ObjectiveTo investigate the possible mechanism of Jishe Qushi Capsule （脊蛇祛湿胶囊， JQC） in treating rheumatoid arthritis （RA） from the perspective of macrophage polarization mediated by neutrophil extracellular traps （NETs）. MethodsTwenty-four female SD rats were randomly divided into four groups， blank control group， model group， JQC group， and peptidylarginine deiminase 4 （PAD4） inhibitor group with 6 rats in each group. All groups but the blank control group were subjected to the induction of collagen-induced arthritis （CIA）. After successful model establishment， rats in the JQC group received intragastric administration of JQC 1.47 g/kg daily； rats in the PAD4 inhibitor group received intraperitoneal injections of the PAD4 inhibitor 4 mg/kg weekly. Rats in the blank， model， and PAD4 inhibitor groups received 2 ml of pure water daily by gavage. All treatments lasted 4 weeks. Joint lesions of each group were assessed on day 7， 14， 21， 28， and 35 after model establishment， and arthritis index （AI） scores were recorded. At 24 h after the final administration， histopathology of knee joints， including HE staining， safranin O-fast green staining， and TRAP staining， was performed. Flow cytometry was used to detect the counts of M1 and M2 macrophages in peripheral blood. ELISA was used to determine serum levels of TRACP， NETs， TNF-α， IL-1β， and iNOS. Western Blotting and qRT-PCR were used to measure MPO， NE， RANKL， OPG， and p65 protein and mRNA expression in knee cartilage tissue. ResultsCompared with the blank control group， the model group showed increased AI scores （P＜0.05）， marked synovial inflammatory infiltration， angiogenesis， and bone-cartilage destruction， increased TRAP-positive osteoclasts， increased M1 macrophages and decreased M2 macrophages， elevated serum TRACP， NETs， TNF-α， IL-1β， and iNOS （P＜0.05）， elevated MPO， NE， RANKL， and p65 protein/mRNA expression and decreased OPG protein/mRNA expression in knee cartilage tissue （P＜0.05）. Compared with the model group， the JQC group exhibited improved synovial inflammation， angiogenesis， and bone-cartilage damage， reduced AI scores on day 21， 28， and 35， decreased osteoclast counts， decreased M1 macrophages and increased M2 macrophages， reduced serum TRACP， NETs， TNF-α， IL-1β， and iNOS （P＜0.05）， decreased MPO， NE， RANKL， and p65 protein/mRNA expression and increased OPG expression （P＜0.05）. Compared with the PAD4 inhibitor group， the JQC group showed significantly lower AI scores， reduced M1 macrophages， increased M2 macrophages （P＜0.05）， reduced serum TRACP， TNF-α， IL-1β， and iNOS， decreased MPO， RANKL， and p65 expression， and increased OPG levels （P＜0.05）. ConclusionThe therapeutic mechanism of JQC for RA may involve inhibition of NETs formation， downregulation of the RANKL/NF-κB signaling pathway， and regulation of macrophage M1/M2 polarization imbalance， thereby suppressing osteoclastogenesis and inflammatory bone destruction.

