Objective:To analyze the clinical characteristics of children with systemic lupus erythematosus (SLE) combined with thrombotic microangiopathy (TMA), and clarify the clinical outcomes and related risk factors of pediatric patients through their treatment and follow-up.Methods:This was a single-center retrospective case-control study. Children diagnosed with SLE combined with TMA between January 2017 and January 2023 at Beijing Children′s Hospital, Capital Medical University, were selected as the TMA group, and SLE children without TMA were selected as the control group.According to the prognosis, children in the TMA group were further divided into the good prognosis group and the poor prognosis group.The data of the children were collected, including age, gender, SLE disease activity, clinical presentations at the time of diagnosis and at the time of thrombosis, laboratory examinations, treatment strategies, prognosis, and follow-up results.The chi-square test and Z-test were used for comparison of count data.The t-test was used for comparison of metrological pairing data.The Fisher′s exact test was used to compare the differences between the 2 groups in categorical variables.The univariate Logistic regression was used to analyze the risk factors of poor prognosis. Results:There were 29 cases in the TMA group, and the incidence of TMA accounted for 2.53% of SLE patients; 33 cases were in the control group.The age at diagnosis of TMA was 13 years and 5 months (ranging from 9 years, 1 month and 5 days to 17 years and 4 months).The common clinical manifestations in order of prevalence were renal involvement (28 cases, 96.55%), hematologic involvement (26 cases, 89.66%), serous effusion (17 cases, 58.62%), rash (13 cases, 44.82%), and neurologic involvement (12 cases, 41.38%).Pleurisy or pericarditis, renal involvement and neurological involvement occurred more often in the TMA group than in the control group (17 cases vs.3 cases, 28 cases vs.10 cases, 12 cases vs.3 cases), and the TMA group showed less facial rash and arthritis than the control group (13 cases vs.25 cases, 4 cases vs.17 cases), and the differences were statistically significant (all P<0.05).The Systemic Lupus Erythematosus Disease Activity Index score in the TMA group [(24.14±9.42) scores] was significantly higher than that in the control group [(10.18±9.42) scores], and the difference was statistically significant ( t=3.233, P<0.05).The hemoglobin level, platelet count, and complement C3 level of the children in the TMA group were significantly lower than those in the control group, whereas the double stranded DNA antibody, lactate dehydrogenase, D-dimer, urea, creatinine, ferritin level, and urine protein quantitation were significantly higher than those in the control group, and the differences were statistically significant (all P<0.05).In the TMA group, 5 cases had decreased ADAMTS13 activity, and 5 cases had significantly increased complement C5b9.A total of 15 cases (51.72%) in the TMA group underwent renal biopsy, and 13 of them had combined renal TMA.In the TMA group, 28 patients (96.6%) received hormone therapy, 17 patients received plasma exchange, and 12 patients were treated with immunosuppressants and biologics; 19 patients (65.5%) improved, and 10 patients (34.5%) gave up the treatment due to deterioration of the disease.The urea level and peripheral blood fragmented erythrocyte rate in the good prognosis group were significantly lower than those in the poor prognosis group [(13.18±4.39) mmol/L vs.(21.16±10.14) mmol/L, t=2.975, P=0.006; 8/17 (47.06%) vs.7/7 (100%), χ2=5.929, P=0.015].The univariate Logistic regression analysis showed that the fragmented erythrocyte, ADAMTS13 activity and urea were the independent risk factors for poor prognosis (all P<0.05). Conclusions:SLE patients with moderate-to-severe disease activity, especially children with hemolytic anemia, thrombocytopenia, and renal dysfunction as prominent manifestations, should be alert to the risk of TMA.Early diagnosis and treatment are crucial.

