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    15 March 2022, Volume 25 Issue 08
    Expert Advice

    Status of Diagnosis and Expert Advice of Developmental Disorder Related to Childhood Rehabilitation

    The Subspecialty Group of Rehabilitationthe Society of PediatricsChinese Medical Association

    2022, 25(08):  899-904.  DOI: 10.12114/j.issn.1007-9572.2022.01.301
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    In order to standardize the diagnosis and nomenclature of dvelopmental disorder in China, and ensure that clinical professionals can be able to diagnose and treat these diseases early and accurately, the Rehabilitation Group of Pediatrics Branch of Chinese Medical Association has organized relevant experts to discuss many times and formulated this recommendation based on the current actual situation in China. The paper mainly includes the diagnosis and naming status, evaluation and expert advice ofhigh-risk infants, developmental delay, global developmental delay, 1anguage disorder, mental retardation, autism spectrum disorder, developmental coordination disorder, the objective is to provide reference and guidance for clinical professionals in the diagnosis, evaluation and treatment of developmental disorderin children.

    Original Research

    A Real-world Data Study on Comprehensive Control Rates in a Large Population of Type 2 Diabetes Patients

    HUANG Jingyuan, HUANG Yanli
    2022, 25(08):  905-912.  DOI: 10.12114/j.issn.1007-9572.2022.01.321
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    Background

    There are differences between RCTs and real-world data in reporting the rate of clinical control of patients with diabetes, which cannot solve the problem of continuous observation in large-scale populations. At present, there is no real-world data cross-sectional survey research and related literature of clinical control indicators of T2DM patients who avoid direct contact with patients and doctors in China.

    Objective

    To explore the clinical control compliance rate of individual and comprehensive indicators in patients with type 2 diabetes mellitus (T2DM) in the real world.

    Methods

    Since 2017, 13 community health service institutions in Wuhou District that have gradually bound the data of the primary care information business system to the EPM through unique ID information were selected as sample areas. T2DM patients with EPM bound in the sample area were selected as the research subjects. The effective follow-up period, within 1 year outside the effective follow-up period, and more than 1 year outside the effective follow-up period of T2DM patients with glycated hemoglobin (HbA1c) , low-density lipoprotein cholesterol (LDL-C) , blood pressure follow-up rate, average level, and clinical control compliance rate were recorded. The follow-up rate of comprehensive indicators of 3B (ie HbA1c, LDL-C, blood pressure) and the rate of clinical control compliance were recorded. The correlation between HbA1c, LDL-C, blood pressure, 3B comprehensive indicators and the number of T2DM patients managed in different community health service institutions, the correlation between the number of patients with HbA1c, LDL-C, blood pressure and the effect of each indicator during the effective follow-up period sex were analyzed.

    Results

    Among the 26 501 contracted T2DM patients, the follow-up rates of HbA1c, LDL-C, blood pressure and 3B comprehensive indicators during the effective follow-up period were 43.54% (11 539/26 501) , 45.66% (12 101/26 501) , 89.18% (23 633/26 501) and 32.89% (8 715/26 501) , respectively. The follow-up rates of HbA1c, LDL-C, blood pressure and 3B composite indicators within 1 year outside the effective follow-up period were 15.81% (4 190/26 501) , 24.02 % (6 366/ 26 501) , 9.29 (2 463/26 501) and 0.97% (257/26 501) respectively. The follow-up rates of HbA1c, LDL-C, blood pressure and 3B comprehensive indicators beyond the effective follow-up period for more than 1 year were 19.20% (5 087/26 501) , 23.41% (6 203/26 501) , 1.28% (339/26 501) and 0.49% (131/26 501) , respectively. During the effective follow-up period, the clinical control rates of HbA1c, LDL-C, blood pressure and 3B comprehensive indicators were 60.79% (7 015/11 539) , 59.74% (7 229/12 101) , 52.57% (12 423/23 633) and 18.75% (1 634/8 715) , respectively. The clinical control rate of HbA1c, LDL-C, blood pressure, and 3B comprehensive indicators within 1 year outside the effective follow-up period were 51.98% (2 178/4 190) , 56.75% (3 613/6 366) , 47.79% (1 177/2 463) and 14.79% (38/257) , respectively. The clinical control rates of HbA1c, LDL-C and blood pressure beyond the effective follow-up period for more than 1 year were 65.62% (3 338/5 087) , 59.46% (3 688/6 203) and 22.71% (77/339) , respectively. There was a high correlation between the blood pressure clinical control compliance rate and the 3B comprehensive index clinical control compliance rate (r=0.949, P<0.01) . HbA1c (r=0.648) , LDL-C (r=0.867) , blood pressure (r=0.988) , and the number of 3B comprehensive indicators (r=0.712) were positively correlated with the number of T2DM patients managed in different community health service institutions within the validity period (P<0.05) . The mean LDL-C was negatively correlated with the number of managed cases of T2DM patients (r=-0.715, P<0.01) , and the number of clinically controlled cases (r=0.888) and the rate of clinically controlled compliance (r=0.704) were positively correlated with the number of managed cases of T2DM patients (P<0.05) . Blood pressure (r=0.791) , the number of clinically controlled cases of 3B comprehensive indicators (r=0.616) were positively correlated with the number of managed cases of T2DM patients (P<0.05) . The standard deviation of HbA1c was negatively correlated with the number of HbA1c follow-up cases within the validity period (r=-0.708, P<0.01) , and the number of clinically controlled cases was positively correlated with the number of HbA1c follow-up cases within the validity period (r=0.943, P<0.01) . The average LDL-C value was negatively correlated with the number of LDL-C follow-up cases within the validity period (r=-0.716, P<0.01) , and the number of clinically controlled cases and the clinical control compliance rate were positively correlated with the number of LDL-C follow-up cases within the validity period (r=0.986, r=0.657, P<0.05) . There was a positive correlation between the number of blood pressure clinical control patients and the number of blood pressure follow-up cases within the validity period (r=0.839, P< 0.01) .

