Simultaneous Detection and Distribution of Five Juvenile Hormones in 58 Insect Species and the Absolute Configuration in 32 Insect Species.

Juvenile hormone (JH) plays an important role in regulating various insect physiological processes. Herein, a novel method (chiral and achiral) for the simultaneous detection of five JHs was established by processing a whole insect without complicated hemolymph extraction. The proposed method was used to determine the distribution of JHs in 58 insect species and the absolute configuration of JHs in 32 species. The results showed that JHSB3 was uniquely synthesized in Hemiptera, JHB3 was unique to Diptera, and JH I and JH II were unique to Lepidoptera. JH III was present in most insect species surveyed, with social insects having generally higher JH III titers. Interestingly, JHSB3 and JHB3, both double epoxidation JHs, were found in insects with sucking mouthparts. The absolute conformation of JH III and the 10C of the detected JHs were all R stereoisomers.

Case report: Aggressive progression of acute heart failure due to juvenile tuberculosis-associated Takayasu arteritis with aortic stenosis and thrombosis.

Background: Takayasu arteritis (TA) is a chronic granulomatous vasculitis with unknown pathophysiology. TA with severe aortic obstruction has a poor prognosis. However, the efficacy of biologics and appropriate timing of surgical intervention remain controversial. We report a case of tuberculosis (TB)-associated TA with aggressive acute heart failure (AHF), pulmonary hypertension (PH), thrombosis, and seizure, who failed to survive after surgery. Case presentation: A 10-year-old boy who developed a cough with chest tightness, shortness of breath, hemoptysis with reduced left ventricular ejection fraction, PH, and increased C-reactive protein and erythrocyte sedimentation rate was hospitalized at the pediatric intensive care unit of our hospital. He had strongly positive purified protein derivative skin test and interferon-gamma release assay result. Computed tomography angiography (CTA) showed occlusion of proximal left subclavian artery and stenosis of descending aorta and upper abdominal aorta. His condition did not improve after administration of milrinone, diuretics, antihypertensive agents, and intravenous methylprednisolone pulse followed by oral prednisone. Intravenous tocilizumab was administered for five doses, followed by two doses of infliximab, but his HF worsened, and CTA on day 77 showed complete occlusion of the descending aorta with large thrombus. He had a seizure on day 99 with deterioration of renal function. Balloon angioplasty and catheter-directed thrombolysis were performed on day 127. Unfortunately, the child's heart function continued to deteriorate and died on day 133. Conclusion: TB infection may be related to juvenile TA. The biologics, thrombolysis, and surgical intervention failed to achieve the anticipated effect in our case with aggressive AHF due to severe aortic stenosis and thrombosis. More studies are needed to determine the role of biologics and surgery in such dire cases.

Assessment of Thigh MRI Radiomics and Clinical Characteristics for Assisting in Discrimination of Juvenile Dermatomyositis.

Magnetic resonance imaging (MRI) is an important non-invasive examination in the early diagnosis of juvenile dermatomyositis (JDM). We aimed to evaluate the feasibility of radiomics to establish a quantitative analysis of MRI images. Radiomics and machine learning were used to retrospectively analyze MRI T2 fat suppression sequences and relevant clinical data. The model associated with radiomics features was established using a cohort of patients who underwent thigh MRI at the children's hospital from June 2014 to September 2021. In total, 75 patients with JDM and 75 control children were included in the training cohort (n = 102) and validation cohort (n = 48). The independent factors including lower muscle strength (OR, 0.75; 95% CI, 0.59-0.90), higher creatine kinase (CK) level (OR, 1.65; 95% CI, 1.20-2.38), and higher radiomics score (OR, 2.30; 95% CI, 1.63-3.62) were associated with a clinical diagnosis of JDM. The combined model achieved good discrimination performance compared the radiomics score model under linear discriminant analyses in the training cohort (AUC, 0.949; 95% CI, 0.912-0.986 vs. AUC, 0.912; 95% CI, 0.858-0.967; p = 0.02) and in the validation cohort (AUC, 0.945; 95% CI, 0.878-1 vs. AUC, 0.905; 95% CI, 0.812-0.998; p = 0.03). The combined model showed the diagnostic value was not weaker than the biopsy (AUC, 0.950; 95% CI, 0.919-0.981, n = 150 vs. AUC, 0.952; 95% CI, 0.889-1, n = 72; p = 0.95) and electromyogram (EMG) (AUC, 0.950; 95% CI, 0.919-0.981 vs. AUC, 0.900; 95% CI, 0.852-0.948; p = 0.10) among all the patients. The combination of radiomics features extracted from the MRI and non-invasive clinical characteristics obtained a pronounced discriminative performance to assist in discriminating JDM.

