Diabetes is a major concern in healthcare worldwide and is detrimental to mothers and fetuses during pregnancy. However, half of the women were unaware of hyperglycemia before pregnancy, and there is no consensus on their identification during pregnancy. We aim to understand the role that diagnostic timing plays in perinatal outcomes. This was a multicenter retrospective study of all pregestational diabetes mellitus (PGDM) women who delivered from January 2021 to June 2023. Diagnoses were made before or during gestation. Characteristics and outcomes were compared among stages, and logistic regression was performed to explore the relationship between adverse outcomes and the diagnostic timing. This study included 2,818 women; 1188 (42.2%) were self-aware before pregnancy, and 286 (10.1%), 1208 (42.9%), and 136 (4.8%) were diagnosed in the first, second, and third trimesters, respectively. Maternal body mass index, hypertensive disorders during pregnancy, glucose profile, large-for-gestational-age (LGA), etc., differed among stages (all P < 0.05). Logistic regression revealed that PGDM diagnosed during any trimester was significantly associated with an increased risk of macrosomia (aOR = 2.632, 1.502, 2.314; all P < 0.05). However, the risk of LGA decreased if the diagnosis was based on the 2 h value of the oral glucose tolerance test (OGTT) alone in the second trimester (aOR = 0.608, 95% CI: 0.444-0.831). No relationship existed between diagnostic timing and neonatal birth defects or hypoglycemia (both P > 0.05). PGDM identified during pregnancy was significantly associated with an increased risk of fetal overgrowth. The role of the 2 h-OGTT alone in diagnosis warrants further exploration. PGDM screening is essential for the entire gestational period.

The global prevalence of pregestational type 2 diabetes mellitus (T2DM) has increased concurrently with increasing rates of overweight and obesity. Effective weight management during pregnancy is critically associated with maternal and neonatal outcomes. However, no universally accepted guidelines for gestational weight gain (GWG) in high-risk pregnancies with T2DM currently exist. A nationwide, multicenter cohort of 2078 T2DM pregnancies was analyzed, categorizing GWG based on latest Chinese guidelines. Multivariate regression analyses were performed to evaluate the impact of GWG deviations on adverse pregnancy outcomes. Interquartile range (IQR) analysis and restricted cubic splines were used to determine BMI-specific GWG targets. The results showed that insufficient GWG was protective against cesarean delivery, large-for-gestational-age (LGA), and macrosomia but increased risks of preterm birth and congenital anomalies. Excessive GWG significantly elevated risks of preeclampsia, LGA, macrosomia, and neonatal hypoglycemia, while protecting against small-for-gestational-age (SGA). Using interquartile range method, we identified GWG ranges for normal-weight, overweight, and obese women were 7.0–12.5 kg, 5.0–11.0 kg, and 4.0–11.2 kg, respectively. Restricted cubic splines suggested relaxing the lower limit to 6 kg for normal BMI but showed risks below 1.8 kg. For overweight and obese women, GWG below guideline limits was beneficial. The current GWG guidelines may not fully suit T2DM pregnancies, particularly for overweight and obese women, highlighting the need for BMI-specific recommendations to optimize maternal and neonatal outcomes.

OBJECTIVE:To examine whether glycemic level modifies the association between gestational weight gain (GWG) and pregnancy outcomes in type 2 diabetes-complicated pregnancies. RESEARCH DESIGN AND METHODS:This multicenter retrospective study stratified 1,642 pregnant women with diabetes by third-trimester glycemic control. Associations between excessive GWG (eGWG) and pregnancy outcomes were analyzed by group. RESULTS:Although birth weight and odds of macrosomia and cesarean delivery were higher for all women with eGWG relative to those with adequate GWG, the effect estimates for birth weight and macrosomia were significantly higher with suboptimal glycemic control compared with optimal control (birth weight increase: 361.04 vs. 126.07 g, respectively, P = 0.007; adjusted odds ratio for macrosomia: 4.26 vs. 2.73, P = 0.002; cesarean delivery: 1.86 vs. 1.52, P = 0.738). CONCLUSIONS:Overly stringent weight control should be treated with caution if optimal glycemic control is not achieved.