    Conclusion

    The individual and comprehensive control levels and control rates of 3B indicators in sample areas are higher, and the differences among institutions are small. The service quality of district as a unit is highly balanced, but there is still a large space for improvement of evidence-based management behavior of lost population.

    Longitudinal Study of Catch-up Growth Assessed by Anthropometric Parameters in Very Premature Infants within 3 Years Old

    QIN Qiaozhi, ZHAO Xueqin
    2022, 25(08):  913-917.  DOI: 10.12114/j.issn.1007-9572.2021.01.604
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    Background

    The improvement in perinatal medicine has promoted the increase of survival rate in very premature infants. Since growth and developmental delays will have a long-term impact on them, early catch-up growth is extremely important. However, there are few longitudinal studies on anthropometric parameters for assessing catch-up growth in such infants.

    Objective

    To investigate the increasing trend of body weight, body length and head circumference (HC) of very premature infants within 3 years old, providing evidence for promoting scientific catch-up growth in such infants.

    Methods

    Participants were selected from Northern Jiangsu People's Hospital during August 2017 to September 2018, including 120 ICU-treated very premature infants delivered at 28-32 weeks of gestation, who were divided into two group 〔small for gestational age (SGA) group (n=11) and appropriate for gestational age (AGA) group (n=109) 〕, and 121 full-term infants. Body weight and length as well as HC were measured at 40 weeks, 3, 6, 12, 24 months of corrected age and 36 months, respectively, and Z-scores and growth rates of these three parameters were calculated.

    Results

    The Z-scores of body weight, body length and HC differed statistically across SGA, AGA and full-term infants within 12 months of corrected age (P<0.05) . The catch-up growth for weight peaked within 3 months of corrected age in AGA infants and full-term infants, and it peaked within 3 to 6 months of corrected age in SGA infants. The growth for height showed a significant increase trend within 6 months of corrected age in AGA and full-term infants. For SGA infants, the catch-up growth for height peaked within 3 to 6 months of corrected age. The HC of AGA infants had an obvious trend of catch-up growth within 3 months of corrected age, while SGA infants'catch-up growth for HC was obvious after 3 months of corrected age, and it gradually slowed down after 12 months of corrected age. The body weight growth rate varied statistically across SGA, AGA and full-term infants during 40 weeks to 12 months of corrected age (P<0.05) . There were statistically differences of growth rates in body length and HC between the three groups during 40 weeks to 24 months of corrected age (P<0.05) .

    Conclusion

    The trends of catch-up growth for body weight, height and HC were significantly different between SGA and AGA infants within 3 years old. Compared with AGA infants, the early catch-up growth rates of these three parameters in SGA infants were slower and imbalanced. Compared to full-term infants, the early catch-up growth rates of the three parameters in very premature infants were significantly slower. And the time point of peak for catch-up growth for each parameter varied significantly between SGA and AGA infants.

    The Clinical Value of PET-CT in the Diagnosis of Pre-pulseless Takayasu's Arteritis Presenting as Fever of Unknown Origine

    ZENG Keqin, YIN Yufeng, REN Tian, ZHOU Erye, WANG Mingjun, WU Jian
    2022, 25(08):  918-923.  DOI: 10.12114/j.issn.1007-9572.2021.01.048
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    Background

    Takayasu's arteritis (TAK) presenting as fever of unknown origin (FUO) is rare in clinic. Diagnosis is difficult in the early stageas the non-specific clinical symptoms and signs, the lack of imaging findings of great artery stenosis and occlusionof patients. With the wide application of positron emission computed tomography/computed tomography (PET-CT) in the diagnosis and differential diagnosis of FUO, it may contribute to the early diagnosis of TAK.

    Objective

    To investigate the application value of PET-CT in the diagnosis and condition assessment of early TAK presenting as FUO.

    Methods

    The clinical presentations, laboratory examinations, PET-CT findings, and treatment outcomes of 7 cases of TAK presenting as FUO that eventually diagnosed by PET-CT from January 2013 to January 2021were retrospectively analyzed, and the medical literature from 1991 to 2021 was reviewed.

    Results

    All the 7 patients were female, the age of onsetranging from 27 to 58 years old, with an average age of (37.9±10.6) years. The course of disease was from 1 to 6 months, with an average of (3.9±2.4) months. FUO was the first symptom of all patients (100.0%) , which may be accompanied by palpitation (14.3%) , dizziness (28.6%) , headache (14.3%) , fatigue (28.6%) and other non-specific clinical symptoms. Laboratory tests showed elevated levels of leukocytes (71.4%) , platelets (57.1%) , erythrocyte sedimentation rate (ESR) (100.0%) , C-reactive protein (CRP) (85.7%) , tumor necrosis factor-α (TNF-α) (42.9%) and interleukin-6 (IL-6) (85.7%) . Color Doppler ultrasound, computed tomography angiography (CTA) and magnetic resonance angiography (MRA) showed no stenosis and occlusion of large arteries, while PET-CT showed inflammatory changes in arterial walls at multiple locations, including thecending aorta (28.6%) , aortic arch (14.3%) , common carotid artery (28.6%) , subclavian artery (28.6%) , thoracic aorta (14.3%) , abdominal aorta (14.3%) and renal artery (14.3%) .

    Conclusion

    PET-CT is helpful in the diagnosis and condition assessment of pre-pulseless Takayasu's arteritis presenting as FUO.

    The Study of the Value of High Mobility Group Protein B1 Combined with Acute Physiological Score in the Diagnosis and Prognosis of Children with Severe Pneumonia

    KANG Ping, LI Yi, TANG Yu
    2022, 25(08):  924-929.  DOI: 10.12114/j.issn.1007-9572.2021.01.410
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    Background

    Severe pneumonia in children is a common respiratory critical illness, and accurate assessment of its prognosis is the key to reasonable clinical decision-making. High mobility group protein B1 (HMGB1) and acute physiology score (APS) have high prognostic significance for adult critically ill patients, but the value of diagnosis and prognosis in children with severe pneumonia is still unclear.