Binder-Free Sodium Zinc Phosphate Protection Layer Enabled Dendrite-Free Zn Metal Anode.

Aqueous Zn battery has been a promising alternative battery in large-scale energy storage systems due to its cost-effectiveness, sustainability, and intrinsic safety. However, its cycle life is impeded by the dendrite formation, severe corrosion, and side reactions on the zinc metal anode. Most ex situ coatings on the zinc surface extend the life span of zinc anodes but have drawbacks in Zn2+ ion conductivity. Herein, a robust sodium zinc phosphate layer was in situ built on zinc metal foil anode (Zn@NZP) via facile electrodeposition. The Zn2+ ion conducting protection layer alleviates corrosion, suppresses zinc dendrites, and lowers the energy barrier of Zn2+ plating and stripping. As a result, the Zn@NZP anode renders dendrite-free plating/stripping with a small overpotential of about 44 mV and a 12-fold enhancement long-life span compared to the bare zinc. Furthermore, a full cell using the Zn@NZP anode shows much improved capacity and cycling stability. This work provides a promising anode candidate for dendrite-free aqueous zinc ion batteries.

Short-term effectiveness of baricitinib in children with refractory and/or severe juvenile dermatomyositis.

Objective: To determine the short-term effectiveness safety of baricitinib in children with refractory and/or severe juvenile dermatomyositis (rsJDM) in a real-world setting. Methods: This was a single-center retrospective study, including 20 children with rsJDM. They were all treated using baricitinib combined with steroids and other immunosuppressive agents. The childhood myositis assessment scale (CMAS) and PRINTO remission criteria were used to evaluate the disease severity and treatment outcome at 0, 4, 12, and 24 weeks after initiation of baricitinib. Results: The skin rash improved in 95% of patients (19/20) at week 24, with a significant decrease of skin-DAS at weeks 12 (6.0 vs. 2.0, p < 0.05] and week 24 [6.0 vs. 1.0, p < 0.05) by median statistics. The CMAS score increased significantly at week 12 (41.0 [29.0, 44.0] vs. 46.0 [42.0, 52.0], p < 0.05) and week 24 (41.0 [29.0, 44.0] vs. 50.0 [45.0, 52.0], p < 0.05), as did the manual muscle testing (MMT)-8 score at week 24 (73.0 [610, 76.0] vs. 79.0 [77.0, 80.0], p < 0.05). At 24 weeks, the complete response (CR) and partial response (PR) were achieved in 75% (15/20) and 15% (3/20), respectively. The dose of corticosteroids (CS) decreased by 37% from the baseline (0.53 [0.42, 1.00] mg/kg) to week 12 (0.33 [0.18, 0.40] mg/kg) (p < 0.05), and by 49% at week 24 (p < 0.05). No serious side effects were observed. Conclusion: Baricitinib combined with traditional immunosuppressants treatment was efficacious in rsJDM. Add-on therapy of baricitinib was helpful for tapering CS dose. No serious side effects were observed in this study.

Efficacy and safety of etanercept biosimilar rhTNFR-Fc in Chinese patients with juvenile idiopathic arthritis: An open-label multicenter observational study.

