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Alternative Splicing in Multiple Sclerosis: A Promising Biomarker of Therapeutic Response to Interferon-β. 多发性硬化症中的替代剪接:干扰素-β治疗反应的有望生物标志物
IF 1.9 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-01 Epub Date: 2024-05-27 DOI: 10.1089/jir.2024.0108
Suhayl Dhib-Jalbut
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引用次数: 0
Age-Dependent Signature of Serum Inflammatory Cytokines in Healthy Children and Young Adults. 健康儿童和青少年血清炎症细胞因子的年龄特征
IF 1.9 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-01 Epub Date: 2024-06-27 DOI: 10.1089/jir.2024.0053
Maarten Buytaert, Rachida El Kaddouri, Levi Hoste, Bram Meertens, Simon Jan Tavernier, Karlien Claes, Veronique Debacker, Jo Dehoorne, Filomeen Haerynck

The study of sensitive and specific biomarkers, such as blood inflammatory cytokines, could provide an answer to the challenges faced in the differential diagnosis of patients with systemic inflammation. Limited data exist on the impact of age on serum levels of inflammatory cytokines. We collected serum samples of 42 healthy children and young adults (1 month to 21 years). Serum levels of interleukin 1 receptor antagonist (IL-1Ra), IL-1β, IL-6, IL-18, tumor necrosis factor-alpha (TNF-α), CXCL9, and CXCL10 were measured. Data were analyzed for three different age groups (<6, 6-17, and 18-21 years). IL-18, TNF-α, and CXCL9 values varied significantly according to age group. Median values of IL-18 and TNF-α decline with age, whereas CXCL9 and CXCL10 are lowest at 6-17 years. IL-1Ra is stable among age groups. In the majority of cases, IL-1β and IL-6 are not measurable above the lower limit of quantification. A scoping literature review revealed highly variable data on IL-1Ra, IL-18, TNF-α, and CXCL10. For CXCL9, pediatric reference data are scarce. In conclusion, we report an age-dependent signature of multiple inflammatory cytokines measured in the serum of healthy children and young adults, suggesting the need to use age-specific reference values in future pediatric studies.

对血液炎症细胞因子等敏感而特异的生物标志物进行研究,可以为全身性炎症患者的鉴别诊断提供答案。关于年龄对血清中炎症细胞因子水平影响的数据十分有限。我们采集了 42 名健康儿童和年轻人(1 个月至 21 岁)的血清样本。测量了血清中白细胞介素 1 受体拮抗剂(IL-1Ra)、IL-1β、IL-6、IL-18、肿瘤坏死因子-α(TNF-α)、CXCL9 和 CXCL10 的水平。对三个不同年龄组 (
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引用次数: 0
The Interplay Between Cytokines and MicroRNAs to Regulate Metabolic Disorders. 细胞因子与 MicroRNA 之间的相互作用可调节代谢紊乱。
IF 1.9 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-01 Epub Date: 2024-07-31 DOI: 10.1089/jir.2024.0059
Li Zhang, Li Zhang, Huan Chen, Xiangyong Xu

Metabolic disorders represent significant public health challenges worldwide. Emerging evidence suggests that cytokines and microRNAs (miRNAs) play crucial roles in the pathogenesis of metabolic disorders by regulating various metabolic processes, including insulin sensitivity, lipid metabolism, and inflammation. This review provides a comprehensive overview of the intricate interplay between cytokines and miRNAs in the context of metabolic disorders, including obesity, type 2 diabetes, and cardiovascular diseases. We discuss how dysregulation of cytokine-miRNA networks contributes to the development and progression of metabolic disorders and explore the therapeutic potential of targeting these interactions for disease management.

