Objective　To understand the clinical and pathological features of Epstein-Barr virus (EBV) associated hemophagocytic syndrome.Methods　The clinical data from one deceased pediatric patient of EBV associated hemophagocytic syndrome combined with severe hepatitis were retrospectively analyzed. The relevant literatures were reviewed. Results　The 1 year and 2 months old patient presented with fever, cytopenia, decreased fibrinogen and natural killer cells, elevated serum ferritin and triglycerides. The abnormal lymphocytes accounted for 5% in blood smear. There were 1.39×108 EBV-DNA copies/ml by fluorescence quantitative detection The autopsy results suggest that the cause of death was multiple organ failure. The EB virus encoded RNAs (EBERs) were detected in liver tissues by in situ hybridization. Approximately 30% lymphocytes were EBERs positive and the hepatocytes were EBERs negative. Conclusions　The patient was confirmed to have EBV associated hemophagocytic syndrome involving multiple organs. However the liver damage was not caused by the direct infection of EB virus.

Objective　To investigate the related risk factors of complicated parapneumonic effusion (CPPE) in children. Method　The clinical data of 88 children with parapneumonic effusion (PPE) were retrospectively analyzed from January 2013 to April 2015. According to the treatment effect of antibiotics, CPPE group and uncomplicated parapneumonic effusion (UPPE) group were divided. The univariate analysis of clinical and laboratory parameters was performed between two groups. Then the multifactor logistic regression was performed further. The receiver operator characteristic (ROC) curve was draw. Results The univariate analysis indicated that the risk factors were the formation of loculation and serum CD3+ and CD19+ levels (Z=2.030~7.457, P<0.05). The multifactor logistic regression showed that the formation of loculation（OR=3.386, P=0.018） and serum CD19+ levels （OR=4.000, P=0.009）were independent risk factors of CPPE. The area under the ROC curve (AUC) is 0.707, which indicated that the regression model had medium diagnostic accuracy (P=0.001). Conclusion　CPPE may be developed in PPE children with the serum level of CD19+ >30% and the formation of loculation.

Objective To explore the factors related to vasovagal syncope (VVS) in children. Methods The clinical data of 125 children with confirmed VVS were collected. According to the frequency of syncope during the five years from first episode to the time of head-up tilt test, the children with 2 or 3 episodes of syncope were assigned into the low episode group, and the children with 4 or more episodes of syncope were assigned into the high episode group. The two groups were analyzed and compared. Results Among the 125 children, 84 children (67.2%) were in the low episode group and 41 children (32.8%) were in the high episode group. The single factor analysis showed that the age at head-up tilt test, onset of syncopal, causes of syncope, history of carsickness, and positive family history were associated with high attack frequency. The results of non-conditional logistic regression analysis showed that causes of syncope (OR = 3.723, 95% CI: 1.163-11.918, P = 0.027), history of carsickness (OR = 5.929, 95% CI: 2.066-17.015, P = 0.001), and positive family history (OR = 6.794, 95% CI: 2.006-23.013, P = 0.002) were the independent risk factors of high attack frequency. Conclusions The causes of syncope (excluding persistent standing), history of carsickness, and positive family history have important clinical significance in predicting high attack frequency of VVS in children.

Objective To explore the effect of postnatal infection on SOX10 expression in cerebral white matter in immature rats. Methods A total of 96 newborn SD rats were randomly divided into hypoxia group, lipopolysaccharide (LPS) group, and control group. At day 3 and 6 after birth, the rats in LPS group and hypoxia group were intraperitoneally injected with 0.25 mg/kg of LPS while the rats in control group were injected with normal saline. Meanwhile the rats in hypoxia group were maintained in a hypoxic tank under atmospheric pressure and thermostatic water bath at 37℃ for 2 hours of ventilation with mixed gas containing 8% O2 and 92% N2 at a rate of 2 L/min starting 3 days after birth. At day 7, 10, 14, 21 after birth, eight rats in each groups were sacrificed and the cerebral white matter was extracted. HE staining was performed to observe the pathological changes of cerebral white matter by light microscopy. The expression of SOX10 in cerebral white matter was determined by immunohistochemical and Western blotting analysis. The expression of TLR-4 was determined by Western blotting. Results In LPS group and hypoxia group, the SOX10 positive cells and expressions of SOX 10 and TLR-4 were increased at day 7, reached the peak at day 10, and then gradually declined. There were significant differences between any two time points (P<0.05). In control group, there were a few positive cells and limited expressions of SOX 10 and TLR-4 and there were no differences between any two time points (P>0.05). At each time point, the difference in the SOX10 positive cells and the expressions of SOX 10 and TLR-4 were statistically significant among three groups (P<0.05) in the order of hypoxia group > LPS group > control group and there were significantly differences between each groups (P<0.05). Conclusions Postnatal infections can lead to cerebral white matter lesions in immature rats. The existence of both hypoxia and infection can aggravate the brain injury. The high expression of SOX 10 may have the protective effect.