OBJECTIVE:To evaluate the application of different uterine artery embolization procedures under balloon occlusion of the abdominal aorta in patients with Placenta Accreta Spectrum (PAS) undergoing cesarean section.MATERIALS AND METHODS:A retrospective analysis was performed on clinical data from 72 patients who underwent uterine artery embolization for hemostasis during cesarean section with PAS. The patients were divided into two groups according to the embolization method used during surgery: group A (n = 43) underwent uterine artery embolization by withdrawing the balloon and inserting a Cobra catheter into the uterine artery for embolization, while group B (n = 29) underwent uterine artery embolization with a Cobra catheter inserted via contralateral puncture of the femoral artery and balloon occlusion. General information, surgical data, and postoperative recovery were compared between the 2 groups.RESULTS:The bleeding and transfusion volumes were lower in group B than in group A and the differences between the 2 groups were statistically significant. There were no significant differences in surgical duration, number of embolized vessels, length of hospital stay, postoperative complications, or menstrual recovery between the 2 groups.CONCLUSION:For patients with PAS undergoing cesarean section, uterine artery embolization for hemostasis is preferably performed by inserting a Cobra catheter via contralateral puncture of the femoral artery under abdominal aortic balloon occlusion.

Objective:To explore the prenatal and postnatal features and genetic characteristics of patients with Lymphedema-Distichiasis syndrome (LDS) due to variants of FOXC2 gene. Methods:A retrospective analysis was carried out on the phenotypic information, fetal ultrasound image, and genetic testing of two Chinese pedigrees diagnosed at the Third Affiliated Hospital of Zhengzhou University. A literature review was also carried out by searching the China National Knowledge Infrastructure (CNKI), Wanfang Database, and PubMed databases dated from January 2010 to June 2024 using keywords "Lymphedema-Distichiasis syndrome" and " FOXC2". This study has been approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethic No.2021-046-01). Results:Neither family was found to harbor chromosomal aneuploidy or pathogenic CNVs larger than 100 kb. The fetuses from pedigree 1 and pedigree 2 were respectively found to be heterozygous for a c. 361C>T (p.R121C) variant and a c. 168C>A (p.Y56*) variant of the FOXC2 gene. Both variants were paternally derived. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variants were classified as pathogenic and likely pathogenic, respectively. Literature search has identified 20 articles, and combined with our cases, a total of 117 patients were identified. Among them, 13 had shown prenatal phenotypes, primarily with increased nuchal translucency (NT) (12/13), urinary abnormalities (5/12), and fetal edema (4/13). Postnatal phenotypes were observed in 110 cases, mainly as distichiasis (87/110) and lymphedema (73/110). Only 6 cases had both prenatal and postnatal phenotypes. A total of 32 genetic variants were identified. Conclusion:The primary prenatal manifestations of LDS include increased NT, fetal edema, pleural and abdominal effusion, and separation of renal collecting system. Postnatal phenotypes are primarily characterized by lymphedema, distichiasis, and spinal extradural arachnoid cysts. Discovery of the c. 168C>A variant has expanded the spectrum of FOXC2 gene mutations in China.

Endometrial cancer (EC) is the most prevalent gynecologic malignancy, with a higher risk in obese women, suggesting the potential involvement of gut microbiota in the progression of EC. However, there is no direct evidence of a connection between EC and the human gut microbiota. Using metagenomic sequencing, we investigated the relationship between gut microbiome imbalance and cancer development in patients with EC. In this prospective case–control study, we included 15 patients with EC based on endometrial biopsy in the case group and 15 women admitted to the hospital for female pelvic floor issues during the same time who did not have endometrial lesions from January 2023 to June 2023 in control group. The microbiota structure of EC cases and controls without benign or malignant endometrial lesions during the same time period was analyzed using metagenomic sequencing technology. We employed Alpha diversity analysis to reflect the richness and diversity of microbial communities. Statistical algorithm Bray-Curtis was utilized to calculate pairwise distances between samples, obtaining a beta diversity distance matrix. Subsequently, hierarchical clustering analysis was conducted based on the distance matrix. The results showed that the composition of bacterial colonies in both groups was dominated by Firmicutes, which had a higher proportion in the control group, followed by Bacteroidetes in the control group and Proteobacteria and Bacteroidetes in the case group. The abundance of Klebsiella (P = .02) was significantly higher, and the abundance of Alistipes (P = .04), Anearobutyricum (P = .01), and bacteria in Firmicutes such as Oscillospira and Catenibacterium was markedly lower in the case group than in the control group. These results demonstrated conclusively that a gut microbiome imbalance was associated with the development of EC.

