Systemic juvenile idiopathic arthritis (sJIA) is an autoinflammatory disorder that impacts children aged ≤ 16 years. This study evaluated the efficacy and safety of firsekibart, a fully human anti-IL-1β monoclonal antibody, in children with active sJIA. This multicenter, randomized, open-label, active-controlled phase 2 study (NCT05925452) enrolled participants aged 2– < 18 years with active sJIA across 14 sites in China. Participants were randomized (1:1:1) to firsekibart 3.0 mg/kg or 4.0 mg/kg subcutaneously every 4 weeks, or tocilizumab intravenously every 2 weeks, for 24 weeks. The primary endpoint was modified JIA American College of Rheumatology Pediatric criteria (ACR Pedi) 30 response at day 28. Secondary endpoints included ACR Pedi 30/50/70/90 responses, corticosteroid tapering, immunogenicity, and safety. Fifty participants were randomized (firsekibart 3.0 mg/kg: n = 17; 4.0 mg/kg: n = 16; tocilizumab: n = 17). At day 28, ACR Pedi 30 response rates were 94.1

Purpose The EARS2 gene, a member of the mt-aaRS family, encodes mitochondrial glutamyl-tRNA synthetase (GluRS), which is involved in the synthesis of mitochondrial proteins. Pathogenic defects in EARS2 may cause mitochondrial OXPHOS deficiency, which is associated with a rare autosomal-recessive mitochondrial disease, leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL). Methods In this study, clinical features were obtained, and whole-exome sequencing was conducted on a patient with LTBL. B- and T-cell immunophenotyping and protein expression were analyzed using flow cytometry, and B-cell metabolism was investigated using confocal microscopy. Results The patient with LTBL exhibited typical neurological manifestations, recurrent respiratory tract infections, and humoral immune disorders. Molecular analysis revealed a compound heterozygous novel mutation in c.1304T > A (p.L435Q) and a previously reported c.319 C > T (p.R107C) mutation of EARS2 . The mutations led to protein structural modifications of EARS2. The patient also exhibited disrupted peripheral B-cell differentiation and B-cell receptor signal transduction. The EARS2 mutation led to decreased expression of CD38 and dysfunction of mitochondrial metabolism, with elevated reactive oxygen species levels in B cells. Conclusion We identified a novel mutation of the EARS2 gene in a patient with LTBL, expanding the mutation database. The mutation of EARS2 modified protein structure and impaired B-cell function, decreased CD38 expression, and led to dysfunction of mitochondrial metabolism, all of which may account for the recurrent respiratory tract infections and humoral immune disorders observed in LTBL.

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.

Since X-linked chronic granulomatosis disease (X-CGD) exhibits no specific clinical symptoms at an early stage, early diagnosis is difficult and depends predominantly on neonatal screening. Therefore, the aim of this study was to explore routine biomarkers for X-CGD in children and provide clues for early diagnosis. The cases of 10 children with X-CGD diagnosed at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from 2013 to 2016 and 122 Chinese children with X-CGD reported in the literature were summarized. Serum biomarkers and clinical symptoms at acute infection were organized. A total of 132 children with X-CGD were enrolled in this study. For 55.8% of the patients, the diagnosis was delayed more than one year after the onset of the first symptoms because no typical clinical symptoms manifested. Children with X-CGD at an acute infection stage showed three recurrent signs in terms of serum biomarkers: (1) the total number of white blood cells (especially N%) was increased significantly, accompanied by anemia in some cases; (2) C-reactive protein (CRP) levels were increased significantly; and (3) most of the patients exhibited very high serum IgG levels (>12 g/L). Diagnosis of X-CGD at an early age is difficult because of its nonspecific clinical features. Our study suggested children with X-CGD suffering acute infection show increases in three typical serum biomarkers, which can provide clues for early diagnosis.

幼年特发性关节炎(juvenile idiopathic arthritis,JIA)是指16岁以下儿童不明原因持续6周以上的慢性关节炎,是一类异质性疾病,发病率为16/100 000～150/100 000[1].根据2001年国际风湿病联盟(International League of Associations for Rheumatology,ILAR)分类,JIA分7型,常见类型包括少关节型、多关节型以及全身型等.其中多关节型JIA (polyarticular juvenile idiopathic arthritis,pJIA)指起病6个月内出现5个及以上关节受累,该疾病不可逆性破坏关节,导致关节畸形,从而引起生长落后,使得患儿生活质量明显下降[2].由于对该疾病的认识以及新兴医疗的进步,pJIA治疗日新月异,生物制剂也逐渐在这一疾病领域发挥显著疗效,文章将就IL-6受体拮抗剂在pJIA中的应用作一总结综述.

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.

