Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

  Objective  To understand the current status of surgical treatment for hemophilia osteoarthropathy (HO) in China.  Methods  Using an online questionnaire, select domestic hospitals that partici-pated in the compilation of the 'Guideline for perioperative management of hemophilia patients undergoing orthopaedic surgery in China ', in addition to members of the National Joint Surgery Group, and the Orthopedic Branch of the Chinese Medical Association for targeted investigation and analysis.  Results  A total of 17 domestic hospitals were included, all of which were general hospitals. Hospitals that started HO surgery treatment before 2000 accounted for 35.29%. A total of 3057 surgical cases of HO were reported by those hospitals. The most commonly performed surgical procedures were hip and knee joint replacement. The most commonly used coagulation factor replacement regimen was recombinant coagulation factor preparation. Ten hospitals reported finding patients with transfusion-related infectious diseases. Bleeding and hematoma formation were the most frequently reported surgical complications. Excessive length of hospital stay and high economic costs were the most frequently reported problems.  Conclusions  Surgical treatment for HO in 17 hospitals is mainly carried out in some large comprehensive medical centers in the eastern region. Compared with the patient base, the popularity and number of surgeries are still relatively insufficient. It is necessary to further standardize the treatment system by standardizing factor replacement and strengthening rehabilitation to improve surgical treatment outcomes.

Objective:To investigate the factors affecting phenotypes in the patients of methylmalonic acidemia combined with homocysteinemia cblC type with MMACHC c. 609G>A homologous variant. Methods:A retrospective study on the clinical manifestations, complications, treatment, and outcome in 164patients of cblC type with MMACHC c. 609G>A homologous variant was conducted.The patients were diagnosed by biochemical and genetic analysisfrom January 1998 to December 2020. Results:Among the 164 patients, 2 cases were prenatally diagnosed and began treatment after birth. They are 3 and 12 years old with normal physical and mental development. Twenty-one cases were diagnosed by newborn screening. Among them, 15 cases had with normal development. They were treated fromthe age of two weeks at the asymptomatic period. Six cases began treatment aged 1 to 3 months after onset. Their development was delayed. One hundred and forty-one cases were clinically diagnosed. Their onset age ranges from a few minutes after birth to 6 years old. 110 cases had early-onset (78.0%). 31 cases had late-onset (22.0%). Five of them died. 24 patients lost to follow-up. Of the 141 clinically diagnosed patients, 130 (92.2%) with psychomotor retardation, 69 (48.9%) with epilepsy, 39 (27.7%) with anemia, 30 (21.3%) had visual impairment, 27 (19.1%) had hydrocephalus, 26 (18.4%) had feeding difficulties, 7 (5.0%) with liver damage, and 5 (3.5%) with metabolic syndrome. The frequency of hydrocephalus and seizures was significantly higher in the early-onset group. The urinary methylmalonic acid increased significantly in the patients with epilepsy. During the long-term follow-up, the level of plasma total homocysteine in the seizure-uncontrolled group was significantly higher than that in the seizure-controlled group, the difference had a statistical significance ( P<0.05). Conclusion:Most of the patients with MMACHC c. 609G>A homozygous variant had early-onset disease, with a high mortality and disability rate. If not treated in time, it will lead to neurological damage, resulting in epilepsy, mental retardation, hydrocephalus, and multiple organ damage. Pre-symptomatic diagnosis and treatment are crucial to prevent irreversible neurological damage. Neonatal screening and prenatal diagnosis are important to improve the outcome of the patients.