Background: Etanercept biosimilar recombinant human TNF-α receptor II: IgG Fc fusion protein (rhTNFR-Fc) has showed its efficacy and safety in Chinese patients with rheumatoid arthritis. However, data on rhTNFR-Fc's application in juvenile idiopathic arthritis (JIA) is limited. Methods: A prospective, observational, multicenter study was performed at 6 institutes in China from July 2020 to December 2021. In a 24-week follow-up, patients with JIA including polyarticular JIA and enthesitis related arthritis received rhTNFR-Fc plus methotrexate (MTX) treatment. The primary outcome parameters were improvements of cJADAS-10 (clinical Juvenile Arthritis Disease Activity Score), and the secondary outcome parameter was an inactive disease. Results: 60 patients completed at least 12-week follow-up, and 57 completed 24-week follow-up. They had high C reactive protein values (11.6 mg/L) and cJADAS-10 (14.6) at baseline. Thirteen patients had morning stiffness. 33 patients showed synovial thickening, and 34 showed bone marrow edemas on MRI. Ultrasonography demonstrated significant joint effusions in 43 patients. The cJADAS-10 sharply decreased from 14.66 at the baseline to 2.4 at 24 weeks of rhTNFR-Fc therapy, respectively (P < 0.01). About half of patients achieved inactive disease at 24 weeks of therapy. Compared with the baseline, the number of patients with morning stiffness, joint effusions, bone marrow edema and synovial thickening on MRI significantly decreased at 24 weeks. Adverse events were consistent with known side effects of biologic agents. Conclusions: The present study indicated that the combination of rhTNFR-Fc and MTX significantly improve symptoms and disease activity of children with JIA. This study suggests etanercept biosimilar rhTNFR-Fc as an effective and safe therapy for children with JIA.

Facile and Rapid Synthesis of Porous Hydrated V2O5 Nanoflakes for High-Performance Zinc Ion Battery Applications.

Hydrated V2O5 with unique physical and chemical characteristics has been widely used in various function devices, including solar cells, catalysts, electrochromic windows, supercapacitors, and batteries. Recently, it has attracted extensive attention because of the enormous potential for the high-performance aqueous zinc ion battery cathode. Although great progress has been made in developing applications of hydrated V2O5, little research focuses on improving current synthesis methods, which have disadvantages of massive energy consumption, tedious reaction time, and/or low efficiency. Herein, an improved synthesis method is developed for hydrated V2O5 nanoflakes according to the phenomenon that the reactions between V2O5 and peroxide can be dramatically accelerated with low-temperature heating. Porous hydrated V2O5 nanoflake gel was obtained from cheap raw materials at 40 °C in 30 min. It shows a high specific capacity, of 346.6 mAh/g, at 0.1 A/g; retains 55.2% of that at 20 A/g; and retains a specific capacity of 221.0 mAh/g after 1800 charging/discharging cycles at 1 A/g as an aqueous zinc ion battery cathode material. This work provides a highly facile and rapid synthesis method for hydrated V2O5, which may favor its applications in energy storage and other functional devices.

Clinical characteristics and outcomes of chronic nonbacterial osteomyelitis in children: a multicenter case series.

OBJECTIVE: The aim of this study was to evaluate demographic, clinical, laboratory, imaging, histopathology characteristics, and treatment responses of children with Chronic nonbacterial osteomyelitis (CNO). METHODS: Retrospective multi-center case series study of pediatric patients diagnosed with CNO treated at five tertiary centers in south China. RESULTS: Totally there were 18 patients diagnosed as CNO between 2014 and 2020. The median age of onset was 9.2 years (range 3.7-13.1) and 55.6% were female. Median delay in diagnosis was 10.9 months (range 1.0-72.0). The most frequent presenting symptoms were bone pain (100%) and fever (44.4%). Most patients had more than one lesion (median of 5, range 1-7). Most frequently affected bones were tibiofibula (88.9%) and femur (77.8%). The MRI characteristics mainly presented as bone edema and hyperintensity in bone marrow. Bone biopsy was conducted in 11 patients (61.1%) with inflammatory cells infiltration manifested as chronic osteomyelitis, and none showed bacterial infection or tumor. In treatment, non-steroid anti-inflamatory drugs (NSAIDs) is used as the first-line drug followed by steriods, methotexate (MTX), salazosulfadimidine (SASP), Bisphosphonates and TNF-α inhibitor. Two refractory cases received combination therapy with Bisphosphonates and TNF-α inhibitor, and achieved good therapeutic effect. CONCLUSIONS: The present study described a multicenter series of CNO from south China and highlighted the clinical features, laboratory tests, imaging characteristics and treatment outcomes. Increasing awareness of this disease is important to decrease time to diagnosis, improve access to treatment, and reduce complications.

Case Report: Macrophage Activation Syndrome and Widespread Neuroimaging Abnormality in Childhood-Onset Systemic Lupus Erythematosus.

