Analysis of choroidal thickness in juvenile systemic lupus erythematosus and its correlation with laboratory tests.

BACKGROUND: The aim of this study is to investigate the alterations of choroidal thickness (CT) in juvenile systemic lupus erythematosus (JSLE) using enhanced depth imaging optical coherence tomography (EDI-OCT). We also aimed to assess whether CT parameters correlated with systemic health status in JSLE patients. METHODS: JSLE patients and age- and sex-matched healthy subjects were recruited. A detailed ophthalmological examination was applied to all participants. CT measurements were acquired in the macular region using EDI-OCT. Moreover, a spectrum of laboratory tests was examined to evaluate the systemic conditions, and the Th1/Th2/Th17/Treg cytokine profiles in the peripheral blood were also analyzed in JSLE group. RESULTS: A total of 45 JSLE patients with no visual impairment and 50 healthy individuals were enrolled in the study. CT values in the macular region were decreased in JSLE patients when compared with healthy controls, even adjusting for age, axial length and refraction. There were no significant correlations between CT and cumulative dose of hydroxychloroquine or duration of hydroxychloroquine use (all P > 0.05). The average macular, temporal and subfoveal CT in JSLE group was negatively correlated with IL-6 and IL-10 (all P < 0.05), but had no significant correlations with other laboratory results (all P > 0.05). CONCLUSIONS: JSLE patients without ocular involvement may have significant variations in choroidal thickness at the macular area. Choroidal alterations might be associated with the systemic cytokine profiles in JSLE.

Size-segregated particle number concentrations and outpatient-department visits for pediatric respiratory diseases in Shanghai, China.

BACKGROUND: Few studies have simultaneously explored which size of particles has the greatest impact on the risk for pediatric asthma, bronchitis and upper respiratory tract infections (URTIs). OBJECTIVES: To investigate the short-term association between size-segregated particle number concentrations (PNCs) and outpatient-department visits (ODVs) for major pediatric respiratory diseases. METHODS: Daily counts of pediatric ODVs for asthma, bronchitis and URTIs were obtained from 66 hospitals in Shanghai, China, from 2016 to 2018. Pollutant effects were estimated using Poisson generalized additive models combined with polynomial distributed lag models. We also fitted co-pollutant cumulative effects models included six criteria air pollutants and conducted stratifying analyses by gender, age, season and geographic distances. RESULTS: We identified a total of 430,103 patients with asthma, 1,547,013 patients with bronchitis, and 2,155,738 patients with URTIs from the hospitals. Effect estimates increased with decreasing particle size. Ultrafine particle (UFP) and PNCs of 0.10-0.40 µm particles (PNC0.10-0.40) were associated with increased ODVs for asthma, bronchitis and URTIs at cumulative lags up to 3d. Associations tended to appear stable after adjusting for criteria air pollutants. At the cumulative lag 0-2d, each interquartile range increase in UFP was associated with increased ODVs due to asthma (relative risk 1.21, 95% CI: 1.07, 1.38), bronchitis (1.20, 95% CI: 1.07, 1.34) and URTI (1.17, 95% CI: 1.06, 1.30), whereas the associations for PNC0.10-0.40 remained significant but attenuated in magnitude. CONCLUSIONS: UFP may be a leading contributor to the adverse respiratory effects of particulate air pollution and the effects increased with decreasing particle size.

Characteristics of childhood allergic diseases in outpatient and emergency departments in Shanghai, China, 2016-2018: a multicenter, retrospective study.

