International immunopharmacology最新文献_第3页

Panobinostat suppresses cGAS-STING pathway activation and ameliorates DSS-induced colitis in mice Panobinostat抑制cGAS-STING通路激活并改善dss诱导的小鼠结肠炎

IF 4.7 2区医学

International immunopharmacology Pub Date : 2025-10-10 DOI: 10.1016/j.intimp.2025.115637

Meizhen Qin , Zijiao Liu , Meng Wang , Wanqing Yang , Zihua Zhou , Mengfei Xue , Fan Xia , Chunyong Ding , Ao Zhang , Zhenliang Sun

引用次数: 0

Pathogenesis of osteoarthritis and treatment with traditional Chinese medicine: New perspectives on platelet aggregation 骨关节炎的发病机制及中医治疗：血小板聚集的新视角

IF 4.7 2区医学

International immunopharmacology Pub Date : 2025-10-10 DOI: 10.1016/j.intimp.2025.115665

Qian-qian Shao , Shuai-nan Zhang , Xu-zhao Li

{"title":"Pathogenesis of osteoarthritis and treatment with traditional Chinese medicine: New perspectives on platelet aggregation","authors":"Qian-qian Shao , Shuai-nan Zhang , Xu-zhao Li","doi":"10.1016/j.intimp.2025.115665","DOIUrl":"10.1016/j.intimp.2025.115665","url":null,"abstract":"<div><div>Osteoarthritis (OA) is a common joint disease affecting more than 500 million people worldwide, with a prevalence rate of 60 % among individuals aged 60 and above. Platelet aggregation plays a crucial role in the pathogenesis of OA, as it is involved in the inflammatory response, among other processes. This paper examines the role of platelet aggregation in the pathogenesis of OA over the past five years (2020–2024). Platelet aggregation releases inflammatory mediators, activating inflammatory signaling pathways and inducing joint inflammation. The release of these mediators can disrupt the proliferation and metabolism of chondrocytes, leading to apoptosis and the destruction of cartilage structure. It also enhances the permeability of synovial blood vessels and stimulates the proliferation of synovial cells, resulting in synovial hyperplasia and joint swelling. Moreover, studies over the past five years have shown that active ingredients of Traditional Chinese Medicines (TCMs) can treat OA by regulating platelet aggregation. Forty-two active ingredients of TCMs and six Chinese medicinal formulations were analyzed, including active ingredients of TCMs such as tanshinone IIA and paeoniflorin. These ingredients can treat OA by anti-inflammatory, modulating signaling pathways such as mitogen-activated protein kinase/nuclear factor kappa-B (MAPK/NF-κB), and protecting cartilage. These active ingredients can serve as an alternative and valuable source of treatment for OA. Currently, the relationship between platelet aggregation and OA is not yet fully understood, and further research and exploration are necessary.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"167 ","pages":"Article 115665"},"PeriodicalIF":4.7,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145270469","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}

引用次数: 0

Corrigendum to "Downregulation of S100A11 promotes T cell infiltration by regulating cancer-associated fibroblasts in prostate cancer" [Int. Immunopharmacol. 128 (2024) 111323]. “下调S100A11通过调节前列腺癌相关成纤维细胞促进T细胞浸润”的更正[j]。免疫药理学报，128(2024):111323。

IF 4.7 2区医学

International immunopharmacology Pub Date : 2025-10-10 Epub Date: 2025-08-28 DOI: 10.1016/j.intimp.2025.115415

Dali Han, Chenhao Guo, Hui Cheng, Jianzhong Lu, Zizhen Hou, Xingxing Zhang, Yao Luo, Bin Zhang, Wenli Zhao, Panfeng Shang

引用次数: 0

Corrigendum to "High glucose intake exacerbates experimental autoimmune prostatitis through mitochondrial reactive oxygen species-dependent TGF-β activation-mediated Th17 differentiation" [Int. Immunopharmacol. 130 (2024) 111682]. “高糖摄入通过线粒体活性氧依赖TGF-β激活介导的Th17分化加剧实验性自身免疫性前列腺炎”的更正[j]。免疫药理学报，130(2024):111682。

IF 4.7 2区医学

International immunopharmacology Pub Date : 2025-10-10 Epub Date: 2025-08-26 DOI: 10.1016/j.intimp.2025.115328

