Immunology最新文献_第10页

Glycans in melanoma: Drivers of tumour progression but sweet targets to exploit for immunotherapy 黑色素瘤中的糖类：肿瘤进展的驱动因素，但也是免疫疗法可利用的甜蜜目标。

IF 4.9 3区医学

Immunology Pub Date : 2024-05-14 DOI: 10.1111/imm.13801

Camille Niveau, Eleonora Sosa Cuevas, Philippe Saas, Caroline Aspord

{"title":"Glycans in melanoma: Drivers of tumour progression but sweet targets to exploit for immunotherapy","authors":"Camille Niveau, Eleonora Sosa Cuevas, Philippe Saas, Caroline Aspord","doi":"10.1111/imm.13801","DOIUrl":"10.1111/imm.13801","url":null,"abstract":"Aberrant glycosylation recently emerged as an unmissable hallmark of cancer progression in many cancers. In melanoma, there is growing evidence that the tumour ‘glycocode’ plays a major role in promoting cell proliferation, invasion, migration, but also dictates the nature of the immune infiltrate, which strongly affects immune cell function, and clinical outcome. Aberrant glycosylation patterns dismantle anti-tumour defence through interactions with lectins on immune cells, which are crucial to shape anti-tumour immunity but also to trigger immune evasion. The glycan/lectin axis represents a new immune subversion pathway that is exploited by melanoma to hijack immune cells and escape from immune control. In this review, we describe the glycosylation features of melanoma tumour cells, and further gather findings related to the role of glycosylation in melanoma tumour progression, deciphering in detail its impact on immunity. We also depict glycan-based strategies aiming at restoring a functional anti-tumour response in melanoma patients. Glycans/lectins emerge as key immune checkpoints with promising translational properties. Exploitation of these pathways could reshape potent anti-tumour immunity while impeding immunosuppressive circuits triggered by aberrant tumour glycosylation patterns, holding great promise for cancer therapy.","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"173 1","pages":"33-52"},"PeriodicalIF":4.9,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13801","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916331","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}

引用次数: 0

Human CD4+ iNKT cell adoptive immunotherapy induces anti-tumour responses against CD1d-negative EBV-driven B lymphoma 人类 CD4+ iNKT 细胞免疫疗法可诱导 CD1d 阴性 EBV 驱动的 B 淋巴瘤的抗肿瘤反应。

IF 4.9 3区医学

Immunology Pub Date : 2024-05-13 DOI: 10.1111/imm.13799

Dana C. Baiu, Akshat Sharma, Jennifer L. Schehr, Jayati Basu, Kelsey A. Smith, Makoto Ohashi, Eric C. Johannsen, Shannon C. Kenney, Jenny E. Gumperz

{"title":"Human CD4+ iNKT cell adoptive immunotherapy induces anti-tumour responses against CD1d-negative EBV-driven B lymphoma","authors":"Dana C. Baiu, Akshat Sharma, Jennifer L. Schehr, Jayati Basu, Kelsey A. Smith, Makoto Ohashi, Eric C. Johannsen, Shannon C. Kenney, Jenny E. Gumperz","doi":"10.1111/imm.13799","DOIUrl":"10.1111/imm.13799","url":null,"abstract":"Invariant natural killer T (iNKT) cells are a conserved population of innate T lymphocytes that are uniquely suitable as off-the-shelf cellular immunotherapies due to their lack of alloreactivity. Two major subpopulations of human iNKT cells have been delineated, a CD4− subset that has a TH1/cytolytic profile, and a CD4+ subset that appears polyfunctional and can produce both regulatory and immunostimulatory cytokines. Whether these two subsets differ in anti-tumour effects is not known. Using live cell imaging, we found that CD4− iNKT cells limited growth of CD1d+ Epstein–Barr virus (EBV)-infected B-lymphoblastoid spheroids in vitro, whereas CD4+ iNKT cells showed little or no direct anti-tumour activity. However, the effects of the two subsets were reversed when we tested them as adoptive immunotherapies in vivo using a xenograft model of EBV-driven human B cell lymphoma. We found that EBV-infected B cells down-regulated CD1d in vivo, and administering CD4− iNKT cells had no discernable impact on tumour mass. In contrast, xenotransplanted mice bearing lymphomas showed rapid reduction in tumour mass after administering CD4+ iNKT cells. Immunotherapeutic CD4+ iNKT cells trafficked to both spleen and tumour and were associated with subsequently enhanced responses of xenotransplanted human T cells against EBV. CD4+ iNKT cells also had adjuvant-like effects on monocyte-derived DCs and promoted antigen-dependent responses of human T cells in vitro. These results show that allogeneic CD4+ iNKT cellular immunotherapy leads to marked anti-tumour activity through indirect pathways that do not require tumour cell CD1d expression and that are associated with enhanced activity of antigen-specific T cells.","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"172 4","pages":"627-640"},"PeriodicalIF":4.9,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11223969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140912092","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}