Background With the development of whole-genome sequencing technology, non-invasive prenatal testing (NIPT) has been applied gradually to screen chromosomal microdeletions and microduplications that cannot be detected by traditional karyotyping. However, in NIPT, some false positives and false negatives occur. This study aimed to investigate the applicability of extended NIPT (NIPT-PLUS) in the detection of chromosomal aneuploidy and microdeletion/microduplication syndrome (MMS). Methods A total of 452 pregnancies that underwent prenatal diagnostic testing (amniocentesis or chorionic villus sampling) by chromosomal microarray analysis (CMA), were screened by NIPT-PLUS from the peripheral blood sample of the pregnant women. The results of the two tested items were compared and analysed. Results Of the 452 cases, 335 (74.12%) had positive CMA results, and 117 (25.88%) had no abnormal results. A total of 86 cases of trisomy 21, 18 and 13 and sex chromosome aneuploidy (SCA) were detected by CMA and NIPT-PLUS, with a detection rate of 96.51% (83/86). Among them, the detection rates of T18, T13; 47, XXY; 47, XXX and 47 XYY were 100%, and the detection rates of T21 and 45 XO were 96.55% and 90%, respectively. The detection sensitivity of rare chromosomal trisomy (RAT) was 80% (4/5). The positive predictive values of NIPT-PLUS for chromosome aneuploidy T21, T18 and T13 and for SCA and RAT were 90.32%, 87.50%, 25.00%, 88.89% and 50%, respectively. A total of 249 cases (74.32%) of chromosomal MMS were detected by CMA. The detection rate of NIPT-PLUS was 63.86% (159/249), and 90 cases (36.14%) were missed. The larger the MMS fragment, the higher the NIPT-PLUS detection sensitivity. In addition, most small fragments were of maternal origin. Conclusion The comparison between the CMA and NIPT-PLUS techniques shows that NIPT-PLUS has high sensitivity for detecting chromosomal aneuploidy and chromosomal copy number variations (CNVs) with fragments > 5 M. However, the sensitivity of CNV for fragments < 5 M is low, and the missed detection rate is high. Additionally, confined placental mosaicism and foetal mosaicism are the key factors causing false negatives in NIPT-PLUS, while maternal chromosomal abnormalities and confined placental mosaicism are key contributors to false positives, so appropriate genetic counselling is especially important for pregnant women before and after NIPT-PLUS testing.