Di Niu, Shao-Yu Yue, Xu Wang, Wei-Yi Li, Li Zhang, He-Xi Du, Chao-Zhao Liang

引用次数: 0

Non-lethal sonodynamic therapy-engineered foam cell exosomes reprograms endothelial immunometabolic crosstalk to stabilize atherosclerotic plaques 非致死性声动力治疗工程泡沫细胞外泌体重编程内皮免疫代谢串扰以稳定动脉粥样硬化斑块

IF 4.7 2区医学

International immunopharmacology Pub Date : 2025-10-10 DOI: 10.1016/j.intimp.2025.115675

Yu Li , Zhiqiang Yang , Xueyuan Ma , Pengbin Fu , Lihong Zhang , Penghao Gao , Yifan Wang , Zhihao Chen , Ye Tian , Yang Yang

{"title":"Non-lethal sonodynamic therapy-engineered foam cell exosomes reprograms endothelial immunometabolic crosstalk to stabilize atherosclerotic plaques","authors":"Yu Li , Zhiqiang Yang , Xueyuan Ma , Pengbin Fu , Lihong Zhang , Penghao Gao , Yifan Wang , Zhihao Chen , Ye Tian , Yang Yang","doi":"10.1016/j.intimp.2025.115675","DOIUrl":"10.1016/j.intimp.2025.115675","url":null,"abstract":"<div><h3>Objective</h3><div>While non-lethal sonodynamic therapy (NL-SDT) demonstrates therapeutic potential for atherosclerosis, its immunomodulatory mechanisms via exosomal signaling remain unexplored. This study investigates how SDT-engineered foam cell exosomes orchestrate plaque stabilization through coordinated immunometabolic reprogramming of endothelial inflammation and matrix dynamics.</div></div><div><h3>Methods</h3><div>Atherosclerotic <em>apolipoprotein E</em>-deficient mice received NL-SDT with GW4869-mediated exosome blockade to confirm SDT-exosome axis dependency. Exosomes from bone marrow-derived foam cells were isolated, sequenced, and functionally validated via miR-17-5p gain/loss-of-function experiments. Dual-luciferase reporter assays confirmed miR-17-5p targeting of ABCA1 (cholesterol metabolism) and TIMP2 (inflammatory matrix regulation). Endothelial cholesterol efflux (using BODIPY-cholesterol) and MMP2/MMP9 levels were quantified.</div></div><div><h3>Results</h3><div>SDT-engineered foam cell exosomes showed endothelial tropism, delivering anti-inflammatory miR-17-5p suppression. Through miR-17-5p downregulation, SDT-engineered exosomes activated ABCA1-dependent cholesterol efflux and enhanced TIMP2-mediated MMP inhibition.</div></div><div><h3>Conclusion</h3><div>We identify SDT-engineered exosomes as novel immunotherapeutic vectors that synchronize metabolic detoxification and immune resolution in atherosclerotic plaques. Mechanistically distinct from direct exosome therapies, SDT amplifies endogenous exosome production while engineering cargo specificity, offering a tunable, lesion-targeted strategy.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"167 ","pages":"Article 115675"},"PeriodicalIF":4.7,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145270474","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}

引用次数: 0

Arsenic trioxide enhances the inhibitory effect of lenvatinib on hepatocellular carcinoma through HMOX1-mediated ferroptosis 三氧化二砷通过hmox1介导的铁凋亡增强lenvatinib对肝癌的抑制作用

IF 4.7 2区医学

International immunopharmacology Pub Date : 2025-10-09 DOI: 10.1016/j.intimp.2025.115656

Shufang Liang , Guokai Huang , Meihuan Fu , Yuanrong Shi , Xiaoyu Tu , Wanfu Lin , Jianhui Tian , Xiaofeng Zhai , Binbin Cheng

