Objective:To explore the value of chromosomal microarray analysis (CMA) in the genetic diagnosis of different types of fetal growth restriction (FGR).Methods:A retrospective analysis was conducted on 120 cases who were diagnosed with FGR by ultrasound and underwent prenatal diagnosis at the Department of Obstetrics & Gynecology and Reproductive Medicine, Peking University First Hospital, from January 2016 to December 2021. The cases were divided into three groups based on the gestational age at the first diagnosis:<28 weeks (40 cases), 28-31 +6 weeks (65 cases), and ≥32 weeks (15 cases). They were also categorized into isolated and non-isolated FGR based on the presence of other ultrasound abnormalities (69 and 51 cases in each). Chromosomal karyotype analysis and CMA were conducted on all patients. The prenatal diagnosis results were analyzed, as well as the detection of chromosomal abnormalities in different gestational age groups and types of FGR. Statistical analysis was performed using Fisher's exact test. Results:(1) A total of 14 abnormalities were detected by CMA and four cases were detected by chromosomal karyotype analysis. The abnormal detection rate of CMA was higher than that of chromosomal karyotype analysis [11.7% (14/120) vs. 3.3% (4/120), P=0.025]. Among the total 14 cases of chromosomal abnormalities, there were seven pathogenic copy number variations (CNVs) and four variants of unknown significance (VUS), as well as two cases of trisomy-18 and one case of Turner syndrome. Among the 14 cases, eight had associated ultrasound abnormalities. Eleven of the 14 cases opted for induced abortion; three continued pregnancy to delivery, with two neonates showing no abnormalities and one exhibiting slightly delayed physical development. Both methods detected three cases of aneuploidy mnumber abnormalities (2.5%, 3/120) For chromosomal abnormalities <10 Mb, the detection rate of CMA was higher than that of chromosomal karyotype analysis [9.2% (11/120) vs. 0.8% (1/120), Fisher's exact, P=0.005]. Both methods detected one case of <10 Mb CNV, while CMA alone detected ten cases of <10 Mb microdeletions/microduplications (8.3%, 10/120), including six cases of pathogenic CNVs and four cases of VUS. (2) Among the 40 cases in the <28 weeks group, six cases (15.0%) of chromosomal abnormalities were detected, including three cases of aneuploidy, two cases of pathogenic CNVs, and one case of VUS. Among the 65 cases in the 28-31 +6 weeks group, seven cases (10.8%) of chromosomal abnormalities were detected, including five cases of pathogenic CNVs and two cases of VUS. Of the 15 cases in the ≥32 weeks group, one case of chromosomal abnormality was detected, which was VUS. (3) No statistically significant difference was found in the detection rate of chromosomal abnormalities between the isolated FGR and the non-isolated FGR groups [8.7%(6/69) vs. 15.7%(8/51), Fisher's exact, P=0.263]. (4) After excluding the ≥32 weeks non-isolated FGR group (only one case), the <28 weeks non-isolated FGR group had the highest detection rate of chromosomal abnormalities (1/18), while no abnormalities were detected in the ≥32 weeks isolated FGR group. Conclusions:Among FGR fetuses, the highest detection rates of chromosomal abnormalities are found in early-onset and non-isolated FGR. Prenatal diagnosis with CMA testing can significantly improve the detection rate of genetic causes in various types of FGR fetuses.