引用次数: 0

The powerful potential of amino acid menthyl esters for anti-inflammatory and anti-obesity therapies 氨基酸薄荷酯在抗炎和抗肥胖疗法中的强大潜力。

IF 4.9 3区医学

Immunology Pub Date : 2024-05-08 DOI: 10.1111/imm.13798

Seidai Takasawa, Kosuke Kimura, Masato Miyanaga, Takuya Uemura, Masakazu Hachisu, Shinichi Miyagawa, Abdelaziz Ramadan, Satoru Sukegawa, Masaki Kobayashi, Seisuke Kimura, Kenji Matsui, Mitsunori Shiroishi, Kaori Terashita, Chiharu Nishiyama, Takuya Yashiro, Kazuki Nagata, Yoshikazu Higami, Gen-ichiro Arimura

{"title":"The powerful potential of amino acid menthyl esters for anti-inflammatory and anti-obesity therapies","authors":"Seidai Takasawa, Kosuke Kimura, Masato Miyanaga, Takuya Uemura, Masakazu Hachisu, Shinichi Miyagawa, Abdelaziz Ramadan, Satoru Sukegawa, Masaki Kobayashi, Seisuke Kimura, Kenji Matsui, Mitsunori Shiroishi, Kaori Terashita, Chiharu Nishiyama, Takuya Yashiro, Kazuki Nagata, Yoshikazu Higami, Gen-ichiro Arimura","doi":"10.1111/imm.13798","DOIUrl":"10.1111/imm.13798","url":null,"abstract":"Our newly developed menthyl esters of valine and isoleucine exhibit anti-inflammatory properties beyond those of the well-known menthol in macrophages stimulated by lipopolysaccharide (LPS) and in a mouse model of colitis induced by sodium dextran sulfate. Unlike menthol, which acts primarily through the cold-sensitive TRPM8 channel, these menthyl esters displayed unique mechanisms that operate independently of this receptor. They readily penetrated target cells and efficiently suppressed LPS-stimulated tumour necrosis factor-alpha (Tnf) expression mediated by liver X receptor (LXR), a key nuclear receptor that regulates intracellular cholesterol and lipid balance. The menthyl esters showed affinity for LXR and enhanced the transcriptional activity through their non-competitive and potentially synergistic agonistic effect. This effect can be attributed to the crucial involvement of SCD1, an enzyme regulated by LXR, which is central to lipid metabolism and plays a key role in the anti-inflammatory response. In addition, we discovered that the menthyl esters showed remarkable efficacy in suppressing adipogenesis in 3T3-L1 adipocytes at the mitotic clonal expansion stage in an LXR-independent manner as well as in mice subjected to diet-induced obesity. These multiple capabilities of our compounds establish them as formidable allies in the fight against inflammation and obesity, paving the way for a range of potential therapeutic applications.","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"173 1","pages":"76-92"},"PeriodicalIF":4.9,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140891505","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}

引用次数: 0

FG-4592 protected haematopoietic system from ionising radiation in mice FG-4592 保护小鼠造血系统免受电离辐射的伤害

