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摘要： Abstract Anemia of inflammation (AI) is the second most common form of anemia and is prevalent in patients with chronic inflammatory states, such as infection, autoimmunity, and cancer. Interleukin 6 (IL-6) is well-known to induce the iron-sequestering hormone hepcidin, which results in iron-restricted anemia. The contributions of other proinflammatory cytokines, such as tumor necrosis factor-α (TNFα) and interferon gamma (IFNγ), are less understood in the pathophysiology of AI. This study investigated the role of TNFα in a mouse model of AI by administering heat-killed Brucella abortus (HKBA) to germ line TNFα knockout (KO) mice. We hypothesized that TNFα possessed an important role in restoring steady-state erythropoiesis after inflammatory insult. TNFαKO injected with HKBA displayed a chronic anemia, with elevated proinflammatory IL12p40 and IFNγ cytokines that did not resolve. However, IFNγKO and TNFαKO/FNγKO double knockout mice showed reduced inflammation and anemia following HKBA administration. Because IFNγKO displayed normal serum TNFα and IL12p40 levels, we hypothesized that the persistent anemia was IFNγ induced and TNFα was necessary for AI cessation. However, treatment with recombinant TNFα (rTNFα) accelerated death, while reducing IFNγ using an anti-IFNγ antibody (Ab) only briefly improved anemia. Only the combination of both the Ab and rTNFα together reversed the hyperinflammatory phenotype, restored erythropoiesis, and prevented death of TNFαKO + HKBA mice. Our data provide compelling evidence for an anti-inflammatory role of TNFα that is necessary for the restoration of erythropoiesis and mitigation of proinflammatory IFNγ action in a mouse model of AI.

关键词： 骨关节炎   香菇多糖   软骨细胞   细胞外基质   ROS/NF-κB信号通路  

摘要： 目的：探讨香菇多糖（LNT）对白细胞介素-1β(IL-1β)诱导的软骨细胞的作用及机制。方法：采用CCK-8法检测不同浓度LNT(0、50、100、200、400和800μg·mL-1)处理24 h或72 h后对人软骨细胞活性的影响。随后将软骨细胞分为对照组、IL-1β组(10 ng·mL-1)、LNT(100μg·mL-1)+IL-1β组和LNT(200μg·mL-1)+IL-1β组，EdU染色检测LNT对IL-1β处理后软骨细胞增殖水平；Western Blot检测软骨细胞基质金属蛋白酶13（MMP13）、血小板反应蛋白解整合素金属肽酶5（ADAMTS5）、Ⅱ型胶原蛋白α1链（Col2a1）和p-P65的蛋白表达；免疫荧光染色检测软骨细胞MMP13、Col2a1的蛋白表达及p-P65核转位；荧光探针DCFH-DA检测软骨细胞活性氧（ROS）的产生。结果：低浓度LNT(50、100、200和400μg·mL-1)较对照组活性无显著性差异，而与LNT(400μg·mL-1)相比，LNT(800μg·mL-1)显著抑制软骨细胞活性（P<0.05）；此外，EdU染色显示LNT(200μg·mL-1)显著改善IL-1β诱导的增殖抑制（P<0.05）；另外，LNT能够显著抑制IL-1β诱导的软骨细胞基质降解酶MMP13和ADAMTS5的蛋白表达，并促进软骨基质Col2a1的蛋白表达（P<0.05或P<0.01）；机制层面，IL-1β诱导的软骨细胞ROS的产生及p-P65核转位能被LNT显著抑制（P<0.05或P<0.01）。结论：LNT通过抑制ROS/NF-κB信号通路，改善IL-1β诱导的软骨细胞增殖抑制及基质降解，为探索骨关节炎新的药物治疗策略提供实验依据。

关键词： 新生儿败血症   IL-6   IL-8联合PCT   CRP   诊断  

摘要： 探讨白细胞介素-6(IL-6)、白细胞介素-8(IL-8)联合降钙素原(PCT)、C反应蛋白(CRP)在新生儿败血症早期诊断中的效果,以提高新生儿败血症的诊断敏感性和精确度,为对新生儿败血症的早期发现提供更多依据。方法 收治的100例疑似新生儿败血症患儿于2023年1月至2024年3月内进行收治,按不同的诊断方式把患儿随机分为对照组(50例)、试验组(50例)。对照组以常规血培养与单一检测生物标志物诊断,试验组以联合检测IL-6、IL-8、PCT、CRP进行早期诊断。通过比较两组的诊断效能、诊断时间差异以及后续预后情况,评估联合检测方案的诊断优势。结果 实验组在诊断灵敏度、特异性和准确度上显著高于对照组。联合检测不仅能够缩短诊断时间,减少延误治疗的风险,还能对新生儿败血症的早期识别起到积极作用。此外,实验组患儿的临床预后明显优于对照组,死亡率和并发症发生率明显降低。结论 IL-6、IL-8联合PCT、CRP的检测方案在新生儿败血症的早期诊断中展现了较高的临床价值。这一方案能够有效缩短诊断时间,提高治疗及时性,并对改善患儿的预后产生积极影响。因此,联合检测不仅具有实际应用前景,也为新生儿败血症的早期诊断提供了新的思路和方法。

