Objective:To explore the optimal regimen of standardized mite allergen immunotherapy for airway allergic diseases in children, and to observe the clinical efficacy, safety and compliance.Method:Use a retrospective real-world study, clinical data from 156 children aged 5-16 years who received subcutaneous immunotherapy (SCIT) with double mite allergen preparation in the pediatrics department of the Third Affiliated Hospital of Sun Yat sen University from June 2019 to September 2020 were selected for allergic rhinitis (AR) and/or allergic asthma (bronchial asthma, BA), including gender, age, total VAS(visual analogue scale) score and CSMS(combined symptom and medication scores) score at different time points (before treatment, 4-6 months, 1 year, and 2 years after initiation of desensitization), peripheral blood eosinophil counts (EOS), serum total IgE (tIgE), specific IgE (tIgE), and serum IgE (tIgE), specific IgE (sIgE), tIgG4, and incidence of local and systemic adverse reactions. All patients had a consistent regimen during the initial treatment phase (dose-escalation phase), which was performed as directed. Among them, 81 cases (observation group) continued to continue subcutaneous injection of 1 ml of vial No. 3 every 4-6 weeks during the dose maintenance phase, while 75 cases (control group) followed the old traditional regimen during the maintenance phase (i.e., change to a new vial to halve the amount of vial No. 3 by 0.5 ml, and then 0.75 ml after 1-2 weeks, and 1 ml in a further interval of 1-2 weeks). The clinical efficacy, safety and adherence to the treatment were compared between the two groups.Results:A total of 81 cases of 156 children were included in the observation group, of which 58 children with AR, 15 children with BA, and 8 children with AR combined with BA; 75 cases were included in the conventional control group, of which 52 children with AR, 16 children with BA, and 7 children with AR combined with BA. In terms of safety, the difference in the incidence of local and systemic adverse reactions between the two groups was not statistically significant ( χ2=1.541 for local adverse reactions in the control group, χ2=0.718 for the observation group; χ2=0.483 for systemic adverse reactions in the control group, χ2=0.179 for the observation group, P value >0.05 for all of these), and there were no grade Ⅱ or higher systemic adverse reactions in any of them. In the control group, there were 15 cases of dropout at 2 years of follow-up, with a dropout rate of 20.0%; in the observation group, there were 7 cases of dropout at 2 years of follow-up, with a dropout rate of 8.6%, and there was a statistically significant difference in the dropout rates of the patients in the two groups ( χ2=4.147, P<0.05). Comparison of serological indexes and efficacy (compared with baseline at 3 different time points after treatment, i.e., 4-6 months, 1 year and 2 years after treatment), CSMS scores of the observation group and the conventional control group at 4-6 months, 1 year and 2 years after treatment were significantly decreased compared with the baseline status ( t-values of the conventional group were 13.783, 20.086 and 20.384, respectively, all P-values <0.001, and t-values of the observation group were 15.480, 27.087, 28.938, all P-values <0.001), and VAS scores also decreased significantly from baseline status in both groups at 4-6 months, 1 year, and 2 years of treatment ( t-values of 14.008, 17.963, and 27.512 in the conventional control group, respectively, with all P-values <0.001, and t-values of 9.436, 13.184, and 22.377 in the observation group, respectively; all P-values <0.001). Intergroup comparisons showed no statistically significant differences in CSMS at baseline status, 4-6 months, 1 year and 2 years ( t-values 0.621, 0.473, 1.825, and 0.342, respectively, and P-values 0.536, 0.637, 0.070, and 0.733, respectively), and VAS was no statistically significant difference in comparison between groups at different time points ( t-values of 1.663, 0.095, 0.305, 0.951, P-values of 0.099, 0.925, 0.761, 0.343, respectively); suggesting that the treatment regimens of the observation group and the conventional control group were clinically effective, and that the two regimens were comparable in terms of efficacy. The peripheral blood eosinophil counts of the observation group and the conventional control group decreased significantly from the baseline status at 4-6 months, 1 year and 2 years of treatment ( t-values of the conventional group were 3.453, 5.469, 6.273, P-values <0.05, and the t-values of the observation group were 2.900, 4.575, 5.988, P-values <0.05, respectively). 4-6 months, 1 year and 2 years compared with the baseline status tIgE showed a trend of increasing and then decreasing ( t-value in the conventional group was -5.328, -4.254, -0.690, P-value was 0.000, 0.000, 0.492, respectively, and t-value in the observation group was -6.087, -5.087, -0.324, P-value was 0.000, 0.000, 0.745, respectively). However, the results of intergroup comparisons showed no statistically significant differences in serological indices and efficacy between the two groups in terms of peripheral blood eosinophil counts at baseline status, 4-6 months, 1 year and 2 years ( t-values of 0.723, 1.553, 0.766, and 0.234, respectively; P-values of 0.471, 0.122, 0.445, and 0.815, respectively), tIgE ( t-values of 0.170, -0.166, -0.449, 0.839, P-values 0.865, 0.868, 0.654, 0.403, respectively), tIgG4 ( t-values 1.507, 1.467, -0.337, 0.804, P-values 0.134, 0.145, 0.737, 0.422, respectively). Conclusion:Both immunotherapy regimens for airway allergic diseases with double mite allergen subcutaneous immunotherapy have significant clinical efficacy, low incidence of adverse reactions, and the observation group has better patient compliance than the control group.