代谢紊乱是全球面临的重大公共卫生挑战。新的证据表明,细胞因子和微 RNA(miRNA)通过调节各种代谢过程,包括胰岛素敏感性、脂代谢和炎症,在代谢紊乱的发病机制中发挥着至关重要的作用。本综述全面概述了细胞因子和 miRNA 在肥胖、2 型糖尿病和心血管疾病等代谢性疾病中错综复杂的相互作用。我们讨论了细胞因子-miRNA 网络失调如何导致代谢紊乱的发生和发展,并探讨了针对这些相互作用进行疾病管理的治疗潜力。
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引用次数: 0
Cytokine Signatures and Immune Dysregulation in COVID-19 Patients: Transcriptomic and Serum Analysis. COVID-19 患者的细胞因子特征和免疫失调:转录组和血清分析
IF 1.9 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-01 Epub Date: 2024-07-01 DOI: 10.1089/jir.2024.0083
Nikola Ralchev, Silviya Lyubenova Bradyanova, Yana Valerieva Doneva, Nikolina Mihaylova, Elena Vikentieva Elefterova-Florova, Andrey Ivanov Tchorbanov, José Francisco Muñoz-Valle, Maria Cristina Petralia, Ferdinando Nicoletti, Paolo Fagone

COVID-19, caused by the SARS-CoV-2 virus, has caused a global health crisis, necessitating a deeper understanding of its pathophysiology. In this study, we explored the immune and hematological dynamics in COVID-19 patients to gain insights into disease severity and prognosis. Our findings revealed distinct cytokine profiles in moderate and severe cases. IL12A was significantly upregulated in peripheral blood mononuclear cells from moderate cases, suggesting a potential role in initiating an effective immune response. Conversely, severe cases exhibited downregulation of key pro-inflammatory cytokines (IL23A, TNFalpha, IL1B, and IFNG) alongside an upregulation of the immunosuppressive IL10, indicative of a dysregulated immune environment. Serum analysis showed elevated IL6 and IL10 levels in both moderate and severe cases, emphasizing their potential as markers for disease severity. Notably, no significant differences in serum cytokines were found between recovery and lethal cases. In lethal cases of COVID-19, elevated D-dimer, urea, and creatinine correlated with IL6 and IL10. This study contributes valuable information to the ongoing efforts to understand and manage the dysregulated immune responses underlying COVID-19 pathology.

由 SARS-CoV-2 病毒引起的 COVID-19 已造成全球健康危机,因此有必要加深对其病理生理学的了解。在本研究中,我们探讨了 COVID-19 患者的免疫和血液动态,以深入了解疾病的严重程度和预后。我们的研究结果显示,中度和重度病例的细胞因子谱各不相同。在中度病例的外周血单核细胞中,IL12A明显上调,这表明它在启动有效的免疫反应中起着潜在的作用。相反,重症病例的主要促炎细胞因子(IL23A、TNFalpha、IL1B 和 IFNG)下调,同时免疫抑制因子 IL10 上调,表明免疫环境失调。血清分析表明,在中度和重度病例中,IL6 和 IL10 水平都有所升高,这说明它们有可能成为疾病严重程度的标志物。值得注意的是,恢复期病例和致死病例的血清细胞因子没有明显差异。在 COVID-19 的致死病例中,D-二聚体、尿素和肌酐的升高与 IL6 和 IL10 相关。这项研究为目前了解和管理作为 COVID-19 病理学基础的失调免疫反应提供了宝贵的信息。
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引用次数: 0
The Role of Interleukin-22 in Controlling Virus Infections at Mucosal Surfaces. 白细胞介素-22 在控制黏膜表面病毒感染中的作用
IF 1.9 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-01 Epub Date: 2024-06-13 DOI: 10.1089/jir.2024.0097
Cuncai Guo, Steeve Boulant, Megan Lynn Stanifer
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引用次数: 0
Alternative Splicing of RNA Is Excessive in Multiple Sclerosis and Not Linked to Gene Expression Levels: Dysregulation Is Corrected by IFN-β. 多发性硬化症患者的 RNA 替代剪接过多,且与基因表达水平无关:IFN-β 可纠正失调。
IF 1.9 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-01 Epub Date: 2024-05-02 DOI: 10.1089/jir.2024.0032
Anthony T Reder, Aika Goel, Tzintzuni Garcia, Xuan Feng
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引用次数: 0
Activated and Naïve Allogenic Human Placental Mesenchymal Stromal Cells Exert an Immunomodulatory Effect on Hidradenitis Suppurativa Patient Peripheral Blood Mononuclear Cells. 活化和新生的异源人胎盘间充质基质细胞对扁平苔藓患者外周血单核细胞有免疫调节作用
IF 1.9 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-01 Epub Date: 2024-04-12 DOI: 10.1089/jir.2024.0035
Vaiva Jariene, Paulius Valiukevicius, Justinas Maciulaitis, Ugne Kuzaityte, Ruta Insodaite, Ieva Ciapiene, Romaldas Maciulaitis, Skaidra Valiukeviciene

