The coronavirus disease 2019 (COVID-19) is a highly transmissible disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that poses a major threat to global public health. Although COVID-19 primarily affects the respiratory system, causing severe pneumonia and acute respiratory distress syndrome in severe cases, it can also result in multiple extrapulmonary complications. The pathogenesis of extrapulmonary damage in patients with COVID-19 is probably multifactorial, involving both the direct effects of SARS-CoV-2 and the indirect mechanisms associated with the host inflammatory response. Recognition of features and pathogenesis of extrapulmonary complications has clinical implications for identifying disease progression and designing therapeutic strategies. This review provides an overview of the extrapulmonary complications of COVID-19 from immunological and pathophysiologic perspectives and focuses on the pathogenesis and potential therapeutic targets for the management of COVID-19.

巨噬细胞活化综合征(MAS)是风湿免疫性疾病中一种较危急的综合征,常继发于全身型幼年特发性关节炎(sJIA).MAS常可累及全身多器官系统,若不及时诊治可导致高致残率.sJIA与MAS在发病机制、临床表现以及实验室检查指标方面均存在相似性,增加了 sJIA与MAS的区分难度.但实际上MAS的炎症反应更剧烈,一旦炎症风暴发生,其临床表现和实验室检查指标变化会更明显.因此,深入研究sJIA与MAS的临床特征和实验室指标,可以为早期识别MAS提供理论基础.

Objective:To compare the clinical characteristics, clinical efficacy and adverse drug reactions of rheumatoid factor (RF) positive (+ ) and negative (-) polyarticular juvenile idiopathic arthritis (PJIA).Methods:The clinical data of 67 PJIA patients admitted into Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, from January 2013 to December 2018 were analyzed retrospectively.They were divided into RF-positive PJIA group [RF (+ ) group, 23 cases] and RF-negative PJIA group [RF (-) group, 44 cases] according to RF titer.The clinical characteristics, laboratory indexes and clinical efficacy evaluation of the two groups were compared.Results:(1)Distribution of affected joints: the top 3 affected joints in the RF (+ ) group were the knuckles (16 cases, 69.57%), the wrists (15 cases, 65.22%) and the ankles (13 cases, 56.52%), and those in the RF (-) group were the knees (33 cases, 75.00%), ankle joints (29 cases, 65.91%) and hip joints (26 cases, 59.09%). The wrist joint involvement of the RF (+ ) group was significantly higher than that of the RF (-) group, while the knee joint involvement was lower than that of the RF (-) group.The difference was statistically significant (all P<0.01). (2)Magnetic resonance changes of the affected joints: articular cavity effusion (54 cases, 84.38%), synovial thickening (44 cases, 68.75%) and bone edema (26 cases, 40.63%) are common in both groups.The incidence of bone destruction (7 cases, 70.00%) and soft tissue edema (7 cases, 70.00%) in the RF (+ ) group was higher than that in the RF (-) group (2 cases, 18.18% and 2 cases, 18.18%), the difference was statistically significant (all P<0.05). (3) Changes in laboratory indicators: the positive rates of C-reactive protein, erythrocyte sedimentation rate, anti-cyclic citrullinated peptide antibody and anti-nuclear antibody in the RF(+ ) group were significantly higher than those in the RF(-) group, the difference was statistically significant (all P<0.05). (4)Juvenile arthritis disease activity score 27 (JADAS27): the score difference between RF(+ ) group and RF(-) group was not statistically significant [(22.83±5.60) scores vs.(23.07±6.66) scores, t=0.148, P>0.05]. (5) Efficacy analysis: 2 patients were lost to follow-up after discharge, and the remaining 65 patients were treated with traditional therapy, of which 30 were given biologics at the first hospitalization, 9 cases were treated with biologics after the failure of traditional treatments, and 35 patients were treated with biologics to control disease activity.In different dosage regimens, the disease remission rate in the RF(-) group is generally higher than that in the RF(+ ) group. Conclusions:PJIA patients have complicated joint involvement, RF-positive patients are more prone to joint destruction, and traditional treatments are less effective.Biological agents can effectively improve the symptoms of severe PJIA patients, especially those with poor prognosis.

