Objective To investigate the relationship between placental endoglin expression and the pathogenesis of severe preeclampsia (SPE). Methods Forty nine pregnant women with SPE and 40 normal pregnant controls were collected in Peking University First Hospital from January 2006 to January 2008,among which,nine SPE patients complicated with fetal growth restriction (FGR),six with hemolysis,elevated liver enzymes and low platelets syndrome (HELLP syndrome) and 12 with heavy proteinuria. The expression of placental endoglin was detected and semi-quantified by immunohistochemistry.Data were analyzed by independent sample t test. Results Endoglin was presented on cell membranes of placental syncytiotrophoblasts and vascular endothelial cells. The endoglin density of SPE group was higher than that of control group (0.1621± 0.0029 vs 0.1576 ± 0.0038,t=- 6.367,P＜0.05).No significant difference in endoglin density was found between FGR group and non-FGR group (0.1611±0.0026 vs 0.1623±0.0029,t=1.107,P＞0.05) ; neither did the heavy proteinuria group and non-heavy proteinuria group (0.1611±0.0032 vs 0.1624±0.0027,t=1.350,P＞0.05).The endoglin density of HELLP group was lower than that of non-HELLP group (0.1595±0.0032 vs 0.1625±0.0027,t=2.495,P=0.016). Conclusions The elevated placental endoglin expression might contribute to the pathogenesis of SPE.

Objective To investigate the relationship between fasting plasma glucose (FPG) in early pregnancy and diagnosis of gestational diabetes mellitus (GDM) and to confirm the rationality of the new standard for GDM diagnosis in early pregnancy set by the International Association of Diabetes and Pregnancy Study Groups (IADPSG).Methods Clinical materials of 2761 pregnant women without diabetes mellitus,who accepted prenatal cares in Peking University First Hospital from April 1,2011 to December 31,2011,were collected and analyzed.The difference between FPG levels of GDM and non-GDM women was compared.According to the early pregnancy FPG level,the subjects were divided into group A (FPG＜5.1 mmol/L,n=2431) and B (FPG≥5.1 mmol/L,n=330).The incidence of GDM and pregnant outcomes of the two groups were compared with t or Chi-square test.Relationship between FPG and GDM was analyzed by Logistic regression and receiver operating characteristic curve.Results (1) Among the 2761 subjects,515 were diagnosed as GDM (18.7％) and the early pregnancy FPG level in GDM group was significantly higher than that in non-GDM group [(4.84±0.46) mmol/L vs (4.57 ± 0.35) mmol/L,t =11.924,P =0.000].In early pregnancy,the risk of GDM increased by 7.984-fold (OR=8.984,95％CI:6.605-12.220) with every 1 mmol/L increase of the FPG level.(2) The diagnostic rate of GDM during mid-and last-trimester in group A (15.2％,370/2431) was lower than that of group B (43.9％,145/330),x2 =123.976,P =0.000.(3) Receiver operating characteristic curve analysis of FPG in early pregnancy and diagnosis of GDM:The largest area under the curve was 0.718 (95％ CI:0.690-0.747).The sensitivity and specificity were 0.600 and 0.612,or 0.735 and 0.726 respectively,when 4.795 mmol/L or 4.785 mmol/L were set as the cut-off value.(4) Among the 1208 cases delivered,GDM was diagnosed in 227 cases.The cesarean section rate (54.2％,123/227) of GDM women was higher than that (39.2％,385/981) of non-GDM women (x2 =16.884,P=0.000).There were no differences in the incidences of macrosomia,neonatal hyperbilirubinemia,low birthweight infant,premature delivery,fetal growth restriction and preeclampsia between GDM and non-GDM group (all P＞0.05).The incidence of premature birth in GDM women with FPG＜ 5.1 mmol/L was lower (5.8％,10/173) than that (14.8％,8/54) of women with FPG≥5.1 mmol/L (x2=4.601,P＜0.05).The incidence of cesarean section,insulin administration,macrosomia and preeclampsia increased from low FPG group to high FPG group,however there was no statistical significances.Conclusions Diagnosing GDM with FPG≥5.1 mmol/L in early pregnancy is not recommended as over diagnosis might happen.But this cut-off value might indicate that the patient are at risk of GDM,and this population should not be ignored.

