Along with the development of screening, diagnostic and therapeutic technologies, the spectrum of fetal abnormalities has been constantly expanded. This brings increasing challenges to the clinical diagnosis and treatment, including but not limited to optimizing multidisciplinary cooperation, options of prenatal genetic testing methods, the uncertainty in the transition period of new technology implementation, and the comprehensiveness of genetic counseling before and after testing. We discuss the above issues aiming to meet the dilemma and achieve the leap of fetal medicine to the advanced level through multidisciplinary collaboration resulting in the improvement of diagnosis and treatment efficiency.

Objective To explore the metabolic phenotype of the adult offspring rats with maternal severe hyperglycemia during pregnancy and overfeeding in early life. Methods The adult Wistar rats were administered intraperitoneally with 20% Streptozotocin (STZ, 50 mg/kg) on day 5 of pregnancy to induce severely gestational diabetes mellitus (SDM) model (blood glucose ≥20 mmol/L). Early postnatal overfeeding models were established through reduction of the number of newborn rats fed by one mother rat. Offsprings were divided into 3 groups according to maternal blood glucose level during the pregnancy and feeding patterns during the lactation period (1) control pups (CP) :maternal euglycemia was achieved during pregnancy and eight pups fed by one mother rat; (2)SDM-normal feeding group: SDM mothers and 8 pups fed by one mother rat;(3)SDM-overfeeding group:SDM mother and 4 pups fed by one mother rat. All pups were fed by standard laboratory chow adlibitum after weaning at 3 weeks of age. The body weight of all pups were measured weekly after weaning. At the age of 26 weeks, the systolic blood pressure (SBP), diastolic blood pressure (DBP) ,heart rate (HR) and metabolic markers, including fasting plasma glucose (FPG), fasting insulin (FINS), total triglyceride (TG), total cholesterol (TC), low density lipoprotein-cholestrol (LDL-C)and high density lipoprotein-cholestrol (HDL-C) were measured in all 3 groups. ANOVA and LSD test were applied in statistical analysis. Results The average plasma glucose level was significantly higher in the SDM mothers than in the controls [(28.34±5.14) mmol/L va (6.25±1.41) mmol/L,P＜0.05]. After weaning at 3 weeks, the weight of SDM-overfeeding group and SDM-normal feeding group was lighter than that of CP group [(43.63±4.83) g, (31.45±10.21) g vs (55.75±8.41) g,P＜0. 05], meanwhile, that of the SDM-overfeeding group were heavier than that of the SDM-normal feeding group (P＜0. 05). Pups in SDM-overfeeding group exhibited catch-up growth during the lactation period, and those in SDM-normal group showed catch-up growth at both lactation period and childhood. At 26 weeks of age, the systolic blood pressure and TG level of pups in SDM-normal feeding and overfeeding group were (153.31 ± 13.91) mm Hg and (147.21 ± 12.29) mm Hg, and (0. 73±0. 22) mmol/L and (0. 71±0.49) mmol/L, respectively, which were higher than those of the CP group [( 132.21 ± 11.26) mm Hg, and (0. 37 ± 0. 08) mmol/L, P＜0.05], but no significant difference was found between the two SDM groups (P＞0.05). There was no difference in FPG levels among the three groups, but the FINS level and HOMA-IR in the SDM-overfeeding group were higher than in the SDM normal feeding and CP group [( 12. 552 ± 3.260) mU/L vs (9.067 ± 1.782) mU/L and (8.590± 0.806) mU/L, 2.400± 0.624 vs 1.797 ± 0.508 and 1.729 ± 0.246; P＜0.05].Conclusions Fetal exposure to maternal severe hyperglycemia during pregnancy may lead to low birth weight infant who will exhibit postnatal catch-up growth. This may lead to the increased risk of metabolic syndrome in the offspings when they grow up, and this process would be accelerated by early overfeeding.

Objective To evaluate the expression and distribution of Toll-like receptor 4 (TLR4) in term placentas of women with gestational diabetes mellitus (GDM). Methods Placental samples were collected from 36 normal full-term singleton pregnant women (control group) and 33 full-term singleton pregnant women with GDM who had elective cesarean section in Peking University First Hospital between November 2014 and June 2015. Immunohistochemical assay was used to detect the expression and distribution of TLR4 in placental tissues. T test was used to compare the expression of TLR4 in various cell types of placenta by semi-quantitative analysis. Results (1) TLR4 was expressed in the cell membrane, cytoplasm or nuclei of trophoblast, decidual cells, vascular endothelial cells and amniotic epithelial cells of term placentas. (2) Compared with the control group, the expression of TLR4 was significantly enhanced in trophoblast and decidual cells of GDM women (0.38±0.01 vs 0.31±0.01, 0.39±0.01 vs 0.34±0.01, t=5.218 and 4.525, all P<0.01). Moreover, the change of TLR4 average optical density was most significant in trophoblast. (3) There was no difference in the expression of TLR4 in vascular endothelial cells and amniotic epithelial cells in term placentas of GDM women compared with the control group (all P>0.05). Conclusions The expression of TLR4 is different in various cell types of GDM term placentas.

