Objective:To explore chromosomal copy number variations (CNVs) and pregnancy outcomes in fetuses with mild to moderate isolated ventriculomegaly (IVM), but without other indications for invasive prenatal diagnosis.Methods:A retrospective analysis was conducted on clinical data of 215 singleton pregnancies with mild to moderate IVM (lateral ventricular width≥10-<15 mm) who underwent chromosomal microarray analysis (CMA), not indicated by advanced age, high risk in serum screening or abnormal history of pregnancy, at the Fujian Maternity and Child Health Hospital between June 2016 and March 2023. The 215 fetuses were grouped into mild ( n=167) and moderate ( n=48) IVM;unilateral ( n=142) and bilateral ( n=73) IVM; first diagnosis of IVM before 28 weeks ( n=138) and thereafter ( n=77). Anomalies other than IVM were excluded via three-dimensional color Doppler ultrasound examination between 22 and 26 weeks of gestation. Out of these cases, 129 were confirmed by fetal cranial MRI, 191 underwent chromosomal karyotype analysis, and 202 cases received cytomegalovirus DNA quantification test for amniotic fluid. The detection rates of pathogenic CNVs in various groups were compared using Fisher's exact test. Results:Among the 215 fetuses, 11 cases (5.1%) of chromosomal abnormalities were detected through CMA, including one trisomy 21, five pathogenic CNVs, and five CNVs of uncertain clinical significance. Within the pathogenic CNVs, there were two de novo mutations with 16p11.2 microdeletion and one de novo mutation with 16p11.2 microduplication, while one 16p11.2 microduplication and one Xp22.31 microdeletion were inherited maternally. Of the CNVs of uncertain significance, there were two 16p13.11 microduplications, each inherited from a different parent, one paternally and one maternally; meanwhile, family validation was refused in the other three cases with 3p22.1 microdeletion, 3p26.3 microdeletion, and 9q21.33q22.31 microduplication. The detection rate of pathogenic CNVs in the moderate IVM group was higher than that in the mild IVM group [6.3% (3/48) vs. 1.2% (2/167)], but the difference was not statistically significant ( P=0.083). Similarly, no significant difference was found in the detection rate of pathogenic CNVs when comparing the unilateral IVM group [2.1% (3/142)] with the bilateral IVM group [2.7% (2/73)], nor between the group diagnosed with VM before 28 weeks gestation [2.2% (3/138)] and that diagnosed ≥28 weeks [2.6% (2/77)] (both P>0.05). After the exclusion of fetuses with chromosomal pathogenic abnormalities ( n=11), cytomegalovirus infection( n=1), and additional ultrasound anomalies ( n=7), and several cases with missing data intrauterine outcomes were followed up in 169 IVM fetuses, including 104 (61.5%) improved, 60 (35.5%) unchanged, and five (3.0%) progressed. Follow-ups were successful for 194 women, of which eight pregnancies were terminated (including one trisomy 21, four pathogenic CNVs, one fetal cytomegalovirus infection, and two progressed to severe IVM). Among the 186 newborns, one was diagnosed with X-linked ichthyosis, and one child who progressed to severe IVM before born was followed until 20 months of age without notable phenotypic abnormalities. The rest 184 babies, including those with CNVs of uncertain clinical significance, exhibited no developmental abnormalities during follow-up between the ages of three months and six years. Conclusions:For those fetuses with isolated mild to moderate IVM, but without indications for prenatal diagnosis such as advanced maternal age, high risk in serum screening or abnormal history of pregnancy, remain having the risk for chromosomal aberrations, and 16p11.2 microdeletion/microduplication might be a frequent CNV associated with this condition. Aside from those with pathogenic chromosomal aberrations, fetal cytomegalovirus infection, or progressive enlargement of the lateral ventricles, most fetuses with isolated mild to moderate IVM have a good prognosis.

