Pedigree analysis for prenatal screening and diagnosis / 中华围产医学杂志

The information arising from pedigree analysis is important for clinicians to understand the inheritance pattern of the disease, filter the testing data, and provide suggestions to other family members. Along with the development and clinical implementation of new genetic testing, an increasing number of "positive" results are obtained and pedigree analysis is required to further verify the pathogenicity.

Exercises down regulate Toll-like receptor 4 signaling pathway in obese and overweight pregnant women / 中华围产医学杂志

Objective:To explore the effect of exercise intervention on regulation of Toll-like receptor 4 (TLR4) signaling pathway in overweight and obese pregnant women.Methods:The cohort was based on a randomized controlled trial (RCT) carried out by the same research group in Peking University First Hospital from December 2014 to July 2016. Overweight and obese patients who delivered by elective cesarean section without pregnancy complications were recruited, among which 12 cases in the exercise group and 11 cases in the control group were selected. Real-time polymerase chain reaction, Western Blot, and Luminex experiments were used to compare the expression of TLR4-myeloid differentiation factor 8(MyD88)-nuclear factor-κB(NF-κB) pathway in peripheral blood mononuclear cell (PBMC), rectus abdominis muscle, omental adipose, and subcutaneous adipose, as well as the levels of inflammatory factors (TNF-α, IL-1β, IL-10) in plasma between the two groups. Two independent samples t-test, generalized estimating equation, Chi-square test, and Pearson correlation analysis were adopted for statistical analysis. Results:(1) The expression of inflammatory factors TNF-α and IL-1β in the exercise group showed a downward trend compared with the control in the second and third trimester, but none of the differences were statistically significant (all P>0.05). (2) The mRNA expression of TLR4, MyD88, and NF-κB and the protein expression of TLR4 and NF-κB in PBMC of the exercise group were significantly lower than those in the control group during pregnancy (TLR4 mRNA: 0.06±0.03 vs 0.10±0.04 in the second trimester, 0.05±0.02 vs 0.11±0.05 in the third trimester, χ2=8.07; MyD88 mRNA: 0.09±0.03 vs 0.11±0.03 in the second trimester, 0.10±0.04 vs 0.17±0.06 in the third trimester, χ2=5.81; NF-κB mRNA: 0.10±0.03 vs 0.17±0.08 in the second trimester, 0.08±0.03 vs 0.20±0.08 in the third trimester, χ2=14.71; TLR4 protein: 1.7±0.5 vs 1.9±0.8 in the second trimester, 1.7±0.4 vs 2.3±0.8 in the third trimester, χ2=5.83; NF-κB protein: 1.0±0.4 vs 1.5±0.4 in the second trimester, 1.2±0.3 vs 1.5±0.5 in the third trimester, χ2=4.73; all P<0.05). Moreover, the differences in the mRNA expression of TLR4, MyD88, and NF-κB and TLR4 protein expression in PBMC between the two groups gradually increased. (3) NF-κB in rectus abdominis and omental adipose tissue (0.04±0.02 vs 0.08±0.04, t=－3.72; 0.25±0.05 vs 0.63±0.21, t=－5.41; both P<0.05) and TLR4 and MyD88 in subcutaneous adipose tissue (0.12±0.03 vs 0.30±0.10, t=－5.30; 0.24±0.09 vs 0.44±0.08, t=－5.38; both P<0.05) were observed a decreased mRNA level in the exercise group compared with the control group. The protein level of MyD88 and NF-κB in omental adipose tissue and NF-κB in subcutaneous adipose tissue in the exercise group were significantly lower than those in the control group (1.1±0.5 vs 2.0±0.8, t=－3.15; 1.3±0.5 vs 2.0±0.9, t=－2.23; 1.2±0.5 vs 1.9±0.8, t=－2.80, all P<0.05). (4) The expressions of TLR4 and NF-κB mRNA ( r=0.453 and 0.485) in rectus abdominis muscle, NF-κB mRNA, TLR4 and MyD88 protein ( r=0.539, 0.437 and 0.527) in omental adipose in the two groups were positively correlated with the level of fasting blood glucose ( P<0.05). Conclusions:Regular exercise during pregnancy can down-regulate the expression and activation of the TLR4-MyD88-NFκB pathway in overweight and obese pregnant women. The expression of related factors along this pathway has a certain correlation with fasting blood glucose.