Macrophage activation syndrome (MAS) and widespread brain lesions are rare and severe complications of childhood-onset systemic lupus erythematosus (SLE). We report an 11-year-old girl who presented with recurrent rashes for half a year and fever for 2 weeks. Clinical and laboratory features at admission pointed to the diagnosis of SLE and SLE-associated MAS. Cerebral magnetic resonance imaging taken on day 4 after admission showed abnormal signals. Glucocorticoid therapy was started on day 5. Two days later, the patient appeared weak and ill, then the next day she exhibited dizziness, drowsiness, apathia, and dysarthria. High-dose methylprednisolone, cyclophosphamide, and intravenous immunoglobulin were used to treat the patient, and intrathecal dexamethasone was given. The patient was discharged on day 30 after admission and showed complete clinical resolution and improved magnetic resonance imaging resolution.

Severe diarrhea in a 10-year-old girl with Aicardi-Goutières syndrome due to IFIH1 gene mutation.

Interferon-induced with helicase C domain 1 (IFIH1) is a cytosolic sensor of dsRNA that induces an anti-viral Type I interferon (IFN) state. A gain-of-function mutation in IFIH1 can cause increased Type I IFN activity and is clinically associated with Aicardi-Goutières syndrome (AGS). AGS is a multisystem disease, characterized as an early-onset progressive encephalopathy with basal ganglia calcification and systemic lupus erythematosus-like features. Gastrointestinal manifestation is rare in AGS patients. We described a 10-year-old female patient with a heterozygous IFIH1 gene mutation who presented with gastrointestinal colitis, cystitis and very severe diarrhea as initial major manifestations of AGS. Proteinuria with high titer of antinuclear antibody and anti-double-stranded DNA was found in this patient. She also had growth retardation and a history of seizures (about two episodes each year) but without attacks until 7 years old. Serum cytokines detected by flow cytometry indicated extremely high level of interleukin 6 (1970.1 pg/ml) and IFN-α (204.1 pg/ml). A contrast-enhanced CT scan of the whole abdomen and an intestinal hydro-MRI indicated that the walls of her stomach, small bowel, colon, and bladder were in various degrees of edema and thickened states. Whole exome sequencing analysis indicated that she harbors an IFIH1 heterozygous mutation (c.2336G > A (p.R779H)) in both blood and intestinal samples. Abundant inflammatory cells infiltration into the intestinal epithelium was observed by immunohistochemical staining. Positive staining of caspase 4 and caspase 5 suggested that the signaling pathway of pyroptosis was involved in the mechanism of intestinal inflammation in AGS. Diarrhea was significantly improved after steroids and intravenous immunoglobulin treatments. Gastrointestinal colitis and cystitis can be rare manifestations of AGS with IFIH1 mutation. Caspase and its related inflammasome pathway may involve in the pathogenesis of AGS.

Sudden Hypotension and Increased Serum Interferon-γ and Interleukin-10 Predict Early Macrophage Activation Syndrome in Patients with Systemic Juvenile Idiopathic Arthritis.

OBJECTIVE: To identify clinical and laboratory predictors for early macrophage activation syndrome (MAS) associated with systemic juvenile idiopathic arthritis (sJIA). STUDY DESIGN: This is a retrospective cohort study of 149 patients with sJIA, of whom 27 had 31 episodes of MAS. We evaluated the clinical and laboratory features of patients with sJIA and MAS and compared them with those without MAS. We focused our analysis on the overall process of MAS development, especially MAS onset. RESULTS: As shown in previous studies, we found a high percentage of fever, absence of arthritis, and central nervous system dysfunction at MAS onset in our study cohort. We also found that 35% of patients with MAS had hypotension although not shock, and 22.6% of patients with MAS had gastrointestinal involvement at MAS onset. Compared with patients with MAS without hypotension, patients with MAS and hypotension had greater rates of admission to the intensive care unit; presented with more arthritis, serositis, pneumonia, and gastrointestinal involvement; and had greater white blood cell and absolute neutrophil counts and serum bilirubin levels and lower serum total protein. We confirmed laboratory markers such as platelet counts, lactate dehydrogenase, and aspartate aminotransferase can help to identify early MAS and that ferritin/erythrocyte sedimentation rate ratio of approximately 20.0 had a high diagnostic sensitivity and specificity for MAS. In addition, we discovered that the combination of interferon-γ >17.1 pg/mL and interleukin-10 >7.8 pg/mL appeared to be a good cytokine pattern for the recognition of MAS onset. CONCLUSIONS: Sudden hypotension, elevated ferritin/erythrocyte sedimentation rate ratio, and the cytokine pattern of significantly increased interferon-γ and interleukin-10 levels are important markers for early identification of MAS in addition to the traditional characteristics of sJIA-associated MAS.