Objective To investigate the association between polymorphism of HLA-DRB1 allele and systemic sclerosis (SSc) and scleroderma-associated renal damage in Han Chinese of Henan Province.Methods Eighty-one SSc patients and 90 normal controls were recruited in this study,among them 59 patients had renal damage (SRD).The genotyping was carried out by nest PCR-SBT and gene clone.Comparisons between groups were performed with x2 test or exact probabilities.Multivariable Logistic regression was used to evaluate the association between prevalence of SSc or SRD and the possible relevant alleles.Results Thirty-three HLA-DRB1 alleles were discovered from the specimens,including 27 in SSc specimens,and 22 in SRD.Among them,the allele frequencies of HLA-DRB1 * 040501 (8.64％), * 110101 (11.11％), * 150201(8.02％) were higher in SSc patients than those of the controls (1.67％,4.44％,2.22％ respectively).After adjusted for other factors,HLA-DRBl * 040501 (P=0.010,OR =5.839,95％CI:1.518-22.460)、* 110101(P=0.019,OR=3.060,95％CI:1.204-7.772)、* 150201(P=0.010,OR=4.780,95％CI:1.444-15.821 )were identified as independent risk factors for SSc.And the allele frequencies of HLA-DRB1*040501 (9.32％),* 150201 (7.63％) were higher in SRD patients than those of the controls (1.67％,2.22％ respectively).After adjusted for other factors,HLA-DRB1 * 040501 (P=0.008,OR=6.363,95％CI:1.614-25.087) and * 150201 (P=0.030,OR =4.043,95 ％CI:1.147-14.243 ) were identified as independent risk factors for SRD.Conclusion Our data suggest that HLA-DRB1 * 040501,* 110101,* 150201 may be susceptible genes for SSc and the HLA-DRB1 * 040501,* 150201 may be susceptible genes for SRD in Han Chinese of Henan Province.

Objective To understand the growth pattern of infants of mothers with maternal glucose metabolism during pregnancy.Methods Totally,7600 infants,born from singleton pregnant women from January 1st,2007 to December 31st,2009 in Peking University First Hospital and were followed up at 6-12 weeks after birth,were included.Altogether,645 mothers were complicated with hyperglycemia and 6955 with normal glucose metabolism during pregnancy.All infants were divided into four groups based on maternal glucose metabolism and their birth weight:Group N1 (n =6432) was consisted of non-macrosomia infants with normal maternal glucose metabolism; Group N2 (n =523) included macrosomia infants with normal maternal glucose metabolism; Group A1 (n =588) were non-macrosomia infants with abnormal maternal glucose metabolism; Group A2 (n =57) were macrosomia infants with abnormal maternal glucose metabolism.Birth weight,body weight at the day of follow-up and average daily weight gain were compared among these four groups.T-test,single variance analysis and LSD was applied in statistics,and the time at follow-up was used as co variance to find out the early growth pattern of infants.Results The birth weight of infants in normal and abnormal glucose metabolism group showed no statistical difference [(3367.0±420.3) g vs (3368.2±475.1) g,t=-0.061,P＞0.05],but body weight at the day of follow-up and the daily weight gain in the former group were lower than in the latter [body weight at follow-up:(5459.3±625.2) g vs (5393.9±647.2) g;daily weight gain:(44.0±9.5) g vs (42.9±9.5) g,t=2.464 and 2.874,all P＜0.05].The birth weight of infants in Group N1,A1,N2 and A2 was (3300.6±359.2) g,(3282.1±397.0) g,(4183.8±203.8) g and (4256.8±248.8) g,respectively;the body weight at the day of follow-up was (5400.5±590.7) g,(5325.8±618.8) g,(6182.7±584.7) g and (6096.5±502.4) g;daily weight gain was (44.1±9.4) g,(43.2±9.4) g,(42.4±10.9) g and (39.6±10.0) g,respectively (F=1140.471,313.376 and 10.830,all P＜0.001).While using co-variance to compare among the four groups,statistically more daily weight gain was shown in Group N1 than in A1,A2 and N2,in Group N2 than in Group A2,in Group A1 than in A2 (all P＜ 0.05).Conclusions The growth speed may slow down in early infantile period for offsprings of mother with hyperglycemia during pregnancy.

