Clinical features and prognosis of 118 children with histiocytic necrotizing lymphadenitis / 中华儿科杂志

Objective: To explore the clinical features and prognosis of children with histiocytic necrotizing lymphadenitis (HNL). Methods: The clinical data of 118 children with HNL diagnosed and treated in the Department of Rheumatology and Immunology of Children's Hospital, Capital Institute of Pediatrics from January 2014 to December 2021 were retrospectively analyzed. The clinical symptoms, laboratory examination, imaging examination, pathological findings, treatment and follow-up were analyzed. Results: Among the 118 patients, 69 were males and 49 were females. The age of onset was 10.0 (8.0, 12.0) years, ranging from 1.5 to 16.0 years. All the children had fever lymph node enlargement, blood system involvement in 74 cases (62.7%), skin injury in 39 cases (33.1%). The main manifestations of laboratory examination were increased erythrocyte sedimentation rate in 90 cases (76.3%), decreased hemoglobin in 58 cases (49.2%), decreased white blood cells in 54 cases (45.8%) and positive antinuclear antibody in 35 cases (29.7%). Ninety-seven cases (82.2%) underwent B-mode ultrasound of lymph nodes, showing nodular lesions with low echo in the neck; 22 cases (18.6%) underwent cervical X-ray and (or) CT; 7 cases (5.9%) underwent cervical magnetic resonance imaging. Lymph node biopsy was performed in all 118 cases, and the pathological results did not support malignant diseases such as lymphoma or Epstein-Barr virus infection, suggesting HNL. Fifty-seven cases (48.3%) recovered without treatment, 61 cases (51.7%) received oral steroid therapy, and 4 cases (3.4%) received indomethacin as anal stopper. The 118 cases were followed up for 4 (2, 6) years, ranging from 1 to 7 years, 87 cases (73.7%) had one onset and did not develop into other rheumatological diseases, and 24 cases (20.3%) had different degrees of recurrence, 7 cases (5.9%) had multiple system injuries, and all of the tested autoantibodies were positive for medium and high titers. All of them developed into other rheumatic immune diseases, among which 5 cases developed into systemic lupus erythematosus and 2 cases developed into Sjogren's syndrome; 7 cases were given oral steroid therapy, including 6 cases plus immunosuppressant and 2 cases receiving methylprednisolone 20 mg/kg shock therapy. Conclusions: The first-onset HNL portion is self-healing, hormone-sensitive and has a good prognosis. For HNL with repeated disease and multiple system injury, antinuclear antibody titer should be monitored during follow-up, and attention should be paid to the possibility of developing into other rheumatological diseases, with poor prognosis.

Chinese Systemic Lupus Erythematosus Treatment and Research Group Registry IX: Clinical Features and Survival of Childhood-Onset Systemic Lupus Erythematosus in China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Approximately 15-20% cases of systemic lupus erythematosus (SLE) are diagnosed in children. There have been a few studies reporting the epidemiological data of pediatric-onset SLE (cSLE) in China, neither comparing the differences between cSLE and adult-onset SLE (aSLE). The aim of this study was to describe the impact of age of onset on clinical features and survival in cSLE patients in China based on the Chinese SLE Treatment and Research group (CSTAR) database.</p><p><b>METHODS</b>We made a prospective study of 225 cSLE patients (aged Results: The mean age of cSLE patients was 12.16 ± 2.92 years, with 187 (83.1%) females. Fever (P < 0.001) as well as mucocutaneous (P < 0.001) and renal (P = 0.006) disorders were found to be significantly more frequent in cSLE patients as initial symptoms, while muscle and joint lesions were significantly less common compared to aSLE subjects (P < 0.001). The cSLE patients were found to present more frequently with malar rash (P = 0.001; odds ratio [OR], 0.624; 95% confidence interval [CI], 0.470-0.829) but less frequently with arthritis (P < 0.001; OR, 2.013; 95% CI, 1.512-2.679) and serositis (P = 0.030; OR, 1.629; 95% CI, 1.053-2.520). There was no significant difference in SLE disease activity index scores between cSLE and aSLE groups (P = 0.478). Cox regression indicated that childhood onset was the risk factor for organ damage in lupus patients (hazard ratio 0.335 [0.170-0.658], P = 0.001). The survival curves between the cSLE and aSLE groups had no significant difference as determined by the log-rank test (0.557, P = 0.455).</p><p><b>CONCLUSIONS</b>cSLE in China has different clinical features and more inflammation than aSLE patients. Damage may be less in children and there is no difference in 5- year survival between cSLE and aSLE groups.</p>