　Objective　The aim of this study is to analyze the etiology and status of bone age of children with short stature. Methods　Anthropological and physical examination data were retrospectively collected and studied in 2132 children with short stature in the department of endocrinology between 2009 and 2014. Growth hormone (GH) levels were determined by arginine-clonidine test. Bone age was determined by CHN scoring. Results　Among the 2132 patients, 1333 were males and 799 were females. Mean age is 9.03 ± 3.04 years old, mean bone age is 6.81 ± 3.05 years. Of them, 324 cases (15.2%) were diagnosed complete GH deficiency, 780 cases (36.59%) were partial GH deficiency, 27cases (1.27%) were multiple pituitary hormone deficiency, 13 cases (1.64%) were hypothyroidism, 893 cases (41.89%) were idiopathic short stature, 19 cases (0.89%) were small for gestational age (SGA), 40 cases (1.88%) were chromosomal disorders, etc. Significant difference in age and bone age was  found using t test (P< 0.05). Significant differences in Δage were found between etiological categories using ANOVA (P=0.000). Δage was significantly and negatively associated with peak GH using Pearson's correlation. Conclusions　GH deficiency is the most common cause of short stature. Bone age of children with short stature is commonly delayed. Δage was significantly and negatively associated with peak GH. Multiple pituitary hormone deficiency has a significant effect on bone age. The etiology of patients with short stature cannot be determined just by bone age.

Cardiac involvement related to iron overload caused by long-term blood transfusion is a major cause of death for patients with thalassemia major. Patients’ survival will be improved greatly if cardiomyopathy resulted from transfusional iron overload could be detected timely and effective iron chelation be initiated promptly. In the present article, various evaluation methods currently used in clinical practice are reviewed, with particular focus on cardiac MRI for the monitoring of myocardial involvement related to iron overload.

With the inappropriate use of antibiotics, the situation of bacterial resistance is more and more severe. The emergence of multidrug-resistant (MDR) bacteria has made it difficult to cure the infections in clinical. For treatment the infections caused by MDR and reducucton of the generation of resistant bacteria, researchers are actively studying on the nonantibiotic substances for antibacterial activity. In this paper, the advances in those with confirmed effects such as phage therapy, metal/chelation therapy, immunization therapy, photodynamic therapy, and nitric oxide (NO)-based therapies, small molecule inhibitors, antimicrobial peptides and Chinese herb were reviewed.

Objective To investigate the changes of pathogens distribution and antimicrobial resistance in children with urinary tract infection (UTI) in 10 years. Methods The results of urine culture and drug sensitivity in children with UTI from January 2001 to December 2003, and from January 2011 to December 2013 were retrospectively analyzed．Results In recent 10 years, there was no obvious change in the ratio of gram-negative bacteria to gram-positive bacteria. Escherichia coli was still the main bacteria causing UTI in children. The detection rate of enterococcus was significantly increased from 18.3% in 2011-2013 to 7.5% in 2001-2003 (P<0.05) and it had become the second pathogenic bacteria. The isolation rate of ESBLs producing strains was significantly higher in 2011-2013 than in 2001-2003 (P<0.05). The rate of Escherichia coli sensitive to imipenem remained at 100% and it is also sensitive to enzyme inhibitors antibiotics and nitrofuranto. Sensitivities to antibiotics were changed in different species of enterococcus. Conclusions The distribution of pathogens and antimicrobial resistance in children with UTI are constantly changing. The clinician should pay close attention to changes of epidemiology in the region and hospital and rational use of antimicrobial drugs.

The incidence of children with iron deficiency (ID) and iron deficiency anemia (IDA) is still higher in our country now, but the relevant prevention and treatment still lag behind. This paper provides a brief summary of the importance and impact of childhood ID and IDA prevention and treatment practice based on the recent literatures and“The recommendations of prevention and treatment for children with iron deficiency and iron-deficiency anemia” recommended by the Pediatric Hematology Group recently.

Mycoplasma pneumonia (MP) is one of common pathogens of community-acquired pneumonia in children. In recent years, the incidence of MP pneumonia (MPP) shows a trend of increasing. The report of severe refractory MPP was more and more. Glucocorticoids has anti-inflammatory, anti-allergic and restraining immune response pharmacological effects and is the most effective anti-inflammatory drug currently. In this paper, pathogenesis of the lower respiratory infection by MP and the therapeutic effects of glucocorticoid were reviewed.

