Rosuvastatin Enhances Lymphangiogenesis after Myocardial Infarction by Regulating the miRNAs/Vascular Endothelial Growth Factor Receptor 3 (miRNAs/VEGFR3) Pathway.

BACKGROUND: Several clinical studies have suggested that the early administration of statins could reduce the risk of in-hospital mortality in acute myocardial infarction (AMI) patients. Recently, some studies have identified that stimulating lymphangiogenesis after AMI could improve cardiac function by reducing myocardial edema and inflammation. This study aimed to identify the effect of rosuvastatin on postinfarct lymphangiogenesis and to identify the underlying mechanism of this effect. METHOD: Myocardial infarction (MI) was induced by ligation of the left anterior descending coronary artery in mice orally administered rosuvastatin for 7 days. The changes in cardiac function, pathology, and lymphangiogenesis following MI were measured by echocardiography and immunostaining. EdU, Matrigel tube formation, and scratch wound assays were used to evaluate the effect of rosuvastatin on the proliferation, tube formation, and migration of the lymphatic endothelial cell line SVEC4-10. The expression of miR-107-3p, miR-491-5p, and VEGFR3 was measured by polymerase chain reaction (PCR) and Western blotting. A gain-of-function study was performed using miR-107-3p and miR-491-5p mimics. RESULTS: The rosuvastatin-treated mice had a significantly improved ejection fraction and increased lymphatic plexus density 7 days after MI. Rosuvastatin also reduced myocardial edema and inflammatory response after MI. We used a VEGFR3 inhibitor to partially reverse these effects. Rosuvastatin promoted the proliferation, migration, and tube formation of SVEC4-10 cells. PCR and Western blot analyses revealed that rosuvastatin intervention downregulated miR-107-3p and miR-491-5p and promoted VEGFR3 expression. The gain-of-function study showed that miR-107-3p and miR-491-5p could inhibit the proliferation, migration, and tube formation of SVEC4-10 cells. CONCLUSION: Rosuvastatin could improve heart function by promoting lymphangiogenesis after MI by regulating the miRNAs/VEGFR3 pathway.

Diagnosis, treatment, and prevention of monkeypox in children: an experts' consensus statement.

Monkeypox is a zoonotic disease. Since the first human monkeypox case was detected in 1970, it has been prevalent in some countries in central and western Africa. Since May 2022, monkeypox cases have been reported in more than 96 non-endemic countries and regions worldwide. As of September 14, 2022, there have been more than 58,200 human monkeypox cases, and there is community transmission. The cessation of smallpox vaccination in 1980, which had some cross-protection with monkeypox, resulted in a general lack of immunity to monkeypox, which caused global concern and vigilance. As of September 14, 2022, there are four monkeypox cases in China, including three in Taiwan province and one in Hong Kong city. Previous foreign studies have shown that children are vulnerable to monkeypox and are also at high risk for severe disease or complications. In order to improve pediatricians' understanding of monkeypox and achieve early detection, early diagnosis, early treatment,  and early disposal, we have organized national authoritative experts in pediatric infection, respiratory, dermatology, critical care medicine, infectious diseases, and public health and others to formulate this expert consensus, on the basis of the latest "Clinical management and infection prevention and control for monkeypox" released by The World Health Organization, the "guidelines for diagnosis and treatment of monkeypox (version 2022)" issued by National Health Commission of the People's Republic of China and other relevant documents. During the development of this consensus, multidisciplinary experts have repeatedly demonstrated the etiology, epidemiology, transmission, clinical manifestations, laboratory examinations, diagnosis, differential diagnosis, treatment, discharge criteria, prevention, disposal process, and key points of prevention and control of suspected and confirmed cases.

Unusual course of congenital complete heart block in an adult: A case report.

BACKGROUND: Congenital complete heart block (CCHB) with normal cardiac structure and negativity for anti-Ro/La antibody is rare. Additionally, CCHB is much less frequently diagnosed in adults, and its natural history in adults is less well known. CASE SUMMARY: A 23-year-old woman was admitted to our hospital for frequent syncopal episodes. She had bradycardia at the age of 1 year but had never had impaired exercise capacity or a syncopal episode before admission. The possible diagnosis of acquired complete atrioventricular block was carefully ruled out, and then the diagnosis of CCHB was made. According to existing guidelines, permanent pacemaker implantation was recommended, but the patient declined. With regular follow-up for 28 years, the patient had an unusually good outcome without any invasive intervention or medicine. She had an uneventful pregnancy and led a normally active life without any symptoms of low cardiac output or syncopal recurrence. CONCLUSION: This case implies that CCHB in adulthood may have good clinical outcomes and does not always require permanent pacemaker implantation.