Relationship between specific microRNAs in plasma and juvenile idiopathic arthritis / 中华实用儿科临床杂志

Objective To investigate the potential possibilities of specific microRNA in plasma as novel biomarkers for the early diagnosis in juvenile idiopathic arthritis (JIA).Methods This research was be segmented into 4 stages.1.Screened candidate microRNAs:5 candidate plasma microRNAs were detected by biochips of microRNAs,corresponding 5 JIA patients with onset of oligoarthritis,5 JIA patients with onset of polyarthritis and 3 age-matched and sex-matched healthy controls individual.2.The feasibility of the microRNAs as novel biomarkers was validated by Realtime quantitative polymerase chain reaction (RT-PCR) in plasma on 80 JIA patients (43 oligoarthritis,37 polyarthritis),29 juvenile ankylosing spondylitis(JAS) patients and 30 healthy control individuals.3.The change of microRNAs was observed by RT-PCR in plasma from another 9 JIA patients before and 3 months after anti-rheumatic drug treatment.4.The correlation between the levels of candidate plasma microRNAs and clinical parameters of JIA patients was analyzed.Results Plasma concentrations of miR-16,miR-146a and miR-223 in JIA patients,including oligoarthritis and polyarthritis,were significantly higher than those in healthy subjects (all P ＜ 0.05) and JAS patients (all P ＜ 0.001),and plasma concentration of miR-132 in JIA were significantly lower than those in healthy subjects and JAS patients (all P ＜ 0.001).Although the plasma concentration of miR-16 in polyarthritis JIA patients was considerably higher than that in oligoarthritis JIA patients (all P ＜ 0.01),the plasma concentrations of miR-146a,miR-223 and miR-132 were no difference between the 2 subtypes of JIA(all P ＞0.05).More importantly,it was found that the expression of miR-16 was considerably reduced in the post-treatment plasma samples when compared to the pre-treatment samples(P =0.061).In addition,the levels of miR-16 in JIA plasma inversely corrected with tender joint.Conclusions Plasma levels of miR-16 were well-discriminated between JIA patients and healthy subjects or JAS patients.It is suggested that plasma miR-16 might serve as a novel and potential biomarker for screening JIA.Furthermore,it might serve as a novel biomarker for joint inflammation but not specifically for differentiating the subtypes of JIA.

Application of Infliximab in treating of severe polyarticular juvenile idiopathic arthritis / 中华实用儿科临床杂志

Objective To investigate the safety and efficacy of infliximab in the treatment of severe polyarticular juvenile idiopathic arthritis(JIA).Methods Forty-four patients with severe polyarticular JIA were treated with infliximab (3 mg/kg) on week 0,2 and 6,respectively,and then they were treated every 8 weeks,plus methotrexate or and leflunomide for oral intake,and meanwhile physical therapy and functional rehabilitation were carried out.Patients were assessed by the American College of Rheumatology (ACR) response criteria (30,50,70) on week 2,6 and 14 and followed up,including swollen joint count,tender joint count,duration of morning stiffness and fever,body functions,lab inflammatory index like CRP,ESR changes.Results Among 44 cases,according to ACR response criteria,which represents 30％,50％,70％ improvement from baseline,the cure rates with infliximab therapy in swollen joint count,tender joint count,duration of morning stiffness,CRP,ESR were achieved in 47.7％ (21/44 cases),20.5％ (9/44 cases),and 11.4％ (5/44 cases) of patients with JIA on week 2 ; 63.6％ (28/44 cases),43.2％ (19/44 cases),and 13.6％ (6/44 cases) of patients on week 6 ;81.8％ (36/44 cases),52.2％ (23/44 cases),27.2％ (12/44 cases) on week 14,respectively.Inflammatory index like CRP,ESR with infliximab treatment decreased considerably compared that before treatment(P ＜0.05).Side effects from infliximab treatment were well-tolerated.There was no abnormality in the liver and kidneys or complicated infections,and no negative cases turned into the positive.Conclusions Treating severe polyarticular JIA with infliximab showed a rapid cure rate,safety and better tolerance.