BACKGROUND: The prevalence of allergic diseases (ADs), such as asthma and allergic rhinitis (AR), is increasing worldwide in both adults and children. Although ADs are common and frequently coexist in outpatient care, city-level data regarding the characteristics of childhood AD remain limited in China. This study aimed to assess the profile and characteristics of ADs in the city of Shanghai. METHODS: A multicenter retrospective study was designed to collect routine administrative data from outpatient and emergency departments from 66 hospitals in Shanghai, China, from 2016 to 2018. Children with asthma, AR, allergic conjunctivitis (AC), and allergic skin diseases were investigated. Demographic characteristics, patients visit pattern, spectrum of diagnosis, and comorbidities were analyzed. RESULTS: A total of 2,376,150 outpatient and emergency visits for ADs were included in the period from 2016 to 2018. Allergic skin diseases accounted for 38.9%, followed by asthma (34.8%), AR (22.9%), and AC (3.3%), with a male predominance in all four diseases. Asthma and allergic skin diseases were most frequent in the 1 to < 4 years of age group, while AR and AC were more common in the 4 to < 7 years of age group. Asthma accounted for the greatest number of annual and emergency visits. The most frequent comorbidity of asthma was lower respiratory tract infection (LRTI) (49.3%), followed by AR (20.5%) and upper respiratory tract infection (14.1%). The most common comorbidities of AR were otitis media (23.4%), adenoid hypertrophy/obstructive sleep apnea (22.1%), followed by LRTI (12.1%), asthma (9.4%) and chronic pharyngitis (8.9%). CONCLUSIONS: Asthma and allergic skin diseases were the most common ADs in outpatient and emergency departments in the study period. Respiratory tract infection was the most common comorbidity of asthma in children. More attention should be devoted to the treatment of comorbidities to improve childhood AD outcomes with a better understanding of the characteristics of ADs in outpatient care.

Temperature changes between neighboring days and childhood asthma: a seasonal analysis in Shanghai, China.

Few evidences are available about the impact of temperature variation on childhood asthma in different seasons. This study aimed to assess the influence of temperature changes between neighboring days (TCN) on the exacerbation of asthma among children. Daily outpatient visits for childhood asthma (DOVCA) were collected from 17 main hospitals in Shanghai, China, from 2016 to 2018. A quasi-Poisson regression combined with distributed lagged nonlinear models was employed to estimate the association between TCN and asthma visits in cool or warm seasons, after controlling for short- and long-term trends, day of week, holidays, daily mean temperature, daily mean relative humidity, and air pollutants. The TCN varied from - 9.6 to 6.7 °C. The relationship between TCN and DOVCA greatly varied by season. In warm seasons, positive TCN (temperature rise) was associated with higher risks of asthma outpatient visits and negative TCN (temperature drop) was associated with lower risks; the associations were present on lag 1 day and lasted for 2 weeks; the cumulative relative risk of childhood asthma over 0 to 14 days was 1.98 (95% confidence interval: 1.42, 2.76) and 0.31 (95% confidence intervals: 0.21, 0.44) comparing a TCN of 2.5 °C (5th percentile) and - 3.2 °C (95th percentile) with 0 °C, respectively. In cool seasons, neither negative nor positive TCN showed significant risks. In conclusion, temperature rise might increase the risk of childhood asthma exacerbation and temperature drop might decrease the risks in warm seasons. There were no statistically significant influences in cool seasons.

Melatonin Enhances Proliferation and Modulates Differentiation of Neural Stem Cells Via Autophagy in Hyperglycemia.

Dysfunction of neural stem cells (NSCs) has been linked to fetal neuropathy, one of the most devastating complications of gestational diabetes. Several studies have demonstrated that melatonin (Mel) exerted neuroprotective actions in various stresses. However, the role of autophagy and the involvement of Mel in NSCs in hyperglycemia (HG) have not yet been fully established. Here, we found that HG increased autophagy and autophagic flux of NSCs as evidenced by increasing LC3B II/I ratio, Beclin-1 expression, and autophagosomes. Moreover, Mel enhanced NSCs proliferation and self-renewal in HG with decreasing autophagy and activated mTOR signaling. Consistently, inhibition of autophagy by 3-Methyladenine (3-Ma) could assist Mel effects above, and induction of autophagy by Rapamycin (Rapa) could diminish Mel effects. Remarkably, HG induced premature differentiation of NSCs into neurons (Map2 positive cells) and astrocytes (GFAP positive cells). Furthermore, Mel diminished HG-induced premature differentiation and assisted NSCs in HG differentiation as that in normal condition. Coincidentally, inhibiting of NSCs autophagy by 3-Ma assisted Mel to modulate differentiation. However, increasing NSCs autophagy by Rapa disturbed the Mel effects and retarded NSCs differentiation. These findings suggested that Mel supplementation could contribute to mimicking normal NSCs proliferation and differentiation in fetal central nervous system by inhibiting autophagy in the context of gestational diabetes. Stem Cells 2019;37:504-515.