Objective　To explore the clinical features and factors influencing the prognosis of childhood non-Hodgkin's lymphoma (NHL). Methods　Pathologically diagnosed 78 pediatric patients with NHL and treated in the Affiliated Hospital of Qingdao University from January 2004 to August 2013 were collected and analyzed. Patients were grouped according to age, sex, tumor size, immunologic classification, B-symptoms, LDH, hemoglobin and clinical staging. The 5-years event-free survival rate (EFS) were calculated and analyzed by Kaplan-Meier method, and the difference of the survival rate between groups were compared. Using Cox proportional hazards model, we analyzed the possible factors that might influence 5-years event-free survival rate EFS , such as age and clinical staging. The OR value and the 95% CI were calculated. Results　Among the 78 cases, median age of onset is 7 years old, male to female ratio is 2.90:1, there are 25 cases of T-cell type and 53 cases of B-cell type. According to pathological types，Burkitt lymphoma is the most common (34.6%), followed by T-lymphoblastic lymphoma (20.5%), diffuse large B-cell lymphoma (11.5%). According to the St. Jude malignant lymphoma staging system, there are 2 cases in stage I, 9 in stage Ⅱ , 35 in stage Ⅲ and 32 in stage Ⅳ. Swelling of periphery lymph node (80.7%) was observed as initial symptom in 26 cases of lymphoblastic lymphoma. Among 45 cases of mature B-cell tumor, the main clinical feature including abdominal cavity and gingival were observed in 27 cases of Burkitt lymphoma. Among the 73 cases received treatments, 66 cases (90.5%) attained CR (complete remission) and 4 cases (5.5%) attained PR (partial remission) by cytology and radiographic assessment after two course of combined chemotherapy, 2 cases (2.7%) rapidly relapsed after the remisson of one course treatment, 1 case (1.3%) appeared the central nervous system infiltration in the chemotherapy. With median follow-up time of 42 months, the 5-year EFS of the 73 cases was (67.0+5.5)%. Single factor analysis showed that B-symptom, LDH, and clinical staging were significantly correlated with prognosis (P<0.05), while age, sex, tumor size, hemoglobin and immune classification was independent of prognosis (P>0.05). Multiple factor analysis showed that LDH and clinical staging influenced the prognosis (OR=3.34，95 ％ CI 2.275−10.683，P<0.01；OR=4.354，95%CI 1.519−12.475，P<0.01) . Conclusion　clinical features of childhood NHL are variable. LDH and clinical staging at primary diagnosis are important factors affecting the prognosis.

Objective　To explore the risk factors of obstructive hydrocephalus secondary to intracranial hemorrhage in premature infants. Methods　A total of 304 premature infants were selected who were diagnosed as sever intracranial hemorrhage (grade III and IV) by cranial bedside ultrasound admitted to our hospital from Jun. 2013 to Sep. 2014. According to whether the obstructive hydrocephalus was followed, all infants were divided into hydrocephalus group (n=59) and non-hydrocephalus group (n=185). The risk factors of obstructive hydrocephalus secondary to intracranial hemorrhage were analyzed and the lateral ventricle size was measured dynamically. Results　The univariate analysis showed the factors related with obstructive hydrocephalus were as follows: gestational age ≤ 32 weeks, birth weight < 1500g, severe asphyxia, cesarean section, RDS, neonatal infection, heart failure, PDA, acidosis, thrombocytopenia, coagulation abnormalities, and intracranial hemorrhage (grade Ⅲ or Ⅳ) (all P<0.05). Multivariate logistic regression analysis showed that acidosis, thrombocytopenia, coagulation abnormalities, gestational age ≤ 32 weeks, severe asphyxia, intracranial hemorrhage (grade Ⅲ or Ⅳ ) were independent risk factors for obstructive hydrocephalus (OR: 1.76~20.46, all P<0.05). At each time point after birth, the ratio of posterior horn of lateral ventricle was significantly higher in hydrocephalus group than that in non-hydrocephalus group (P<0.05). There were significant differences in the changes of the posterior horn ratio of left or right lateral ventricle with time in hydrocephalus group (P=0.000), increasing at 14 days and reaching the peak at 28 days after birth. Conclusions　The risk factors for obstructive hydrocephalus secondary to intracranial hemorrhage in neonates are important. Regular and dynamical monitoring of ventricle size by cranial ultrasound is needed in infants with sever intracranial hemorrhage.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection which affects children's health. The intestinal flora play an important regulatory role in host metabolism and immunity and are associated with a variety of diseases. Studies have shown that sepsis and clinical treatments can lead to intestinal flora imbalance in children, which further affects the prognosis of the disease; while healthy intestinal flora can reduce the susceptibility of children to sepsis and improve the survival of sepsis, and ameliorate the damage to the function of organs. This article reviews the related research on intestinal flora and sepsis, in order to contribute to the prevention and treatment of sepsis in children.