Objective:To determine the causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema using Mendelian randomization (MR) analyses.Methods:This study was a secondary data analysis based on the summary data of genome-wide association studies (GWAS), which involved 293 723 participants (educational attainment) from the Social Science Genetics Association Consortium and 462 013 participants [allergic rhinitis and (or) eczema] from the UK Biobank. Genetic variants that were closely related to educational attainment were identified as instrumental variables. Two-sample MR analyses, including inverse-variance weighted (IVW), MR-Egger regression, weighted median method and weighted model-based estimation, were performed to investigate the causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema, in which the odds ratio ( OR) values were used as indicators. Results:A total of 70 single-nucleotide polymorphisms (SNPs) were chosen as instrumental variables. The MR-Egger regression results suggested that the genetic pleiotropy was unlikely to bias our results ( P=0.107). In the univariable MR analyses, IVW regression showed that the risk of allergic rhinitis and (or) eczema was OR=1.044 (95% CI: 1.020-1.069, P<0.001) and OR=1.170 (95% CI: 1.074-1.256, P<0.001), respectively, for the increase in the duration of education by one year or one standard deviation ( SD) (3.71 years). In the reverse MR analysis, IVW regression showed little evidence that allergic rhinitis and (or) eczema affected educational attainment ( OR=1.020, 95% CI: 0.927-1.023, P=0.683). The results of the weighted median method and weighted mode-based estimation were consistent with the results of IVW. Conclusion:This study suggests that there is a positive causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema, which means that educational attainment can increase the occurrence of allergic rhinitis and (or) eczema.