Objective:To explore the value of chromosomal microarray analysis (CMA) in the genetic diagnosis of different types of fetal growth restriction (FGR).Methods:A retrospective analysis was conducted on 120 cases who were diagnosed with FGR by ultrasound and underwent prenatal diagnosis at the Department of Obstetrics & Gynecology and Reproductive Medicine, Peking University First Hospital, from January 2016 to December 2021. The cases were divided into three groups based on the gestational age at the first diagnosis:<28 weeks (40 cases), 28-31 +6 weeks (65 cases), and ≥32 weeks (15 cases). They were also categorized into isolated and non-isolated FGR based on the presence of other ultrasound abnormalities (69 and 51 cases in each). Chromosomal karyotype analysis and CMA were conducted on all patients. The prenatal diagnosis results were analyzed, as well as the detection of chromosomal abnormalities in different gestational age groups and types of FGR. Statistical analysis was performed using Fisher's exact test. Results:(1) A total of 14 abnormalities were detected by CMA and four cases were detected by chromosomal karyotype analysis. The abnormal detection rate of CMA was higher than that of chromosomal karyotype analysis [11.7% (14/120) vs. 3.3% (4/120), P=0.025]. Among the total 14 cases of chromosomal abnormalities, there were seven pathogenic copy number variations (CNVs) and four variants of unknown significance (VUS), as well as two cases of trisomy-18 and one case of Turner syndrome. Among the 14 cases, eight had associated ultrasound abnormalities. Eleven of the 14 cases opted for induced abortion; three continued pregnancy to delivery, with two neonates showing no abnormalities and one exhibiting slightly delayed physical development. Both methods detected three cases of aneuploidy mnumber abnormalities (2.5%, 3/120) For chromosomal abnormalities <10 Mb, the detection rate of CMA was higher than that of chromosomal karyotype analysis [9.2% (11/120) vs. 0.8% (1/120), Fisher's exact, P=0.005]. Both methods detected one case of <10 Mb CNV, while CMA alone detected ten cases of <10 Mb microdeletions/microduplications (8.3%, 10/120), including six cases of pathogenic CNVs and four cases of VUS. (2) Among the 40 cases in the <28 weeks group, six cases (15.0%) of chromosomal abnormalities were detected, including three cases of aneuploidy, two cases of pathogenic CNVs, and one case of VUS. Among the 65 cases in the 28-31 +6 weeks group, seven cases (10.8%) of chromosomal abnormalities were detected, including five cases of pathogenic CNVs and two cases of VUS. Of the 15 cases in the ≥32 weeks group, one case of chromosomal abnormality was detected, which was VUS. (3) No statistically significant difference was found in the detection rate of chromosomal abnormalities between the isolated FGR and the non-isolated FGR groups [8.7%(6/69) vs. 15.7%(8/51), Fisher's exact, P=0.263]. (4) After excluding the ≥32 weeks non-isolated FGR group (only one case), the <28 weeks non-isolated FGR group had the highest detection rate of chromosomal abnormalities (1/18), while no abnormalities were detected in the ≥32 weeks isolated FGR group. Conclusions:Among FGR fetuses, the highest detection rates of chromosomal abnormalities are found in early-onset and non-isolated FGR. Prenatal diagnosis with CMA testing can significantly improve the detection rate of genetic causes in various types of FGR fetuses.

Objective To discuss the efficacy of transumbilical single-incision laparoscopic surgery for neonatal congenital intestinal atresia.Methods A retrospective analysis was conducted on data of 27 children admitted to our hospital from September 2019 to September 2022 who underwent transumbilical single-incision laparoscopic assisted surgery.A curved incision on the right side of the umbilicus to 1/2 circumference was made.A 3.5 cm disposable single hole multi-channel port(Port)was inserted.The intestinal atresia was located under direct vision.The proximal hypertrophic intestinal tube was removed,and the distal intestinal tube to the mesenteric side was cut open.Intermittent single layer suture with 5-0 absorbable suture was performed for end-oblique incision anastomosis.Then the CO2 pneumoperitoneum was established,and the entire abdominal cavity was observed to deal with combined deformities.Results The surgery was successfully completed in all the 27 patients,without conversion to open surgery.During the surgery,15 cases of jejunal atresia and 12 cases of ileal atresia were confirmed.There were 8 cases of type Ⅰ,5 cases of type Ⅱ,12 cases of type Ⅲa,and 2 cases of type Ⅲb.During the surgery,there were 5 cases of meconium peritonitis,1 case of biliary atresia,2 cases of intestinal malrotation,1 case of Meckel's diverticulum,2 cases of cryptorchidism,and 1 case of inguinal hernia.The median surgical time was 110.0(90.0,122.5)min.The median postoperative feeding time was 11.0(7.0,14.5)d.No anastomotic leakage occurred.The median postoperative hospital stay was 18.0(15.0,33.5)d.One child underwent the second surgery.A total of 22 cases were followed up for 0.5-4 years(average,2.3 years)without re-operations.Conclusions Transumbilical single-incision laparoscopic surgery for neonatal congenital intestinal atresia is scarless and easy to operate.Combined with the use of a Port,it can reduce intestinal compression and facilitate traction.Laparoscopy can simultaneously handle combined deformities.