　Objective　To study the epidemic characteristics and disease spectrum of Epstein-Barr virus (EBV) infected children in Zhongshan region, Guangdong province. Methods Clinical data from the children with positive EBV-DNA detected by real-time fluorescent quantitative PCR between 2011 and 2013 was retrospectively analyzed. Results A total of 409 cases were detected with EBV-DNA positive from 3402 cases, with a total positive rate 12%, and the positive rate is 8.1% in 2011, 10.4% in 2012, 19.5% in 2013, there were significant differences among positive rate (χ2=6804.00, P<0.05). There was no statistically significant difference in the positive rate of EBV-DNA between different gender (χ2=0.239, P>0.05) and different age groups (χ2=136.96, P<0.05). The positive rate of pre-school group is the highest. EBV infection can cause multiple system diseases. The most common disease caused by EBV infection was infectious mononucleosis (61.6%), followed by respiratory tract infection (26.7%), neck lymphadenitis (3.4%), idiopathic thrombocytopenic purpura (2.4%), etc. Among the 409 cases of EBV infection, the concurrent other pathogen specific IgM positive cases as MP-IgM positive (n=79), CP-IgM positive (n=47), Parvovirus B19-IgM positive (n=20), HSV-IgM positive (n=11), CMV-IgM positive (n=10), and RV-IgM positive (n=4) were found. Conclusions Infectious mononucleosis is the leading disease in children infected by EBV in Zhongshan region, the annual positive rate is increasing. Multiple pathogen specific IgM may be detected positive in children with EBV infection, which should be interpreted in combination with clinical status.

Objective To systematic review the methodological quality of guidelines for Guillain-Barré syndrome (GBS) in children, to provide a reference for clinical evidence-based medicine. Methods Guidelines concerning GBS were electronically retrieved from PubMed, EMbase, CBM, Wanfang data, CNKI and Vip. The guide databases includes major medical institutions and industry sites such as NGC, GIN, TRIP , CDC, IDSA, AAP, WHO, Chinese Health and Family Planning Committee website, library of clinical guidelines China and Chinese clinical guidelines for collaboration. All the data were searched from inception of the database or network to Oct. 2013. Two reviews independently screened literature according to the inclusion and exclusion criteria, and assessed the quality of guideline using the AGREEⅡ . Intraclass correlation coefficient (ICC) was used to examine the conformance of the raters' evaluation scores. Results A total of 5 guidelines concerning GBS were included, with a time range from 2003 to 2012, and origins from USA, EU and Canada. The final recommendation levels of the 5 articles were level B. According to the AGREEⅡ, domain 3 and 4 showed the higher scores, and scores were generally low in domain 5. Plasma exchange (PE) and intravenous immuneglobulin (IVIG) showed positive effects on the treatment of GBS. But it was not recommended that combined PE and IVIG. Corticosteroids are also not recommended for GBS treatment. Conclusions The recommendations of medicines for GBS are basically consistent. However, the classification criteria of the levels of evidence and recommendation are still unconsistent and suboptimal. The guidelines on GBS should be improved in “Applicability” in future.

This paper explains most important points in the 2013 Guideline, including updated required RDI for total calorie, fluid and macronutrients such as protein, fat and carbohydrate in neonates, especially premature infants. It also covers the ways of delivering the nutrition (enteral vs parenteral), different dairy category and the handling of possible side effect in PN. The unified nutrition management is important.

In recent years, IgA nephropathy and Henoch-Sch?nlein purpura nephritis attract more and more attention on their unclear pathogenesis, single diagnostic criteria, long duration and poor prognosis, etc.. Research suggests that IgA nephropathy and purpura nephritis are IgA immune complex diseases, and serum galactose-deficient is elevated in patients with these two diseases, which might become a noninvasive biomarker for the diagnosis, prognosis prediction and disease development monitoring for IgA nephropathy and purpura nephritis. Galactose-deficient IgA1 is reviewed for its discovery, structure, process, the possible pathogenic mechanism and its significance in details in this paper.

Despite that improved neonatal intensive care unit therapies have reduced the mortality of preterm neonates, neonatal neurodevelopmental morbidity persists at high rates. There is increasing recognition that following perinatal brain injury, cognitive deficits in preterm neonates can often occur in the absence of significant impairment and cerebral palsy often due to non-severe white matter injury (WMI). Minicystic and diffusive white matter lesions that need MRI detecting make up the predominant role in the preterm brain injury. The target cells and tissue of WMI in the preterm infant not only focus to preoligodendrocytes and white matter, but also involve neurons and grey matter. In fact, brain developmental trajectory in the premature infant with WMI is a mixed disorder of destructive and dysmature processes. Current MRI applied with high resolution could detect the punctate and diffusive WMI at early stage, distinguish the hemorrhagic lesions from reactive gliosis, analyze cerebral metabolism, and even describe the developmental progresses of myelination, fiber tract, cortex and cerebral connectome. But the predictive value of different MRI techniques in brain development requires more and long-term research through the all life stages.

Acute myeloid leukemia accounts for about 15%-20% of childhood leukemia, and nearly 40% of pediatric patients still relapse after standard chemotherapy. Allogeneic hematopoietic stem cell transplantation is a powerful means to prevent its recurrence. However, some patients still relapse, and the 2-year survival rate of these patients is less than 20%. Some patients with relapse cannot tolerate or are insensitive to conventional chemotherapy. Recurrence is the main cause of death after transplantation. The prevention of relapse after transplantation ought to start before transplantation, optimize each part of the transplantation chain, and strictly follow the follow-up monitoring. In recent years, new molecular targeted drugs, new immunotherapy and CRISPR genome-edited hematopoietic stem cell therapy have also provided more treatment strategies for pediatric patients with AML relapse after transplantation. According to the procedure of transplantation chain, this paper summarized the preventive measures of each link and the treatment options of post-transplantation recurrence, in order to provide the direction and strategy for the clinic.

