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    15 July 2022 Volume 40 Issue 7
      
    Commentary
    Research status of predictive model for IVIG resistance in Kawasaki disease
    HUANG Yujuan, HUANG Min
    Journal of Clinical Pediatrics. 2022, 40(7):  481-487.  doi:10.12372/jcp.2022.22e0740
    Abstract ( 343 )   HTML ( 42 )   PDF (1132KB) ( 226 )  
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    Kawasaki disease (KD) is an acute autoimmune systemic vasculitis, which is the leading cause of acquired heart disease in children in developed countries. The most serious consequence of KD is coronary artery diseases (CALs), which is associated with the prognosis of KD. Studies have confirmed that intravenous immunoglobulin (IVIG) resistance is an independent risk factor for CALs. In recent years, a series of predictive models have been developed to assess the risk of IVIG resistance. However, at present, the IVIG drug resistance prediction scoring system based on the demographic characteristics, clinical manifestations, laboratory tests and genetic characteristics of KD children has significant differences among different ethnic groups and among populations in different regions of the same ethnic group, and no prediction model suitable for the general population has been established.

    Expert Review
    Diagnosis and treatment of postural tachycardia syndrome in children
    LIAO Ying
    Journal of Clinical Pediatrics. 2022, 40(7):  488-493.  doi:10.12372/jcp.2022.22e0412
    Abstract ( 568 )   HTML ( 38 )   PDF (1248KB) ( 216 )  
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    Postural orthostatic tachycardia syndrome (POTS) is a group of clinical syndromes characterized by chronic orthostatic intolerance and an excessive orthostatic heart rate increment. It is common both in children and adolescents and it can significantly affect children's learning and quality of life. POTS symptoms involve multiple systems and can be associated with multiple comorbidities. Since the clinical manifestations are complex, detailed history taking, correct interpretation of the results of standing test, careful differential diagnosis as well as comprehensive assessment of comorbidities are required when make a diagnosis of POTS for children. The pathogenesis of POTS mainly includes three core mechanisms: central hypovolemia, hyperadrenergic state and vascular dysfunction (partial autonomic neuropathy). In the treatment of POTS children, non-pharmacological therapy should be used as the basis. The main pathogenesis should be evaluated according to the clinical characteristics and certain biomarkers of the children, and attention should be paid to the management of comorbidities, so as to carry out individualized comprehensive treatment.

    Research status of cardiac autonomic nervous system regulation in vasovagal syncope in children
    XU Meng, XIE Lijian
    Journal of Clinical Pediatrics. 2022, 40(7):  494-499.  doi:10.12372/jcp.2022.22e0413
    Abstract ( 283 )   HTML ( 26 )   PDF (1147KB) ( 223 )  
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    Vasovagal syncope (VVS) is the commonest type of autonomic nerve mediated syncope, and the pathogenesis of VVS is complex. The autonomic nervous system consists of the sympathetic nervous system and the parasympathetic nervous system. The two systems keep the cardiac balance. It is generally accepted that VVS has the imbalance of cardiac autonomic nerve regulation. In this paper, we summarize the research results about the role of cardiac autonomic nerves and their major neurotransmitters, application of cardiac autonomic nerve function tests, and treatment of autonomic nerve dysfunction in VVS.

