滋肾育胎丸加减方预防ACA阳性者不良妊娠结局的效果及机制研究＊

目的 探讨滋肾育胎丸加减方预防抗磷脂抗体（ACA）阳性者不良妊娠结局的效果及机制研究。方法 选取2016年2月至2019年2月我院收治的89例ACA阳性，先兆性流产或有习惯性流产（RSA）史患者，将采用西医治疗的40例作为对照组，将采用西医联合滋肾育胎丸加减方治疗的49例作为观察组，比较两组中医证候疗效、中医证候积分、ACA-IgA、ACA-IgM、ACA-IgG、凝血指标［血小板聚集功能（PAF）、活化蛋白C（PC）、抗凝血酶（AT）、纤溶酶原激活抑制物-1（PAI-1）］、Th1/Th2细胞因子［干扰素γ（IFN-γ）、白介素-2（IL-2）、白介素-4（IL-4）、白介素-10（IL-10）］、妊娠结局、安全性。结果 治疗2周后检测ACA，观察组2例未降低，对照组11例未降低，观察组未降低患者占比低于对照组（P<0.05）；观察组总有效率100.00%高于对照组85.00%（P<0.05）；观察组治疗4周、7周后中医证候积分低于对照组（P<0.05）；观察组治疗4周、7周后ACA-IgA、ACA-IgM、ACA-IgG低于对照组（P<0.05）；观察组治疗4周、7周后PAF、PAI-1低于对照组，PC、AT高于对照组（P<0.05）；观察组治疗4周、7周后IFN-γ、IL-2低于对照组，IL-4、IL-10高于对照组（P<0.05）；观察组活产率95.92%高于对照组80.00%（P<0.05）；组间不良反应总发生率比较，差异无统计学意义（P>0.05）。结论 动态监测ACA对滋肾育胎丸加减方精准应用具有指导意义，指导滋肾育胎丸加减方通过调理脏腑、气血、经络功能，改善先兆性流产或有RSA史患者临床症状及凝血因子指标，降低ACA水平，并可改善患者免疫耐受功能，提高胎儿活产率，且安全性高。     

Prognostic tools for hypertrophic scar formation based on fundamental differences in systemic immunity

Unpredictable hypertrophic scarring (HS) occurs after approximately 35% of all surgical procedures and causes significant physical and psychological complaints. Parallel to the need to understanding the mechanisms underlying HS formation, a prognostic tool is needed. The objective was to determine whether (systemic) immunological differences exist between patients who develop HS and those who develop normotrophic scars (NS) and to assess whether those differences can be used to identify patients prone to developing HS. A prospective cohort study with NS and HS groups in which (a) cytokine release by peripheral blood mononuclear cells (PBMC) and (b) the irritation threshold (IT) after an irritant (sodium lauryl sulphate) patch test was evaluated. Univariate regression analysis of PBMC cytokine secretion showed that low MCP‐1, IL‐8, IL‐18 and IL‐23 levels have a strong correlation with HS (P < .010‐0.004; AUC = 0.790‐0.883). Notably, combinations of two or three cytokines (TNF‐a, MCP‐1 and IL‐23; AUC: 0.942, Nagelkerke R²: 0.727) showed an improved AUC indicating a better correlation with HS than single cytokine analysis. These combination models produce good prognostic results over a broad probability range (sensitivity: 93.8%, specificity 86.7%, accuracy 90,25% between probability 0.3 and 0.7). Furthermore, the HS group had a lower IT than the NS group and an accuracy of 68%. In conclusion, very fundamental immunological differences exist between individuals who develop HS and those who do not, whereas the cytokine assay forms the basis of a predictive prognostic test for HS formation, the less invasive, easily performed irritant skin patch test is more accessible for daily practice.     

Immunogenicity and protective efficacy of adenoviral and subunit RSV vaccines based on stabilized prefusion F protein in pre-clinical models

Respiratory Syncytial Virus (RSV) remains a leading cause of severe respiratory disease for which no licensed vaccine is available. We have previously described the derivation of an RSV Fusion protein (F) stabilized in its prefusion conformation (preF) as vaccine immunogen and demonstrated superior immunogenicity in naive mice of preF versus wild type RSV F protein, both as protein and when expressed from an Ad26 vaccine vector. Here we address the question if there are qualitative differences between the two vaccine platforms for induction of protective immunity. In naïve mice, both Ad26.RSV.preF and preF protein induced humoral responses, whereas cellular responses were only elicited by Ad26.RSV.preF. In RSV pre-exposed mice, a single dose of either vaccine induced cellular responses and strong humoral responses. Ad26-induced RSV-specific cellular immune responses were detected systemically and locally in the lungs. Both vaccines showed protective efficacy in the cotton rat model, but Ad26.RSV.preF conferred protection at lower virus neutralizing titers in comparison to RSV preF protein. Factors that may contribute to the protective capacity of Ad26.RSV.preF elicited immunity are the induced IgG2a antibodies that are able to engage Fcγ receptors mediating Antibody Dependent Cellular Cytotoxicity (ADCC), and the induction of systemic and lung resident RSV specific CD8 + T cells. These data demonstrate qualitative improvement of immune responses elicited by an adenoviral vector based vaccine encoding the RSV preF antigen compared to the subunit vaccine in small animal models which may inform RSV vaccine development.     