Objective To dynamically monitor and analyze infants with cow’s milk protein allergy (CMPA), milk protein tolerance and changes in gut microbiome during clinical treatment. Methods Fifty infants with CMPA attended the pediatric outpatient clinic were selected as the CMPA group, and 20 infants underwent health checkups were selected as the healthy control groupat the Child Health Development Center of Peking University Third Hospital from September 2020 to March 2021. The differences in gut microbiome between the two groups were compared. Results There were 50 patients in the CMPA group, including 21 males and 29 females, with a median age of 4 months. The control group consisted of 20 cases, of 12 males and 8 females, with a median age of 4 months. There were no statistically significant differences between the CMPA group and the control group in terms of age inmonths, sex, birth mass, mode of delivery, and feeding mode (all P>0.05). The baseline data of the children in the two groups were comparable. Follow-up of treatment and regression of children in the CMPA group at months 1, 3, and 6 revealed that a total of 38 children had established immune tolerance by 6 months, and 12 others still had CMPA. The Shannon index and Shannoneven index were statistically higher in the CMPA group compared with the control group (P<0.05), and the Anosim test showed statistically significant differences in community composition between the two sample groups (R=0.26, P=0.001). The relative abundance of Actinobacteria was significantly lower in the CMPA group. The relative abundance of Firmicutes was higher in the tolerant group than in the allergic group after six months of follow-up. During the treatment of CMPA-tolerant infants, species with progressively higher abundance were observed for Bifidobacterium (P<0.01), Blautia (P<0.01), Ruminococcus (P<0.01) and Faecalibacterium (P<0.01). Except for Bifidobacterium, all other species were known as butyrate producers. Conclusion The gut microbiome of children with CMPA differs from that of healthy children. The relative abundance of Bifidobacterium and butyrate-producers microbiome in the intestine of children with CMPA was increased during the establishment of immune tolerance.

Developmental and epileptic encephalopathy (DEE) is a group of heterogeneous disorders characterized by early-onset epilepsy, abnormal electroencephalography and developmental retardation or regression. The etiology of DEE is complex, with high disability rate and fatality rate. With the development of next-generation sequencing technology, more and more genetic causes related to DEE have been discovered, which also deepens the acknowledgement on the pathogenesis of DEE. These researches provide a basis for exploring different treatment methods, especially gene therapy. It is expected that gene therapy will be carried out in the future to improve the prognosis of DEE.

　Objective　To investigate the occurrence trend and risk factors of recurrent respiratory tract infection during the first year after Mycoplasma pneumoniae pneumonia (MPP) in children. Methods The clinical data of 133 children completely recoved from MPP and one year follow-up after MPP were included in this study, MPP IgM IgG double antibody titer were measured in different time slots (3 month, 6 months, 9 months, 12 months) after discharge. Information on frequency of recurrent respiratory tract infections, respiratory tract infection site, and drug use within one year were collected. Possible factors affecting the occurrence of recurrent respiratory tract infection were analyzed by means of single factor and multi factor analyses. Results In 133 patients, the recurrent rate was 31.58% in the first year; aged 3-6 years old (OR=2.29，95%CI：1.13~4.64), or continuous positive or negative to positive antibodies (OR=4.47，95%CI：1.47~13.65), or low CD4/CD8 (OR=10.26，95%CI：3.30~31.90), or low IgA (OR=1.90，95%CI：1.06~3.40) is independent risk factor of recurrent respiratory tract after MPP; immune enhancer therapy is an independent protective factor (OR=0.29，95%CI：0.11~0.78). Conclusions Immune function disorders in the first year after MPP were independent risk factors of recurrent respiratory tract infection. MP antibody positive without clinical symptoms and sustained antibody positive can not prevent the recurrence of respiratory tract infection without use of antibiotics. Immune enhancer was advocate to adjust immune function and reduce the incidence of repeated respiratory tract infection.

The complement system, the chief component of innate immunity, is not only required for host defense against pathogens and homeostasis, but also related to the pathogenesis and development of various kidney diseases. Recent study has shown that tissue-derived complement and immune cell-derived complement can each mediate local inflammation. The complement system acts as a bridge between innate and adaptive immunity. Furthermore it’s also a functional bridge between pathogenic humoral and cellular immune responses in an array of kidney diseases. Increasing evidence links inappropriate complement activation and deficiencies of complement proteins to the pathogenesis of kidney autoimmune disease, ischemia-reperfusion injury, transplant rejection and complications in hemodialysis. The development of pharmacologic agents that target complement in patients with this assortment of immune and/or inflammatory kidney diseases has the potential to abrogate disease progression and improve patient health.