The effects of observing good swallowing on the swallowing ability of stroke survivors / 中华物理医学与康复杂志

Objective:To observe the effect of observing good swallowing on the swallowing action of stroke survivors with dysphagia.Methods:Eighteen stroke survivors with dysphagia were randomly divided into a treatment group ( n=9) and a control group ( n=9). In addition to routine swallowing rehabilitation therapy, the treatment group was asked to simulate swallowing after watching a video of normal people′s swallowing action. They did so 5 times a week for 10 minutes, while the control group just watched landscape videos at the same time. The treatment lasted 8 weeks. Before and after the treatment, both groups were assessed using the eating assessment tool (EAT-10), the functional oral intake scale (FOIS) and the penetration and aspiration scale (PAS). Functional magnetic resonance imaging (fMRI) was also used to observe their swallowing action. Results:There was no significant difference between the two groups in any of the measurements before the treatment. After the 8 weeks of treatment the average EAT-10, FOIS and PAS scores of the treatment group were all significantly better than before the treatment and better than the control group′s averages at the time. fMRI showed significantly more areas activated in the precuneus, parietal lobe, posterior central gyrus, BA7, BA5, frontal lobe and paracentral lobule in the treatment group compared with before the intervention and also more than in the control group.Conclusions:Observing proper swallowing action can improve dysphagia and activation of the swallowing-related brain areas of stroke survivors.

Challenge in prenatal diagnosis of monogenic and microdeletion/microduplication disorders / 中华围产医学杂志

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.

Optimal risk cut-off of sequential screening for Down syndrome: a cost-effectiveness analysis / 中华围产医学杂志

Objective:To investigate the optimal cut-off of sequential screening for Down syndrome (DS) with a cost-effectiveness analysis.Methods:A theoretical model, covering 1 000 000 singleton pregnancies, was established with the parameters from published articles and on-the-spot investigation. Two screening strategies were involved and both required conventional second-trimester serum triple screening first. For the next step, strategyⅠ was followed by cell-free fetal DNA (cffDNA) testing if the cut-offs were higher than 1/300 (Ⅰ-1) or 1/1 000 (Ⅰ-2), and if cffDNA testing indicated high risk, prenatal diagnostic testing would be performed. While strategy Ⅱ was followed by prenatal diagnostic testing in high-risk populations with cut-offs higher than 1/10 (Ⅱ-1), 1/50 (Ⅱ-2), 1/100 (Ⅱ-3), 1/150 (Ⅱ-4), 1/200 (Ⅱ-5), 1/250 (Ⅱ-6) or 1/300 (Ⅱ-7), or cffDNA testing for those with intermediate risks. The primary outcome was an incremental cost analysis on the baseline and alternative assumptions. The strategy was defined as "appropriate" when the incremental cost was less than the cost of raising one DS child. The secondary outcomes included total cost, cost-effectiveness analysis, cost-benefit analysis, and screening efficiency.Results:(1) More DS cases and less survived miss-diagnosed cases were detected by strategy Ⅱthan strategyⅠ (Ⅰ-1: 1 921, Ⅰ-2: 2 199 vs Ⅱ-1 to Ⅱ-7: 2 202-2 212; Ⅰ-1: 312; Ⅰ-2: 100 vs Ⅱ-1 to Ⅱ-7: 98-90). The total prenatal diagnosis cases and the number of case requring prenatal diagnosis for detecting one DS case were the lowest in strategy Ⅰ-1 group (2 081; 1.1, 2 081/1 921) and were the highest in Strategy Ⅱ-7 group (82 385; 37.2, 82 385/2 212). (2) Strategy Ⅰ-1 was the most cost-effective approach with the lowest total cost (￥928.896 million) and cost-effectiveness (￥237 000), and the highest benefit/cost ratio (4.90), followed by strategy Ⅱ-7 (￥957.380 million, ￥371 000 and 3.11). The most costly strategy was Ⅰ-2 (￥1 040.883 million, ￥404 000 and 2.85). (3) Setting strategyⅠ-1 as the baseline, strategyⅠ-2 had the highest incremental cost (￥1.580 million). The incremental cost of strategy Ⅱ ranged from ￥1.535 million (Ⅱ-1) to ￥1.259 million (Ⅱ-7), close to or less than the cost of raising a DS child (￥1.52 million). (4) The cost of cffDNA was a major factor in decision-making based on sensitivity analysis. When the price went down to ￥1 075, the incremental cost of strategy Ⅱ-1 was the lowest (￥757 000). If it further lowered to ￥697, strategy Ⅰ-2 was optimal (lower than ￥523 000). (5) The sensitivity analysis also suggested that the acceptance rate of cffDNA testing had no influence on the incremental cost-related findings (incremental cost: in strategy Ⅱ-7 was least and less than costs for one Down Syndrome patient). When the acceptance rate of prenatal diagnostic testing was lower than 80%, the incremental cost of strategy Ⅱ-7 (￥1.669 million) was the lowest, which was higher than raising a DS child.Conclusions:cffDNA testing in high-risk populations (strategyⅠ-1) could significantly reduce unnecessary diagnostic tests and is appropriate in total cost, cost-effectiveness and cost-benefit analysis, but misses more DS livebirths. Implementing prenatal diagnostic testing among pregnancies with risk cut-offs higher than 1/300 (strategy Ⅱ-7) could improve screening efficiency and reduce incremental costs, but require more cases to be tested. The cost of cffDNA testing is the most important influencing factor. On the premise of achieving substantial screening efficiency, strategy Ⅱ-1 and Ⅰ-2 are optimal with the lowest incremental costs if cffDNA testing cost drops to ￥1 075 and ￥697, respectively. Lower acceptance of prenatal diagnostic testing is accompanied by less detected DS cases and increased incremental costs than the baseline, which is not conducive to the prevention of birth defects.

