Objective To investigate the correlation between the level of circulating placental growth factor(PLGF)and the severity of preeclampsia(PE),maternal and infant outcomes and placental pathology.Methods A total of 159 PE patients were selected as the study subjects and divided into the PE1 group(62 PE patients with termination of pregnancy<34 weeks)and the PE2 group(97 PE patients with termination of pregnancy≥34 weeks)according to the gestational age of pregnancy termination.A total of 107 non-PE patients who gave birth during the same period were selected as the control group.Patients were divided into two groups according to the gestational age of termination:the non-PE1 group(41 non-PE patients with termination of pregnancy at<34 weeks)and the non-PE2 group(66 non-PE patients with termination of pregnancy at≥34 weeks).General data were collected in each group of pregnant women,including age,body mass index(BMI),admission systolic blood pressure,diastolic blood pressure,24 h urinary protein quantity,gestational times,presence of FGR and fetal embarrassment.General information of newborns during the operation were collected,for example,whether there was fecal contamination of amniotic fluid,neonatal asphyxia,and days of newborn stayed in NICU.PLGF in venous blood of pregnant women was detected on the day of delivery.The placenta was pathologically detected and scored.After delivery,blood gas of umbilical artery was analyzed,and PH(pH),base surplus(BE),lactic acid(LAC)were recorded.Results There were no significant differences in age,gestational times and delivery times between the PE1 group and the PE2 group and the corresponding the non-PE1 group and the non-PE2 group.BMI was higher in the PE1 group and the PE2 group than that in the non-PE1 group and the non-PE2 group.PLGF was lower in the PE1 group and the PE2 group than that in the non-PE1 group and the non-PE2 group,respectively,and PLGF was lower in the PE1 group than that in the PE2 group(P＜0.05).The 24 h urinary protein quantity,systolic blood pressure,diastolic blood pressure and pathological changes of placenta were higher in the PE1 group than those in the PE2 group(P＜0.05).There were no significant differences in fecal staining of amniotic fluid,fetal embarrassed condition and pH value of umbilical artery blood gas during delivery between the PE1 group and the PE2 group.Compared with the PE2 group,the proportion of neonatal asphyxia and FGR,the umbilical artery blood gas LAC were increased,the BE value was decreased,and the time of staying in NICU was prolonged in the PE1 group(P＜0.05).Conclusion The level of circulating PLGF is decreased in patients with preeclampsia.PLGF has certain value in evaluating PE and predicting adverse pregnancy outcome.

Objective To explore the myopia control effect of orthokeratology(OK)lenses and build a prediction model of myopia control effect based on random forest and Logistic regression,so as to provide a basis for further impro-ving adolescent vision.Methods A total of 289 patients who wore OK lenses after seeing an ophthalmologist in Shiji-azhuang People's Hospital from January to June 2019 were selected as the OK lens group,and a total of 289 patients who wore framed glasses during the same period were selected as the framed glass group.After 2 and 4 years of wearing,the in-crease in axial length(AL)of the patients was observed.The patients were divided into a well-controlled myopia group and a poorly-controlled myopia group according to the changes in AL of the eyes after wearing OK lenses for 4 years.The fac-tors influencing the myopia control effect were analyzed based on random forest and Logistic regression,and a nomogram prediction model was constructed.The performance of the model was evaluated using the receiver operating characteristic(ROC)curve,calibration curve,and decision curve analysis(DCA).Results After 2 and 4 years,the diopter increase and AL increase of patients wearing OK lenses were lower than those of patients wearing framed glasses(all P＜0.001).There were no significant changes in corneal endothelial cell parameters and central corneal thickness at the thinnest point before,2 years and 4 years after wearing between the two groups(all P＞0.05).The random forest model showed that basic AL,daily wear time,correct eye health behavior,pupil diameter,daily outdoor activity time,homework time after school,and daily sleep time were the top 7 variables in importance ranking.Logistic regression analysis showed that home-work time after school was a risk factor for poor myopia control in OK lens wearers,while basic AL,pupil diameter,daily wear time,correct eye health behavior,daily outdoor activity time,and daily sleep time were protective factors for myopia control.The ROC curve,calibration curve,and DCA suggested that the nomogram prediction model constructed based on random forest and Logistic regression analysis had good accuracy,consistency and clinical effectiveness.Conclusion OK lens shows good myopia control effect,has little effect on corneal endothelial cells and corneal thickness,and demon-strates high safety.Homework time after school,basic AL,pupil diameter,daily wear time,correct eye health behavior,daily outdoor activity time,and daily sleep time are influencing factors of myopia control.Strengthening the construction of a prediction model is helpful in identifying high-risk groups with poor myopia control and guiding clinical interventions in time.