Objective:To evaluate the efficacy of curative esophagectomy versus definitive chemoradiotherapy (dCRT) in patients with clinical T1bN0M0 thoracic esophageal cancer.Methods:The propensity score matching (PSM) and retrospective cohort study was conducted. The clinico-pathological data of 163 patients with clinical T1bN0M0 thoracic esophageal cancer who were admitted to Henan Provincial People′s Hospital from January 2014 to December 2020 were collected. There were 125 males and 38 females, aged (58.9±7.0)years. Of 163 patients, 124 cases undergoing curative transthoracic esophagectomy were allocated into the radical resection group, 39 cases undergoing dCRT were allocated into the dCRT group. Observation indicators:(1) PSM and compari-son of clinicopathological characteristics of patients between the two groups after matching; (2) complications in the radical resection group and treatment status in the dCRT group; (3) survival analysis; (4) analysis of factors influencing patients′ prognosis. Comparison of measurement data with normal distribution between groups was conducted using the Welch t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the Mann-Whitney U test. The Cox proportional hazard model was used for univariate and multivariate analyses. The Kaplan-Meier method was used to calculate survival rate and plot survival curve, and Log-rank test was used for survival analysis. PSM was performed using the 2∶1 nearest neighbor matching method. The caliper value was set as 0.05. Results:(1) PSM and comparison of clinicopathological charac-teristics of patients between the two groups after matching. Of the 163 patients, 117 cases were successfully matched, with 78 cases in the radical resection group and 39 cases in the dCRT group. After PSM, the elimination of tumor differentiation degree confounding bias ensured comparability. (2) Complications in the radical resection group and treatment status in the dCRT group.Among the 78 patients in the curative esophagectomy group, 22 cases developed complications within 30 days after surgery. There was no death within 30 days after surgery. Among the 39 patients in the dCRT group, 25 cases received concurrent chemoradiotherapy alone, 8 cases received induction chemo-therapy followed by concurrent chemoradiotherapy, 3 cases received sequential chemoradiotherapy, and 3 cases received radiotherapy alone. Among the 33 patients who received concurrent chemo-radiotherapy, 29 cases were treated with the XP regimen, and 4 cases with the FP regimen. Efficacy evaluation showed that 37 patients achieved complete remission, and 2 patients had residual lesions. Twenty-two patients developed treatment-related adverse reactions. (3) Survival analysis. After PSM, the follow-up duration was 58(range, 13-125)months in the radical resection group and 56(range, 10-129)months in the dCRT group. The postoperative 5-year overall survival rates were 95.7% and 97.1% in the radical resection group and dCRT group, respectively, showing no significant difference between the two groups ( χ2=0.001, P>0.05). The postoperative 5-year disease-free progression survival rates were 88.2% and 94.2% in the radical resection group and dCRT group, respectively, showing no significant difference between the two groups ( χ2=0.652, P>0.05). (4) Analysis of factors influencing patients prognosis. Age and pathological TNM stage were indepen-dent influencing factors for overall survival time in patients with clinical T1bN0M0 thoracic esophageal cancer ( hazard ratio=1.312, 2.945, 95% confidence interval as 1.042-1.711, 2.204-5.517, P<0.05). Age and pathological TNM stage were independent influencing factors for disease-free survival time in patients with clinical T1bN0M0 thoracic esophageal cancer ( hazard ratio=1.215, 3.301, 95% confidence interval as 1.012-1.699, 2.012-6.321, P<0.05). Conclusions:There is no significant difference in overall survival and disease-free survival between patients with clinical T1bN0M0 thoracic esophageal cancer undergoing curative esophagectomy and dCRT. The treatment modality is not an independent prognostic factor.