Objective:To explore the optimal regimen of standardized mite allergen immunotherapy for airway allergic diseases in children, and to observe the clinical efficacy, safety and compliance.Method:Use a retrospective real-world study, clinical data from 156 children aged 5-16 years who received subcutaneous immunotherapy (SCIT) with double mite allergen preparation in the pediatrics department of the Third Affiliated Hospital of Sun Yat sen University from June 2019 to September 2020 were selected for allergic rhinitis (AR) and/or allergic asthma (bronchial asthma, BA), including gender, age, total VAS(visual analogue scale) score and CSMS(combined symptom and medication scores) score at different time points (before treatment, 4-6 months, 1 year, and 2 years after initiation of desensitization), peripheral blood eosinophil counts (EOS), serum total IgE (tIgE), specific IgE (tIgE), and serum IgE (tIgE), specific IgE (sIgE), tIgG4, and incidence of local and systemic adverse reactions. All patients had a consistent regimen during the initial treatment phase (dose-escalation phase), which was performed as directed. Among them, 81 cases (observation group) continued to continue subcutaneous injection of 1 ml of vial No. 3 every 4-6 weeks during the dose maintenance phase, while 75 cases (control group) followed the old traditional regimen during the maintenance phase (i.e., change to a new vial to halve the amount of vial No. 3 by 0.5 ml, and then 0.75 ml after 1-2 weeks, and 1 ml in a further interval of 1-2 weeks). The clinical efficacy, safety and adherence to the treatment were compared between the two groups.Results:A total of 81 cases of 156 children were included in the observation group, of which 58 children with AR, 15 children with BA, and 8 children with AR combined with BA; 75 cases were included in the conventional control group, of which 52 children with AR, 16 children with BA, and 7 children with AR combined with BA. In terms of safety, the difference in the incidence of local and systemic adverse reactions between the two groups was not statistically significant ( χ2=1.541 for local adverse reactions in the control group, χ2=0.718 for the observation group; χ2=0.483 for systemic adverse reactions in the control group, χ2=0.179 for the observation group, P value >0.05 for all of these), and there were no grade Ⅱ or higher systemic adverse reactions in any of them. In the control group, there were 15 cases of dropout at 2 years of follow-up, with a dropout rate of 20.0%; in the observation group, there were 7 cases of dropout at 2 years of follow-up, with a dropout rate of 8.6%, and there was a statistically significant difference in the dropout rates of the patients in the two groups ( χ2=4.147, P<0.05). Comparison of serological indexes and efficacy (compared with baseline at 3 different time points after treatment, i.e., 4-6 months, 1 year and 2 years after treatment), CSMS scores of the observation group and the conventional control group at 4-6 months, 1 year and 2 years after treatment were significantly decreased compared with the baseline status ( t-values of the conventional group were 13.783, 20.086 and 20.384, respectively, all P-values <0.001, and t-values of the observation group were 15.480, 27.087, 28.938, all P-values <0.001), and VAS scores also decreased significantly from baseline status in both groups at 4-6 months, 1 year, and 2 years of treatment ( t-values of 14.008, 17.963, and 27.512 in the conventional control group, respectively, with all P-values <0.001, and t-values of 9.436, 13.184, and 22.377 in the observation group, respectively; all P-values <0.001). Intergroup comparisons showed no statistically significant differences in CSMS at baseline status, 4-6 months, 1 year and 2 years ( t-values 0.621, 0.473, 1.825, and 0.342, respectively, and P-values 0.536, 0.637, 0.070, and 0.733, respectively), and VAS was no statistically significant difference in comparison between groups at different time points ( t-values of 1.663, 0.095, 0.305, 0.951, P-values of 0.099, 0.925, 0.761, 0.343, respectively); suggesting that the treatment regimens of the observation group and the conventional control group were clinically effective, and that the two regimens were comparable in terms of efficacy. The peripheral blood eosinophil counts of the observation group and the conventional control group decreased significantly from the baseline status at 4-6 months, 1 year and 2 years of treatment ( t-values of the conventional group were 3.453, 5.469, 6.273, P-values <0.05, and the t-values of the observation group were 2.900, 4.575, 5.988, P-values <0.05, respectively). 4-6 months, 1 year and 2 years compared with the baseline status tIgE showed a trend of increasing and then decreasing ( t-value in the conventional group was -5.328, -4.254, -0.690, P-value was 0.000, 0.000, 0.492, respectively, and t-value in the observation group was -6.087, -5.087, -0.324, P-value was 0.000, 0.000, 0.745, respectively). However, the results of intergroup comparisons showed no statistically significant differences in serological indices and efficacy between the two groups in terms of peripheral blood eosinophil counts at baseline status, 4-6 months, 1 year and 2 years ( t-values of 0.723, 1.553, 0.766, and 0.234, respectively; P-values of 0.471, 0.122, 0.445, and 0.815, respectively), tIgE ( t-values of 0.170, -0.166, -0.449, 0.839, P-values 0.865, 0.868, 0.654, 0.403, respectively), tIgG4 ( t-values 1.507, 1.467, -0.337, 0.804, P-values 0.134, 0.145, 0.737, 0.422, respectively). Conclusion:Both immunotherapy regimens for airway allergic diseases with double mite allergen subcutaneous immunotherapy have significant clinical efficacy, low incidence of adverse reactions, and the observation group has better patient compliance than the control group.