Current status and recent advances on the use of ultrasonography in pediatric rheumatic diseases.

BACKGROUND: Ultrasonography has become a useful tool in the clinical rheumatology settings in the last two decades, but its use has only recently been explored by pediatric rheumatologists. The aim of this article is to review the literature on the current status and recent advances on the use of ultrasound in pediatric rheumatic diseases. DATA SOURCES: We have retrieved and reviewed the relevant articles from MEDLINE/PubMed databases published so far, on the applications of ultrasound in juvenile idiopathic arthritis (JIA), systemic lupus erythematosus, dermatomyositis, enthesitis, Sjogren's syndrome, and other rheumatic diseases. In addition, articles on novel ultrasound imaging technology of potential use in pediatric rheumatology are also reviewed. RESULTS: In JIA, ultrasound can be used to detect subclinical synovitis, to improve the classification of patients in JIA subtypes, to capture early articular damage, to monitor treatment response, and to guide intraarticular injections. Ultrasound is also considered useful in other rheumatic disorders for the evaluation of musculoskeletal symptoms, assessment of parotid gland pathology, and measurement of skin thickness and pathology. Novel ultrasound techniques developed to augment the functionality of ultrasonography may also be applicable in pediatric rheumatic disorders. CONCLUSIONS: Ultrasound shows great promise in the assessment and management of children with rheumatologic disorders. However, standardization and validation of ultrasound in healthy children and in patients with rheumatic diseases are still needed.

Clinical and laboratory features, treatment, and outcomes of macrophage activation syndrome in 80 children: a multi-center study in China.

BACKGROUND: Macrophage activation syndrome (MAS) is a major cause of morbidity and mortality in pediatric rheumatology. We aimed to further understand the clinical features, treatment, and outcome of MAS in China. METHODS: A multi-center cohort study was performed in seven hospitals in China from 2012 to 2018. Eighty patients with MAS were enrolled, including 53 cases with systemic juvenile idiopathic arthritis (SJIA-MAS), 10 cases of Kawasaki disease (KD-MAS), and 17 cases of connective tissue disease (CTD-MAS). The clinical and laboratory data were collected before (pre-), at onset, and during full-blown stages of MAS. We compared the data among the SJIA-MAS, KD-MAS, and CTD-MAS subjects. RESULTS: 51.2% of patients developed MAS when the underlying disease was first diagnosed. In patients with SJIA, 22.6% (12/53) were found to have hypotension before the onset of SJIA-MAS. These patients were also found to have significantly increased aspartate aminotransferase (AST) and lactate dehydrogenase (LDH), as well as decreased albumin (P < 0.05), but no difference in alanine aminotransferase, ferritin, and ratio of ferritin/erythrocyte sedimentation rate (ESR) at onset of MAS when compared to pre-MAS stages of the disease. In addition, ferritin and ratio of ferritin/ESR were significantly elevated in patients at full-blown stages of SJIA-MAS compared to pre-MAS stage. Significantly increased ferritin and ratio of ferritin/ESR were also observed in patients with SJIA compared to in KD and CTD. Receiver-operating characteristic analysis showed that 12,217.5 µg/L of ferritin and 267.5 of ferritin/ESR ratio had sensitivity (80.0% and 90.5%) and specificity (88.2% and 86.7%), respectively, for predicting full-blown SJIA-MAS. The majority of the patients received corticosteroids (79/80), while biologic agents were used in 12.5% (10/80) of cases. Tocilizumab was the most commonly selected biologic agent. The overall mortality rate was 7.5%. CONCLUSIONS: About half of MAS occurred when the underlying autoimmune diseases (SJIA, KD, and CTD) were first diagnosed. Hypotension could be an important manifestation before MAS diagnosis. Decreased albumin and increased AST, LDH, ferritin, and ratio of ferritin/ESR could predict the onset or full blown of MAS in patient with SJIA.

Kawasaki disease shock syndrome: clinical characteristics and possible use of IL-6, IL-10 and IFN-γ as biomarkers for early recognition.