This pilot study aimed to evaluate the immunomodulatory effect of placental mesenchymal stem/stromal cells (MSCs) on peripheral blood mononuclear cells (PBMCs) from patients with hidradenitis suppurativa (HS). Blood samples were collected from 3 healthy and 3 patients with HS. Isolated PBMCs were stained with carboxyfluorescein succinimidyl ester (CFSE) and stimulated with phorbol 12-myristate 13-acetate (PMA)/Ionomycin solution. The PBMCs of patients with HS were co-cultured with naïve MSCs (n-MSCs), activated with tumor necrosis factor (TNF)-α (10 ng/mL) and interferon (IFN)-γ (10 ng/mL) MSCs (a-MSCs), or adalimumab (30 μg/mL). The division index (proliferation inhibition) of PBMCs was analyzed by flow cytometry using the Proliferation Modeling tool after 5 days of coculture. The relative inflammatory gene expression dynamics and cytokine secretion were quantified in triplicate using real-time polymerase chain reaction (PCR) and Luminex assays. PBMCs from the HS control group showed statistically significant increases in interleukin (IL)-6 and IFN-γ cytokine concentrations and IL-17A gene expression when compared with healthy subjects. Statistically significant reduction of the division index was found in the a-MSCs group (P = 0.04). Also, the Luminex assay revealed significantly reduced proinflammatory cytokine concentrations of IL-9 (P = 0.022) and IL-17A (P = 0.022) in the a-MSCs group with the same trend of numerical lowering in n-MSCs group when compared to HS control. The results of real-time PCR revealed a numerical increase in the expression of the IL-1β, IL-36α, and TNF-α genes in both the a-MSCs and n-MSCs groups compared with the HS control. In conclusion, our findings suggest that MSCs can effectively curb PBMCs proliferation and suppress the production of inflammatory cytokines. Moreover, the preactivation of MSCs with IFN-γ and TNF-α before use can enhance their therapeutic effectiveness. Nevertheless, a larger sample size is imperative to validate these results.