OBJECTIVE: To analyze the clinical characteristics and spectrum of SPTB gene variants among 16 Chinese children with Hereditary spherocytosis (HS) and explore their genotype-phenotype correlation. METHODS: Sixteen children who were diagnosed with HS at the Affiliated Hospital of Capital Institute of Pediatrics from November 2018 to July 2022 were selected as the research subjects. Genetic testing was carried out by whole exome sequencing. Candidate variants were verified by Sanger sequencing and subjected to bioinformatic analysis and prediction of 3D structure of the protein. Correlation between the SPTB genotypes and clinical phenotypes was analyzed using Chi-squared test. RESULTS: The male-to-female ratio of the HS patients was 6 : 10, with the median age being 7-year-and-10-month. Clinical features of the patients have included anemia, reticulocytosis and gradual onset of splenomegaly. Mild, moderate and severe anemia have respectively occurred in 56.25% (9/16), 31.25% (5/16) and 12.50% (2/16) of the patients. SPTB gene variants were detected in all patients, among which 10 were unreported previously and 7 were de novo in origin. Loss of function (LOF) variants accounted for 93.75% (15/16). Only one missense variant was detected. Eleven, 4 and 1 of the variants had occurred in the repeat domain, CH1 domain, and dimerization domain, respectively. There was no significant correlation between the type or domain of the SPTB gene variants with the clinical features such as severity of anemia (x² = 3.345, P > 0.05). All of the variants were predicted to be pathogenic or likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics. CONCLUSION Mild to moderate anemia are predominant clinical features of the HS children harboring a SPTB gene variant, for which LOF variants are the main mutational type. The clinical feature of HS is unaffected by the type of the variants.
Child ; Female ; Humans ; Male ; Computational Biology ; Genetic Testing ; Genomics ; Genotype ; Spherocytosis, Hereditary/genetics* ; East Asian People/genetics* ; Spectrin/genetics*

Copy number variants (CNVs) are common causes of human genetic diseases. CNVs detection has become a routine component of genetic testing, especially for pediatric neurodevelopmental disorders, multiple congenital abnormalities, prenatal evaluation of fetuses with structural anomalies detected by ultrasound. Although the technologies for CNVs detection are continuously improving, the interpretation is still challenging, with significant discordance across different laboratories. In 2020, the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen) developed a guideline for the interpreting and reporting of constitutional copy number variants, which introduced a quantitative, evidence-based scoring framework. Here, we detailed the key points of interpreting the copy number gain based on the guideline, used six examples of different categories to illuminate the scoring process and principles. We encourage a professional understanding and application of this guideline for the detected copy number gains in China in order to further improve the clinical evaluation accuracy and consistency across different laboratories.
Child ; DNA Copy Number Variations ; Female ; Genetic Testing ; Genetics, Medical ; Genome, Human/genetics* ; Genomics ; Humans ; Pregnancy ; United States

Objective:To evaluate the utility of whole-exome sequencing (WES) in early diagnosis for children with language delay/disorder.Methods:Children with language delay/disorder who were admitted to the Department of Health Care, Children′s Hospital Affiliated to the Capital Pediatric Institute from January 2019 to December 2020 were analyzed retrospectively. Based on informed consent, the peripheral blood of the children and their parents was collected for WES. Combining the clinical phenotypes of the children, the candidate variants, including single nucleotide variants (SNVs) and copy number variations (CNVs), were selected for validation and family segregation analysis using Sanger sequencing, real-time PCR or CNV-Seq. The pathogenicity of variants was evaluated based on ACMG guideline following with finial genetic diagnosis. Based on whether genetic diagnosis was achieved or not, 125 children with comprehensive examination of the Children Neuropsychological and Behavioral Scale(CNBS-R2016) were sub-grouped (positive/negative group), and the total scores and the detailed scores of five developmental sections (gross motor, fine motor, adaptive ability, language and social behavior ability) between two subgroups were compared.Results:A total of 165 children with language delay/disorder were recruited, including 109 males and 56 females. The ratio of boys to girls was 1.95∶1.The age of the children was (3.2±1.2) years old, the median age was 3.0 years. 45 children carry disease-related pathogenic/likely pathogenic variants, including 36 SNVs and 9 CNVs. The genetic diagnostic yield of this cohort was 27.3% (45/165). The inheritance analysis for core family members showed de novo variant accounted for 86% of genetic diagnosis (31/36). The positive diagnosis rate in girls was 45% (25/56), which was significantly higher than that in boys (18.3%, 20/109, χ2=12.171, P<0.05). There was no significant difference in the rate of positive diagnosis among all age groups (χ2=4.349, P>0.05). Interestingly, the scores of gross motors of positive group were significantly lower than that of negative group (61.5 vs. 69.4, t=-2.610, P<0.05). Otherwise, no significant difference was seen between two groups( t=-0.933, -1.298, -0.114, -0.214, all P>0.05). Conclusions:Language delay/disorder has complex genetic heterogeneity. WES has important application value in early etiological diagnosis for children with language delay/disorder.