Endothelial Microparticle-Mediated Transfer of microRNA-19b Inhibits the Function and Distribution of Lymphatic Vessels in Atherosclerotic Mice.

In recent years, the function of the lymphatic system in atherosclerosis has attracted attention due to its role in immune cell trafficking, cholesterol removal from the periphery, and regulation of the inflammatory response. However, knowledge of the mechanisms regulating lymphangiogenesis and lymphatic function in the pathogenesis of atherosclerosis is limited. Endothelial microparticles carrying circulating microRNA (miRNA)s are known to mediate cell-cell communication, and our previous research showed that miRNA-19b in EMPs (EMPmiR-19b) was significantly increased in circulation and atherosclerotic vessels, and this increase in EMPmiR-19b promoted atherosclerosis. The present study investigated whether atherogenic EMPmiR-19b influences pathological changes of the lymphatic system in atherosclerosis. We first verified increased miR-19b levels and loss of lymphatic system function in atherosclerotic mice. Atherogenic western diet-fed ApoE-/- mice were injected with phosphate-buffered saline, EMPs carrying control miRNA (EMPcontrol), or EMPmiR-19b intravenously. The function and distribution of the lymphatic system was assessed via confocal microscopy, Evans blue staining, and pathological analysis. The results showed that lymphatic system dysfunction existed in the early stage of atherosclerosis, and the observed pathological changes persisted at the later stage, companied by an increased microRNA-19b level. In ApoE-/- mice systemically treated with EMPmiR-19b, the distribution, transport function, and permeability of the lymphatic system were significantly inhibited. In vitro experiments showed that miRNA-19b may damage the lymphatic system by inhibiting lymphatic endothelial cell migration and tube formation, and a possible mechanism is the inhibition of transforming growth factor beta receptor type II (TGF-ßRII) expression in lymphatic endothelial cells by miRNA-19b. Together, our findings demonstrate that atherogenic EMPmiR-19b may destroy lymphatic system function in atherosclerotic mice by downregulating TGF-ßRII expression.

Therapeutic targets of rosuvastatin on heart failure and associated biological mechanisms: A study of network pharmacology and experimental validation.

To explore the potential targets underlying the effect of rosuvastatin on heart failure (HF) by utilizing a network pharmacology approach and experiments to identify the results. PharmMapper and other databases were mined for information relevant to the prediction of rosuvastatin targets and HF-related targets. Then, the rosuvastatin-HF target gene networks were created in Cytoscape software. Eventually, the targets and enriched pathways were examined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Furthermore, we constructed an HF animal model and used rosuvastatin to treat them, identifying the changes in heart function and related protein expression. We further used different cells to explore the mechanisms of rosuvastatin. Thirty-five intersection targets indicated the therapeutic targets linked to HF. GO analysis showed that 481 biological processes, 4 cellular components and 23 molecular functions were identified. KEGG analysis showed 13 significant treatment pathways. In animal experiments, rosuvastatin significantly improved the cardiac function of post-myocardial infarction mice and prevented the development of HF after myocardial infarction by inhibiting IL-1Β expression. Cell experiments showed that rosuvastatin could reduce the expression of IL-1B in HUVEC and THP-1 cells. The therapeutic mechanism of rosuvastatin against HF may be closely related to the inhibition of the expression of apoptosis-related proteins, inflammatory factors, and fibrosis-related genes. However, IL-1Β is one of the most important target genes.

Efficacy and safety of catheter-based renal denervation for heart failure with reduced ejection fraction: a systematic review and meta-analysis.