Objective To investigate the values and characteristics of 75 g oral glucose tolerance test (OGTT) in pregnant women.Methods A total of 6 103 singleton pregnant women aged (30.4±3.8) years (18-49 years) who delivered in Peking University First Hospital between May 1,2011 and December 31,2012 underwent the 75 g OGTT at gestational age of 24-28 weeks.They were divided into five groups based on maternal age:＜25 years (n=222,3.6％),25-years (n=2 485,40.7％),30-years (n=2 573,42.2％),35-years (n=683,11.2％),and ≥ 40 years (n=140,2.3％).The normal values of the fasting,1 h and 2 h blood glucose were lower than 5.1,10.0 and 8.5 mmol/L.Gestational diabetes mellitus (GDM) was diagnosed when blood glucose of any point was higher than or equal to normal value.Comparison between groups was tested by analysis of variance and LSD test.Logistic regression was used to calculate the risk for GDM in different age groups.Results (1) The fasting,1 h and 2 h blood glucose levels were in Gaussian distribution.The （-x）+2s were 5.51,11.12 and 9.49 mmol/L.The 97.5 percentile were 5.63,11.32 and 9.95 mmol/L.Fasting plasma glucose of ＜ 25,25-,30-,35-,and ≥ 40 years were (4.53±0.40),(4.60±0.40),(4.67±0.43),(4.74±0.46) and (4.82±0.49) mmol/L.The 1 h blood glucose were (6.98± 1.70),(7.55± 1.60),(7.92± 1.63),(8.30± 1.71) and (8.76± 1.86) mmol/L.The 2 h blood glucose were (6.11±1.33),(6.53±1.27),(6.89±1.33),(7.23±1.50) and (7.57±1.60) mmol/L.Therewas statistical difference in the blood glucose levels at a same time-point test among different age groups (F=29.61,60.17 and 72.29,all P＜0.01).(3) The total prevalence rate of GDM was 21.1％ (1 290/6 103) ; and the prevalence rates were 9.9％ (22/222),16.7％ (414/2 485),22.7％ (583/2 573),32.1％ (219/683) and 37.1％ (52/140) among the five age groups,respectively,with significant differences (x2=120.68,P=0.00).Compared with the group aged ＜25 years,the OR (95％CI) of the prevalence among 25-,30-,35-,and ≥40 years group were 1.82 (1.16-2.86),2.66 (1.70-4.18),4.29 (2.69-6.86) and 5.37 (3.08-9.39),respectively.Conclusions Advanced age is a risk factor for GDM.The risk of GDM increases significantly after 35 years old and pregnancy in women aged ＜ 35 years can reduce the risk of GDM.

Objective To discuss the serum endoglin expression in severe pre-eclampsia and eclampsia women and their relationships. Methods Forty-two severe pre-eclamptic patients and 4 eclamptic patients in Peking University First Hospital from Dec. 2005 to Dec. 2007 were enrolled in the study group, with the mean gestational week of 35 ± 4, the mean age of 29.3 ± 5.7 and the mean BMI (30.1 ± 4.1 ) kg/ m2. This group included 25 cases of early onset pre-eclampsia, 21 cases of late onset pre-eclampsia, 8 cases of fetal growth restriction and 5 cases of HELLP syndrome. The control group included 29 cases of normal pregnant women during the same period, with the mean gestational week of 33±4, the mean age of 30.7± 3.4 and the mean BMI(27.2±2. 2) kg/m2. Peripheral serum endoglin was determined by ELISA in these two groups. Results (1)There is positive correlation between serum soluble endoglin level and the gestational weeks during 27 to 37 gestational weeks in the control group (r=0.79, P<0.05), but there is no distinct relationship in the study group (r=0.31, P>0.05). (2) Serum endoglin level of severe pre-eclampsia group was higher than the normal group [(14.2±5.6)μg/L vs. ( 10.9 ± 4.2 ) μg/L, P<0.05]. (3) Serum endoglin level of early onset group did not differ from late onset group [(14.3±5.7)μg/L vs. (13.6±5.0)μg/L, P >0.05]. (4) No difference of serum endoglin between HELLP group and non-HELLP group was found [(10.1±2.9) μg/L vs. ( 14.4±5.4) μg/L, P>0.05 ]. (5) Serum endoglin level of FGR sub group was higher than non-FGR sub group [(17.3±6.1) μg/L vs. (13.0±4.8) μg/L, P < 0.05] in the stady group. Conclusion The elevated peripheral serum endoglin level may contributes to the pathogenesis of severe pre-eclampsia and FGR, but not the week of the onset of the disease.