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Objective To investigate the underlying mechanism of Hongyu Decoction in the treatment of inflammatory bowel disease(IBD)based on serum amino acid metabolism.Methods A total of 50 male C57BL/6J mice were divided into control group,model group,sulfasalazine(SASP)group and Hongyu Decoction low-and high-dosage groups,with 10 mice in each group.Except for the control group,the rest groups were treated with 3%dextran sulfate sodium freely for seven consecutive days to establish the IBD model.The SASP group was given SASP solution at a dosage of 200 mg/kg by gavage,while the Hongyu Decoction low-and high-dosage groups were given Hongyu Decoction freeze-dried powder solution at dosages of 0.5 and 2.0 g/kg respectively by gavage for 11 consecutive days.The general condition was monitored and DAI score were calculated.After the mice were sacrificed,the length of colons was measured,ELISA was used to detect serum TNF-α,IL-1β,IL-17 contents,HE staining was used to observe the morphology of colon tissue,and Alizarin blue staining was used to evaluate the secretion of mucin levels by intestinal epithelial goblet cells,UPLC-MS and multivariate statistical methods were used to analyze the serum amino acid metabolism profiles of mice in the control group,model group and Hongyu Decoction high-dosage group,and differential amino acids were screened.Pathway enrichment analysis was performed on differential amino acids using MetaboAnalyst 5.0.Results Compared with the control group,the DAI score of the model group mice significantly increased(P<0.001),the colon length was significantly shortened(P<0.001),and the serum contents of TNF-α,IL-1β and IL-17 significantly increased(P<0.001);with widespread ulceration of colon tissue,disappearance of mucosal epithelium and intestinal crypt structure,infiltration of lymphocytes and neutrophils,congestion and edema of intestinal mucosa,proliferation of submucosal connective tissue,reduced number of colonic goblet cells and mucin secretion.Compared with the model group,the Hongyu Decoction high-dosage group showed a significant decrease in DAI score(P<0.001),while the SASP group and the Hongyu Decoction low-and high-dosage groups showed a significant increase in colon length(P<0.05,P<0.001),and the serum contents of TNF-α,IL-1β and IL-17 were significantly reduced(P<0.001);the colonic villi were relatively intact,the glands were clear and arranged neatly,the branches of the intestinal crypts were obvious,no obvious edema was observed,and the number of colonic goblet cells and mucin secretion increased.Seven potential biomarkers for IBD in mice were identified through serum metabolomics screening,including tryptophan,serine,glutamate,valine,histidine,methionine and phenylalanine;two potential biomarkers for the treatment of IBD with Hongyu Decoction were identified,namely valine and tyrosine.The results of pathway enrichment analysis showed that the differential amino acids in the model group mainly involved the biosynthesis of phenylalanine,tyrosine and tryptophan,histidine metabolism,cysteine and methionine metabolism,phenylalanine metabolism and arginine biosynthesis;the differential amino acids in Hongyu Decoction high-dosage group mainly involved the biosynthesis of phenylalanine,tyrosine and tryptophan,as well as the metabolism of alanine,aspartate and glutamate,and the biosynthesis of arginine.Conclusion Hongyu Decoction can improve intestinal epithelial damage and inflammatory cell infiltration in IBD mice,protect the integrity of the intestinal mucosal barrier,and may be related to regulating amino acid metabolism in the body.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.

Objective:To compare the efficacy and safety of crisaborole ointment 2% versus pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged 2 years or older.Methods:A multicenter, randomized, open-label, controlled clinical trial was conducted. A total of 120 pediatric patients aged 2 - 17 years with mild to moderate atopic dermatitis were enrolled from departments of dermatology of 8 hospitals in China between March 2022 and February 2023. The participants were randomly assigned in a 1∶1 ratio to the crisaborole group and the pimecrolimus group, and received the treatment with crisaborole ointment 2% and pimecrolimus cream 1% respectively, twice a day for 4 weeks. Visits were scheduled at baseline/on day 1, as well as on days 8, 15, and 29. The primary efficacy outcome was the percentage of patients achieving the Investigator's Static Global Assessment (ISGA) success (defined as clear [0] or almost clear [1] on the ISGA scale, combined with ≥ 2‐grade improvement from baseline) on day 29. The secondary efficacy outcomes included changes in the Eczema Area and Severity Index (EASI) total scores from baseline to day 29, percentages of patients achieving ISGA improvement (defined as