Objective To explore the application value of prenatal chromosome microarray analysis（CMA） in fetuses with isolated mild lateral ventricle widening（IMVM） and the related factors affecting the prognosis of fetuses with IMVM.Methods Retrospective analysis of CMA results, pregnancy outcome and neonatal prognosis of 337 fetuses with IMVM who underwent regular prenatal examination in the Third Affiliated Hospital of Zhengzhou University from January 2017 to March 2022. According to the gestational age of IMVM and the width of lateral ventricle, they were divided into group A（the gestational age of IMVM was ＜28 weeks and the width of lateral ventricle was ＜11 mm）, group B（the first gestational week was ＜28 weeks, and the first lateral ventricle width was ≥11 mm）, group C（the first gestational age was ≥28 weeks, and the width of lateral ventricle was ＜11 mm）, Group D（the first gestational week was ≥28 weeks, and the first lateral ventricle width was≥11 mm）. Pearson χ~2 test or Fisher exact probability method were used to compare the rates between groups.Results The abnormal rate of CMA in IMVM fetuses was 8.9%（30/337） and the positive rate of pathogenic CNVs was 2.7%（9/337）. In Group A, the abnormal rate of CMA was 9.3%（13/140）, and the positive rate of pathogenic CNVs was 1.4%（2/140）. In Group B, the abnormal rate of CMA was 15.3%（15/98）, and the positive rate of pathogenic CNVs was 7.1%（7/98）. In Group C, the abnormal rate of CMA was 10.6%（2/47）, and no pathogenic CNVs were detected. No abnormal results of CMA were found in Group D. The incidence of pathogenic CNVs in fetuses with first ventricle width ＜11 mm was lower than that in fetuses with first ventricle width ≥ 11 mm（P=0.045）. The prevalence of CNVs in fetuses with gestational age ＜28 weeks at first diagnosis was higher than that fetuses with gestational age ≥28 weeks at first diagnosis（P=0.042）. The detectable rate of CMA pathogenic CNVs in Group B was higher than that in Group A and Group D（P=0.027, 0.047）. Follow-up of 268 cases of fetal pregnancy outcome and neonatal prognosis, 7 cases（7/268,2.6%） chose to induce labor to terminate pregnancy, 253 cases（253/268, 94.4%） had normal growth and development, 8 cases（8/268, 3.0%） were complicated with postpartum speech motor system growth retardation or growth restriction.Conclusion IMVM fetuses are recommended to undergo CMA examination. Fuses usually have a better prognosis. Initial lateral ventricular width was positively correlated with the detection of fetal pathogenic CNVs in IMVM, but not with fetal prognosis. IMVM with first onset in the third trimester has lower risk of pathogenic CNVs and better prognosis. The benefit of CMA in IMVM fetuses with first diagnosis of lateral ventricle width ＜11 mm or first diagnosis of gestational age ≥28 weeks should be carefully evaluated.

目的 探讨凝血指标和血尿素(UREA)水平与子痫前期(PE)发病的关联程度,旨在发现可以预测PE发生的化验指标.方法 选取 2021 年 1-12 月在河南省妇幼保健院分娩的 220 例孕妇为研究对象,PE患者60例,重度子痫前期(sPE)患者60例,正常孕妇100例,回顾性分析三组孕妇的临床资料、血凝指标[凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、D-二聚体(D-D)]和UREA水平,使用受试者工作特征曲线(ROC)分析血凝指标和UREA水平对PE发病的预测价值.结果 三组年龄比较,差异无统计学意义(P>0.05).三组分娩孕龄、血压、体重指数(BMI)、新生儿出生体重、血凝指标(PT、APTT、D-D)、UREA比较,差异均有统计学意义(P<0.05).ROC曲线结果显示,APTT、D-D和UREA对PE有辅助诊断价值,曲线下面积(AUC)分别为 0.72、0.80、0.84(P<0.05).结论 血凝指标(PT、APTT、D-D)和UREA可反映PE早期凝血功能变化和肾功能损害,APTT、D-D和UREA对PE有预测价值.