    Cardiovascular Disease
    Changes and significance of dendritic cell subsets in children with Kawasaki disease
    WANG Nana, MENG Lijun, ZHANG Qianwen, ZHANG Fan, HOU Miao, CHEN Ye, WANG Bo, YAN Wenhua, LYU Haitao, SUN Ling, HUANG Jie
    Journal of Clinical Pediatrics. 2022, 40(7):  500-504.  doi:10.12372/jcp.2022.21e1680
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    Objective To investigate the changes of dendritic cell (DC) subsets in children with acute Kawasaki disease (KD) and their significance. Methods The clinical data of children with initial acute KD from December 2020 to May 2021 were retrospectively analyzed. Blood samples of KD children were taken before and after intravenous immunoglobulin (IVIG) treatment. Flow cytometry was used to detect the number and proportion of DC subgroup plasmacytoid dendritic cells (pDC) and CD1c+ myeloid dendritic cells (mDC) in peripheral blood as well as the expression levels of human leucocyte antigen-DR (HLA-DR), CD86 and CD40 proteins. Children who underwent physical examination at the same period were selected as the control group. Results There were 32 children (19 boys and 13 girls) in the KD group, and the median age was 37.0 (22.3-58.5) months. In the control group, there were 23 children (14 boys and 9 girls) and the median age was 52.0 (30.0-65.0) months. The proportion of pDC and CD1c+mDC in peripheral blood DCs before and after IVIG treatment in KD group was lower than that in control group, and the proportion of CD1c+mDC in peripheral blood DCs after treatment was higher than that before treatment. The number of pDC and CD1c+mDC in pre-treatment group was lower than that in control group and post-treatment group, and the differences were statistically significant (P<0.05). The expression levels of CD86 and CD40 on pDC surface and the expression levels of HLA-DR and CD86 on CD1c+mDC surface were lower than those in control group and post-treatment group, with statistical significance (P<0.05). The number of pDC and CD1c+mDC in KD children in acute stage was significantly negatively correlated with c-reactive protein and neutrophil to lymphocyte ratio (P<0.05). The number of CD1c+mDC was also negatively correlated with ESR (P<0.05). Conclusions The number of pDC and CD1c+mDC in peripheral blood circulation of KD children was insufficient and their function was impaired. Circulating pDC and CD1c+mDC may be involved in the immunological pathogenesis of KD.

    Comprehensive evaluation of autonomic nerve function in overweight/obese children
    ZHANG Li, LI Yun, WANG Jianyi, XIAO Tingting, XIE Lijian, XU Meng
    Journal of Clinical Pediatrics. 2022, 40(7):  505-509.  doi:10.12372/jcp.2022.21e1232
    Abstract ( 233 )   HTML ( 20 )   PDF (1137KB) ( 242 )  
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    Objective To evaluate the autonomic nervous function in overweight and obese children. Methods Heart rate variability (HRV) and heart rate deceleration force (DC) of holter electrocardiogram results were studied. Exercise equivalent, exercise time to peak heart rate (HRmax), heart rate recovery at 1 min after exercise (HRR1), recovery time to resting heart rate, systolic blood pressure at resting period, systolic blood pressure at peak exercise and systolic blood pressure at 3 min during exercise recovery period were used to evaluate autonomic nervous function in overweight and obese children. Results There were 31 children (23 boys and 8 girls) in the obesity group, with an average age of (10.4±2.6) years. There were 69 children (35 boys and 34 girls) in the overweight group, with an average age of (10.9±2.7) years. The control group consisted of 100 children (57 boys and 43 girls) with an average age of (10.2±2.7) years. There were statistically significant differences among overweight, obesity and control groups in standard deviation of normal R-R intervals (SDNN), squares of differences between adjacent NN intervals (RMSSD), averages of NN intervals in all 5-min segments (SDANN), percent of NN 50 in the total number NN intervals (pNN50), low frequency (LF)/high frequency (HF) and DC value (P<0.05). The HRmax, exercise equivalent, HRR1/HRRmax, the time to recover to resting heart rate, the systolic blood pressure at resting period, the peak exercise systolic blood pressure and the systolic blood pressure/peak systolic blood pressure in the third minute of recovery among overweight, obesity and control groups were statistically significant (P<0.05). Conclusions Overweight and obese children have cardiac autonomic nervous dysfunction, especially impaired vagus nerve function, which requires sufficient attention and active intervention to prevent the occurrence of cardiovascular events.

