Clinical science最新文献_第2页

Untangling the role of tau in sex hormone responsive cancers: lessons learnt from Alzheimer's disease. 厘清 tau 在性激素反应性癌症中的作用：从阿尔茨海默病中汲取的经验教训。

IF 6.7 2区医学

Clinical science Pub Date : 2024-11-06 DOI: 10.1042/CS20230317

Rachel M Barker, Alfie Chambers, Patrick G Kehoe, Edward Rowe, Claire M Perks

{"title":"Untangling the role of tau in sex hormone responsive cancers: lessons learnt from Alzheimer's disease.","authors":"Rachel M Barker, Alfie Chambers, Patrick G Kehoe, Edward Rowe, Claire M Perks","doi":"10.1042/CS20230317","DOIUrl":"10.1042/CS20230317","url":null,"abstract":"Tubulin associated unit has been extensively studied in neurodegenerative diseases including Alzheimer's disease (AD), whereby its hyperphosphorylation and accumulation contributes to disease pathogenesis. Tau is abundantly expressed in the central nervous system but is also present in non-neuronal tissues and in tumours including sex hormone responsive cancers such as breast and prostate. Curiously, hormonal effects on tau also exist in an AD context from numerous studies on menopause, hormone replacement therapy, and androgen deprivation therapy. Despite sharing some risk factors, most importantly advancing age, there are numerous reports from population studies of, currently poorly explained inverse associations between cancer and Alzheimer's disease. We previously reviewed important components of the phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) signalling pathway and their differential modulation in relation to the two diseases. Similarly, receptor tyrosine kinases, estrogen receptor and androgen receptor have all been implicated in the pathogenesis of both cancer and AD. In this review, we focus on tau and its effects in hormone responsive cancer in terms of development, progression, and treatment and in relation to sex hormones and PI3K/Akt signalling molecules including IRS-1, PTEN, Pin1, and p53.","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":"138 21","pages":"1357-1369"},"PeriodicalIF":6.7,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11522895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

IFN-γ induces acute graft-versus-host disease by promoting HMGB1-mediated nuclear-to-cytoplasm translocation and autophagic degradation of p53. IFN-γ 通过促进 HMGB1 介导的核到细胞质转位和 p53 的自噬降解，诱导急性移植物抗宿主疾病。

IF 6.7 2区医学

Clinical science Pub Date : 2024-10-16 DOI: 10.1042/CS20241144

Shiyu Wang, Tingting Cheng, Xu Chen, Cong Zeng, Wei Qin, Yajing Xu

{"title":"IFN-γ induces acute graft-versus-host disease by promoting HMGB1-mediated nuclear-to-cytoplasm translocation and autophagic degradation of p53.","authors":"Shiyu Wang, Tingting Cheng, Xu Chen, Cong Zeng, Wei Qin, Yajing Xu","doi":"10.1042/CS20241144","DOIUrl":"10.1042/CS20241144","url":null,"abstract":"Acute graft-versus-host disease (aGVHD) poses a significant impediment to achieving a more favourable therapeutic outcome in allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our prior investigations disclosed a correlation between p53 down-regulation in CD4+ T cells and the occurrence of aGVHD. Notably, the insufficiency of the CCCTC-binding factor (CTCF) emerged as a pivotal factor in repressing p53 expression. However, the existence of additional mechanisms contributing to the reduction in p53 expression remains unclear. Interferon (IFN)-γ, a pivotal proinflammatory cytokine, assumes a crucial role in regulating alloreactive T-cell responses and plays a complex part in aGVHD development. IFN-γ has the capacity to induce autophagy, a vital catabolic process facilitating protein degradation, in various cell types. Presently, whether IFN-γ participates in the development of aGVHD by instigating the autophagic degradation of p53 in CD4+ T cells remains an unresolved question. In the present study, we demonstrated that heightened levels of IFN-γ in the plasma during aGVHD promoted the activation, proliferation, and autophagic activity of CD4+ T cells. Furthermore, IFN-γ induced the nuclear-to-cytoplasm translocation and autophagy-dependent degradation of p53 in CD4+ T cells. The translocation and autophagic degradation of p53 were contingent upon HMGB1, which underwent up-regulation and translocation from the nucleus to the cytoplasm following IFN-γ stimulation. In conclusion, our data unveil a novel mechanism underlying p53 deficiency in CD4+ T cells among aGVHD patients. This deficiency is induced by IFN-γ and relies on autophagy, establishing a link between IFN-γ, HMGB1-mediated translocation, and the autophagic degradation of p53.","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":"1287-1304"},"PeriodicalIF":6.7,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11479981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