Objective: To explore the influencing factors of pregnancy-induced hypertensive disorders in pregnancy (HDP) with organ or system impairment in pregnant women, and to analyze and compare the differences of HDP subtypes in different regions of China. Methods: A total of 27 680 pregnant women with HDP with complete data from 161 hospitals in 24 provinces, autonomous regions and municipalities were retrospectively collected from January 1, 2018 to December 31, 2018. According to their clinical manifestations, they were divided into hypertension group [a total of 10 308 cases, including 8 250 cases of gestational hypertension (GH), 2 058 cases of chronic hypertension during pregnancy] and hypertension with organ or system impairment group [17 372 cases, including 14 590 cases of pre-eclampsia (PE), 137 cases of eclampsia, 2 645 cases of chronic hypertension with PE]. The subtype distribution of HDP in East China (6 136 cases), North China (4 821 cases), Central China (3 502 cases), South China (8 371 cases), Northeast China (1 456 cases), Southwest China (2 158 cases) and Northwest China (1 236 cases) were analyzed. By comparing the differences of HDP subtypes and related risk factors in different regions, regional analysis of the risk factors of HDP pregnant women with organ or system impairment was conducted. Results: (1) The proportions of HDP pregnant women with organ or system impairment in Northeast China (79.05%, 1 151/1 456), Central China (68.42%, 2 396/3 502) and Northwest China (69.34%, 857/1 236) were higher than the national average (62.76%, 17 372/27 680); the proportions in North China (59.18%, 2 853/4 821), East China (60.85%, 3 734/6 136) and South China (59.56%, 4 986/8 371) were lower than the national average, and the differences were statistically significant (all P<0.05). (2) Univariate analysis showed that the proportions of primiparas, non-Han, non-urban household registration, irregular prenatal examination and PE history in the hypertension with organ or system impairment group were higher than those in the hypertension group, and the differences were statistically significant (all P<0.05). Multivariate logistic regression analysis showed that primiparas, non-Han, non-urban household registration, irregular prenatal examination and PE history were independent risk factors for HDP pregnant women with organ or system impairment (all P<0.05). (3) Primipara: the rates of primipara in Northeast China, North China and Southwest China were higher than the national average level, while those in South China, Central China and Northwest China were lower than the national average level. Non-Han nationality: the rates of non-Han nationality in Northeast China, North China and Northwest China were higher than the national average, while those in East China, South China and Central China were lower than the national average. Non-urban household registration: the rates of non-urban household registration in Northeast China, North China, and Southwest China were lower than the national average, while those in East China, Central China were higher than the national average. Irregular prenatal examination: the rates of irregular prenatal examination in North China, South China and Southwest regions were lower than the national average level, while those in Northeast China, Central China and Northwest China were higher than the national average level. History of PE: the incidence rates of PE in Northeast China, North China, South China and Southwest China were lower than the national average level, while those in Central China and Northwest China were higher than the national average level. Conclusions: Primiparas, non-Han, non-urban household registration, irregular prenatal examination, and PE history are risk factors for HDP pregnant women with organ or system impairment. Patients in Northeast, Central and Northwest China have more risk factors, and are more likely to be accompanied by organ or system function damage. It is important to strengthen the management of pregnant women and reduce the occurrence of HDP.

Objective To investigate the clinical application value of chromosomal microarray analysis（CMA） and wholeexome sequencing（WES） in fetuses with increased nuchal translucency（NT）. Methods From January 2020 to April 2022, clinical data of 1013 fetuses were collected who underwent invasive prenatal diagnosis due to NT thickening [defined as NT ≥95th centile for the crown-rump length（CRL）] in the Third Affiliated Hospital of Zhengzhou University. All fetuses were undergone CMA detection, 49 fetuses with negative CMA results underwent further prenatal WES. According to NT value, fetuses were divided into the following four groups: ＜3.5 mm group（529 cases, 21 cases underwent WES）, 3.5-4.5 mm group（273 cases, 8 cases underwent WES）, 4.5-5.5 mm group（98 cases, 7 cases underwent WES）, and ≥5.5 mm group（113 cases, 13 cases underwent WES）. According to the results of ultrasound examination, all fetuses were divided into structural malformation group（88 cases, 23 cases underwent WES） and isolated increased NT group（925 cases, 26 cases underwent WES）. The possible chromosomal anomalies were analyzed by CMA first. Furthermore, 49 cases with increased NT but negative CMA results were investigated by WES, and the outcomes were followed up. Results CMA showed that, among the 1013 cases of NT thickened fetus, 224 cases（22.1%） of causative genetic defects were detected, including 182（18.0%） cases with chromosomal aneuploidy and 42（4.1%） cases with pathogenic copy number variation（pCNVs）. Among different NT value groups, the positive rate of CMA in NT ≥5.5 mm group was the highest（47.8%）. In addition, the positive rate of CMA in fetuses with increased NT and structural malformations was higher than in isolated increased NT（45.5% vs. 19.9%）. WES detected monogenic disease in 5 of 49 fetuses（10.2%） with increased NT and negative CMA results, including 3 cases of autosomal dominant disease, 1 case of autosomal recessive hereditary disease and 1 case of X-linked recessive hereditary disease. All the five fetuses had structural malformations, two of them with increased NT ＜3.5 mm, and only one of them was born alive. Conclusion WES can detect out monogenic disease in fetuses with increased NT combined structural malformations with negative CMA results. Fetuses with increased NT should also be alert for the possibility of monogenic disease even if the NT value less than 3.5 mm.