这项试验性研究旨在评估胎盘间充质干/基质细胞(MSCs)对化脓性扁桃体炎(HS)患者外周血单核细胞(PBMCs)的免疫调节作用。采集了3名健康人和3名化脓性扁桃体炎患者的血液样本。分离出的 PBMC 用羧基荧光素琥珀酰亚胺酯(CFSE)染色,并用 12-肉豆蔻酸 13-醋酸酯(PMA)/异诺米霉素溶液刺激。将 HS 患者的 PBMC 与天真间充质干细胞(n-MSCs)、用肿瘤坏死因子(TNF)-α(10 ng/mL)和干扰素(IFN)-γ(10 ng/mL)激活的间充质干细胞(a-MSCs)或阿达木单抗(30 μg/mL)共培养。共培养 5 天后,使用增殖模型工具通过流式细胞仪分析 PBMC 的分裂指数(增殖抑制)。使用实时聚合酶链反应(PCR)和 Luminex 检测法对一式三份的相对炎症基因表达动态和细胞因子分泌进行量化。与健康受试者相比,HS 对照组的白细胞介素(IL)-6 和 IFN-γ 细胞因子浓度以及 IL-17A 基因表达均有统计学意义的显著增加。经统计发现,a-间充质干细胞组的分裂指数明显下降(P = 0.04)。此外,Luminex 检测显示,与 HS 对照组相比,a-间充质干细胞组的促炎细胞因子 IL-9 浓度(P = 0.022)和 IL-17A 浓度(P = 0.022)明显降低,n-间充质干细胞组的数值降低趋势相同。实时 PCR 结果显示,与 HS 对照组相比,a-间充质干细胞组和 n-间充质干细胞组中 IL-1β、IL-36α 和 TNF-α 基因的表达量均有增加。总之,我们的研究结果表明,间充质干细胞能有效抑制 PBMC 的增殖并抑制炎症细胞因子的产生。此外,使用前用 IFN-γ 和 TNF-α 预激活间充质干细胞可提高其治疗效果。不过,要验证这些结果,还需要更大的样本量。
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引用次数: 0
The Effective Inhibitory Concentration of Interferon-β Correlates with Infectivity and Replication Fitness of SARS-CoV-2 Variants. 干扰素-β的有效抑制浓度与SARS-CoV-2变体的感染性和复制能力有关
IF 1.9 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-01 Epub Date: 2024-04-01 DOI: 10.1089/jir.2024.0016
Janmejay Singh, Anbalagan Anantharaj, Parveen Kumar, Rajesh Pandey, Anil Kumar Pandey, Guruprasad R Medigeshi

India saw a spike in COVID-19 cases in early 2023, and this wave of infection was attributed to XBB sublineages of SARS-CoV-2 Omicron variant. The impact of XBB wave was significantly shorter with low burden of severe cases or hospitalization as compared with previous SARS-CoV-2 variants of concern. Although a combination of old and new mutations in the spike region of XBB.1.16 variant led to a drastic reduction in the ability of antibodies from prior immunity to neutralize this virus, additional nonspike mutations suggested a possible change in its ability to suppress innate immune responses. In this study, we tested the sensitivity of Delta, BA.2.75, and XBB.1.16 variants to interferon-β (IFN-β) treatment and found that XBB.1.16 variant was most sensitive to IFN-β. We next tested the ability of serum antibodies from healthy individuals to neutralize XBB.1.16. We showed that most of the individuals with hybrid immunity maintained a low but significant level of neutralizing antibodies to XBB.1.16 variant. Therefore, our observations indicated that both hybrid immunity because of natural infection and enhanced sensitivity to IFNs may have contributed to the low impact of XBB.1.16 infections in India.

2023 年初,印度的 COVID-19 病例激增,这次感染潮是由 SARS-CoV-2 Omicron 变体的 XBB 亚系引起的。与之前令人担忧的 SARS-CoV-2 变体相比,XBB 波的影响时间明显较短,重症病例或住院人数较少。虽然XBB.1.16变异株尖峰区的新旧变异结合导致先前免疫的抗体中和该病毒的能力急剧下降,但额外的非尖峰变异表明其抑制先天性免疫反应的能力可能发生了变化。在这项研究中,我们检测了Delta、BA.2.75和XBB.1.16变体对干扰素-β(IFN-β)处理的敏感性,发现XBB.1.16变体对IFN-β最敏感。接下来,我们检测了健康人血清抗体中和 XBB.1.16 的能力。结果表明,大多数具有混合免疫力的个体都能维持较低水平的 XBB.1.16 变体中和抗体。因此,我们的观察结果表明,自然感染导致的混合免疫和对 IFNs 的敏感性增强可能是印度 XBB.1.16 感染影响较低的原因。
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引用次数: 0
Evaluation of Serum/Plasma Levels of Interleukins (IL-6, IL-12, IL-17, IL-18, and IL-23) in Adults and Children with Obstructive Sleep Apnea: A Systematic Review, Meta-Analysis, and Trial Sequential Analysis. 评估成人和儿童阻塞性睡眠呼吸暂停患者的血清/血浆白细胞介素(IL-6、IL-12、IL-17、IL-18 和 IL-23)水平:系统综述、元分析和试验序列分析》。
IF 1.9 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-01 Epub Date: 2024-05-17 DOI: 10.1089/jir.2024.0057
Amin Golshah, Masoud Sadeghi, Edris Sadeghi