Objective:To analyze the clinical features, genetic characteristics, treatment and follow-up results of patients with hydrocephalus caused by methylmalonic acidemia combined with homocysteinuria, and to discuss the optimal strategies for assessing and treating such patients.Methods:From January 1998 to December 2020, 76 patients with hydrocephalus due to methylmalonic acidemia combined with homocysteinuria in the Department of Pediatrics in 11 hospitals including Peking University First Hospital were diagnosed by biochemical, genetic analysis and brain imaging examination. The patients were divided into operation-group and non-operation-group according to whether they underwent ventriculoperitoneal shunt. The clinical features, laboratory examinations, genotype, and follow-up data were retrospectively analyzed. Data were compared between the two groups using rank sum test, and categorical data were compared using χ 2 test. Results:Among the 76 patients (51 male, 25 female), 5 were detected by newborn screening, while 71 were diagnosed after clinical onset, 68 cases (96%) had early-onset, 3 cases (4%) had late-onset. The most common clinical manifestations of 74 cases with complete data were psychomotor retardation in 74 cases (100%), visual impairment in 74 cases (100%), epilepsy in 44 cases (59%), anemia in 31 cases (42%), hypotonia or hypertonia in 21 cases (28%), feeding difficulties in 19 cases (26%) and disturbance of consciousness in 17 cases (23%). Genetic analysis was performed in 76 cases, all of whom had MMACHC gene variations, including 30 homozygous variations of MMACHC c.609G>A. The most common variations were c.609G>A (94, 62.7%), followed by c.658_660del (18, 12.0%), c.567dupT (9, 6.0%) and c.217C>T (8, 5.3%). Therapy including cobalamin intramuscular injection, L-carnitine and betaine were initiated immediately after diagnosis. A ventriculoperitoneal shunt operation was performed in 41 cases (operation group), and 31 patients improved after metabolic intervention (non-operation group). There was no significant difference in the age of onset, the age of diagnosis, the blood total homocysteine, methionine, and urinary methylmalonic acid concentration between the two groups (all P>0.05). The symptoms of psychomotor development, epilepsy, and visual impairments improved gradually after a long-term follow-up in the operation group. Conclusions:Hydrocephalus is a severe complication of methylmalonic acidemia combined with homocysteinuria. The most common clinical manifestations are psychomotor retardation, visual impairment, and epilepsy. It usually occurs in early-onset patients. Early diagnosis and etiological treatment are very important. Hydrocephalus may improve after metabolic intervention in some patients. For patients with severe ventricular dilatation, prompt surgical intervention can improve the prognosis.

Objective To study the diagnostic value of glycosylated hemoglobin(HbA1c)combined with ho-meostasis model assessment of insulin resistance( HOMA-IR)in obese children with prediabetes. Methods Five hundred and ninety-five obese children diagnosed at Outpatient Department of Pediatrics,Tianjin Medical University General Hospital were enrolled in the study from October 2012 to March 2016. Oral glucose tolerance test(OGTT)and HbA1c test were performed after fasting 8 to 10 hours for all the subjects. According to the World Health Organization (WHO)criteria,the obese children were divided into non-prediabetes group(483 cases)and prediabetes group(112 cases). The levels of HOMA-IR and HbA1c were compared between 2 groups. The receiver operating characteristic (ROC)curve was drawn for screening prediabetes,and the diagnosis value of area under curve( AUC)and different cutoff value were calculated. Logistic regression model was used to analyze the combined diagnosis of prediabetic AUC with preserved probability as a single variable and ROC curve. Z test was used to compare the statistical differences of each AUC. Results The levels of HbA1c and HOMA-IR of the prediabetes obese children group[(5. 65 ± 0. 36)%and 11. 60 ± 8. 86]were all higher than those of the non-prediabetes obese children group[(5. 47 ± 0. 32)% and 6. 49 ± 4. 61],and there were significant differences between 2 groups(all P<0. 01). The AUC of HbA1c ROC for prediabetes was 0. 633. When the cutoff was 5. 585%,the sensitivity and specificity were 0. 584 and 0. 601,respective-ly. The AUC of HOMA-IR ROC for prediabetes was 0. 758. When the cutoff was 7. 244,the sensitivity and specificity were 0. 779 and 0. 669,respectively. When combined with HOMA-IR and HbA1c,the AUC was 0. 764. Compared with HbA1c,there were significant differences in AUC of ROC curve between HOMA-IR alone or HOMA-IR com-bined with HbA1c in the diagnosis of prediabetes mellitus(all P<0. 01). There was no significant difference in AUC of ROC curve between HOMA-IR alone and HOMA-IR combined with HbA1c in the diagnosis of prediabetes melli-tus(P>0. 05). Conclusions Only HOMA-IR or HOMA-IR combined with HbA1c may be the optimal indexes for diagnosing obese children with prediabetes.