BACKGROUND: As an acute febrile and inflammatory disease, Kawasaki disease (KD) could develop Kawasaki disease shock syndrome (KDSS) sometimes. However its pathogenesis was still not well known. This study was to learn more about the clinical features and evaluate the role of cytokines in the pathogenesis of KDSS. METHODS: We collected clinical and laboratory data retrospectively for all patients with KDSS(KDSS, n = 27)who were hospitalized at our hospital from Jan 2014 to Oct 2017. For patient with KDSS, we randomly identified 43 patients with KD as control subjects (KD, n = 43). Clinical features, laboratory evaluations were collected. Cytokines IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ in serum were assayed using flow cytometric bead array. RESULTS: The patients with KDSS were older age (43.41 ± 31.42 vs 28.81 ± 21.51 months, P < 0.05), longer duration of fever (10.63 ± 5.12 vs 6.98 ± 2.45 days, P < 0.05), higher WBC count, neutrophils, CRP, ESR, PCT and D-dimer, and lower hemoglobin and albumin, more severe hyponatremia and hypokalemia, more refractory to IVIG therapy, more coronary artery abnormalities (CAAs), aseptic meningitis, and longer duration of hospitalization than patients with KD (all P < 0.05). The levels of serum IL-6 [184.1 (27.7-2577.3) vs 54.1 (4-425) pg/ml], IL-10 [42.6 (5-236.7) vs 9.4 (3-94) pg/ml], TNF-α [2.6 (1.0-23.4) vs 2.1 (1-6) pg/ml] and IFN-γ [18.3 (4.5-94.4) vs 6.7 (2-56) pg/ml] in KDSS patients were significant higher than KD patients (all P < 0.05). ROC curves showed that 66.7 pg/ml of IL-6, 20.85 pg/ml of IL-10 and 8.35 pg/ml of IFN-γ had sensitivity and specificity for identifying KDSS as 85.2 and 62.8%; 66.7 and 83.7%; 74.1 and 74.4% respectively. No fatality was recorded in this series. CONCLUSIONS: KDSS were characteristic as more cytokine production and prone to developing IVIG non-responsiveness and CAAs. KD patients with IL-6 above 66.7 pg/ml, IL-10 above 20.85 pg/ml, and IFN-γ above 8.35 pg/ml suggested higher risk for KDSS.

[Efficacy and safety of humanized interleukin-6 receptor antibody in treatment of systemic juvenile idiopathic arthritis].

OBJECTIVE: To evaluate the efficacy and safety of humanized anti-IL-6 receptor monoclonal antibody (tocilizumab) in treatment of systemic juvenile idiopathic arthritis (sJIA). METHODS: Thirteen sJIA patients admitted between December 2015 and November 2016 and received tocilizumab treatment were enrolled in the study. The complete blood count (CBC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6) and ferritin levels were measured; American College of Rheumatology Pediatric(ACR Pedi)30/50/70/90 scores were assessed; and the use of glucocorticosteroid and adverse events were documented. RESULTS: Compared with the baseline levels, the CRP and ESR at d3 were decreased (all P<0.05); hemoglobin was increased and platelet was decreased at week 2 (all P<0.05), ferritin decreased at week 4, white blood cell (WBC) decreased at week 8 after treatment with tocilizumab (all P<0.05). The level of IL-6 was rising at d3 and week 2 and descending at week 4, but no significant difference was observed compared with the baseline level (all P>0.05). All 13 patients achieved ACR Pedi 30 remission at week 4, 61.5% achieved ACR Pedi 90 remission and glucocorticosteroids were withdrawn at week 20. Twenty two adverse events occurred, and infection accounted for 54.5% (12/22); no severe adverse reactions were observed during 20-week follow-up. CONCLUSIONS: Tocilizumab is safe and effective in treatment of sJIA, with decreasing inflammation, improving disease activity and reducing glucocorticosteroid use.

[Clinical and laboratory features of macrophage activation syndrome].