The increased incidence of macrosomia has caused an enormous burden after the transition from the almost 40-year one-child policy to the universal two-child policy in 2015 and further to the three-child policy in 2021 in China. However, studies on risk factors of macrosomia in multipara under the new fertility policy in China are limited. We aim to explore the incidence and risk factors for macrosomia in multipara to provide the scientific basis for preventing macrosomia in multipara. A multi-center retrospective study was conducted among 6200 women who had two consecutive deliveries in the same hospital and their second newborn was delivered from January to October 2018 at one of 18 hospitals in 12 provinces in China. Macrosomia was defined as birth weight ≥ 4000 g. Logistic regression models were performed to analyze risk factors for macrosomia in multipara. The incidence of macrosomia in multipara was 7.6% (470/6200) and the recurrence rate of macrosomia in multipara was 27.2% (121/445). After adjusting for potential confounders, a higher prepregnancy BMI, higher gestational weight gain, history of macrosomia, a longer gestation in the subsequent pregnancy were independent risk factors of macrosomia in multipara (p < 0.05). Healthcare education and preconception consultation should be conducted for multipara patients with a history of macrosomia to promote maintaining optimal prepregnancy BMI and avoid excessive gestational weight gain to prevent macrosomia.

目的:探讨血清组织型转谷氨酰胺酶(tTG)、胎盘生长因子(PLGF)、游离脂肪酸(FAA)、T-钙粘蛋白(T-cadherin)与早发型子痫前期(EOPE)患者子宫动脉血流参数的关系,并分析围产儿不良结局的影响因素.方法:选择2019年9月～2021年5月在我院接受治疗的116例EOPE患者作为EOPE组,另选取同期80例来我院例行产检的健康志愿者孕妇作为对照组.对比EOPE组、对照组的血清FFA、PLGF、tTG、T-cadherin水平和子宫动脉血流参数.采用Pearson法分析血清FFA、PLGF、tTG、T-cadherin与EOPE患者子宫动脉血流参数的相关性.采用多因素Logistic回归分析围产儿不良结局的危险因素.结果:EOPE组的血清FFA、tTG高于对照组,PLGF、T-cadherin则低于对照组(P＜0.05).EOPE组的阻力指数(RI)、收缩期和舒张期血流流速比值(S/D)、搏动指数(PI)高于对照组(P＜0.05).Pearson相关性分析结果显示,RI、PI、S/D与FFA、tTG均呈正相关,而与PLGF、T-cadherin均呈负相关(P＜0.05).多因素Logistic回归分析结果显示,白蛋白偏低、丙氨酸氨基转氨酶偏高、血肌酐f偏高、FFA偏高、PLGF偏低、tTG偏高、T-cadherin偏低、RI偏高、PI偏高、S/D偏高均是围产儿不良结局的危险因素(P＜0.05).结论:EOPE患者血清中FFA、tTG表达升高,PLGF、T-cadherin表达下降,且与子宫动脉血流参数具有一定的相关性.白蛋白、丙氨酸氨基转氨酶、血肌酐等均是围产儿不良结局的危险因素,应加强对上述指标的监测,尽早进行相关干预,以降低围产儿不良结局的发生率.

Preterm complications and neonatal asphyxia are the leading causes of death in those under 5 years of age. However, little information exists for the province of Henan, China. The purpose of this study was to explore changes in the live birth profile in a provincial hospital over the past 32 years in Henan, China. A retrospective analysis was conducted to reveal the characteristics of live neonates from 1987 to 2018. There were 118 253 live births during the period, including 19 798 (16.74%) preterm births. The neonatal death rate was 6.45‰, and the top risk factor was preterm birth complications and birth asphyxia. Before 1998, neonatal death occurred primarily among term infants. Between 1999 and 2018, preterm infants, especially extreme and very preterm infants with very low birthweight, constituted more than half of all mortalities, and the preterm birth rate increased from 5.94% in 1999 to 16.69% in 2018. The risk factors associated with preterm birth were being male (aOR = 1.18, P < 0.001), advanced maternal age (>35 years old; aOR = 1.08, P = 0.008), gravidity ≥2 (aOR = 1.15, P < 0.001), parity ≥2 (aOR = 1.50, P < 0.001), placenta previa (aOR = 7.41, P < 0.001), twin or multiple births (aOR = 10.63, P < 0.001), hypertension (aOR = 2.08, P < 0.001), and rupture of membrane (aOR = 5.03, P < 0.001). The preterm birth rate has increased over the past 32 years from 4.98% to 16.69% in a provincial hospital in China. Preterm birth was the leading reason for neonatal death, and birth asphyxia was the major risk factor for death in term infants.

