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Clinical significance of serum GPX2 levels in patients with osteoarthritis was suppressed and reduced inflammation of osteoarthritis through STAT3 function STAT3功能对骨关节炎患者血清GPX2水平的抑制和减轻炎症的临床意义
IF 0.7 4区 医学 Q4 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/20587392211070411
Jinli Du, Jieying Zhang
The main alterations of osteoarthritis are degenerative lesions of articular cartilage and secondary hyperostosis. Despite the unclear pathogenic mechanism, experimental studies have confirmed that the incidence of osteoarthritis is closely associated with inflammation-related substances. In this study, we explored the significance of serum GPX2 levels in patients with osteoarthritis and the mechanism of GPX2 in the anti-inflammation effects in osteoarthritis. As a result, serum GPX2 level was down-regulated and there was a negative correlation between GPX2 levels and IL-1β levels in patients with osteoarthritis. Over-expression of GPX2 decreased the inflammatory levels and down-regulation of GPX2 increased inflammatory levels in vitro. In contrast, GPX2 combined and regulated STAT3 protein expression. Over-expression of GPX2 promoted ubiquitination-STAT3 protein expression to decrease p-STAT3 protein expression in vitro. The inhibition of STAT3 attenuated the anti-inflammation effects of GPX2 in osteoarthritis. Thus, we proposed that GPX2 was down-regulated in patients with osteoarthritis and GPX2 played vital roles in osteoarthritis for clinical diagnosis or therapy.
骨关节炎的主要改变是关节软骨退行性病变和继发性骨质增生。尽管致病机制尚不清楚,但实验研究证实,骨关节炎的发病率与炎症相关物质密切相关。在本研究中,我们探讨了骨关节炎患者血清GPX2水平的意义以及GPX2在骨关节炎抗炎作用中的机制。结果,骨关节炎患者血清GPX2水平下调,GPX2水平与IL-1β水平呈负相关。GPX2的过度表达降低了体外的炎症水平,而GPX2的下调增加了体外的炎性水平。相反,GPX2结合并调节STAT3蛋白的表达。GPX2的过表达促进了泛素化STAT3蛋白的表达,从而降低了p-STAT3蛋白在体外的表达。STAT3的抑制减弱了GPX2在骨关节炎中的抗炎作用。因此,我们提出GPX2在骨关节炎患者中下调,GPX2在临床诊断或治疗骨关节炎中发挥着至关重要的作用。
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引用次数: 0
Alternariol ameliorates lung carcinoma via reprogramming cytokine signaling associated with PI3K/Akt cascade in vitro and in vivo 在体外和体内实验中,Alternariol通过与PI3K/Akt级联相关的细胞因子信号重编程改善肺癌
IF 0.7 4区 医学 Q4 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/1721727X221106505
Qiufang Li, Yanzi Yang, Xiaokai Wang, Xiaopeng Yang, Yao-Jie Zhao, Qiuge Wu, Yanli Zhao
Objectives The lung cancer is most frequently diagnosed cancer incidence worldwide. A large number of populations are heavily affected to this every year with poor prognosis. Methods Our study investigated the anticancer effect of alternariol, a secondary metabolite, on A549 lung cancer cell line and benzo-α-pyrene induced lung carcinoma model on balb/c mice. The cytotoxicity assay, DAPI staining and the flow cytometry was performed to assess the anticancer efficacy of alternariol in A549 lung cancer cell. For in vivo study the toxicity study was performed. The lung cancer was developed in the animals via intraperitoneal administration of benzo-α-pyrene and subsequently 2 weeks later alternariol treatment was carried out for 24 weeks. The chemotherapeutic effect of alternariol was assessed through histopathological analysis, followed by immunohistochemistry and in vivo antioxidant study. Results The in vitro data suggested a significant percentage of early and late apoptotic events in A549 cells with G0/G1 phase arrest which ultimately caused apoptosis followed by alternariol therapy. The in vivo study showed that alternariol therapy decreased the pulmonary fibrosis and formation of granuloma in lung tissue and restored the normal histopathological characteristics of lung. Furthermore, alternariol treatment downregulated the expression of PI3K, Akt and inflammatory mediators such as IL-6, TNF-α and increased the expression of apoptotic markers, p53. Conclusion In conclusion, the treatment with alternariol effectively decreased the progression of lung cancer through the inhibition of carcinogenic markers by reprogramming the p53/PI3K/Akt pathway and IL-6/TNF-α mediated cytokine signaling in mice.