Objective:To evaluate the utility of whole-exome sequencing (WES) in early diagnosis for children with language delay/disorder.Methods:Children with language delay/disorder who were admitted to the Department of Health Care, Children′s Hospital Affiliated to the Capital Pediatric Institute from January 2019 to December 2020 were analyzed retrospectively. Based on informed consent, the peripheral blood of the children and their parents was collected for WES. Combining the clinical phenotypes of the children, the candidate variants, including single nucleotide variants (SNVs) and copy number variations (CNVs), were selected for validation and family segregation analysis using Sanger sequencing, real-time PCR or CNV-Seq. The pathogenicity of variants was evaluated based on ACMG guideline following with finial genetic diagnosis. Based on whether genetic diagnosis was achieved or not, 125 children with comprehensive examination of the Children Neuropsychological and Behavioral Scale(CNBS-R2016) were sub-grouped (positive/negative group), and the total scores and the detailed scores of five developmental sections (gross motor, fine motor, adaptive ability, language and social behavior ability) between two subgroups were compared.Results:A total of 165 children with language delay/disorder were recruited, including 109 males and 56 females. The ratio of boys to girls was 1.95∶1.The age of the children was (3.2±1.2) years old, the median age was 3.0 years. 45 children carry disease-related pathogenic/likely pathogenic variants, including 36 SNVs and 9 CNVs. The genetic diagnostic yield of this cohort was 27.3% (45/165). The inheritance analysis for core family members showed de novo variant accounted for 86% of genetic diagnosis (31/36). The positive diagnosis rate in girls was 45% (25/56), which was significantly higher than that in boys (18.3%, 20/109, χ2=12.171, P<0.05). There was no significant difference in the rate of positive diagnosis among all age groups (χ2=4.349, P>0.05). Interestingly, the scores of gross motors of positive group were significantly lower than that of negative group (61.5 vs. 69.4, t=-2.610, P<0.05). Otherwise, no significant difference was seen between two groups( t=-0.933, -1.298, -0.114, -0.214, all P>0.05). Conclusions:Language delay/disorder has complex genetic heterogeneity. WES has important application value in early etiological diagnosis for children with language delay/disorder.

