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 explore the relationship between the polymorphism of excision repair cross-complementation group 1 (ERCC1) C8092A locus and the efficacy and prognosis of platinum-based chemotherapy for lung cancer (LC), and to provide a theoretical basis for precision treatment of LC. Methods From January 2014 to October 2017, 120 patients from two tertiary hospitals in Haikou City, and with pathologically confirmed lung cancer treated with platinum-based chemotherapy were selected as the research objects. After informed consent was obtained, peripheral blood samples were collected for DNA extraction, and the genotype of ERCC1 C8092A locus was detected by mass spectrometry. WHO's Response Evaluation Criteria in Solid Tumours (RECIST) was used to judge patients' chemotherapy efficacy and patients' survival status was obtained by telephone follow-up and other means. Results Among the 120 LC patients, the genotype frequencies of ERCC1 C8092A locus were 67 cases of CC wildtype (55.8%), 45 cases of CA heterozygous type (37.5%), and 8 cases of AA rare mutation type (6.7%), which conformed to Hardy-Weinberg equilibrium (χ2=0.140, P>0.05). The total effective rate of chemotherapy was 32.5%, with the highest effective rate in patients with the CA genotype (42.2%) at the ERCC1 C8092A locus and the lowest in patients with the CC genotype (25.4%). The overall one-year survival rate was 68.3% and the three-year survival rate was 35.8%. The patients with ERCC1 C8092A AA genotype had the lowest survival rate, with a one-year survival rate of 50.0% and three-year survival rate of only 25.0%. However, there were no statistical differences in the overall survival rate among the three genotypes of carriers of ERCC1 C8092A (χ2=0.328, P=0.849). Conclusions The polymorphism of ERCC1 C8092A locus is associated with the efficacy of platinum-based chemotherapy for LC, and patients with CA genotype have the highest efficacy. The one-year and three-year survival rates of patients with CC genotype are significantly higher than those of CA and AA genotypes.

Objective: To investigate the intake of liquid dairy products and identify its influencing factors among the fourth grade students in Nanjing City. Methods: The fourth grade students were selected as the study subjects in Nanjing City using a multi-stage random cluster sampling method in September 2020. Their general information, frequency of liquid dairy product intake one week prior to survey and mean intake amount per time were collected. According to the 2016 Dietary Guidelines for Chinese Residents, weekly intake of liquid dairy products of 2 100 g and greater was defined eligible. Factors affecting the frequency and amount of liquid dairy product intake were identified using multivariable logistic regression analysis. Results: A total of 2 268 questionnaires were allocated and 2 216 valid questionnaires were recovered, with an effective recovery rate of 97.71%. The respondents included 1 199 boys ( 54.11% ) and 1 017 girls ( 45.89% ). The frequency of liquid dairy product intake was (6.41±4.86) times per week, and the median intake amount was 1 250.00 g per week (interquartile range, 1 750.00 g per week). There were 607 students ( 27.39% ) consuming liquid dairy products of 2 100 g and greater a week, and 1 016 students ( 45.85% ) consumed liquid dairy products for 7 times and more a week. Multivariable logistic regression analysis showed that living in urban areas ( OR=1.204, 95%CI: 1.005-1.443 ), knowing nutrition labels ( OR=1.221, 95%CI: 1.021-1.460 ), periodical measurement of body weight (OR=1.486, 95%CI: 1.098-2.011) and restricted intake of sugar-containing drinks ( OR=1.264, 95%CI: 1.005-1.590 ) facilitated the intake of liquid dairy products for 7 times and more a week, and students with periodical measurement of body weight were more likely to consume liquid dairy products for 2 100 g and greater a week ( OR=1.821, 95%CI: 1.240-2.676 ). Conclusions Inadequate intake of liquid dairy products is found among the fourth grade students in Nanjing City. Residence, awareness of nutrition labels, periodical measurement of body weight, and parental restriction of sugar-containing drink intake affect the intake of liquid dairy products.