Abstract The aim of this study was to clarify the distribution of SCN1A variants in each condition of SCN1A seizure disorders and the proportion of the SCN1A variant types in different conditions of SCN1A seizure disorders.This study consisted of querying SCN1A variants in ClinVar, reclassificating ClinVar P/LP SCN1A missense variants provided by a singgle submitter, validating conditions of SCN1A Seisure Disorders by reclassification of P/LP variants and screening variant types of conditions of SCN1A Seisure Disorders by validation.The result showed that most of the P/LP SCN1A missense variants provided by a single submitter in ClinVar remained at the P/LP level (247/383), and a few variants were converted from P/LP to VUS (136/383). The condition "Early infantile epileptic encephalopathy with suppression bursts" shown in ClinVar was actually all other conditons, such as Dravet syndrome/Severe myoclonic epilepsy of infancy(DS/SMEI)(69/89) and Generalized epilepsy with febrile seizures plus/Borderline severe myoclonic epilepsy of infancy(GEFS+/SMEB) (3/89). Both in missense and trunction, DS/SMEI-related SCN1A variants had the highest proportion (291/371, 78.4%),and there were still quite a few some SCN1A variants are associated with other conditions such as GEFS+, FMH, DEE, Lennox-Gastaut Syndrome and Intractable childhood epilepsy with generlaized tonic-clonic seizures (80/371, 21.6%).This provided data support for clinicians to grasp the severity of epilepsy caused by these SCN1A variants.

Introduction To investigate the expression of miR-146a in severe preeclampsia (PE) and its effect on trophoblast cell proliferation, invasion and apoptosis, as well as its relationship with SMAD4. Material and Methods Participants were divided into the severe PE group (n = 30) and the normal group (n = 30). The expression of miR-146a and SMAD4 in placenta tissue was detected by immunohistochemistry, qRT-PCR, and western blot. Trophoblast cell lines HTR-8/SVneo were cultured to detect the expression of miR-146a under the Cobalt chloride (CoCl2)-simulated hypoxia. The effects of miR-146a transfection on cell proliferation, invasion, apoptosis, and SMAD4 expression were analyzed. Results Compared with the normal group, miR-146a expression was decreased and the protein and mRNA levels of SMAD4 were increased in placenta tissues of the severe PE group. Our in vitro experiments showed that the expression of miR-146a decreased after CoCl2 treatment. Silencing miR-146a caused increased expression of SMAD4 and decreased expression of VEGF. After transfection with miR-146a inhibitor, compared with the NC group, the invasion and proliferation of HTR-8/Svneo cells were decreased, while the apoptosis was enhanced. Conclusion The expression of miR-146a decreased in severe PE and was negatively correlated with SMAD4 expression. The expression of miR-146a was inhibited under hypoxia, and the low expression of miR-146a affected the proliferation, invasion, and apoptosis of trophoblast cells.

BACKGROUND AND OBJECTIVE:Asparagine synthetase deficiency (ASNSD) is a rare neurometabolic disease caused by variations of the ASNS gene. It manifests as microcephaly, severe developmental delay, and spastic quadriplegia. 71% of ASNSD patients died during early infancy. We aim to investigate mutations related to intractable epilepsy in one Chinese genealogy.MATERIAL AND METHODS:Head Magnetic Resonance Imaging (MRI), whole exome sequencing (WES), and Liquid Chromatography-Mass Spectrometry (LC-MS) to help 2 patients with intractable epilepsy find the underlying mechanisms of disease.RESULTS:These two patients had a compound heterozygous mutation (c.224A > G, p.N75S and c.1612A > G, p.M538V) in the ASNS gene, of which c.1612A > G was a novel mutation. The asparagine levels in patients' plasmas were normal. In addition, they had a later onset, longer survival, and were milder than previously reported ASNSD patients.CONCLUSIONS:Two patients were diagnosed with a milder form of ASNSD. Clinically, the asparagine level in the patient's plasma cannot be used as the only basis to diagnose this disease. This study has expanded the disease phenotype spectrum of ASNSD and broadened the variation profile of the ASNS gene, which can assist in the clinical diagnosis and treatment of ASNSD patients.