It is the current confusion encountered by integrated Chinese and Western medicine that how to find the breakthrough direction of integrating Chinese and Western medicine， from crossover to integration to innovation， and open up a new horizon of integrated Chinese and Western medicine. The progress of Chinese medicine lay in expanding the scope of diagnosis and treatment with the help of modern diagnostic and therapeutic equipments and developing “micro” identification， while the progress of Western medicine lay in looking at “macro” and developing systemic medicine and integrated medicine， both of which are in the direction of each other. The “state-target identification and treatment” may become an important way to build a modern diagnosis and treatment system of integrated Chinese and Western medicine， and the thinking mode of “from target to state” is a further refinement and development on the basis of the theoretical system of “state-target identification and treatment”， which provided a clearer solution for the current stage of the integrated Chinese and Western medicine model， and pointed out the important development direction for the future integrated Chinese and Western medicine. From the perspective of strategic level and diagnosis and treatment practice， it integrated the “target-state” thinking mode into the modern diagnosis and treatment model of the integrated Chinese and Western medicine， i.e.， “Western medicine as the basis and treating with Chinese medicine； Chinese medicine as the basis and treating with Western medicine”. On the one hand， Western medicine should strengthen the reference to the traditional theories and holism of Chinese medicine， and advocate a higher level of education on the integrated Chinese and Western medicine under the guidance of the traditional theories of Chinese medicine. On the other hand， the “from target to state” mode of thinking should be applied to guide the establishment of diagnostic and treatment strategies and clinical selection of medicines in clinical practice， so as to locate the target and adjust the body state in a gradual and orderly manner， and to provide practical methods for the modern clinical work of the integrated Chinese and Western medicines. Chinese and Western medicine systems can learn from each other， combine organically， give full play to their respective strengths， and form an internal law， so as to make breakthroughs and innovations in the integrated Chinese and Western medicine model.

This study was performed to investigate the effects of mitogen-activated protein kinase(MAPK)pathway inhibitors on the expression of PD-L1 in dendritic cells and the T lymphocyte immune response in gram negative bacterial sepsis.The immunosuppression model of bacterial sepsis was established by treating the dendritic cells with bacterial endotoxin.The MAPK pathways inhibitors were applied to block pathways of dendritic cells,and then the PD-L1 expression on dendritic cells were detected by flow cytometry and Western blotting.Furthermore,the levels of T lymphocyte proliferation response and cytotoxic T cell response in mixed lymphocyte co-culture experiments were detected by cell proliferation assay kit and enzyme-linked immunospot assay kit,respectively.Data showed that the PD-L1 expression of dendritic cells were significantly up-regulated in the model group compared with the control group,while the levels of T lymphocyte proliferation response and cytotoxic T cell response in the model group were significantly reduced(P<0.05).Then compared with the model group,the PD-L1 expression of dendritic cells were significantly down-regulated in the SB203580/model group(P<0.05),meanwhile the levels of T lymphocyte proliferation response and cytotoxic T cell response were both significantly increased in SB203580/model group and αPD-L1/model group(P<0.05).In conclusion,the p38 signaling pathway could regulate PD-L1 expression of dendritic cells in bacterial sepsis.The application of p38 pathway inhibitors could partially reduce the PD-L1 expression of dendritic cells and reverse T lymphocyte immunosuppression in bacterial sepsis.

The eukaryotic genome is folded into higher-order conformation accompanied with constrained dynamics for coordinated genome functions. However, the molecular machinery underlying these hierarchically organized three-dimensional (3D) chromatin architecture and dynamics remains poorly understood. Here by combining imaging and sequencing, we studied the role of lamin B1 in chromatin architecture and dynamics. We found that lamin B1 depletion leads to detachment of lamina-associated domains (LADs) from the nuclear periphery accompanied with global chromatin redistribution and decompaction. Consequently, the inter-chromosomal as well as inter-compartment interactions are increased, but the structure of topologically associating domains (TADs) is not affected. Using live-cell genomic loci tracking, we further proved that depletion of lamin B1 leads to increased chromatin dynamics, owing to chromatin decompaction and redistribution toward nucleoplasm. Taken together, our data suggest that lamin B1 and chromatin interactions at the nuclear periphery promote LAD maintenance, chromatin compaction, genomic compartmentalization into chromosome territories and A/B compartments and confine chromatin dynamics, supporting their crucial roles in chromatin higher-order structure and chromatin dynamics.
Chromatin ; Chromosomes ; Genome ; Humans ; Lamin Type B/genetics*

