Objective To analyze the natural changes of maternal thyroid function among women with subclinical thyroid dysfunction and euthyroid women during pregnancy.Methods A total of 4 042 singleton pregnant women received routine antenatal care in the Obstetrics and Gynecology Hospital of Fudan University between April and November 2012 were enrolled.Thyroid-stimulatinghormones (TSH),freetriiodothyronine (FT3) and free thyroxine (FT4) of 7 136 samples from 4 042 singleton pregnant women were tested at 8-12+6,13-19+6,20-27+6,and 28-40 weeks of gestation and were used to establish the normal gestationalspecific reference values of thyroid function.Among 3 895 women having thyroid function tested at 8-19+6 weeks of gestation with negative thyroid antibodies,there were 93 cases of subclinical hyperthyroidism,91 cases of subclinical hypothyroidism (SCH),three cases of hyperthyroidism and 3 708 cases euthyroid.There were 1 118 women [1 607 euthyroid cases,17 cases of subclinical hypothyroidism (SCH) and 34 cases of subclinical hyperthyroidism] had thyroid function retested at 20-27+6 and 28-40 weeks of gestation,and without medicinal intervention.Analysis of variance and LSD test were used to analyze the changes of maternal thyroid function.Results (1) The reference ranges of TSH at 8-12+6,13-19+6,20 27+6 and 28-40 weeks of gestation [median (Pz5-P97.5)] were 1.32 (0.03-4.17),1.83 (0.19-4.94),2.27 (0.70-5.42) and 2.34 (0.63-5.52) mU/L respectively.(2) Without medicinal intervention,thyroid function became normal in 80％ (45/56) SCH women at 20-27+6 weeks,but 20％ (9/45) of them developed SCH again at 28-40 weeks.The thyroid function became normal in 75％ (70/93) women with subclinical hyperthyroidism at 20-27+6 weeks,but in 15％ (14/93) of them,thyroid function remained abnormal at 28-40 weeks.9.40％ (30/319) and 6.25％ (21/336) euthyroid women with TSH ≥ 3 mU/L at 8-19+6 weeks of gestation developed SCH at 20-27+6 weeks and 28-40 weeks,while 0.42％ (5/1 202) and 0.86％ (10/1 163) euthyroid women with TSH ＜3 mU/L had SCH.1.66％ (20/1 202) and 1.98％ (23/1 163) euthyroid women with TSH＜3 mU/L at 8-19+6 weeks of gestation developed subclinical hyperthyroidism at 20-27+6 weeks and 28-40 weeks of gestation.(3) In comparison between 8-19+6 weeks and 20-27+6 weeks of gestation,TSH levels increased by (0.47±0.03) mU/L in euthyroid women,and more significantly in subclinical hyperthyroidism women [(0.82±0.06) mU/L],but decreased by (1.67±0.25) mU/L in SCH women (LSD test,all P＜0.05).The FT3 levels decreased by (0.47±0.02) pmol/L in euthyroid women,and more significantly in subclinical hyperthyroidism and SCH groups [(1.02± 0.18) and (0.72±0.08) pmol/L,LSD test,all P＜0.05].FT4 decreased by (2.31 ±0.04) pmol/L in euthyroid women,and more significanly in subclinical hyperthyroidism women [(4.63± 0.62) pmol/L] (LSD test,P＜0.05),but the decrement in SCH group [(1.78±0.28) pmol/L] was similar to euthyroid women (LSD test,P＞0.05).There were no significant differences in changes of TSH,FT3 and FT4 at 20-27+6 weeks and 28-40 weeks among euthyroid women,SCH and subclinical hyperthyroidism groups (F=1.01,1.14 and 2.04,all P＞0.05).Conclusions Women with subclinical thyroid dysfunction with negative thyroid antibodies experience significantly different natural changes when compared with euthyroid women,especially before 28 weeks of gestation.