Obstructive sleep apnea (OSA) is a chronic inflammatory disease characterized by partial or complete upper airway obstruction during sleep. We aimed to evaluate serum/plasma levels of several cytokines (interleukin [IL]-6, IL-12, IL-17, IL-18, and IL-23) in a systematic review meta-analysis in both adults and children with OSA compared with controls. We conducted a comprehensive search of 4 digital databases (PubMed, Web of Science, Scopus, and Cochrane Library) up until October 19, 2023, without any limitations. For our meta-analysis, we used Review Manager, version 5.3, and displayed the data as the standardized mean difference (SMD) and 95% confidence interval (CI) to assess the correlation between cytokine levels and OSA. We utilized Comprehensive Meta-Analysis version 3.0 software to conduct bias analyses, meta-regression, and sensitivity analyses. From 1881 records, 84 articles were included in the systematic review and meta-analysis. In adults, the pooled SMDs for IL-6 level were 0.79 (P value < 0.00001), for IL-17 level were 0.74 (P value = 0.14), and for IL-18 level were 0.43 (P value = 0.00002). In children, the pooled SMD for IL-6 was 1.10 (P value < 0.00001), for IL-12 was 0.47 (P value = 0.10), for IL-17 was 2.21 (a P value = 0.24), for IL-18 was 0.19 (P value = 0.07), and for IL-23 was 2.46 (P value < 0.0001). The subgroup analysis showed that the ethnicity, mean body mass index, and mean apnea-hypopnea index for IL-6 levels in adults and the ethnicity for IL-6 levels in children were effective factors in the pooled SMD. The findings of the trial sequential analysis revealed that adequate evidence has been obtained. The analysis of IL levels in adults and children with OSA compared with those without OSA revealed significant differences. In adults, IL-6 and IL-18 levels were significantly higher in the OSA group, while in children, only IL-6 and IL-23 levels were significantly elevated.

阻塞性睡眠呼吸暂停(OSA)是一种慢性炎症性疾病,其特点是睡眠时上气道部分或完全阻塞。我们的目的是通过系统综述荟萃分析评估几种细胞因子(白细胞介素 [IL]-6、IL-12、IL-17、IL-18 和 IL-23)的血清/血浆水平,将成人和儿童 OSA 患者与对照组进行比较。截至 2023 年 10 月 19 日,我们对 4 个数字数据库(PubMed、Web of Science、Scopus 和 Cochrane Library)进行了全面检索,没有任何限制。在进行荟萃分析时,我们使用了5.3版的Review Manager,并将数据显示为标准化平均差(SMD)和95%置信区间(CI),以评估细胞因子水平与OSA之间的相关性。我们使用 Comprehensive Meta-Analysis 3.0 版软件进行了偏倚分析、元回归和敏感性分析。在1881条记录中,有84篇文章被纳入系统综述和荟萃分析。在成人中,IL-6水平的集合SMD为0.79(P值<0.00001),IL-17水平的集合SMD为0.74(P值=0.14),IL-18水平的集合SMD为0.43(P值=0.00002)。在儿童中,IL-6的集合SMD为1.10(P值<0.00001),IL-12为0.47(P值=0.10),IL-17为2.21(P值=0.24),IL-18为0.19(P值=0.07),IL-23为2.46(P值<0.0001)。亚组分析表明,成人IL-6水平的种族、平均体重指数和平均呼吸暂停-低通气指数以及儿童IL-6水平的种族是影响集合SMD的有效因素。试验序列分析结果显示,已获得了充分的证据。对患有 OSA 的成人和儿童的 IL 水平与未患有 OSA 的成人和儿童的 IL 水平进行的分析表明,两者之间存在显著差异。在成人中,OSA组的IL-6和IL-18水平显著升高,而在儿童中,只有IL-6和IL-23水平显著升高。
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引用次数: 0
The Effects of Convalescent Plasma Transfusion on Serum Levels of Macrophage-Associated Inflammatory Biomarkers in Patients with Severe COVID-19. 康复期血浆输注对严重 COVID-19 患者血清中巨噬细胞相关炎症生物标志物水平的影响
IF 1.9 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-01 Epub Date: 2024-05-13 DOI: 10.1089/jir.2024.0018
Mojtaba Shohan, Mohammad Reza Mahmoudian-Sani, Ali Saeedi-Boroujeni, Sara Iranparast, Roohangiz Nashibi, Farhad Abolnezhadian, Farid Yousefi, Seyed Mohammad Alavi, Bahman Cheraghian, Ali Khodadadi