Objective To analyze the influences of maternal high-fat diet on male rat offspring's blood lipid level and hepatic lipid deposition as well as on the expression of two key factors,sterol regulatory element binding protein-1 (SREBP-1) and SREBP cleavage acting protein (SCAP),involved in hepatic cholesterol regulatory cascade during childhood and adulthood.Methods Pregnant Wistar rats were randomly divided into two groups:high fat diet (HF) group and normal intake control (NC) group (both n=20).Rats in the HF group were fed with high-fat diet till delivery before changing to a normal-fat diet,while the NC group was given the normal-fat diet all through the study.Male offspring born appropriate for gestational age (AGA) in different feeding groups were randomly selected as experimental subjects.Physical development,serum lipid levels and hepatic lipid deposition at the age of 7 and 24 weeks were compared between offspring of the two groups.Expression of SCAP and SREBP-1 at protein level was detected with immunohistochemistry.T test or Chi-square test was used for statistical analysis.Results The average birth weight of HF group was higher than that of NC group [(6.95± 0.25) vs (6.79 ±0.78) g,t=2.088,P=0.038].Large for gestational age (LGA),AGA and small for gestational age (SGA) offspring accounted for 18.6％ (21/113),77.9％ (88/113)and 3.5％ (4/113) in HF group and 7.6％ (10/132),87.9％ (116/132) and 4.5％ (6/132) in NC group (x2=13.500,P=0.001).At the age of 7 weeks,the offspring's body weight in HF group was higher than that in NC group [(68.78±7.55) vs (66.61 ±3.92) g,t=2.303,P=0.023].At the age of 24 weeks,the body weight,body length and abdominal circumference of adult offspring in HF group were significantly higher than those in NC group [(251.74±24.04) vs (216.24±33.42) g,(22.60±0.79) vs (21.59± 1.34) cm,(17.93±0.59) vs (16.83±0.88) cm;t=2.220,2.379,2.927,all P＜0.05].At the age of 7 weeks,offspring's serum total cholesterol (TC) level in HF group was higher than that in NC group [(1.94±0.62) vs (1.23 +0.77) mmol/L,t=2.379,P＜0.05].At the age of 24 weeks,adult offspring's liver index,serum TC,triglyceride (TG),low density lipoprotein-cholesterol (LDL-C) and very low density lipoprotein-cholesterol (VLDL-C) levels were all higher in HF group than in NC group,while the high density lipoprotein-cholesterol (HDL-C) level was lower in HF group [(2.75±0.31)％ vs (2.46±0.39)％,(1.98±0.14) vs (1.45±0.27) mmol/L,(2.96±0.21) vs (2.71 ±0.29) mmol/L,(0.97±0.32) vs (0.71 ±0.21) mmol/L,(0.81 ±0.13) vs (0.52±0.17) mmol/L,(1.74±0.20) vs (1.59±0.29) mmol/L;t=2.264,2.333,2.359,2.088,5.336,1.994,all P＜0.05].Comparative analysis of nonalcoholic fatty liver disease activity scores (NAS) between the two groups showed that the liver lobular inflammation in HF group's offspring was more severe at both 7 and 24 weeks of age (2.29±0.49 vs 1.92±0.45,2.83±0.47 vs 2.22±0.55;t=2.157,3.251,all P＜0.05).At the age of 24 weeks,adult offspring in HF group also showed higher liver steatosis scores (2.81 ± 0.35 vs 2.25 ± 0.30,t=4.609,P＜0.05).Immunohistochemical detection showed that there was no significant difference in SCAP protein expressions in liver tissues of 7-week-old offspring between the two groups (P＞0.05),but higher expression of SREBP-1 protein was observed in HF group than in NC group [(34.16±5.08)％ vs (18.09±3.99)％,t=9.697,P＜0.05].At the age of 24 weeks,the expression levels of both SCAP and SREBP-1 proteins in liver tissues were higher in HF group than in NC group [(31.22±6.01)％ vs (17.98+7.89)％,(61.33± 16.25)％ vs (29.76± 11.21)％;t=2.303,2.274,both P＜0.05].Conclusions High-fat intake during pregnancy can increase offspring's birth weight and the risk for LGA offspring.Maternal high-fat diet even up-regulates the expression of SCAP and SREBP-1 in male offspring born AGA in childhood and this impact become more obvious when reaching adulthood,resulting in excessive increase of body weight,body length and abdominal circumference and elevated serum lipid level and liver lipid deposition.

Objective:To investigate the relationship between plasma placental growth factor(PIGF) levels and perinatal outcomes in patients with early onset preeclampsia(EOPE).Methods:125 patients with EOPE undergoing cesarean section were enrolled in this study.Enzyme-linked immunosorbent assay(ELISA) was used to detect the level of maternal plasma PIGF.According to the plasma PIGF level,≤ 12 pg/ml was divided into PlGF≤12 pg/ml group(n =64) and PIGF ＞12 pg/ml was in PIGF ＞12 pg/ml group(n =61).The blood gas analysis and the level of lactic acid(LAC) were measured within 1 hour after fetal birth.The routine and biochemical indexes of two groups and their relation with perinatal outcomes were compared.Results:①In PIGF ≤ 12 pg/ml EOPE group,the Hb,HCT,24h urine protein level,BUN and Cr levels were higher than those in PIGF ＞ 12 pg/ml group (P ＜ 0.05).While the ALB level was lower than that of PIG F ＞ 12 pg/ml group (P ＜ 0.05).②The gestational age of PIGF≤12 pg/ml group was less than that of PIGF ＞ 12 pg/ml group,but the proportion of oligohydramnios,meconium stained amniotic fluid and less than gestational age infants(SGA) were all higher than those of PIGF ＞ 12 pg/ml group(P＜0.05).③In the PIGF≤12 pg/ml group,neonatal birth weight(BW),1 minute Apgar score,pH,serum Ca,BE were all lower than those in PIGF ＞12 pg/ml group.But the level of LAC and the NICU hospital stay were all higher than those in PIGF ＞ 12 pg/ml group (P ＜ 0.05).Conclusions:In EOPE patients,plasma PIGF level has certain clinical value in predicting perinatal outcome.If PIGF is ≤ 12 pg/ml,the maternal renal dysfunction may be more obviously,and there is higher incidence of oligohydramnios,meconium stained fluid,SGA and neonatal asphyxia,and the newborn is more susceptible to metabolic imbalance and acid-base disorders.Mother and child care should be strengthened.