目的癌症是世界上诊断最常见的癌症发病率。每年都有大量人群受到严重影响,预后不佳。方法研究二级代谢产物交链孢酚对A549肺癌癌症细胞株和苯并α-芘诱导的balb/c小鼠肺癌模型的抗癌作用。采用细胞毒性试验、DAPI染色、流式细胞术等方法,评价交链烯酚对A549肺癌癌症细胞的抗癌作用。对于体内研究,进行了毒性研究。通过腹膜内给予苯并-α-芘使动物患上癌症,随后2周后进行了为期24周的交链孢酚治疗。通过组织病理学分析、免疫组织化学和体内抗氧化研究来评估交链孢醇的化疗效果。结果体外数据表明,A549细胞G0/G1期阻滞的早期和晚期凋亡事件占显著比例,并最终导致细胞凋亡,随后进行交链霉素治疗。体内研究表明,交链孢醇治疗减少了肺纤维化和肺组织肉芽肿的形成,恢复了正常的肺组织病理学特征。此外,交链孢醇治疗下调了PI3K、Akt和炎症介质如IL-6、TNF-α的表达,并增加了凋亡标志物p53的表达。结论交链烯酚治疗可通过重编程小鼠p53/PI3K/Akt通路和IL-6/TNF-α介导的细胞因子信号传导,抑制肿瘤标志物,从而有效地降低癌症的进展。
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引用次数: 1
Immune cell responses in pancreatic cancer and their clinical application 癌症的免疫细胞反应及其临床应用
IF 0.7 4区 医学 Q4 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/20587392211044381
Xulin Zhou, Yongmin Yan, Min Xu
Pancreatic cancer is one of the most lethal diseases around the world, for hardly detection and poor prognosis. Recent years, functions of the tumor microenvironment and immune cells attract people’s view and there is emerging evidence implicating some immune cells hold the key points in the metabolism, invasion, and metastasis in pancreatic cancer. In this review, we highlight some main immune cells, such as Tumor-associated neutrophils (TANs) and macrophages (TAMs), Pancreatic stellate cells (PSCs), Myeloid-derived suppressor cells (MDSCs), and Regulatory T cells (Tregs). Furthermore, we review current clinical applications and discuss potential values in future.
癌症是世界上最致命的疾病之一,几乎无法发现,预后不佳。近年来,肿瘤微环境和免疫细胞的功能引起了人们的关注,有新的证据表明某些免疫细胞在癌症的代谢、侵袭和转移中起着关键作用。在这篇综述中,我们重点介绍了一些主要的免疫细胞,如肿瘤相关中性粒细胞(TANs)和巨噬细胞(TAMs)、胰腺星状细胞(PSCs)、骨髓源性抑制细胞(MDSCs)和调节性T细胞(Tregs)。此外,我们还回顾了目前的临床应用,并讨论了未来的潜在价值。
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引用次数: 2
Role of serum IL-6 and TNF-α in coronavirus disease 2019 (COVID-19) associated renal impairment 血清IL-6和TNF-α在2019冠状病毒病(COVID-19)相关肾损害中的作用
IF 0.7 4区 医学 Q4 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/1721727X221126117
Li-da Chen, Lan Hu, Yang Song, Yaping Huang, Si-jiu Yang, Juan Yang, Xiao-bin Zhang
Objectives: Association of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and kidney injury has been noted in previous studies. However, the mechanisms remain unknown. The present study aimed to explore the potential mechanisms of kidney injury in COVID-19. Methods: Demographic characteristics, underlying diseases, signs, symptoms, and laboratory data of 100 COVID-19 patients were collected and analyzed in this retrospective study. Patients were divided into three groups: mild, moderate, and severe to critical group. Kidney injury was evaluated by markers including estimated glomerular filtration rate (eGFR), serum creatinine, blood urea nitrogen, and cystatin C. Results: A total of 100 patients with 12 mild, 63 moderate, and 25 severe to critical COVID-19 were included in this study. The kidney injury markers including eGFR, serum creatinine, blood urea nitrogen, and cystatin C all worsened significantly with an increase in disease severity. The correlation test showed that cytokines IL-2R, IL-6, IL-8, and tumor necrosis factor (TNF)-α were statistically correlated with eGFR and cystatin C. In multivariate analysis, log IL-6 (β = −0.331, p = .001 for eGFR and β = 0.405, p < .001 for cystatin C) and log TNF-α (β = −0.316, p = .001 for eGFR and β = 0.534, p < .001 for cystatin C) were found to be the major independent predictors of kidney injury. Conclusion: Serum IL-6 and TNF-α levels were the major independent predictors of kidney injury in COVID-19.