Objective:To investigate the significance of abnormal morphology of Sylvian fissure detected by fetal neurosonogram (NSG) in prenatal diagnosis of malformations of cortical development (MCD).Methods:This retrospective study involved fetuses with abnormal morphology of Sylvian fissure on prenatal NSG in Peking University First Hospital between January 2016 and December 2021. Clinical data including the basic information as well as the results of NSG, genetic examinations and MRI were collected. The diagnosis of MCD could be made when both brain morphological abnormalities and pathogenic/likely pathogenic genetic abnormalities were presented. The association between the abnormal morphology of Sylvian fissure and MCD was analyzed by descriptive analysis.Results:Thirteen participants who had complete genetic information were included in this study [defined as those who were found with pathogenic/likely pathogenic copy number variation (CNV) or those who further underwent whole-exome sequencing (WES) as no pathogenic/likely pathogenic CNV were detected]. Twelve fetuses (12/13) were eventually diagnosed with MCD. Pathogenic CNV were found in seven fetuses and pathogenic point mutations in five, involving six pathogenic genes and four genetic syndromes. Symmetric morphologic abnormality of Sylvian fissure was detected in 10 cases by prenatal NSG with shallow and broad shape in six and abnormal angle of Sylvian fissure in four. The other two fetuses showed asymmetric abnormal morphology of Sylvian fissure that was shallow and broad shape on one side and abnormal angle on the other. The imaging features of MCD present by prenatal NSG and were consistent with those of MRI.Conclusions:Abnormal morphology of Sylvian fissure detected by prenatal NSG is important in MCD diagnosis. Genetic examination are recommended to the fetuses with abnormal morphology of Sylvian fissure. For those requiring for genetic analysis, chromosomal microarray analysis together with WES might be an optimal choice.

Global developmental delay/intellectual disability (GDD/ID) is an enormous group of neurodevelopmental disorders with diverse clinical and genetic heterogeneity. The estimated prevalence of GDD/ID was 1%-3%, affecting about 150 million people. GDD/ID is one of the leading causes of disability in children worldwide. The causes of GDD/ID are complex, comprising genetic and environmental factors. It is often co-morbid with a variety of psychiatric behavioral disorders, such as autism spectrum disorder and attention deficit hyperactivity disorder. Owing to the improvement of genetic technology, monogenic GDD/ID has been one of the hot-spot research in genomic era, and the relevant preventive measures deserve extensive attention. In this review, we summarized the advances in genetics and prevention of monogenic GDD/ID.