Objective:To evaluate the association between weight gain in late gestation and glycated albumin (GA),visfatin level and neonatal body composition in gestational diabetes mellitus (GDM) patients who are non-obese.Methods:200 pregnant women were enrolled.The preconception body mass index(BMI) of all the research object was less than 25 kg/m2.According to the speed of body mass growth from 28th week of gestation to delivery,the subjects were divided into two groups:excessive weight gain group (n =77) and appropriate weight gain group(n=123).Variance of serum GA,visfatin levels and neonatal birth weight(BW),the percent of body fat in newborn(F％) between two groups were compared,and the relationship between weight gain in late pregnant GDM patients and above values was analyzed.Results:①Serum GA,HbA1 c,visfatin and total cholesterol,triglyceride,low density lipoprotein,very low density lipoprotein levels in excessive weight gain group were higher than those in appropriate weight gain group(P ＜ 0.05).②Mean gestational age,newborn Apgar score immediately,the ratio of baby boys and vaginal delivery rate in two group had no significant difference(P＞0.05).Compared with the appropriate weight gain group,the excessive weight gain group had higher average birth weight and lower blood glucose levels.The proportion of large for gestational ages(LGA) was increased in appropriate weight gain group,and the ratio of abdomen circumference (AC) and head circumference (HC) and the percent of body fat in newborn(F％) were significantly increased in this group(P ＜0.01).③The speed of body mass growth in late pregnancy in GDM patients was positively related with serum GA,visfatin,HbA1c levels and newborn birth weight and the percent of body fat in newborn(r=0.524,0.470,0.456,0.329,0.473,P＜0.001).Conclusions:The monitoring of the serum GA and visfatin levels may have certain clinical value to evaluate the weight gain in late pregnancy of GDM patients.The rapid body mass growth in those patients may accelerate the visceral fat accumulation and worsen existing glucolipid metabolic disorders,and is also closely related to the increase of neonatal BW and F％.

Objective To explore clinical characteristics and the perinatal effects of multiple systems in pre-pregnancy obesity patients with early-onset preeclampsia. Methods A total of 111 cases with early-onset preeclampsia in our Inpatient Obstetric Department were reviewed in this study. According to pre-pregnancy body mass index (BMI), patients were divided into normal before pregnancy group (BMI<28 kg/m2, n=56) and obese before pregnancy group (BMI≥28 kg/m2, n=55) . The body weight, BMI, weight gain during pregnancy, risk factors, clinical features, and clinical features of neonatal index were compared between two groups. The correlation between maternal and neonatal indexes and glucose and lipid indexes were compared. Results Obese before pregnancy was more prone to blood concentration and disorders of lipid metabolism. The serum levels of lipid, glycosylated hemoglobin (HbA1c), hematocrit, platelet and fibrinogen were significantly higher in obese before pregnancy group than than those of normal group. The induced neonatal acidosis and other organ damage, newborn Apgar score, pH, glucose were significantly lower in obese before pregnancy group than those of normal group. The residual alkali (BE), lactic acid (LAC), creatine kinase (CK) and creatine kinase (CKMB) were higher in obese before pregnancy group than those of normal before pregnancy group. Correlation analysis showed that maternal low density lipoprotein cholesterol (LDL-C), total cholesterol (TC), three acyl glycerol (TG) and HbA 1c were negatively correlated with neonatal Apgar score and pH, and which were positively correlated with neonatal LAC and CKMB. Both differences were significant (P<0.05 or P<0.01). Conclusion The dyslipidaemia in early onset preeclampsia in obesity patients before pregnancy is closely related with maternal and perinatal outcomes.