    Clinical characteristics of tachycardia-induced cardiomyopathy in children and the comparative analysis with dilated cardiomyopathy
    XIANG Wanyi, ZHANG Lei, LIU Xiaoyan
    Journal of Clinical Pediatrics. 2022, 40(7):  510-516.  doi:10.12372/jcp.2022.21e1073
    Abstract ( 250 )   HTML ( 24 )   PDF (1146KB) ( 131 )  
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    Objective To investigate the clinical features, treatment and prognosis of tachycardia-induced cardiomyopathy (TIC) in children. Methods The clinical data of 18 hospitalized children with TIC from January 2013 to September 2020 were retrospectively analyzed and the patients were followed up. Forty children with dilated cardiomyopathy (DCM) were selected at the same time. The clinical characteristics, treatment and prognosis between TIC and DCM groups were compared. Results Among 18 children with TIC, 15 (83.3%) had atrial tachycardia and among the 15 children, 8 were persistent atrial tachycardia. The percentage of arrhythmia in total heart rate was 100% (91.9% -100%) in patients with moderate to severe left ventricular systolic function decline (n=7), and 38.7% (32.9% -99.8%) in patients with mild left ventricular systolic function decline (n=7), and the difference was statistically significant (P<0.05). All 18 patients were given drug therapy at first, 6 patients maintained sinus rhythm after drug cardioversion, and 7 of the 12 patients who could not maintain sinus rhythm after drug cardioversion underwent radiofrequency ablation, and all patients succeeded in cardioversion. The other 5 patients were given drugs to control heart rhythm and ventricular rates, and the ventricular rates decreased obviously, and the frequency and load of arrhythmia decreased significantly. Compared with the DCM group, the children in the TIC group was diagnosed at a younger age, had a faster heart rate and a larger heart rate index in the acute phase, a less frequent occurrence of moderate-to-severe heart failure, a smaller left ventricular end-diastolic dimension Z value (LVEDD-Z) after normalized body surface area at the first visit, a higher left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), a higher percentage of atrial tachycardia, a lower ratio of ventricular tachycardia, a higher total heart rate in 24h-dynamic electrocardiogram, a higher arrhythmias percentage of total heart rate, a lower ratio of serum B-type natriuretic peptide (BNP) increase within 2 weeks of treatment, and a higher ratio of BNP before treatment to BNP within two weeks after treatment (BNP-R), and the differences were significant (P<0.05). Conclusions If the heart rate of the child increases significantly, the load of ectopic rhythm tachycardia is high, and there is impaired left ventricular systolic function and cardiac enlargement at the same time, and after cardioversion treatment or control of ventricular rate by medication, the impaired left ventricular systolic function recovers quickly and completely, and the enlarged heart shrinks significantly, the diagnosis of TIC should be considered. The overall prognosis of TIC is good.

    Efficacy evaluation on transcatheter closure of patent ductus arteriosus with mitral regurgitation in children
    CHEN Yanhua, YIN Dan, ZHENG Ming, LYU Tiewei, YI Qijian, LI Mi, XIANG Ping
    Journal of Clinical Pediatrics. 2022, 40(7):  517-521.  doi:10.12372/jcp.2022.21e1493
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    Objective To analyze the medium - and long-term efficacy of simple transcatheter closure in the treatment of children with patent ductus arteriosus (PDA) complicated with moderate and severe mitral regurgitation (MR), and to explore its safety and feasibility. Methods Clinical data of children diagnosed with PDA complicated with moderate and severe MR and treated with transcatheter closure from March 2013 to March 2019 were retrospectively analyzed. Results A total of 121 children (27 boys and 94 girls) with a median age of 19.8 (8.0-28.0) months were included. There were 94 cases with moderate MR and 27 cases with severe MR. Echocardiography showed that the diameter of PDA was (6.4±1.8) mm. There were statistically significant differences in the main pulmonary artery (MPA) diameter, left atrium (LA) diameter, left ventricular end diastolic diameter (LVEDD) and left ventricular end systolic diameter (LVESD) among different time points (preoperative, postoperative 24 h, postoperative 1, 3, 6, 12 and 24 months) (P<0.05). Compared with pre-operation, MPA diameter, LA diameter, LVEDD and LVESD were all shortened at each follow-up time point after surgery, with statistical significance (P<0.05). During the follow-up period, 120 children (93.4%) had less MR than pre-operation. There were statistically significant differences in MR areas of all children among different time points (preoperative, postoperative 24 h, postoperative 1, 3, 6, 12 and 24 months) (P<0.05). The postoperative MR area at each follow-up time point was significantly smaller than that before surgery (P<0.05), but there was no significant difference in MR area between 12 and 24 months after surgery (P>0.05). Conclusions On the premise of strictly grasping the surgical indications, simple transcatheter closure can improve MR degree and reduce left heart load in PDA combined with moderate and severe MR in children, which is safe and effective.