目的:严重急性呼吸系统综合征冠状病毒2型(SARS-CoV-2)感染与肾损伤之间的关系在以前的研究中已经被注意到。然而,其机制仍然未知。本研究旨在探讨新冠肺炎肾损伤的潜在机制。方法:收集并分析100例新冠肺炎患者的人口学特征、潜在疾病、体征、症状和实验室数据。患者分为三组:轻度、中度和重度至危重症组。肾损伤通过估计肾小球滤过率(eGFR)、血清肌酐、血尿素氮和胱抑素C等指标进行评估。结果:本研究共纳入100名患者,包括12名轻度、63名中度和25名重度至危重症新冠肺炎患者。肾损伤标志物,包括eGFR、血清肌酐、血尿素氮和胱抑素C,都随着疾病严重程度的增加而显著恶化。相关性检验显示,细胞因子IL-2R、IL-6、IL-8和肿瘤坏死因子(TNF)-α与eGFR和胱抑素C具有统计学相关性,log IL-6(eGFRβ=−0.331,p=.001,胱抑素Cβ=0.405,p<.001)和log TNF-α(eGFRβ=−0.316,p=0.001,cystatin Cβ=0.534,p<0.001)被发现是肾损伤的主要独立预测因素。结论:血清IL-6和TNF-α水平是新冠肺炎肾损伤的主要独立预测因素。
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引用次数: 0
Small-sized shiny sclerotic plaques: Think early morphea 小尺寸有光泽的硬化斑块:考虑早期睡眠
IF 0.7 4区 医学 Q4 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/1721727X221105130
Hiroki Hashimoto, T. Nakahara
Morphea is a rare fibrosing disorder of the skin and underlying tissues. To date, the size of morphea has not been adequately discussed. Here, we report two cases of small-sized superficial circumscribed morphea. Both cases clinically revealed single circumscribed, round to oval area of shiny sclerotic plaque at distal extremities. There are several options for the treatment of superficial circumscribed morphea, such as topical corticosteroid and phototherapy. The early recognition of small-sized morphea enables appropriate diagnosis and follow-up, leading to improve disease prognosis.
吗啡是一种罕见的皮肤和底层组织纤维化疾病。到目前为止,人们还没有充分讨论过变形虫的大小。在这里,我们报告了两例小面积浅表局限性变形。这两个病例临床上都显示远端有一个圆形到椭圆形的有光泽的硬化斑块。治疗浅表局限性变形有几种选择,如局部皮质类固醇和光疗。早期识别小面积变形可以进行适当的诊断和随访,从而改善疾病预后。
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引用次数: 0
Potential role of interleukin-33 in systemic lupus erythematosus by regulating toll like receptor 4 白细胞介素-33通过调节toll样受体4在系统性红斑狼疮中的潜在作用
IF 0.7 4区 医学 Q4 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/1721727X221094455
Yi Li, Y. Shao, Yan He, Qiugen Li, L. Duan
Introduction Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by immune activation and multi-immunologic phenotypes. Interleukin-33 (IL-33) has been shown to be a critical and pleiotropic immunoregulatory mediator in the pathogenesis of many autoimmune diseases. At present, there are conflicting findings in the research of IL-33 in SLE. The purpose of this study was to investigate whether and how IL-33 is involved in the occurrence and development of SLE. Methods 43 SLE patients and 43 healthy volunteers were recruited for this study. Serum levels of IL-33, IL-4, IL-6, IL-10 and IL-21 were measured by ELISA. The expression of IL-33 was investigated in kidney sections by immunohistochemistry in lupus nephritis patients (n = 5) and controls (n = 3). The mRNA expressions of Toll like receptor 4 (TLR4), TLR2, and tumorigenicity 2 (ST2)L were quantified in peripheral blood mononuclear cells (PBMCs) by real-time PCR. The surface expression of TLR4 on T cells, B cells, monocytes, and neutrophils was assessed by flow cytometry (n = 22). Mann–Whitney U-test and Spearman’s test were used for statistical analysis. Results Serum concentrations of IL-33 were significantly higher in SLE patients than in healthy controls (p < 0.0001). IL-33 expressions were positively correlated with IL-4 and IL-6 levels in SLE patients, which play pivotal roles in the autoantibody production. In addition, TLR4 and TLR2 mRNA were markedly increased in PBMCs from SLE patients (p < 0.05). TLR4 was positively associated with IL-33, while TLR2 was not. Conclusions These results imply that upregulated expression of serum IL-33 together with increased TLR4 in PBMCs may contribute to the pathogenesis of SLE via promotion of inflammatory cytokines production.