Lignin catabolic pathways reveal unique characteristics of dye-decolorizing peroxidases in Pseudomonas putida.

Lignin is one of the largest carbon reservoirs in the environment, playing an important role in the global carbon cycle. However, lignin degradation in bacteria, especially non-model organisms, has not been well characterized either enzymatically or genetically. Here, a lignin-degrading bacterial strain, Pseudomonas putida A514, was used as the research model. Genomic and proteomic analyses suggested that two B subfamily dye-decolorizing peroxidases (DypBs) were prominent in lignin depolymerization, while the classic O2 -dependent ring cleavage strategy was utilized in central pathways to catabolize lignin-derived aromatic compounds that were funnelled by peripheral pathways. These enzymes, together with a range of transporters, sequential and expression-dose dependent regulation and stress response systems coordinated for lignin metabolism. Catalytic assays indicated these DypBs show unique Mn2+ independent lignin depolymerization activity, while Mn2+ oxidation activity is absent. Furthermore, a high synergy between DypB enzymes and A514 cells was observed to promote cell growth (5 × 1012 cfus/ml) and lignin degradation (27%). This suggested DypBs are competitive lignin biocatalysts and pinpointed limited extracellular secretion capacity as the rate-limiting factor in bacterial lignin degradation. DypB production was, therefore, optimized in recombinant strains and a 14,141-fold increase in DypB activity (56,565 U/l) was achieved, providing novel insights for lignin bioconversion.

Serum IP-10 is useful for identifying renal and overall disease activity in pediatric systemic lupus erythematosus.

BACKGROUND: Traditional serological biomarkers often fail to assess systemic lupus erythematosus (SLE) disease activity and discriminate lupus nephritis (LN). The aim of this study was to identify novel markers for evaluating renal and overall disease activity in Chinese patients with pediatric systemic lupus erythematosus (pSLE). METHODS: The study included 46 patients with pSLE (35 girls, 11 boys; average age 13.3 ± 2.6 years) and 31 matched healthy controls (22 girls, 9 boys; average age 12.3 ± 2.4 years). The SLE Disease Activity Index (SLEDAI) and renal SLEDAI were used to assess disease activity. Nine different soluble mediators in plasma, including tumor necrosis factor alpha (TNF-α), platelet-derived growth factor-BB (PDGF-BB), interferon (IFN) gamma inducible protein 10 (IP-10), interleukin (IL)-1ß, IFN-γ, IL-17A, IL-2, Fas and Fas ligand, were measured by Luminex assay and compared between patients with active and inactive pSLE as well as between patients with pSLE with active and inactive renal disease. Receiver operating characteristic curve analysis was used to measure the discrimination accuracy. RESULTS: Of the 46 patients with pSLE, 30 (65.2%) had LN. These patients had significantly elevated levels of serum TNF-α, PDGF-BB, IP-10 and Fas. The serum levels of IP-10 were also significantly higher in patients with active pSLE. We found that IP-10 was also more sensitive and specific than conventional laboratory parameters, including anti-double-stranded DNA and complement components C3 and C4, for distinguishing active lupus from quiescent lupus. The serum level of IP-10 was also significantly increased in children with pSLE with active renal disease relative to those with inactive renal disease. There was also a positive correlation between serum IP-10 levels and renal SLEDAI scores as well as with 24 h urine protein. CONCLUSIONS: Serum IP-10 is useful for identifying renal and overall disease activity in children with pSLE.

Identification of potential peripheral blood diagnostic biomarkers for patients with juvenile idiopathic arthritis by bioinformatics analysis.