PURPOSE: To perform a comprehensive meta-analysis of all available evidence on the efficacy and safety of catheter-based renal denervation for heart failure with reduced ejection fraction. METHODS: We searched English and Chinese databases and calculated the weighted mean difference or standardized mean difference and 95% confidence intervals to estimate the efficacy and safety of renal denervation for heart failure. All relevant studies were screened and a meta-analysis was conducted using Review Manager 5.4. RESULTS: A total of 11 studies were identified for the meta-analysis. For the primary outcomes, the results showed that renal denervation significantly improved ejection fraction (weighted mean difference 6.42), left ventricular end-systolic diameter (weighted mean difference -3.95), left ventricular end-diastolic diameter (weighted mean difference -4.17) and left atrial diameter (weighted mean difference -4.09). For the secondary outcomes, renal denervation reduced the B-type natriuretic peptide level, heart rate, systolic blood pressure and diastolic blood pressure. However, further analysis revealed that renal denervation improved heart function but did not further reduce the heart rate and blood pressure compared with the control group. CONCLUSION: Treatment with renal denervation can significantly improve heart function and structure in patients with heart failure. In addition, the level of B-type natriuretic peptide can be reduced after renal denervation treatment. Renal denervation did not further reduce heart rate and blood pressure compared with the control group. Therefore, the treatment of heart failure with renal denervation is effective and safe.

Cytosolic DNA sensor cGAS plays an essential pathogenetic role in pressure overload-induced heart failure.

Growing evidence shows that activation of inflammation in the heart provokes left ventricular (LV) remodeling and dysfunction in humans and experimental animals with heart failure (HF). Moreover, recent studies found that cyclic GMP-AMP synthase (cGAS), serving as a cytosolic DNA sensor, was essential for activating innate immunity against infection and cellular damage by initiating the STING-IRFs-type I IFN signaling cascade, which played important roles in regulating the inflammatory response. However, the pathophysiological role of cGAS in pressure overload-induced HF is unclear. Wild-type C57BL/6J mice and cGAS inhibition mice were subjected to transverse aortic constriction (TAC) to induce HF or sham operation. Inhibition of cGAS in the murine heart was performed using adeno-associated virus 9 (AAV9). Alterations of the cGAS/STING pathway were examined by qPCR and Western blotting. Cardiac remodeling was assessed by echocardiography as well as histological and molecular phenotyping. Compared with sham-operated mice, the cGAS/STING pathway was activated in LV tissues in TAC mice. Whereas TAC mice exhibited significant pathological cardiac remodeling and LV dysfunction, inhibition of cGAS improved early survival rates after TAC, preserved LV contractile function, and blunted pathological remodeling, including cardiac hypertrophy, fibrosis, and apoptosis. Furthermore, downregulation of cGAS diminished early inflammatory cell infiltration and inflammatory cytokine expression in response to TAC. These results demonstrated that cGAS played an essential pathogenetic role in pressure overload-induced HF to promote pathological cardiac remodeling and dysfunction. Our results suggest that inhibition of cGAS may be a novel therapeutic approach for HF.NEW & NOTEWORTHY In this study, we first revealed a novel role of cGAS in the regulation of pathological cardiac remodeling and dysfunction upon pressure overload. We found that the cGAS/STING pathway was activated during pressure overload. Moreover, we also demonstrated that inhibition of the cGAS/STING pathway alleviated pathological cardiac remodeling and downregulated the early inflammatory response during pressure overload-induced HF. Together, these findings will provide a new therapeutic target for HF.

Updated diagnosis, treatment and prevention of COVID-19 in children: experts' consensus statement (condensed version of the second edition).

In the early February, 2020, we called up an experts' committee with more than 30 Chinese experts from 11 national medical academic organizations to formulate the first edition of consensus statement on diagnosis, treatment and prevention of coronavirus disease 2019 (COVID-19) in children, which has been published in this journal. With accumulated experiences in the diagnosis and treatment of COVID-19 in children, we have updated the consensus statement and released the second edition recently. The current version in English is a condensed version of the second edition of consensus statement on diagnosis, treatment and prevention of COVID-19 in children. In the current version, diagnosis and treatement criteria have been optimized, and early identification of severe and critical cases is highlighted. The early warning indicators for severe pediatric cases have been summarized which is utmost important for clinical practice. This version of experts consensus will be valuable for better prevention, diagnosis and treatment of COVID-19 in children worldwide.

Association between polymorphisms in interleukin-18 promoter and risk of coronary artery disease: a meta-analysis.