Abstract Introduction: Thrombocytopenia (TP) is a common complication of childhood-onset systemic lupus erythematosus (SLE), and can range from mild to life-threatening. However, severe TP with multiple hemorrhagic complications is very rare and often predicts a poor prognosis. We describe a 12-year-old Chinese girl who had a history of idiopathic thrombocytopenic purpura who developed SLE that presented as subdural hemorrhage and retinal hemorrhage because of severe TP. Patient concerns: A 12-year-old girl was admitted into our hospital because of fever, purpura, and gum bleeding lasting for 12 days. She had a history of idiopathic thrombocytopenic purpura 2 years ago previously. Diagnosis: SLE was diagnosed according to American College of Rheumatology classification criteria. Subdural hemorrhage and retinal hemorrhage were diagnosed based on brain MRI and funduscopy. Severe TP was defined as platelet count <20 × 109/L. Interventions: She was treated first with intravenous immunoglobulin, but it was not efficacious. High-dose methylprednisolone showed short-term efficacy. Then, she was given a glucocorticoid and cyclosporine A plus mycophenolate mofetil. Outcomes: Fever, purpura, and gum bleeding were resolved before hospital discharge. Subdural hemorrhage and left hemorrhagic retinopathy were improved remarkably. She had a durable response to refractory TP with no adverse effects during >1-year follow-up. Conclusion: Isolated TP may be an early symptom of childhood-onset SLE . A child with severe TP is prone to develop life-threatening hemorrhagic complications. Glucocorticoids and combined immunosuppressive drugs had a durable response to refractory TP in this patient with no adverse effects.

1病例资料患儿,男,11岁,因"反复发热伴双下肢疼痛2月余"入院.入院查体:贫血貌,皮肤可见陈旧性瘀斑,无其他阳性体征.血常规:白细胞2.50×109/L,中性粒细胞0.98×109/L,血红蛋白76.0g/L,血小板123.0×109/L.骨髓细胞学示幼稚淋巴细胞占94.4％,考虑急性淋巴细胞白血病.流式细胞学示87％细胞为恶性B系淋巴细胞,该群细胞白血病相关免疫表现特征为TdTCD19+CD20+ CD34+CD10+CD58+CD38+CD44-CD24+CD200p+CD56p+,考虑为急性淋巴细胞白血病(Common-B),43种白血病相关融合基因检测均阴性,检测到IKZF1基因IKAROS6剪接变异条带.

Objective:To investigate the change of serum visfatin concentration in simple obese children and its correlation with inflammatory markers, glucose and lipid parameters.Methods:A total of 44 obese children (23 males, 21 females) who met the diagnostic criteria of simple obesity were selected, and 50 age- and gender-matched normal weight children (23 males, 27 females) were used as the healthy controls.A complete physical examination, including anthropometric parameters (height, body mass, waist circumference and blood pressure), was carried out by a specially assigned person.The fasting serum levels of visfatin, high sensitivity C-reactive protein(hs-CRP), interleukin (IL)-6, tumor necrosis factor (TNF)-α, blood glucose, insulin and blood lipid were measured and analyzed by SPSS 15.0 software.Results:(1) The serum levels of total cholesterol (TC), triacylglycerol (TG) and low density lipoprotein-cholesterol (LDL-C) of obese children were significantly higher than those of healthy children (all P<0.05), while the serum high density lipoprotein cholesterol (HDL-C) level was significantly lower than that of healthy children (all P<0.01). The fasting blood glucose level, fasting insulin level and the value of homeostatic model assessment of insulin resistance (HOMA-IR) of obese children were significantly higher than those of healthy children ( P<0.01). (2) The serum levels of visfatin, hs-CRP and IL-6 in obese children were significantly higher than those in the healthy control group (all P<0.05); there was no significant difference between the serum levels of TNF - α in obese children and the healthy control group ( P>0.05). (3) The serum visfatin level was significantly positively correlated with body mass index(BMI) ( r=0.218, P<0.05), waist circumference ( r=0.332, P<0.05), TG ( r=0.283, P<0.01), IL-6 ( r=0.376, P<0.05), and hs-CRP ( r=0.321, P<0.05), but not significantly correlated with fasting blood glucose, fasting insulin, HOMA-IR, and TNF-α ( r=0.085, P>0.05). (4) There were gender differences in the correlation of visfatin with anthropometric parameters, metabolic parameters and inflammatory factors.Visfatin were positively correlated with waist circumference, TG and hs-CRP in both boys and girls, but only positively correlated with BMI ( r=0.247, P=0.029) and IL-6 ( r=0.427, P=0.013) in boys. Conclusions:Obese children have obvious disorders of glucose and lipid metabolism and insulin resistance.Visfatin, as a visceral adipokine, has double functions of regulating glucose and lipid metabolism and promoting inflammation.It may be involved in obesity related metabolic disorders and inflammation.The detection of serum visfatin in obese children can be used as a new inflammatory marker to reflect the low level of inflammatory response.