SDMA as a marker and mediator in cerebrovascular disease. 作为脑血管疾病标志物和介质的 SDMA。

IF 6.7 2区医学

Clinical science Pub Date : 2024-10-16 DOI: 10.1042/CS20241021

Alexandra Riddell, Arun Flynn, Hugo Bergugnat, Laura B Dowsett, Alyson A Miller

{"title":"SDMA as a marker and mediator in cerebrovascular disease.","authors":"Alexandra Riddell, Arun Flynn, Hugo Bergugnat, Laura B Dowsett, Alyson A Miller","doi":"10.1042/CS20241021","DOIUrl":"10.1042/CS20241021","url":null,"abstract":"Symmetric dimethylarginine (SDMA) is a methylated derivative of arginine, generated by all cells as a by-product of cellular metabolism and eliminated via the kidney. For many years SDMA has been considered inert and of little biological significance. However, a growing body of evidence now suggests this view is outdated and that circulating SDMA levels may, in fact, be intricately linked to endothelial dysfunction and vascular risk. In this review, we specifically examine SDMA within the context of cerebrovascular disease, with a particular focus on ischaemic stroke. We first discuss pre-clinical evidence supporting the notion that SDMA has effects on nitric oxide signalling, inflammation, oxidative stress, and HDL function. We then appraise the most recent clinical studies that explore the relationship between circulating SDMA and cerebrovascular risk factors, such as chronic kidney disease, hypertension, atrial fibrillation, and atherosclerosis, exploring whether any associations may arise due to the existence of shared risk factors. Finally, we consider the evidence that elevated circulating SDMA is linked to poor outcomes following ischaemic and haemorrhagic stroke. We draw upon pre-clinical insights into SDMA function to speculate how SDMA may not only be a marker of cerebrovascular disease but could also directly influence cerebrovascular pathology, and we highlight the pressing need for more mechanistic pre-clinical studies alongside adequately powered, longitudinal clinical studies to fully evaluate SDMA as a marker/mediator of disease.","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":"138 20","pages":"1305-1323"},"PeriodicalIF":6.7,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11479986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Retraction: BMSC-derived exosomes carrying microRNA-122-5p promote progression of osteoblasts in osteonecrosis of the femoral head. 撤回：携带microRNA-122-5p的BMSC衍生外泌体可促进股骨头坏死中成骨细胞的进展

IF 6.7 2区医学

Clinical science Pub Date : 2024-10-16 DOI: 10.1042/CS-2018-1064_RET

引用次数: 0

Correction: Perinatal iron restriction is associated with changes in neonatal cardiac function and structure in a sex-dependent manner. 更正：围产期铁限制与新生儿心脏功能和结构的变化有关，其变化与性别有关。

IF 6.7 2区医学

Clinical science Pub Date : 2024-10-16 DOI: 10.1042/CS-2023-0594_COR

引用次数: 0

REV-ERBα agonist SR10067 attenuates Th2 cytokine-mediated barrier dysfunction in human bronchial epithelial cells. REV-ERBα激动剂 SR10067 可减轻 Th2 细胞因子介导的人支气管上皮细胞屏障功能障碍。