    Objective

    To investigate the value of HMGB1 combined with APS in the diagnosis and prognosis of children with severe pneumonia.

    Methods

    The data of 55 children with severe pneumonia (severe pneumonia group) treated in Children's Hospital affiliated to Zhengzhou University from May 2020 to February 2021 were collected and the childrenwere divided into the improvement subgroup (n=41) and the poor outcome subgroup (n=14) according to the prognosis. Data of 60 children with common pneumonia (common pneumonia group) and 40 children with healthy physical examination (control group) who were treated in this hospital during the same period. The APS score and HMGB1 level at admission of each groupwere compared. The correlation between APS and HMGB1 was analyzed. The risk factors affecting the prognosis of severe pneumonia were analyzed by multivariate Logistic regression. The value of HMGB1, APS and combined variables in the diagnosis and prognosis of children with severe pneumonia was analyzed by ROC curve.

    Results

    The HMGB1 level and APS score of the severe pneumonia group were significantly higher than those of the normal pneumonia group (P<0.05) ; the HMGB1 level and APS score of the poor prognosis subgroup were significantly higher than those of the prognosis subgroup (P<0.05) . The results of correlation analysis showed that there was a positive correlation between HMGB1 and APS in severe pneumonia group (r=0.542, P<0.001) . Multivariate Logistic regression analysis showed that HMGB1 level〔OR=8.411, 95%CI (1.411, 50.137) , P<0.05〕, APS score〔OR=5.724, 95%CI (1.108, 29.572) , P<0.05〕 were the influence factors for poor prognosis in children with severe pneumonia. The area under ROC curve for the combined diagnosis of HMGB1 and APS for the diagnostic value was 0.975〔95%CI (0.918, 0.996) 〕, and the optimal cut-off value was -0.203, and the sensitivity was 98.18%, and the specificity was 96.67%. The area under ROC curve for the combined diagnosis of HMGB1 and APS for the prognosis of pneumonia was 0.923〔95%CI (0.819, 0.978) 〕, and the optimal cut-off value was -0.030, and the sensitivity was 97.56%, and the specificity was 92.86%.

    Conclusion

    Both HMGB1 level and APS score at admission are influence factors for the poor prognosis of severe pneumonia, and the combination of the two can further improve the diagnostic performance and prognosis of pneumonia.

    Bioinformatic Analysis of Potential Key Genes in Castration-resistant Prostate Cancer Development

    DONG Jingting, HENG Li, KANG Shaosan, LIU Jian, TIAN Zhichong, ZHANG Liguo, ZHANG Jincun, LI Zhiguo, SHEN Hong, CAO Fenghong
    2022, 25(08):  937-944.  DOI: 10.12114/j.issn.1007-9572.2022.02.010
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    Background

    Castration-resistant prostate cancer (CRPC) is one of the most prevalent cancers in males with a high fatality rate. Its molecular mechanism is still unclear, and there is no effective treatment.

    Objective

    To explore the key genes involved in CRPC development using bioinformatic analysis, offering new ideas for the diagnosis and treatment of CRPC.

    Methods

    The data set GSE32269 which contains human primary prostate cancer and CRPC was downloaded from the Gene Expression Omnibus database for further bioinformatic analysis. R language was used to identify differentially expressed genes (DEGs) in CRPC. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEGs were further performed by using DAVID. A protein-protein interaction (PPI) network of DEGs was constructed by using STRING database for screening potential key genes. And the identified potential key genes were further analyzed by survival analysis and receiver operating characteristic (ROC) curve analysis.

    Results

    279 DEGs were identified in microarray dataset GSE32269. GO enrichment analysis and KEGG pathway analysis revealed that cell division, mitosis and cell cycle signaling pathways may play an important role in the development of CRPC. PPI network screening revealed that there were 15 potential key genes, among which CDC20, MAD2L1 and NUSAP1 expressed differentially in CRPC patients: those with highly expressed CDC20, MAD2L1 and NUSAP1 had statistically lower overall survival rate and disease-free survival rate than did those with low expressed CDC20, MAD2L1 and NUSAP1 (P<0.05) . The area under the ROC curve of CDC20, MAD2L1 and NUSAP1 to predict the occurrence of CRPC were 0.933, 0.762, and 0.950, respectively, indicating that each of them may have a high diagnostic value for CRPC.

    Conclusion

    CDC20, MAD2L1 and NUSAP1 may be key candidate genes associated with the development of CRPC.

    Analysis of Gut Flora in a Mouse Model of Esophageal Squamous Cell Carcinoma in Situ

    ZHANG Yushuang, YU Fuyang, WU Zhongbing, WANG Yiran, LI Jing
    2022, 25(08):  945-951.  DOI: 10.12114/j.issn.1007-9572.2021.01.501
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    Background

    With the application and development of high-throughput sequencing-based approaches for gut flora analysis, increasing studies have confirmed that gut flora is closely related to the development of various cancers. The relationship of gut floras with esophageal squamous cell carcinoma (ESCC) , a common cancer threatening the health of Chinese people, has attracted extensive attention.

    Objective

    To analyze the diversity of gut floras between a rat model of ESCC in situ and normal mice, to identify the carcinoma-specific bacterial genus in ESCC.

    Methods

    From August 2020 to May 2021, 20 female SPF C57BL/6 mice were randomly and equally divided into control group and model group. Rice in control group were routinely fed and given ordinary drinking water for 32 weeks, and those in model group were routinely fed and received water containing 0.1 mg/ml cancer inducer 4-nitroquinoline-1-oxide for 16 weeks, and then only fed with ordinary drinking water for another 16 weeks. Stool samples of both groups were collected, and DNA in faeces was extracted and amplified by PCR, followed by high-throughput sequencing. The obtained sequencing data were divided into operational taxonomic units (OTU) based on the similarity between sequences. The α-diversity, β-diversity and species abundance were further analyzed according to species annotation.