BACKGROUND: Previous studies have explored associations between interleukin-18 (IL-18) promoter polymorphisms and coronary artery disease (CAD). However, the results were controversial. We conducted a meta-analysis to clarify the association between the two polymorphisms and CAD risk. METHODS: We searched English and Chinese databases and calculated the odds ratio (OR) and 95% confidence interval (CI) to estimate whether there are genetic associations between IL-18 promoter polymorphisms and the risk of CAD. All relevant studies were screened and meta-analyzed using STATA 15.0. RESULTS: A total of 15 studies, including 12 studies for -137 G/C and 9 studies for -607 C/A, were identified for the meta-analysis. For -137 G/C, the results showed a significantly reduced risk of CAD in the dominant model (OR = 0.85) and heterozygous model (OR = 0.88) in the overall analysis. However, in subgroup analysis, decreased CAD risks were only observed in Asian populations for heterozygous genetic models. For -607 C/A, the overall OR revealed a reduced risk of CAD in all five genetic models (allelic, OR = 0.78; recessive, OR = 0.75; dominant, OR = 0.68; homozygous, OR = 0.61; heterozygous, OR = 0.72). In subgroup analysis, reduced CAD risk was also found in five genetic models of the Asian population. We also found that the IL-18 polymorphisms were correlated with myocardial infarction (MI) and multivessel (MV) disease. CONCLUSION: Our results suggested that the -137 polymorphism and -607 polymorphism in the IL-18 promoter were negatively associated with CAD, especially in the Asian population. In addition, some genetic models were correlated with the severity of CAD.

Effects of mindfulness-based stress reduction on prenatal stress, anxiety and depression.

Low well-being is common among Chinese pregnant women but few effective interventions currently exist to improve prenatal stress and negative emotions. Mindfulness-based stress reduction (MBSR) has been proved to be effective in reducing stress and rarely studies were focused on Chinese pregnant women. The aim of the current paper is to investigate the effects of 8-week MBSR on prenatal stress, anxiety and depression among Chinese pregnant women. A sample of 66 pregnant women randomly allocated into either the MBSR group (n=34) or the control group (n=32). Participants in the MBSR group received a group 8-week, 90-min each time intervention. The results found a significant interaction between time and condition for prenatal stress (F=45.51, p<0.001, η 2=0.427), anxiety (F=19.30, p<0.001, η 2=0.240), while depression showed no time-by-group interaction (F=0.29, p=0.589, η 2=0.005). As for the sub-scale of state anxiety, while there was only no time effect (F=3.68, p=0.060, η 2=0.057). The findings of this study preliminary indicated effects of the MBSR intervention on self-reported prenatal stress and anxiety in comparison to a treatment-as-usual control. Effect on depression was not observed may due to the low level of depression of participants. This study provides preliminary evidence that MBSR is suitable for Chinese pregnant women and be effective in decreasing prenatal stress, anxiety.

[Association of vitamin D level with asthma control and pulmonary function in asthmatic children aged 4-12 years].

OBJECTIVE: To study the association of vitamin D level with asthma control and pulmonary function in children with asthma. METHODS: A total of 150 children with asthma were enrolled as observation group, and 55 healthy children were enrolled as control group. According to the level of asthma control, the children were divided into good control group, partial control group, and non-control group. Chemiluminescence microparticle immunoassay was used to measure the serum level of 25-hydroxyvitamin D [25(OH)D] for all groups. According to the level of 25(OH)D, the asthmatic children were divided into normal vitamin D group, vitamin D insufficiency group, and vitamin D deficiency group. Pulmonary function was measured for all asthmatic children. RESULTS: The observation group had a significantly lower serum level of 25(OH)D than the control group (25± 7 ng/mL vs 29± 4 ng/mL; P<0.05). The normal vitamin D group had the highest asthma control rate, followed by the vitamin D insufficiency group and the vitamin D deficiency group (P<0.05). There was no significant difference in pulmonary function among the three groups (P>0.05). CONCLUSIONS: Asthmatic children have a lower serum level of 25(OH)D than healthy children. The serum level of 25(OH)D is associated with the level of asthma control and has no association with pulmonary function.

[Application of flexible bronchoscopy in children with respiratory diseases].