Objective:To investigate the application value of intrathoracic double-flap tech-nique (Kamikawa anastomosis) in combined thoracoscopic and laparoscopic radical resection for esophagogastric junction cancer.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 10 patients with esophagogastric junction cancer who were admitted to the First Affiliated Hospital of Xiamen University between July 2022 and April 2023 were collec-ted. There were 7 males and 3 females, aged 62(range, 53-71)years. All the 10 patients underwent combined thoracoscopic and laparoscopic radical resection for esophagogastric junction cancer. Reconstruction was performed with an intrathoracic Kamikawa anastomosis. Observation indicators: (1) intraoperative and postoperative situations; (2) postoperative pathological examination; (3) follow-up and survival. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results:(1) Intraoperative and postoperative situations. All the 10 patients underwent surgery successfully. The operation time and volume of intraoperative blood loss were (347±41)minutes and (91±41)mL. The time to postoperative fluid diet intake, time to removal of postoperative abdominal drainage tube, time to removal of postoperative chest drainage tube, duration of postoperative hospital stay were (4.3±1.1)days, (5.0±1.6)days, (10.5±3.9)days, (13.3±3.8)days. Six patients had postoperative complications, including 1 case of Clavien-Dindo grade ⅢB, 3 cases of Clavien Dindo grade Ⅱ, 2 cases of Clavien Dindo grade Ⅰ. An upper gastrointestinal contrast at postoperative day 7 showed no anastomotic leak or anastomotic stricture in the 10 patients. (2) Postoperative pathological examination. Results of postoperative pathological examination in the 10 patients showed negative surgical margin. The number of lymph node dissected was 22±6. There were 3 patients with 5 positive lymph nodes. The tumor diameter and distance from center of tumor to squamocolumnar mucosal junction were (3.3±0.5)cm and (1.9±1.4)cm. One patient had tumor differentiation degree as high and moderate differentiation, 5 cases as moderate differentiation, 3 cases as moderate and low differentiation, 1 case as low differentiation. There were 5 patients with squamous cell carcinoma of the esophagogastric junction and 5 patients with adenocarcinoma of the esophagogastric junction. (3) Follow-up and survival. All the 10 patients were followed up for 7(range, 3?12)months, achieving disease-free survival. The visick quality of life grade Ⅰ, Ⅱ, Ⅲ, Ⅳ were observed in 7, 3, 0, 0 patients. Postoperative gastroscopy was completed in 7 patients, in which mild anastomotic strictures were noted in 2 patients, but no treatment was required. There was no reflux esophagitis.Conclusion:Intrathoracic Kamikawa anastomosis in combined thoracoscopic and laparoscopic radical resection for esophagogastric junction cancer is safe and feasible, with satisfactory short-term efficacy.

Objective To explore the clinical significance of the combined application of palpebral margin cleaning and antibiotic eye drops in inhibiting bacterial growth in the palpebral margin and conjunctival sacs before cataract extraction. Methods In this study, 61 patients (97 eyes) with age-related cataract who underwent phacoemulsification and intraocular lens implantation were selected, and randomly grouped. In the experimental group, the combined application of palpebral margin cleaning with cotton pads and levofloxacin eye drops was given for three days before the surgery. In the control group, levofloxacin eye drops alone were applied for three consecutive days. Bacteria samples from the conjunctival sac and eyelid margins were cultivated and identified before and three days after taking antimicrobial measures, respectively. Results In the experimental group, the positive rates of the two bacteria samples were 100％ (50/50) and 40％ (20/50) before and 10％ (5/50) and 0％ (0/50) after the treatment. In the control group, the positive rates of the two bacteria samples were 97.9％ (46/47) and 29.8％ (14/47) before and 40.4％ (19/47) and 10.6％ (5/47) after the treatment. The positive rates between the two groups were not significantly different before taking antimicrobial measures (P = 0.485 and 0.395), while they were significantly different after taking antimicrobial measures (P = 0.001 and 0.024). Conclusion Combined application of eyelid and palpebral margin cleaning with cotton pads and antibiotic eye drops before cataract extraction imparted excellent antibacterial effects.

Objective:To summarize the prenatal diagnostic characteristics of monogenic global developmental delay/intellectual disability(GDD/ID) pedigrees.Methods:This study retrospectively collected the prenatal molecular diagnostic results of 43 pedigrees that were affected with monogenic GDD/ID in the genetic counseling clinic of Peking University First Hospital from January 2015 to June 2019. The results of prenatal molecular tests were validated after birth or pregnancy termination. Pregnancy outcomes and healthy condition of the offspring were followed up. All data were analyzed by descriptive statistical analysis.Results:Among the 43 pedigrees, 24 were affected with autosomal recessive inheritance (AR) GDD/ID, in which six (25%) fetuses were found to carry two pathogenic variants; 13 (55%) had only one pathogenic variant; five (20%) did not harbor any variant. GDD/ID inherited in an autosomal dominant inheritance (AD) pattern was found in 13 pedigrees, in which 11 fetuses carried no variants while the other two fetuses had the same variants as the proband had (in one pedigree, a low-level variant was detected in the peripheral blood sample of the father while absent in peripheral blood samples of parents in the other pedigree, so it was suspected that the variants of these two affected fetuses were inherited from parental mosaicism). In the other six pedigrees with X-linked inheritance (XL) of GDD/ID, one male fetus was found to harbor the pathogenic variant, while no variants were detected in the others. Maternal contamination was excluded in all prenatal samples using short tandem repeat for linkage analysis. Postnatal validations were consistent with the prenatal tests. All nine affected fetuses were terminated, and the other thirty-four children were delivered and in good health.Conclusions:Prenatal molecular diagnostic test is an effective method to detect pathogenic variants during the first and second trimesters for pedigrees affected by monogenic GDD/ID. For pedigrees affected with AD or XL patterns caused by de novo mutations, potential parental mosaicism should be noted and prenatal diagnostic tests are also recommended.