    Results

    No death occurred in the experiment, and the modeling of ESCC was successfully established in model group. Compared with control group, the proportion of Bacteroidota and Firmicutes increased, while the proportion of Verrucomicrobiota and Proteobacteria decreased in model group. Analysis showed that the α-diversity measured by Shannon Diversity Index in model group was lower than that of control group (P<0.05) . As for β-diversity analysis, PCoA diagram showed that the gut floras of control and model groups clustered in different quadrants, suggesting a significant discrepancy between the groups (t=22.444, P=0.004) . At the phylum level, the abundances of unidentified bacteria, Cyanobacteria, Elusimicrobia and Campilobacterota were higher in model group than those in control group (P<0.05) . At the genus level, the abundances of Prevotellaceae_UCG-003, Bacteroides and Lachnospiraceae_NK4A136_group, Ruminococcus, Prevotellaceae_UCG-001, Prevotella, Colidextribacter, Lachnospiraceae_UCG-006 were higher while those of Romboutsia and Turicibacter were lower in model group than those in control group (P<0.05) . LEfSe analysis showed that, at the genus level, the abundances of Prevotellaceae_UCG-003, Escherichia-Shigella, Bacteroides, Lachnospiraceae_NK4A136_group were increased significantly in model group (P<0.05) , but the abundance of Romboutsia was increased significantly in control group DZ (P<0.05) .

    Conclusion

    By comparing the composition of gut flora, we identified the rat model of ESCC may have less diversity of species and specially differentiated bacteria, and Prevotellaceae_UCG-003, Bacteroides, Lachnospiraceae_NK4A136_group, and Romboutsia could be used as biomarkers for ESCC.

    Clinicopathological Manifestations of Kidney Injury in Leukemia

    WANG Yina, DONG Bao, LI Xin, SHAO Chunying, ZUO Li, WANG Mei, YAN Yu
    2022, 25(08):  952-956.  DOI: 10.12114/j.issn.1007-9572.2021.01.504
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    Background

    Kidney is a major extramedullary organ involved in leukemia, but clinicians have insufficient understanding of it due to rare case reports.

    Objective

    To analyze the clinicopathological manifestations of kidney injury in leukemia.

    Methods

    Five patients with kidney injury in leukemia were recruited from Peking University People's Hospital from June 2010 to June 2020. Their demographics, clinical manifestations, ultrasonic and laboratory examination results, pathological examination results of renal biopsy species, therapeutic regimen and follow-up were retrospectively analyzed.

    Results

    All these patients were male, with an onset age ranging from 19 to 73 years old. Two of them had B-cell acute lymphoblastic leukemia after allogeneic stem cell transplantation, the remaining three had B-cell chronic lymphocytic leukemia. All of them had acute kidney injury with proteinuria, and pathologically manifestation of acute interstitial nephritis. In addition, two of them also had leukemia-related glomerular disease. Renal pathology indicated extramedullary recurrence in the two cases of B-cell acute lymphoblastic leukemia, and progression in the other three cases of B-cell chronic lymphoblastic leukemia. Four patients received regular chemotherapy, and two of them obtained a reduction in serum creatinine levels, but the other two showed no improvement in renal function.

    Conclusion

    Kidney injury in leukemia commonly manifests as acute kidney injury clinically, acute interstitial nephritis pathologically, and may be complicated by secondary glomerulopathy. Prompt renal biopsy, especially immunohistochemical staining for renal interstitial infiltrating cells, may be helpful for accurate diagnosis and appropriate treatment guidance.

    Clinical Study of Venetoclax with Chemotherapy for Relapsed/Refractory Acute Myeloid Leukemia

    CHEN Xiaofeng, WANG Meng, LI Zhongyu, LI Jiajia
    2022, 25(08):  957-962.  DOI: 10.12114/j.issn.1007-9572.2022.02.005
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    Background

    Adults with relapsed/refractory acute myeloid leukemia (AML) have poor prognosis, very low long-term survival rate and cure rate, and limited chemotherapy regimens.

    Objective

    To investigate the safety and efficacy of venetoclax (VEN) with HAAG 〔homoharringtonine (HHT) , Cytarabine (Ara-C) , aclacinomycin (Acla) , granulocyte stimulating factor (G-CSF) 〕 in relapsed/refractory AML.

    Methods

    The clinical data of 10 adult patients with relapsed/refractory AML treated in the First Affiliated Hospital of Bengbu Medical College were analyzed retrospectively, including: clinical characteristics (sex, age, diagnosis, chromosome, gene mutation, prognosis) , peripheral blood and bone marrow cytology, and the effect of Ven+Aza+HAAG regimen.

    Results

    Among the 10 patients, there were 7 men and 3 women, with an average age of (47.9±11.3) years; 4 cases of M2 and 6 cases of M5 by FAB classification; 3 cases of good prognosis, 2 cases of fair and 5 cases of poor. The median levels of WBC count, hemoglobin content, and platelet count, as well as median percentage of bone marrow blast cells before chemotherapy of the patients were 4.10×109/L, 87.5 g/L, 66.00×109/L, and 63.5%, respectively, and after chemotherapy, the values of these four indicators were 3.28×109/L, 107.0 g/L, 78.00×109/L and 5.5%, respectively. Before VEN+Aza+HAAG regimen combined chemotherapy, the median number of chemotherapy used by the patients was 5. And after the combined therapy, there were 1 case of complete remission (CR) and 4 cases of CR with incomplete count recovery (CRi) , 3 cases of partial remission (PR) , and 2 cases of non-remission (NR) . The objective response rate of 10 patients was 80%, and median survival time was 〔6.5 (3.0, 8.5) 〕months. The toxic and side effects were mainly bone marrow suppression and infection. No patients died of treatment-related complications and other toxic and side effects.

