Inhibition of Bcl-6 Expression Ameliorates Asthmatic Characteristics in Mice

Objective The function of Bcl-6 in T follicular helper(Tfh)cell maturation is indispensable,and Tfh cells play a pivotal role in asthma.This study investigated the impact of Bcl-6 on asthmatic traits.Methods The microscopic pathological alterations,airway resistance(AR),and lung compliance(LC)were determined in asthmatic mice and Bcl-6 interference mice.The surface molecular markers of Tfh cells and the Bcl-6 mRNA and protein expression were determined by flow cytometry,RT-qPCR,and Western blotting,respectively.The relationships between the Tfh cell ratio and the IgE and IgG1 concentrations in peripheral blood mononuclear cells(PBMCs)and bronchoalveolar lavage fluid(BALF)were determined.Results Asthmatic inflammatory changes were observed in the lung tissue and were attenuated by Bcl-6 siRNA and dexamethasone(DXM).Asthmatic mice exhibited an increased AR and a decreased LC,while Bcl-6 siRNA or DXM mitigated these changes.The percentages of Tfh cells and eosinophils were significantly increased in the asthmatic mice,and they significantly decreased after Bcl-6 inhibition or DXM treatment.RT-qPCR and Western blotting analyses revealed that the Bcl-6 expression level in PBMCs was significantly higher in asthmatic mice,and it decreased following Bcl-6 inhibition or DXM treatment.The IgE expression in the serum and BALF and the B cell expression in PBMCs exhibited a similar trend.In asthmatic mice,the ratio of Tfh cells in the peripheral blood showed a strong positive correlation with the IgE levels in the serum and BALF,but not with the IgG1 levels.Conclusion The amelioration of airway inflammation and airway hyper-responsiveness is achieved through Bcl-6 suppression,which effectively hinders Tfh cell differentiation,ultimately resulting in a concurrent reduction in IgE production.

小鼠视神经损伤后视网膜中TLR-9与MyD88表达变化

目的:探讨Toll样受体-9(TLR-9)与髓样分化因子(MyD88)在小鼠视神经损伤(ONI)后视网膜中的表达变化。方法:选取8周大小的雄性C57BL/6J小鼠36只,随机分为6组:空白对照组(未做任何处理)、ONI 1d组(视神经损伤后1d取材)、ONI 3d组(视神经损伤后3d取材)、ONI 5d组(视神经损伤后5d取材)、ONI 7d组(视神经损伤后7d取材)、ONI 14d组(视神经损伤后14d取材)。分组后通过视神经夹持的方法制作小鼠视神经损伤模型,利用RT-qPCR与Western-blot检测各组小鼠视网膜中TLR-9与MyD88的mRNA和蛋白水平。结果:ONI 1d组视网膜中TLR-9与MyD88的mRNA和蛋白水平与空白对照组比较无差异(P>0.05);ONI 3d、ONI 5d、ONI 7d、ONI 14d组视网膜中TLR-9与MyD88的mRNA和蛋白水平与空白对照组比较均明显增加(P<0.01)。与空白对照组比较视网膜中TLR-9与MyD88的mRNA和蛋白水平在小鼠ONI 3d开始升高(P<0.01),ONI 5d达到峰值(P<0.001),ONI 7d开始逐渐下降(P<0.01)。结论:小鼠视神经损伤能够激活视网膜中TLR-9与MyD88表达,TLR-9与MyD88可能在视神经损伤的进程中起重要作用。

2型糖尿病肠黏膜屏障损伤研究及治疗进展

2型糖尿病(T2DM)的发病率较高,但其病因和发病机制尚未完全阐明。随着微生态技术的发展,肠道屏障功能与T2DM的联系受到越来越多的关注。肠黏膜屏障在维持机体内环境和抵御外来病原菌入侵等生理功能方面具有重要作用。因此,肠黏膜屏障很可能是治疗T2DM的重要位点,该文将综述肠黏膜屏障损伤在T2DM中的发生、发展及治疗方面的作用,旨在为T2DM的治疗提供新的思路。

Meta-analysis of late course accelerated hyperfractionated radiotherapy combined with FP chemotherapy for esophageal carcinoma