Objective:To explore the diagnostic value of ultrasound shear wave elastography and portal vein hemodynamic parameters for chronic hepatitis and liver fibrosis.Methods:The clinical data of 48 hospitalized patients with chronic hepatitis diagnosed in Fuyang Second People's Hospital from May 2019 to July 2020 were collected and analyzed retrospectively. The patients voluntarily received portal vein hemodynamics and ultrasonic shear wave elastography. According to Scheuer's method, 48 patients were classified into 5 stages of liver fibrosis, including 10 patients in S0 stage, 13 patients in S1 stage, 10 patients in S2 stage, 10 patients in S3 stage and 5 patients in S4 stage. The average velocity of portal vein, peak portal vein velocity (PVVmax), portal vein diameter (PVD), liver stiffness measurement (LSM) and Young's modulus of liver were compared. Pathological and liver biopsy was the gold standard to analyze the sensitivity and specificity of various detection methods. The normally distributed measurement data were expressed as xˉ± s, the comparison between multiple groups was performed by one-way ANOVA, and the pairwise comparison was performed by LSD-t test. Spearman method was used to analyze the correlation between liver function classification and various parameters. ROC curve was used to analyze the diagnostic value of ultrasonic shear wave elastography, portal vein hemodynamics and combined detection in predicting liver fibrosis in chronic hepatitis. Results:In the staging of liver fibrosis, the LSM of the patients in the S0 stage was (5.29±0.19) kPa, and the Young's modulus of the liver was (21.65±2.35) kPa; the LSM of the patients in the S1 stage was (6.38±1.25) kPa, and the Young's modulus of the liver ( 22.89±3.19) kPa, LSM (9.76±1.33) kPa and hepatic Young's modulus (23.77±3.52) kPa in S2 group, LSM (15.44±2.44) kPa, hepatic Young's modulus (25.14±2.29) in S3 group, LSM (18.08±1.22) kPa and hepatic Young's modulus (27.94±2.58) kPa in patients with S4 stage, the differences between groups were statistically significant (F values ??were 115.47, 4.84, P values?were <0.001, 0.003), and the difference was statistically significant (all P<0.05). The average flow velocity of patients in S0 stage was (20.56±4.21) cm/s, PVVmax (22.19±4.33) cm/s, the average flow velocity of S1 stage was (18.39±3.79) cm/s, PVVmax (20.69±3.12) cm/s, and the average of S2 stage Flow velocity (13.46±2.21) cm/s, PVVmax (16.65±2.54) cm/s, average flow velocity in S3 stage (10.56±2.85) cm/s, PVVmax (13.42±2.46) cm/s, average flow velocity in S4 stage (8.15±1.65) cm/s, PVVmax (11.89±2.89) cm/s, the difference between the groups was statistically significant (F values were 21.35, 16.96, all P<0.001), and the difference between the two groups was statistically significant (all P<0.05). Correlation analysis by Spearman method showed that liver function grades were negatively correlated with average flow velocity and PVVmax (r values ?were -0.75 and -0.88, respectively; all P<0.001), and were positively correlated with liver Young's modulus and LSM. (r values ??were 0.54 and 0.86, respectively; all P<0.001). According to the ROC curve analysis, the AUC predicted by ultrasonic shear wave elastography was 0.75, AUC predicted by portal vein hemodynamics predicts was 0.68, and AUC predicted by combined detection predicts was 0.94. Conclusion:The combination of portal vein hemodynamics and ultrasonic shear wave elastography has a certain diagnostic power for the assessment of chronic hepatitis and liver fibrosis, with high specificity and sensitivity.