    Conclusion

    Compared with traditional chemotherapy regimen, the use of Ven + Aza + HAAG with chemotherapy could significantly improve the objective response rate and remission degree, and prolong the survival in patients with relapsed/refractory AML, which is worthy of further study and has a prospect of clinical application.

    Predictive Value of Hemodynamic Indicators for Bronchopulmonary Dysplasia in Preterm Infants

    JIA Nan, HE Yujuan, ZHAO Xiaoxiao, ZHANG Weixing
    2022, 25(08):  963-968.  DOI: 10.12114/j.issn.1007-9572.2021.01.414
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    Background

    In China, the growing prevalence of bronchopulmonary dysplasia (BPD) in increased number of survived very preterm and extremely preterm infants, seriously endangers the life and impairs quality of life in this population. There are different degrees of hemodynamic changes in preterm infants in the process of developing BPD, however, there are relatively few studies about the correlation between the occurrence of BPD and hemodynamic indicators in preterm infant.

    Objective

    To examine predictive value of the hemodynamic indexes for BPD in premature infants.

    Methods

    One hundred and sixty-one premature infants (hospitalized within 1 hour of birth, gestational age <32 weeks) were selected from Xinxiang Central Hospital from September 2018 to December 2020. The general data (gestational age, birth weight, sex, and mode of delivery) were collected; the basic diseases and other complications of preterm infants were collected, compared between two groups of infants divided by the prevalence of BPD (n=65) or not (n=96) . PI values (measured at 1, 12, 48, 72 and 96 hours after delivery, and on the 5th, 6th, and 7th days after delivery, respectively) , and serum lactic acid levels (measured at 1, 12, and 24 hours after admission, respectively) were collected. Mean arterial pressure (MAP) levels measured by arterial pressure monitoring at 1, 12 and 24 hours after admission for 33 infants (16 in BPD group and 17 in the control group) with critical or extremely critical conditions suggested by neonatal critical illness score were also collected. Compare the results between two groups, the receiver operating characteristic (ROC) curve was plotted to evaluate the predictive value of PI, serum lactic acid and MAP for BPD in preterm infants.

    Results

    Sixty-five out of the 161 cases 〔40.3% (65/161) 〕were diagnosed with BPD. Preterm infants with and without BPD had no statistically significant differences in gestational age, birth weight, gender, and mode of delivery (P>0.05) . Preterm infants with BPD had higher incidence of neonatal asphyxia, neonatal respiratory distress syndrome, neonatal pneumonia, and retinopathy of prematurity than those without (P<0.05) . Preterm infants with and without BPD had no statistically significant differences in sepsis, pulmonary hemorrhage, PDA, IVH, purulent meningitis and anemia (P>0.05) . PI values at 1, 12 and 24 hours after birth differed significantly between the two groups (P<0.05) . Serum lactic acid at 1 hour after admission differed significant between the two groups (P<0.05) . MAP levels at different time periods showed no significant differences between critical and extremely critical preterm infants with and without BPD (P>0.05) . In predicting BPD, the PI at 1-hour, 12-hour, and 24-hour was 0.847〔95%CI (0.788, 0.906) , P<0.001〕, 0.776〔95%CI (0.705, 0.846) , P<0.001〕, 0.695〔95%CI (0.613, 0.778) , P<0.001〕, respectively; the optimal cutoff value was chosen as 0.55, 1.15, 1.45, with the sensitivity of 76.9%, 86.2%, 81.5% and the specificity of 75.0%, 60.4%, 51.0%; serum lactic acid at 1 hour after birthhad an AUC of 0.762〔95%CI (0.686, 0.837) , P<0.001〕, the optimal cutoff value was chosen as 6.55, with the sensitivity of 81.5%, and the specificity of 68.7%.

    Conclusion

    In preterm infants with a gestational age <32 weeks, the change of hemodynamic indicatou PI and lactic acid value maybe correlated with the occurrence of BPD. PI value within 24 hours after birth may be an earlypredictor for BPD, but further research is still needed.

    Autoimmune Neutropenia in ChildrenClinical Characteristics

    SUN Qing, XIE Yao, WU Penghui, LI Shuo, ZHAO Weihong
    2022, 25(08):  969-972.  DOI: 10.12114/j.issn.1007-9572.2021.01.605
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    Background

    Autoimmune neutropenia (AIN) is a common chronic neutropenia in children, but it in children has been rarely reported.

    Objective

    To analyse clinical characteristics, diagnosis, treatment, and follow-up of children with AIN, aiming at providing support for clinicians.

    Methods

    A retrospective design was used. Participants were 22 children with AIN recruited from Department of Pediatrics, Peking University First Hospital from 2012 to 2020. Their clinical and follow-up data were collected and analyzed.

    Results

    Of the 22 cases, 15 were male and 7 were female; with 6 months as the median initial diagnosis age. Among the results of 82 routine blood tests performed for all cases, severe, moderate and mild neutropenia accounted for 62.2% (51/82) , 30.5% (25/82) , and 7.3% (6/82) , respectively. Two cases (9.1%) were diagnosed with moderate neutropenia and other 20 (90.1%) were diagnosed with severe neutropenia by the lowest absolute neutrophil count (ANC) . Six children (27.3%) also had other clinical manifestations besides neutropenia. Twelve cases (54.5%) underwent the examination of bone marrow cell morphologies. Six cases (27.3%) underwent gene test. 95.5% of the cases had infections, and 54.5% of them had severe infections, but no life-threatening infections. The leading pathogen of infections was virus. The upper respiratory tract was the most common infected area. By the end of September 2021, the ANC of 11 cases returned to the normal level, and the median of AIN of them was 25 (range: 7-42) months.

    Conclusion

    Most AIN children had moderate to severe neutropenia, and they were prone to infections mostly caused by virus, and the most usually were upper respiratory tract infections, but rarely life-threatening. The median duration of AIN, a self-limited disease, for our reported cases was 25 months.