IF 4.9 3区医学

Immunology Pub Date : 2024-04-29 DOI: 10.1111/imm.13797

Yuedong Wang, Ying Cheng, Pei Zhang, Daqian Huang, Xuanlu Zhai, Zhenlan Feng, Duo Fang, Cong Liu, Jicong Du, Jianming Cai

{"title":"FG-4592 protected haematopoietic system from ionising radiation in mice","authors":"Yuedong Wang, Ying Cheng, Pei Zhang, Daqian Huang, Xuanlu Zhai, Zhenlan Feng, Duo Fang, Cong Liu, Jicong Du, Jianming Cai","doi":"10.1111/imm.13797","DOIUrl":"10.1111/imm.13797","url":null,"abstract":"Ionising radiation exposure can lead to acute haematopoietic radiation syndrome. Despite significant advancements in the field of radioprotection, no drugs with high efficacy and low toxicity have yet been approved by the Food and Drug Administration. FG-4592, as a proline hydroxylase inhibitor, may play an important role in radioprotection of the haematopoietic system. Mice were peritoneal injected with FG-4592 or normal saline. After irradiation, the survival time, body weight, peripheral blood cell and bone marrow cell (BMC) count, cell apoptosis, pathology were analysed and RNA-sequence technique (RNA-Seq) was conducted to explore the mechanism of FG-4592 in the haematopoietic system. Our results indicated that FG-4592 improved the survival rate and weight of irradiated mice and protected the spleen, thymus and bone marrow from IR-induced injury. The number of BMCs was increased and protected against IR-induced apoptosis. FG-4592 also promoted the recovery of the blood system and erythroid differentiation. The results of RNA-Seq and Western blot showed that the NF-κB signalling pathway and hypoxia-inducible factor-1 (HIF-1) signalling pathway were upregulated by FG-4592. Meanwhile, RT-PCR results showed that FG-4592 could promote inflammatory response significantly. FG-4592 exhibited radioprotective effects in the haematopoietic system by promoting inflammatory response and targeting the NF-κB, HIF signalling pathway.","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"172 4","pages":"614-626"},"PeriodicalIF":4.9,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13797","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140841975","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}

引用次数: 0

Oligodeoxynucleotides containing CpG motifs (CpG-ODN) restores immune regulatory functions of airway macrophages of patients with asthma 含有 CpG 基序的寡脱氧核苷酸（CpG-ODN）可恢复哮喘患者气道巨噬细胞的免疫调节功能

IF 4.9 3区医学

Immunology Pub Date : 2024-04-18 DOI: 10.1111/imm.13792

Huanping Zhang, Lihuan Wang, Aizhi Zhang, Xiangyu Wang, Yun Liao, Xiaoxue Chen, Xuejie Xu, Litao Yang, Yu Liu, Aifa Tang, Pingchang Yang

{"title":"Oligodeoxynucleotides containing CpG motifs (CpG-ODN) restores immune regulatory functions of airway macrophages of patients with asthma","authors":"Huanping Zhang, Lihuan Wang, Aizhi Zhang, Xiangyu Wang, Yun Liao, Xiaoxue Chen, Xuejie Xu, Litao Yang, Yu Liu, Aifa Tang, Pingchang Yang","doi":"10.1111/imm.13792","DOIUrl":"10.1111/imm.13792","url":null,"abstract":"Allergic asthma is characterized by the polarization of Th2 cells and impaired immune regulation. Macrophages occupy the largest proportion of airway immune cells. This study aims to discover the mechanism that hinders the immune regulatory functions of airway macrophages. In this study, macrophages were isolated from cells in bronchoalveolar lavage fluids (BALF) collected from asthma patients and normal control (NC) subjects. The results indicated that macrophages occupied the largest portion of the cellular components in BALF. The frequency of IL-10+ macrophage was significantly lower in asthma patients than in NC subjects. The expression of IL-10 in macrophages of BALF was associated with the levels of asthma-related parameters. The immune-suppressive functions of BALF M0 cells were defective in asthma patients. The inducibility of IL-10 expression was impaired in BALF macrophages of asthma patients, which could be restored by exposing to CpG. In conclusion, the induction of IL-10 in macrophages of BALF in asthma patients was impaired, and it could be restored by exposure to CpG.","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"172 4","pages":"588-599"},"PeriodicalIF":4.9,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140626189","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}