　Conotruncal heart defects (CTDs) are complex congenital heart defects caused by abnormal development of ventricular outflow tract during embryonic period. They are common types of congenital heart disease and have poor prognosis after birth, which seriously endanger children’s health. In recent years, researchers at home and abroad have carried out a large amount of genetic study on CTDs. The specific disease-causing genes and their mechanism yet remain unknown, however, numbers of recognized candidate genes have been screened out from experimental animals and patients. The article focuses on summarizing researches on candidate gene mutations and provides reference for the etiology study of CTDs.

Objective To explore the efficacy and safety of lactase additive in improving lactose intolerance in premature infants. Methods Preterm infants with lactose intolerance admitted to Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai First Maternal and Infant Health Hospital, Children's Hospital Affiliated to Zhejiang University School of Medicine and Children's Hospital Affiliated to Soochow University from January 2018 to December 2019, who met the inclusion criteria were included in the study. They were divided into lactase treatment group and control group randomly, with 80 cases in each group. For the patients in the lactase treatment group, 4 drops (180 mg) of lactase were added to each feeding of breast milk or formula milk for premature infants, and Bifidobacterium triple viable powder was orally administered and abdominal massage was used as adjuvant therapy. For patients in the control group, 4 drops (180 mg) of placebo were added to each feeding, and the same probiotics and abdominal massage as the treatment group were given, After 1 and 2 weeks treatment, symptoms of lactose intolerance, weight, fecal pH, fecal reducing sugar and other indicators were compared between the two groups. Results seventy-eight patients in the lactase treatment group and 77 patients in the control group, respectively, completed the whole study. After the first week intervention, the positive rate of reducing sugar in the lactase treatment group was lower than that in the control group (P<0.05). At the end of the second week treatment, the proportion of abdominal distension in the lactase treatment group were lower than those in the control group (P<0.05), and the positive rate of reducing sugar was lower than that in the control group (P<0.05). The increase of feeding amount was also higher than that of the control group (P<0.05). During the course of the study, no adverse reactions to lactase additives or probiotics were found in both groups. Conclusions Lactase supplementation can effectively and safely improve the clinical symptoms caused by lactose intolerance in premature infants.

Objective To explore the clinical features and prognosis of acute myeloid leukemia (AML) with positive TLS/ERG gene in children. Methods The clinical data of TLS/ERG gene positive AML in 6 children admitted from June 2008 to December 2018 were retrospectively analyzed, and the prognosis data of 62 similar cases of children reported in domestic and foreign literature were summarized and analyzed. Results Six AML children with positive TLS/ERG gene was 1 . 3 % of the AML children from 0 to 18 years admitted in the same period. They were 4 boys and 2 girls with a median age of 9 . 1 years ( 4 . 0 - 14 . 0 years). One case was complicated with central nervous system (CNS) leukemia at the onset. In addition to expressed myeloid markers CD 117 , CD 13 , CD 33 , and CD 34 , immunophenotypic expression of CD 56 was found in 4 ( 66 . 7 %) children. There was no remission after induction chemotherapy in 3 children. Bone marrow recurrence occurred in 3 of 5 children receiving allogeneic hematopoietic stem cell transplantation, and the median recurrence time was 11 . 6 months ( 3 . 0 - 22 . 0 months) after transplantation. After transplantation, one patient relapsed in the form of CNS leukemia, but the bone marrow was in sustained remission. Bone marrow had the sustained remission in 1 case. By summarizing the prognostic data of children with TLS/ERG positive AML reported in the literature, it was found that all patients in the chemotherapy group experienced recurrence, and the recurrence rate in the transplantation group was 69 . 2 %. One of the patients had sustained remission and long-term survival after a second transplant following recurrence. Conclusions The incidence of TLS/ERG positive AML is extremely low, most of its immunophenotypes are associated with CD 56 expression, and the overall prognosis is poor. Hematopoietic stem cell transplantation can improve the prognosis, which is still the recommended treatment for the first remission period, but the recurrence rate after transplantation is still high. It is needed to improve treatment methods and find new treatment options.

Objective　To investigate the clinical characteristics and pedigree genetics of  neurodegeneration with brain iron accumulation 5. Methods　Clinical features and imaging findings of two patients with neurodegeneration with brain iron accumulation 5 were analyzed, and whole-exome sequencing was used to identify WDR45 gene mutations. Results　A ten month old male infant and a three-year-old female child had history of comprehensive development retardation, the boy had a history of suspected seizures, magnetic resonance imaging (MRI) showed progressive brain atrophy; and the girl had a history of epilepsy, cranial MRI showed slightly hyperintense on T2-weighted images and T2 Flair in the globus pallidus. Whole-exome sequencing identified a novel frameshift mutation c.276-c277insC in exon 6 of WDR45 in the boy  and a reported mutation c.19C> Tin in the girl, which were not found in both parents. Conclusion  The WDR45 gene sequencing combined with medical history and cranial MRI can be used to diagnose neurodegeneration with brain iron accumulation 5 .