{"title":"Arsenic trioxide enhances the inhibitory effect of lenvatinib on hepatocellular carcinoma through HMOX1-mediated ferroptosis","authors":"Shufang Liang , Guokai Huang , Meihuan Fu , Yuanrong Shi , Xiaoyu Tu , Wanfu Lin , Jianhui Tian , Xiaofeng Zhai , Binbin Cheng","doi":"10.1016/j.intimp.2025.115656","DOIUrl":"10.1016/j.intimp.2025.115656","url":null,"abstract":"<div><div>Currently, Lenvatinib, a tyrosine kinase inhibitor, is used as a first-line treatment for advanced hepatocellular carcinoma (HCC), but its efficacy remains unsatisfactory. Therefore, we investigated the effect of Lenvatinib in combination with Arsenic trioxide (ATO) on HCC and the underlying mechanisms. The antitumor activity of the combination was evaluated in vitro using MTT and colony formation assays, and in vivo using xenograft models in nude mice. mRNA-seq was performed to explore the potential mechanisms. Reactive oxygen species (ROS) and intracellular Fe<sup>2+</sup> were measured to evaluate ferroptosis in HCC cells. Our findings showed that the addition of ATO significantly enhanced the anti-HCC effects of Lenvatinib both in vitro and in vivo. Moreover, RNA sequencing analysis indicated that ATO augmented the anti-HCC effect of Lenvatinib by inducing ferroptosis. Both ATO alone and the combination treatment markedly induced a significant elevation of ROS and ferroptosis, which was effectively blocked by the administration of ferrostatin-1 and deferoxamine mesylate. Furthermore, ATO upregulated the levels of heme oxygenase 1 (HMOX1) and Fe<sup>2+</sup> in HCCLM3 and Huh7 cells. Knockdown of HMOX1 attenuated the effect of ATO on HCC cell viability, ROS and Fe<sup>2+</sup> levels in HCC cells. Additionally, ATO and the combination of Lenvatinib and ATO also decreased the expression of GPX4 protein both in vitro and in vivo. In conclusion, ATO enhances the antitumor activity of Lenvatinib against HCC by inducing ferroptosis through upregulation of HMOX1 and downregulation GPX4.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"167 ","pages":"Article 115656"},"PeriodicalIF":4.7,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145247916","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}

引用次数: 0

Phellodendrine alleviates acute pancreatitis by inhibiting p38 MAPK-p47phox pathway-mediated neutrophil extracellular traps formation and ROS production 黄柏碱通过抑制p38 MAPK-p47phox途径介导的中性粒细胞胞外陷阱的形成和ROS的产生来缓解急性胰腺炎

IF 4.7 2区医学

International immunopharmacology Pub Date : 2025-10-09 DOI: 10.1016/j.intimp.2025.115658

Jingjing Zhang , Pin Li , Xingmeng Xu , Yishao He , Chenchen Yuan , Fei Han , Weiming Xiao , Guotao Lu , Weijuan Gong , Jinqiang Zhuang , Weixuan Yang

{"title":"Phellodendrine alleviates acute pancreatitis by inhibiting p38 MAPK-p47phox pathway-mediated neutrophil extracellular traps formation and ROS production","authors":"Jingjing Zhang , Pin Li , Xingmeng Xu , Yishao He , Chenchen Yuan , Fei Han , Weiming Xiao , Guotao Lu , Weijuan Gong , Jinqiang Zhuang , Weixuan Yang","doi":"10.1016/j.intimp.2025.115658","DOIUrl":"10.1016/j.intimp.2025.115658","url":null,"abstract":"<div><h3>Background</h3><div>Acute pancreatitis (AP) is an inflammatory disorder of pancreas, where the formation of neutrophil extracellular traps (NETs) plays a crucial role in its pathogenesis. This study examined the therapeutic effect of Phellodendrine (PHE), a <em>Phellodendron</em>-derived alkaloid, on AP by assessing NETs formation and underlying mechanisms.</div></div><div><h3>Methods</h3><div>Mouse bone marrow neutrophils were isolated and stimulated to form NETs in vitro to assess PHE's impact. A Caerulein-induced AP mouse model was developed to assess the in vivo efficacy of PHE. Network pharmacology and RNA-seq analysis were utilized to investigate the mechanisms through which PHE alleviates AP. The functional role of the identified target was verified using a p38 inhibitor.</div></div><div><h3>Results</h3><div>PHE markedly inhibited NETs formation and reactive oxygen species (ROS) generation in vitro. In vivo experiments further revealed PHE treatment alleviated pancreatic injury and inflammation, which was accompanied by reduced NETs formation and neutrophil infiltration in the mouse of AP. Mechanistically, PHE targeted the p38 MAPK pathway, suppressing its activation and the subsequent membrane translocation of p47<sup>phox</sup>. Furthermore, co-administration with a p38 inhibitor abolished the inhibitory effects of PHE on NETs formation and ROS production.</div></div><div><h3>Conclusion</h3><div>PHE mitigates pancreatic injury and inflammation in AP through its inhibitory effect on NETs formation and ROS production, mediated by targeting the p38 MAPK-p47<sup>phox</sup> pathway. This indicates its potential as an innovative therapeutic agent for the treatment of AP.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"167 ","pages":"Article 115658"},"PeriodicalIF":4.7,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145247948","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}