Background and Objective:Although there are many randomized clinical trials of late course accelerated hyperfractionated radiotherapy (LCAHFR) combined with FP chemotherapy for esophageal cancer, the efficacy and toxicity are controversial. This study was to evaluate the efficacy and toxicity of LCAHFR combined with FP chemotherapy in treating esophageal cancer. Methods: Reports of randomized clinical trials on LCAHFR combined with FP chemotherapy for esophageal cancer published between January 1999 and January 2009 were researched through Wanfang, CNKI, and PubMed databases. RevMan4.2 software was used for Meta-analysis. Results: Twenty-one reports, including 2030 patients, were included in the meta-analysis. Of the 2030 patients, 1006 underwent LCAHFR (LCAHFR group), and 1024 underwent LCAHFR combined with FP chemotherapy (combination group). Compared with those of the LCAHFR group, the 1-, 2-, 3-, 5-years survival rates and 1-, 2-, 3-year local control rates of the combination group were significant increased, and the acute toxicity was also increased, but chronic toxicity showed no significant difference. C onclusions: LCAHFR combined with FP chemotherapy can improve the survival rate and the local control rate of the patients with esophageal cancer. The increased acute toxicity need to be concerned, whereas the chronic toxicity needs a long-term observation.

Synchronous diagnosis and treatment of acute myeloid leukemia and chronic lymphocytic leukemia:Two case reports

BACKGROUND The concurrence of acute myeloid leukemia(AML)and chronic lymphocytic leukemia(CLL)is rare.Previous reports of such cases have focused mainly on clinical diagnosis and characteristics,so the mechanism remains unclear,and therapy options have been poorly explored.CASE SUMMARY Here,we report two cases of synchronous AML and CLL.Flow cytometry revealed two distinct abnormal cell populations(myeloblasts and lymphoid cells)according to scatter characteristics.CD5-positive B cell lymphoma with myeloid leukemia invasion was observed on lymph node biopsy.Chemotherapy regimens indicated for both AML and CLL were used in our patients,and our patients achieved complete response after chemotherapy.Next-generation sequencing of 88 genes was performed.CONCLUSION We conclude that early mutation and dysregulation at the hematopoietic stem cell stage and the accumulation of multiple rearrangements may cause the concurrence of CLL and AML.The treatment of infection and combination therapy aimed at the CLL component are significant in the management of patients with concurrent CLL and AML.

A new diagnostic model of primary open angle glaucoma based on FD-OCT parameters

AIM： To build a clinical diagnostic model of primary open angle glaucoma （POAG） using the normal probability chart of frequency-domain optical coherence tomography （FD-OCT）. METHODS： This is a cross-sectional study. Total 133 eyes from 133 healthy subjects and 99 eyes from 99 early POAG patients were included in the study. The retinal nerve fibre layer （RNFL） thickness parameters of optic nerve head （ONH） and RNFL3.45 scan were measured in one randomly selected eye of each subject using RTVue-100 FD-OCT. Then, we used these parameters to establish the diagnostic models. Four different diagnostic models based on two different area partition strategies on ONH and RNFL3.45 parameters, including ONH traditional area partition model （ONH-T）, ONH new area partition model （ONH-N）, RNFL3.45 traditional area partition model （RNFL3.45-T） and RNFL3.45 new area partition model （RNFL3.45-N）, were built and tested by cross-validation. RESULTS： The new area partition models had higher area under the receiver operating characteristic （AROC; ONH-N： 0.990; RNFL3.45-N： 0.939） than corresponding traditional area partition models （ONH-T： 0.979; RNFL3.45-T： 0.881）. There was no statistical difference among AROC of ONH-T, ONH-N, and RNFL3.45-N. Nevertheless, ONH-N was the simplest model. CONCLUSION： The new area partition models had higher diagnostic accuracy than corresponding traditional area partition models, which can improve the diagnostic ability of early POAG. In particular, the simplest ONH-N diagnostic model may be convenient for clinical application.

