Objective To elucidate the differences between invasive micropapillary carcinoma (IMPC) and invasive ductal carcinoma(IDC),and explore the clinicopathological and immunohistochemistry characteristics of invasive micropapillary carcinoma of the breast.Methods Invasive micropapillary carcinoma was identified in 51 patients by retrospective review of database from October 2004 to November 2007.Data were compared with 102 patients identified as invasive ductal carcinoma available in this hospital during the same period.Results Significant differences were observed in mammilla invasion,lymphatic vessel invasion,positivity of lymph node,lymph node metastatic level,extranodal extension,estrogen receptor,progestin receptor,triple negative between the two groups; while there was no significant differences between the two groups as to amenorrhea status,lesion laterality,number of metastatic lymph nodes,human epidermal growth factor receptor-2,local recurrence and distant organ metastasis.The median follow-up time of the invasive micropapillary carcinoma group were 46 months ( 16 - 75 months),and the 3-year overall survival and disease free survival was 90.2％ and 84.3％,respectively.Conclusions Invasive micropapillary carcinoma is a unique subtype of breast cancer which manifests an aggressive behavior tending to involve lymph node and extranodal soft tissues.Invasive micropapillary carcinoma of the breast had high expression of hormonal receptors,and triple negative breast cancer is less common in this type of breast cancer.

Objective To investigate the correlation between neural tube defects (NTDs) and DACT1 gene, and provide the basic data for disease diagnosis and genetic counseling. Methods Blood samples were obtained from 163 NTDs patients and 480 unrelated healthy individuals. Mutation detection of DACT1 gene and DNA direct sequencing was carried out by PCR amplification. Bioinformatics analysis of these mutated loci was performed. Results Six mutations were found in NTDs patients, including 4 missense mutations (p.R45W, p.D142G, p.N356K and p.V702G). But these mutations were not found in 480 healthy individuals. Three mutated amino acid residues (p.45R, p.142D and p.356N) were highly conservative in evolution, and the mutated carriers were female patients, and suffered from anencephaly. Conclusion DACT1 gene mutation may be a risk factor of NTDs in Han population of northern China.

Objective:To explore the cytogenetic characteristics of hypospadias in children by karyotype analysis.Methods:From June 2008 to May 2018, 45 children with hypospadias in Tianjin Children's Hospital had cytogenetic abnormalities. Their median age was 10 months(range 3 hours to 5 years old). Of the 45 cases, 20 were proximal hypospadias, 1 was middle hypospadias. All 24 cases had varying degrees of genitourinary malformations. Among them, 15 cases had unilateral or bilateral cryptorchidism, 5 cases had scrotal division, 3 cases had penile scrotal transposition, 3 cases had small penis, 3 cases had indirect inguinal hernia, 1 case had repeated urethra, 1 case had hydrocele and 1 case had concealed penis. To the other systemic malformations, there was 1 with cleft lip and palate and 1 with congenital heart disease. G-banding karyotype analysis of peripheral blood lymphocytes was performed in all 45 cases.Results:Among the 45 cases of hypospadias with abnormal karyotypes, with an abnormal rate of 14.0%, 28 cases (62.22%) had sex chromosome abnormalities, including (47, XXY), (46, XX/47, XXY), (45, X0/47, XYY), etc. Sexual inversion occurred in 8 cases (17.78%), all of which were 46, XX. There were 4 autosomal abnormalities (8.89%), including (46, XY, 9p+ ), (46, XY, 10p+ ) and (46, XY, 1q+ ). Chromosome polymorphism was found in 4 cases (8.89%), including [46, XY, inv(9)] and [46, XY, 16qh+ ], and the equilibrium translocation of 1 case (2.22%) was [45, XY, -21, -22, + t(21; 22)]. Among the 45 cases, 8 sex reversal children with (46, XX) chromosome karyotype were all proximal hypospadias.Conclusions:Children with hypospadias may be associated with chromosomal karyotype abnormalities, including sex chromosomal abnormalities, autosomal abnormalities, chromosome polymorphism and balanced translocation. Among them, sex chromosome abnormality was the most common and balanced translocation was the least.

Objective To investigate the methylation alteration of genomic DNA (gDNA) and its significance in pedigree neural tube defects (NTDs).Methods Twelve subjects from 3 NTDs pedigrees were enrolled in this study.NTDs patients were served as the case group,and their family members with normal phenotype were served as the control group.Peripheral vein blood was extracted,then gDNA was extracted.The extracted gDNA was treated with sodium bisulfite propagated as DNA segments in the way of whole genome amplification,which was put in I11umina Infinium human methylation 450k bead chip to perform hybridization,elution,extension,and imaging.The chip was scanned by iScan.Genome Studio was used to read the outcome.Illumina methylation analyzer software was used to analyze the methylation data.Results Gene differential methylation analysis showed that differential methylation sites only accounted for 0.2％ of the detected CpG sites and there were 617 differential hypermethylation sites (P ＜ 0.05),and 63 of them represented significant difference(P ＜ 1 × 10-4),including zinc finger E-box binding homebox 2,5,10-methylenetetrahydrofolate dehydrogenase 1 etc;there were 104 differential hypomethylation sites (P ＜ 0.05),and 65 of them represented significant difference (P ＜ 0.01),including Homeobox B7 and runt-related transcription factor 3 etc.Clustering analysis indicated that the tendency of DNA hypermethylation was consistent with NTDs patients,but the tendency of DNA hypomethylation was consistent with the controls.Conclusion In NTDs pedigree,the abnormal DNA methylation alterations may be the risk factor for NTDs occurrence.

