肺炎支原体感染对川崎病的影响及机制探讨

目的分析肺炎支原体感染对川崎病的影响及其机制,以期指导临床诊疗。方法回顾性分析2013年8月至2018年8月我科住院的496例川崎病患儿临床资料,其中合并肺炎支原体感染组193例,未合并肺炎支原体感染组303例。应用倾向评分匹配法1∶1校正2组的年龄、性别、是否为不完全型川崎病、是否使用糖皮质激素、丙种球蛋白使用时间、丙种球蛋白使用方法和阿司匹林初始剂量,比较2组患儿的总发热天数、冠状动脉直径、冠状动脉扩张发生率、冠状动脉瘤发生率和丙种球蛋白无反应发生率。结果川崎病合并肺炎支原体感染组男性患儿多,更易发生颈部淋巴结肿大,年龄、中性粒细胞百分比、血沉和低密度脂蛋白高于川崎病未合并肺炎支原体感染组,血钾、血钙、高密度脂蛋白和白蛋白低于川崎病未合并肺炎支原体感染组,差异有统计学意义(均P<0.05)。应用倾向评分匹配法1∶1配对后发现,川崎病合并肺炎支原体感染组患儿总发热时间更长[8(6~10)d vs 7(6~9)d,Z=-2.089,P<0.05),冠状动脉直径值更大[(2.81±0.81)mm vs(2.63±0.45)mm,t=2.532,P<0.05],冠状动脉瘤发生率更高(5.5% vs 1.1%,χ²=5.516,P<0.05)。结论肺炎支原体感染可能引起川崎病患儿脂质代谢及电解质的紊乱,其炎症反应更强,持续时间更长,对冠状动脉损伤更大。     

淀粉样蛋白A、D-二聚体、肌酸激酶同工酶联合检测对川崎病患儿冠状动脉损伤的诊断价值分析

摘要 目的：探讨血清淀粉样蛋白A(SAA)、D-二聚体(D-D)、肌酸激酶同工酶(CK-MB)联合检测对川崎病患儿冠状动脉损伤(CAL)的诊断价值。方法：选取2018年9月～2021年5月我院收治的80例川崎病患儿,根据是否合并CAL分为CAL组(n=34)和NCAL组(n=46)。收集患儿基础资料,并检测SAA、D-D、CK-MB水平。多因素Logistic回归分析川崎病患儿CAL影响因素,受试者工作特征（ROC）曲线分析血清SAA、D-D、CK-MB水平对川崎病患儿CAL的诊断价值。结果：与NCAL组比较,CAL组C反应蛋白(CRP)、红细胞沉降率(ESR)、SAA、D-D、CK-MB水平升高(P＜0.05)。多因素Logistic回归分析显示,CRP、ESR、SAA、D-D、CK-MB为川崎病患儿CAL独立影响因素(P＜0.05)。SAA、D-D、CK-MB、三项联合诊断川崎病患儿CAL的曲线下面积（AUC）分别为0.661、0.687、0.746、0.799,联合应用的诊断效能最高。结论：血清SAA、D-D、CK-MB是川崎病患儿CAL独立影响因素,且联合检测以上指标可辅助诊断川崎病患儿CAL。     

Vasculitis induced by immunization with Bacillus Calmette-Guérin followed by atypical mycobacterium antigen: a new mouse model for Kawasaki disease

Kawasaki disease causes systemic vasculitis. The development of skin lesions at the vaccination site with Bacillus Calmette-Guérin (BCG) is an important diagnostic symptom. We hypothesized that infection with ubiquitous microorganisms immunogenically related to BCG might induce an immunopathologic reaction leading to the development of Kawasaki disease. Mice were first inoculated with BCG, and then secondarily inoculated 4 weeks later with crude extract from Mycobacterium intracellulare (cMI), an abundant atypical mycobacterium. Animals inoculated with BCG followed by cMI developed coronary arteritis with infiltration of inflammatory cells, whereas control animals inoculated with only cMI or BCG did not, suggesting that the immune response to the mycobacteria induced autoimmunity to the vascular wall. Intravenous injection with antibodies to peroxiredoxin II, a modulator of vascular remodeling and a suggested target for autoimmune vasculitis, also resulted in coronary arteritis, but only after prior inoculation with BCG. Tumor necrosis factor-alpha, MCP1 and interferon-gamma production were significantly higher in the animals inoculated with BCG than in the control groups (P<0.05). BCG immunization was required for the development of coronary arteritis, suggesting that these cytokines might play important roles. The results indicate that BCG induces primary autoimmunity and stimulates cytokine induction, and that atypical mycobacterial infection boosts the autoimmunity resulting in coronary arteritis.     