Background: Tuberous sclerosis complex (TSC) is a rare autosomal dominant hereditary neurodermal syndrome with diverse clinical manifestations, implicating multiple organs including the nervous system, skin, kidney, lung, heart, eyes and others. Most of the children are first diagnosed with seizures or facial hemangiofibroma, 45% to 60% of patients with TSC lesions can affect the heart resulting in cardiac rhabdomyoma. Although most cardiac rhabdomyomas are asymptomatic, some children may develop severe symptoms such as hemodynamic abnormalities, arrhythmias, and even heart failure in the neonatal period and early infancy. But Tuberous sclerosis complex with apical hypertrophic cardiomyopathy as the first manifestation is rare. Hence, physicians may delay diagnosis and treatment of TSC due to the lack of comprehensive thinking on this atypical presentation. Case presentation A 5-year-old girl was admitted to our hospital due to syncope for more than 10 days. When she was 8 months old, she was diagnosed with hypertrophic cardiomyopathy and received long-term oral propranolol treatment. After her admission, a thorough examination was performed. Heart exam revealed the revelant problem. Brain MRI demonstrated mutiple nodules in bilateral frontal parietal occipital cortex, subcortical cortex and bilateral lateral ventricular margin consistent with TSC. Genetic analysis (high-precision clinical display PLUS, JiaJian Medicine Company) revealed that the patient had inherited the TSC2 mutation c.1343T> C (p.L448P) from her mother (heterozygous), who was clinically unaffected. Conclusions: This report highlights that TSC occurs in different ways. Given the possibility of insidious and atypical tuberous sclerosis, when apical hypertrophy or cardiac tumors are identified, it is recommended to broaden the systemic examination even including genetic testing to further determine the cause, in order to reduce the misdiagnosis rate of tuberous sclerosis.

Huai Qi Huang (HQH) exerts great effects in clinic, such as anti-inflammation, immune-regulation, anti-cancer, and so on. However, the mechanism by which HQH protects juvenile idiopathic arthritis (JIA) is obscure. Thus, we explored deeply the protective mechanisms in juvenile collagen-induced arthritis (CIA) rat model. Pyroptosis is Gasdermin D (GSDMD)-dependent programmed cell death, involved in many diseases, such as sepsis. We investigated whether GSDMD-induced pyroptosis take part in mechanisms of juvenile CIA arthritis. Juvenile Wistar rats (3-4 weeks) were injected intradermally with fully emulsified bovine type II collagen and complete Freund’s adjuvant to establish CIA rat models. Later, the CIA rats received oral administration of HQH (4.16 g/kg) once a day from the day 21 of modeling, with the treatment lasting for 28 days. Varieties of indicators were measured for evaluation of anti-inflammation effect of HQH, including hind paw swelling, arthritis scores, micro CT, and histopathological changes and the level of pro-inflammatory cytokines in the serum, including tumor necrosis factor alpha (TNF-±) and interleukin-18 (IL-18). The expression of GSDMD and caspase-1 in the joint synovial tissues was detected. The results demonstrated that the expression of the pyroptotic protein GSDMD and its upstream caspase-1 was significantly increased in the synovial tissues of CIA rats. The treatment of HQH ameliorated the symptoms in CIA rats, reduced levels of pro-inflammatory cytokines and hind paw swelling, down-regulated the expression of GDSMD and caspase-1. GSDMD-induced pyroptosis participated in the pathogenesis of CIA rats. The study supported that HQH can effectively improve joints inflammation of juvenile collagen-induced arthritis rats by inhibiting pyroptosis pathway in the joint synovial tissues.

