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关键词： High-power   Low-temperature plasma (LTP)   Psoriasis   NO   Th17/IL-23 cell axis  

摘要： This study aims to evaluate the therapeutic efficacy and potential underlying mechanisms of a novel high-power low-temperature plasma (hLTP) therapy for treatment of psoriasis. Imiquimod (IMQ)-induced rat psoriasis model was used to evaluate the therapeutic efficacy of hLTP. Potential mechanisms were explored using bioinformatics analysis and molecular biology validation based on transcriptomic data. hLTP treatment alleviated IMQ-induced psoriasis as evidenced by a significantly reduced psoriasis area and severity index scores (PASI), and pathological changes. Based on the transcriptomic data, the differential expressed genes (DEGs) positively or negatively related to the hLTP treatment was identified and bioinformatics analysis was further performed. The results of the verification experiment indicate that hLTP treatment significantly elevated nitric oxide (NO) levels and FKBP5 expression in psoriasis, which was associated with inhibition of the NF-kappa Bpathway, as indicated by reduced p-IKK/IKK and p-P65/P65 ratios. Apoptosis was suppressed, evidenced by a decreased cleavedcaspase3/caspase3 ratio and lower self-DNA levels. Antioxidant capacity was enhanced, shown by increased glutathione (GSH) levels, while the inflammatory response was mitigated with reduced cathelicidin (LL-37) levels. These effects resulted in reduced psoriasis-related pro-inflammatory cytokines (IL-23, IL-6, and TGF-beta) from dendritic cells and macrophages, preventing Th17 cell differentiation and suppressing it related cytokines (IL-17 A, IL-22, IL-17F, TNF-alpha). Consequently, the Th17/IL-23 cell axis was disrupted under hLTP *** is a novel study that provides conclusive data demonstrating that hLTP exerts significant therapeutic effects on psoriasis through its anti-inflammatory, antioxidant, and anti-apoptotic effects by significantly up-regulating NO and FKBP5, while inhibiting NF-kappa B pathway and Th17/IL-23 cell axis.

关键词： HMGB1   IL-1R   IL-1β   TLR4   clinical translation   epilepsy   therapeutic targets  

摘要： Epilepsy is one of the most prevalent and disabling neurological disorders, affecting approximately one percent of the population. Due to the complex pathophysiology underlying drug-resistant epilepsy, nearly one-third of patients with epilepsy do not benefit from current treatments. Neuroinflammation is one of the most well-studied pathways in epileptogenesis, and inflammatory mediators play a crucial role in this process. The IL-1β/IL-1R1/IL-1Ra and HMGB1/TLR4 pathways play significant roles in epileptogenesis in both animal and human studies. Interventional investigations on the IL-1β/IL-1R1/IL-1Ra and HMGB1/TLR4 pathways showed antiseizure effects, suggesting that these pathways could be therapeutic targets for epilepsy. However, related targeted treatments are limited in clinical practice. In this work, we evaluated the advances of the IL-1β/IL-1R1/IL-1Ra and HMGB1/TLR4 pathways in epileptogenesis, as well as clinical trials or interventional investigations of current medications or substances targeting these pathways. To facilitate clinical translation, we highlighted the gap between research advancements and clinical practice and presented several strategies for closing the gap to fulfill the urgent requirements of patients with epilepsy.

关键词： 嵌合抗原受体T细胞疗法   细胞因子释放综合征   危重病护理  

摘要： 总结1例浆细胞疾病患者行嵌合抗原受体T细胞免疫治疗后并发细胞因子释放综合征的护理体会。针对患者出现的意识淡漠、畏寒高热、血压下降、三系血细胞减少等临床表现，采取严密病情监测、及时启动应急预案、循环支持、连续性肾脏替代治疗、感染预防等综合护理措施，患者成功救治并顺利出院，随访生活质量良好。