Different characteristics of gut microbiota before and after management of women with gestational diabetes mellitus and the association with blood glucose level / 中华围产医学杂志

Objective To investigate the gut microbial profiles of gestational mellitus diabetes (GDM) patients before and after treatment,and the relationship between gut microbiota and blood glucose level measured in 75 g oral glucose tolerance test (OGTT).Methods A prospective cohort-based nested case-control study was conducted in Peking University First Hospital from October 2016 to December 2017.Forty-five pregnancies at 24-28 gestational weeks with GDM (GDM group) and 45 healthy gravidas (control group)matched for age and pre-pregnancy body mass index (BMI) were involved.Stool samples of all participants were collected before (24-28 gestational weeks) and after (36-40 gestational weeks) treatment.The V3-V4 region of the 16S rRNA gene was sequenced on the Illumina Hiseq 2500 platform,and the results were analyzed.QIIME software was used for bioinformatics analysis.Student's t-test,Mann-Whitney U test,and Chi-square test were used for statistical analysis.Results (1) Before treatment,the Alpha diversity of the GDM group was significantly reduced compared with that of the control group (Chaol index:443.9±72.9 vs 474.0± 63.3,t=2.104,P＜0.05;Shannon index:5.6±0.5 vs 6.0±0.5,t=2.002,P＜0.05),and a significant difference in Beta diversity was also observed between the two groups (R2=0.04,P＜0.05).However,a significant difference was shown in neither Alpha nor Beta diversity between the two groups after the treatment.(2) Before treatment,the relative abundances of Blautia and Faecalibacterium of the GDM group were significantly higher than those of the control group [M (P25-P75):0.016 (0.009-0.022) vs 0.011 (0.007-0.016),U=782.000;0.114 (0.076-0.14 1) vs 0.091 (0.061-0.126),U=752.000;both P＜0.05],but the relative abundances ofAkkermansia,Odoribacter and Butyricimonas were significantly lower [0.001 (0.000-0.002) vs 0.001 (0.000-0.005),U=745.000;0.001 (0.000-0.004) vs 0.004 (0.001-0.006),U=766.500;0.001 (0.000-0.003) vs 0.003 (0.001-0.005),U=710.000;all P＜0.05].(3) A negative relationship was found between the fasting glucose level of OGTT and the relative abundances of Akkermansia,Odoribacter and Butyricimonas (r=-0.325,-0.273 and-0.284;all P＜0.05),and between the one-hour-OGTT glucose level and the relative abundances of Akkermansia and Butyricimonas (r=-0.285 and -0.265,both P＜0.05).The two-hour-OGTT glucose level was positively related to the relative abundance of Faecalibacterium (r=0.278,P＜0.05),but negatively related to the relative abundance ofAkkermansia (r=-0.245,P＜0.05).The area under the OGTT time-glucose curve was negatively related to the relative abundances of Akkermansia and Butyricimonas (r=-0.321 and-0.264,both P＜0.05).Conclusions There are significant differences in gut microbial composition and structure between GDM and healthy pregnant women,which are significantly associated with OGTT blood glucose level.Euglycemia achieved after GDM management could improve gut microbiota disorder.