引用次数: 0

Inhibition of Pannexin1 alleviates the damage of pilocarpine-induced status epilepticus through diminishing inflammatory PANoptosis-like neuron death 抑制Pannexin1可通过减少炎症性Pannexin1样神经元死亡，减轻匹罗卡品诱导的癫痫持续状态的损害。

IF 4.7 2区医学

International immunopharmacology Pub Date : 2025-10-07 DOI: 10.1016/j.intimp.2025.115639

Bowen Sun , Jiao Wu , Zhiqiang Li , Yudie Zhang , Xi Lu , Jialu Wang , Xiaoxue Xu

{"title":"Inhibition of Pannexin1 alleviates the damage of pilocarpine-induced status epilepticus through diminishing inflammatory PANoptosis-like neuron death","authors":"Bowen Sun , Jiao Wu , Zhiqiang Li , Yudie Zhang , Xi Lu , Jialu Wang , Xiaoxue Xu","doi":"10.1016/j.intimp.2025.115639","DOIUrl":"10.1016/j.intimp.2025.115639","url":null,"abstract":"<div><div>Neuroinflammation has been closely associated with epileptogenesis, which is one of the contributors to neuronal cell death. PANoptosis is a newly defined form of inflammatory cell death characterized by a cascade interaction of pyroptosis, apoptosis, and necroptosis. As a large-pore channel permeable to ions and metabolites, Pannexin 1 (Panx1) is known to drive inflammatory responses and multiple programmed cell death patterns. However, the specific role of Panx1 in PANoptosis in epilepsy remains unclear. This study aims to investigate the involvement of Panx1 in inflammatory PANoptosis-like neuron death in pilocarpine-induced status epilepticus (SE) models. Elevated Panx1 levels were discovered in serum from patients with epilepsy, as well as in SE mice and pilocarpine-treated HT22 cells. Utilizing the Panx1 inhibitor probenecid improved the epileptic EEG and cognitive dysfunction in SE mice by mitigating neuron loss. The application of antagonists of pyroptosis, apoptosis, or necroptosis alone could not completely prevent cell death, while the combination of these three inhibitors provided the greatest neuroprotective effect. PANoptosome-related proteins were found to be up-regulated. Additionally, changes in morphological features, along with abnormal protein levels of several key proteins involved in pyroptosis, apoptosis, and necroptosis, indicated the occurrence of PANoptosis <em>in vivo</em> and <em>in vitro</em>. Moreover, pharmacological blockade of Panx1 ameliorated PANoptosis. These results suggest the presence of PANoptosis-like neuron death in epileptic injury. Our findings also suggest that Panx1 may be involved in PANoptosis, identifying Panx1 as a crucial regulator of the neuroinflammatory response in the context of epilepsy.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"166 ","pages":"Article 115639"},"PeriodicalIF":4.7,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250929","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}

引用次数: 0

FOSL1: The core regulatory hub of tumor-neural interactions and its clinical translational prospects FOSL1：肿瘤-神经相互作用的核心调控枢纽及其临床转化前景。

IF 4.7 2区医学

International immunopharmacology Pub Date : 2025-10-06 DOI: 10.1016/j.intimp.2025.115645