引用次数: 0

Unravelling CD4+ T cell diversity and tissue adaptation of Tregs in abdominal aortic aneurysms through single-cell sequencing 通过单细胞测序揭示腹主动脉瘤中 CD4+ T 细胞的多样性和 Tregs 的组织适应性

IF 4.9 3区医学

Immunology Pub Date : 2024-04-18 DOI: 10.1111/imm.13796

Luna Zhai, Wangling Hu, Jingyong Li, Dan Li, Ni Xia, Tingting Tang, Shaofang Nie, Min Zhang, Jiao Jiao, Bingjie Lv, Fen Yang, Yuzhi Lu, Lingfeng Zha, Muyang Gu, Xiajun Hu, Shuang Wen, Desheng Hu, Li Zhang, Weimin Wang, Xiang Cheng

{"title":"Unravelling CD4+ T cell diversity and tissue adaptation of Tregs in abdominal aortic aneurysms through single-cell sequencing","authors":"Luna Zhai, Wangling Hu, Jingyong Li, Dan Li, Ni Xia, Tingting Tang, Shaofang Nie, Min Zhang, Jiao Jiao, Bingjie Lv, Fen Yang, Yuzhi Lu, Lingfeng Zha, Muyang Gu, Xiajun Hu, Shuang Wen, Desheng Hu, Li Zhang, Weimin Wang, Xiang Cheng","doi":"10.1111/imm.13796","DOIUrl":"10.1111/imm.13796","url":null,"abstract":"Immune cell infiltration is a significant pathological process in abdominal aortic aneurysms (AAA). T cells, particularly CD4+ T cells, are essential immune cells responsible for substantial infiltration of the aorta. Regulatory T cells (Tregs) in AAA have been identified as tissue-specific; however, the time, location, and mechanism of acquiring the tissue-specific phenotype are still unknown. Using single-cell RNA sequencing (scRNA-seq) on CD4+ T cells from the AAA aorta and spleen, we discovered heterogeneity among CD4+ T cells and identified activated, proliferating and developed aorta Tregs. These Tregs originate in the peripheral tissues and acquire the tissue-specific phenotype in the aorta. The identification of precursors for Tregs in AAA provides new insight into the pathogenesis of AAA.","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"172 4","pages":"600-613"},"PeriodicalIF":4.9,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13796","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140626072","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}

引用次数: 0

TLR8-activating miR-146a-3p is an intermediate signal contributing to fetal membrane inflammation in response to bacterial LPS TLR8激活的miR-146a-3p是促使胎膜对细菌LPS产生炎症反应的中间信号