AIM: To construct recombinant lentiviral vector with short hairpin RNA (shRNA) of CREB gene, and to investigate the effect of CREB gene silencing on mitochondrial morphology and cell apoptosis in oxygen-glucose deprivation/reoxygenation (OGD/R)-induced cortical neurons.METHODS: Three lentiviral vectors pLentiLox3.7 (PLL) inserted shRNA fragments targeting CREB gene were co-transfected with the packaging plasmids psPAX2 and pMD2.G to the 293T cells, and the virus particles, which was infected with the primary cortical neurons, was encapsulated.The protein expression of CREB was detected by Western blot.The mitochondrial morphology, cell apoptosis and the expression of Bcl-2 and Bax were evaluated by the methods of MitoTracker red, TUNEL and Western blot in OGD/R induced cortical neurons after CREB gene silencing.RESULTS: The pLL-CREB-shRNA1 was the most effective shRNA, which inhibited 80% CREB gene expression in the cortical neurons.The mitochondrial was appeared dot and fragment morphology in OGD/R induced cortical neurons with transfected pLL-CREB-shRNA1 plasmid.In addition, the expression of Bcl-2 was decreased, the expression of Bax, and the apoptosis of the neurons were increased by tranfected with pLL-CREB-shRNA1.CONCLUSION: CREB shRNA recombinant lentiviral vector specifically inhibits the expression of CREB gene.CREB gene silencing promotes the cell apoptosis and mitochondrial morphological changes in the cortical neurons induced by OGD/R.

Objective To elaborate the glucose and lipid metabolism 1 year postpartum on the foundation of postpartum 6-12 weeks in patients with prior gestational abnormal glucose metabolism in Beijing area.Methods Seventy-three patients who delivered during February to December,2007,aged (32.0 ± 3.6) years,were enrolled.46 cases (63％) were diagnosed as cases of gestational diabetes mellitus (GDM) while 27 (37％) as gestational impaired glucose tolerance (GIGT).All of the patients were revisited twice by 6-12 weeks and 1 year postparaum.Body weight,waist andhip circumferences,oral glucose tolerance test(OGTT),and lipids profile were determined.Results Compared with 6-12 weeks postpartum,the body weight,waist and hip circumferences,and waist-to-hip ratio were decreased by 1 year postpartum,fasting plasma glucose was increased [(5.19 ± 0.06) vs (4.84 ± 0.57) mmol/L,P＜0.01],and 4 cases were diagnosed as cases with impaired fasting glucose (IFG; 4 vs 0).By 6-12 weeks and 1 year postpartum,postprandial plasma glucose levels were (6.84± 1.93) and (7.33 ± 1.50) mmol/L(P=0.017),and the incidences of impaired glucose tolerance(IGT) were 28.8％ and 38.4％ (P=0.167),respectively,with 6 cases of newly diagnosed IGT by 1 year postpartum.There were more cases of hypertriglyceridenia (19.2％ vs 13.7％),less cases of hypercholesterolemia(19.7％ vs 30.0％,P＜0.01),more cases with improved high-densit.y lipoprotein-cholesterol (21.9％ vs 4.1％,P＜0.01),and less cases with raised low-density lipoproteincholesterol(21.9％ vs 49.3％,P＜0.01).No difference was found in body weight,body mass index,waist circumference,hip circumference,and waist-to-hip ratio between GIGT and GDM groups.Conclusion GDM is an important cause of the increasing prevalence of diabetes in women of reproductive age.Although body weight and waist-to-hip ratio have been improved,they would still develop glucose intolerance and dyslipidemia 1 year postpartum.