OBJECTIVE： To investigate the potential mechanism of Sophora tonkinensis in the treatment of leukemia. METHODS： The active components and their target proteins of S. tonkinensis were searched by the analysis of traditional Chinese medicine system pharmacology platform， and UniProt database and PubMed database were used to query corresponding gene names of target proteins of active components. Cytoscape 3.6.0 software was used to construct compound-target network. The genes related to leukemia were searched by DisGeNET databases， and OmicShare platform was used to screen the intersection genes of the active component targets of S. tonkinensis and leukemia disease targets. STRING database and Cytoscape 3.6.0 software were used to construct PPI network， and topological analysis was performed. GO analysis and KEGG pathway enrichment analysis were performed by using DAVID bioinformatics database. RESULTS： There were 13 active components and 204 target proteins in S. tonkinensis. The components and targets with high node degree included quercetin， kaempferol， PTGS2， PRSS1， CAMKK2， etc. There were 24 intersection genes between the active component target and leukemia target， including IRF1， BCL2， CYP1A1， PIM1， etc. PPI network of the above intersection genes contained 24 nodes and 142 edges， with an average node degree of 6.5 and an average medium of 0.045. The results of GO analysis showed that the biological process of the above-mentioned genes involved in apoptosis signaling pathway in vitro without ligands， negative regulation of apoptosis process， positive regulation of B cell proliferation， etc. Molecule function mainly included that protein homology activity and binding of the same protein. Cell components mainly included extracellular region， mitochondria and so on. KEGG pathway enrichment showed that above-mentioned genes were mainly associated with T cell receptor signaling pathway， JAK/STAT signaling pathway， HTLV-Ⅰ infection. CONCLUSIONS： Through JAK/STAT signaling pathway and HTLV-Ⅰ infection pathway， the active components of S. tonkinensis may act on PTGS2， PRSS1， CAMKK2 and other targets， and then play a therapeutic role on leukemia， showing the characteristics of multi-component， multi-target and multi-channel.

Objective: To analyze the prenatal clinical characteristics and genetic diagnosis of two fetuses with chromosome 17q12 deletion syndrome mainly manifested by renal structural abnormalities. Methods: Clinical data of two pregnant women admitted to Peking University First Hospital in 2017 due to ultrasound indication of fetal kidney structure abnormality in the second trimester were collected. Results of fetal chromosome karyotype analysis and array-based comparative genomic hybridization (aCGH), and aCGH detection of peripheral blood in the two couples were reviewed. Results: (1) In both pregnancies of case 1 and case 2, no abnormal chromosome karyotype was found. In case 2, the fetal fluorescence in situ hybridization (FISH) results showed no abnormality. (2) During the first pregnancy of case 1, there was a 1.351 Mb of single-copy deletion in chromosome 17q12 (34 817 422-36 168 104) and a 1.187 Mb of single-copy duplication in chromosome 3p26.3 (838 934-2 026 269) extracted from umbilical cord blood. Moreover, a 1.299 Mb of single copy duplication in chromosome 3p26.3 (726 645-2 026 269) extracted from maternal peripheral blood was detected. (3) DNA analysis of the umbilical cord blood of case 2 showed a 1.351 Mb of single copy deletion in 17q12. No abnormal copy number variants (CNVs) were detected in the peripheral DNA of the couple. Conclusions Invasive prenatal detection of CNVs in cases with abnormal fetal kidney ultrasound findings might help to confirm the diagnosis and guide genetic counseling.