IF 6.7 2区医学

Clinical science Pub Date : 2024-10-02 DOI: 10.1042/CS20240064

Santhosh Kumar Duraisamy, Isaac Kirubakaran Sundar

{"title":"REV-ERBα agonist SR10067 attenuates Th2 cytokine-mediated barrier dysfunction in human bronchial epithelial cells.","authors":"Santhosh Kumar Duraisamy, Isaac Kirubakaran Sundar","doi":"10.1042/CS20240064","DOIUrl":"10.1042/CS20240064","url":null,"abstract":"Allergens and Th2 cytokines affect the homeostatic environment in the airways, leading to increased mucus production by goblet cells associated with altered adherens junctional complex (AJC) and tight junction (TJ) proteins responsible for maintaining epithelial barrier function. Circadian clock-dependent regulatory mechanisms such as inflammation and epithelial barrier function are gaining more attention due to their therapeutic potential against allergic inflammatory lung diseases. Currently, there are no studies to support whether REV-ERBα activation can attenuate Th2 cytokine-induced epithelial barrier dysfunction in human bronchial epithelial cells. We hypothesized that Th2 cytokine-induced epithelial barrier dysfunction may be protected by activating REV-ERBα. Treatment with Th2 cytokines or HDM significantly reduced the cell impedance, as confirmed by transepithelial electrical resistance (TEER). However, pre-treatment with SR10067 attenuated Th2 cytokine-induced barrier dysfunction, such as decreased permeability, improved TEER, localization of AJC and TJ proteins, and mRNA and protein levels of selected epithelial barrier and circadian clock targets. Overall, we showed for the first time that REV-ERBα activation regulates altered epithelial barrier function that may have direct implications for the treatment of asthma and other allergic diseases.","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":"1209-1226"},"PeriodicalIF":6.7,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105071","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

Oncogenic plasmid DNA and liver injury agent dictates liver cancer development in a mouse model. 致癌质粒 DNA 和肝损伤剂决定了小鼠模型中肝癌的发展。

IF 6.7 2区医学

Clinical science Pub Date : 2024-10-02 DOI: 10.1042/CS20240560

Vincent Chiu, Christine Yee, Nathan Main, Igor Stevanovski, Matthew Watt, Trevor Wilson, Peter Angus, Tara Roberts, Nicholas Shackel, Chandana Herath

{"title":"Oncogenic plasmid DNA and liver injury agent dictates liver cancer development in a mouse model.","authors":"Vincent Chiu, Christine Yee, Nathan Main, Igor Stevanovski, Matthew Watt, Trevor Wilson, Peter Angus, Tara Roberts, Nicholas Shackel, Chandana Herath","doi":"10.1042/CS20240560","DOIUrl":"10.1042/CS20240560","url":null,"abstract":"Primary liver cancer is an increasing problem worldwide and is associated with significant mortality. A popular method of modeling liver cancer in mice is plasmid hydrodynamic tail vein injection (HTVI). However, plasmid-HTVI models rarely recapitulate the chronic liver injury which precedes the development of most human liver cancer. We sought to investigate how liver injury using thioacetamide contributes to the pathogenesis and progression of liver cancer in two oncogenic plasmid-HTVI-induced mouse liver cancer models. Fourteen-week-old male mice received double-oncogene plasmid-HTVI (SB/AKT/c-Met and SB/AKT/NRas) and then twice-weekly intraperitoneal injections of thioacetamide for 6 weeks. Liver tissue was examined for histopathological changes, including fibrosis and steatosis. Further characterization of fibrosis and inflammation was performed with immunostaining and real-time quantitative PCR. RNA sequencing with pathway analysis was used to explore novel pathways altered in the cancer models. Hepatocellular and cholangiocellular tumors were observed in mice injected with double-oncogene plasmid-HTVI models (SB/AKT/c-Met and SB/AKT/NRas). Thioacetamide induced mild fibrosis and increased alpha smooth muscle actin-expressing cells. However, the combination of plasmids and thioacetamide did not significantly increase tumor size, but increased multiplicity of small neoplastic lesions. Cancer and/or liver injury up-regulated profibrotic and proinflammatory genes while metabolic pathway genes were mostly down-regulated. We conclude that the liver injury microenvironment can interact with liver cancer and alter its presentation. However, the effects on cancer development vary depending on the genetic drivers with differing active oncogenic pathways. Therefore, the choice of plasmid-HTVI model and injury agent may influence the extent to which injury promotes liver cancer development.","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":"1227-1248"},"PeriodicalIF":6.7,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11427747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Maternal ketone supplementation throughout gestation improves neonatal cardiac dysfunction caused by perinatal iron deficiency. 在整个妊娠期补充母体酮可改善围产期铁缺乏引起的新生儿心脏功能障碍