Diabetes secondary to pancreatic exocrine insufficiency is commonly referred to as pancreatogenic diabetes or type 3c diabetes.Among all diabetic patients in the western population,the prevalence of type 3c diabetes is about 5%-10%,but some patients with pancreatogenic diabetes are misdiagnosed as type 2 diabetes.So far,researches on pancreatogenic diabetes are being explored.The definition,diagnosis,prevalence,pathogenesis,clinical features and treatment status of pancreatogenic diabetes are described and analyzed in this paper.

Syncope belongs to the transient loss of consciousness (TLOC), characterized by a rapid onset, short duration, and spontaneous complete recovery. It is common in children and adolescents, accounting for 1% to 2% of emergency department visits.Recurrent syncope can seriously affect children's physical and mental health, learning ability and quality of life and sometimes cardiac syncope even poses a risk of sudden death. The present guideline for the diagnosis and treatment of syncope in children and adolescents was developed for guiding a better clinical management of pediatric syncope. Based on the globally recent development and the evidence-based data in China, 2018 Chinese Pediatric Cardiology Society (CPCS) guideline for diagnosis and treatment of syncope in children and adolescents was jointly prepared by the Pediatric Cardiology Society, Chinese Pediatric Society, Chinese Medical Association (CMA)/Committee on Pediatric Syncope, Pediatricians Branch, Chinese Medical Doctor Association (CMDA)/Committee on Pediatric Cardiology, Chinese College of Cardiovascular Physicians, Chinese Medical Doctor Association (CMDA)/Pediatric Cardiology Society, Beijing Pediatric Society, Beijing Medical Association (BMA). The present guideline includes the underlying diseases of syncope in children and adolescents, the diagnostic procedures, methodology and clinical significance of standing test and head-up tilt test, the clinical diagnosis vasovagal syncope, postural orthostatic tachycardia syndrome, orthostatic hypotension and orthostatic hypertension, and the treatment of syncope as well as follow-up.

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.

Kawasaki disease(KD) is an acute,self-limited vasculitis of childhood and has become the leading cause of acquired pediatric heart disease.The underlying etiology remains unknown.The disease itself may be the characteristic manifestation of a common pathway of immune-mediated vascular inflammation in susceptible hosts.Intravenous immunoglobulin (IVIG) is now widely accepted as the first-line therapy for KD.However,approximately 10％-20％ of patients are resistant to IVIG.Although,an additional administration of IVIG is often chosen for the treatment of KD patients resistant to the first administration of IVIG,its efficacy is reported to be lower than that of the first IVIG dose.Thus,it is clear that some KD patients can not be treated successfully by IVIG alone,even if it is used repetitively.Currently,methylprednisolone(MP) is used for the treatment of IVIG-resistant KD.However,the proper use of MP for maximum effect and safety has not yet been elucidated.Tumor necrosis factor-α blocker,infliximab effective in the control of inflammation in patients with resistant KD.Cyclosporin treatment is also a promising option for patients with refractory KD.Plasma exchange was a safe,effective prophylactic measure against coronary artery lesions in children with KD refractory to intravenous gamma globulin therapy.

Rifapentine is a rifamycin derivate approved by the US Food and Drug Administration in 1998 for the treatment of active, drug-susceptible tuberculosis (TB). In 2014, rifapentine was approved for the treatment of latent TB infection in patients at high risk of progression to active disease and is currently under evaluation by the European Medicines Agency. Expanding indications of rifapentine largely affect diabetes patients, since about one-third of them harbor latent TB. Clinical consequences of rifapentine use in this population and potentially harmful interactions with hypoglycemic agents are widely underexplored and generally considered similar to the ones of rifampicin. Indeed, rifapentine too may decrease blood levels of many oral antidiabetics and compete with them for protein-binding sites and/or transporters. However, the two drugs differ in protein-binding degree, the magnitude of cytochrome P450 induction and auto-induction, the degree of renal elimination, and so on. Rifapentine seems to be more suitable for use in diabetes patients with renal impairment, owing to the fact that it does not cause renal toxicity, and it is eliminated via kidneys in smaller proportions than rifampicin. On the other hand, there are no data related to rifapentine use in patients >65 years, and hypoalbuminemia associated with diabetic kidney disease may affect a free fraction of rifapentine to a greater extent than that of rifampicin. Until more pharmacokinetic information and information on the safety of rifapentine use in diabetic patients and drug-drug interactions are available, diabetes in TB patients treated with rifapentine should be managed with insulin analogs, and glucose and rifapentine plasma levels should be closely monitored.

Systemic juvenile idiopathic arthritis ( sJIA ) is a special type of JIA. It is an inflammatory condition characterized by fever, lymphadenopathy, arthritis, rash and serositis. It is the most acute and severe type, which has a disproportionately high morbidity compared with other subtypes. In sJIA, systemic inflammation has been associated with dysregulation of the innate immune system, suggesting that it is an autoinflammatory disorder. Dysregulation of the innate immune system in sJIA results in increased production of inflammatory cytokines, leading to the distinctive clinical features of the disease. IL-1 and IL-6 play a major role in the pathogenesis of sJIA and treatment with IL-1 and IL-6 inhibitors has shown to be highly effective.