系统性红斑狼疮(SLE)是一种以免疫激活和多种免疫表型为特征的自身免疫性疾病。白细胞介素33(IL-33)在许多自身免疫性疾病的发病机制中已被证明是一种关键的多效性免疫调节介质。目前,对SLE患者白细胞介素33的研究存在争议。本研究的目的是探讨IL-33是否以及如何参与SLE的发生和发展。方法选择43例SLE患者和43名健康志愿者进行研究。ELISA法测定血清IL-33、IL-4、IL-6、IL-10和IL-21水平。通过免疫组织化学方法研究了狼疮性肾炎患者(n=5)和对照组(n=3)肾切片中IL-33的表达。通过实时PCR定量外周血单核细胞(PBMC)中Toll样受体4(TLR4)、TLR2和致瘤性2(ST2)L的mRNA表达。通过流式细胞术评估TLR4在T细胞、B细胞、单核细胞和中性粒细胞上的表面表达(n=22)。Mann-Whitney U检验和Spearman检验用于统计分析。结果SLE患者血清IL-33浓度明显高于健康对照组(p<0.0001),IL-33的表达与SLE患者血清中IL-4和IL-6水平呈正相关,在自身抗体的产生中起着关键作用。此外,SLE患者PBMC中TLR4和TLR2mRNA显著增加(p<0.05),TLR4与IL-33呈正相关,而TLR2与IL-33不呈正相关。结论PBMC中血清IL-33的表达上调和TLR4的增加可能通过促进炎性细胞因子的产生而参与SLE的发病机制。
{"title":"Potential role of interleukin-33 in systemic lupus erythematosus by regulating toll like receptor 4","authors":"Yi Li, Y. Shao, Yan He, Qiugen Li, L. Duan","doi":"10.1177/1721727X221094455","DOIUrl":"https://doi.org/10.1177/1721727X221094455","url":null,"abstract":"Introduction Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by immune activation and multi-immunologic phenotypes. Interleukin-33 (IL-33) has been shown to be a critical and pleiotropic immunoregulatory mediator in the pathogenesis of many autoimmune diseases. At present, there are conflicting findings in the research of IL-33 in SLE. The purpose of this study was to investigate whether and how IL-33 is involved in the occurrence and development of SLE. Methods 43 SLE patients and 43 healthy volunteers were recruited for this study. Serum levels of IL-33, IL-4, IL-6, IL-10 and IL-21 were measured by ELISA. The expression of IL-33 was investigated in kidney sections by immunohistochemistry in lupus nephritis patients (n = 5) and controls (n = 3). The mRNA expressions of Toll like receptor 4 (TLR4), TLR2, and tumorigenicity 2 (ST2)L were quantified in peripheral blood mononuclear cells (PBMCs) by real-time PCR. The surface expression of TLR4 on T cells, B cells, monocytes, and neutrophils was assessed by flow cytometry (n = 22). Mann–Whitney U-test and Spearman’s test were used for statistical analysis. Results Serum concentrations of IL-33 were significantly higher in SLE patients than in healthy controls (p < 0.0001). IL-33 expressions were positively correlated with IL-4 and IL-6 levels in SLE patients, which play pivotal roles in the autoantibody production. In addition, TLR4 and TLR2 mRNA were markedly increased in PBMCs from SLE patients (p < 0.05). TLR4 was positively associated with IL-33, while TLR2 was not. Conclusions These results imply that upregulated expression of serum IL-33 together with increased TLR4 in PBMCs may contribute to the pathogenesis of SLE via promotion of inflammatory cytokines production.","PeriodicalId":55162,"journal":{"name":"European Journal of Inflammation","volume":"24 4","pages":""},"PeriodicalIF":0.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41261754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
The dual role of interleukin-17 in the growth of human papillomavirus-negative cervical cancer cells 白细胞介素-17在人乳头瘤病毒阴性宫颈癌细胞生长中的双重作用
IF 0.7 4区 医学 Q4 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/1721727X221128089
Yi-ling Pan, Xishao Luo, Jinghang Ma, Zhen Feng, Yan Hu, Jisen Xue