Indications of percutaneous umbilical cord blood sampling in prenatal diagnosis / 中华围产医学杂志

Objective To investigate the tendency and safety of percutaneous umbilical cord blood sampling (PUBS) in prenatal screening and diagnosis,and the possibilities of avoiding unnecessary PUBS.Methods This was a retrospective study of pregnant women who underwent PUBS for prenatal diagnosis in Peking University First Hospital from January 2015 to December 2017.Clinical indications,timing of PUBS,further investigations (chromosome karyotype,molecular genetics and pathogen testing),results,and pregnancy outcomes were collected and analyzed.One-way analysis of variance (ANOVA),Chi-square test for linear trend,Fisher's exact probability test/Cochran-Armitage analysis and Cruskal-Wallis rank-sum test were used for statistical analysis.Results (1)A total of 412 singleton pregnancies underwent PUBS at 20-38 gestational weeks during the study period,and 379 (92.2％) of them received PUBS before 34 gestational weeks.The positive test results accounted for 10.4％ (43/412).There were six (1.5％) miscarriages after PUBS.In vitro cell culture failure occurred in two cases,one in 2015 and the other in 2016.(2) Among the 412 cases,304 (73.8％) had only one indication.Fourteen cases could be identified as high risk in the first trimester,such as advanced maternal age (AMA,＞35 years),pregnant history with chromosomal abnormal fetus and one of the couples carrying abnormal genes.There were four,zero and one case receiving PUBS only for AMA in 2015,2016 and 2017,respectively.Indications,including high risk suggested by serum screening and fetal abnormality found by ultrasound were identified in 290 cases (70.4％) in the second or third trimester.Other than AMA,there were no statistically significant differences in single indicators.The proportion PUBS with double indicators increased from 2015 to 2017 but without significant difference.AMA and positive serum screening as indicators of aneuploidy screening accounted for 7.6％ (8/105) in double-indicator group and 1.9％ (8/412) in all.(3) There were 363 PUBS (88.1％) performed for ultrasound abnormalities.Among them,76.9％ (280/363) only had abnormal ultrasound findings,and the percentage was decreased year by year.The other 83 cases (80 with double indicators and three with triple indicators) also presented with other indicators,including AMA,adverse pregnancy history and positive serum screening.The proportion of PUBS performed with the presence of multiple indicators tended to increase recently,but no statistically significant difference was found.All the 18 cases with abnormality diagnosed by molecular genetic testing had abnormal ultrasound findings.Conclusions Although PUBS's complications are rare,it carries some risks.The constitution of single indication has been declined every year.With the improvement of prenatal screening system and application of molecular karyotyping,the necessity of invasive prenatal diagnosis with PUBS is greatly reduced.An improvement in reasonable and standardized application of PUBS needs to be achieved.