Niu Pu , Xitong Bo , Haimin Lu, Fuxiang Chen, Yilong Zhou, Qiong Cheng

{"title":"FOSL1: The core regulatory hub of tumor-neural interactions and its clinical translational prospects","authors":"Niu Pu , Xitong Bo , Haimin Lu, Fuxiang Chen, Yilong Zhou, Qiong Cheng","doi":"10.1016/j.intimp.2025.115645","DOIUrl":"10.1016/j.intimp.2025.115645","url":null,"abstract":"<div><div>As a core AP-1 transcription factor, FOS like-1 (FOSL1) drives cell proliferation, differentiation, transformation, and tumorigenesis by regulating downstream targets via heterodimer formation. Pan-cancer analyses confirm its characteristic overexpression in solid tumors, with expression levels strongly correlating with tumor invasiveness and metastasis. Emerging evidence highlights tumor-nerve crosstalk in the tumor microenvironment (TME) as a key driver of progression, and recent studies identify FOSL1 as a central regulatory hub linking tumors and the nervous system. It modulates tumor-neural interactions through mechanisms that include Schwann cell reprogramming, chemokine network construction, axon orientation regulation, synaptic connection modulation, and immune-neuro-tumor synergy, thereby promoting neural remodeling, invasion, metastasis, and TME reprogramming. Elucidating FOSL1's multidimensional regulation of tumor-nerve crosstalk not only offers new insights into tumor neural dependency but also establishes a theoretical basis for developing FOSL1-based diagnostic markers, prognostic tools, and novel targeted therapies, with substantial clinical translational potential.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"166 ","pages":"Article 115645"},"PeriodicalIF":4.7,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244576","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}

引用次数: 0

Mitochondrial protease ClpP deficiency protects against tubulointerstitial damage in diabetic kidney disease 线粒体蛋白酶ClpP缺乏可预防糖尿病肾病的小管间质损伤。

IF 4.7 2区医学

International immunopharmacology Pub Date : 2025-10-06 DOI: 10.1016/j.intimp.2025.115641

Huafen Wang , Yifei Liu , Jialu Liu , Shumin Zhang , Xiaohui Li , Lin Sun , Fuyou Liu , Yu Liu , Li Xiao

{"title":"Mitochondrial protease ClpP deficiency protects against tubulointerstitial damage in diabetic kidney disease","authors":"Huafen Wang , Yifei Liu , Jialu Liu , Shumin Zhang , Xiaohui Li , Lin Sun , Fuyou Liu , Yu Liu , Li Xiao","doi":"10.1016/j.intimp.2025.115641","DOIUrl":"10.1016/j.intimp.2025.115641","url":null,"abstract":"<div><div>Mitochondrial quality control (MQC) imbalance has been implicated in tubulointerstitial damage of diabetic kidney disease (DKD). The mitochondrial unfolded protein response (UPRmt) is a stress-adaptive transcriptional response required for MQC. Caseinolytic peptidase P (ClpP), the critical component of the UPRmt proteolytic system, plays an essential role in regulating mitochondrial function with both beneficial and detrimental outcomes. Still, its effects on kidney pathobiology remain unclear. Here, we observed that ClpP was distributed in renal tubules and was significantly increased in the kidneys of DKD patients and db/db mice, accompanied by increased expression of the UPRmt-related molecular chaperones heat shock protein 60 (HSP60), heat shock protein 10 (HSP10) and activating transcription factor 5 (ATF5) and positively correlated with renal oxidative stress, cell apoptosis and tubulointerstitial fibrosis. ClpP shRNA alleviated tubular cell apoptosis, oxidative damage and tubulointerstitial injury in diabetic mice. The expression of HSP60, HSP10 and ATF5 was inhibited, indicating that lowering ClpP suppressed UPRmt activation. In vitro, ClpP was localized in the mitochondria of HK-2 cells. High glucose (HG) treatment upregulated ClpP expression and UPRmt-related proteins, concurrent with enhanced mitochondrial reactive oxygen species (mtROS), fibrosis markers and apoptosis. These alterations were reduced by ClpP siRNA. Instead, ClpP overexpression further exacerbated these abnormalities in HK-2 cells, while these facilitation effects were partially reversed by UPRmt suppression. Our results indicated that ClpP deficiency ameliorated renal oxidative stress and tubulointerstitial injury in DKD by inhibiting excessive UPRmt activation. These results suggest that ClpP is a valuable therapeutic target for DKD.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"166 ","pages":"Article 115641"},"PeriodicalIF":4.7,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244603","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}

引用次数: 0