OBJECTIVE: To investigate the significance of flexible bronchoscopy in children with respiratory diseases. METHODS: A retrospective analysis was performed for the clinical data of 80 children who were hospitalized due to respiratory diseases (including severe pneumonia, Mycoplasma pneumoniae pneumonia with atelectasis/lung consolidation/local emphysema, protracted pneumonia, coughing and wheezing of unknown cause, chronic cough of unknown cause, and laryngeal stridor) and who underwent flexible bronchoscopy/alveolar lavage. RESULTS: Bronchoscopy found that all the 80 children had endobronchial inflammation, among whom 28 children had severe airway obstruction by secretion. Twenty-four children had congenital airway dysplasia besides endobronchial inflammation, and three children had bronchial foreign bodies. In the children with coughing and wheezing of unknown cause and laryngeal stridor, some had congenital airway dysplasia or bronchial foreign bodies. Among the 27 children with Mycoplasma pneumoniae pneumonia, 26 had severe airway obstruction/embolization by secretion; 25 children (93%) underwent chest imaging again at 2 weeks after alveolar lavage, and the results showed complete or partial lung recruitment. Among the 80 children who underwent bronchoscopy, 3 had severe hypoxemia during surgery, 1 had epistaxis, 1 had minor bleeding during alveolar lavage, 3 had transient bronchospasm, and 5 had postoperative fever; these children were all improved after symptomatic treatment. CONCLUSIONS: Flexible bronchoscopy is safe and reliable in children with respiratory diseases. Early alveolar lavage under a flexible bronchoscope is recommended for children with severe/refractory Mycoplasma pneumoniae pneumonia to improve prognosis. Flexible bronchoscopy is recommended for children with recurrent coughing and wheezing and persistent laryngeal stridor, in order to directly observe the throat and airway under an endoscope.

Characteristics of elevated cardiac troponin I in patients with acute ischemic stroke.

OBJECTIVE: To study prognostic characteristics of cardiac troponin I (cTnI) elevation in acute ischemic stroke. METHODS: We retrospectively studied patients (n = 248) with acute ischemic stroke, acute ST-segment elevation myocardial infarction, and acute non-ST-elevation myocardial infarction who were treated between January 2013 and October 2015. Baseline demographic data and changes in cTnI levels among these three groups were compared. Patients with acute ischemic stroke were assigned to either the cTnI elevation group (cTnI > 0.034 ng/mL) or the no cTnI elevation group (cTnI ≤ 0.034 ng/mL). Logistic regression analysis was used to identify risk factors associated with elevated serum cTnI in patients with acute ischemic stroke. Moreover, the duration of hospital stay and incidence of major cardiovascular outcomes were compared in patients with acute ischemic stroke, with or without elevated cTnI. RESULTS: In this study population of patients with acute ischemic stroke (n = 178), acute ST-segment elevation myocardial infarction (n = 35), and acute non-ST-elevation myocardial infarction (n = 35), patients with acute ischemic stroke with elevated cTnI comprised 18.5% of subjects. Patients with elevated cTnI were older and more likely to have a history of hypertension. In addition, these patients had higher levels of inflammatory markers, reduced renal functions, increased D-dimer levels, higher NIH stroke scores, and lower left ventricular ejection fractions. Logistic regression analysis showed that both percentage of neutrophil and NIH stroke scores were elevated; estimated glomerular filtration rate and left ventricular ejection fraction were decreased in patients with acute ischemic stroke who had elevated cTnI, and they had more frequent major cardiovascular events during hospital stay. CONCLUSION: Elevated cTnI detected in patients with acute ischemic stroke, indicated a greater likelihood of poor short-term prognosis during hospital stay.

[Association of serum vitamin D level with severity and treatment in children with Henoch-Schönlein purpura].

OBJECTIVE: To investigate the association of serum vitamin D [25-(OH)D3] level with the severity and treatment in children with Henoch-Schönlein purpura (HSP). METHODS: A total of 50 children with newly-diagnosed HSP between January and December, 2015 were enrolled as HSP group, and 49 healthy children were enrolled as control group. Fasting serum samples were collected, and ELISA was used to measure serum 25-(OH)D3 level. According to the serum 25-(OH)D3 level, the HSP group were further divided into normal group (>20 ng/mL) (n=9), insufficiency group (15-20 ng/mL) (n=15), deficiency group (≤15 ng/mL) (n=25), and severe deficiency group (≤5 ng/mL) (n=1). The general data, clinical manifestations, hormone therapy, course of disease before admission, and length of hospital stay were compared between groups. RESULTS: The HSP group had a significantly lower serum 25-(OH)D3 level than the control group (16±6 ng/mL vs 29±5 ng/mL; P<0.01). Compared with the normal and insufficiency groups, the deficiency and severe deficiency groups had significant increases in the incidence rate of renal involvement, rate of hormone application, and median length of hospital stay (P<0.05), while there was no significant difference in course of disease before admission (P>0.05). CONCLUSIONS: Children with HSP have a low serum 25-(OH)D3 level, and such children may have a high risk of renal involvement, a high rate of hormone application, and a prolonged length of hospital stay. However, further studies are needed to investigate whether vitamin D supplementation is helpful to the treatment of HSP and can shorten the course of disease in children with HSP.