    Application of electric impedance in monitoring cardiac function of pediatric critically ill patients
    LIU Xue, XIONG Xiaoyu, JIANG Kunfeng, QIU Wei, LI Jing
    Journal of Clinical Pediatrics. 2022, 40(7):  522-526.  doi:10.12372/jcp.2022.21e1541
    Abstract ( 203 )   HTML ( 21 )   PDF (1130KB) ( 261 )  
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    Objective To investigate the correlation and consistency of electric impedance (ICON) and echocardiography (ECHO) in monitoring the heart function of pediatric critically ill patients. Methods A total of 53 children treated in the intensive care unit from January 2020 to March 2021 were recruited. ECHO and ICON were used to monitor cardiac function, and stroke volume (SV) and cardiac output (CO) were recorded to compare the correlation and consistency between the two methods. Results A total of 53 children (37 boys and 16 girls) were included, with a median age of 15.0 (5.1-63.0) months. There was no statistically significant difference in SV and CO measured by ICON and ECHO (P>0.05), and there was a significantly positive correlation (r=0.91 and 0.85, both P<0.001). The consistency of SV and CO monitored by ICON and ECHO was good, and the intra- class correlation coefficients (ICC) were 0.89 and 0.87, respectively (P<0.001). Bland-altman method was used for consistency analysis. The average SV difference between ECHO and ICON was 2.29 mL, and the consistency interval was -17.02-21.60 mL. The average difference of CO monitored by ECHO and ICON was 0.27mL, and the consistency interval was -1.83-2.36mL. Under the condition of using ventilator, the correlation coefficients of SV and CO measured by the two methods were 0.88 and 0.82 (both P<0.001), and the ICC values were 0.86 and 0.87 (both P<0.001). The correlation coefficients of SV and CO measured by the two methods without using the ventilator were 0.89 and 0.89 (both P<0.001), and the ICC valueswere 0.91 and 0.86 (both P<0.001). Conclusions ICON and ECHO have good consistency and correlation in monitoring the cardiac function of critically ill children, and are not affected by the use of ventilators. Therefore, they have certain application values in pediatric intensive care.

    General Report
    Construction and validation of the prognosis nomogram of pediatric medulloblastoma based on clinical and tumor biological characteristics
    ZHANG Zaiyu, LIANG Ping
    Journal of Clinical Pediatrics. 2022, 40(7):  527-533.  doi:10.12372/jcp.2022.21e1377
    Abstract ( 225 )   HTML ( 19 )   PDF (1328KB) ( 81 )  
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    Objective To identify potential prognostic markers of pediatric medulloblastoma (MB) in immunohistochemical results, and to construct a risk stratification system based on the integration of clinical characteristics, so as to guide the postoperative personalized management of MB children. Methods The clinical data of children with MB undergoing resection from January 1, 2011 to August 1, 2020 were retrospectively analyzed, and the logistic regression model was constructed to predict the short-term outcomes (STO) (postoperative tumor residue). The children were divided into high-risk group and low-risk group according to postoperative STO and imaging metastasis characteristics. The COX regression model was used to analyze the independent risk factors for long-term outcome (LTO) including recurrence, reoperation and survival. R software was used to construct the nomogram, and the nomogram was evaluated by C-index, calibration curve and decision curve analysis (DCA). Results A total of 111 children (67 boys and 44 girls) with MB were included, with a median age of 7.0 (4.0-9.0) years. Tumor diameter >5.0 cm (OR=8.07, 95% CI: 2.62-24.89) and MYC protein expression (OR=4.03, 95% CI: 1.29-12.63) can predict STO (AUC=0.81, 95% CI: 0.69-0.92, P<0.001). The 12-month LTO-free survival (LOFS) of the high-risk group (n=50) was 76.0% (95% CI: 70.0%-82.0%), and that of the low-risk group (n=61) was 83.6% (95% CI: 78.9% -88.3%). The difference between the two groups was statistically significant (HR=2.77, 95% CI: 1.53-5.01). COX regression model showed that risk grouping, age≤3 years, diameter>5.0 cm, and MYC positive were independent risk factors for poor LTO (P<0.05). Based on the above clinical-biological independent risk factors, LOFS can be accurately predicted by establishing a nomogram, with a C-index of 0.715. Moreover, the calibration curve showed a high degree of consistency between the predicted risk and the actual risk. The net benefit was good in DCA for a wide range of prediction probabilities, demonstrating a good clinical utility. Conclusions The nomogram constructed based on risk grouping, age, tumor diameter and MYC are conducive to the targeted monitoring and management of pediatric MB.