关键词： 免疫球蛋白   美罗培南   新生儿败血症   炎症反应   免疫水平  

摘要： 分析免疫球蛋白与美罗培南治疗对新生儿败血症患儿的效果。方法 选取我院的60例败血症新生儿患儿,分入研究组(30例,采用免疫球蛋白联合美罗培南治疗)和对照组(30例,采用美罗培南治疗),比较两组效果。结果 研究组效果优于对照组(P<0.05)。结论 免疫球蛋白联合美罗培南治疗对败血症患儿的效果优于单独美罗培南治疗,更有利于促进患儿炎症反应与免疫指标改善,提升总体疗效,缩短症状消除时间。

关键词： 儿童川崎病   静注人免疫球蛋白   阿司匹林   氯吡格雷   效果评估  

摘要： 进一步剖析川崎病儿童分别应用阿司匹林联合静注人免疫球蛋白及氯吡格雷联合静注人免疫球蛋白的治疗效果与价值,为不适合应用阿司匹林药物治疗的川崎病儿童在药物选择上提供可靠性分析。方法 一共纳入100例川崎病患儿,全部患儿均来源上林县人民医院,使用黑白球法分为例数均衡的两组,形成对照组(n=50)和观察组(n=50),对应采用静注人免疫球蛋白尿联合阿司匹林和静注人免疫球蛋白联合氯吡格雷,并量化评估最终的治疗效果和应用价值。结果 两组对比,在炎症水平、BNP水平、临床总有效率、不良反应以及住院时间等方面均无统计学意义(P>0.05)。结论 在儿童川崎病的治疗中,静注人免疫球蛋白联合氯吡格雷治疗方案在降低炎症指标无明显优势,在总体疗效、药物不良反应与传统应用静注人免疫球蛋白联合阿司匹林无明显差异,应用于合并阿司匹林禁忌症的川崎病患儿是有效的、安全的。

摘要： Chronic inflammation, resulting from infections, is characterized by increased levels of cytokines including interleukin-1 (IL-1), but little is known about how IL-1 contributes to cognitive impairment, potentially via epigenetic processes. Here we demonstrate that mice chronically infected with the parasite Toxoplasma gondii exhibit impaired spatial memory, which is dependent on neuronal IL-1 signaling and mimicked by chronic exposure to IL-1β. Both T. gondii infection and chronic IL-1β drive H2A.X-dependent DNA double-strand break signaling in hippocampal neurons and invalidating neuronal H2A.X-dependent signaling blocks memory impairments caused by either exposure. Our results highlight the instrumental role of cytokine-induced double-strand-break-dependent signaling in spatial memory defects, which may be relevant to multiple brain diseases.

关键词： 急性淋巴细胞白血病   诱导缓解   化疗   护理干预   疗效评估  

摘要： 钻研急性淋巴细胞白血病(ALL)患者诱导缓解化疗期间护理干预的作用,估量护理手段对患者化疗成果、不良反应、生活水平及疗效延续时间的效应,方法 这项研究选取80例急性淋巴细胞白血病患者入组,随机把对象分为对照组与观察组,分别采用常规化疗及常规化疗结合个性化护理方式。对比两组化疗后缓解比率、不良反应出现率、生活质量得分以及疗效持续时间,结果 观察组完全缓解率为45.00%这一数值,显著比对照组的25.00%要高;观察组呈现出82.50%的总体缓解率,显著高于对照组的65.00%,p<0.001,差异极为显著;观察组出现不良反应的比率明显低于对照组,尤其是恶心呕吐出现的概率,p计作0.014;观察组体现出的无病生存时长为9.2个月,显著胜过对照组的6.5个月,结论 护理干预可大幅提升急性淋巴细胞白血病患者的治疗成效,降低不良反应几率,提高生活质量水平,并可延长治疗效果的维持期,暗示护理干预应成为ALL治疗的关键成分。

关键词： 5-hydroxymethylcytosine   cytokine   inflammation   mesenchymal stem cells   obesity  