Rituximab therapy for severe pediatric systemic lupus erythematosus / 中华儿科杂志

<p><b>OBJECTIVE</b>To analyze the safety and efficacy of anti-CD20 monoclonal antibody in treatment of severe pediatric systemic lupus erythematosus (PSLE).</p><p><b>METHOD</b>The diagnosis of PSLE was made according to the criteria for the classification of systemic lupus erythematosus revised by the American College of Rheumatology in 1997. Severe cases with PSLE was selected by the following criteria: age ≤ 16 years, number of important organs involved > 1, SLEDAI score > 10 points and poor response to conventional immunosuppressive treatment. These patients received 2 doses of 375 mg/m(2) rituximab (RTX), 2 weeks apart. Clinical, laboratory findings and drug side effects were recorded at RTX initiation, 2 weeks, 1 month, 3, 6 and 12 months after infusion.</p><p><b>RESULT</b>A total of 20 patients. Male to female ratio was 1:3, were enrolled. They were 5-16 years old. The course of disease was (3.0 ± 2.5) years (range: 1 month-7 years), patients were followed up for 12 - 36 months [median: (27.0 ± 7.8) months]. Delirium and cognitive disorders were significantly improved in 10 cases of lupus encephalopathy after 1 month. Lupus nephritis in children were eased slowly, 14/15 patients with lupus nephritis were improved after 2-3 months. Four cases of lupus pneumonia were significantly improved within 1 month. Decreased blood cells counts were relieved at 1 month in 16/18 cases. Cellular immune function was assessed 2 weeks after application of anti-CD20 monoclonal antibody; we found B-cell clearance in 19 patients (95%). B lymphocyte count of 18 patients (90%) was restored within one year. SLEDAI score was reduced obviously. Dose of corticosteroid ranged from (45.0 ± 4.7) mg/m(2) before drug use to (12.0 ± 2.7) mg/m(2) 12 months later (P < 0.001). After the drug use, 5 patients had pneumonia within 6 months; 2 cases who suffered from aspergillus pneumonia and Pneumocystis carinii pneumonia respectively were severe. They accepted mechanical ventilation and anti-inflammatory support after being transferred to the intensive care unit, and their conditions improved at last. No death occurred. In 2 patients the disease recurred with B-cell recovery after 15 months and 18 months. Administration of another cycle of rituximab resulted in remission again in one case but not in the other.</p><p><b>CONCLUSION</b>Anti-CD20 monoclonal antibody is effective and safe in treatment of severe PSLE. But severe infections may occur in some cases. Focusing on prevention and early treatment can reduce the probability of adverse reactions.</p>

Clinical features, mutation of the GNAS1 and pathogenesis of progressive osseous heteroplasia / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the clinical features, mutation of the GNAS1 and pathogenesis of progressive osseous heteroplasia (POH).</p><p><b>METHOD</b>The typical clinical, pathological and radiographic features of a boy with POH were collected and summarized following family survey. The GNAS1 gene sequence of all family members were amplified by polymerase chain reaction (PCR) and the products were sequenced directly to identify the mutations. A literature review and long-term follow up were also conducted.</p><p><b>RESULT</b>The patient was an 11-year-old boy who had the onset in infancy, which indicates a chronic progressive cause of disease. The clinical features include the unsmooth local skin of the right shank where spread many rigid rice-like or irregular slabby uplifts, slabby bone-like sclerosis on the left lower mandible, left masticatory muscles, in lateral subcutaneous site of left hip joint and deep tissue, accompanied by gradually progressive difficulty in opening mouth. Histopathology showed that there were loosened hyperplasia of fibroblast and interstitial edema with punctiformed ossification. Radiographs showed flocculence hyperdense image in the subcutaneous tissues and muscles around left lower mandible, and the left masticatory muscles were obviously involved. The 3-dimensional computed tomography showed dislocations of the left temporomandibular joint. Sheeted hyperdense image with inequable density could be noted in lateral muscles of the left hip. And lamellar hyperdense image parallel to the long axis of the bone could be seen in the subcutaneous dorsum of the left foot and achilles tendon. Macro-thumb and of brachydactylia of the hands and feet were not present. The level of calcium, phosphorus and alkaline phosphatase in the blood were normal. Brother of same father but different mothers was free of the disease and no patient of the same disease was found in maternal line and paternal lines. A mutated allele in exon 7 and a polymorphism in exon 5 were found in GNAS1 gene in both of the patient and his father.</p><p><b>CONCLUSION</b>There is possibility/likelihood/probability that Chinese children could develop POH. Translocated dermal ossification began in infancy and shows a progressive cause in childhood. The disease is characterized by the heterotopic ossification of the skin, deep tissue, muscles and facial surface tissues. The location of the mutation in this study was different from that reported in abroad studies although exist in the same exons.</p>

Content of gentiopicroside and loganic acid in Radix gentianae and their fingerprints / 药学学报