Objective To observe the difference and clinical significance of expression levels of microRNA-155(miR-155)mRNA and interleukin-6(IL-6)in very preterm neonates with preeclampsia.Methods Twenty-eight cases of very preterm newborns(gestational age<32 weeks and/or body weight<1500 g)from preeclampsia pregnant women admitted to the department of obstetrics of Liaocheng People's Hospital from January to December 2021 were selected as the observation group,and 26 cases of very preterm neonates hospitalized for other reasons during the same period were selected as the control group.Electronic medical record clinical data related to children were collected,and the differences between the two groups were compared,including general conditions of preterm infants and pregnant mothers(gender,gestational age,birth weight,preeclampsia or not),proportion of invasive ventilation,proportion of bronchopulmonary dysplasia(BPD),incidence of acute respiratory distress syndrome(ARDS)and early-onset sepsis,white blood cell count(WBC),neutrophil count(NEUT),and expression of miR-155 mRNA and IL-6 levels in the serum of umbilical arterial blood after birth.Pearson correlation analysis was used to analyze the correlation between miR-155 and IL-6 levels Results The birth body weight of the observation group was significantly lower than that of the control group(kg:1.21±0.22 vs.1.32±0.33,P<0.05),the proportion of invasive ventilation,the proportion of BPD,the incidence of ARDS and sepsis were significantly higher than those in the control group[the proportion of invasive ventilation:75.0%(21/28)vs.57.7%(15/26),the proportion of BPD:35.7%(10/28)vs.11.5%(3/26),incidence of ARDS:100.0%(28/28)vs.84.6%(22/26),incidence of sepsis:71.4%(20/28)vs.53.8%(14/26),all P<0.05],the level of miR-155 mRNA expression and IL-6 were significantly higher than those in the control group[miR-155 mRNA(2-ΔΔCt):0.93±0.18 vs.0.17±0.03,IL-6(ng/L):73.84(33.44,429.00)vs.19.05(9.30,47.20),both P<0.05].Pearson correlation analysis showed that miR-155 and IL-6 levels were significantly positively correlated(r=0.782,P<0.01).With the extension of birth time,both WBC and NEUT gradually decreased in the two groups,and there were statistically significant differences in WBC and NEUT at each time point after birth,with counts significantly lower at 48 hours and 72 hours compared to 24 hours after birth(both P<0.05).The WBC of the observation group at 24,48 and 72 hours after birth was significantly lower than that of the control group(×109/L:7.85±2.44 vs.12.28±6.81 at 24 hours after birth,7.31±3.53 vs.10.98±7.91 at 48 hours after birth,4.97±2.05 vs.7.82±4.65 at 72 hours after birth,all P<0.05),NEUT in observation group was significantly lower than of control group at 24 hours and 48 hours after birth(×109/L:24 hours after birth was 4.13±1.93 vs.7.45±5.67,48 hours after birth was 3.96±2.64 vs.6.89±6.24,both P<0.05).Conclusion The expression level of miR-155 mRNA and IL-6 in very preterm neonates with preeclampsia is significantly up-regulated at the time of birth,and the inflammatory response of the body is disturbed,which has certain value for early assessment of the disease.

Objective The occurrence of chickenpox in rapidly developing areas poses substantial seasonal risk to children.However,certain factors influencing local chickenpox outbreaks have not been studied.Here,we examined the relationship between spatial clustering,heterogeneity of chickenpox outbreaks,and socioeconomic factors in Southern China. Methods We assessed chickenpox outbreak data from Southern China between 2006 and 2021,comprising both relatively fast-growing parts and slower sub-regions,and provides a representative sample of many developing regions.We analyzed the spatial clustering attributes associated with chickenpox outbreaks using Moran's I and local indicators of spatial association and quantified their socioeconomic determinants using Geodetector q statistics. Results There were significant spatial heterogeneity in the risk of chickenpox outbreaks,with strong correlations between chickenpox risk and various factors,particularly demographics and living environment.Furthermore,interactive effects among specific are factors,such as population density and per capita residential building area,percentage of households with toilets,percentage of rental housing,exhibited q statistics of 0.28,0.25,and 0.24,respectively. Conclusion This study provides valuable insights into the spatial dynamics of chickenpox outbreaks in rapidly developing regions,revealing the socioeconomic factors affecting disease transmission.These implications extend the formulation of effective public health strategies and interventions to prevent and control chickenpox outbreaks in similar global contexts.