TNF-α induces vascular endothelial cells apoptosis through overexpressing pregnancy induced noncoding RNA in Kawasaki disease model

Kawasaki disease (KD) is an autoimmune disease in which the medium-sized blood vessels throughout the body become inflamed. The increased evidences showed that TNF-α was association with vascular inflammation in KD patients. However the detailed mechanism was still unclear. Recent studies indicated abnormal expressed long non-coding RNAs (LncRNAs) involved in many diseases. Thus the purpose of this study is to explore the role of lncRNAs in KD and find out the new target for KD treatment. In this study, firstly we verified the overexpressed TNF-α in KD patients, and found TNF-α was able to induce HUVECs apoptosis and inhibit HUVECs proliferation. After this we screened out pregnancy induced noncoding RNA (PINC) was significantly overexpression in TNF-α treated HUVECs. We also found PINC overexpressed in KD patients. For further study, we designed two siRNA of PINC. After silenced the expression of PINC in HUVECs, we found the Knockdown of PINC enhanced the viability of HUVECs treated with TNF-α, and increased the expression of anti-apoptotic and reduced the expression of apoptotic gene. These results suggest PINC involves in the process of TNF-α induces vascular endothelial cell apoptosis, it may become a new target for KD treatment.     

Pathogenetic determinants in Kawasaki disease: the haematological point of view

Kawasaki disease is a multisystemic vasculitis that can result in coronary artery lesions. It predominantly affects young children and is characterized by prolonged fever, diffuse mucosal inflammation, indurative oedema of the hands and feet, a polymorphous skin rash and non‐suppurative lymphadenopathy. Coronary artery involvement is the most important complication of Kawasaki disease and may cause significant coronary stenosis resulting in ischemic heart disease. The introduction of intravenous immunoglobulin decreases the incidence of coronary artery lesions to less than 5%. The etiopathogenesis of this disease remains unclear. Several lines of evidence suggest that an interplay between a microbial infection and a genetic predisposition could take place in the development of the disease. In this review, we summarize the state of the art of pathogenetic mechanisms of Kawasaki disease underscoring the relevance of haematological features as a novel field of investigation.     

Nystroemiaceae,a new family of Permian gymnosperms from China with an unusual combination of features

Nystroemiaceae is proposed as a new family of gymnosperms from the Permian of Cathaysia that adds to the diversity of gymnosperms known from this critical time in seed plant evolution. This family is characterized by bifurcating and highly branched pinnate ovuliferous organs bearing bicornute ovules (seeds) and entire leaves with anastomozing veins that are born on complex and modern-looking branching systems with clear axillary branching. The reconstruction is based on numerous large specimens from two localities in North China, in which the different plant parts are attached to each other. The ovulate structures show some apparently plesiomorphic (primitive) character states more typical of early seed plants, whereas the leaves and branches show the clearly apomorphic (derived) character states of broad-leaved gymnosperms.     

川崎病患儿并发冠状动脉损伤的危险因素及预测模型的构建与评价

摘要 目的：分析川崎病患儿并发冠状动脉损伤（CAL）的危险因素，并构建和评价川崎病患儿并发CAL的预测模型。方法：选取2019年1月～2022年5月我院收治的342例川崎病患儿，根据是否并发CAL分为CAL组和非CAL组。收集所有患儿临床资料，采用单因素和多因素Logistic回归分析川崎病患儿并发CAL的影响因素，并构建预测模型，H-L检验和受试者工作特征（ROC）曲线检验预测模型拟合优度和对川崎病患儿并发CAL的预测价值。结果：342例川崎病患儿CAL发生率为16.67％（57/342）。单因素分析显示，CAL组发热持续时间≥10 d、静脉注射免疫球蛋白（IVIG）治疗延迟、IVIG无反应比例和单核细胞比例（MO％）、嗜酸性粒细胞比例（EO％）、C反应蛋白（CRP）、红细胞沉降率（ESR）、降钙素原（PCT）、心肌肌钙蛋白I（cTnI）、肌酸激酶同工酶（CK-MB）水平高于非CAL组（P均＜0.05）。多因素Logistic回归分析显示，发热持续时间≥10 d、IVIG治疗延迟、IVIG无反应和MO％、CRP、ESR、PCT、cTnI升高为川崎病患儿并发CAL的独立危险因素（P均＜0.05）。H-L检验川崎病患儿并发CAL的预测模型拟合效果良好。ROC曲线分析显示，该模型预测川崎病患儿并发CAL的曲线下面积（AUC）为0.911（95％CI：0.876～0.939）。结论：发热持续时间≥10 d、IVIG治疗延迟、IVIG无反应和MO％、CRP、ESR、PCT、cTnI升高为川崎病患儿并发CAL的危险因素，根据危险因素构建的川崎病患儿并发CAL预测模型价值较高。     