Age and mean platelet volume-based nomogram for predicting the therapeutic efficacy of metoprolol in Chinese pediatric patients with vasovagal syncope

Background Vasovagal syncope(VVS)is the most common type of orthostatic intolerance in children.We investigated whether platelet-related factors related to treatment efficacy in children suffering from VVS treated with metoprolol.Methods Metoprolol-treated VVS patients were recruited.The median duration of therapy was three months.Patients were followed and divided into two groups,treament-effective group and treatment-ineffective group.Logistic and least absolute shrinkage selection operator regressions were used to examine treatment outcome variables.Receiver-operating characteristic(ROC)curves,precision-recall(PR)curves,calibration plots,and decision curve analyses were used to evaluate the nomogram model.Results Among the 72 patients who complete the follow-up,treatment-effective group and treatment-ineffective group included 42(58.3%)and 30(41.7%)cases,respectively.The patients in the treatment-effective group exhibited higher mean platelet volume(MPV)[(11.0±1.0)fl vs.(9.8±1.0)fl,P<0.01]and platelet distribution width[12.7%(12.3%,14.3%)vs.11.3%(10.2%,12.2%),P<0.01]than those in the treatment-ineffective group.The sex ratio was significantly different(P=0.046).A fit model comprising age[odds ratio(OR)=0.766,95%confidence interval(CI)=0.594-0.987]and MPV(OR=5.613,95%CI=2.297-13.711)might predict therapeutic efficacy.The area under the curve of the ROC and PR curves was computed to be 0.85 and 0.9,respectively.The P value of the Hosmer-Lemeshow test was 0.27.The decision curve analysis confirmed that managing children with VVS based on the predictive model led to a net advantage ranging from 0.01 to 0.58.The nomogram is convenient for clinical applications.Conclusion A novel nomogram based on age and MPV can predict the therapeutic benefits of metoprolol in children with VVS.

Prediction of intravenous immunoglobulin resistance in Kawasaki disease in children

Background We aimed to explore predictive measures for intravenous immunoglobulin(IVIG)resistance in children with Kawasaki disease(KD).Methods Patients diagnosed with KD were enrolled in this study.Univariate analysis and multiple logistic regression were utilized to analyze the clinical features and laboratory results prior to IVIG-treatment of the two groups.Independent predictors of IVIG resistance were analyzed,and a predictive model for KD children with IVIG resistance was constructed.Results A total of 277 children with KD,180 boys and 97 girls,aged 2-128(median 23)months,were enrolled in the study.Compared with the IVIG-responsive group,the IVIG-resistant group had higher levels of the peripheral neutrophil count,mean platelet volume,mean platelet volume-to-lymphocyte ratio and C-reactive protein,and total serum bilirubin,but lower levels of peripheral lymphocyte count,serum albumin and serum prealbumin.Age(in months),peripheral neutrophil count,lymphocyte count and mean platelet volume and serum albumin were independent indicators for IVIG resistance by multivariate logistic regression analysis.A logistic regression model and a scoring system were set up,where cut-off values of—0.46 and 6.5 points yielded sensitivities of 83.9%and 77.4%,and specificities of 74.8%and 61.0%,respectively.The areas under the curve(AUC)were 0.808 in the logistic regression model,and 0.750 in the scoring system.Conclusion Our model for predicting IVIG-resistant children with KD,involving age(months),peripheral neutrophil count,lymphocyte count and mean platelet volume and serum albumin prior to IVIG-treatment,is helpful for clinical prediction of children with IVIG-resistant KD.

Body mass index is a promising predictor of response to oral rehydration saline in children with vasovagal syncope

Background:Vasovagal syncope(VVS)greatly impairs quality of life.The therapeutic efficacy of oral rehydration saline(ORS)for unselected VVS patients is not satisfactory due to the diverse mechanisms of the disease.Body mass index(BMI)was demonstrated to reflect blood volume to a certain extent.Therefore,the present study explored the capability of BMI to predict the therapeutic response of children with VVS to ORS treatment.Methods:Seventy-four children with VVS who visited the Syncope Unit of Pediatrics at Peking University First Hospital from November 2010 to June 2019 receiving ORS treatment were enrolled for this retrospective case-control study.A comparison of demographic,clinical,and hemodynamic characteristics was performed between responders and non-responders.The correlation between baseline BMI and response time was analyzed.To determine the value of baseline BMI in predicting the therapeutic efficacy of ORS in children with VVS,a receiver operating characteristic curve analysis was performed.Results:Fifty-two children were identified as responders,and the remaining 22 children were identified as non-responders.The baseline BMI of the responders was much lower than that of the non-responders(16.4[15.5,17.8]kg/m2vs.20.7±3.6 kg/m2,P<0.001),and baseline BMI was positively correlated with response time in the head-up tilt test after adjusting for sex(r=0.256,95%confidence interval[CI]:0.067-0.439,P=0.029).The area under the receiver operating characteristic curve of baseline BMI was 0.818(95%CI:0.704-0.932,P<0.001),and an optimal cut-off value of 18.9 kg/m2 yielded a sensitivity of 83%and a specificity of 73%to predict the efficacy of ORS in VVS.Conclusion:Prior to treatment,baseline BMI is a promising predictor of response to ORS in children with VVS.