Indications of percutaneous umbilical cord blood sampling in prenatal diagnosis / 中华围产医学杂志

Objective@#To investigate the tendency and safety of percutaneous umbilical cord blood sampling (PUBS) in prenatal screening and diagnosis, and the possibilities of avoiding unnecessary PUBS.@*Methods@#This was a retrospective study of pregnant women who underwent PUBS for prenatal diagnosis in Peking University First Hospital from January 2015 to December 2017. Clinical indications, timing of PUBS, further investigations (chromosome karyotype, molecular genetics and pathogen testing), results, and pregnancy outcomes were collected and analyzed. One-way analysis of variance (ANOVA), Chi-square test for linear trend, Fisher's exact probability test/Cochran-Armitage analysis and Cruskal-Wallis rank-sum test were used for statistical analysis.@*Results@#(1) A total of 412 singleton pregnancies underwent PUBS at 20-38 gestational weeks during the study period, and 379 (92.2%) of them received PUBS before 34 gestational weeks. The positive test results accounted for 10.4% (43/412). There were six (1.5%) miscarriages after PUBS. In vitro cell culture failure occurred in two cases, one in 2015 and the other in 2016. (2) Among the 412 cases, 304 (73.8%) had only one indication. Fourteen cases could be identified as high risk in the first trimester, such as advanced maternal age (AMA, >35 years), pregnant history with chromosomal abnormal fetus and one of the couples carrying abnormal genes. There were four, zero and one case receiving PUBS only for AMA in 2015, 2016 and 2017, respectively. Indications, including high risk suggested by serum screening and fetal abnormality found by ultrasound were identified in 290 cases (70.4%) in the second or third trimester. Other than AMA, there were no statistically significant differences in single indicators. The proportion PUBS with double indicators increased from 2015 to 2017 but without significant difference. AMA and positive serum screening as indicators of aneuploidy screening accounted for 7.6% (8/105) in double-indicator group and 1.9% (8/412) in all. (3) There were 363 PUBS (88.1%) performed for ultrasound abnormalities. Among them, 76.9% (280/363) only had abnormal ultrasound findings, and the percentage was decreased year by year. The other 83 cases (80 with double indicators and three with triple indicators) also presented with other indicators, including AMA, adverse pregnancy history and positive serum screening. The proportion of PUBS performed with the presence of multiple indicators tended to increase recently, but no statistically significant difference was found. All the 18 cases with abnormality diagnosed by molecular genetic testing had abnormal ultrasound findings.@*Conclusions@#Although PUBS's complications are rare, it carries some risks. The constitution of single indication has been declined every year. With the improvement of prenatal screening system and application of molecular karyotyping, the necessity of invasive prenatal diagnosis with PUBS is greatly reduced. An improvement in reasonable and standardized application of PUBS needs to be achieved.

Clinical pathway selection based on chromosomal microarray analysis in prenatal diagnosis / 中华围产医学杂志

Chromosomal microarray analysis (CMA) is an emerging approach in prenatal diagnosis.Apart from accurate identification of the number of chromosomes and major chromosomal aneuploidy,CMA can also be used to detect submicroscopic changes such as chromosomal microdeletions and microduplications with high-resolution,short turnaround time and objectivity.However,CMA is limited in detecting balanced translocation,inversion of chromosomes and low-level mosaicism.This review summarized three clinical situations where CMA is mainly applied:fetus with certain structural abnormalities in ultrasound scan,high-risk gravidas identified by non-invasive prenatal testing and general screening for all for prenatal diagnosis.

Management of hyperglycemia in pregnancy: a major step to promote the health of whole life cycle / 中华围产医学杂志

As one common complication,hyperglycemia in pregnancy (HIP) can lead to short-and long-term effects on maternal-offspring and result in a vicious cycle when euglycemia is not achieved.HIP is proposed as the priority by multiple global stakeholders,from health policy makers (United Nation,Chinese government),academic organization (International Federation of Gynecology and Obstetrics,International Diabetes Federation and Developmental Origin of Health and Disease in China),health care providers,to the public.To solve the issue,united actions should be undertaken in various capacities to address the link between HIP and chronic non communicable diseases,including obesity and diabetes.