AIM:This retrospective study aimed to investigate the value of exome sequencing (ES) in fetuses with isolated first-trimester increased nuchal translucency (NT) and normal chromosomes. METHODS:ES was performed on 103 fetuses with isolated first trimester increased NT and normal chromosomes. The detection rate of monogenic conditions was analyzed. RESULTS:Diagnostic variants were detected in nine cases in which phenotypes and genotypes correlated well, two positive cases were Thanatophoric dysplasia type I, and one case was Kabuki syndrome, which had been detected in previous studies. Eight of the nine cases with diagnostic variants developed additional structural malformations later in pregnancy. Among the nine positive cases, six had a NT thickness between 95th percentile (95th-3.4 mm), and three cases with an increased NT of 3.5 mm or greater. Also, there was no statistical difference in the diagnosis of diagnostic variants in cases with or without a thickened nuchal fold (NF). CONCLUSIONS:The diagnostic yield of prenatal ES is low for fetuses with an isolated increased NT. In addition to Noonan syndrome, there are additional genetic syndromes such as Kabuki syndrome and Thanatophoric dysplasia type I that are potentially associated with an increased NT. A cut-off of greater than the 95th percentile may be useful in case selection for ES. Whether it is clinically meaningful to monitor NF values for fetuses with isolated increased NT and normal chromosomes worth considering.

Background: Previous studies have identified hundreds of constantly changing metabolic genes in cervical cancer, however, their prog-nostic effect remains to be explored. Methods: In this paper, Cox univariate regression and Lasso regression models were used to identify metabolic genes associated with squamous cervical cancer prognosis, and developed a prognostic risk score. Next, on the basis of the median risk score, cervical squamous cancer patients were divided into two groups: high-and low-risk patients. Kaplan-Meier analysis and receiver operating characteristic (ROC) curves were used to evaluate the predictive efficacy of the metabolic gene prognostic risk model. In addition, we analysed the correlation between drug sensitivity, immune cell infiltration, and Gene set variation analysis (GSVA) and the metabolic gene prognostic risk model. Results: The results showed that the prognosis of patients in the high-risk group was worse. The metabolic gene prognostic model was correlated with immune cell infiltration. It is also correlated with sensitivity to common chemotherapeutic drugs. In addition, gene set enrichment analysis results revealed several significantly enriched pathways, which may help to explain the underlying mechanisms of cervical carcinogenesis. Conclusions: The proposed prediction model can be potentially used for prognosis prediction of cervical cancer.

To explore pathogenic/likely pathogenic copy number variations (P/LP CNVs) and regions of homozygosity (ROHs) in fetal central nervous system (CNS) malformations. A cohort of 539 fetuses with CNS malformations diagnosed by ultrasound/MRI was retrospectively analyzed between January 2016 and December 2019. All fetuses were analyzed by chromosomal microarray analysis (CMA). Three cases with ROHs detected by CMA were subjected to whole-exome sequencing (WES). The fetuses were divided into two groups according to whether they had other structural abnormalities. The CNS phenotypes of the two groups were further classified as simple (one type) or complicated (≥ 2 types). (1) A total of 35 cases with P/LP CNVs were found. The incidence of P/LP CNVs was higher in the extra-CNS group [18.00% (9/50)] than in the isolated group [5.32% (26/489)] (P < 0.01), while there was no significant difference between the simpletype and complicated-type groups. (2) In the simple-type group, the three most common P/LP CNV phenotypes were holoprosencephaly, Dandy–Walker syndrome, and exencephaly. There were no P/LP CNVs associated with anencephaly, microcephaly, arachnoid cysts, ependymal cysts, or intracranial hemorrhage. (3) Only four cases with ROHs were found, and there were no cases of uniparental disomy or autosomal diseases. The P/LP CNV detection rates varied significantly among the different phenotypes of CNS malformations, although simple CNS abnormalities may also be associated with genetic abnormalities.