Proteinuria is one of the common symptoms of kidney disease in children. At present, there is neither unanimous understanding of the classification of proteinuria, nor clear thoughts of diagnosis of proteinuria in pediatrics. This paper summarizes and organizes the classification and diagnosis of proteinuria, and proposes the concept of proteinuria in a broad and narrow sense, as well as the four-step diagnosis idea of qualitative, quantitative, location， and cause determination. It especially points out that the ratio of α 1 microglobulin to microalbumin close to or greater than 1 in urine can be used as the judgment standard for the location diagnosis of proteinuria in small molecule proteinuria.

　The incidence of malnutrition in hospitalized children is high, and nutritional risk screening for hospitalized children is important for timely and appropriate nutritional therapy. The current nutritional risk screening tools for pediatric inpatient include subjective global nutritional risk assessment (SGNA), simple pediatric nutritional risk score (PNRS), screening tool for the assessment of malnutrition in pediatrics (STAMP), screening tool for risk of impaired nutritional status and growth (STRONG-kids), pediatric Yorkhill malnutrition score (PYMS), pediatric nutrition screening tool (PNST) and pediatric digital scaled malnutrition risk screening tool (PeDiSMART). All kinds of screening tools have their own advantages and disadvantages. Further studies are needed to find a simple, rapid and reliable screening tool. This article reviews the application of various nutritional risk screening tools for hospitalized children in recent years.

Primary ciliary dyskinesia (PCD) is an autosomal recessive or x-linked disorder of cilia structure and (or) function, with a morbidity of 1:10 000–1:50 000 from foreign reports, while epidemic data of PCD in China is not available yet. PCD is due to cilia biallelic gene mutations leading to impaired tissue structure and organ function. Clinical phenotypes includechronic infections of the respiratory tract, fertility problems, disorders of organ laterality, etc, and the percent age of Kartagener syndrome is about 50%. The frequently used diagnostic methods are nasal NO examination, high-speed video microscopy, electron microscopy, genetic tests, chest high-resolution computed tomography and spirometry at present. Each method has its highlights and disadvantages, meanwhile, effective diagnostic algorithm and therapeutic protocols are needed for further research.

　Objectives　To retrospectively analyze the clinicopathological features of neuroblastoma (NB) and investigate the significance of abnormality of N-myc and anaplastic lymphoma kinase (ALK) gene copy number change as well as ALK mutations in NB. Methods Eighty-three NB patients were collected and classified into different subgroups according to the clinical stage and histology. Fluorescence in situ hybridization (FISH) was performed to detect the abnormalities of N-myc and ALK genes. The extracted DNA was amplified by PCR and sequenced to investigate the point mutations of the ALK gene. Follow-up data were collected and survival analysis was performed. Results　FISH detection showed that the aberration of N-myc gene copy number presented as gain and amplification. The aberration of ALK gene presented as point mutation and gain. It was shown that 17 cases had the abnormality of both N-myc and ALK gene. Survival analysis showed that the prognostic factors included the clinical stage, age and abnormality of N-myc genes. Conclusion　Detection of N-myc and ALK abnormality in NB would be helpful for evaluating the prognosis and providing theoretical basis for ALK target therapy.

Inherited platelet function disorders (IPFDs) is a rare disorder. The clinical manifestations were heterogeneous, mainly characterized by spontaneous cutaneous and mucosal hemorrhage, menorrhagia, difficulty in hemostasis after trauma, with or without thrombocytopenia. Its incidence has been underestimated due to difficulties in clinical diagnosis. Treatment and management of the disease are also challenging. This study summarized the classification, clinical manifestations, diagnosis, treatment and management of IPFDs, to improve the understanding of IPFDs and provide reference for diagnosis, treatment and management of IPFDs for front-line pediatricians.

Objective To analyze the clinical characteristics, treatment, and prognosis of post-infectious bronchiolitis obliterans (PIBO) in children. Methods Clinical data from 35 children diagnosed with PIBO were retrospectively analyzed from April 2010 to June 2015. The children were divided into different groups according to the length of glucocorticoid use, and the prognosis were compared. Results Thirty-five children all presented cough and wheezing. There were 12 cases in the group of less than one year of glucocorticoid treatment, 8 cases in the group of 1-2 years of glucocorticoid treatment, and 6 cases in the group of great than or equal to 2 years of glucocorticoid treatment. There was no significant difference in the prognosis among the groups (P > 0.05). Conclusions The overall prognosis is poor in children with PIBO, even if the symptoms are improved. Glucocorticoid is helpful to remiss the symptoms of cough and wheezing, but prolonged use have no significant effect on the prognosis.

Klebsiella pneumoniae is well known as a causative agent of both community and nosocomial infections and is generally believed to be the cause of 10% of the nosocomial infection. Recently, with the widespread using of carbapenem, the isolation of carbapenem-resistant strains has been greatly increased, which bring great difficulties and challenges in clinical treatment. In this article, the progresses in the mechanisms of carbapenem, resistance in Klebsiella pneumoniae such as the acquisition of carbapenemases, hyperproduction of AmpC cephalosporinases or extended spectrum beta-lactamases (ESBLs) in combination with loss of the outer membrane protein, efflux pump system, and biofilm were reviewed.