关键词： NF-κB受体激活蛋白配体   抗体，单克隆   纯化   原液  

摘要： 目的:开发抗NF-κB受体激活蛋白配体（receptor activator of NF-κB ligand，RANKL）单克隆抗体（单抗）的纯化工艺。方法:采用深层过滤澄清上游细胞培养液去除细胞，澄清后的培养液经过亲和层析捕获、低pH病毒灭活、阴离子交换层析、阳离子交换层析、除病毒过滤、超滤浓缩、透析置换、除菌过滤等步骤，获得单抗原液。通过收率和产品相关杂质去除情况评价亲和层析纯化效果，通过监测穿透点计算填料的动态载量（dynamic binding capacity，DBC）;通过考察不同的pH和温度条件对样品的纯度和活性影响，确定低pH病毒灭活条件;通过考察目的蛋白在不同缓冲体系下的稳定性、工艺相关杂质去除情况，确定合适的阴离子交换层析缓冲体系并考察纯化效果和DBC;通过线性洗脱，分段收集考察杂质情况确定阳离子交换层析工艺参数;通过处理量、通量、流量衰减确定病毒滤器的型号;根据浓缩、透析及过滤除菌说明书和平台技术确定滤膜孔径、进液流速和跨膜压力，再根据确定的参数进行浓缩及透析置换;最后经0.2 μm膜除菌过滤获得原液，并检测纯度和杂质。结果:以MabSelect SuRe为亲和层析填料，DBC 45.3 mg/mL填料，25 mmol/L 三羟甲基氨基甲烷（Tris）-盐酸（pH7.5）为平衡液，150 mmol/L醋酸（pH2.8）为洗脱液;pH3.5灭活1 h;以Sepharose QFF为阴离子填料，最大DBC 60 mg/mL 填料，50 mmol/L Tris-醋酸（pH7.5）为平衡液;SP HP为阳离子填料，上样量21.9 mg/mL，100%缓冲液A（10 mmol/L柠檬酸，pH5.5）—100%缓冲液B（10 mmol/L柠檬酸+1 mol/L NaCl，pH5.5）线性洗脱20柱体积;以Viresolve Pro为除病毒过滤器;采用PLCTK 30 kDa超滤膜包（C流道）超滤透析浓缩至（40.00±5.00）mg/mL，并以等体积方式10倍体积置换成原液缓冲液后除菌过滤;单抗纯度和杂质含量均符合质量标准。结论:成功开发出抗RANKL单抗的纯化工艺，产品符合要求。

关键词： cervical intraepithelial neoplasia   cytokines   CD4   CD8   IL-10   high-risk human papillomavirus infection   cervical cancer  

摘要： Background: Cluster of Differentiation-4(CD4),Cluster of Differentiation-8(CD8), and interleukin-10 (IL-10) have long been considered to be related to cervical cancer, but the exact relationship remains unclear. Few studies investigated the relationship between CD4,CD8,IL-10, and high-risk human papillomavirus (HPV) with risk of cervical intraepithelial neoplasia (CIN). Objective: Our aim is to evaluate the relationship between CD4, CD8, IL-10, and high-risk HPV infection with the risk of CIN, as well as their interactions on CIN. Design: In 2014-2015, a cross-sectional study of screening data was conducted among 2285 women aged 19-65 years who participated in an ongoing community-based cohort of 40,000 women in Shanxi, China. Using categorical and spline analyses to evaluate the relationship between local vaginal fluids of CD4,CD8,CD4/CD8,IL-10, and CIN risk. A total of 1,503 controls were followed up until January 31, 2019. A nested case-control study was used to assess the relationship between vaginal lavage CD4, CD8, CD4/CD8, and IL-10 levels and the risk of CIN progression. Results: After adjusting for possible confounding factors,CD4 and CD8 levels were positively related to CIN risk (the 1st versus 4th quartile CD4,CD8 OR = 0.45[0.34, 0.60] and 0.34[0.26, 0.45] for CIN1, 0.32 [0.21, 0.48] and 0.24 [0.16, 0.38] for CIN2/3). Increased CD4 and CD8 levels were positively related to the occurrence of CIN(P-overall<0.01).CD4/CD8 levels and the risk of CIN1 followed a nonlinear "U-shape" (P-nonlinear <0.01). IL-10 levels and the risk of CIN1 followed a nonlinear "n-shape"(P-nonlinear <0.01).IL-10 levels were inversely related to the occurrence of CIN2/3(OR = 3.87, [2.49, 6.00],P-overall<0.01). The highest risk of CIN was observed in women with high-risk HPV, whose CD4 and CD8 levels were the highest(P-interaction < 0.01).Patients with the lowest IL-10 levels(IL-10 <= 53.17pg/ml) who are positive for high-risk HPV infection have the highest risk of CIN2/3(OR = 18.46,