Objective This study aimed to explore the heterogeneity and gene ontology of Wnt1-Cre-marked and Pax2-Cre-marked first branchial arch cranial neural crest cells(CNCs)in mice.Methods The embryos of Wnt1-Cre;R26RmTmG and Pax2-Cre;R26RmTmG at embryonic day(E)8.0-E9.25 were collected for histological observation.We per-formed immunostaining to compare green fluorescent pro-tein(GFP)-positive CNCs in Pax2-Cre;R26RAi9 and Wnt1-Cre;R26RAi9 mice at E15.5.Single-cell RNA sequencing(scRNA-seq)was used to analyze the first branchial arch GFP-positive CNCs from Wnt1-Cre;R26RmTmG and Pax2-cre;R26RmTmGmice at E10.5.Real time fluorescence quantitative polymerase chain reaction(q-PCR)was performed to val-idate the differential genes.Results Wnt1-Cre-marked and Pax2-Cre-marked CNCs migrated from the neural plateto first and second branchial arches and to the first branchial arch,respectively,at E8.0.Although Wnt1-Cre-marked and Pax2-Cre-marked CNCs were found mostly in cranial-facial tissues,the former had higher expression in palate and tongue.The results of scRNA-seq showed that Pax2-Cre-marked CNCs specifically contributed to osteoblast differentia-tion and ossification,while Wnt1-Cre-marked CNCs participated in limb development,cell migration,and ossification.The q-PCR data also confirmed the results of gene ontology analysis.Conclusion Pax2-Cre mice are perfect experimen-tal animal models for research on first branchial arch CNCs and derivatives in osteoblast differentiation and ossification.

Objective:To investigate the effects of peripartum administration of low-dose corticosteroids or intravenous immunoglobulin (IVIG) on delivery outcomes in pregnant patients with primary immune thrombocytopenia (ITP).Methods:This prospective cohort study involved pregnant women (≥34 gestational weeks) who were diagnosed with ITP in Peking University People's Hospital from January 2017 to December 2021. Their platelet counts were between 20×10 9/L to 50×10 9/L without bleeding and none of them had been treated with any medications. All patients were divided into medication group (prednisone or IVIG) and platelet transfusion group based on their preference. Differences in vaginal delivery rate, postpartum hemorrhage rate and platelet transfusion volume between the two groups were compared using t-test, Wilcoxon rank sum test and Chi-square test. Binary logistic regression was used to investigate the factors influencing the rates of vaginal delivery and postpartum hemorrhage. Multiple linear regression was used to analyze the factors influencing the platelet transfusion volume. Results:A total of 96 patients with ITP were recruited with 70 in the medication group and 26 in the platelet transfusion group. The vaginal delivery rate in the medication group was higher than that in the platelet transfusion group [60.0% (42/70) vs 30.8% (8/26), χ 2=6.49, P=0.013]. After adjusted by the proportion of multiparae and the gestational age at delivery, binary logistic regression showed that the increased vaginal delivery rate in patients undergoing the peripartum treatment ( OR=4.937, 95% CI: 1.511-16.136, P=0.008). The incidence of postpartum hemorrhage in the two groups was 22.9% (16/70) and 26.9% (7/26), respectively, but no significant difference was shown ( χ 2=0.17, P=0.789). The median platelet transfusion volume was lower in the medication group than in the platelet transfusion group [1 U(0-4 U) vs 1 U(1-3 U), Z=－2.18, P=0.029]. After adjustment of related factors including the platelet count at enrollment, obstetrical complications and anemia, multiple linear regression showed that the platelet transfusion volume was also lower in the medication group (95% CI:0.053-0.911, P=0.028). Ninety-six newborns were delivered without intracranial hemorrhage. The overall incidence of neonatal thrombocytopenia was 26.0% (25/96). There was no significant difference in birth weight, and incidence of neonatal asphyxia or thrombocytopenia between the two groups. Conclusion:Peripartum therapy in ITP patients may increase vaginal delivery rate and reduce platelet transfusion volume without causing more postpartum hemorrhage.