Objective To investigate the clinical and laboratory diagnosis in a rare case with dwarfism and multisystem abnormalities. Methods Whole-exome sequencing was performed and data was processed using high-throughput data analysis pipeline. Genetic test result is verified by Sanger sequencing. Results This is a 14 -year-old boy with short stature (the height is 132 cm) and autoimmune hemolytic anemia. He was treated with long-term oral prednisone. Head CT from other hospital found multiple calcifications on both sides of the basal ganglia, two sides of the frontal lobe, and the left side of parietal lobe. Lateral spinal X-ray photography showed flat in thoracolumbar vertebral body. Valgus was surgically corrected. He also has facial pigmentation spot and onychomycosis. Whole-exome sequencing combined with Sanger sequencing identified a known homozygous pathogenic mutation in ACP5 genes (c. 643 G>A, p.G 215 R). Identification of such a mutation results in the diagnosis of spondylo enchondrody splasia with immune dysregulation (SPENCDI). Conclusions Wholeexome sequencing is one of the effective methods for detection of rare disease, the SPENCDI case reported here is a good example of it.

Objective To investigate the clinical significance of perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) in children with systemic lupus erythematosus. Methods The clinical data of SLE children treated from January 2016 to July 2021 were retrospectively analyzed. The autoantibody related indexes, immune function, renal function and renal pathology of pANCA positive and negative children were analyzed. Results A total of 191 SLE children (160 girls and 31 boys) were enrolled, and the average age was (12.0±3.5) years. There were 81 children in pANCA positive group, among whom 26 were formaldehyde-resistant pANCA positive and 55 were formaldehyde-sensitive pANCA positive. Anti-myeloperoxidase (MPO) antibody was positive in 29 children, accounting for 35.8% of pANCA positive children. Compared with pANCA negative group, children in pANCA positive group had higher ESR, lower Hb, and higher positive rates of antinuclear antibody, anti-double-stranded DNA (dsDNA) antibody, anti-Sjögren's-syndrome-related antigen A (SSA) autoantibody, anticentromere protein B (CENP-B) antibody, anti-histone antibody, anti-ribosome ribonucleoprotein (rRNP) antibody, anti-nucleosome antibody and anti-Ro-52 antibody. The differences were statistically significant (P<0.05). Compared with pANCA negative group, pANCA positive group had lower levels of complement C3 and C4, higher levels of urinary creatinine (UCr), urinary immunoglobulin G/UCr, α1-microglobulin/UCr, β1-microglobulin/UCr and urinary microalbumin/UCr, and higher proportion of urinary occult blood and urinary protein, and the differences were statistically significant (P<0.05). A total of 112 children with SLE underwent renal biopsy. Compared with the pANCA negative group, the proportion of mesangial hyperplasia and the deposition proportion of IgG, IgM, IgA, C1q and C3 in glomerular mesangium and capillary loop was higher in the pANCA positive group, and the differences were statistically significant (P<0.05). Conclusions In children with SLE, pANCA positive children are more likely to have renal injury and more severe symptoms.

　Congenital hypothyroidism (CH) refers to abnormalities in the occurrence, development and functional metabolism of hypothalamus-pituitary-thyroid axis during embryonic period due to some causes, resulting in a decrease in thyroid hormone levels in the blood circulation of children. Without timely diagnosis and treatment, the growth and development of children will be seriously affected. In recent years, gene detection has been gradually applied to the clinic, and the discovery of disease-causing genes will be beneficial for early diagnosis or pre-symptomatic diagnosis of CH and prenatal diagnosis. The article describes the research progress in related gene mutations causing CH from both syndromic and nonsyndromic aspects.

Objective　To investigate the copy number variants of a developmental delay patient by applying single nucleotide polymorphisms array technique and to analyze the relationship between the clinical manifestation and copy number variants. Methods　Single nucleotide polymorphisms array was used to detect genomic copy number variants in a child with development delay and her phenotypic normal parents. Results　The patient had a 7. 9-Mb deletion at 8p23.3-p23.1 and a 27.4-Mb duplication at 8p23.1-p11.23, which were confirmed as pathogenic copy number variants after comparative analysis with database. Conclusions　Single nucleotide polymorphisms array could serve as a useful method to diagnose developmental delay patients and analyze pathogenesis.

Immune thrombocytopenia (ITP) is the most common bleeding disorde characterized by isolated thrombocytopenia in children. It is mediated by a variety of autoimmune mechanisms. Children with ITP usually have acute onset. A considerable proportion of patients can be traced back to the history of precursor infection or vaccination, which can make them immune intolerant, resulting in the occurrence of ITP. There is strong heterogeneity of ITP in children. At present, more and more children tend to relapse. The first-line treatment is not effective, and the protracted treatment leads to chronic ITP. Clinicians should make corresponding individualized treatment and give reasonable management according to the characteristics of each child to reduce treatment-related complications and improve the quality of life of children.