Juvenile idiopathic arthritis (JIA) is common childhood rheumatic disease harming children health. However, there is still lack of effective biomarkers for diagnosis JIA at early onset. We aim to construct a classification model to predict JIA disease. The peripheral blood gene expression profile data of JIA were downloaded from GEO database. We compared and analyzed differentially expressed genes (DEGs) between different JIA samples through Pearson's correlation coefficient method and unsupervised clustering analysis. Diagnostic model were constructed based on the deviation pathway through bioinformatics method. Eighteen specific correlated DEGs were obtained, but the correlations altered in different disease states. Although most JIA and control samples were clustered by unsupervised clustering analysis, respectively, a few JIA samples could not be clustered well. Four co-expression networks were next constructed with gene connections dynamically altered under variable conditions. Eight signaling pathways were significantly enriched including B/T cell receptor, ErbB and MAPK signaling pathways. The deviation scores of pathways were calculated. Applying these eight signaling pathways as feature to construct a classification model could predict JIA disease with high accuracies. Our data provide some light into pathogenic mechanism of JIA, the specific gene sets and the related signaling pathways may be potential biomarkers for diagnosis or therapeutic targets of JIA.

[Effect of allergic rhinitis on disease condition and treatment in patients with juvenile-onset systemic lupus erythematosus].

OBJECTIVE: To investigate the effect of allergic rhinitis (AR) and its intervention on disease condition and medications in patients with juvenile-onset systemic lupus erythematosus (JSLE). METHODS: The clinical data of 96 children diagnosed with JSLE were collected, and according to the presence or absence of AR or other allergic diseases, they were divided into AR group (n=44), non-AR group (n=20), and non-allergic group (n=32). The children in the AR group were randomly administered with or without intervention (n=22 each). All the children were given standard JSLE treatment. The systemic lupus erythematosus disease active index (SLEDAI) and application of hormones and immunosuppressants were compared between groups. RESULTS: The AR and non-AR groups had significantly higher SLEDAI scores, daily cumulative doses of glucocorticoids, and number of types of immunosuppressants used than the non-allergic group before treatment (P<0.05), while there were no significant differences between the AR and non-AR groups (P>0.05). After one month of treatment, the AR group with intervention had significantly lower SLEDAI scores and daily cumulative doses of glucocorticoids than the AR group without intervention (P<0.05), while there was no significant difference in the application of immunosuppressants between these two groups (P>0.05). After 3 and 6 months of treatment, the AR group with intervention had significantly lower SLEDAI scores, daily cumulative doses of glucocorticoids, and number of types of immunosuppressants than the AR group without intervention (P<0.05). CONCLUSIONS: JSLE combined with allergic diseases such as AR has an adverse effect on disease condition and treatment, and the intervention for AR helps with the control of JSLE.

Foxp3 regulates ratio of Treg and NKT cells in a mouse model of asthma.

Chronic inflammatory disorder of the airways causes asthma. Regulatory T cells (Treg cells) and Natural killer T cells (NKT cells) both play critical roles in the pathogenesis of asthma. Activation of Treg cells requires Foxp3, whereas whether Foxp3 may regulate the ratio of Treg and NKT cells to affect asthma is uncertain. In an ovalbumin (OVA)-induced mouse model of asthma, we either increased Treg cells by lentivirus-mediated forced expression of exogenous Foxp3, or increased NKT cells by stimulation with its activator α-GalCer. We found that the CD4+CD25+ Treg cells increased by forced Foxp3 expression, and decreased by α-GalCer, while the CD3+CD161+ NKT cells decreased by forced Foxp3 expression, and increased by α-GalCer. Moreover, forced Foxp3 expression, but not α-GalCer, significantly alleviated the hallmarks of asthma. Furthermore, forced Foxp3 increased levels of IL_10 and TGFß1, and α-GalCer increased levels of IL_4 and INFγ in the OVA-treated lung. Taken together, our study suggests that Foxp3 may activate Treg cells and suppress NKT cells in asthma. Treg and NKT cells may antagonize the effects of each other in asthma.