clear [0] or almost clear [1] on the ISGA scale), as well as changes in the Peak Pruritus Numerical Rating Scale (NRS) scores, Dermatology Life Quality Index (DLQI) /Infants' Dermatology Life Quality Index (IDLQI) /Children's Dermatology Life Quality Index (CDLQI) scores, and in the Dermatitis Family Impact (DFI) scores. Drug safety was evaluated according to the incidence of adverse events. Categorical data were compared using the chi-square test. Since measurement data did not follow a normal distribution, the rank sum test was used for comparisons of measurement data between groups.Results:A total of 106 children with mild to moderate atopic dermatitis were included in the per-protocol analysis set, with 52 in the crisaborole group (26 males and 26 females) and 54 in the pimecrolimus group (27 males and 27 females). There were no significant differences in age, disease duration, ISGA and EASI scores at baseline between the two groups (all P > 0.05). On day 29, 22 patients (42.31%) in the crisaborole group and 25 (46.30%) in the pimecrolimus group achieved ISGA success, with no significant difference between the two groups ( χ2 = 0.17, P = 0.68) ; 35 patients (67.31%) in the crisaborole group and 45 (83.33%) in the pimecrolimus group achieved ISGA improvement, also with no significant difference between the two groups ( χ2 = 3.68, P = 0.06) ; additionally, there were no significant differences in the EASI, pruritus NRS, DLQI/IDLQI/CDLQI, or DFI scores between the two groups (all P > 0.05). Adverse reactions to the two topical agents were mainly local reactions such as mild to moderate pain, itching, or worsening of itching, and no obvious systemic adverse reactions occurred. The incidence of drug-related adverse reactions was 46.15% (24 cases) in the crisaborole group and 37.04% (20 cases) in the pimecrolimus group, with no significant difference between the two groups ( χ2 = 0.91, P = 0.34) . Conclusion:The efficacy of crisaborole ointment 2% was comparable to that of pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged ≥ 2 years, and it yielded early and rapid improvement in the quality of life of patients and their families, with good safety and tolerability profiles.

Objective:To explore the trend of influenza positive rate in Beijing by using classic autoregressive integrated moving average (ARIMA) model, autoregressive integrated moving average model with exogenous variables (ARIMAX) and vector autoregression model (VAR) to compare the performance of three models in influenza prediction and select the most suitable one for Beijing.Methods:The weekly positive rate of influenza virus nucleic acid test and meteorological data in Beijing from week 1 of 2013 to week 40 of 2024 were collected. The data were divided into four groups with expanding training sets and corresponding testing sets. The training set of the first group was from week 1 of 2013 to week 40 of 2016, and the testing set was from week 41 of 2016 to week 40 of 2017. Subsequent groups extended the training set by one year each time. Data from 2020 to 2023 were excluded due to COVID-19 pandemic. The fourth group used data from the week 1 of 2013 to week 40 of 2023 for training and from the week 41 of 2023 to week 40 of 2024 for testing.Results:The incidence of influenza had seasonality in Beijing with higher incidence in winter and spring. The positive rate of influenza virus was positively correlated with the weekly average atmospheric pressure ( r=0.482, P<0.001) and weekly average wind speed ( r=0.003, P=0.034), and negatively correlated with the weekly average temperature ( r=-0.541, P<0.001). The ARIMAX model incorporating meteorological factors had the best prediction performance, with test set's root mean square error ( RMSE) of 0.115 3 and mean absolute error ( MAE) of 0.076 7 (the RMSE and MAE values for ARIMA and VAR models were 0.117 1 and 0.163 8, and 0.078 6 and 0.122 3, respectively). The prediction results of the optimal model showed that the positive rate of influenza virus would continue to rise in Beijing after October 2024 and reach peak in the second week of 2025, but the peak positive rate would be lower than that of previous influenza season. Conclusions:Compared with the ARIMA model and the VAR model,the ARIMAX model which used meteorological parameters is more suitable for prediction of long-term influenza trend in Beijing. The influenza trend peak was predicted to occur in the second week of 2025, but lower than that in previous influenza season.