目的 观察血浆中N末端脑钠肽前体(NT-proBNP)水平在不完全川崎病(IKD)急性期的变化,探讨其在IKD中的诊断意义,并进一步研究NT-proBNP对早期预测川崎病静脉注射丙种球蛋白(IVIG)无反应的作用.方法 选取2013年7月至2014年12月在华中科技大学同济医学院附属同济医院儿科住院治疗的川崎病患儿239例,其中典型川崎病(TKD) 110例,IKD 129例,分别于急性期采取血样本,检测血浆中NT-proBNP水平,同时检测血白细胞计数、中性粒细胞比例、血小板计数、C反应蛋白(CRP)、红细胞沉降率(ESR)、丙氨酸转移酶(ALT)、天冬氨酸转移酶(AST)以及白蛋白水平,并选取同期65例呼吸道感染患儿作为对照组,运用方差分析比较3组之间的差异.同时运用ROC曲线分析评价NT-proBNP对川崎病的诊断意义,并与其他差异具有统计学意义的检测项目进行对比.所有川崎病患儿入院后均给予IVIG2 g/kg及口服阿司匹林治疗,运用t检验比较IVIG无反应组与敏感组之间血浆NT-proBNP水平的差异.结果 IKD患儿急性期NT-proBNP水平为(796.24± 1324.26) ng/L,明显高于对照组[(168.85±208.24) ng/L,P＜0.05],与TKD患儿NT-proBNP水平[(1362.70±2576.49) ng/L]比较,差异无统计学意义.NT-proBNP诊断川崎病ROC曲线下面积(AUC)为0.786,取临界值191.5 ng/L时,灵敏度和特异度分别为70.0％和76.9％,与白蛋白、血白细胞计数、CRP以及ESR结果相近.IVIG无反应组和敏感组NT-proBNP水平分别为(1215.15±1663.33) ng/L和(1043.66±2056.45) ng/L,两组比较差异无统计学意义(P=0.700).结论 血浆中NT-proBNP在IKD急性期显著增高,可作为早期诊断IKD的参考指标之一,但对早期预测川崎病IVIG无反应无明显作用.

We determined the effects of histamine and its antagonists on the surface marker expression of dendritic cells (DCs) and the influence of lipopolysaccharide (LPS), histamine, and histamine receptor antagonists on DCs and T-cells. The bone marrow was extracted from the femurs and tibiae of 6- to 8-week-old female Balb/c mice and cultured in medium containing penicillin, streptomycin, L-glutamine, fetal calf serum, or granulocyte macrophage colonystimulating factor (GM-CSF) alone or with interleukin (IL)-4. The cells received three different doses of LPS and histamine, plus three different doses of descarboethoxyloratadine (DCL). We assayed the supernatant for various cytokines. The spleen cells of DO11.10 mice were examined by flow cytometry, which included labeling and sorting CD4+ T-cells, as well as coculture of DCs and T-cells with ovalbumin (OVA) 323-339 peptide. Histamine or histamine plus DCL did not affect the expression of major histocompatibility complex class II, CD11c, CD11b, CD86, and CD80. However, GM-CSF increased the expression of all markers except CD80. Histamine increased interferon-gamma production in GM-CSF + IL-4-cultured cells; it also enhanced IL-10 production, but suppressed IL-12 production in LPS-stimulated DCs with no DCL. Cimetidine inhibited IL-10 production and restored IL-12 secretion in LPS-treated DCs. LPS increased IL-10 and decreased IL-12 levels. GM-CSF + IL-4-generated DCs had a stronger stimulatory effect on DO11.10 T-cell proliferation than GM-CSF-generated DCs. Inducible costimulator ligand expression was higher in GM-CSF + IL-4-than in GM-CSF-generated DC groups after 2 days of coculture, but decreased 4 days later. IL-13 production was higher in bone marrow DCs generated with GMCSF than in those generated with GM-CSF + IL-4. OVA-pulsed DCs and OVA-plus-DCL DCs showed increased IL-12 levels. OVA plus LPS increased both IL-10 and interferon-alpha. Although histamine or histamine receptor-1 antagonists did not influence DC LPS-driven maturation, they influenced cytokine production. LPS and GM-CSF influenced surface marker expression and cytokine production.