Cardiac syncope is due to cardiac disorders or rhythm disorders as the main cause of syncope,etiolo-gy is accounted for the second in the cause of syncope in children. Compared with other causes of syncope,cardiac syn-cope is the risk for sudden death with high mortality and the prognosis is relatively poor. A preliminary assessment was made through medical history,physical examination and routine electrocardiogram exam. Routine electrocardiogram is the most basic examination for these patients. Long term electrocardiogram,color Doppler ultrasound and electrophysio-logic examination are recommended for the patients with cardiac syncope. In clinical work,the doctor should further im-prove the understanding of syncope in order to early identify cardiac syncope and comprehensive assess the risk of it, then effort to identify the cause of the cardiac syncope. Early diagnosis and standardized management will improve the quality of life and reduce the risk of sudden death in children with cardiac syncope.

The pathogenesis of Kawasaki disease are still not well understood. It was designed to investigate the relationship between adipokines including chemerin, omentin-1, adiponectin and acute Kawasaki disease.

Objective To evalute the affect on secretion levels and protein expression of the key enzyme of lipid metabolism(LPL, HSL, perilipin, DGAT), and the affect on protein expression of classical signaling pathways of insulin (IRS-1, PI3K) in 3T3-L1 adipocytes with acylation stimulating protein (ASP) stimulated under the condition which produce insulin resistance by free fatty acids. Methods The different concentrations of the Oleate and Palmitate(0, 0. 125, 0. 5, 1. 0mmol /L) were added to cultured 3T3-L1 adipocytes overnight. The real-time-PCR were used to detected mRNA of LPL, HSL, Perilipin, DGAT. The western blot were used to detected protein of HSL, prelipin, IRS-1, PI3K. Results After incubated with ASP, comparing with that of 0mmol /L, the levels of HSL, perilipin, LPL and DGAT mRNA expression were increased. In insulin and ASP stimulating condition, comparing with the 0mmol / L, the levels of HSL, perilipin, PI3K protein expression were increased. And comparing with the insulin stimulated, the protein expression of HSL, perilipin IRS-1 and PISK failed to significantly increase with the ASP stimulated. Conclusion Under the condition of insulin resistance, ASP can increase the mRNA expression of HSL, LPL, perilipin and DGAT by increasing the expression of these enzymes to improve the sensitivity and improve the use of the body's fat cell, to regulate the glucose and lipid metabolism. INS and ASP can increase the protein expression of the key enzyme of lipid metabolism (HSL, perilipin), and the classical insulin signaling pathway (PI3K).

目的 了解川崎病(KD)患病情况及临床特征,探讨KD冠状动脉损害(CAL)及IVIG耐药的危险因素.方法 回顾性分析华中科技大学同济医学院附属同济医院2012年1月1日至2016年12月31日初诊的KD患儿的临床资料,比较分析KD治疗前后,典型和不完全KD,KD伴或不伴CAL,IVIG敏感或耐药的临床特征,分析CAL发生和IVIG耐药的危险因素.结果 725例KD患儿进入本文分析,男:女为1.61:1,平均年龄(2.7±2.3)岁;不完全KD 206例(28.4％),典型KD 519例;CAL 216例(29.8％),IVIG耐药61例(8.4％);治疗中仅使用阿司匹林者70例(9.6％).KD伴CAL的危险因素为IVIG耐药(OR=5.138,95％CI:1.835～14.836)和氨基末端脑钠肽前体(NT-proBNP)≥1000 pg·mL-1(OR=2.723,95％CI:1.110～6.679).IVIG耐药的危险因素为出现CAL(OR=2.586,95％CI:1.067～6.271).结论 KD患病人数、CAL和IVIG耐药患儿有增加趋势.IVIG耐药和NT-proBNP≥1000 pg·mL-1为KD伴CAL的危险因素,而发生CAL为IVIG耐药的危险因素.