托珠单抗在新型冠状病毒肺炎的应用研究探讨

2019年12月以来,新型冠状病毒肺炎(Coronavirus Disease 2019,COVID-19)在武汉暴发并蔓延至全国,给整个社会带来巨大的挑战。部分COVID-19感染者早期发病并不十分凶险,但后期会突然加速进展,病人很快进入多脏器功能衰竭的状态,李兰娟院士等提出了"细胞因子风暴"概念。但目前并没有特效药物,认为IL-6是诱发细胞因子风暴的重要通路,本文结合相关文献的复习和分析,旨在综述IL-6受体阻断剂托珠单抗在新型冠状病毒肺炎危重患者使用的可行性。     

中药在抗新型冠状病毒肺炎（COVID-19）引起的细胞因子风暴中的应用分析

2019年12月底新型冠状病毒肺炎(COVID-19)在我国爆发,截止2020年2月23日已感染超7万人,感染者遍布全球28个国家和地区。其传染性强,传播迅速广泛,重症患者可出现急性呼吸窘迫综合征、多器官衰竭等严重并发症。而病毒感染引起的免疫过度激化导致的"细胞因子风暴"是重症患者产生严重并发症的重要原因。目前《新型冠状病毒感染的肺炎诊疗方案》中采用糖皮质激素作为免疫抑制剂,用于遏制重症患者的免疫激化反应,但是糖皮质激素的使用可能会造成二次感染、病程延长等不良预后,且存在严重后遗症风险。而中药在整体免疫调控方面具有明显优势,目前在COVID-19临床治疗中,中西医结合治疗也收到了积极效果。从免疫调控作用入手,分析了单味中药及中药方剂在遏制COVID-19引起的免疫过度激化及细胞因子风暴、抗急性肺损伤的潜在应用价值,有望对现有的诊疗方案中药临床应用做有益补充,发挥抗击疫情的重要作用。     

基于细胞因子的人参败毒散治疗新型冠状病毒肺炎(COVID-19)的网络药理学研究

目的从细胞因子角度,探究人参败毒散多成分、多靶点、多途径抗新型冠状病毒肺炎(COVID-19)的作用机制。方法应用中药系统药理分析平台(TCMSP)收集人参败毒散中活性化合物,结合药物靶点数据库收集细胞因子风暴相关靶点,利用Cytoscape构建"药材-化合物-疾病靶点"网络。通过String和DAVID数据库对靶点的互作网络、GO功能和KEGG通路进行分析。结果人参败毒散"药材-活性化合物-疾病靶点"网络包括10种药材,211个活性成分和151个疾病靶点。互作网络发现人参败毒散抑制细胞因子风暴治疗COVID-19的靶点可能包含STAT3、MAPK1、NFκB1、PIK3CA、MAPK3、TNF、CXCR4、VEGFA、IL-6、IL-2等。GO功能分析发现上述靶点在生物功能方面涉及趋化性、类固醇代谢过程等;在分子功能方面涉及血红素结合、铁离子结合、氧结合等;在细胞组成方面涉及细胞表面、细胞膜等。KEGG通路富集发现上述靶点参与查加斯病通路、HIF-1信号通路、肿瘤坏死因子信号通路等的调控。结论人参败毒散可能通过调节趋化性细胞因子,增加血氧饱和度,抑制STAT、MAPK、NFκB、PIK3K、IL-6等炎症相关信号通路,实现多成分-多靶点-多途径抑制细胞因子风暴形成的抗COVID-19作用。     

复方甘草酸苷联合盐酸左西替利嗪治疗皮炎湿疹的效果及对Th1/Th2型细胞因子的影响

目的 分析复方甘草酸苷联合盐酸左西替利嗪治疗皮炎湿疹的效果及对Th1/Th2 型细胞因子的影响。方法 选取2018 年10 月～2019 年10 月于我院接受治疗的皮炎湿疹患者80 例，分为对照组（40 例）和观察组（40 例）。两组采取不同的方法进行治疗，其中对照组采取盐酸左西替利嗪治疗，观察组采取复方甘草酸苷联合盐酸左西替利嗪治疗。治疗后比较两组患者的Th1/Th2 型细胞因子水平指标及临床疗效。结果 治疗后，观察组的Th1 型细胞因子中的IFN-γ 及IL-2 明显高于对照组，差异有统计学意义（P＜0.05）。观察组的Th2 型细胞因子中的IL-4、IgE 与对照组比较，差异有统计学意义（P＜0.05）。治疗后，观察组的瘙痒症状分数及糜烂症状分数与对照组比较，差异有统计学意义（P＜0.05）。观察组的总有效率明显高于对照组（P＜0.05）。结论 对皮炎湿疹患者进行治疗的过程中，使用复方甘草酸苷联合盐酸左西替利嗪进行治疗能够有效改善患者Th1、Th2 型细胞炎症因子，疗效确切，值得推广和应用。