AIM: To investigate the impact of corneal fluorescein sodium(NaF)staining on the examination results of iTrace visual function analyzer(iTrace).METHODS: Prospective cohort study. Totally 100 patients(100 eyes)with ametropia who visited the outpatient department of Anhui Eye Hospital from April to November 2024 were recruited. They were divided into an experimental group and a control group, with 50 patients(50 eyes, and only the right eyes were selected for inclusion)in each group. In the experimental group, corneal staining was performed using fluorescein sodium staining test strips, while in the control group, 1 drop of 0.9% normal saline was instilled into the eyes. The iTrace examination was conducted before the intervention and at 5, 10, and 20 min after the intervention. The total corneal higher-order aberrations, spherical aberration, coma aberration, trefoil aberration, best sphere value(RO value), asphericity factor(Q value), and corneal vertical refractive power difference(IS value)at each time of examination were recorded and compared.RESULTS: There was no statistically significant difference in the baseline levels between the two groups(all P>0.05). Intra-group comparison revealed that the total higher-order aberrations, spherical aberration, coma aberration, and trefoil aberration measured 5 min after NaF staining in the experimental group were significantly increased compared with those before staining(all P<0.05). Inter-group comparison showed that the changes(differences from the baseline)in the total corneal higher-order aberrations, spherical aberration, coma aberration, and trefoil aberration measured by iTrace 5 min after the intervention in the experimental group were significantly greater than those in the control group(all P<0.05). There was no statistically significant difference in the changes(differences from the baseline)of various iTrace parameters measured at 10 and 20 min after the intervention between the two groups(all P>0.05). There was no statistical significance in the RO value, Q value, and IS value in the two groups(all P>0.05).CONCLUSION: Corneal NaF staining can cause a short-term increase in the wavefront aberration values(total corneal higher-order aberrations, spherical aberration, coma aberration, trefoil aberration)measured by iTrace, and it gradually disappears with the passage of time. However, it has no impact on the measurement of corneal topography parameters(RO value, Q value, IS value).

Objective:To investigate factors influencing frequent episodes (≥ 4 episodes within 1 year) in children with moderate-to-severe atopic dermatitis (AD) in China.Methods:A national multicenter cross-sectional study was conducted. Patients under the age of 18 years diagnosed with moderate-to-severe AD were enrolled at dermatology clinics in 18 medical institutions across 12 provinces and municipalities in China between June 12 and August 8, 2023. At the time of the visit, their guardians completed a structured questionnaire covering demographic characteristics, clinical features of AD, personal and family history, factors associated with frequent episodes of moderate-to-severe AD, compliance with treatment, and disease awareness. Statistical analyses included t tests, one-way analysis of variance, rank-sum tests, and chi-square tests, with multiple-response analysis applied for multiple-choice questions. Results:A total of 965 valid questionnaires were collected, and 965 children with moderate-to-severe AD were included. Among them, there were 531 males and 434 females, 678 (70.3%) were aged 2 - < 12 years, 837 (86.7%) were from urban areas, the age at onset was 2.47 ± 3.03 years, and the median frequency of AD episodes in the past year was 4 times. These children were divided into 2 groups based on the median episode frequency: < 4-episode group (439 cases, 45.5%) and ≥ 4-episode group (526 cases, 54.5%). Compared with the < 4-episode group, children in the ≥ 4-episode group showed younger ages at onset (2.22 ± 2.98 years vs. 2.76 ± 3.06 years, P = 0.006) and higher proportions of patients with comorbid allergic diseases in both the children themselves (82.9% [436/526] vs. 69.7% [306/439], χ2 = 23.42, P < 0.001) and their relatives (66.0% [347/526] vs. 57.4% [252/439], χ2 = 7.46, P = 0.006). Children in the ≥ 4- episode group also had higher monthly usage of moisturizers (150 [30, 300] g vs. 60 [6, 200] g) and daily frequency of moisturizer use, greater disease awareness, but more severe fear of medication use (all P < 0.05). The region and the human development index level were both significantly associated with the episode frequency (both P < 0.001), with the highest proportion of children from South China in the ≥ 4- episode group (36.3%, 191/526). Children in the ≥ 4-episode group also had a longer duration of topical glucocorticoid use than those in the < 4-episode group ( Z = -2.21, P = 0.027). External triggers associated with AD episodes mainly included heat exposure (50.36%, 486/965), hot water bathing (40.73%, 393/965), seafood (23.52%, 227/965), and dust mites (33.37%, 322/965) . Conclusion:In children with moderate-to-severe AD in China, factors influencing frequent episodes may include residence in southern or economically developed regions, earlier age at onset, having a personal or family history of allergic diseases, and fear of medication use.