IF 6.7 2区医学

Clinical science Pub Date : 2024-10-02 DOI: 10.1042/CS20241386

Ronan M N Noble, Shubham Soni, Si Ning Liu, Jad-Julian Rachid, Heather E Mast, Alyssa Wiedemeyer, Claudia D Holody, Richard Mah, Andrew G Woodman, Mourad Ferdaoussi, Helene Lemieux, Jason R B Dyck, Stephane L Bourque

{"title":"Maternal ketone supplementation throughout gestation improves neonatal cardiac dysfunction caused by perinatal iron deficiency.","authors":"Ronan M N Noble, Shubham Soni, Si Ning Liu, Jad-Julian Rachid, Heather E Mast, Alyssa Wiedemeyer, Claudia D Holody, Richard Mah, Andrew G Woodman, Mourad Ferdaoussi, Helene Lemieux, Jason R B Dyck, Stephane L Bourque","doi":"10.1042/CS20241386","DOIUrl":"10.1042/CS20241386","url":null,"abstract":"Iron deficiency (ID) is common during gestation and in early infancy and has been shown to adversely affect cardiac development and function, which could lead to lasting cardiovascular consequences. Ketone supplementation has been shown to confer cardioprotective effects in numerous disease models. Here, we tested the hypothesis that maternal ketone supplementation during gestation would mitigate cardiac dysfunction in ID neonates. Female Sprague-Dawley rats were fed an iron-restricted or iron-replete diet before and throughout pregnancy. Throughout gestation, iron-restricted dams were given either a daily subcutaneous injection of ketone solution (containing β-hydroxybutyrate [βOHB]) or saline (vehicle). Neonatal offspring cardiac function was assessed by echocardiography at postnatal days (PD)3 and 13. Hearts and livers were collected post-mortem for assessments of mitochondrial function and gene expression profiles of markers oxidative stress and inflammation. Maternal iron restriction caused neonatal anemia and asymmetric growth restriction at all time points assessed, and maternal βOHB treatment had no effect on these outcomes. Echocardiography revealed reduced ejection fraction despite enlarged hearts (relative to body weight) in ID offspring, resulting in impaired oxygen delivery, which was attenuated by maternal βOHB supplementation. Further, maternal ketone supplementation affected biochemical markers of mitochondrial function, oxidative stress and inflammation in hearts of neonates, implicating these pathways in the protective effects conferred by βOHB. In summary, βOHB supplementation confers protection against cardiac dysfunction in ID neonates and could have implications for the treatment of anemic babies.","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":"1249-1264"},"PeriodicalIF":6.7,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281485","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

Pathways to precision medicine: deciphering the secrets of physiological and pathological atrial enlargement. 精准医疗之路：破解生理性和病理性心房扩大的秘密。