Objective:To investigate the clinical value of isolated fetal echogenic bowel (FEB) as an indicator for invasive prenatal diagnosis.Methods:This retrospective study enrolled 183 pregnant women who were diagnosed with isolated FEB and underwent invasive prenatal diagnosis in Fujian Maternity and Child Health Hospital from August 2013 to January 2021. Clinical data including the results of conventional karyotyping and chromosomal microarray analysis (CMA), cytomegalovirus (CMV) DNA loads in amniotic fluid and pregnancy outcomes were reviewed analyzed. Chi-square test was used for statistical analysis Results:Karyotyping was performed on all of the 183 fetuses and three (1.64%) aneuploidies (one case of trisomy 21, one trisomy 18 and one 47,XYY syndrome) were detected. One trisomy 21 and four pathogenic (P)/likely pathogenic (LP) copy number variation (CNV) were detected among 108 fetuses who received CMA. The detection rate of P/LP chromosomal abnormalities by CMA was higher than that by karyotyping, but there was no significant difference between them [4.63% (5/108) vs 0.93% (1/108), χ 2=1.54, P>0.05]. In addition, three cases of variants of uncertain significance (VOUS) were detected by CMA. CMV DNA loads of fetal cells in the amniotic fluid samples of the 166 cases were determined, and only one (0.6%) was positive (CMV DNA up to 7.01×10 6 copies/ml), and no abnormalities were found in karyotype analysis and CMA detection. A total of 176 cases were followed up, and among them only one case of intrauterine infection and seven cases (three aneuploidies and four P/LP CNV) of chromosomal abnormalities were terminated after genetic counseling. Three fetuses with VOUS and other 165 fetuses without chromosomal abnormalities had a good prognosis after birth. Conclusions:Isolated FEB may be the abnormal ultrasound finding in fetuses with chromosomal abnormalities or CMV infection. Prenatal genetic testing and the exclusion of intrauterine infection are important for management during pregnancy and prognosis assessment of FEB.

Humans ; Uric Acid ; Cross-Sectional Studies ; Spondylarthritis/diagnostic imaging* ; C-Reactive Protein ; Spondylitis, Ankylosing

Objective To investigate the preventive therapeutic effect and possible mechanism of single chain variable fragments chimeric protein (SD) of ovalbumin epitopes internalizing receptor DEC-205 antibody on food allergy in mice. Methods Mice were randomly divided to five groups (control, PBS, scFv DEC 100 μg, SD 50 μg, SD 100 μg) and treated for 24 hours before OVA administration. After challenge, the serum level of OVA-specific IgE, IgG1, IgG2a and IL-4 were detected by ELISA. Infiltration of eosinophils and mast cells in the jejunum was observed by HE staining and toluidine blue staining respectively. The bone marrow of tibia and femur was isolated and cultured to obtain immature dendritic cells(BMDCs), which were further treated with LPS (10 ng/mL), TSLP (50 ng/mL), scFv DEC protein (1000 ng/mL) and SD protein (10,100,1000)ng/mL for 24 hours, and the IL-10 level of supernatant was assayed by ELISA. Results Compared with PBS group, the number of SD-treated mice with diarrhea was markedly reduced. The difference in rectal temperature and the levels of serum OVA-specific IgE, IgG1, IgG2a and IL-4 decreased significantly after prophylactic administration of SD; The number of eosinophils and mast cells in jejunum also decreased significantly while the IL-10 level in the supernatant of BMDCs increased significantly after SD intervention. Conclusion SD mitigates experimental FA response by fosters the immune tolerance property of dendritic cells.
Mice ; Animals ; Ovalbumin ; Interleukin-10 ; Single-Chain Antibodies/genetics* ; Immunoglobulin E ; Epitopes/therapeutic use* ; Interleukin-4 ; Food Hypersensitivity/prevention & control* ; Immunoglobulin G ; Recombinant Fusion Proteins/genetics* ; Mice, Inbred BALB C ; Disease Models, Animal