川崎病患儿血清NT-proBNP、SAA、CRP、Cysc的表达及其联合检测对冠状动脉损害发生风险的预测效能研究

摘要 目的：探讨川崎病（KD）患儿血清N末端B型利钠肽（NT-proBNP）、淀粉样蛋白A（SAA）、C反应蛋白（CRP）、胱抑素C（Cysc）的表达及其联合检测对冠状动脉损害（CAL）发生风险的预测效能。方法：纳入我院2019年1月到2021年12月期间收治的98例KD患儿,根据超声心动图检查结果分为CAL组（n=31）和无CAL组（n=67）,对比两组血清NT-proBNP、SAA、CRP、Cysc水平差异。收集患者资料,采用Logistic多因素分析CAL发生的影响因素。绘制受试者工作特征（ROC）曲线分析血清NT-proBNP、SAA、CRP、Cysc联合检测对CAL发生风险的预测效能。结果：CAL组患儿的血清NT-proBNP、SAA、CRP、Cysc水平均高于无CAL组（P＜0.05）。单因素分析结果显示：KD患儿并发CAL与年龄、治疗前发热时间、是否为典型KD以及血小板计数（PLT）、白细胞计数（WBC）水平有关（P＜0.05）。多因素Logistic回归分析结果显示：血清NT-proBNP、SAA、CRP、Cysc、WBC水平较高、年龄＜3岁、治疗前发热时间＞6 d、非典型KD是KD患儿并发CAL的危险因素（P＜0.05）。血清NT-proBNP、SAA、CRP、Cysc预测CAL发生的曲线下面积分别为0.761、0.759、0.753、0.746,四项联合检测预测CAL发生的曲线下面积为0.906,预测价值更高。结论：血清NT-proBNP、SAA、CRP、Cysc、WBC、年龄、治疗前发热时间、非典型KD是KD患儿并发CAL的影响因素,联合检测血清NT-proBNP、SAA、CRP、Cysc对CAL发生风险具有较好的预测效能。     

DDIAS在川崎病患儿血液中的表达及意义

目的:研究DNA损伤诱导凋亡抑制因子(DDIAS)在川崎病(KD)患儿血液中的表达及意义。方法:通过彩色多普勒超声心动图检查96例KD患儿的冠状动脉损伤(CAL)情况,根据CAL存在情况将患儿分为CAL组和非CAL组。选取我院同期体检的30例健康儿童作为对照组。通过ELISA试剂盒检测受试者外周血中DDIAS的水平。将靶向DDIAS的小干扰RNA(siRNA)(DDIAS-siRNA)和阴性对照siRNA(NC-siRNA)转染到人冠状动脉内皮细胞(HCAEC)中,并用10 ng/mL TNF-α处理细胞。通过RT-PCR分析细胞中的TNF-α、IL-6和HO-1 mRNA水平,通过Western blot分析DDIAS、NF-κB p65和I-κBα的蛋白水平。此外,评估了各组HCAEC细胞中的超氧化物和谷胱甘肽(GSH)含量及其与单核细胞的粘附。结果:与对照组比较,KD组的DDIAS水平显著升高(P<0.001)。与非CAL组比较,CAL组的DDIAS水平显著升高(P<0.01)。外周血DDIAS诊断KD的AUC、敏感性和特异性依次为0.747、65.62%和80.65%,外周血DDIAS诊断CAL的AUC、敏感性和特异性依次为0.733、63.83%和75.51%。与NC-siRNA+TNF-α组相比,DDIAS-siRNA+TNF-α组HCAEC细胞中的TNF-αmRNA表达水平降低了51.45%,IL-6 mRNA表达水平降低了59.46%,细胞核NF-κB p65的蛋白表达水平降低了26.40%,细胞质I-κBα的蛋白水平升高了91.30%(P<0.05)。与NC-siRNA+TNF-α组相比,DDIAS-siRNA+TNF-α组粘附实验的相对荧光强度降低了53.42%(P<0.05)。与NC-siRNA+TNF-α组相比,DDIAS-siRNA+TNF-α组HCAEC细胞中的超氧化物相对荧光强度降低了35.38%,HO-1 mRNA水平升高了1.35倍,GSH水平升高了94.59%(P<0.05)。结论:DDIAS对KD及CAL均有较高的诊断价值,下调DDIAS减轻TNF-α诱导的HCAEC细胞损伤。