Objective: To evaluate reliability and validity of ATQ. Methods: A total of 350 undergraduates and 102 Psychiatric patients were tested by ATQ and BDI. Results:The ATQ attained good psychometric properties: Cronbach α of ATQ was 0.95, spit-half correlations ranged from 0.90 to 0.94; correlation coefficient between ATQ and BDI was 0.54 for normal undergraduates, 0.60 for schizophrenics, and 0.75 for depressive subjects (p<0.001). There were significant difference among non-depressed undergraduates、depressed undergraduates、schizophrenics and depressive patients. Conclusion: The present study provided empirical support for the reliability and validity of ATQ.

OBJECTIVE:To establish the method for the simultaneous determination of clopidogrel (CLO) and its active metabolites (CATM) and inactive metabolites (CCAM),and to conduct pharmacokinetic study. METHODS:The plasma sam-ple had been derivatized by 2-bromine-3′-methoxy acetophenone(MPB),and was precipitated by acetonitrile. Using carbam-azepine as internal standard,UPLC-MS/MS was adopted. The separation was performed on Waters ACQUITY UPLC HSS T3 column with mobile phase consisted of water(containing 0.1% formic acid)-acetonitrile(containing 0.1% formic acid)using a gradient elution program at the flow rate of 0.50 ml/min. The ESI was equipped and quantitative analysis was operated in posi-tive ion and MRM mode. The mass transition ion-pairs were followed as m/z 322.1→211.8(CLO),m/z 504.1→155.0(the alkyl-ation derivatives of CATM,CATMD),m/z 308.3→198.0(CCAM),m/z 273.2→194.3(internal standard). RESULTS:The lin-ear calibration curves for CLO,CATMD and CCAM were obtained in the concentration range of 0.03-20.00 ng/ml,0.30-200.00 ng/ml and 10.00-10 000.00 ng/ml in plasma,respectively;intra-day and inter-day RSD for them were all less than 15%,and relative error(RE)ranged from -3.5% to 5.7%. Main pharmacokinetic parameters of CLO,CATMD and CCAM in 5 healthy volunteers after oral administration of CLO 300 mg were as follows:cmax were(7.89±5.46),(15.58±8.08),(8 023.33± 1 047.39)ng/ml;tmax were(1.25 ± 0.43),(1.25 ± 0.43),(1.67 ± 0.29)h;t1/2 were (2.31 ± 0.61),(0.64 ± 0.08),(6.53 ± 2.55)h;AUC0-t were(17.19±14.59),(21.39±9.58),(30 648.85±8 026.63)ng·h/ml. CONCLUSIONS:The established method is sensi-tive,rapid and convenient,which is suitable for pharmacokinetic study and plasma concentration determination of CLO and its metabolites.

Objective To elucidate the influence of fetal genotype in both non-diabetic gravidas and pregnant women on gestational diabetes mellitus (GDM) through analysis of the genotype discrepancy between maternal and fetal Pro12A1a single nucleotide polymorphism (SNP) of peroxisome proliferator-activated receptor gamma 2 (PPARG2) genes.Methods Pregnant women,who delivered in the Obstetrics and Gynecology Hospital of Fudan University from October 2005 to February 2007,and their newborn babies were selected,and were divided into GDM and control group.The GDM group consisted of 55 gravidas with GDM and 40 newborns born to the GDM mothers,and the control group consisted of 173 healthy gravidas and their 50 neonates.Polymerase chain reaction-denaturing high-performance liquid chromatography was applied to detect the distribution of PPARG2 Pro12Ala alleles in all subjects.The concentrations of plasma fasting blood sugar (FBS) and several bio-markers of lipids,including total cholesterol,triglyceride,apoprotein A,high-density lipoprotein and low-density lipoprotein,were also tested for the mothers.Results (1) No significant difference was found in the frequencies of Pro/Pro genotype between the GDM mothers and control mothers (94.6% vs 90.8%,P > 0.05),nor between the GDM offspring and control offspring (95.0% vs 94.0%,P >0.05) or between the GDM mothers and GDM offspring (P > 0.05).The same was shown in the frequencies of Pro/Ala genotype both between the GDM mothers and control mothers (5.5% vs 9.2%,P >0.05) and between the GDM offspring and control offspring (2.5% vs 3.0%,P > 0.05).(2) Within both GDM and control group,the maternal FBS and various lipids concentrations of Pro/ Pro genotype gravidas showed no significant difference compared to those of Pro/Ala genotype mothers (P > 0.05).(3) Based on the four possible PPARG2 genotype pairs between the mothers and fetuses,Pro/Pro mother and her Pro/Pro fetus,Pro/Ala mother and her Pro/Ala fetus,Pro/Ala mother and her Pro/Pro fetus,and Pro/Pro mother and her Pro/Ala fetus,less Pro/Pro pairs and more Pro/Ala pairs were found in the GDM group than in the control (72.5% vs 92.0%,P=0.014; 27.5% vs 6.0%,P< 0.05).Conclusions Neither the maternal nor the offspring's Pro/Ala genotypes is associated with the genesis of GDM.However,the discrepancy of PPARG2 Prol2Ala polymorphism between mother and her fetus implies a possible cause of GDM.