Objective: To investigate the current status and influence factors of HBV intrauterine transmission (BIT) in HBsAg-positive parturients and understand the outcome of HBV transmission and response to hepatitis B vaccine immunization in children in Xi’an. Methods: An epidemiological survey was conducted in 341 HBsAg-positive parturients who gave birth in Northwest Women and Children Hospital of Shaanxi Province from January 2015 to January 2018. Serological tests were performed by using venous blood from 344 newborns within 24 hours after birth and at the age of 1 year old. A nested case-control study was conducted to analyze the infection rates of intrauterine dominate HBV infection (DBI) and intrauterine occult HBV infection (OBI) in BIT and their influencing factors in newborns. The epidemiological survey was conducted to collect the information about the outcome of HBV transmission and the positive rate of HBsAb in children at high-risk from August 2016 to October 2018. Results: The BIT rate was 46.51%(160/344) in HBsAg-positive parturients, the DBI rate was 8.14% (28/344), the OBI rate was 38.37% (132/344), and the odds ratio of DBI and BIT in neonates of HBeAg-positive parturients were respectively 2.60 (95%CI: 1.19-5.70) and 2.21 (95%CI: 1.36-3.61) times higher than that of HBeAg-negative parturients. The odds ratio of BIT in neonates with maternal peripheral blood HBV DNA load ≥200, ≥10³ and>10⁶ copies/ml were 1.99 (95%CI: 1.29-3.08), 1.73 (95%CI: 1.11-2.69) and 2.33 (95%CI: 1.33-4.10) times higher than those in neonates with maternal peripheral blood HBV DNA<200,<10³, and ≤10⁶ copies/ml respectively. The incidence of DBI in neonates of parturients with placenta previa was 14.07 times higher than that of parturients without placenta previa (95%CI: 1.23-160.76). The incidence of BIT in neonates of parturients who received no hepatitis B immunoglobulin during pregnancy was 1.60 times higher than that in neonates of those who received hepatitis B immunoglobulin (95%CI: 1.02-2.53). Follow-up results showed that HBsAg negative conversion was found in 9 of 14 children with DBI, and 24.17%(22/91) of children had OBI. The overall rate of immune response to hepatitis B vaccine was 69.23%(63/91). The immune response rate in children with OBI was only 59.09%(13/22). Conclusion Newborns of HBsAg-positive parturients had high rate of OBI and lower rate of immune response to hepatitis B vaccine detected in follow-up, indicating a gap in hepatitis B prevention and control. HBV monitoring and intervention in HBsAg-positive women of childbearing age and hepatitis B antibody monitoring in children at high-risk are important measures to control infection source and protect susceptible population.

Objective: To explore the role of TLR 9 in intrauterine transmission of hepatitis B virus (HBV) through blood pathway and placenta. Methods: Epidemiological investigation was carried out in 290 HBsAg positive parturients and 45 normal parturients (control group) in Northwest Women and Children Hospital of Shaanxi Province. Enzyme-linked immunosorbent assay (ELISA) was used to detect five serological makers of hepatitis B and TLR 9 levels in peripheral blood of pregnant women and newborns. HBV DNA was detected by real-time fluorescence quantitative PCR. Detection of TLR 9 expression in placenta by immunohistochemical method. A case-control study was conducted to analyze the difference of TLR 9 levels in placenta and peripheral blood of HBsAg- positive pregnant women with intrauterine transmission of HBV. Results: The incidence of dominant HBV infection (DBI), occult HBV infection (OBI) and intrauterine transmission of HBV were 9.28% (27/291), 40.21% (117/291) and 49.48% (144/291) respectively. (1) The level of TLR 9 in peripheral blood of HBsAg-positive parturients, non-HBV intrauterine transmission (NBIT) group and OBI group were significantly lower than that of control group (P<0.001). The level of TLR 9 in DBI group was significantly higher than those in NBIT group and OBI group (P=0.000). (2) The TLR 9 level in HBeAg-negative group was significantly lower than that in HBeAg-positive parturients in OBI group (P=0.01). (3) With the increased severity of intrauterine transmission of HBV in each HBV DNA load group, the TLR 9 level in maternal peripheral blood increased significantly (P<0.05). (4) With the increased severity of intrauterine transmission of HBV, the levels of TLR 9 increased significantly in antiviral therapy, immunoglobulin injection and non-hepatitis B vaccine groups (P<0.05). (5) The expression of TLR 9 in placenta tissues with DBI group was significantly higher than that in OBI group and NBIT group (P<0.05). Conclusions HBV can inhibit the secretion of TLR 9 in parturient to some extent, but HBeAg can stimulate the secretion of TLR 9. However, with the increased severity of intrauterine transmission of HBV, the level of TLR 9 in parturients is increased by intra-group cross-differentiation. Therefore, TLR 9 is not an independent marker for screening and grouping, but it can be used as an reference indicator for the monitoring and management of HBsAg-positive parturients.