OBJECTIVE: To explore the genetic basis for a child with succinate semialdehyde dehydrogenase deficiency. METHODS: Peripheral blood samples of the proband and his parents were collected and subjected to Sanger sequencing. High-throughput sequencing was used to verify the gene variants. Bioinformatic software was used to analyze the pathogenicity of the variant sites. RESULTS: Sanger sequencing showed that the proband carried a homozygous c.1529C>T (p.S510F) variant of the ALDH5A1 gene, for which his mother was a carrier. The same variant was not detected in his father. However, high-throughput sequencing revealed that the child and his father both had a deletion of ALDH5A1 gene fragment (chr6: 24 403 265-24 566 986). CONCLUSION The c.1529C>T variant of the ALDH5A1 gene and deletion of ALDH5A1 gene fragment probably underlay the disease in the child. High-throughput sequencing can detect site variation as well as deletion of gene fragment, which has enabled genetic diagnosis and counseling for the family.
Amino Acid Metabolism, Inborn Errors/genetics* ; Child ; Developmental Disabilities ; Humans ; Infant ; Mutation ; Succinate-Semialdehyde Dehydrogenase/genetics*

Objective:To explore the clinical efficacy of ultrasound-indicated cervical cerclage in twin pregnancies.Methods:This retrospective cohort study included 96 asymptomatic twin pregnancies with cervix length (CL)≤2.5 cm at 16-27 +6 weeks indicated by transvaginal ultrasound from January 2013 to May 2022 in Fujian Maternity and Child Health Hospital. They received either cervical cerclage (cerclage group, n=45) or conservative treatment (conservative group, n=51). The subgroup analysis was further performed after stratifying the subjects into the CL≤1.0 cm subgroup, the CL>1.0-≤1.5 cm subgroup, and the CL>1.5 cm subgroup. Two independent samples t-test, Mann-Whitney U test, and Chi-square test were used to compare the differences in the pregnancy and perinatal outcomes between different groups. Multivariate logistic regression was used to analyze the impact of cervical cerclage on pregnancy outcomes of women with different CLs. Results:The average gestational age at delivery and the prolonged gestation were significantly greater in the cerclage group than those in the conservative group [35.9 (34.9-37.0) weeks vs 34.9 (29.1-36.1) weeks; 10.7 (9.6-13.1) weeks vs 8.7 (4.8-11.0) weeks, Z=－2.59 and -3.63, both P<0.05]. The incidences of preterm birth before 34 weeks and 28 weeks, chorioamnionitis, and preterm premature rupture of membrane were lower in the cerclage group than those in the conservative group [17.8% (8/45) vs 45.1% (23/51), χ2=8.16; 2.2% (1/45) vs 15.7% (8/51), Fisher' exact test; 8.9% (4/45) vs 25.5% (13/51), χ2=4.52; 15.6% (7/45) vs 33.3% (17/51), χ2=4.03; all P<0.05]. There were no statistically significant differences in the proportion of postpartum hemorrhage and live births between the two groups (both P>0.05). In the women with CL≤1.0 cm, the cerclage group had a greater gestational age at delivery [36.0 (34.8-37.3) weeks vs 34.9 (28.6-35.4) weeks, Z=－2.61, P=0.009], greater prolonged gestation [12.3 (9.7-13.9) weeks vs 7.3 (3.4-9.1) weeks, Z=－3.34, P=0.001], higher birthweight [2 430.0 (2 173.8-2 646.3) g vs 1 900.0 (1 372.5-2 435.0) g, Z=－3.06, P=0.002], lower incidence of adverse neonatal outcomes [16.7% (6/36) vs 36.7% (11/30), χ2=4.22, P=0.048] compared with the conservative group. Multivariate Logistic regression analysis showed that cerclage reduced the risks of preterm birth before 34 and 32 weeks [ aOR (95% CI)=0.083 (0.009-0.790) and 0.092 (0.009-0.939), both P<0.05]. However, cerclage did not reduce the risk of preterm birth in women with CL>1.5 cm or CL>1.0-≤1.5 cm (both P>0.05). Conclusion:Ultrasound- indicated cervical cerclage can reduce the risk of preterm birth before 34 and 32 weeks, prolong pregnancy, and improve perinatal outcomes in asymptomatic twin pregnancies with CL≤1.0 cm.