  Objective  To study the demographic and clinical characteristics, correlation of genotype and phenotype and treatment of Blau syndrome to facilitate early diagnosis and timely treatment of Blau syndrome.  Methods  Seventy-two patients with Blau syndrome from 11 centers from May 2006 to April 2022 were retrospectively analyzed, and their general information, clinical data, laboratory examination and treatment medication were collected.  Results  The distribution of patients with Blau syndrome was uniform in geographical north and south of China, and there was no obvious gender bias. The mean age of onset was (14.30±12.81) months, and the age of diagnosis was (55.18±36.22) months. 35% of patients with Blau syndrome happened before 1 year old, and all patients developed before 5 years old. 87.50% (63/72) had granulomatous arthritis, 65.28% (47/72) had rash, 36.11% (26/72) had ocular involvement, 27.78% (20/72) had fever, and 15.28% (11/72) had pulmonary involvement. Arthritic manifestations of Blau syndrome were most at risk, followed by rash, ocular involvement, and fever.The first 25 months of the disease, the risk of developing a rash was the greatest. The risk of developing arthritis was the greatest between 25 months and 84 months. The main mutations were p.R334Q and p.R334W, and patients with p.R334Q mutation had relatively high incidence of fever (35.71%[5/14] vs. 14.29%[1/7], P=0.43) and ocular involvement (42.86%[6/14]vs. 28.57%[2/7], P=0.51). There was a relatively high incidence of rash (85.71%[6/7] vs. 64.29%[9/14], P=0.59) in patients with the p.R334W mutation. Forty-five patients(62.50%)were treated with a combina-tion of glucocorticoid and methotrexate. Twenty-two patients were treated with tumor necrosis factor antagonist in addition to glucocorticoid and methotrexate.  Conclusions  The risk of different clinical manifestations of Blau syndrome from high to low was arthritis, followed by rash, ocular involvement and fever. The main treatment was glucocorticoid combined with methotrexate, to which biological agents could be added.

Objective:To explore the correlation between autoantibodies and organ involvement in children with systemic lupus erythematosus (SLE).Methods:From June 2006 to October 2020, 581 children with SLE who were hospitalized in Beijing Children's Hospital for the first time and had autoantibody detection and clinical data in our hospital were selected. A correlation study was carried out on the clinical manifestations and autoantibodies. Data were analyzed with Pearson χ2 or Fisher's exact test. P<0.05 was considered statistically significant. Results:A total of 581 children with SLE were included in this study, with a male to female ratio of 1∶3.6. The average age at diagnosis was (10.6±2.8) years, and the main symptoms were rash (388, 66.8%), fever (335, 57.7%), and joint swelling and pain (170, 29.3%). The most commonly affected organ is the blood system (414, 71.3%), followed by lupus nephritis (257, 44.2%) and arthritis (170, 29.3%). In this study, the positive rate of ANA was 100%, and the positive rates of anti-dsDNA antibody and anti-Sm antibody were 59.7% and 21.2%, respectively. The children with anti-dsDNA antibody positive were more likely to have fever (64.6% vs 47.4%, χ2=16.77, P<0.001), and the kidneys (53.3% vs 30.8%, χ2=28.80, P<0.001) and blood systems (76.1% vs 64.1%, χ2=9.79, P=0.002) were more likely to be involved than anti-dsDNA antibody negative. The proportion of renal involvement (27.8% vs 47.5%, χ2=12.69, P<0.001), blood system (57.7% vs 74.0%, χ2=10.40, P=0.001), lung involvement (12.4% vs 21.1%, χ2=3.88, P=0.049) and cardiac involvement (9.3% vs 17.8%, χ2=4.11, P=0.042) in patients with anti-SSB antibody positive were lower than those in patients with anti-SSB antibody negative. Anti-histone antibody-positive patients were prone to lupus nephritis (56.9% vs 36.6%, χ2=22.62, P<0.001), arthritis (37.6% vs 24.2%, χ2=11.77, P=0.001) and lung involvement (24.3% vs 16.8%, χ2=4.87, P=0.027). Anti-Sm antibody positive patients were prone to skin manifestations such as butterfly erythema (52.8% vs 31.7%, χ2=11.38, P<0.001) and sunlight allergy (13.8% vs 7.4%, χ2=4.96, P=0.026), but the proportion of joint involvement (22.0% vs 31.2%, χ2=4.03, P=0.045) and thrombocytopenia (17.1% vs 27.3%, χ2=5.38, P=0.026) were lower than those of anti-Sm antibody negative. Arthritis (44.4% vs 24.8%, χ2=19.00, P<0.001), secondary SS (28.6% vs 5.4%, χ2=57.98, P<0.001) and parotid gland involvement (25.6% vs 2.9%, χ2=70.84, P<0.001) were more common in RF factor positive children, but the proportion of kidney involvement (30.8% vs 48.2%, χ2=12.57, P<0.001) was lower than in RF negative children. Conclusion:The clinical manifestations of childhood SLE are diverse and highly heter-ogeneous. A variety of autoantibodies are associated with organ involvement and clinical phenotypes, and anti-SSB antibodies may have protective effects in kidney and other organ damage.

10.3969/j.issn.1000-3606.2013.06.005