关键词： EGFP蛋白   细胞融合   单克隆抗体   亲和力   表面等离子体共振  

摘要： 为制备高特异性和亲和力的EGFP单克隆抗体（monoclonal antibody， mAb），本研究以纯化的EGFP蛋白为抗原，经弗氏佐剂乳化后免疫Balb/c小鼠，将小鼠脾细胞与SP2/0骨髓瘤细胞进行融合，应用间接ELISA方法筛选阳性孔并利用有限稀释法进行亚克隆，获得稳定分泌抗体的杂交瘤细胞株。采用叠加试验、亚型鉴定、Western blotting及表面等离子体共振（surface plasmon resonance， SPR）技术，系统分析抗体的表位特异性、反应性及亲和力。结果发现，本研究成功筛选出2株能稳定分泌特异性针对EGFP蛋白单抗的杂交瘤细胞株1F11和3C11，其亚型分别为IgG2a和IgG2b；叠加试验显示叠加系数（additivity index， AI）大于40%，说明两者识别不同抗原表位；抗体效价检测发现效价均可达1:512 000；Western blotting分析证实其可特异性识别大小约为27 kDa的EGFP蛋白；SPR分析测得亲和力常数分别为3.806×10-10mol/L和2.631×10-10mol/L，均属于高亲和力水平。由此可见，本研究制备的mAbs具有良好的特异性、反应性及高亲和力，为EGFP标记蛋白的免疫学检测及疫苗株体内监测提供了特异性的重要生物工具。

关键词： Non-small cell lung cancer   Ferroptosis   FEZF1-AS1   TNF-alpha   NF-kappa B  

摘要： ObjectiveThe purpose of this research was to examine the impact of FEZ family zinc finger 1 antisense RNA 1 (FEZF1-AS1) on ferroptosis regulation in non-small cell lung cancer (NSCLC) cells and to understand its molecular *** effects of FEZF1-AS1 silencing on NSCLC cell proliferation, invasion, migration, and apoptosis were evaluated through functional assays, utilizing the Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine, flow cytometry, and Transwell assays. The levels of cellular reactive oxygen species, malondialdehyde, glutathione, and Fe2+ were measured using commercial assay kits. Proteins related to ferroptosis and the tumor necrosis factor-alpha (TNF-alpha)/nuclear factor-kappa B (NF-kappa B) axis were analyzed using Western blot. Finally, rescue experiments were carried out by treating the cells with ***1-AS1 expression was significantly upregulated in NSCLC cells. Moreover, FEZF1-AS1 silencing suppressed proliferation, migration, and invasion, while enhancing ferroptosis sensitivity in NSCLC cell lines. This knockdown also inhibited the TNF-alpha/NF-kappa B pathway. TNF-alpha attenuated both pro-ferroptotic and anti-tumor effects of FEZF1-AS1 silencing in NSCLC cells. Mechanistically, knockdown of FEZF1-AS1 modulates ferroptosis and malignant behaviors in NSCLC cells through suppression of the TNF-alpha/NF-kappa B *** study uncovers a previously unrecognized mechanistic axis in which FEZF1-AS1 promotes NSCLC progression through suppressing ferroptosis by activating the TNF-alpha/NF-kappa B axis.

关键词： SpyCatcher-SpyTag system   PEGylation   Outer membrane vesicles, Pyroptosis   IL-1Ra   IL-1Ra  

摘要： Mortality resulting from sepsis is highly associated with secondary acute lung injury, and although the gut-lung axis is of significant importance, treatment strategies leveraging this understanding remains limited. Here, we developed an Escherichia coli strain named Delta PESI that highly expresses IL-1Ra via outer membrane vesicles (OMVs) and PEGylated this strain through the SpyCatcher-SpyTag system for enhanced activity and colonization. Oral administration of Delta PESI reinforces epithelial barrier integrity in the gut, inhibits inflammatory cascade in the peripheral circulation, modulates macrophage polarization and pyroptosis in the lung, thereby significantly mitigating the dysregulated systemic inflammatory response. Furthermore, Delta PESI exhibits favorable biosafety characteristics, thus demonstrating strong potential for clinical translation. Hence, this study proposes a promising strategy for the oral administration of engineered probiotics to effectively alleviate intestinal and pulmonary inflammatory responses through modulation of the gut-lung crosstalk.