    Is the Change of Cytokines Related to Renal Damage in Children with IgA Vasculitis

    WANG Mengdi, DU Yue
    2022, 25(08):  973-978.  DOI: 10.12114/j.issn.1007-9572.2021.01.041
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    Background

    The long-term prognosis of IgA vasculitis (IgAV) depends on thedegreeof renal damage. Studies on the pathogenesis of renal injury in IgAV have found that cytokines play an important role in mediating and driving the process of renal damage.

    Objective

    To investigate the significance and value of cytokine in the process of renal damage in IgAV by exploring the changes of serum cytokine level in children with IgAV renal damage.

    Methods

    194 IgAV children hospitalized in the Department of Pediatric, Shengjing Hospital of China Medical University from January 2018 to June 2020 were selected as research subjects. They were divided into IgAV group (n=97) and IgAV renal damage group (n=97) according to the presence or absence of renal damage, and 60 healthy children who underwent physical examination in the pediatric health department of our hospital during the same period were selected as the control group. The cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, IFN-γ, and TNF-α) , absolute lymphocyte count, immunoglobulin A, and immunoglobulin E were collected from the children. Multivariate Logistic regression was used to analyze the factors influencing IgAV renal damage, and the receiver operating curve (ROC) of the diagnostic value of cytokines on the characteristics of IgAV renal damage was drawn.

    Results

    The IL-2 level in the lgAV group were higher than those in the lgAV renal damage group and the control group, and the IL-2 level in the lgAV renal damage group was higher than that in the control group (P<0.05) ; IL-17 level in the lgAV renal damage group were higher than those in the lgAV group and the control group, and IL-17 level in the lgAV group was higher than that in the control group (P<0.05) ; IL-6, IL-10, and TNF -α level were higher in the lgAV renal damage group than those in the lgAV renal damage group and the control group (P<0.05) ; IFN-γ level were higher in the lgAV renal damage group and the control group than that in the lgAV group (P<0.05) . Multivariate Logistic regression analysis showed that IL-2, IL-17, IFN-γ, and TNF-α were influencing factors in developing IgAV renal damage (P<0.05) . The AUC of IL-12 for predicting IgAV renal damage was 0.589, with a sensitivity of 38.0% and specificity of 47.0%. The AUC of IL-17 for predicting IgAV renal damage was 0.621, with a sensitivity of 47.4% and specificity of 77.3%. The AUC of IFN-γ for predicting IgAV renal damage was 0.688, with a sensitivity of 75.0% and specificity of 55.7%. The AUC of TNF-α for predicting IgAV renal damage was 0.614, with a sensitivity of 42.0% and specificity of 37.0%. The AUC of IL-17 and IFN-γ combined for predicting IgAV renal damage was 0.710, with a sensitivity of 71.1% and specificity of 66.0%.

    Conclusion

    Serum cytokines IL-17 and IFN-γ are closely associated with the development of renal damage in IgA vasculitisrenal damage, early detection of both levels and dynamic monitoring of their changes can serve as an early warning for early detection of renal involvement and adjustment of treatment plans.

    Ethnic-specific Clinical Features in Children with Non-M3 Acute Myeloid Leukaemia from Yunnan Province

    MAO Xiaoyan, ZHOU Yan, LIU Li, YIN Runxiu, YANG Chunhui, CUI Tingting, FANG Chunlian, JIANG Hongchao, TIAN Xin
    2022, 25(08):  979-983.  DOI: 10.12114/j.issn.1007-9572.2022.02.016
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    Background

    Childhood acute myeloid leukaemia (AML) is a higly heterogenous disorder. But its clinical characteristics according to ethic groups have been rarely studied.

    Objective

    To explore ethnic-specific clinical characteristics and prognosis of paediatric patients with non-M3 AML from Yunnan province.

    Methods

    Paediatric patients with newly diagnosed non-M3 AML were rectuited from Kunming Children's Hospital between January 1, 2015 and March 1, 2020. Basic baseline clinical data, including demographic characteristics (ethnic group, gender, age) , general information (white blood cell count, haemoglobin, platelet count, lactate dehydrogenase, bone marrow blast cell, FAB classification) , karyotype, and genetic information were collected. All patients were followed up from enrolment to 2020-05-31, and treatment protocols, risk stratifications, and prognoses were collected.

    Results

    Seventy-two cases〔51 cases of Han, 21 cases of minorities (5 Yi, 4 Hui, 3 Hani, 2 Bai, 2 Miao, 1 Zhuang, 1 Wa, 1 Buyi, 1 Mongolian and 1 Dai) 〕 were enrolled, with a follow-up of 2-60 months. Children of ethnic minorities had higher mean white blood cell count did those of Han (P<0.05) . Follow-up analysis showed that compared with children of Han, children of ethnic minorities had higher risk and moratlity (P<0.05) , but domonstrated simailar complete remission rate, recurrence rate and bone marrow transplantation rate after the first course of induction therapy (P>0.05) . Event-free survival rate and overall survival rate of children of Han were higher than those of children of ethnic minorities (χ2=8.098, P=0.004; χ2=12.547, P<0.001) .

    Conclusion

    Non-M3 AML children of Han had lower risk and better prognosis than those of ethnic minorities in Yunnan, but the reason has not been identified.

    Epidemiological Study

    Characteristics of Cancer Epidemiology among 0-14 years old Chinese Children20052015

    TANG Hui, GUO Hong, CAO Fang, YAN Yizhong, HE Jia, GUO Heng, CUI Xiaobin, HU Yunhua
    2022, 25(08):  984-989.  DOI: 10.12114/j.issn.1007-9572.2021.01.607
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    Background

    Cancer has become a leading cause of death for Chinese children, imposing a great economic burden on society and families. Therefore, it is extremely important to understand the epidemicsizes and trends of childhood malignancies.

    Objective

    To analyze the epidemiological characteristics of childhood cancer in China from 2005 to 2015, so as to provide evidence for the formulation of prevention and control strategies and rational allocation of health resources concerning childhood cancer in China.