Objective To identify one runny mucoid-like Gram-negative bacteria with pink pigment isolated from clinical pus sample. Methods The pus sample was aseptically extracted from a deep lesions of one patient, then stored in Amies medium at room temperature for transportation. One sheep blood plate and one chocolate plate were used to detect the possible pathogens from the specimens. After inoculation, the plates were placed in a humidified incubator with 5% CO2 at 35 ℃. To identify the obtained isolates, we used the commercial Vitek2 and API systems, combining some traditional morphological examination and classical biochemical and physiological characteristics. For pure cultures, the cellular fatty acids were extracted, methylated, and determined by gas chromatography method. The 16S rRNA gene was amplified and sequenced by a commercial broad-spectrum PCR primers. The phylogenetic tree based on 16S rRNA gene was constructed by Mega 4.1 software using the neighbour-joining methods with 1 000 bootstrap replications. Results One runny mucoid-like Gram-negative bacterium, named K8756, was isolated both on sheep blood and chocolate plates after 72 h incubation. The API 20NE profile was 1245045 after a 3-day culture, which would be identified as Ochrobactrum anthropi with a good confidence of 98% probability. It was identified as Ralstonia pickettii and Bordetella bronchiseptica by VITEK 2 GN kits. However, further comparative 16S rRNA gene sequences showed that strain K8756 was closely related to the valid published Roseomonas mucosa MDA 5527 with 100% identity. Colonial morphologic features, phenotypic characteristics and major cellular fatty acid composition were also with high similarity to Roseomonas mucosa. Conclusions Strain K8756( = GIMCC 1.0030 ) is identified as Roseomonas mucosa by the polyphasic phenotypic and genotypic characteristics. The comparative analysis based on 16S rRNA gene sequences is a useful method for identifying the problematic and newly named bacteria.

Objective To investigate the appropriate screening method for thyroid diseases during early pregnancy.Methods We collected information of 4 044 pregnant women who attended to the Department of Obstetrics and Gynecology of Peking University First Hospital from September 1,2013 to September 30,2014 for antenatal care and underwent one step screening for thyroid diseases in first trimester,which meant blood test for thyroid stimulating hormone(TSH),free thyroxine(FT4) and thyroid peroxidase antibody(TPOAb) at the same time.Simulation analysis was performed on these 4 044 women with twostep screening (TSH first and then FT4 and TPOAb if TSH was abnormal).The incidence,missed diagnosis rate,costs of screening,and outcomes of the missed diagnosed cases of women with thyroid diseases were compared between one-step and two-step screening based on the cutoff value determined by American Thyroid Association (ATA) or our hospital (0.23-4.08 mU/L).The positivel rate of TPOAb was compared among the three groups classified according to TSH value (≥ 0.1-＜ 2.5 mU/L,≥ 2.5-＜ 4.08 mU/L and ≥ 4.08 mU/L).T-test,Chi-square test or Fisher's exact test were applied for statistical analysis.Results When the cutoff value of TSH was set at ≥ 0.1-＜ 2.5 mU/L (ATA recommendation),7.9％ (320/4 044) of the women required medical treatment.It was significantly higher than 3.2％ (129/4 044),which was obtained when the normal reference value of TSH was set based on data from our hospital.The positive rates of TPOAb were 7.2％(214/2 976),13.9％(103/777) and 28.6％(55/192) for TSH ≥ 0.1-＜ 2.5,≥ 2.5-＜ 4.08 mU/L and ≥ 4.08 mU/L group,respectively.When we set the OR value for TOPAb as one in the TSH ≥ 0.1-＜ 2.5 mU/L group,the OR(95％C1)s of the other two groups were 1.972(1.537-2.532) and 5.181(3.679-7.297).If two-step screening protocol and ATA recommendations were applied,0.7％ (27/4 044) of women who needed treatment would be missed.However,312 480 yuan (RMB) would be saved compared with one-step screening (77.27 yuan per person).When the hospitalized reference value was applied,1.1％(45/4 044) of women would not be treated and 384 720 yuan would be saved (95.13 yuan per person) compared to one-step screening.For those missed diagnosed cases,no more adverse pregnant outcomes (all P＞0.05),including fetal distress,gestational diabetes mellitus,preterm birth,fetal growth restriction,oligohydroamnios,polyhydroanmios,fetal death,gestational hypertension with pre-eclampsia,placental abruptio and neonatal asphyxia were reported although no standard treatment had been provided,no matter ATA recommendation or unique reference in our hospital was adopted.Conclusions We recommend the two-step method for thyroid function screening during early pregnancy.For the purpose of cost-saving,reduction of missed diagnosis rate and avoidance of overtreatment,the management protocol should be individualized for those women with TSH value between 2.5 mU/L and the normal reference value of our hospital during pregnancy.