Atopy in children with the enthesitis-related arthritis (ERA) subtype of juvenile idiopathic arthritis is associated with a worse outcome.

UNLABELLED: We aimed to assess the influence of co-existing atopy on the prognosis of enthesitis-related arthritis (ERA). Patients diagnosed with ERA between March 2006 and August 2012 were enrolled in a prospective cohort study and followed for 2 years. Management of patients was evaluated using the American College of Rheumatology (ACR) pediatric (Pedi) 30/50/70 criteria and laboratory variables. A total of 151 ERA patients were enrolled at diagnosis and were divided into those with atopy (n = 62) and those without (n = 89). When compared with the non-atopic group, atopic patients had significantly more active joints at disease onset (4.72 vs. 3.75), more joints with limitation of motion (LOM) (1.45 vs. 0.87), more painful joints (3.61 vs. 2.80), and more swollen joints (1.02 vs. 0.69) (p < 0.05 for all comparisons). At 3, 6, 12, 18, and 24 months, fewer ERA patients with atopy reached the ACR Pedi 50 and 70 criteria (at 3 months, 25.8 vs. 60.7 % and 11.3 vs. 34.8 %, respectively; at 6 months, 50 vs. 77.5 % and 22.6 vs. 58.4 %, respectively; at 12 months, 53.2 vs. 70.8 % and 33.9 vs. 55.1 %, respectively; at 18 months, 62.9 vs. 86.5 % and 56.5 vs. 78.7 %, respectively; at 24 months, 66.1 vs. 89.9 % and 61.3 vs. 78.7 %, respectively; all p < 0.05). During the 2 years of follow-up, the number of flares was significantly higher in ERA patients with co-existing atopy (1.48 vs. 0.70, p < 0.05). CONCLUSION: Co-existing atopy in children with ERA may exert an adverse influence on ERA, with atopic patients manifesting more active disease at diagnosis and poorer outcome. \

Bacterial lysate increases the percentage of natural killer T cells in peripheral blood and alleviates asthma in children.

AIMS: To assess the efficacy of conventional treatment combined with bacterial lysate [OM-85 Broncho-Vaxom (BV)] in the prevention of asthma in children as well as its influence on the number of natural killer T (NKT) cells and their cytokine production. MATERIALS AND METHODS: Sixty children diagnosed with asthma were divided into either a BV-treated group (with oral OM-85 BV) or a conventional inhaled corticosteroid (ICS) group. The numbers of NKT cells and CD4+ NKT cells were measured in the peripheral blood by flow cytometry. The levels of IFN-γ, IL-4, and IL-10 after the blood cells had been cultured with an NKT cell agonist were detected by ELISA. RESULTS: After therapy, asthma attacks were significantly decreased compared with before therapy in both groups. However, after therapy, respiratory tract infections were reduced compared with before therapy in the BV-treated group only. Additionally, the frequency of asthma attacks and use of antibiotics in the BV-treated group were lower than in the ICS group. With BV treatment, the numbers of peripheral blood NKT cells and CD4+ NKT cells were higher after therapy than before therapy. After therapy, the ratio of IFN-γ/IL-4 and IL-10 levels were increased in the BV-treated group, whereas IL-4 was reduced in the BV-treated group compared with the ICS group. CONCLUSION: BV combined with conventional asthma treatment can prevent recurrent respiratory tract infections and suppress the severity of asthma attacks, possibly by altering the rates and cytokines of NKT cells.

GSTT1 genetic polymorphism and susceptibility to childhood acute lymphoblastic leukemia: a meta-analysis.