    Methods

    Data regarding cancer incidence and mortality in Chinese 0-14 years old children during 2008 to 2018 were collected from the Chinese Cancer Registry Annual Report. Age-standardized incidence and mortality rates were computed by dividing the number of child deaths caused by cancer by the fifth national population census (2010) and multiplying by 100 000. Joinpoint Regression Program was used to compute the annual percentage change (APC) to analyze the temporal trends of annual child cancer incidence and mortality rates.

    Results

    (1) During the period of 2005 to 2015, the median crude incidence rate and median crude mortality rate of cancer in 0-14 years old were 9.35/100 000, and 3.91/100 000, respectively. The median crude incidence and median crude mortality rate of 0-4 years old group were higher than those of 5-9 years old group and 10-14 years old group (P<0.05) . (2) The median crude incidence rate (10.21/100 000 vs 8.91/100 000) and median crude mortality rate (4.18/100 000 vs 3.47/100 000) of cancer in male children aged 0-14 years old were higher than those of female children of the same age (P<0.05) . (3) The median crude incidence rate (10.87/100 000 vs 7.20/100 000) and median crude mortalityrate (4.08/100 000 vs 3.54 /100 000) of cancer in urban children aged 0-14 years old were higher than those of rural children of the same age (P<0.05) . (4) The median crude mortality rate of cancer showed an upward trend in 0-14 years old in the period of 2005 to 2015 (APC=1.01%, P<0.05) ; amomg them, the median crude mortality rate in the 0-4 years old group showed an decreased trend (APC=-1.19%, P<0.05) ; the median crude mortality rate in the 5-9 years old group showed an increased trend (APC=2.50%, P<0.05) ; the median crude mortality rate in the 10-14 years old group was stable over time. (5) The median crude incidence rate and median crude mortality rate of cancer in rural 0-14 years old in rural areas presented an upward trend over the period 2005 to 2015 (APC=7.73%, 2.22%, P<0.05) . (6) The top six cancers among children aged 0-14 years old in this period were: leukemia, brain cancer, lymphoma, bone cancer, kidney cancer and liver cancer.

    Conclusion

    The cancer incidence and mortality rate in Chinese 0-14 years old children showed different features by time, age group or geographical region (rural or urban) . Priorities for containing cancer should be given to rural children, 5-9 years old children or children with brain cancer or leukemia.

    Ovarian Cancer in ChinaTrends in Incidence and Mortality20052016

    HUANG Haitao, CHEN Shuyu, GENG Xu, WAN Xiao, JIA Ruiying, LIANG Dandan, CHEN Chaoran
    2022, 25(08):  990-994.  DOI: 10.12114/j.issn.1007-9572.2021.01.606
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    Background

    The health impairment caused by ovarian cancer in female population has become a global focus. However, there is a lack of research on ovarian cancer incidence and mortality trends in Chinese female population.

    Objective

    To describe the trends of ovarian cancer incidence and mortality in China from 2005 to 2016 by analyzing the incidence and death data of ovarian cancer collected from Chinese Cancer Registry Annual Report, providing a basis for the scientific prevention and control of ovarian cancer in China.

    Methods

    The incidence and mortality of ovarian cancer in China during 2005 to 2016 were collected and input into Excel spreadsheets, then the annual age-standardized incidence rate, age-standardized mortality rate, age-specific incidence rate and age-specific mortality rate were computed. Joinpoint Regression Program was used to estimate the annual percentage change (APC) , and average annual percentage change (AAPC) to analyze the temporal trends of annual ovarian cancer incidence and mortality rates.

    Results

    The incidence rate of ovarian cancer showed a trend of rapid increase over the period of 2005 to 2016 (AAPC=7.25%, P<0.05) . The annual age-standardized ovarian cancer incidence rate in urban areas was higher than that in rural areas in each year. The ovarian cancer incidence rate increased obviously with age in women over the age of 35, and peaked in those aged 55 years old. From 2005 to 2016, the overall ovarian cancer mortality rate showed a rapid upward trend (AAPC=6.06%, P<0.05) . The age-standardized ovarian cancer mortality rate in urban areas was higher than that in rural areas. The mortality rate increased rapidly with age in women over 35 years of age, but decreased gradually in those aged over 75 years.

    Conclusion

    Both ovarian cancer incidence and mortality rates during 2005 to 2016 in China increased rapidly, but with age-specific and urban-rural differences. Therefore, targeted interventions should be taken, and strategies for ovarian cancer prevention and treatment should be developed to reduce the risk of ovarian cancer.

    Evidence-based Medicine

    Efficacy and Safety of Spironolactone in the Treatment of Resistant Hypertensiona Meta-analysis

    ZHANG Ping, ZOU Jing, GAO Cunzhou, WU Aiping, LI Rongshan
    2022, 25(08):  995-1006.  DOI: 10.12114/j.issn.1007-9572.2021.01.046
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    Background

    As a special type of hypertension, resistant hypertension has complex etiology, is difficult to treat, and more likely to lead to target organ damage. Recent studies have found that common triple combination antihypertensive therapies plus low-dose spironolactone could effectively control blood pressure in patients with resistant hypertension, but the efficacy and safety of such treatments need to be further verified due to small scales of these studies.

    Objective

    To perform a systematical review of the efficacy and safety of spironolactone for resistant hypertension.

    Methods

    Randomized controlled trials (RCTs) on spironolactone for resistant hypertension were identified in databases of PubMed, Web of Science, The Cochrane Library, CNKI, VIP, and WanFang Date from inception to May 3rd, 2021. Two researchers separately screened the RCTs, extracted data and assessed the risk bias of eligible studies. Meta-analysis was conducted using RevMan 5.3.