OBJECTIVE: To study the clinical and laboratory features of macrophage activation syndrome (MAS) at the early stage of diagnosis, and to explore a method for early identification of MAS. METHODS: A retrospective analysis was performed for the demographic data, clinical and laboratory features, and treatment outcomes of 21 MAS patients. RESULTS: Of the 21 MAS patients, 14 had systemic juvenile idiopathic arthritis, 5 had Kawasaki disease (KD), and 2 had connective tissue disease (CTD) as primary diseases. The median time of MAS onset was 19 days. The KD patients had the shortest time of MAS onset, while the CTD patients had the longest onset time (P=0.009). The top 10 clinical symptoms were fever (95%), rash (86%), lymph node enlargement (67%), hemophagocytic phenomenon in bone marrow (63%), pulmonary disease (62%), serous effusion (62%), hepatomegaly (52%), cerebrospinal fluid abnormalities (50%), central nervous system damage (43%), and splenomegaly (38%). The median of hemoglobin level was lower than the normal value. The medians of C-reactive protein level and erythrocyte sedimentation rate were higher than the normal values. There were significant increases in serum ferritin, glutamic-pyruvic transaminase, aspartate aminotransferase, lactate dehydrogenase, and triglyceride. The median of fibrinogen level was lower than the normal value. There were significant increases in D-dimer, interleukin-6 (IL-6), interleukin-10 (IL-10), and interferon-γ (IFN-γ). Of the 21 patients, 20 were improved and discharged. CONCLUSIONS: If patients with rheumatic disease have persistent fever, hepatic dysfunction, coagulation disorders, multiple organ impairment, significantly increased IL-10 and IFN-γ, and a persistent increase in serum ferritin, the development of MAS should be considered.

Serum levels of Th1/Th2 cytokines in children with non-systemic juvenile idiopathic arthritis / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the serum levels of Th1/Th2 cytokines in children with non-systemic juvenile onset idiopathic arthritis (non-SOJIA).</p><p><b>METHODS</b>Clinical data of 41 children with non-SOJIA, including 11 cases of polyarthritis, 10 cases of oligoarthritis and 20 cases of enthesitis related JIA (ERA), admitted in Children's Hospital of Zhejiang University School of Medicine during November 2012 and May 2015 were retrospectively analyzed. Serum levels of Th1/Th2 cytokines including IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ were measured by flow cytometry in patients with non-SOJIA, and compared with those in patients with SOJIA (SOJIA group, n=85) and healthy children (control group, n=202); their correlations with erythrocyte sedimentation rate and C reactive protein and CRP were analyzed.</p><p><b>RESULTS</b>Compared with the healthy control group, serum levels of IL-2, IL-6 and IFN-γ were significantly increased in patients with non-SOJIA (2.9 vs. 2.6 pg/mL, 9.9 vs. 6.4 pg/mL, 6.3 vs. 5.1 pg/mL, allP<0.05),while levels of TNF-α and IL-10 were significantly decreased (2.7 vs. 3.9 pg/mL, 2.9 vs. 7.1 pg/mL, both P<0.01). Compared with the SOJIA group, serum levels of IL-6 and IL-10 were significantly decreased in patients with non-SOJIA (9.9 vs. 33.5 pg/mL, 2.9 vs. 4.1 pg/mL, both P<0.01), while levels of IL-4 and IL-10 were significantly increased (3.1 vs. 2.3 pg/mL, 6.3 vs. 4.4 pg/mL, both P<0.05). Serum levels of IL-6 in patients with polyarthritis or ERA were higher than that in patients with oligoarthritis (12.7 and 11.0 vs. 4.2 pg/mL, both P<0.05). A positive correlation of IL-6 or TNF-α level with C reactive protein was observed in patients with ERA.</p><p><b>CONCLUSIONS</b>The results indicate that Th1/Th2 imbalance and Th1 predominance may exist in children with non-SOJIA; and IL-6 may be involved in the pathogenesis of non-SOJIA children with polyarthritis.</p>

[Association of vitamin D concentrations with juvenile idiopathic arthritis].

