enhance tumor growth and lung metastasis. Mechanistically, our studies suggest that ALKBH5 accelerates the malignant progression of ccRCC by binding to heterogeneous nuclear ribonucleoprotein D-like (HNRNPDL), facilitating the nuclear translocation of MEK, ERK, and p38, and activating downstream targets such as c-Myc and PCNA.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"145 ","pages":"113776"},"PeriodicalIF":4.8,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of anti-CD19 CAR-T in a mouse model of IgG4-related disease.","authors":"Yeting Sun, Sicheng Huang, Bo Zhang, Yu Peng, Hui Lu, Yimeng Jia, Ruijie Sun, Fenghua Zhang, Jiaxin Zhou, Linyi Peng, Mengtao Li, Wen Zhang, Yunyun Fei","doi":"10.1016/j.intimp.2024.113779","DOIUrl":"10.1016/j.intimp.2024.113779","url":null,"abstract":"<p><p>Dysregulated B-cell activation plays pivotal roles in IgG4-related disease (IgG4-RD), which makes B-cell depletion a potential strategy for IgG4-RD treatment. In this study, we aimed to investigate the feasibility of applying anti-CD19 chimeric antigen receptor T(CAR-T) cell therapy to IgG4-RD treatment in a mouse disease model based on LatY136F knock-in (Lat) mice. We constructed murine anti-CD19 CARs with either CD28 or 4-1BB as the intracellular costimulatory motif and evaluated the therapeutic function of the corresponding CAR-T cells by infusing them into Lat mice. Next, we assessed the safety of CAR-T infusion by evaluating the risk of cytokine release syndrome (CRS) and the antiviral capabilities in a mouse influenza infection model. Finally, we performed human anti-CD19 CAR-T manufacturing from IgG4-RD patients and evaluated its activation level and functional effects in vitro. Compared with 1D3 antibody treatment, the adoptive transfer of anti-CD19 CAR-T cells with CD28 costimulatory motif showed comparable B-cell-depletion effect in Lat mice. Furthermore, the transfer of syngeneic anti-CD19 CAR-T cells also decreased the percentage of plasma cells as well as IL-4 secreting Th cells, therefore attenuating the inflammation and fibrosis condition. CAR-T cells with CD28 costimulatory motif showed better therapeutic efficiency without the incidence of serious CRS events or increasing the risk of infection. In addition, we validated the feasibility of human CAR-T preparation in vitro from IgG4-RD patients. Taken together, these results show that anti-CD19 CAR-T therapy was effective in the treatment of a murine model of IgG4-RD, indicating its potential for clinical use in patients.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"145 ","pages":"113779"},"PeriodicalIF":4.8,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CircSugp1 interacts with CPSF6 to modulate intestinal mucosa repair by regulating alternative polyadenylation-mediated shortening of the Wdr89 3'UTR.","authors":"Yu Liao, Ran Li, Hao Zhang, Qi Li, Xiaoqing Xu, Fanze Meng, Yong Sun","doi":"10.1016/j.intimp.2024.113793","DOIUrl":"10.1016/j.intimp.2024.113793","url":null,"abstract":"<p><p>Circular RNAs are a single-stranded non-coding RNAs and play an important role in the development of many diseases. Alternative polyadenylation (APA) regulates the gene 3'UTR length for controlling gene expressions. Although the APA mechanism has been widely studied in the development of diseases, there is no data on its role in the burned intestinal mucosa. We thus herein assessed the role of the circSugp1-initiating APA mechanism in the burned intestinal mucosa. CircSugp1 was downregulated in the intestinal mucosa of burned mice. CircSugp1 promoted proliferation and migration in vitro and in vivo. CircSugp1 promotes the expression of CPSF6; the overexpression of CPSF6 can shorten the gene 3'UTR within the transcript APA range. The promoting effect of circSugp1 on value-added migration was mediated by the APA regulation of the Wdr89 short 3'UTR isoform. CircSugp1 targeted the upregulation of the expression of CPSF6, followed by upregulation of the expression of Wdr89 through APA, promoting the repair of intestinal mucosal damage in burned mice.