Glutathione S-transferase T1 (GSTT1) genetic polymorphism has been considered as a risk factor for developing malignant diseases including acute lymphoblastic leukemia; however, the results from previous studies are inconsistent. We performed a meta-analysis of 16 published studies to investigate the association between GSTT1 null variant and risk of acute lymphoblastic leukemia in childhood. Between-study heterogeneity was assessed using the I (2) statistic method. Odds ratios (ORs) with corresponding 95 % confidence intervals (95 %CI) were pooled to assess the association. Those 16 studies were from 14 publications and included a total of 2,424 cases and 3,447 controls. Meta-analysis of a total of 16 studies showed that GSTT1 null variant was significantly associated with risk of childhood acute lymphoblastic leukemia (fixed-effect OR = 1.22, 95 %CI 1.07-1.39, P = 0.003, I (2) = 35 %). Subgroup analysis showed that GSTT1 null variant was significantly associated with risk of childhood acute lymphoblastic leukemia in Asians (fixed-effect OR = 1.47, 95 %CI 1.16-1.85, P = 0.001, I (2) = 0 %). However, there was no obvious association in both Caucasians (random-effect OR = 1.07, 95 %CI 0.83-1.38, P = 0.59, I (2) = 53 %) and Africans (random-effect OR = 0.99, 95 %CI 0.31-3.10, P = 0.98, I (2) = 72 %). Therefore, the GSTT1 null variant is significantly associated with susceptibility to childhood acute lymphoblastic leukemia in Asians.

Atopy in children with systemic onset juvenile idiopathic arthritis (SoJIA) is associated with a worse outcome.

CONTEXT: Atopy and systemic onset juvenile idiopathic arthritis (SoJIA) are two potential outcomes of a dysregulated immune system. Although rare, SoJIA causes 60% of the morbidity of JIA patients which exhibit a wide heterogeneity of prognosis and treatment. Co-morbidities can complicate the responses to therapy. OBJECTIVE: To study the influence of co-existing atopy on the prognosis of SoJIA. MATERIALS AND METHODS: Patients diagnosed with SoJIA between Jan 2006 and Sep 2010 were screened, enrolled in this prospective cohort study, and followed for 2 years. Management of SoJIA patients was assessed by ACR Pedi30/50/70 criteria, laboratory variables, and systemic feature score. RESULTS: At disease onset, 61 SoJIA patients (34 male and 27 female) were enrolled and were divided into SoJIA patients with atopy (n = 27) or those without atopy (n = 34). Atopic group at disease onset had significantly higher numbers of affected joints, ferritin levels and IgE serum levels than the non-atopic group. At 3 and 6 months, fewer SoJIA patients with atopy reached the ACR Pedi50 criteria (p < 0.02). During the 2 years of follow-up time, the number of infections and the number of flares were significantly higher in the SoJIA with atopy group (p < 0.01). CONCLUSION: Atopy may exert an adverse influence on SoJIA, as patients with atopy had a more active disease at diagnosis and poorer outcome. This prospective study showed that the TH1/TH2 hypothesis was too simplistic to explain the interaction between atopy and SoJIA.

[Application of asthma predictive index-based group therapy in wheezing children under 5 years of age].

OBJECTIVE: To study the application value of asthma predictive index (API)-based group therapy in wheezing children under 5 years of age. METHODS: A total of 239 wheezing children under 5 years of age were divided into API-positive (n=126) and API-negative groups (n=113). Each group was randomly assigned to inhaled corticosteroids (ICS) subgroup and montelukast sodium (leukotriene receptor antagonist, LTRA) subgroup. The ICS and LTRA subgroups received the same drug therapy at the same dosage within the first four weeks of treatment. In the stable period of disease, the ICS subgroup only received aerosol inhalation of budesonide suspension, while the LTRA group was orally given montelukast sodium only. Asthma symptom scores were assessed and recorded at different time points. RESULTS: In the first four weeks of treatment, ICS and LTRA were effective both in the API-positive and API-negative groups; the two groups showed significant improvements in asthma symptom scores, and the asthma symptom score showed no significant difference between the ICS and LTRA subgroups of each group. After 24 weeks of treatment, the two therapies were still effective; in the API-positive group, the LTRA subgroup had a better treatment outcome than the ICS subgroup, but there was no significant difference in treatment outcome between the LTRA and ICS subgroups of the API-negative group. CONCLUSIONS: For wheezing children under 5 years of age, therapeutic strategies can be chosen based on API in the stable period of disease, so as to better control wheezing.