Objective To investigate the possible association of circulating components of GH-IGFs-IGFBPs system with the GHR-exon 3 genotype in idiopathic short stature (ISS) children. Methods Genomic DNA was extracted and isolat-ed from peripheral leukocytes in 108 ISS children. GHR-exon 3 polymorphism was analyzed with multiplex poly-merase chain reactions (PCR) assay. According to the results of genotype, ISS children were divided into GHRfl group and GHRd 3 group. The height and weight were recorded in two groups. The body mass index (BMI) and BMI standard deviation score (SDS) were measured. The serum levels of insulin-like growth factor (IGF)-1, IGF-binding protein (IGFBP)-3, IGF-1 SDS and IGFBP3 SDS were calculated. GH stimulation test was used to measure the serum GH peak value. Fifty-five ISS chil-dren were treated with recombine human GH [0.15 IU/(kg·d)] for three months to analyse the association of IGF-1 response of GH treatment and genotypes. Results There were 63 GHRfl and 45 GHRd3 in 108 ISS children. There were no signifi-cant differences in BMI, IGF-1, IGFBP3, GH peak, IGF-1 SDS and IGFBP3 SDS between two groups (P>0.05). Multiple stepwise regression analysis showed that age, IGFBP3, lg (BMI) and lg (GH peak) were influencing factors of lgIGF-1 (P<0.05). In 55 ISS children treated with rhGH, there were 34 cases of GHRd3. The differences of △IGF-1 and △IGF-1 SDS were higher in GHRd3 group than those of GHRfl group (n=21). Conclusion The GH sensitivity may be a risk factor in ISS children, which may not be related with GHR polymorphism.

Objective To investigate the characteristics of plasma glucose, insulin secretion and changes of insulin resistance (IR) after a glucose load in obese children, and to predict islet β-cell function. Methods A total of 635 obese children were classified into normal glucose tolerance (NGT) group (n=483), impaired glucose regulation (IGR) group (n=112) and type 2 diabetes mellitus (DM) group (n=40) based on their glucose levels. Subjects were also divided into G1 group (23 kg/m2≤BMI<30 kg/m2, n=393) and G2 group (BMI≥30 kg/m2, n=242) based on their different BMI levels. Level of fast plasma glucose (FPG, 0.5 h-PG, 1 h-PG, 2 h-PG and 3 h-PG) and insulin (FINS, 0.5 h-INS, 1 h-INS, 2 h-INS and 3 h-INS) were measured 0 h, 0.5 h, 1 h, 2 h and 3 h after a glucose load. Insulin resistance index (HOMA-IR), whole body insulin sensitivity index (WBISI), function of pancreatic beta-cell (HOMA-β), first-phase insulin secretion index (ΔI30/ΔG30) and area under curve of insulin (AUCI) were calculated and compared between groups. Results The value of insulin at each time point was significantly higher in IGR group than that of NGT group. The values of insulin at 0.5 h, 1 h, and 2 h were significantly lower in DM group than those of IGR group, respectively (all P<0.05). Compared with NGT group, AUCI, HOMA-IR and HOMA-β increased, but WBISI and ΔI30/ΔG30 decreased in IGR group (all P<0.05). HOMA-IR increased but WBISI, HOMA-βandΔI30/ΔG30 decreased in DM group (all P<0.05). Compared with IGR group, AUCI, HOMA-βandΔI30/ΔG30 decreased in DM group (all P<0.05). Values of FINS, AUCI, HOMA-IR, 2h-PG and HOMA-βwere significantly higher in G2 group than those of G1 group, but WBISI decreased (all P<0.05). There were no significant differences in FPG and ΔI30/ΔG30 between these two groups. Conclusion From NGT, IGR to DM, the peak of insulin secretion is postponed, insulin resistance is getting heavier and the compensation of insulin secretion after a glucose load is increased first and then decreased.