目的 观察棕榈酸(PA)及C5aR拮抗剂(PMX53)干预后小胶质细胞的炎症改变,探讨C5a受体(C5aR)及C5L2在PA诱导的小胶质细胞炎症中的作用.方法 取新生1日龄小鼠,分离脑组织,原代培养小胶质细胞并进行分离纯化及鉴定.纯化小胶质细胞随机分成3组:正常对照组、PA处理组、PA+PMX53处理组.分别应用Western blot检测PA及PA+PMX53干预后小胶质细胞C5aR、C5L2、p38M APK蛋白表达;RT-PCR检测C5L2 mRNA表达及ELISA法检测IL-6表达变化.结果 通过免疫组化鉴定,成功培养小胶质细胞.PA干预后,C5aR蛋白表达较对照组明显上升(P＜0.001),而加入PMX53后,C5aR蛋白表达较PA组显著下降(P＜0.001);PA干预后,C5L2蛋白及mRNA表达较对照组增加(P＜0.001),而加入PMX53后,C5L2蛋白表达与PA组差异无统计学意义(P=0.978),而C5L2 mRNA表达较PA组明显上升(P＜0.001);PA组较对照组p38MAPK蛋白的表达增加(P=0.002),PA+PMX53组p38MAPK蛋白表达较PA组降低(P=0.004);PA干预后,IL-6浓度较对照组显著升高(P＜0.001),而PMX53干预后,PA+PMX53组较PA组IL-6浓度显著下降(P＜0.001).结论 PA可能通过C5a-C5aR激活MAPK信号途径中的p38MAPK通路,从而诱发小胶质细胞炎症反应,而C5L2在此过程中可能发挥抗炎作用.

Afebrile Kawasaki Disease Presenting as Intestinal Pseudo-Obstruction Yu Wen, Ying Chen, Huiling Lu, and Xiufen Hu Department of Pediatrics, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China Corresponding author: Xiufen Hu, Department of Pediatrics, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China, E-mail: xfhu2007@163.com

OBJECTIVE:To study the expression of serum cytokines, interleukin-38 (IL-38) and interleukin-1β (IL-1β) in the acute phase of Kawasaki disease (KD) in children and the association of IL-38 and IL-1β with inflammatory response in the acute phase and the development of coronary artery lesion (CAL). METHODS:A total of 40 children with KD who were hospitalized in the hospital between July 2015 and June 2016 were enrolled, with 21 children in the CAL group and 19 in the non-CAL (NCAL) group. Thirty healthy children and 19 children with infection and pyrexia, who were matched for sex and age, were enrolled as healthy control group and pyrexia control group respectively. ELISA was used to measure the serum levels of IL-38 and IL-1β in the 40 children in the acute phase of KD. Spearman's rank correlation analysis was used to investigate the correlations of IL-1β and IL-38 with interleukin-6 (IL-6), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), N-terminal pro-brain natriuretic peptide (NT-proBNP), triglyceride (TG), and total cholesterol (TC). RESULTS:The serum level of IL-38 in the children in the acute phase of KD was significantly lower than that in the healthy control group (P<0.05), but significantly higher than that in the pyrexia control group (P<0.05). There was no significant difference in the level of IL-38 between the CAL and NCAL groups (P>0.05). The children in the acute phase of KD had a significantly higher level of IL-1β than the healthy control group (P<0.05), while there was no significant difference between this group and the pyrexia control group (P>0.05). There was also no significant difference in the level of IL-1β between the CAL and NCAL groups (P>0.05). Serum IL-1β and IL-38 levels were not correlated with serum levels of CRP, ESR, PCT, IL-6, and NT-ProBNP or blood lipids (TG and TC) (P>0.05). CONCLUSIONS:IL-38 is involved in an inflammatory response in the acute phase of KD and may exert an anti-inflammatory effect, which is opposite to the effect of IL-1β to promote inflammatory response. However, there is no significant correlation between these two cytokines and the development of CAL in KD.