Clinical trial of etanercept tapering in juvenile idiopathic arthritis during remission.

To explore the possibility of step-down method and low dose of etanercept for long-term stable remission of patients with juvenile idiopathic arthritis (JIA). Patients with JIA were enrolled into this study between February 2008 and March 2010 and then followed up for 2 years. The inclusion criteria were clinical remission and use of etanercept for therapy. On the first year of the study, the dose of etanercept was kept at 0.4 mg/kg per week, the half dose of what those patients had been used. On the second year, the dose of etanercept was further lowered to 0.4 mg/kg per month. DMARDs were allowed in this study. MR images were performed to observe joint changes. The primary end point was disease flare defined according to clinical and/or radiological data. The flare rate curve was analyzed by Kaplan-Meier, and logistic regression model was used to find factors associating with disease flare. MRI was performed to prove no active changes or progressions of bone erosions on joints. Thirty-one patients were enrolled in this study. There were 4 patients experiencing disease flare during the first 12th month. During the second year, disease flare was not occurred. Thus, the cumulative flare rate was 12.9 % on 12th month and then unchanged on the second year. Logistic regression model indicates there are no differences in sex, age of disease initiation, disease duration, subtypes, DMARDs, HLA-B27, months of etanercept duration and scores on MRI between patients with remission and those experiencing flares. At the end of the study, MRI found no progressions of joints to the patients keeping stable remission. Step-down method can be used for etanercept tapering. Long-term remission and low flare rate can be got by this method.

Status of asthma control in children and the effect of parents' knowledge, attitude, and practice (KAP) in China: a multicenter study.

BACKGROUND: Asthma is the most common chronic respiratory disease seriously endangering the health of children. But disease awareness and self-management skills are relatively poor in children; parents play an important role in the control of childhood asthma. OBJECTIVE: To investigate the status of asthma control and severity of asthma in children and to identify impact factors. METHODS: We studied 1 tertiary hospital in each of the 29 provinces. A total of 2,960 parents with children with asthma who visited those hospitals were selected for the knowledge, attitude, and practice (KAP) questionnaire survey, and separated into the controlled asthma group and uncontrolled asthma group according to children's asthma conditions in the past 12 months. Multivariate analysis was carried out based on the answers to 28 tested factors. RESULTS: In the past 12 months, 66.0% of children with asthma had asthma attacks, 26.8% visited an emergency room, and 16.2% were hospitalized. The total cost for asthma was significantly higher in the uncontrolled group than controlled group (χ(2) = 23.14, P < .01). Twelve protective factors of asthma control were founded, such as older age of children, long disease course, high KAP scores of parents, compliance with using nasal steroids, and knowledge of "3 or more times recurrent wheezing suggesting asthma." The risk factors were eczema and family history of asthma. CONCLUSION: Children's asthma is poorly controlled. The cost of asthma is significantly higher in uncontrolled asthma than in controlled. The age of children, course of asthma, personal history of allergy, family history of asthma, parents' education level, and parents' KAP are factors that affect asthma control.

Second malignant neoplasms in childhood malignant brain tumour: a long-term population-based study.

AIM: To provide a profile of second malignant neoplasms (SMN) in patients with childhood primary malignant brain tumour originating from neuroepithelial tissues with latest data in a population-based study. METHODS: Surveillance, Epidemiology, and End Results (SEER) database (1973-2007) was used to identify above-stated patients. SMN patients were further identified, and standardised incidence ratios (SIRs) and excess absolute risks (EARs) for risk-factor-decided subgroups were calculated. Univariate and multivariate analyses of the association between cumulative incidence of SMN and the risk factors were performed in the whole population. RESULTS: A total of 106 patients were identified as having SMNs. EARs peaked at age at primary diagnosis of 10-14. Males had higher SIRs and EARs than females. Both SIRs and EARs increased after 1990. Age was statistically significant in both univariable and multivariable analyses for cumulative incidence of SMN and RT was not significant in both the analyses, in the whole population of 9075 patients. After follow-up recalculation, matched patients in the ≥1990 group had slightly shorter median interval between primary and secondary cancer than those in the <1990 group, but with no significance. CONCLUSION: The risk of SMN in children with primary malignant brain tumours in a more advanced treatment era might have changed. During making further advances in the treatment of these neoplasms, minimising toxicities while maintaining promising prognostic outcomes will keep being our goal.