A predictive model of response to metoprolol in children and adolescents with postural tachycardia syndrome

Background The present work was designed to explore whether electrocardiogram(ECG)index-based models could predict the effectiveness of metoprolol therapy in pediatric patients with postural tachycardia syndrome(POTS).Methods This study consisted of a training set and an external validation set.Children and adolescents with POTS who were given metoprolol treatment were enrolled,and after follow-up,they were grouped into non-responders and responders depending on the efficacy of metoprolol.The difference in pre-treatment baseline ECG indicators was analyzed between the two groups in the training set.Binary logistic regression analysis was further conducted on the association between significantly different baseline variables and therapeutic efficacy.Nomogram models were established to predict therapeutic response to metoprolol.The receiver-operating characteristic curve(ROC),calibration,and internal validation were used to evaluate the prediction model.The predictive ability of the model was validated in the external validation set.Results Of the 95 enrolled patients,65 responded to metoprolol treatment,and 30 failed to respond.In the responders,the maximum value of the P wave after correction(Pcmax),P wave dispersion(Pd),Pd after correction(Pcd),QT interval dis-persion(QTd),QTd after correction(QTcd),maximum T-peak-to-T-end interval(Tpemax),and T-peak-to-T-end interval dispersion(Tped)were prolonged(all P<0.01),and the P wave amplitude was increased(P<0.05)compared with those of the non-responders.In contrast,the minimum value of the P wave duration after correction(Pcmin),the minimum value of the QT interval after correction(QTcmin),and the minimum T-peak-to-T-end interval(Tpemin)in the responders were shorter(P<0.01,<0.01 and<0.01,respectively)than those in the non-responders.The above indicators were screened based on the clinical significance and multicollinearity analysis to construct a binary logistic regression.As a result,pre-treatment Pcmax,QTcmin,and Tped were identified as significantly associated factors that could be combined to provide an accurate prediction of the therapeutic response to metoprolol among the study subjects,yielding good discrimination[area under curve(AUC)=0.970,95%confidence interval(CI)0.942-0.998]with a predictive sensitivity of 93.8%,specificity of 90.0%,good calibration,and corrected C-index of 0.961.In addition,the calibration curve and standard curve had a good fit.The accuracy of internal validation with bootstrap repeated sampling was 0.902.In contrast,the kappa value was 0.769,indicating satisfactory agreement between the predictive model and the results from the actual observations.In the external validation set,the AUC for the prediction model was 0.895,and the sensitivity and specificity were 90.9%and 95.0%,respectively.Conclusions A high-precision predictive model was successfully developed and externally validated.It had an excellent predictive value of the therapeutic effect of metoprolol on POTS among children and adolescents.

Increased Risk of Psychiatric Disorders in Women with Polycystic Ovary Syndrome in Southwest China

Background： Polycystic ovary syndrome （PCOS） and its characteristic symptoms have been associated with physical and psychological issues in women of reproductive age. The current study was conducted in response to the dearth of systematic research related to psychological functioning and quality of life in patients with PCOS in Southwest China, and to determine whether patients with PCOS exhibit poorer mental health （MH） compared to healthy women of the same age and living in the same region, without a PCOS diagnosis. Methods： We enrolled 120 outpatients with PCOS and 100 healthy controls in this study. Standardized questionnaires were administered to assess general MH conditions （General Health Questionnaire-12-item version）, anxiety （State-Trait Anxiety Inventory）, depression （Beck Depression Inventory）, as well as health-related quality of life （HRQoL） measured using the 36-item short-form health survey. The independent samples t-test was conducted for continuous study variables. For categorical variables, the Pearson Chi-square test, Fisher＇s exact test, and logistic regression were perlbrmed. Results： The prevalence of anxiety （13.3% vs. 2.0%） and depression （27.5% vs. 3.0%） was higher in patients with PCOS compared to the controls （both P 〈 0.05）. Patients with PCOS had decreased HRQoL. Patients with PCOS who had fertility requirements were more likely to be anxious and depressed than those without fertility requirements （anxiety： 22.6% [1 2/53] vs. 5.9% [4/67],Z： = 7.117, P = 0.008： depression： 37.7% （20/53） vs. 19.4% （13/67）, Х^2 = 4.988, P - 0.026）. Conclusions： PCOS and related synaptoms may be risk factors for depression and anxiety. Professionals should be concerned with the MH of women with PCOS, and psychological therapy should be considered.