    Value of noninvasive liver fibrosis evaluation in the diagnosis of advanced liver fibrosis in children with Wilson’s disease
    JIANG Tao, OUYANG Wenxian, TAN Yanfang, TANG Lian, ZHANG Hui, LI Shuangjie
    Journal of Clinical Pediatrics. 2022, 40(7):  534-538.  doi:10.12372/jcp.2022.21e1399
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    Objective To investigate the value of clinical biochemical parameters, transient elastography and noninvasive liver fibrosis score in the diagnosis of advanced liver fibrosis in children with Wilson's disease (WD). Methods The clinical data of 22 WD patients from October 2018 to July 2021 were collected. All the children underwent liver biopsy, and the liver stiffness measurement (LSM) was measured by transient elastography. According to the pathological examination results, the children were divided into advanced liver fibrosis (S3 and S4) group and non-advanced liver fibrosis (S0, S1 and S2) group. Three kinds of non-invasive liver fibrosis scores (Sheth, APRI and FIB-4 index) were calculated, and the differences of clinical biochemical indexes, non-invasive liver fibrosis score and LSM between the two groups were compared. Receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of each index for advanced liver fibrosis. Results Twenty-two WD children (12 boys and 10 girls) were included, with an average age of (8.6±2.7) years. There were 13 cases (59.1%) with non-advanced liver fibrosis and 9 cases (40.9%) with advanced liver fibrosis. Compared with non-advanced liver fibrosis group, the levels of albumin, aspartate aminotransferase (AST) and platelet (PLT) in advanced liver fibrosis group were lower, the prothrombin time (PT) and international standardized ratio (INR) were higher, and the indexes of LSM, Sheth and FIB-4 were higher, and the differences were significant (P<0.05). ROC curve analysis indicated that LSM (AUC=1.0) had the highest diagnostic efficacy for advanced liver fibrosis, followed by AST, PLT, PT, INR, FIB-4 and Sheth index (AUC>0.7). Conclusions AST, PLT, PT, INR, LSM, Sheth and FIB-4 index have certain diagnostic values in children with WD advanced liver fibrosis, and they can be used as a noninvasive diagnostic reference index in advanced liver fibrosis.