Objective:To understand the epidemiological characteristics of public health emergency events (PHEE) of varicella in China from 2006 to 2021 and related response performances.Methods:The data of varicella PHEE in 31 provinces of China from 2006 to 2021 were collected through the Public Health Emergency Management Information System, Microsoft Excel 2019 software and SPSS 26.0 statistical software were used to conduct descriptive epidemiological, statistical analysis on the time, area, location distribution, scale and epidemic management.Results:A total of 11 443 PHEE involving 341 048 related cases were reported from 2006 to 2021, with an annual attack rate of 1.78%-3.80% and a total attack rate of 2.33% (341 048/14 624 042). The number of PHEE and related cases of varicella decreased from 1 107 (35 349) in 2007 to 262 (6 884) in 2012 ( Z=-2.40, P<0.001), then increased year by year to 1 318 (42 649) in 2019 ( Z=2.58, P<0.001), with a significant decline since 2020. The varicella PHEE in China presents the seasonal characteristics,the peak is from April to June and from October to December, respectively. The sub-peak of varicella PHEE in eastern China generally appears 1-2 months earlier than in central and western China. Varicella PHEE reports are mainly distributed in eastern China, the attack rate is relatively high in western China, school-reported varicella PHEE was 88.26% of the total reports (10 099/11 443). The epidemic scale of varrcella PHEE typically range from 10 to 29 cases per year among the given outbreaks. The M ( Q1, Q3) of average number of cases, average duration, and average reporting interval of PHEE were 23 (16,35), 20 (14, 26) days, and 9 (5,19) days, respectively, and the reporting interval was positively correlated with the duration ( r=0.854, P<0.001). Conclusions:The varicella PHEE in China from 2006 to 2021 has not been effectively controlled. Schools are the key places to prevent and control varicella PHEE. Improving the sensitivity of varicella PHEE monitoring, strengthening the timely disposal of varicella epidemic, and promoting varicella vaccination are effective measures to prevent and control varicella PHEE.

OBJECTIVE: To analyze the intrauterine phenotype and genotype of eight fetuses carrying a 16p11.2 microdeletion. METHODS: 5100 fetuses undergoing routine prenatal diagnosis were subjected to single nucleotide polymorphism-based microarray (SNP-array) analysis. Fetuses harboring a 16p11.2 microdeletion were analyzed for their ultrasonographic characteristics. RESULTS: Eight fetuses were found to harbor a microdeletion in the 16p11.2 region. Among these, six had a typical 500-600 kb deletion, while the remaining two had an atypical 220 kb deletion at the distal part of 16p11.2. Four fetuses showed vertebral malformations, two had mild left ventriculomegaly, one had hydrocephalus, and one had pulmonary valve stenosis with regurgitation. The parents of five fetuses have accepted pedigree verification, and the results confirmed that the 16p11.2 microdeletions carried by fetuses all had a de novo origin. CONCLUSION The intrauterine phenotypes of fetuses carrying a 16p11.2 microdeletion may be variable, and the deletion can be effectively detected with the SNP-array assay.
Chromosome Deletion ; Female ; Fetus ; Genetic Testing ; Humans ; Phenotype ; Pregnancy ; Prenatal Diagnosis