Effect of Inhaled Budesonide on Interleukin-4 and Interleukin-6 in Exhaled Breath Condensate of Asthmatic Patients

Background： Studies of interleukin （IL）-4 and IL-6 in the exhaled breath condensate （EBC） of asthmatic patients are limited. This study was to determine the effect of inhaled corticosteroid （ICS） treatment on IL-4 and IL-6 in the EBC ＆asthmatic patients. Methods： In a prospective, open-label study, budesonide 200 μg twice daily by dry powder inhaler was administered to 23 adult patients with uncontrolled asthma （mean age 42.7 years） for 12 weeks. Changes in asthma scores, lung function parameters （forced expiratory volume in 1 s [FEV1], peak expiratory flow [PEF], forced expiratory flow at 50% of forced vital capacity [FEFs0], forced expiratory flow at 75% of forced vital capacity, maximum mid-expiratory flow rate） and the concentrations of IL-4 and IL-6 in EBC were measured. Results： Both asthma scores and lung function parameters were significantly improved by ICS treatment. The mean IL-4 concentration in the EBC was decreased gradually, from 1.92 ± 0.56 pmol/L before treatment to 1.60 ± 0.36 pmolJL after 8 weeks of treatment （P 〈 0.05） and 1.54 ± 0.81 pmol/L after 12 weeks of treatment （P 〈 0.01）. However, the IL-6 concentration was not significantly decreased. The change in the IL-4 concentration was correlated with improvements in mean FEVt, PEF and FEFso values （correlation coefficients -0.468, -0.478, and -0.426, respectively）. Conclusions： The concentration of IL-4 in the EBC of asthmatic patients decreased gradually with ICS treatment. Measurement of IL-4 in EBC could be useful to monitor airway inflammation in asthmatics.

Endoscopic or laparoscopic resection for small gastrointestinal stromal tumors: a cumulative meta-analysis

Background:Despite the recent large number of studies comparing endoscopic and laparoscopic resection for small gastrointestinal stromal tumors(GISTs)(diameter≤5 cm),the results remain conflicting.The objective of this work was to perform a cumulative meta-analysis to assess the advantages and disadvantages of endoscopic resection vs.laparoscopic resection.Methods:The meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.We searched medical databases up to January 2020.Meta-analytical random or fixed effects models were used in pooled analyses.Meta-regression,cumulative meta-analyses,and sub-group analyses were performed to improve the accuracy of the conclusion.Sensitivity analyses were applied to assess the robustness of the results.Results:A total of 12 cohort studies with 1383 participants comparing endoscopic resection and laparoscopic resection were identified,while three cohort studies with 167 participants comparing endoscopic resection and laparoscopic and endoscopic cooperative surgery were found.We found that endoscopic resection had shorter operation times(weighted mean difference[WMD]=-27.1 min,95%confidence interval[CI]:-40.8 to-13.4 min)and lengths of hospital stay(WMD=-1.43 days,95%CI:-2.31 to-0.56 days)than did laparoscopic resection.The results were stable and reliable.There were no significant differences in terms of blood loss,hospitalization costs,incidence of complications or recurrence rates.For tumor sizes 2 to 5 cm,endoscopic resection increased the risk of positive margins(relative risk[RR]=5.78,95%CI:1.31-25.46).Although operation times for endoscopic resection were shorter than those of laparoscopic and endoscopic cooperative surgery(WMD=-41.03 min,95%CI:-59.53 to-22.54 min),there was a higher incidence of complications(RR=4.03,95%CI:1.57-10.34).Conclusions:In general,endoscopic resection is an alternative method for gastric GISTs≤5 cm.Laparoscopic and endoscopic cooperative surgery may work well in combination.Further randomized controlled trials are recommended to validate or update these results.