    Comparative study of metagenomic next-generation sequencing and traditional pathogen detection in leukemia children with febrile neutropenia
    KANG Lei, GUO Fang, BAI Xinfeng, XU Meixian
    Journal of Clinical Pediatrics. 2022, 40(7):  539-544.  doi:10.12372/jcp.2022.21e1444
    Abstract ( 262 )   HTML ( 9 )   PDF (1142KB) ( 106 )  
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    Objective To investigate the application value of metagenomic next-generation sequencing (mNGS) in leukemia children with febrile neutropenic (FN). Methods The clinical data of leukemia children combined with FN after chemotherapy admitted to the pediatric intensive care unit from January 1, 2018 to July 1, 2021 was retrospectively analyzed. The children were divided into group A (bloodstream infection group) and group B (pulmonary infection group) according to the infection foci, and the efficacy of mNGS and traditional pathogen detection (TPD) in the two groups was compared. Results A total of 56 children (27 boys and 29 girls) were included, with a median age of 4.0 (2.0-7.8) years. There were 39 cases in group A (28 cases of ALL and 11 cases of AML) and 17 cases in group B (10 cases of ALL and 7 cases of AML). The commonest pathogens in group A and B were Aspergillus, Candida and Acinetobacter baumannii. The consistency of positive rate of mNGS and TPD was poor (Kappa=0.039). The mNGS positive rate (80.4%) was significantly higher than TPD (58.9%), and the difference was statistically significant (P=0.023). In group A, the positive rates of mNGS for Aspergillus (35.9% vs. 12.8%), Candida (28.2% vs. 10.3%) and Acinetobacter baumannii (28.2% vs. 7.7%) were higher than those of TPD; in group B, the positive rate of mNGS for Aspergillus (41.2% vs. 5.9%) was higher than that of TPD, and the differences were statistically significant (P<0.05). The mNGS can detect rare pathogens, and the detection rate of mNGS for mixed infection was significantly higher than that of TPD, and the difference was statistically significant (P<0.05). Conclusions In leukemia children with FN who failed in initial antibiotic therapy, the commonest pathogens were Aspergillus, Candida, and Acinetobacter baumannii. As a complementary tool for TPD, mNGS has a higher positive detection rate for common pathogens and outstanding efficacy for mixed infections and rare pathogens.

    Rare Disease & the Difficult and Complicated Disease
    Cord blood transplantation in leukocyte adhesion deficiency type-1: a case report with 4 years follow-up
    CHEN Jiao, LIU Zhouyang, FAN Shifen, JIANG Fan, JIANG Zhixin, SUN Yuan
    Journal of Clinical Pediatrics. 2022, 40(7):  545-549.  doi:10.12372/jcp.2022.21e0551
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    Leukocyte adhesion deficiency type-1 (LAD-1) is a primary immunodeficiency disease. It is caused by mutations in the ITGB2 gene that cause damage to leukocyte adhesion. It is characterized by recurrent infections, delayed detachment of the umbilical cord, impaired wound healing and leukocytosis. It can be cured by allogeneic hematopoietic stem cell transplantation. The patient was a boy. He started to have recurrent fever, pneumonia and enteritis at 1 month old. He was diagnosed as LAD-1 based on markedly elevated leukocyte counts and ITGB2 gene homozygous mutation. He was cured after undergoing cord blood transplantation at 6.5 months old. Umbilical cord blood stem cell transplantation is a safe and effective method to cure LAD-1.

    Literature Review
    Effects of systemic lupus erythematosus during pregnancy on offspring and its mechanism
    Reviewer: SONG Yating, Reviser: SUN Jianhua
    Journal of Clinical Pediatrics. 2022, 40(7):  550-554.  doi:10.12372/jcp.2022.21e1174
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    Systemic lupus erythematosus (SLE) is a serious multi-system autoimmune disease, and the vast majority of patients are women of childbearing age. The fetus, newborns and offspring in the long term will be affected by the SLE during pregnancy, including stillbirth, miscarriage, placental abruption, intrauterine growth retardation and the increase in preterm birth incidence. A few cases can also cause neonatal lupus (NL), and even have negative effect on the neurocognition of offspring. Moreover, women with SLE need oral medications before and during pregnancy to control the disease, which will affect offspring in most cases. Therefore, it is recommended that patients with SLE are monitored closely before and during pregnancy. Meanwhile, the optimized treatment and overall evaluation of their offspring will be applied to reduce the adverse effects on the offspring. The effect of SLE during pregnancy on offspring and its mechanism is summarized in this paper by literature review. The effects of drugs for SLE during pregnancy on offspring were also discussed.

    Continuing Medical Education
    Progress in childhood arterial ischemic stroke
    ZHOU Ji, REN Xiaotun
    Journal of Clinical Pediatrics. 2022, 40(7):  555-560.  doi:10.12372/jcp.2022.21e1317
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    Arterial ischemic stroke (AIS) in children is an important global health problem. In recent years, a series of international cooperative studies have made important progresses in the diagnosis and treatment of AIS in children. Based on these studies, our study reviews the new developments in pediatric AIS, mainly including the classification and treatment of cerebral arteriopathy, genes associated with AIS and recanalization therapy.