Objective To investigate the association of eosinophils with glucose and lipid metabolism disorder in obese children. Methods A total of 180 subjects,102 boys and 78 girls,aged 7 to 14 years were enrolled in General Hospital,Tianjin Medical University. The subjects were divided into 3 quartiles according to eosinophil percentage. E1 (0 to<37% of eosinophils),E2(37% to<73% of eosinophils),and E3(73% to 100% of eosinophils). Forty-six chil-dren were selected as control group with matched age and sex (26 boys and 20 girls). The body weight,height,waist circumference,blood pressure,blood routine examination,fasting plasma glucose (FPG),fasting insulin (FINS),and blood lipid in 4 groups were measured. The values of glucose and lipid metabolism and the indexes of physical examina-tion were compared among each group. Results The values of eosinophil percentage,body mass index (BMI),trig-ly-ceride,total cholesterol, low-density lipoprotein cholesterol, FINS, FPG,homeostasis model assessment of insulin resistance(HOMA-IR) and waist circumference in E1,E2,E3 group were significantly higher than those in control group,and the value of high-density lipoprotein cholesterol was significantly lower than that in control group,and there were significant differences (all P<0. 05). The blood pressure was significantly higher in E1 groups than that in other 3 groups (all P<0. 05). The values of BMI and HOMA-IR in E1 group were higher than those of E3 group(all P<0. 05). Eosinophil percentage was positively correlated with FINS (r=0. 190,P=0. 01),and negatively correlated with BMI and HOMA-IR(r=-0. 259,-0. 190 respectively,all P<0. 05). Conclusions Obese children have emerged glucose and lipid metabolism disorders. Peripheral eosinophil percentage may be an early marker of insulin resistance.

Objective To study clinical value and significance of thyroid receptor stimulating antibody (TSAb) and thyroid stimulating-blocking antibody (TSBAb) on diagnosis and treatment for children with Graves’disease (GD) and Hashimoto’s thyroiditis (HT). Methods Eighty-eight children with autoimmune thyroid disease (AITD) and treatment time less six months were divided into GD group (n=55) and HT group (n=33). Thirty-eight healthy children were used as control (Normal group). Human serum TSAb ELISA kit and human TSBAb ELISA kit were used to detect the serum TSAb and serum TSBAb in three groups. The serum levels of TSAb and TSBAb were compared between three groups. The correla? tion between TSAb and TSBAb, TSAb/TSBAb and free triiodothyronine three (FT3), free thyroxine (FT4), ultra sensitive thy?roid stimulating hormone (TSH) were analyzed. Results The serum level of TSAb was significantly higher in GD group than that of HT group and Normal group (P<0.05). The serum level of TSBAb was significantly higher in HT group than that of Normal group (P<0.05). There was no significant correlation between serum TSAb and serum TSBAb (P>0.05). There were no significant correlation between serum TSAb, TSBAb and FT3, FT4, TSH (P>0.05). Conclusion TSAb and TSBAb are related to the pathogenesis of GD and HT in children. TSAb and TSBAb have an important clinical value in the diagnosis and treatment for children with GD and HT.

Objective To study the relationship between the level of serum epithelial fatty acid binding protein (E-FABP) and cardiovascular disease in obese children. Methods Thirty children with metabolic syndrome (MS), 32 obesity children with no MS and 50 healthy children were recruited. Serum E-FABP and glucose/lipid metabolic indices were measured. Results Com-pared with the healthy children, levels of serum E-FABP in MS children were signiifcantly elevated (P=0.001). Compared with obesity children, levels of serum E-FABP of MS children were elevated, but the difference was not signiifcant (P>0.05). The cor-relations of E-FABP with waist to hip ratio, waist-to-height ratio, atherogenic index, fasting insulin, insulin resistance index were positive (P<0.05). According to the multivariate stepwise regression analysis, E-FABP was the independent risk of atherogenic index (P=0.018). Conclusions E-FABP plays a role in the development of atherosclerosis in obesity and MS.