The DIRECT consortium and the REST-meta-MDD project:towards neuroimaging biomarkers of major depressive disorder

Despite a growing neuroimaging literature on the pathophysiology of major depressive disorder(MDD),repro-ducible findings are lacking,probably reflecting mostly small sample sizes and heterogeneity in analytic approaches.To address these issues,the Depression Imaging REsearch ConsorTium(DIRECT)was launched.The REST-meta-MDD project,pooling 2428 functional brain images processed with a standardized pipeline across all participating sites,has been the first effort from DIRECT.In this review,we present an overview of the moti-vations,rationale,and principal findings of the studies so far from the REST-meta-MDD project.Findings from the first round of analyses of the pooled repository have included alterations in functional connectivity within the default mode network,in whole-brain topological properties,in dynamic features,and in functional lat-eralization.These well-powered exploratory observations have also provided the basis for future longitudinal hypothesis-driven research.Following these fruitful explorations,DIRECT has proceeded to its second stage of data sharing that seeks to examine ethnicity in brain alterations in MDD by extending the exclusive Chinese original sample to other ethnic groups through international collaborations.A state-of-the-art,surface-based preprocessing pipeline has also been introduced to improve sensitivity.Functional images from patients with bipolar disorder and schizophrenia will be included to identify shared and unique abnormalities across diag-nosis boundaries.In addition,large-scale longitudinal studies targeting brain network alterations following antidepressant treatment,aggregation of diffusion tensor images,and the development of functional magnetic resonance imaging-guided neuromodulation approaches are underway.Through these endeavours,we hope to accelerate the translation of functional neuroimaging findings to clinical use,such as evaluating longitudinal effects of antidepressant medications and developing individualized neuromodulation targets,while building an open repository for the scientific community.

Effect of solution pH,Cl- concentration and temperature on electrochemical behavior of PH13-8Mo steel in acidic environments

The effect of solution pH,Cl;concentration and temperature on the electrochemical corrosion behavior of PH13-8Mo steel in acidic solution was investigated by using the electrochemical tests,scanning electron microscopy and X-ray photoelectron spectroscopy.The PH13-8Mo martensitic precipitation hardened stainless steel is in the passivity state when the pH value is above 3.0,below which the anodic polarization curves of the steel are actively dissolved.The corrosion current density gradually decreases with increasing the solution pH and decreasing Cl;concentration and solution temperature.Pits are initiated on the sample surface in the presence of the Cl;and gradually developed into uniform corrosion with increasing the Cl;concentrations.Moreover,the corrosion is more serious with an increase in solution temperature.

Altered cerebral activities and functional connectivity in depression:a systematic review of fMRI studies

Background:As one of the leading causes of global disability,major depressive disorder(MDD)places a noticeable burden on individuals and society.Despite the great expectation on finding accurate biomarkers and effective treatment targets of MDD,studies in applying functional magnetic resonance imaging(fMRI)are still faced with challenges,including the representational ambiguity,small sample size,low statistical power,relatively high false positive rates,etc.Thus,reviewing studies with solid methodology may help achieve a consensus on the pathology of MDD.Methods:In this systematic review,we screened fMRI studies on MDD through strict criteria to focus on reliable studies with sufficient sample size,adequate control of head motion,and a proper multiple comparison control strategy.Results:We found consistent evidence regarding the dysfunction within and among the default mode network(DMN),the frontoparietal network(FPN),and other brain regions.However,controversy remains,probably due to the heterogeneity of participants and data processing strategies.Conclusion:Future studies are recommended to apply a comprehensive set of neuro-behavioral measurements,consider the heterogeneity of MDD patients and other potentially confounding factors,apply surface-based neuroscientific network fMRI approaches,and advance research transparency and open science by applying state-ofthe-art pipelines along with open data sharing.

Impact of comorbidities on the prognosis of pediatric vasovagal syncope

Vasovagal syncope(VVS)is the primary entity of neurally mediated syncope(NMS)in childhood,and its prognosis is usually considered benign.However,it is found in clini-cal practice that some children with VVS appear to have a frequent recurrence of syncope and poor response to treat-ment[1],which might seriously affect their quality of life[2].In recent years,an increasing number of comorbidities of VVS have been reported.Liao et al.found that 31%of pediatric patients with NMS suffered from allergic disease[3],and Vallejo M reported that more than 50%of patients had headaches[4].These comorbidities might make the clinical manifestations even more complex.However,until now,it has been unclear whether comorbidities are associated with the prognosis of children and adolescents suffering from VVS.Therefore,the present study was conducted to examine whether there is any impact of comorbidities on the prognosis of pediatric VVS to better understand the outcome and management of children and adolescents with VVS.