As an antibody-based therapy, plasma therapy has been used as an emergency therapeutic strategy against severe acute respiratory syndrome coronavirus type 2 infection. Due to the critical role of macrophages in coronavirus disease-19 (COVID-19)-associated hyperinflammation, the main objective of this study was to assess the effect of plasma transfusion on the expression levels of the inflammatory biomarkers involved in activation and pulmonary infiltration of macrophages. The target population included 50 severe hospitalized COVID-19 patients who were randomly assigned into 2 groups, including intervention and control. Serum levels of chemokine (C-C motif) ligand (CCL)-2, CCL-3, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 were measured by enzyme-linked immunosorbent assay. Moreover, quantitative real-time polymerase chain reaction (PCR) was carried out to assess the relative expression of nuclear factor (NF)-κB1, NF-κB2, nuclear factor erythroid 2 p45-related factor 2 (NRF-2), and thioredoxin-interacting protein genes. Sampling was done at baseline and 72 h after receiving plasma. The intervention group demonstrated significantly lower serum levels of IL-6, TNF-α, and CCL-3. In addition, real-time PCR data analyses showed that the relative expression of NF-κB2 was significantly declined in the patients who received plasma. The use of convalescent plasma probably has a significant inhibitory effect on the cytokines, chemokines, and inflammatory genes related to macrophage activation, which are closely associated with the worsening of clinical outcomes in severe COVID-19.

作为一种基于抗体的疗法,血浆疗法已被用作应对严重急性呼吸系统综合征冠状病毒2型感染的紧急治疗策略。由于巨噬细胞在冠状病毒病-19(COVID-19)相关的高炎症中起着关键作用,本研究的主要目的是评估输注血浆对巨噬细胞活化和肺浸润相关炎症生物标志物表达水平的影响。研究对象包括 50 名严重的 COVID-19 住院患者,他们被随机分配到两组,包括干预组和对照组。采用酶联免疫吸附法测定血清中趋化因子(C-C 矩阵)配体(CCL)-2、CCL-3、肿瘤坏死因子(TNF)-α 和白细胞介素(IL)-6 的水平。此外,还进行了定量实时聚合酶链反应(PCR),以评估核因子(NF)-κB1、NF-κB2、核因子红细胞 2 p45 相关因子 2(NRF-2)和硫氧还蛋白相互作用蛋白基因的相对表达。分别在基线和接受血浆 72 小时后进行采样。干预组的血清中 IL-6、TNF-α 和 CCL-3 水平明显降低。此外,实时 PCR 数据分析显示,接受血浆的患者 NF-κB2 的相对表达量明显下降。使用康复血浆可能对与巨噬细胞活化相关的细胞因子、趋化因子和炎症基因有明显的抑制作用,而巨噬细胞活化与重症 COVID-19 临床预后的恶化密切相关。
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引用次数: 0
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Journal of Interferon and Cytokine Research
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