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"145 ","pages":"113793"},"PeriodicalIF":4.8,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An injectable hydrogel loaded with Icariin attenuates cartilage damage in rabbit knee osteoarthritis via Wnt/β-catenin signaling pathway.","authors":"Hanxiao Zheng, Limin Qu, Lei Yang, Xianmin Xie, Ling Song, Qiuen Xie","doi":"10.1016/j.intimp.2024.113725","DOIUrl":"10.1016/j.intimp.2024.113725","url":null,"abstract":"<p><p>Knee osteoarthritis (KOA) is a chronic disease characterized by joint wear and cartilage degeneration. Current clinical treatments are based on symptomatic relief and are not effective in regenerating cartilage, and inflammation-induced cartilage damage accelerates the progression of osteoarthritis, making the protection of articular cartilage important for controlling the development of knee osteoarthritis. In this study, a biodegradable hydrogel (HA-Ca-Alg@Ica) loaded with Icariin (Ica) was prepared by in situ cross-linking of hyaluronic acid-calcium complex (HA-Ca) and sodium alginate (Alg-Na) for local sustained delivery of Ica. The hydrogel promoted chondrocyte proliferation and inhibited the degradation of cartilage matrix by regulating key factors (Wnt3a, β-catenin and GSK-3β) in the Wnt/β-catenin signaling pathway. In addition, the hydrogel reduced the expression of inflammatory factors, including IL-1β, IL-6, TNF-α, COX-2, and MMP13, leading to a reduction in inflammation and pain relief. In summary, this hydrogel containing Icariin has shown significant effects in reducing chondrocyte degradation and promoting chondrocyte proliferation, which can play a role in delaying osteoarthritis by protecting chondrocytes. These findings offer innovative prospects for the therapeutic management of knee osteoarthritis.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"145 ","pages":"113725"},"PeriodicalIF":4.8,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of curcumin regulated memory Th7 cells in mice with DSS-induced colitis.","authors":"Lizhao Song, Yifei Deng, Jiaqi Huang, Xiyan Zhu, Youbao Zhong, Qin Zhong, Wen Zhou, Yali Liu, Haimei Zhao, Wei Ge, Duanyong Liu","doi":"10.1016/j.intimp.2024.113770","DOIUrl":"10.1016/j.intimp.2024.113770","url":null,"abstract":"<p><p>Abnormal activation or dysfunction of memory helper T (mTh) cells is closely associated with the development of ulcerative colitis (UC). Curcumin (Cur), the main component of turmeric, plays a critical role in the treatment of UC due to its favorable anti-inflammatory and immunomodulatory bioactivities. However, whether Cur modulates mTh7 cells to alleviate UC is unknown. In the present study, dextran sulphate sodium (DSS) was administered to establish a colitis model in mice. Our current findings indicated that Cur effectively ameliorated the manifestations of colitis in mice, and had a significant effect in reducing disease activity index (DAI), as well as in the colonic weight and the proportion of colonic weight to colonic length. While Cur reduced the pathological injuries of the colon, restore the length of the colon, inhibited the secretion of IL-7 and IL-21, restored the secretion of IL-2, IL-4, and IL-10. Furthermore, Cur had a regulatory effect on mTh7 cells and their subpopulation status. The results of molecular docking simulations and Surface Plasmon Resonance (SPR) indicated that Cur demonstrates strong interaction capabilities with both IL-7 and IL-7R and reduced the expression levels of IL-7/IL-7R mRNA and protein. It is suggested that the alleviation of DSS-induced colitis by Cur may be achieved by reducing the level of mTh7 cells and inhibiting the activation of IL-7/IL-7R signaling.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"145 ","pages":"113770"},"PeriodicalIF":4.8,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating scRNA-seq and Visium HD for the analysis of the tumor microenvironment in the progression of colorectal cancer.","authors":"Chun Wang, Mengying Lu, Cuimin Chen, Jiajun Chen, Yusi Cai, Hao Wang, Lili Tao, Weihua Yin, Jiakang Chen","doi":"10.1016/j.intimp.2024.113752","DOIUrl":"10.1016/j.intimp.2024.113752","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) development is a complex, multi-stage process, transitioning from normal to adenomatous tissue, and then to invasive carcinoma. Despite research, there's a knowledge gap on using high-resolution spatial omics to understand CRC's tumor microenvironment dynamics.</p><p><strong>Methods: </strong>We used single-cell transcriptomics to study major biological changes and cell interactions in CRC progression. Additionally, high-resolution spatial transcriptomics helped us examine the spatial distribution of cells with significant pathway changes, offering insights into the tumor microenvironment's development throughout CRC stages.</p><p><strong>Results: </strong>In the progression of CRC, plasma cells, neutrophils, and fibroblasts exhibit the most significant changes in hallmark pathways, while epithelial cells show the most pronounced alterations in metabolic pathways. We also identified a population of NOTUM + epithelial cells and IGHG1/3 + plasma cells that are concentrated at the boundary between normal tissue and adenomas. Pathway analysis further suggests that these NOTUM + cells activate numerous cancer-related pathways, despite the absence of significant pathological morphological changes. Additionally, we conducted a targeted drug prediction analysis to identify potential therapeutic agents for NOTUM-expressing epithelial cells.