IF 4.9 3区医学

Immunology Pub Date : 2024-04-17 DOI: 10.1111/imm.13794

Hanah M. Georges, Caterina Cassin, Mancy Tong, Vikki M. Abrahams

{"title":"TLR8-activating miR-146a-3p is an intermediate signal contributing to fetal membrane inflammation in response to bacterial LPS","authors":"Hanah M. Georges, Caterina Cassin, Mancy Tong, Vikki M. Abrahams","doi":"10.1111/imm.13794","DOIUrl":"10.1111/imm.13794","url":null,"abstract":"Preterm birth is the largest contributor to neonatal morbidity and is often associated with chorioamnionitis, defined as inflammation/infection of the fetal membranes (FMs). Chorioamnionitis is characterised by neutrophil infiltration of the FMs and is associated with elevated levels of the neutrophil chemoattractant, interleukin (IL)-8 and the proinflammatory cytokine, IL-1β. While FMs can respond to infections through innate immune sensors, such as toll-like receptors (TLRs), the downstream mechanisms by which chorioamnionitis arises are not fully understood. A novel group of non-classical microRNAs (miR-21a, miR-29a, miR-146a-3p, Let-7b) function as endogenous danger signals by activating the ssRNA viral sensors TLR7 and TLR8. In this study, the pro-inflammatory roles of TLR7/TLR8-activating miRs were examined as mediators of FM inflammation in response to bacterial lipopolysaccharide (LPS) using an in vitro human FM explant system, an in vivo mouse model of pregnancy, and human clinical samples. Following LPS exposure, miR-146a-3p was significantly increased in both human FM explants and wild-type mouse FMs. Expression of miR-146a-3p was also significantly elevated in FMs from women with preterm birth and chorioamnionitis. FM IL-8 and inflammasome-mediated IL-1β production in response to LPS was dependent on miR-146a-3p and TLR8 downstream of TLR4 activation. In wild-type mice, LPS exposure increased FM IL-8 and IL-1β production and induced preterm birth. In TLR7−/−/TLR8−/− mice, LPS exposure was able to initiate but not sustain preterm birth, and FM inflammation was reduced. Together, we demonstrate a novel signalling mechanism at the maternal-fetal interface in which TLR8-activating miR-146a-3p acts as an intermediate danger signal to drive FM inflammasome-dependent and -independent mechanisms of inflammation and, thus, may play a role in chorioamnionitis and subsequent preterm birth.","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"172 4","pages":"577-587"},"PeriodicalIF":4.9,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140630161","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}

引用次数: 0

Immunotherapy and the ovarian cancer microenvironment: Exploring potential strategies for enhanced treatment efficacy 免疫疗法与卵巢癌微环境：探索提高疗效的潜在策略

IF 4.9 3区医学

Immunology Pub Date : 2024-04-15 DOI: 10.1111/imm.13793

Zhi-Bin Wang, Xiu Zhang, Chao Fang, Xiao-Ting Liu, Qian-Jin Liao, Nayiyuan Wu, Jing Wang

引用次数: 0

The TRIF-RIPK1-Caspase-8 signalling in the regulation of TLR4-driven gene expression TRIF-RIPK1-Caspase-8信号在TLR4驱动的基因表达调控中的作用

IF 4.9 3区医学

Immunology Pub Date : 2024-04-15 DOI: 10.1111/imm.13795

Chengyang Zhang, Yang Zhou, Shuangtong Xi, Danlin Han, Ziyu Wang, Jingwen Zhu, Yizhe Cai, Haifeng Zhang, Ge Jin, Yang Mi

引用次数: 0

Homotherapy for heteropathy: Interleukin-41 and its biological functions 异病同治：白细胞介素-41 及其生物功能

IF 4.9 3区医学

Immunology Pub Date : 2024-04-09 DOI: 10.1111/imm.13791

Runfeng Shi, Meixin He, Yongzheng Peng, Xu Xia

{"title":"Homotherapy for heteropathy: Interleukin-41 and its biological functions","authors":"Runfeng Shi, Meixin He, Yongzheng Peng, Xu Xia","doi":"10.1111/imm.13791","DOIUrl":"10.1111/imm.13791","url":null,"abstract":"Interleukin-41 (IL-41) is a newly discovered cytokine, named Cometin, Subfatin, meteorin-like transcription (Metrnl), and so forth. It is widely expressed in animals and can exert its biological roles through autocrine and paracrine forms. It has functions such as anti-inflammatory, improving body metabolism, regulating immunity, regulating fat metabolism and participates in the process of autoimmune disease or inflammatory injury. It plays an important role in psoriasis, diabetes, Crohn's disease (CD), osteoarthritis, Kawasaki disease (KD), Graves' disease, autoimmune hepatitis, infertility, obesity, sepsis, cardiovascular diseases and respiratory diseases. This paper reviews the biological functions of IL-41, the relationship between IL-41 and diseases, the effects of IL-41 in the cytokine network and the possible signalling pathways. In order to explore the same target or the same drug for the treatment of different diseases from the perspective of homotherapy for heteropathy, cytokine strategies based on IL-41 have been put forward for the precise treatment of immune diseases and inflammatory diseases. It is worth noting that IL-41 related preparations for lung protection and smoking cessation are interesting research fields.","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"173 1","pages":"1-13"},"PeriodicalIF":4.9,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13791","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140573023","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}

引用次数: 0