Karyotype analysis has been considered as the key tool for prenatal diagnosis .Although it is cost-effective, it has great challenge to meet the growing demand of efficiency and quality in clinical settings.To improve the effeiciency and detection quality , cytogenomic microarray analysis ( CMA ) is developed, with high detection rate.However, traditional karyotype analysis at different resolution should also be used as the reference for CMA .

Objective To study the clinical significance of chromosome karyotyping in pregnant women with a history of abnormal pregnancy. Methods The fetal chromosome karyotypes of 1 193 pregnant women with a history of abnormal pregnancy in Peking University First Hospital from January 4, 2005 to December 31, 2013 were analyzed. According to the etiology of their previous abnormal pregnancy, these women were divided into four groups: 273 women had children with inherited metabolic disorders or single-gene genetic diseases (group A), 81 women had children or fetuses with chromosome abnormalities (group B), eight cases had an abnormal chromosomal karyotype in either husband or wife (group C), and 833 women had abnormal pregnancy of unknown causes(group D). Results Forty-eight [4.0%(48/1 193)] and fetuses were found to have abnormal chromosomal karyotypes, including 26 cases of chromosome polymorphism variations and 22 cases of numerical and structural abnormalities (four cases of trisomy 21, four cases of numerical sex chromosome abnormalities, three cases of trisomy 18, three cases of extra small chromosome mosaicism, three cases of reciprocal translocation, one case of Robertsonian translocation, one case of chromosome six inversion between the arms, one case of chromosome three inversion between the arms, one case of mosaicism of trisomy 14 and one case of structural abnormality of chromosome 14). In group A, four cases (1.5%) of chromosomal abnormalities of clinical significance and four cases of chromosome polymorphism variations were detected. Meanwhile, 61 fetuses with inherited metabolic disorders or single-gene genetic diseases and two cases of gene mutation carriers were detected in group A, but among whom, there were no abnormal chromosome karyotype cases. In group B, two cases (2.5%) of chromosomal abnormalities were found. In group C, two cases (2/8) of reciprocal translocation were found, whose karyotypes were the same as the parents. In group D, three cases of trisomy 21, three cases of trisomy 18, two cases of extra small chromosome mosaicism and two cases of numerical sex chromosome abnormalities were found. All the mothers in this group were of advanced age. Four cases of structural abnormalities and 22 cases of chromosome polymorphism variations were also found in this group, chromosomal analysis was subsequently performed in those couples, and found that the abnormal chromosomal karyotypes in the fetuses were the same as those in the parents. Conclusions Appropriate prenatal cell genetic diagnostic methods should be chosen according to the causes of abnormal pregnancy history.

Objective:To determine synchronously protocatechuic aldehyde and danshensu in Compound Danshen Lozenge and Dropping Pills.Methods:HPLC method was used.Results:The average recoveries(n=5) were 100.47% for Danshensu of Compound Danshensu Lozenge(RSD=1.08%) and 99.27% for protocatechuic aldehyde(RSD=1.22%), respectively. And the average recoveries(n=3) were 100.40% for Danshensu of Compound Danshen Dropping Pills(RSD=0.65%) and 98.47% for protocatechuic aldehyde(RSD=1.76%).Conclusion:This method is simple, quick with a good separation.

Objective To compare the contents of total flavonoids, forsythoside A and phillyrin in Forsythiae Fructus leaves tea under different drying conditions; To determine the best drying method for Forsythiae Fructus leaves tea. Methods With the sodium nitrite-aluminum trichloride-sodium hydroxide solution as color reagent, total flavonoids in forsythiae Fructus leaves tea were determined by UV spectrophotometry at the wavelength of 500 nm. HPLC was used to determine the contents of forsythiaside A and phillyrin. The analysis was performed on a Diamosil C18 (2) column (4.6 mm × 250 mm, 5 μm); the mobile phase was composed of acetonitrile and 0.4% acetic acid with gradient elution; the detection wavelength was set at 277 nm; the flow rate was 1.0 mL/min at column temperature of 30 ℃. Results The content of total flavonoids of Forsythiae Fructus leaves tea under different drying conditions was basically the same; the sequence of the contents of forsythoside A and Forsythin of Forsythiae Fructus leaves tea under different drying conditions was: ventilated drying > vacuum drying > blast drying. Conclusion Different drying conditions have no effect on the contents of total flavonoids in Forsythiae Fructus leaves tea, but have obvious effects on the contents of forsythiaside A and phillyrin. Ventilation shade is better than blast drying and vacuum drying for preverence of forsythiaside A and forsythin.