Objective:To determine the causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema using Mendelian randomization (MR) analyses.Methods:This study was a secondary data analysis based on the summary data of genome-wide association studies (GWAS), which involved 293 723 participants (educational attainment) from the Social Science Genetics Association Consortium and 462 013 participants [allergic rhinitis and (or) eczema] from the UK Biobank. Genetic variants that were closely related to educational attainment were identified as instrumental variables. Two-sample MR analyses, including inverse-variance weighted (IVW), MR-Egger regression, weighted median method and weighted model-based estimation, were performed to investigate the causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema, in which the odds ratio ( OR) values were used as indicators. Results:A total of 70 single-nucleotide polymorphisms (SNPs) were chosen as instrumental variables. The MR-Egger regression results suggested that the genetic pleiotropy was unlikely to bias our results ( P=0.107). In the univariable MR analyses, IVW regression showed that the risk of allergic rhinitis and (or) eczema was OR=1.044 (95% CI: 1.020-1.069, P<0.001) and OR=1.170 (95% CI: 1.074-1.256, P<0.001), respectively, for the increase in the duration of education by one year or one standard deviation ( SD) (3.71 years). In the reverse MR analysis, IVW regression showed little evidence that allergic rhinitis and (or) eczema affected educational attainment ( OR=1.020, 95% CI: 0.927-1.023, P=0.683). The results of the weighted median method and weighted mode-based estimation were consistent with the results of IVW. Conclusion:This study suggests that there is a positive causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema, which means that educational attainment can increase the occurrence of allergic rhinitis and (or) eczema.

Objective To investigate and analyze the similarities of allergens in children of the same family with susceptibility to the same genetic background and environmental factors. Methods From January 2013 to December 2017,a total of 142 pairs of children with allergic diseases aged 0-15 years and their siblings ( 284 cases) were collected from the outpatient or hospitalized treatment of Pediatrics and otolaryngology department of the First People′s Hospital of Foshan City,the Third Affiliated Hospital of Sun Yat-sen University. The elder group was brother or sister (142 cases),and the younger group was brother or sister ( 142 cases ) . The serum allergen sIgE was tested by Allergy Screen allergen detection system (developed by Germany MEDIWISS Company) and the similarity of allergens was analyzed. Results A total of 142 siblings ( 284 cases ) had systemic symptoms of allergic diseases in varying degrees, including respiratory symptoms ( cough ( 47 cases in the old group,32 cases in the young group), χ2 ＝3. 946, P＝0. 047),nasal obstruction ( 41 cases in the old group,19 cases in the young group, χ2 ＝ 10. 227, P ＝0. 001),runny nose (46 cases in the old group,26 cases in the young group,χ2＝7. 442,P＝0. 006), gastrointestinal symptoms (abdominal pain (11cases in the old group,7 cases in the young group,χ2＝4. 63, P＝0. 031),skin symptoms(urticaria (18 cases in the old group,8 cases in the young group,χ2＝4. 234,P＝0. 037)) and so on,the difference was statistically significant. Some children have multiple organ system symptoms at the same time. There was no significant difference between the old group and the young group in the early use of antibiotics,mode of production and feeding mode within 6 months (all P＞0. 05). Among the two groups,house dust mite and cockroach (r＝0. 831,P＜0. 05),dog hair and house dust ( r＝0. 717,P＜0. 05),cypress,elm,willow,birch,oak,maple,walnut,sycamore,poplar and Dianqing,branching,yanqu, and heiqu ( r ＝ 0. 683, P＜ 0. 05 ) . Conclusion With the same genetic background and the same environmental factors,the allergens in siblings are similar.

Objective To investigate the clinical outcomes of immunocompromised (IC) children with pediatric acute respiratory distress syndrome (PARDS) in pediatric intensive care unit (PICU).Methods Fifty-six PADRS children were enrolled and the data of clinical characteristics,immunological status,complications,treatments and outcomes were collected and analyzed by using univariate and multivariate regression models.Results There were 20 children in the immunocompromised group and 36 in the control group.Immunocompromised children were older and weighted greater than the control ones (P=0.003 and P＜0.01,respectively).Peripheral blood leukocyte,neutrophil and platelet counts were significantly lower in IC group compared with control group (P=0.060,P=0.006 and P=0.023,respectively).In addition,high-frequency oscillatory ventilation (HFOV) was used less frequently in the IC group (P=0.015).The PICU mortality of the IC group was significantly higher than that of control group (P=0.003).The proportion of IC patients and the incidence of ventilator-associated lung injury differed significantly between survivors and non-survivors (P=0.003 and P=0.046,respectively).After adjusting for other confounding factors by using multivariate logistic regression analysis,IC was associated with a higher mortality (OR=6.986,95％ CI:1.812-26.930,P=0.005).Survival analysis also indicated that IC children with ARDS had lower 28-day survival rate than the non-IC children (P=0.022).Conclusions IC children with PARDS have a higher PICU mortality than children with normal immune function.Immunocompromise is an important predictor of poor outcomes in children with PARDS.