OBJECTIVE: 25-Hydroxyvitamin D3 [25(OH)D3] is the main product of vitamin D and can reflect the absolute concentration of active vitamin D in the body. This study examined serum 25(OH)D3 levels in children with juvenile idiopathic arthritis (JIA) in order to explore the association of vitamin D concentrations with the pathogenesis and disease activity of JIA. METHODS: Serum samples were collected from 53 children confirmed as having JIA between January 2013 and March 2014, as well as 106 healthy children (control group) who underwent physical examination in the same period. Serum concentrations of 25(OH)D3 were measured using ELISA and compared between the cases and healthy controls. The association of serum 25(OH)D3 levels with JIA subtypes, ACR Pediatric 30 Score, peripheral blood C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were analyzed in children with JIA. RESULTS: Compared with the control group, the JIA group had significantly reduced serum 25(OH)D3 levels (median: 42.6 nmol/L vs 49.9 nmol/L; P<0.01). The percentage of subjects with severe deficiency of vitamin D in the JIA group was significantly higher than that in the control group (17.0% vs 6.6%; P<0.05). Serum 25(OH)D3 showed no significant correlations with JIA subtypes, ACR Pediatric 30 Score, CRP, and ESR in children with JIA. CONCLUSIONS: Vitamin D concentrations are significantly decreased in children with JIA. Decreased vitamin D concentrations may be associated with the pathogenesis of JIA. However, vitamin D concentrations may have no correlations with JIA subtypes, disease severity, and disease activity.

[Serum cytokine levels in children with newly diagnosed active systemic juvenile idiopathic arthritis].

OBJECTIVE: To study the changes in serum cytokines levels in children with newly diagnosed active systemic juvenile idiopathic arthritis (SJIA) and to explore the role of cytokines in the development and progression of SJIA. METHODS: Seventy-four pediatric patients with active SJIA between January 2010 and December 2013 were included in the study. Serum levels of interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukine-10 (IL-10), tumor necrosis factor (TNF), and interferon gamma (IFN-γ) were measured by flow cytometry in these patients. The levels of cytokines were also determined in 202 healthy children as the control group. Routine laboratory parameters including white blood cell (WBC) count, percentage of neutrophils, hemoglobin level, platelet count, hypersensitive C-reactive protein (hs-CRP), and erythrocyte sedimentation rate (ESR) were monitored in the patient group. RESULTS: The WBC count, percentage of neutrophils, hs-CRP, and ESR in 74 cases of SJIA were significantly above the normal range, their platelet counts were within the normal range, whereas hemoglobin levels were below the normal range. Compared with the control group, the patient group showed a significantly increased level of IL-6 (P<0.01) and significantly reduced levels of IL-4, IL-10, and TNF (P<0.01). However, there were no significant changes in serum levels of IL-2 and IFN-γ in the patient group (P>0.05). In SJIA children, IL-6 level, which was significantly elevated, was negatively correlated with hemoglobin level, which was significantly reduced (r=-0.244, P<0.05). CONCLUSIONS: Serum level of IL-6 is significantly increased in children with SJIA, and it has a negative correlation with anemia.

[Risk factors for pleural lung disease in children with juvenile idiopathic arthritis].

OBJECTIVE: To investigate the risk factors for pleural lung disease (PLD) in children with juvenile idiopathic arthritis (JIA) and to provide a basis for the early diagnosis and timely treatment of this disease. METHODS: A total of 360 children with a confirmed diagnosis of JIA were enrolled, and their clinical data were retrospectively analyzed. All patients underwent a chest X-ray. The patients with PLD were assigned to PLD group, while those without PLD were assigned to non-PLD group. The clinical, imaging, and laboratory results of JIA patients with PLD were analyzed. RESULTS: Among the 360 JIA patients, 43 (11.9%) had PLD, and 9 (21%) of them had respiratory symptoms. Chest X-ray findings mainly included interstitial pneumonitis (53.5%) and pleurisy and/or pleural effusion (38.1%). In the 43 cases of JIA-PLD, 4 (9.3%) had normal chest X-ray findings but abnormal chest CT findings. The incidence of PLD was relatively high in patients aged under 3 years and those aged 12 years or above. Children with systemic JIA had a relatively high incidence of PLD. Compared with the non-PLD group, the PLD group had a significantly higher incidence of anemia, elevated white blood cell (WBC) count and IgG levels in peripheral blood, and positive rheumatoid factors or antinuclear antibodies (P<0.05). CONCLUSIONS: Among children with JIA, PLD is mostly seen in patients with systemic JIA or aged <3 years or ≥ 12 years, especially those with anemia, elevated WBC count and IgG levels, and positive rheumatoid factors or antinuclear antibodies. For JIA patients with PLD, interstitial pneumonitis is usually seen on chest X-ray or CT, but respiratory symptoms are rarely observed. Routine use of high-resolution chest CT is recommended for early diagnosis and timely treatment of PLD in children with JIA.