To develop a HPLC-DAD-ESI-TOF/MS analysis method for the determination of gentiopicroside and loganic acid in Radix gentianae samples and for the research of their fingerprints. The samples were extracted using ASE for 10 min under 100 degrees C and 9.65 MPa, and divided into water phase and chloroform phase and analyzed them with HPLC-DAD-ESI-TOF/MS method respectively. Based on this method, the HPLC fingerprints of Radix gentianae were established. Comparing the spectrogram and mass spectrum of the chromatogram peak with the reference value, three compounds in water phase were identified as gentiopicroside, asafetida acid and loganic acid. There is no report of the compounds in chloroform phase. The content of gentiopicroside and loganic acid in samples of different groups were determined, separately. The fingerprints were compared by the software of the similarity evaluation system for chromatographic fingerprint. The water phase fingerprint congruence coefficients of samples from six different areas were above 0.90, however, the chloroform phase fingerprint congruence coefficients were within 0.62 -0.99. This method can be used for determination of potent component in Radix gentianae and its quality control. Radix gentianae from different producing areas have the largest diversities, and the diversities embodied in the content of chloroform phase compounds.

Treatment of refractory rheumatism among preschool children with autologous peripheral blood hematopoietic stem cell transplantation / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the feasibility and safety of autologous peripheral blood hematopoietic stem cell transplantation (auto-PBHSCT) and its therapeutic effect on refractory rheumatism among preschool children.</p><p><b>METHODS</b>Three boys with juvenile rheumatoid arthritis (JRA), juvenile systemic lupus erythematosus (JSLE) and juvenile dermatomyositis (JDM) respectively, 3 to 6 years old with the mean age of 5 years with 3.5 to 22 months course of disease with 14 months on average, received auto-PBHSCT. Their conditions were so severe that conventional therapy failed to control the diseases. The changes of both clinical manifestations and immunologic indexes were observed before and after transplantation with long term following up at specialty clinic of rheumatism.</p><p><b>RESULT</b>The time when neutrophil count >or= 0.5 x 10(9)/L in the 3 children was days +9, +13 and +11 respectively, that of platelet count >or= 20 x 10(9)/L was days +14, +18 and +13 respectively. The cellular immune function remained abnormal with CD4 cells at a low level and CD4/CD8 being inverted. As to the JDM child, the skin rash had disappeared and his muscle tone was improved to grade 5 within one month after the transplantation. The EMG and serum creatase level returned to normal and muscle MRI findings were improved greatly within 2 months after the transplantation. As to the JSLE child, skin rash and proteinuria had disappeared, MRI of brain showed that the pathological changes had been absorbed and EEG returned to normal 3 months after the transplantation, all the autoantibodies turned to negative within 8 months after transplantation. As to the JRA child, the arthritis had been improved remarkably within 3 weeks after auto-PBHSCT. There was no swelling of joints nor movement limitation 3 months post transplantation. The steroids and immunosuppressive drugs were discontinued post transplantation. Cushing syndrome disappeared. Their body heights increased by 10 to 15 cm in the past 18 months, and they all returned to school. There was no relapse during follow-up periods of 25 - 27 months.</p><p><b>CONCLUSION</b>The therapy with auto-PBHSCT for refractory rheumatism among preschool children was remarkably effective in a short-term, yet the safety and long-term effect still need to be further studied.</p>

Changes of CD4~+CD_(25)~+ Regulatory T Cells in Children with Autoimmune Diseases / 实用儿科临床杂志

Objective Through detecting CD4+CD25+ T regulatory cells(Treg)in the peripheral blood in children suffering autoimmune diseases and normal controls to learn about the changes of Tregs during the diseases and to acquire some references for clinical diagnosis and treatment.Methods The data were reviewed for CD4+CD25+ Treg cells of the 93 children diagnosed as pediatric autoimmune disease in Children′s Hospital Affiliated to Capital Institute of Pediatrics from Nov.2007 to Jun.2008.Thirty-five normal children in the contempora-neous physical examination were selected as the control group.The percentage of CD4+CD25+ Treg cells and CD4+ T cells to the total T cells were determined by flow cytometric method.Data of the JRA group(22 cases),SLE group(12 cases) and HSP group(12 cases),which were the first three according to the number of cases,were respectively compared with the controls.Independent-samples t test was performed for a statistic analysis with SPSS 11.5 software.Results 1.The percentages of CD4+CD25+ Treg cells to the total T cells and CD4+ T cells in the autoimmune diseases children[(6.14?3.21)% and(21.85?11.68)%,respectively] were both higher than those in the control group[(3.68?1.02)% and(12.83?3.61)%,respectively Pa