Distribution of gut microbiome in infants with different delivery modes and feeding patterns / 中华围产医学杂志

Objective To investigate the distribution characteristics of the gut microbiome in infants with different delivery mode and feeding pattern at six weeks of life.Methods A total of 60 infants delivered between June and September in 2017 at Peking University First Hospital were recruited.According to delivery modes and feeding patterns,they were respectively divided into two groups,which were vaginal delivery (n=42)and cesarean delivery (n=18) groups,and exclusively breastfeeding (n=40) and mixed-feeding (n=20) groups.Stool samples of all subjects were collected at six weeks after birth.The V3-V4 region of 16s rRNA gene was sequenced on Illumina Hiseq 2500 platform,and the results were analyzed with SILVA database and QIIME software.Independent samples t-test or Mann-Whitney U test was used for statistical analysis.Results (1)Eight bacterial phyla and 146 genera were identified in the 60 stool samples.Firmicutes,Proteobacteria,Actinobacteria and Bacteroidetes were four dominant phyla,and Bifidobacterium,Clostridium,Klebsiella,Bacteroides,Streptococcus,Escherichia-Shigella,Veillonella and Faecalibacterium were the top eight most abundant genera.(2) At the phyla level,the vaginal delivery group was characterized with reduced Firmicutes (0.56 ± 0.1 0 vs 0.42± 0.20,t=2.94,P＜0.05) and increased Actinobacteria and Bacteroidetes [0.04 (0.01-0.11)vs 0.20 (0.05-0.36),U=223,P＜0.05;0.05 (0.01-0.23) vs 0.09 (0.02-0.29),U=315,P＜0.05] as compared with the cesarean delivery group.However,there was no significant difference in the four dominant phyla between exclusively breastfeeding and mixed-feeding groups (all P＞0.05).At the genus level,the relative abundance of Bifidobacterium was higher in the vaginal delivery group than in the cesarean delivery group [0.19 (0.02-0.36) vs 0.01 (0.00-0.07),U=210,P＜0.01].Similarly,there was no significant difference in the eight dominant genus between exclusively breastfeeding and mixed-feeding groups(all P＞0.05).(3) The vaginal delivery group showed significantly lower Shannon and Simpson indexes than the cesarean delivery group [4.26 (3.61-5.52) vs 5.48± 1.19,U=227,P＜0.05;0.86±0.08 vs 0.94 (0.92-0.97),U=194,P＜0.05],while no significance was found in operational taxonomic unit (OTU) number and Chaol index (all P＞0.05).However,there was no significant difference in OTU number,Chaol,Shannon or Simpson index between the exclusively breastfeeding and the mixed-feeding groups (all P＞0.05).Conclusion The early infancy is a critical period for the establishment of gut microbiome.Significant differences in the composition and diversity of gut microbiota are found between infants born vaginally and abdominally,but not in infants with different feeding patterns.

Microbiome research shed light on perinatal medicine / 中华围产医学杂志

Along with the application of next generation sequencing,multidisciplinary cooperation among bioinformatics,clinical research and microbiology,has made rapid and impressive progress in microbiome in various fields.During perinatal period,which is the key and plastic for development,focus on different locations of microbiota from maternal-infant shed light on the pathophysiological mechanism,and help to find potential non-invasive biomarker and treatment target.

Comparison of Effects of Different Drying Methods on Contents of Effective Components of Forsythiae Fructus Leaves Tea / 中国中医药信息杂志

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.

Expression and distribution of Toll-like receptor 4 in term placentas of women with gestational diabetes ;mellitus / 中华围产医学杂志

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 P0.05). Conclusions The expression of TLR4 is different in various cell types of GDM term placentas.

Cytotoxic effect of geniposide and its metabolite genipin on HepG2 cells and mechanism / 中国药理学通报

Aim To compare the cytotoxicity of geni-poside (GS)and its metabolite genipin (GP)on hu-man hepatocelluar HepG2 cells and explore the sub-stance and mechanism of hepatotoxicity induced by Fructus Gardeniae.Methods The cytotoxic effect of GS and GP was analyzed by MTT method;the antioxi-dant enzyme activities of manganese superoxide dis-mutase (Mn-SOD),catalase (CAT)and levels of glu-tathione (GSH)were detected by respective kits;the change of intracellular reactive oxygen species (ROS ) was measured by 2′,7′-dichlorofluorescin diacetate (DCFH-DA)staining method;multiparameter cytotox-icity analysis (cell loss,nuclear size and morphologi-cal changes,DNA content,cell membrane permeabili-ty,mitochondrial membrane potential changes,cyto-chrome C release ) were measured simultaneously by high content screening (HCS)assays.Results No cytotoxicity was found in GS (20~1 000 μmol·L-1 ) groups (P>0.05 ),but GP was found to exert obvi-ous cytotoxic effect,and 50μmol·L-1 GP could obvi-ously inhibit HepG2 cell proliferation (P0. 0 5 ),GP could significantly decrease the activity of Mn-SOD,CAT and the level of GSH,and obviously increase the content of ROS (P0.05 ). Conclusion GP is the direct substance of hepatotox-icity induced by Fructus Gardeniae,and the mecha-nism might be associated with oxidative stress,mito-chondria injury and apoptosis.