</p><p><strong>Conclusions: </strong>Analyzing scRNA-seq and Visium HD data, we found that IGHG1/3 + plasma cells and tumor-associated neutrophil (TANs) may significantly affect colorectal tissue transformation from normal to adenoma and carcinoma. These cells are concentrated at the transition between normal and adenomatous tissue. We also found NOTUM-expressing cells at the edge of normal and adenomatous areas, possibly indicating a morphological transition as normal cells evolve into adenoma cells.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"145 ","pages":"113752"},"PeriodicalIF":4.8,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide screen based on 2DG activated NLRP3 inflammasome reveals the priming signal of TLR2/4 to IKKβ but not IKKα.","authors":"Hui Gao, Mengning Sun, Hang Gao, Yi Sun, Wenjuan Chen, Na Dong","doi":"10.1016/j.intimp.2024.113781","DOIUrl":"10.1016/j.intimp.2024.113781","url":null,"abstract":"<p><p>NLRP3 inflammasome activation is a pivotal area of research in innate immunity, yet the precise priming and activation signal remain unclear. In this study, we demonstrate that glycolysis inhibitor 2-Deoxy-D-glucose (2DG) triggers NLRP3-driven pyroptosis in human leukemia monocyte THP-1 cells by interfering glycosylation rather than glycolysis, which occurs independent of potassium efflux but requires the involvement of glycolysis rate-limiting enzyme PFKP. Using a CRISPR-Cas9 mediated large-scale screen, with 2DG as a new tool for probing NLRP3 activation, we identified that TLR2, rather than TLR4, initiates a rapid and robust priming signal for NLRP3 inflammasome activation. Importantly, both TLR2 and TLR4 depend entirely on MyD88, but not TRIF, for signal transduction. Furthermore, we discovered that TAK1, IKKβ and NEMO, but not IKKα, are essential for the priming signal. Additionally, we observed that deficiency in the linear ubiquitin assembly complex (LUBAC) subunits HOIP and HOIL-1, but not SHARPIN, is sufficient to inhibit 2DG-induced pyroptotic cell death. Collectively, our study reveals some common mechanism in the NLRP3 priming signals, as well as specific mechanisms upstream of NLRP3 triggered by 2DG, and underscores the potential of 2DG as a trigger to facilitate further detailed analysis of the underlying mechanisms of NLRP3 inflammasome activation. One Sentence Summary: Priming signal by IKKβ is essential for NLRP3 activation.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"145 ","pages":"113781"},"PeriodicalIF":4.8,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyperoside attenuates sepsis-induced acute lung injury by Nrf2 activation and ferroptosis inhibition.","authors":"Kuida Chen, Shipeng Lu, Ke Shi, Mustafa Hussein Ali, Jian Liu, Fangzhou Yin, Wu Yin","doi":"10.1016/j.intimp.2024.113734","DOIUrl":"10.1016/j.intimp.2024.113734","url":null,"abstract":"<p><p>Sepsis-induced acute lung injury (ALI) is a life-threatening condition associated with high morbidity and mortality rates in intensive care units (ICUs). Emerging evidence from clinical studies suggests that compounds derived from traditional Chinese medicine (TCM) have shown promising therapeutic effects in treating sepsis-induced ALI. Hyperoside is a bioactive compound extracted from TCM. Prior studies reported that hyperoside exhibits potent anti-inflammatory, antioxidant, and organ-protective properties, however, the underlying mechanisms of its effects on ALI remain unclear. Hyperoside pretreatment significantly reduced inflammation, iron accumulation, and lipid peroxidation in the pulmonary tissues of ALI mice induced by CLP and in LPS-stimulated MLE-12 cells. In particular, hyperoside preferentially binds with Keap1 at Arg380 and Arg415, thereby inhibiting the ubiquitin-mediated degradation of nuclear Nrf2, promoting its translocation to the nucleus, and leading to upregulation of anti-ferroptosis gene expression. Moreover, the protective effects of hyperoside were significantly abrogated after Nrf2 expression was silenced or its activity was inhibited by chemical inhibitors, highlighting that Nrf2 is critically involved in the impact of hyperoside. This study confirms that hyperoside exhibits a therapeutically protective effect against sepsis-induced ALI by inhibiting ferroptosis through Nrf2-mediated signaling pathway. Hyperoside acts as an Nrf2 activator by preferentially binding to Arg380 and Arg415 of Keap1 and disrupting the Keap1/Nrf2 interaction.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"145 ","pages":"113734"},"PeriodicalIF":4.8,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}