摘要： BACKGROUND:Mesenchymal stromal cells (MSCs) possess therapeutic properties that mediate repair. Obesity impairs MSC functionality and therapeutic efficacy, possibly by eliciting dynamic modifications of epigenetic markers, like 5-hydroxymethylcytosine (5hmC). We hypothesized that human obesity alters the 5hmC landscape and anti-inflammatory capacity of adipose tissue-derived MSCs to activate the prominent inflammatory signaling mediator Interleukin (IL)-1β. METHODS:Adipose tissue samples were collected from obese and lean individuals (body mass index ≥30 or < 30kg/m2, respectively, n = 11 each) during weight-loss or kidney donation surgery. MSCs were harvested and analyzed for 5hmC profiles (MeDIP-seq) and mRNA expression (RNA-seq) (n = 5 each). Subsequently, MSCs or a vehicle were injected into mice, (n = 6 each) and two-weeks later, kidneys were evaluated using in-vivo magnetic resonance imaging and ex-vivo studies. The role of interleukin(IL)-1β was then studied in-vitro in MSC-induced immunomodulation using siRNA in macrophages. RESULTS:Compared to MSC from lean patients, obese-MSC genes showed 2,087 differential 5hmC modifications and 175 differential mRNA expression. Among them, 14 genes with overlapping alterations were involved in regulation of cytokine production, prominently IL-1β. Injecting obese MSCs elevated renal expression of IL-1β and M1 macrophage count but lowered kidney perfusion. Silencing IL-1β in obese-MSCs in vitro reduced M1 phenotype switching in co-incubated macrophages. CONCLUSION:Obesity induces epigenetic and gene expression changes in MSCs, particularly in IL-1β, associated with impaired anti-inflammatory functionality of MSCs. Targeting IL-1β could be a useful therapeutic approach to modulate the decline in MSC functionality resulting from obesity.

关键词： IL‐4   IL‐5   IgE allergen‐specific   allergy   equine   insect bite hypersensitivity   vaccination  

摘要： BACKGROUND:Skin allergies are among the most frequent types of allergies, where continuous investigation of the pathological immune mechanisms is required for a better understanding and a more effective treatment of the disease. In this study, we aimed to investigate the effect of interleukin (IL)-5 vaccination on allergen-specific IgE antibodies as well as T cell cytokine modulation in skin allergy using a mouse model and a naturally occurring disease in horses. METHODS:Ovalbumin (OVA)-sensitized mice, as well as horses affected by equine insect bite hypersensitivity (IBH) were administered an anti-IL-5 vaccination, and allergen-specific IgE and IgG were quantified in the blood. Additionally, mRNA and protein expression of T cell cytokines of in vitro allergen re-stimulated murine splenocytes and equine peripheral blood mononuclear cells (PBMCs), as well as in IBH lesional skin biopsies, were investigated using qPCR and ELISA. Clinical signs were recorded by ear swelling in mice. RESULTS:Our data showed a significant decrease in allergen-specific immunoglobulins (Igs) in IL-5-vaccinated mice, as well as a reduction in allergen-specific IgE in horses. Furthermore, protein production of T cell cytokines IL-4 and IFNγ in mice, as well as mRNA expression of IL-4, IL-5, IL-13, and IFNγ in lesional skin of the horses, was significantly decreased upon vaccination when compared to the placebo group. Furthermore, we demonstrated that CD4 cells in IBH-affected horses are highly enriched with the GATA3 transcription factor, responsible for IL-5 mRNA production and differentiation of Th2 cells. Additionally, increased IL-4 mRNA expression in IBH horses was shown to be CD4MHC-IIcell dependent. CONCLUSION:IL-5 vaccination significantly decreased allergen-specific IgE in both the murine skin allergy model and horses with naturally occurring allergic skin disease, as well as alleviated clinical signs of the diseases. We suggest that the IL-5 depletion may modulate the IL-4 levels

摘要： Abstract Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic cell transplantation (HCT). Palifermin, a recombinant N-truncated keratinocyte growth factor (KGF), protects epithelial tissues, including the thymus and gut. Although high-dose KGF prevents GVHD in preclinical models, lower doses of palifermin were ineffective in humans. We conducted a phase 1/2 trial evaluating high-dose palifermin for preventing severe chronic GVHD (CGVHD) in matched unrelated donor T-cell replete peripheral blood HCT after reduced-intensity conditioning (RIC). Using a 3+3 design, we determined the recommended phase 2 dose (RP2D), followed by an expansion phase. Palifermin (180-720 μg/kg) was given on day −7 before HCT. All 31 patients received fludarabine/cyclophosphamide RIC with tacrolimus, methotrexate, and sirolimus for GVHD prophylaxis. Palifermin was well tolerated, with self-limiting rash and pancreatic enzyme elevations as notable grade 3/4 adverse events. The RP2D was 720 μg/kg. Remarkably, no patients at this dose developed grade 2 to 4 acute GVHD (AGVHD [0/19]), although severe CGVHD rates (primary end point) remained unchanged compared to historical controls. Posttransplant lymphocyte phenotyping suggests palifermin modulates regulatory and naïve CD4 + T-cell numbers. These findings indicate that high-dose palifermin with RIC is safe and may prevent AGVHD, although it did not affect CGVHD rates in this study. This trial was registered at *** as #NCT02356159.