To explore the relationship between IL-17 mediated immune response and HPV-negative cervical cancer, we established the co-culture system of cervical cancer C-33A cells and PBMC, and treated with different concentrations of rhIL-17. PBMC were extracted from 10ml anticoagulant blood provided by healthy female volunteers and colleagues in our hospital, which were co-cultured with cervical cancer C-33A cells. After treatment with different concentrations of rhIL-17, the proliferation, apoptosis, invasion behavior and VEGF expression level of cancer cells in each group, were determined by CCK-8, flow cytometry, transwell invasion assay and ELISA, respectively. The proliferation rate of C-33A cells slightly increased with the ascending of IL-17 concentration, but no statistical significance was found among each group (P > 0.05). When at low concentration of IL-17, the cell apoptosis rate seems to slightly decline. With the increase of concentration, the decrease of apoptosis rate became more obvious (P < 0.05). However, differing from those shown above, we found that IL-17 slightly inhibited the cancer cell invasion at high concentration, while it was more obvious at low concentration (P < 0.05). Furthermore, we found that there was no significant correlation between IL-17 and VEGF (P > 0.05). In summary, there is a close correlation between IL-17 mediated immune response and HPV-negative cervical cancer. Also, we think that IL-17 may play a dual role in tumor progression and could be a possible significant influence on tumor proliferation, apoptosis, and metastasis, which provides a basic theoretical basis for the further study of immunotherapy measures for cervical cancer.
为了探讨IL-17介导的免疫应答与HPV-阴性宫颈癌症的关系,我们建立了宫颈癌症C-33A细胞和PBMC的共培养体系,并用不同浓度的rhIL-17处理。从我院健康女性志愿者及其同事提供的10ml抗凝血中提取PBMC,并与宫颈癌症C-33A细胞共培养。分别用CCK-8、流式细胞仪、transwell侵袭试验和ELISA法测定各组癌症细胞经不同浓度的rhIL-17处理后的增殖、凋亡、侵袭行为和VEGF表达水平。C-33A细胞的增殖率随IL-17浓度的升高而略有增加,但各组间无统计学意义(P>0.05),低浓度IL-17时细胞凋亡率似乎略有下降。随着浓度的增加,细胞凋亡率的降低更为明显(P<0.05),但与上述结果不同的是,IL-17在高浓度时对癌症细胞的侵袭有轻微的抑制作用,而在低浓度时则更为显著(P<0.01)。此外,我们发现IL-17与VEGF之间没有显著相关性(P>0.05),IL-17介导的免疫应答与HPV-阴性宫颈癌症之间存在密切相关性。此外,我们认为IL-17可能在肿瘤进展中起双重作用,并可能对肿瘤增殖、凋亡和转移产生重要影响,这为进一步研究癌症免疫治疗措施提供了基本的理论依据。
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引用次数: 1
Synovial tuberculosis in wrist diagnosed based on metagenomic next-generation sequencing: A case report 基于宏基因组下一代测序诊断手腕滑膜结核一例报告
IF 0.7 4区 医学 Q4 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/20587392221075507
Meimei Wu, Xianfeng Lan, Shibei Lin, T. Lai, Wei-Sha Lin, Haomin Wu
Synovial tuberculosis in the wrist is a rare disease that is usually misdiagnosed at the early stage. In this case, we presented a 67-year-old male with wrist joint tuberculosis who presented repeated left wrist joint edema for more than 2 years. The patient received surgery twice. During the second surgery, the combination of metagenomic next-generation sequencing (mNGS) and pathological analysis contributed to the detection of Mycobacterium tuberculosis in lesion tissues. Conventional anti-tubercular therapy confirmed the diagnosis of synovial tuberculosis in the wrist joint. In conclusion, mNGS contributed to the rapid and accurate detection of tubercle bacillus.