Objective: To investigate the potential clinical role of nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) in infants suffering from infantile cytomegalovirus hepatitis (ICH). Methods: NO and eNOS were measured in 56 ICH infants and 50 healthy controls by using ELISAmethod . Results: NO and eNOS were significantly increased in ICH group as compared with the controls (P<0.01) accompanied by increased ALT in infants of ICH group (P<0.05). Both of NO and eNOS levels were significantly positively correlated with the level of ALT(r=0.682, r=0.746, P<0.05). However, neither NO level nor eNOS level was significantly correlated with the number of copies of HCMV-DNA (r=-0.087, r=-0.134, P>0.05). Conclusions The expressions of NO and eNOS were significantly increased in infants with human cytomegalovirus hepatitis, and were closely related to the severity of liver lesion.

Objective To study the immune system regulatory effects of CD8+CD28-regulatory T lymphocytes in an experimental bone marrow mesenchymal stem cell treatment of autoimmune encephalomyelitis.Methods A model of autoimmune encephalomyelitis (EAE) was established in twenty-eight C57BL/6 female mice,6 to 8 weeks old weighing 16 to 20 g using myelinoligodendrocyte glycoprotein 35-55 amino acid peptide (MOG35-55).The mice were randomly divided into a phosphate-buffered solution (PBS) group (n =7),an MSCs-Low group [n =7 which received an injection of 2× 105 mesenchymal stem cells (MSCs)],an MSCs-Med group (n=7,1× 106 MSCs),and an MSCs-High group (n=7,5×106 MSCs).Their clinical condition was then evaluated daily.On the 15th day after the MOG35-55 immunization,the different MSC doses were administered intravenously via the tail.On the 30th day the mice were sacrificed to observe any neuropathology of the spinal cord.At the same time,FACS flow cytometry was used to assay CD8+CD28-T cells in the spleen.Results Compared with the PBS control group,the MSC treatment effectively alleviated illness among the mice by the 15th day after the immunization.The maximum and average disease scores and clinical illness scores had all improved significantly.The medium dosage worked best.Neuropathological analysis showed that the MSC treatment could significantly reduce the invasion of inflammatory cells and minimize demyelination in the spinal cord.Furthermore,the CD8+ CD28-regulatory T cells in the spleens of the MSCtreated animals increased compared with the PBS control group,though the secreted levels of IL-10 showed no obvious difference.Conclusions Treatment with MCSs can promote the recovery of neural function in autoimmune encephalomyelitis,at least in mice.CD8+CD28-regulatory T cells may not be the main effector cells,playing only a synergistic therapeutic role.

Pediatric acute respiratory distress syndrome (PARDS) is one of the most severe disease in pediatric critical care medicine with high mortality.Pediatric practitioners have recognized that ARDS in children is different from ARDS in adults.In the absence of identification of these differences,however,children have been characterized as having ARDS based on the adult definitions.Therefore,the managements for PARDS were conducted without specific considerations of children,and have limitations when applied to patients.With the purpose to highlight the gaps of ARDS between children and adults,the new insights into PARDS on the epidemiology,pathophysiology,diagnosis,treatment and prognosis in the recent years were summarized.

[ ABSTRACT] AIM:To investigate the therapeutic effect of intranasal administration of CpG oligodeoxynucleotides (CpG-ODN), compared with intradermal administration, on lower airway inflammation in ovalbumin (OVA)-induced al-lergic combined airway disease (ACAD) mouse model.METHODS: Totally 30 female BALB/c mice aged from 6 to 8 weeks were randomly divided into control group , allergic rhinitis model group (AR group), ACAD group, ACAD intrana-sally treated with CpG-ODN group (CpG i.n.group) and ACAD intradermally treated with CpG-ODN group (CpG i.d. group).The mice were sensitized and challenged with OVA .Treatment with CpG-ODN was also performed during chal-lenge, either intranasally or intradermally .Immunologic variables and nasal symptom were studied .RESULTS:Compared with CpG i.d.group and ACAD group, the percentage of eosinophils from bronchoalveolar lavage fluid (BALF), the levels of Th2 cytokine production in BALF and supernatants of cultured splenic lymphocytes , OVA-specific IgE from blood , peri-bronchial inflammation score in the lung , and nasal symptoms were significantly reduced in CpG i .n.group.CONCLU-SION:Allergic rhinitis treated by CpG-ODN has a significant improvement on lower airway inflammation in ACAD mouse model;and it may be more effective when administrated intranasally than intradermally .