IF 6.7 2区医学

Clinical science Pub Date : 2024-09-18 DOI: 10.1042/CS20241421

Shuai Zhao, Xander H T Wehrens

{"title":"Pathways to precision medicine: deciphering the secrets of physiological and pathological atrial enlargement.","authors":"Shuai Zhao, Xander H T Wehrens","doi":"10.1042/CS20241421","DOIUrl":"https://doi.org/10.1042/CS20241421","url":null,"abstract":"Cardiac functional, morphological, and histological analysis, coupled with liquid chromatography and mass spectrometry, of two transgenic mouse models with cardiomyocyte-specific overexpression of insulin-like growth factor 1 receptor (IGF1R) or a dominant-negative PI3K mutant (DCM-dnPI3K) revealed distinctive functional and molecular profiles during physiological (driven by IGF1R overexpression) and pathological (driven by dn-PI3K overexpression) atrial remodeling. The current study confirmed previously reported findings, including ventricular dilatation and enhanced systolic function with no evidence of arrhythmia in IGF1R model, as well as ventricular hypertrophy and decreased systolic function with intermittent atrial fibrillation in DCM-dnPI3K model. Novel findings obtained from the left atrial (LA) characterization of female mice revealed that physiological atrial enlargement resulted from increased atrial myocyte size and was associated with preserved atrial function, as determined by maintained LA ejection fraction (EF). The proteomic profile of IGF1R transgenic (Tg) mice was enriched for metabolic remodeling and showed a protein expression pattern similar to that of healthy human atria; on the other hand, pathological atrial enlargement resulted from increased atrial fibrosis with normal myocyte size and was associated with impaired atrial function due to a reduced LA EF. The proteomic profile of DCM-dnPI3K mice was enriched to both metabolic and structural remodeling and showed a protein expression pattern similar to that of human AF atria.","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":"138 18","pages":"1173-1177"},"PeriodicalIF":6.7,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281489","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

PDCD10 promotes the tumor-supporting functions of TGF-β in pancreatic cancer. PDCD10 在胰腺癌中促进 TGF-β 的肿瘤支持功能。

IF 6.7 2区医学

Clinical science Pub Date : 2024-09-18 DOI: 10.1042/CS20240450

Qianwen Zhou, Katja Breitkopf-Heinlein, Haristi Gaitantzi, Emrullah Birgin, Christoph Reissfelder, Nuh N Rahbari

{"title":"PDCD10 promotes the tumor-supporting functions of TGF-β in pancreatic cancer.","authors":"Qianwen Zhou, Katja Breitkopf-Heinlein, Haristi Gaitantzi, Emrullah Birgin, Christoph Reissfelder, Nuh N Rahbari","doi":"10.1042/CS20240450","DOIUrl":"10.1042/CS20240450","url":null,"abstract":"The progression of pancreatic ductal adenocarcinoma (PDAC) is significantly affected by transforming growth factor (TGF)-β but targeting TGF-β can also compromize physiological effects in patients. Our study examined the functions of the ubiquitously expressed protein, PDCD10, as a modulator of TGF-β signaling in PDAC. Using in silico analyses we found that in patient samples, PDCD10 is significantly higher expressed in PDAC tumor tissue compared with normal pancreas and it is highly correlated with reduced survival. We created stable KO's of PDCD10 in two PDAC lines, PaTu 8902 (SMAD4 +/+) and PaTu 8988t (SMAD4 -/-), and found that KO lines are more sensitive to 5-FU and Gemcitabine treatment than their wild-type counterparts. Performing viability and wound closure assays we further found that PDCD10 promotes cell survival and proliferation by enhancing specifically the mitogenic functions of TGF-β. The molecular mechanism underlying this effect was further investigated using Western blots and with primary organoid lines derived from patient PDAC tissue samples. The data imply that PDCD10 mediates an increase in p-ERK through a non-SMAD4 pathway, leading to EMT promotion. Furthermore, PDCD10 facilitates deactivation of RB via a SMAD4-dependent pathway, thereby counter-acting the anti-proliferative actions of TGF-β. By performing proximity ligation assays (PLA) we found that PDCD10 associates with the kinase MST4, translocates it intracellularly and thereby facilitates phosphorylations of RB and ERK1/2. Our study indicates that PDCD10 promotes the proliferative function and EMT induction of TGF-β in pancreatic cancer cells. Therefore, targeting PDCD10 in PDAC patients could represent a promising new strategy to optimize TGF-β targeted therapies.","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":"1111-1129"},"PeriodicalIF":6.7,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11405861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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