摘要腕部滑膜结核是一种罕见的疾病,早期常被误诊。在这个病例中,我们报告了一位67岁的男性腕关节结核患者,他反复出现左腕关节水肿超过2年。病人接受了两次手术。在第二次手术中,结合宏基因组下一代测序(mNGS)和病理分析,在病变组织中检测到结核分枝杆菌。常规抗结核治疗证实了腕关节滑膜结核的诊断。综上所述,mNGS有助于快速准确地检测结核杆菌。
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引用次数: 0
Retrospective analysis of immune-related adverse events of the immune checkpoint inhibitors of PD-1/PD-l1 in the Fujian provincial hospital 福建省医院PD-1/PD-l1免疫检查点抑制剂免疫相关不良事件回顾性分析
IF 0.7 4区 医学 Q4 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/1721727X221091540
Jianping Zheng, T. Cui, Yu Gao, Ting Li
Introduction: The effectiveness of programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1) on tumor has been reported. However, the immune-related adverse events (irAEs) and its clinical management of the immune checkpoint inhibitors (ICIs) have not been fully understood. We aimed to analyze the irAEs and its ICIs targeting the PD-1/PD-L1. Methods: The retrospective analysis was performed on the irAEs of cancer patients treated with anti-PD1/PD-L1 monoclonal antibodies from January 2020 to August 2021 including 240 patients/547 cycles. The following aspects including the categories and the grades of the adverse events (AEs), the time of onset and duration, management plan, and prognosis were evaluated. Results: Among 240 patients, 93 patients (38.75%) experienced irAEs, and 10 patients (4.16%) had AEs that involved multiple organ systems at the same time. There were 83 cases (34.58%) of grade 1–2 AEs and 10 cases (4.17%) of grade three and above AEs. AEs above grade three included five cases of grade three AEs (3 cases of hepatic toxicity, one case of colitis, and one case of skin toxicity), three cases of grade four AEs (pneumonia); and 2 cases of grade five AEs (two deaths due to pneumonia). The complete remission of AEs was achieved in 10 patients by corticosteroid impulse therapy, maintenance therapy, and symptomatic therapy. Among them, six cases continued to use anti-PD1/PD-L1 monoclonal antibodies, two cases stopped, and two patients died from systemic multi-organ failure due to the delayed observation of autoimmune pneumonia. IrAEs occurred at different times and durations in different systems or organs. Conclusion: The safety of PD-1/PD-L1 inhibitors was approved in clinical applications. The prevalence of grade three and above AEs is relatively low. Timely diagnosis and early glucocorticoid therapies are adequate and effective approaches for the management of irAEs.