Objective To detect serum interleukin 6(IL-6), N-terminal pro-brain natriuretic peptide (NT-proBNP) and serum ferritin in acute Kawasaki disease (KD), and explore their values in the diagnosis of KD, and further to explore the relationship with intravenous immunoglobulin (IVIG) unresponsiveness and coronary arterial lesions (CALs). Methods Totally 108 patients with KD (81 IVIG responders and 27 IVIG non-responders, 31with CALs and 77 non-CALs) were recruited from October 2014 to February 2016 at Department of Pediatrics of Tongji Hospital affiliated to Tongji Medical College, Huazhong University of Science and Technology, 64 were boys and 44 were girls. Their ages ranged from 2 months to 11 years and 5 months. A total of 30 children with respiratory tract infection were selected as the control group, 18 were boys and 12 were girls, ages ranged from 4 months to 10 years. Serum IL-6, NT-proBNP and serum ferritin were measured at the day of admission. The differences between groups were analyzed by t-test. To compare the power of serum level of interleukin 6(IL-6), N-terminal pro-brain natriuretic peptide (NT-proBNP) and serum ferritin levels in predicting KD, IVIG unresponsiveness and CALs, receiver-operating characteristic (ROC) curves were plotted and areas under the curve (AUC) were calculated. All data are presented as means ± standard deviation. Results (1) The levels of IL-6 135 ± 268ng /L, NT-proBNP 1008 ± 1675ng /L and ferritin 227 ± 238μg /L were significantly higher in the acute phase patients with KD than those of the control group 27 ± 29ng /L for IL-6 (t = 2. 192, P = 0. 03), 109 ± 100ng /L for NT-proBNP(t = 5. 463, P = 0. 000) and 72 ± 101μg /L for ferritin (t = 3. 437, P = 0. 001). (2) The levels of NT-proBNP 1837 ± 2666ng /L in IVIG unresponsive group were significantly higher than those of the IVIG responsive group 720 ± 1032ng /L (t = 3. 108, P = 0. 002). However, there were no significant difference of IL-6 and serum ferritin between the two groups. (3) The levels of NT-proBNP in CALs group 1703 ± 2569ng /L vs 742 ± 1080ng /L, serum ferritin 340 ± 405μg /L vs 183 ± 99μg /L were significantly higher than those of the non-CALs group (P ＜ 0. 05). However, there was no significant difference of IL-6 between the two groups. (4) The area under the curve for predicting KD with various variables were as follows: serum IL-6 0. 773, NT-proBNP 0. 835 and serum ferritin 0. 793. The area under the curve for predicting resistance to IVIG with serum NT-proBNP was 0. 623. The area under the curve for predicting CALs with various variables were as follows: NT-proBNP 0. 612 and ferritin 0. 671. The ROC of ferritin for predicting CALs is better than NT-proBNP. A ferritin cut-off value of 160. 2μg /L yielded a sensitivity of 73. 7％, specificity of 52. 1％. Conclusion The serum IL-6, NT-proBNP and serum ferritin can be used as useful parameters in early diagnosis of KD. Elevated NT-proBNP or serum ferritin may be useful to predict IVIG resistance and CALs in KD patients.

Obesity closely correlates with metaflammation and characterizes with systemic-chronic-low inflammation. This study aims to evaluate effects of C5a on the inflammatory response and insulin resistance in 3T3-L1 adipocytes. 3T3-L1 pre-adipocytes were induced to the mature 3T3-L1 adipocytes. Then, 3T3-L1 were intervened with anaphylatoxin C5a, lipopolysaccharide (LPS) and C5a+ LPS, respectively. Levels of Omentin, Chemerin, Vaspin and Apelin 12 in supernatants of medium were examined using ELISA. C5L2, C5a receptor (C5aR), I kappa B (IkB), IkB kinase (IKK), insulin receptor substrate 1 (IRS-1), IRS-2, PI3 K, p-PI3 K and beta-actin were examined using RT-PCR and western blot assay, respectively. C5L2-C5aR colocalization was identified using immunofluorescence double label. NF-kB expression or activity was evaluated using electrophoretic mobility shift assay (EMSA), dual luciferase assay and immunofluorescence assay, respectively. The glucose uptake and insulin sensitivity were also evaluated. Results showed that C5a intervention significantly enhanced inflammatory molecule levels in supernatants of 3T3-L1 adipocytes. IKK inflammatory signaling pathway participated in C5a induced inflammation of 3T3-L1 adipocytes. C5a triggered the colocalization of C5L2 and C5aR and activated the NF-kB inflammatory signaling pathway. C5a intervention in 3T3-L1 adipocytes decreased the glucose uptake and resulted in reduction of insulin sensitivity. Insulin signaling pathway participated in C5a caused insulin sensitivity reduction. C5a intervention triggered the phosphorylation of PI3 K. In conclusion anaphylatoxin C5a induced inflammatory response by activating TLR4/NF-kB signaling pathway and generating C5L2-C5aR dimer, and caused insulin sensitivity reduction by activating PI3 K signaling pathway.