Objective To evaluate the trend in prenatal diagnosis of single gene disorders (SGD) and role ofmultidisciplinary cooperative mode.Methods In January l,2012,amultidisciplinarycooperativemode for SGD diagnosis was established in the Peking University First Hospital,involving Departments of Obstetrics,Pediatrics,Neurology,Dermatology and Central Laboratory.For each pregnant woman with a family history of SGD for prenatal diagnosis,propositus should be diagnosed in the relevant departments,and then further diagnosed,managed and followed up by the Obstetrics Department.Up to December 31,2014,of 6 681 women for prenatal diagnosis,279 women had a family history of SGD:76 of them received chorionic villus sampling (CVS) at 11-14 gestational weeks,and 203 received amniocentesis (AC) at 16-22 gestational weeks.The trend in SGD diagnosis and the safety of CVS and AC were analyzed using Chi-square test.Results The proportion of SGD family history in AC group was 3.2％ (203/6 355),which stayed stable with 2.3％ (47/2 054) in 2012,3.9％ (78/2 023) in 2013 and 3.4％ (78/2 278) in 2014,and there was no significant difference between 2013 and 2014 (x2=0.571,P=0.463).In CVS group,the proportion of SGD family history was 23.3％ (76/326),showing an increasing trend with 18.2％ (8/44) in 2012,17.6％ (19/108) in 2013 and 28.2％ (49/174) in 2014,and there were significant differences between 2013 and 2014 (x2=4.067,P=0.046).The proportion of SGD family history in CVS group was higher than in AC group in year 2012,2013 and 2014 (x2＝42.626,44.531 and 201.400,all P=0.000).Among the 279 cases of SGD family history,no complications and adverse outcome were observed except an intra-uterine fetal death occurring 6 months after CVS in one woman,but 3 fetuses were found to have chromosome anomalies with one trisomy 18,one 45,X,and one mosaicism of 45,X/46,XY which was determined to be normal by AC.Conclusions SGD family history is one of the important indicators in prenatal diagnosis,and CVS is feasible for prenatal diagnosis of SGD family history as early as in the first trimester.Multidisciplinary cooperative mode is helpful in SGD family history diagnosis.

Objective To understand the correlation between chromosome deletion and the phenotypes in cases of ring chromosome 6 syndrome.Methods Two cases of ring chromosome 6 syndrome persented to the Peking University First Hospital in 2013 were studied.Case 1 was a fetus diagnosed as having ring chromosome 6 with karyotype 46,XY,r (6) [14]/46,XY,r (6; 6) [1]/45,XY,-6[15] from a pregnant woman who received prenatal examination because of high risk found in serum screening for Down's syndrome at 21 +1 weeks of gestation.Case 2 was an eight-month-old female infant with growth retardation and congenital facial anomaly,whose karyotype was 46,XX,r (6) /47,XX,r (6) × 2/46,XX,r (6; 6) /45,XX,-6.Multiplex ligation-dependent probe amplification and array-based comparative genomic hybridization were used to detect the location of chromosome telomeric loss and its size,and the correlation between chromosome deletion and the phenotypes was analyzed by reviewing related literatures.Results Case 1 was confirmed to have short-arm terminal deletions on 6p25.3-25.2 (2.42 Mb) which mainly included DUSP22,IRF4,EXOC2,FOXC1,FOXF2 and FOXQ genes,and long-arm terminal deletions on 6q26-27 (7.84 Mb) mainly included PARK2,PACRG,LOC28596 and RPS6KA2 genes.Case 2 had short-arm terminal deletions on 6p25.3-25.1 (5.44 Mb) which included DUSP22,IRF4,EXOC2,FOXC1,FOXF2,FOXQ and SERPINB6 genes,and long-arm terminal deletions on 6q27 (0.16 Mb) which included PSMB1,TBP and PDCD2 genes.Except for the growth retardation,the common feature of ring syndrome,in both cases,cerebellum hypoplasia was observed in case 1,and microcephaly and esotropia were observed in case 2.Conclusions The difference of phenotypes in patients with a ring chromosome 6 is closely associated with the location and size of the deletion in chromosome 6.

Objective To analyze the clinical application of fluorescence in situ hybridization ( FISH) and karyotype analysis in prenatal diagnosis of chromosomal abnormalities .Methods The prenatal diagnosis of chromosome aneuploidies by FISH analysis of chromosome-specific probes (chromosome 13,18, 21,X,Y) in interphase amniocytes of 1 809 pregnant women of 17-38 weeks of gestational age was used , comparisons with the karyotyping results was done simultaneously.All the 1 809 cases came from Peking University First Hospital from July 1,2012 to December 31,2013, and the relevant clinical data and birth follow-up information were collected.Results All the 1 809 cases had been successfully examined by FISH , including 1 767 normal cases and 42 cases of numerical abnormality (39 cases of aneuploid, 1 case of triploid and 2 cases of mosaicism),which were consistent with the karyotyping analysis .What′s more,34 cases of chromosomal structural abnormalities , 5 cases of chimera and 12 cases of normal variant were failed to detected by FISH.Conclusion With the advantages of high-speed,simplicity,high accuracy,etc,FISH can be an effective tool in clinical applications , and had great significances in cytogenetic prenatal diagnosis combined with karyotyping analysis.