前言:程序性细胞死亡蛋白1(PD-1)和程序性细胞凋亡配体1(PD-L1)对肿瘤的治疗作用已有报道。然而,免疫相关不良事件(irAE)及其对免疫检查点抑制剂(ICIs)的临床管理尚不完全清楚。我们旨在分析靶向PD-1/PD-L1的irAE及其ICI。方法:对2020年1月至2021年8月癌症患者应用抗PD1/PD-L1单克隆抗体治疗的irAE进行回顾性分析,包括240例患者/547个周期。评估了以下方面,包括不良事件(AE)的类别和级别、发病时间和持续时间、管理计划和预后。结果:在240名患者中,93名患者(38.75%)出现irAE,10名患者(4.16%)同时出现涉及多个器官系统的AE。1–2级AE 83例(34.58%),3级及以上AE 10例(4.17%)。三级以上AE包括5例三级AE(3例肝毒性,1例结肠炎,1例皮肤毒性),3例四级AE(肺炎);5级AE 2例(2例因肺炎死亡)。通过皮质类固醇脉冲治疗、维持治疗和症状治疗,10名患者的AE完全缓解。其中,6例继续使用抗PD1/PD-L1单克隆抗体,2例停止使用,2例因自身免疫性肺炎延迟观察导致全身多器官衰竭死亡。IrAE发生在不同系统或器官的不同时间和持续时间。结论:PD-1/PD-L1抑制剂在临床应用中是安全的。三级及以上AE的患病率相对较低。及时诊断和早期糖皮质激素治疗是治疗irAE的充分有效的方法。
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引用次数: 1
Quercetin exerts an ameliorative effect in the rat model of diclofenac-induced renal injury through mitigation of inflammatory response and modulation of oxidative stress 槲皮素通过减轻炎症反应和调节氧化应激,在双氯芬酸肾损伤大鼠模型中发挥改善作用
IF 0.7 4区 医学 Q4 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/1721727X221086530
Farzad Izak-Shirian, Maryam Najafi-Asl, Behzad Azami, E. Heidarian, M. Najafi, Mansoor Khaledi, A. Nouri
Diclofenac (DIC) is administrated to treat pain, inflammatory disorders, and dysmenorrhea but kidney problems are the main worries of the agent. The literature has revealed that quercetin (QR) has anti-inflammatory and antioxidant attributes. This study aims to highlight the possible nephroprotective effects of QR on DIC-exposed rats. In this study, the animals after exposure to DIC (50 mg/kg, i.p) were administrated to QR (100 mg/kg, p.o). Then, the levels, as well as the activity of several oxidant and anti-oxidant mediators, were evaluated. Our results showed that DIC treatment was coupled with the elevation in the levels of malondialdehyde (MDA), nitric oxide (NO), and some pro-inflammatory factors such as TNF-α, NF-κB, and IL-1β, suggesting that probably this agent exert its toxicity in the kidney tissue through inducing both oxidative stress and inflammation. Interestingly, QR was successful in restoring the activity of antioxidant compounds such as GSH, GPx, SOD, and CAT in the kidney tissue of DIC-treated rats. Moreover, in the presence of QR, DIC was unable to increase the expression of pro-inflammatory cytokines, suggesting that perhaps QR might have anti-inflammatory properties. In agreement with this, the results of the histopathological evaluation also showed that while DIC increased the lymphocyte infiltration into the kidney tissue, QR reduced the number of lymphocytes in DIC-treated rats. The results revealed that QR exerted a supportive effect against diclofenac-induced renal injury in male rats through modulation of oxidative stress and mitigation of inflammatory response.
双氯芬酸(DIC)用于治疗疼痛、炎症性疾病和痛经,但肾脏问题是该药物的主要担忧。文献表明槲皮素(QR)具有抗炎和抗氧化特性。本研究旨在强调QR对暴露于dic的大鼠可能的肾保护作用。在本研究中,暴露于DIC (50 mg/kg, i.p)后的动物给予QR (100 mg/kg, p.o)。然后,评估了几种氧化和抗氧化介质的水平以及活性。我们的研究结果表明,DIC治疗伴随着丙二醛(MDA)、一氧化氮(NO)和一些促炎因子如TNF-α、NF-κB和IL-1β水平的升高,表明这种药物可能通过诱导氧化应激和炎症在肾组织中发挥其毒性。有趣的是,QR成功地恢复了抗氧化化合物如GSH、GPx、SOD和CAT在dic处理大鼠肾组织中的活性。此外,在QR存在的情况下,DIC无法增加促炎细胞因子的表达,这表明QR可能具有抗炎特性。与此相一致的是,组织病理学评价结果也显示DIC在增加肾组织淋巴细胞浸润的同时,QR减少了DIC处理大鼠的淋巴细胞数量。结果显示,QR通过调节氧化应激和减轻炎症反应,对双氯芬酸诱导的雄性大鼠肾损伤具有支持作用。
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引用次数: 3
期刊
European Journal of Inflammation
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