    Results

    Twenty RCTs were included, nine of which did not report randomization methods, one used randomization based on the sequence of numbers including odd and even numbers of admission (pseudo-randomization) , seven did not report whether blinding was used, four were open-labeled, three described allocation concealment, and one had no complete results with no safety parameters for post-treatment of the controls. Meta-analysis revealed that compared to placebo and blank control groups, spironolactone-treated group had much lower clinic blood pressure, 24-hour ambulatory blood pressure (ABP) , daytime blood pressure and nighttime blood pressure (P<0.05) . Compared with patients treated with other antihypertensive drugs, spironolactone-treated patients had notably lower clinic systolic blood pressure (SBP) , 24-hour ABP, daytime SBP, nighttime SBP and self-measured home SBP (P<0.05) . Compared with those treated with renal nerve denervation, spironolactone-treated patients had significantly reduced daytime blood pressure and nighttime SBP (P<0.05) .In terms of safety, compared with those treated with placebo, spironolactone-treated patients had elevated serum potassium and creatinine (P<0.05) . Compared with patients treated with other antihypertensive drugs, spironolactone-treated patients had elevated serum potassium level (P<0.05) . Compared with those with renal nerve denervation, spironolactone-treated patients had elevated serum creatinine level (P<0.05) .

    Conclusion

    Comparatively speaking, spironolactone is effective and safe for resistant hypertension. Due to limited quantity and quality of included studies, the conclusion still needs to be further verified by more high-quality studies.

    Curative Effect of EGFR-TKIs with Anti-angiogenic Drugs as the Treatment for Patients with Advanced EGFR-mutant Non-small Cell Lung Cancera Meta-analysis

    LI Yong, LONG Yong, ZHAO Chong, ZHANG Guanqing, SU Yanhe
    2022, 25(08):  1007-1013.  DOI: 10.12114/j.issn.1007-9572.2021.01.413
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    Background

    Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) will eventually occur in almost all advanced EGFR-mutant non-small cell lung cancer (EGFR-mutant NSCLC) patients although the therapy has been a standard treatment for such patients. But EGFR-TKIs in combination with anti-angiogenic drugsmay prolong the survival time of these patients.

    Objective

    To explore the efficacy and safety of EGFR-TKIs with anti-angiogenic drugs as the treatment for patients with advanced EGFR-mutant NSCLC.

    Methods

    Databases including CNKI, CQVIP, Wanfang Data Knowledge Service Platform, PubMed, EMBase, and The Cochrane Library were searched from inception to July 2021 using subject headings with free-text words, for randomized controlled trials (RCTs) about the first-line treatment of advanced EGFR-mutant NSCLC patients with EGFR-TKIs in combination with anti-angiogenic drugs (combination therapy group) versus EGFR-TKIs alone (monotherapy group) . Two researchers performed literature screening, data extraction (the first author, publication time, the country where the author coming from, study type, sample size, stage of NSCLC, sex, average age, treatment regimen, ECOG PS score, median follow-up time, pathological type, gene mutation type, outcome indicators) , separately, and assessed risk of bias in the included RCTs. STATA 15.0 was used formeta-analysis.

    Results

    Nine RCTs were included, involving 1 553 patients. Meta-analysis results showed that the combination therapy was associated with longer progression-free survival (PFS) 〔HR=0.61, 95%CI (0.54, 0.70) , P<0.001〕. Further analysis based on PFS revealed that the combination therapy did not significantly prolong the PFS in those aged ≥65 yearsand in those with brain metastases (P>0.05) . Moreover, the combination therapy was not superior to monotherapy in terms of prolonging the overall survival, and improving the objective response rate, and disease control rate (P>0.05) . However, the rate of adverse eventsabove grade 3〔RR=1.77, 95%CI (1.62, 1.94) , P<0.001〕was significantly increased.

    Conclusion

    By using the combination therapy, advanced EGFR-mutant NSCLC patients may obtain a prolonged PFS, but with increased risk of serious adverse events. In addition, the patients could not obtain a prolonged overall survival, higher objective response rate and disease control rate.

    Latest Developments

    Metabolomics in Childhood Asthma

    WU Ruijian, HUANG Yuge, LUO Lianxiang
    2022, 25(08):  1014-1020.  DOI: 10.12114/j.issn.1007-9572.2021.01.043
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    As the most common chronic disease in children, bronchial asthma is highly underdiagnosed with complex pathogenesis. By qualitative and quantitative analyses of changes in low molecular weight molecules or metabolites in biological samples, metabolomics provides a new method to search biomarkers and pathogenesis. We reviewed the application of metabolomics in childhood asthma, which attempts to find the potential biomarkers and pathogenesis of childhood asthma by analyzing the samples of blood, exhaled breath, feces and urine of asthmatic children and healthy children using targeted or untargeted research approaches, providing help for clinical diagnosis and treatment of childhood asthma. Considerable progress has been made in metabolomics in childhood asthma, but due to factors such as individual differences, sample collection, data analysis, and genomic heterogeneity, metabolomics analysis of childhood asthma is still facing challenges.

    Novel Developments in the Relationship of Gut Microbiota and Immune Regulation with Childhood Asthma

    CUI Tianyi, LIU Jiarui, LYU Bin, GAO Xiumei, ZHAO Xin
    2022, 25(08):  1021-1026.  DOI: 10.12114/j.issn.1007-9572.2021.01.045
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    Bronchial asthma, commonly known as asthma, is a frequently seen chronic respiratory disease that seriously threatens human health. More than 300 million people have had asthma worldwide, and most of them are children. Epidemiological investigations have shown that the prevalence of asthma among Chinese children aged 0-14 is 2.32%, and it is increasing year by year. Children are more prone to gut flora imbalance due to underdeveloped immune system, and physiologically successional changing of gut flora, which leads to the destruction of the intestinal mucosal barrier and local immune imbalance, eventually causing the development of asthma. We reviewed the latest advances in the immune regulatory mechanism of childhood asthma, and its association with gut microbiota, as well as interventions targeting gut microbiota, providing new ideas for the treatment of childhood asthma.