Objective: To investigate the mRNA expression of chemokine receptors in human villi and trophoblasts of first trimester gestation . Methods: The authors first obtained villous tissues from fifteen women who had undergone selective termination at 5 - 10 weeks of normal gestation. Total RNA was then extracted, using the TRIzol reagent, from villous tissues or Percoll-gradient purified trophoblasts. Consequently, the expressions of chemokine receptors in villous tissues and trophoblasts were investigated by way of semi-quantitative reverse transcriptase-polymerase chain reaction.Results: The chemokine receptors, CXCR4 and CXCR6, were highly expressed in each villous tissue, while the CCR6, CCR7, XCR1 and CX3CR1 were moderately expressed in villi. The chemokine receptors, CCR1- CCR5, CCR8 - CCR10, CXCR1 -CXCR3, were expressed only in some villous samples, while no CXCR5 mRNA was found in any villous tissue. The authors also found that the freshly isolated and Percoll-purified trophoblasts expressed CCR1, CCR3 - CCR5, CCR8 - CCR9, CXCR1 - CXCR4, CXCR6, XCR1 and CX3CR1 mRNA. Conclusion: A variety of chemokine receptors were expressed in villous tissues and trophoblasts of human first trimester gestation, hence, these receptors may play an important biological role at the materno-fetal interface in normal human pregnancy.

BACKGROUND: The dynamic changes of pneumocyte apoptosis and aspartate-specific cysteine proteases-3 (caspase-3) expression in lung tissue of rats during the process of lung ischemia/reperfusion (I/R) injury and the possible action mechanisms remain unclear.OBJECTIVE: This study was to observe the dynamic changes of pneumocyte apoptosis and caspase-3 expression in the rat lung tissue during the process of lung I/R injury, and to analyze the role of pneumocyte apoptosis and the possible action mechanism.DESIGN: A randomized controlled animal experiment.SETTING: Emergency Center, First Hospital, Nanjing Medical University.MATERIALS: This study was carried out in the Animal Laboratory of the First Hospital of Nanjing Medcial University and Nanjing Center for Radioimmunity between April 2006 and September 2006. Twenty-eight male healthy SD rats of clean grade, with body weight of 250 to 350 g, aged 49 to 76 days, were provided by the Experimental Animal Center of Nanjing Medical University. The involved rats were randomized into experimental group and control group, with 14 rats in each.METHODS: ①Experimental intervention: Rats in the experimental group were created into models of lung I/R injury according to the method of Eppinger et al. They were occluded for 45 minutes at the porta of lung (no systolic and diastolic reactions in lung tissue being considered as successful occlusion), and then they were reperfused (recovery of systolic and diastolic function being considered as successful reperfusion); After that, lung tissues were harvested at 3 and 6 hours after lung I/R injury, 7 rats at each time point. Each rat in the control group was subjected to a thoracotony only, but lung tissues were isolated at the same time point by the same method. ②Experimental evaluation: Apoptotic cells in the lung tissue were detected with a flow cytometer by Annexin-V-PI staining, and apoptosis rate was calculated. Caspase-3 expression in the lung tissue was observed by immunohistochemical method and image analysis. Wet to dry weight ratio(W/D) of lung tissue of rats in the two groups was calculated; the number of injured pulmonary alveoli at I/R 3 hours/that at I/R 6 hours was calculated for quantitative evaluation of injured lung tissue; Patho-morphological changes of lung tissue were observed by haematoxylin & eosin staining under an optical microscope.MAIN OUTCOME MEASURES: ①Pneumocyte apoptosis rate and caspase-3 expression in the lung tissue. ②W/D of lung tissue and quantitative evaluation of injured lung tissue. ③Patho-morphological changes of lung tissue.RESULTS: Twenty-eight rats were involved in the final analysis, without deletion. ①Pneumocyte apoptosis rates in the experimental group at I/R 3 and 6 hours were significantly increased as compared with control group (P＜0.01). In the experimental group, pneumocyte apoptosis rate was decreased a little at I/R 6 hours than at I/R 3 hours (P＜0.05). ②Caspase-3 expression in the lung tissue of rats of experimental group reached its top at I/R 3 hours, and was decreased a little at I/R 6 hours. At each time point, caspase-3 expression in the experimental group was increased as compared with control group (P＜0.01). ③In the experimental group, the number of injured pulmonary alveoli at I/R 3 hours/that at I/R 6 hours and W/D ratios of lung tissues were significantly increased as compared with control group (P＜0.01). In the experimental group, two ratios at I/R 6 hours were higher than those at I/R 3 hours (P＜0.05).④In the experimental group, the structure of pulmonary alveoli was destructed, collapsed and disappeared; lots of inflammatory cell infiltration was found; Patho-morphological changes of injured lung tissue at I/R 6 hours were severer than those at I/R 3 hours. No obvious changes were found in the control group.CONCLUSION: At the early stage of lung I/R injury, the alteration of caspase-3 maybe activate pneumocyte apoptosis and induce the apoptosis of lung tissue, and thereby leads to lung injury.