Objective To observe the effect of complement 5a receptor(C5aR)antagonist(PMX53)and palmitic acid(PA)on the inflammatory reaction of microglia,and to investigate the roles and mechanisms of com-plement C5a-C5aR in PA induced microglia inflammation.Methods Microglia from one day old mice was collect-ed,purified and identified by primary culture and immunohistochemical staining,and then was randomly divided into three groups including PA group,PA+PMX53 group and control group.The expressions of tumor necrosis factor-α(TNF-α),Iba-1 and ERK1/2 were determined by ELISA,Western blot and QT-PCR.Results In PA group, the levels of Iba-1 and TNF-α were higher significantly than the control group(P<0.001).Similarly,the levels of ERK1/2 mRNA(P = 0.005 6)and p-ERK1/2 protein(P < 0.001)in the PA group were higher significantly than that in control group in spite of no difference in ERK1/2 protein in all groups. However,the levels of Iba-1,p-ERK1/2 protein,ERK1/2 mRNA and TNF-α in the PA+PMX53 group were significantly lower than that in the PA group(P<0.001),although there was no difference in ERK1/2 protein in all groups.Conclusions C5a receptor antagonist suppresses inflammatory reaction of microglia induced byPA,suggesting that C5a-C5aR-ERK may par-ticipate in the inflammation of microglia induced byPA. Therefore,C5a receptor antagonist may protect the brain tissues from inflammation-induced damage.

自川崎富作医生于1961年在日本发现第1例川崎病患者以来,人们对该病的认识逐渐加深,Yamamoto于1963年成为第一个在美国发现该病的医生,紧接着川崎病逐渐被世界各地的人们所熟知[1]. 川崎病是一种以全身非特异性血管炎为主要病理改变的发热性疾病, 又称皮肤黏膜淋巴结综合征,主要发生在5岁以下儿童以及男性患者,其中未经治疗的患者约15%~25%发生冠状动脉损伤,现在已经成为儿童后天性心脏病的主要病因[2]. 虽然其发病机制仍不清楚,但已有越来越多的研究发现川崎病发病可能与感染、 环境毒素、遗传易感性等因素有关,也有学者认为可能与超抗原导致的多克隆T细胞活化和大量细胞因子释放有关[3]. 脂肪因子是主要由脂肪组织分泌的多种信号分子,脂肪因子不仅与能量平衡、摄食行为、胰岛素抵抗关系密切,并在炎症反应、免疫功能、心血管功能等方面发挥重要作用. 本文就脂肪因子与川崎病之间的关系做一综述, 探讨脂肪因子在川崎病诊断、判断预后和预测冠状动脉损伤方面的临床价值.

Objective To observe the inflammatory changes of microglial cells after the intervention of oleic acid (OA) and complement 5a (C5a) receptor antagonist (PMX53),explore the role of C5a-C5aR in inflammation of microglial cells induced by OA.Methods The brain tissue samples were isolated from neonatal one-day-old mice,primary microglial cells were isolated,purified,and identified.Purified microglial cells were randomly divided into normal control group,OA 100 μaol/L treatment group,OA 100 μmol/L+PMX53 100 nmol/L treatment group,OA 200 μmol/L treatment group,OA 200 μmol/L+PMX53 100 nmol/L treatment group.The expression changes of Iba-1,C5aR protein and tumor necrosis factor-or (TNF-c) in microglial cells after intervention of different concentrations of OA and OA+PMX53 were detected by Western blot and ELISA.Results Primary microglial cells were successfully cultured,and the puritification was no less than 99％.Mter intervention of different concentrations of OA,the expressions of Iba-1 and C5aR protein and concentrations of TNF-α were statistically significantly higher than those in control group (P＜0.01),the expression of Iba-1 and concentrations of TNF-α in OA+PMX53 intervention group were statistically significantly lower than those in OA group (P＜0.01).The expression of C5aR protein in OA+PMx53 intervention group was statistically significantly lower than that in OA group (OA 100 μmol/L treatment group vs.OA 100 μ mol/L+PMX53 100 nmol/L treatment group:P＜0.05;OA 200 μmol/L treatment group vs.OA 200 μmol/L+PMX53 100 nmol/L treatment group:P＜0.01).The expressions of Iba-1 and C5aR protein and concentrations of TNF-α in OA 200 μmol/L treatment group were statistically significantly higher than those in OA 100 μmol/L treatment group (P＜0.01).Conclusion C5aR receptor antagonist can suppress inflammatory reaction of microglial cells induced by OA,which indicates that C5a-C5aR may participate in inflammatory reaction of microglial cells induced by OA.Therefore,C5aR receptor antagonist may protect the brain tissues from inflammation-induced damage.