Cytogenomic microarray analysis is not the only solution to fetal karyotyping / 中华检验医学杂志

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 .

Quantitative Analysis of Amygdalin inKuxingren Formula Granules and Study on Characteristic Chromatogram / 中国中医药信息杂志

ObjectiveTo establish an HPLC analytic method for amygdalin inKuxingrenFormula Granules and HPLC characteristic chromatogram.MethodsRP-HPLC method was adopted. The determination was performed on Dionex C18 column (4.6 mm×250 mm, 5μm) with acetonitrile-0.1% phosphoric acid solution (8:92) at the flow rate of 0.6 mL/min. The detection wavelength was set at 207 nm and sample size was 10μL. The column temperature was 30℃. The peak of amygdalin was set as refernce, and 10 batches of samples were analyzed. TCM Chromatogram Fingerprint Similarity Evaluation System (2004 A) was adopted to evaluate similatity.Results The linear equation of amygdalin wasY=6.176×10-7X?3.058×10-3, with a good linear relationship in the range of 0.122 5–1.225μg (r= 0.999 8). The average recovery rate was 98.75% (RSD=1.30%). There were 6 common peaks in the characteristic chromatogram ofKuxingrenFormula Granules, and the similarity of 10 batches of samples was higher than 0.981. ConclusionThe HPLC method is simple, accurate and reproducible, which can be used for the quality control of Kuxingren Granules.

Prenatal diagnosis of single gene disorders and role of multidisciplinary cooperative mode / 中华围产医学杂志

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.

Correlation between chromosome deletion and phenotypes in two cases of ring chromosome 6 syndrome / 中华围产医学杂志

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.

Feasibility of rapid prenatal diagnosis in advanced maternal age women / 中华围产医学杂志

Objective To analyze the feasibility of rapid prenatal diagnosis in the advanced maternal age women with or without positive serologic screening results.Methods We conducted a retrospective study of the women who underwent a mid-trimester amniocentesis in Peking University First Hospital from January 1,2001 to December 31,2012.Maternal age,indication for invasive prenatal diagnosis,karyotyping and pregnancy outcome were documented.Using a young population with high risk in serologic screening (S) as the standard,chromosome abnormalities in the advanced maternal age (A) group and the advanced maternal age with high risk in serologic screening (A+S) group were compared with the S group.Chromosome abnormalities were divided into detectable (D) and undetectable (U) during rapid prenatal diagnosis.Results Of 9 606 cases,222 (2.3％,222/9 606) cases with chromosome abnormalities were detected,23.0％ (51/222) of which were undetectable by rapid prenatal diagnosis.The detection rate of detectable chromosome abnormalities was 1.8％ (57/3 177) in group A,1.4％(13/925) in group A+S,and 1.8％(57/3 250) in group S (x2=0.662,P＞0.05).The rate of undetectable chromosome abnormalities was 0.5％ (15/3 177) in group A,0.3％ (3/925) in group A+S,and 0.5％ (16/3 250) in group S (x2=0.452,P＞0.05).The most common indications for undetectable chromosome abnormalities in the young population were abnormal history of pregnancy,abnormal family history and chromosome abnormality history (16.4％,9/55),and abnormal ultrasound in the advanced maternal age population (4.4％,3/68).Conclusions The performance of rapid prenatal diagnosis in the advanced maternal age population with or without high risk in screening without abnormal findings in ultrasound,was similar to the young population with high risk in screening.Fluorescent in situ hybridization may be integrated into the strategy of prenatal diagnosis for this group of women.