Objective To investigate the effects of Shenfu injection ( SF,a Chinese herbal medicine preparation made of Codonopsis pilosula and Aconitum carmichaeli) on the cell apoptosis of focal cerebral ischemic-reperfusion injured rats and the expression of heme oxygenase-1 (HO-1). Methods Forty-two male Sprague-Dawley rats used for producing unilateral brain ischemia reperfusion model were randomly divided into three groups:sham operation group ( Sham group),ischemia reperfusion group ( IR group),and SF Injection group (SF group).The model of focal cerebral ischemia-reperfusion injury was induced by transient occlusion of middle cerebral artery (ischemia for 2 h,and reperfusion for 3,6 h respectively).In SF group,SF ( 10 mg/kg) was intraperitoneally injected duri(n)g reperfusion.Cell apoptosis rate in brain tissue was detected by the technique of Annexin-V-PI double staining and was counted in flow cytometer.Expression of HO-1 in brain was measured by RT-PCR,while the pathological and ultra structure changes of cerebral tissue were also observed.Results Cell apoptosis rate of brain tissue were significantly higher in IR group than that in Sham group (P ＜0.01 ),while SF group had less significant changes in cell apoptosis rate, HO-1 level of brain tissue than IR group (P ＜ O.01 ).The ultra structure change of brain tissue was less in SF group than that in IR group.Conclusions During early stage of brain IR injury,SF inhibits cellular apoptosis and in turn protects the brain from injury which is attributed to the increase in HO-1 expression induced by SF.