Circulating microRNAs as potential biomarkers for unstable angina.

BACKGROUND: Chest pain is a typical presentation in the emergency department (ED), often due to acute coronary syndrome. Accurate and fast identification is crucial. The diagnosis and proper treatment of unstable angina (UA) can reduce the chance of acute myocardial infarction, and reduce high mortality and morbidity rates. However there is a lack of reliable and valid biomarkers in the diagnosis of UA. This study investigated the usefulness of circulating microRNAs (miRNAs) for differentiating UA from non-ischemic chest pain (NICP) in the ED. Methods The expressions of circulating miRNAs in patients with UA were evaluated relative to individuals with NICP (control subjects). Circulating miR-21, miR-25, miR-92a, miR-106b, miR-126* and miR-451 levels were measured in 98 patients with UA and 95 control subjects in the ED. To investigate the underlying functions of miRNAs in UA, bioinformatic analysis of validated miRNAs was conducted. RESULTS: Circulating miRNAs were upregulated in UA compared with the control group. The combination of the modified HEART score (m-HS) and miR-25 (AUC 0.901, NRI 0.096) could better distinguish UA than m-HS alone. Bioinformatic analysis indicated that miRNAs may take part in platelet activation, cGMP-PKG signaling pathways etc. Conclusion: The circulating levels of miRNAs (miR-21, miR-25, miR-106b, miR-126*) are significantly higher in UA patients compared with patients with NICP, and the addition of the m-HS that combined ECG, age, risk factors and troponin is useful to detect or rule out UA. The associated signaling pathways are involved in the pathogenesis of vulnerable plaque.

Inhibitory effect of arsenic trioxide on neuronal migration in vitro and its potential molecular mechanism.

Primary neuron cultures were established from the brains of neonatal rats and the effects of arsenic trioxide (As2O3) on the migration of neurons and the potential mechanism of As2O3 were investigated. Boyden chamber assay was used to detect the effect of AS2O3 on neuronal migration. Matrix metalloproteinase-2 (MMP-2) and MMP-9 RNA expression and doublecortin (DCX) protein expression were measured. Neuronal migration ability was significantly lower in the 20 µmol/L group compared with the other three groups (all p < 0.001). The expression of both MMP-2 and MMP-9 was significantly inversely correlated with As2O3 concentration. The expression of DCX was significantly higher in the control group compared with the other three groups (all p ≤ 0.003). Thus, the inhibitory effect of As2O3 on the migration of primary neurons might be related to the reduction in MMP-2 and MMP-9 activities and decrease in ß-actin and DCX expression.

Efficacy and safety of sublingual immunotherapy in children aged 3-13 years with allergic rhinitis.

BACKGROUND: Sublingual immunotherapy (SLIT) is recommended for allergic diseases. However, clinical studies containing evidence-based data of this treatment in young children, which is rarely reported in the literature, are needed. This study was designed to assess the efficacy and safety of SLIT in children, including very young children. METHODS: Two hundred sixty-four children aged 3-13 years old (133 children, 3-5 years old) with Dermatophagoides farinae-induced allergic rhinitis with or without asthma treated by standard pharmacotherapy had randomly received either SLIT (SLIT group) or no SLIT (control group) for 12 months. Symptoms, medications, visual analog scale (VAS) and presence of adverse events (AEs) were assessed at monthly visits. Skin-prick test and Dermatophagoides farinae-specific IgE and IgG4 were measured before and after treatment. RESULTS: Both treatments were effective in the global clinical scores during the first seven visits when compared with baseline (all, p < 0.01), and SLIT showed lower symptoms scores and VAS scores throughout this period (all, p < 0.01). These improvements continued until the later visits only in the SLIT group. Also, the asthma medication consumption was decreased by SLIT treatment only at the end of study (p < 0.01). The specific IgG4 was significantly increased after SLIT treatment when compared with the control group, but no significant change of specific IgE was observed in either groups. In the SLIT group, there was no significant difference between children less than or more than 5 years old in terms of clinical efficacy, onset of action, immunologic parameters, and safety. No severe systemic AEs were reported. CONCLUSION: SLIT is effective and well-tolerated in children with allergic rhinitis 3-13 years old.