Evaluation of the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus in children and adults.

OBJECTIVE: To evaluate the performance of the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR-2019) classification criteria for systemic lupus erythematosus (SLE) compared with the ACR-1997 and Systemic Lupus International Collaborating Clinics (SLICC) 2012 criteria in childhood-onset SLE (cSLE) and adult-onset SLE (aSLE) patients. METHODS: We conducted a retrospective study of SLE patients (221 children and 221 adults) and controls (214 children and 214 adults) with defined rheumatic diseases to establish each ACR-1997, SLICC-2012, and EULAR/ACR-2019 criterion fulfilled. Demographic, clinical, and laboratory features were evaluated through chart review. RESULTS: For cSLE, sensitivities of ACR-1997, SLICC-2012, and EULAR/ACR-2019 criteria were 63.3%, 94.6%, and 98.2%, with specificities 99.5%, 98.6%, and 93.5%, respectively. For aSLE, sensitivities of ACR-1997, SLICC-2012, and EULAR/ACR-2019 criteria were 72.9%, 96.8%, and 99.1%, with specificities 97.2%, 92.5%, and 90.2%, respectively. When including only ANA positive patients, receiver operating characteristics analysis demonstrated that the cutoff value for EULAR/ACR-2019 criteria in cSLE and aSLE patients was 13 (sensitivity, 92.2%; specificity, 93.1%) and 10 (sensitivity, 99.1%; specificity, 85.1%), respectively. Twelve cSLE patients and seven aSLE patients only met the EULAR/ACR-2019 criteria, among whom eleven and four cases had single organ involvement, respectively. CONCLUSION: The EULAR/ACR-2019 criteria showed similar sensitivity to cSLE and aSLE patients and was more sensitive than ACR-1997 and SLICC-2012 criteria, allowing earlier recognition of patients with single or major organ involvement. The adoption of a EULAR/ACR total score ≥ 13 in this study, instead of the initially proposed ≥ 10 points, could further improve the diagnostic performance of the EULAR/ACR-2019 criteria in cSLE. Key Points • Sensitivity of the EULAR/ACR-2019 criteria was high in both cSLE and aSLE patients. • The EULAR/ACR-2019 criteria allowed earlier recognition of patients with single or major organ damage. • The adoption of a EULAR/ACR total score ≥13 could further improve the diagnostic performance of the EULAR/ACR-2019 criteria in cSLE.

P2RY8 variants in lupus patients uncover a role for the receptor in immunological tolerance.

B cell self-tolerance is maintained through multiple checkpoints, including restraints on intracellular signaling and cell trafficking. P2RY8 is a receptor with established roles in germinal center (GC) B cell migration inhibition and growth regulation. Somatic P2RY8 variants are common in GC-derived B cell lymphomas. Here, we identify germline novel or rare P2RY8 missense variants in lupus kindreds or the related antiphospholipid syndrome, including a "de novo" variant in a child with severe nephritis. All variants decreased protein expression, F-actin abundance, and GPCR-RhoA signaling, and those with stronger effects increased AKT and ERK activity and cell migration. Remarkably, P2RY8 was reduced in B cell subsets from some SLE patients lacking P2RY8 gene variants. Low P2RY8 correlated with lupus nephritis and increased age-associated B cells and plasma cells. By contrast, P2RY8 overexpression in cells and mice restrained plasma cell development and reinforced negative selection of DNA-reactive developing B cells. These findings uncover a role of P2RY8 in immunological tolerance and lupus pathogenesis.