目的 观察3T3-L1成熟脂肪细胞胰岛素抵抗状态下促酰化蛋白(acylation stimulating protein,ASP)对炎性因子(IL-6、MCP-1、MIP-1α和TNF-α)分泌水平以及炎性信号因子(JNK1、IKKβ)蛋白表达的影响.方法 3T3-L1成熟脂肪细胞分别给予不同浓度(0、0.125、0.5、1.0mmol/L)油酸(C18:1)或棕榈酸(C16:0)温育过夜,诱导胰岛素抵抗,在此基础上给予ASP刺激,用ELISA测定IL-6、MCP-1、MIP-1α和TNF-α 4种细胞炎性因子的分泌水平,采用Western blot法检测JNK1和KKβ蛋白表达.结果 油酸诱导的胰岛素抵抗下,ASP刺激的脂肪细胞IL-6和MCP-1的分泌水平轻度下调,但差异无统计学意义;而ASP刺激的脂肪细胞MIP-1α和TNF-α的分泌水平显著下降,MIP-1α和TNF-α的分泌分别下调57％(P＜0.05)和48％ (P ＜0.05)(1.0mmol/L油酸组).棕榈酸诱导的胰岛素抵抗下,ASP刺激的脂肪细胞IL-6分泌水平呈下降趋势,最大下调50％ IL-6(P＜0.05);22％ MCP-1(P＞0.05),35％ MIP-1α(P ＞0.05)和38％ TNF-α(P ＞0.05)的分泌.高浓度(1.0mmol/L)油酸和棕榈酸诱导的脂肪细胞胰岛素抵抗状态下,ASP刺激的炎性信号蛋白JNK1蛋白表达显著下调,分别为34％ (P ＜0.05)和54％ (P ＜0.01).但IKKβ蛋白表达差异无统计学意义.结论 在脂肪酸诱导的脂肪细胞胰岛素抵抗状态下,ASP在一定程度上调节炎性因子分泌,参与调节JNK、IKK/NF-κB信号通路中重要信号分子的功能,ASP参与了脂肪细胞脂毒性-炎性反应的调控.

目的:观察英夫利西单抗治疗多关节型幼年特发性关节炎患儿的短期疗效及安全性.方法:经确诊为多关节型JIA患儿26例,分别于0,2,6周给予3 mg·kg-1静脉滴注英夫利西单抗,以后每隔8周按相同剂量注射1次,同时口服甲氨蝶呤(MTX)和非甾类抗炎药治疗,理疗和功能康复同步进行.分别在治疗前及治疗2,6,14,22,30周对累关节数(包括关节肿胀、疼痛、活动受限)、炎性指标ESR、CRP的变化及安全性进行.结果:26例多关节炎型JIA患儿由治疗前平均受累关节数目(7.1±2.4)个,治疗2周后,平均受累关节数目下降至(3.2±1.3)个(P＜0.05),经治疗6周、14周、22周和30周后,平均受累关节数目进一步的减少,治疗30周后,大部分患儿关节症状消失;治疗前平均血沉水平为(65.5±20.6)mm· h-1,治疗2周后,平均血沉水平下降至(37.84±11.2)mm·h-1(P＜0.05),治疗6周、14周、22周和30周后,平均血沉水平进一步下降;治疗前平均CRP水平为(87.6±25.4)mg·L-1,治疗2周后,平均CRP水平下降至(40.2±15.2)mg·L-1 (P＜0.05),治疗6周、14周、22周和30周时,CRP水平进一步下降(P＜0.05).治疗过程中未见严重感染及真菌、结核、慢性病毒感染的发生,未见肝肾功能损伤.结论:英夫利西单抗治疗多关节型JIA显效快,在较短的时间内可以明显缓解关节症状,并减轻机体的炎症反应,同时不良反应较少,主要表现为症状较轻的速发过敏反应,不影响本药物的继续使用,安全性较高.

Tocilizumab is a recombinant humanized monoclonal antibody against interleukin(IL)- 6 receptor (IL - 6R). It can prevent IL - 6 from binding to membrane - bound or soluble IL - 6R,thus blocking IL - 6 mediated signal transduction,and clinically alleviating inflammation and joint destruction in rheumatoid arthritis(RA). Both in the American and European Union,intravenous Tocilizumab has been approved for the treatment of both systemic juve-nile idiopathic arthritis(sJIA)and polyarticular JIA(pJIA)in patients aged ﹥ 2 years old. The approval was based on the favorable results from 2 randomized,double - blind,placebo - controlled,multinational,phase Ⅲ trials conducted in patients aged 2 - 17 years old with active sJIA or pJIA. Tocilizumab was generally well tolerated in patients with sJIA and pJIA. The most frequently reported adverse events in Tocilizumab recipients were infections,neutropenia,impaired liver function,etc.

川崎病的治疗一般使用丙种球蛋白及阿司匹林,难治型川崎病患儿的治疗可加用糖皮质激素。该文报道的川崎病患儿对丙种球蛋白、糖皮质激素、乌司他汀、环磷酰胺均无反应,而通过注射用英夫利西单抗的治疗后患儿临床症状及炎症指标均好转。