Objective:To summarize the characteristics of genetic variation and prenatal diagnosis in pedigrees with X-linked adrenoleukodystrophy (X-ALD) and elucidate the value of prenatal diagnosis in preventing the birth of children with X-ALD.Methods:Twenty pedigrees, clinically diagnosed with X-ALD in Peking University First Hospital from November 2012 and March 2019, were included in this retrospective study. Genomic DNA was extracted from peripheral blood and amniotic fluid or chorionic villi samples of probands and their families for detecting variants in ATP-binding cassette subfamily D member 1 ( ABCD1) gene using polymerase chain reaction (PCR)-Sanger sequencing. Linkage analysis was also performed on five microsatellite markers near ABCD1 gene to exclude maternal contamination. Characteristics of ABCD1 gene variants and prenatal diagnosis of X-ALD pedigrees were summarized by descriptive statistics. Results:Twenty ABCD1 gene variants were identified in the 20 pedigrees. The variants in three probands that were not detected by next-generation sequencing were identified by PCR-Sanger sequencing. Among the mothers of the 20 probands, 17 carried ABCD1 variants and three did not. We performed 24 prenatal diagnoses on 20 pregnancies (24 fetuses) and identified eight fetuses with variants who were finally terminated. The 16 cases without variants were born alive. The validation results obtained after termination or delivery were consistent with those performed prenatally. Conclusions:No hotspot variants in ABCD1 gene are detected in these X-ALD patients and most variants are maternally inherited. PCR-Sanger sequencing is an effective method for detecting ABCD1 variants. Prenatal diagnosis for mothers who had a body with X-ALD could prevent another one from birth.

Objective:To explore the role of parental origin verification in chromosomal microarray analysis (CMA) on the determination of the clinical significance of copy number variations (CNVs).Methods:This retrospective study collected clinical information from 73 core families who underwent prenatal diagnosis at Peking University First Hospital from November 2017 to December 2019. Indications for prenatal diagnosis included ultrasound abnormality in 54 cases (including 12 with thickened nuchal translucency (≥2.5 mm), four with fetal growth restriction, seven with abnormal pregnancy history, and 31 with isolated ultrasound abnormality), NIPT indicated high-risk in four cases, advanced age in nine cases, abnormal pregnancy history alone in three cases, intrauterine death in two cases and one with maternal mental retardation. Genomic DNA of amniotic fluid sample, chorionic villi, cord blood, fetal tissues, and fetal heart blood were extracted using genomic DNA extraction kit. The CNVs of prenatal samples in 73 subjects were analyzed using array-based comparative genomic hybridization (array-CGH) analysis and single nucleotide polymorphism array (SNP-array). Peripheral blood DNA of the couples, and relevant families if necessary, were collected and analyzed in the same way. The results of parental origin detection in CMA were summarized.Results:A total of 76 CNVs were detected in these 73 samples, out of which nine were pathogenic and parental origin detection revealed that six were de novo, two were maternally, and one was paternally inherited; six CNVs were likely pathogenic, including three de novo, two maternally inherited and one paternally inherited; 20 CNVs were variants of uncertain significance, including five paternally inherited, three maternally inherited and 12 de novo; 41 CNVs were likely benign, among which 38 were inherited from parents with normal phenotype. Conclusions:Parental origin verification plays an important role in explaining the clinical significance of detected fetal CNVs and thereby can help to analyze its clinical effect and reproductive risk.