Objective To investigate the characteristics of diet in patients with gestational diabetes mellitus(GDM) and analyze their dietary nutrition.Methods Clinical data of 978 cases of pregnant women in our hospital were collected and divided into GDM group(458 cases) and the healthy control group (520 cases).Dietary questionnaire was designed and diet characteristics were analyzed retrospectively.Daily calories and nutrients intake were calculated by software calculation.Results There were significant differences on the dietary pattern between the two groups:daily coarse grains:(35.12 ±4.87) g vs (46.35 ±5.23) g;seafood:(22.10 ± 8.45) g vs (39.34 ± 12.45) g;grilled:(6.72 ± 1.76) g vs (3.45 ±0.34) g;fried:(25.34 ± 7.84)g vs (10.56 ±4.76) g;sausage:(5.38 ± 1.81) g vs (3.45 ± 0.45) g;dessert type products intake:(50.41 ±20.76) g vs (35.86 ± 10.45) g (t =2.582,10.346,15.452,20.239,18.195,8.472,respectively,P ＜0.05).There was only significant difference between the two groups on calcium supplements in daily intake of nutritional supplements(GDM group 43.89％,control group 72.69％,x2 =83.660,P ＜ 0.001),and there was no significant difference on the rests(all P ＞ 0.05).Vitamin A,B1,B2,C and calcium,iron,zinc,selenium daily intake in GDM patients were less than those in the control group,but there was significant difference only in calcium compared with the control group (GDM group (785.2 ± 194.5) mg,control group (945.5 ± 245.2)mg,t =2.795,P =0.005).Multivariate logistic regression found that excessive intake of fried class (OR =3.357,95％ CI =2.012-11.340),barbecue (OR =2.652,95％ CI =1.834-8.578),sausage type products (OR =2.518,95％ CI =1.743-7.421) etc.were dietary factors of GDM (all P ＜ 0.05).Incidence of GDM was significantly increased if taking more.While the increased intake of coarse grains (OR =0.632 95％ CI =0.134-1.489),seafood class(OR =0.408,95％ CI =0.105-1.189) can reduce the occurrence of GDM(all P ＜ 0.05).Conclusion Many unscientific ways of eating involved in pregnant women with GDM.Dessert,sausage,grilled,fried products intake increased the risk factors for GDM.Coarse grains,seafood intake were the protective factors of GDM.Timely adjustment of maternal diet and adequate calcium supplementation played an important role in the prevention of GDM.

Objective To improve the awareness of fetal cardiac rhabdomyomas (CRs) and investigate a better model for prenatal diagnosis and treatment through analyzing imaging findings and prognosis.Methods A retrospective study was conducted on 23 cases of CRs which were diagnosed by ultrasound in Obstetrics and Gynecology Hospital of Fudan University from January 2008 to November 2015.General conditions,imaging features,prognosis and follow-up data of the 23 cases were described.Results The average gestational age of the 23 fetuses at diagnosis was (29.8±4.1) (22.4-35.7) weeks.Seventeen out of the 23 gravidas received prenatal multidisciplinary consultation.Among all 23 gravidas,three (13％) were lost to follow-up,12 (52％) decided to terminate the pregnancy,and the other eight (35％) continued to term pregnancy and their babies were followed up for three years.Of these eight cases,two cases received prenatal brain MRI and no tuberous sclerosis complex (TSC) was detected,no CRs was identified during the follow-up,and their physical and mental developments were both normal.One case was diagnosed with suspected subependymal nodules by prenatal brain MRI in our hospital,but the MRI images was normal when scanned in the other hospital,and follow-up data revealed neither CRs nor abnormal physical and mental developments.Four cases did not received prenatal brain MRI,but the MRI images of neonatal brains indicated TSC,besides,follow-up data showed that seizures were observed,physical developments were all normal,but three of the four cases had mental retardation;CRs disappeared in only two of the four cases.One case had neither prenatal nor neonatal MRI,but follow-up data showed that CRs had disappeared and physical and mental developments were both normal.Conclusions Prenatal diagnosis of fetal tuberous sclerosis is crucial to the prognosis of CRs.Prenatal ultrasonography in combination with cranial MRI improves the accuracy of prenatal diagnosis of CRs complicated with TSC and assists in clinical decision-making and prognosis analysis.

Objective:To investigate the effects of methylprednisolone(MP)on pneumocyte apoptosis during lung ischemia/reperfusion injury in rats and to study the possible role of MP in pneumocyte apoptosis.Methods:Forty-two male Sprague-Dawley rats used for unilateral lung ischemia/reperfusion model were randomly divided into three groups:sham operation group(Sh group),ischemia/reperfusion group(I/R group),and methylprednisolone group(MP group).Each group has two subgroups of three hours and six hours.Apoptosis rate in lung tissue was detected by the way of Annexin-V-PI in flow cytometer.Expression of I?B-? in lung was observed by immunohistochemical stain.The index of quantitative assessment of histological lung injury(IQA),the wet to dry weight ratio(W/D),the pathological and ultrastructure changes of lung tissue were measured.Results:Apoptosis rate,W/D,IQA of lung tissue were significantly higher in I/R group than which in Sh group(P