Phthalate esters (PAEs) are commonly used plasticizers and have caused pollution to the environment due to their widespread use.Therefore, many countries have listed such compounds as a priority list of pollutants, and it is of great significance to establish an accurate analysis method for monitoring the pollution of PAEs in water.A method of solid phase membrane extraction combined with ultrasonic wave desortion-gas chromatography-mass spectrometer for analysis of PAEs in water was established in this study.The extraction and desorb conditions were optimized.In this study, the samples were ultrasonic wave desorbed for 7 min at bath temperature of 40℃ and ultrasonic powder of 50%.The detection limits (S/N>3) of this method were between 0.05 μg/L and 0.26 μg/L, the recoveries in different matrixes were between 76.2% and 112.3%, and the relative standard deviations were below 10%.

Artificial sweeteners ( ASs ) have gained more and more attention by environmental scientists because some of them such as acesulfame, have the potential to be the ideal tracers of domestic wastewater for environmental monitoring. In contrast to the existing methods of artificial sweeteners, the analytical method of ASs as a new tracer for environmental samples requires better sensitivity and selectivity to avoid matrix interference. A highly sensitive method for the simultaneous determination of four frequently-used artificial sweeteners in water samples using solid-phase extraction and ion chromatography triple quadrupole mass spectrometer with an electrospray ionization source ( IC-MS/MS) in negative ion mode was developed. The separation effect of different separation columns was compared and a 2-mm ion chromatography column AS19 was chosen in the experiment. Chromatographic separation of all the 4 artificial sweeteners was carried out in 9 min in isocratic elution mode using 60 mmol/L sodium hydroxide as eluent. Different kinds of solid phase extraction cartridges were evaluated to obtain satisfactory recoveries of all of the analytes. Merk LiChrolut EN (200 mg, 3 mL) was preconditioned with 2 mL of methanol, followed by 2 mL of H2 O. About 200 mL of sample (pH<2. 0) was passed through the cartridge at a flow rate of 4 mL/min, and then the cartridge was eluted using 2 mL of methanol. 2 mm suppresser (75 mA) was used to reduce the background noise and to remove the matrix interference. The limits of detection were below 5. 0 ng/L for various artificial sweeteners based on 3-fold the S/N. The recoveries of different matrices in the samples were 65%-120%. The method described here is time-saving, accurate and precise, and is suitable for monitoring artificial sweeteners in different water matrices. The method has also the potential to trace other contaminants in groundwater.

Objective To investigate the effect of subclinical hypothyroidism during pregnancy on hippocampus insulin-like growth factor Ⅰ (IGF-Ⅰ) signaling pathway in rat offspring.Methods A total of 60 female Wistar rats were evenly divided into control(CON),subclinical hypothyroidism(SCH),and clinical hypothyroidism (CH) groups.The hippocampus of progenies were collected on the postnatal day 3,postnatal day 7 to measure protein kinase B (Akt) and phosphorylated-Akt (p-Akt) by Western blot,IGF-Ⅰ and insulin-like growth factor Ⅰ receptor (IGF-Ⅰ R) by Elisa.Morris water maze and field excitatory postsynaptic potential long-term potentiation were measured at the postnatal 40 day.Results Western blot and Elisa revealed that levels of IGF-Ⅰ,IGF-Ⅰ R,and p-Akt of pups from SCH group were lower than that of CON group and were higher than CH group on day 3 (P ＜ 0.05).On day 7,the levels of IGF-Ⅰ,IGF Ⅰ R,and p-Akt of pups from SCH group were lower than CON group (P＜ 0.05),but no difference was observed in p-Akt and IGF-Ⅰ R level between SCH group and CH group (P ＞ 0.05).Latencies of all groups had shortened in Morris water maze test with increasing of training trials.The slope of field excitatory postsynaptic potenial was increased in all groups after Theta burst stimulation.The amplification percentage of slope of field excitatory postsynaptic potenial in SCH group's was lower than control group's but was higher than CH group's(all P values＜0.05).Conclusions Maternal subclinical hypothyroidism impairs long-term potentiation induction in hippocampus of rat might be associated with the levels of IGF-Ⅰ,IGF-Ⅰ R,and p-Akt.

Objective To investigate the early diagnostic and prognostic value of plasma D-dimer level in acute aortic dissection.Method Data of totally 500 acute chest pain patients were studied,in which 250 cases were in group of acute aortic dissection (group AAD) confirmed by aortic computerized tomographic angiography (CTA) or cardiac ultrasonography,and the rest 250 cases were in non AAD group (group control).The D-dimer test was performed in all patients within 72 hours after onset of chest pain,and comparison of plasma D-dimer concentration was carried out between two groups.The D-dimer diagnostic value in AAD was analyzed by plotting the receiver operating characteristic (ROC) curve.According to AAD patients with aortic CTA findings,the whole aortic artery was divided into four segments by the major vascular branches,and the false lumen area was measured by degree score,the relationship between the score and D-dimer level were analyzed.To study the prognostic value of D-dimer in AAD,the comparison of D-dimer level was carried out between survival group and death group,and the AAD patients were further stratified by the surgery and Stanford type.Results The plasma D-dimer concentrations in AAD group were significantly higher than those in controls (P ＜0.01).The sensitivity,specificity,positive predictive value and negative predictive value of D-dimer (＞ 1.14 mg/L) in the diagnosis of AAD were 81.2％,79.39％,74.63％ and 72.4％ respectively,and the area under the ROC curve was 0.083.The elevated level of D-dimer was positively correlated with the extent of AAD false lumen (Spearman-Rho =0.418,P ＜ 0.01).D-dimer levels in the death group were higher than those in the survival group.Conclusions D-dimer may be a valuable biomarker in early diagnosis of AAD.The elevated level of D-dimer was useful to evaluate the extent of the dissection and prognosis of AAD.

Objective To investigate the efficacy and optimal time of levothyroxine (L-T4) treatment in pregnant rats with subclinical hypothyroidism.Methods Female adult Wistar rats were divided into six groups (n =10 per group):control,hypothyroid (H),subclinical hypothyroid (SCH),and SCH treated with L-T4 starting from the tenth,thirteenth,and seventeenth gestational day (GD10,GD13 and GD17),to restore normal thyroid hormone levels.Spatial learning was assessed in progenies by a water maze test and fEPSPs recording.Results Progenies from the SCH and H groups demonstrated significantly longer mean latency in the water maze test and a lower amplification percentage of the fEPSPs' amplitude and slope compared with the offspring of the control group.L-T4 treatment in the GD10 and GD13 groups significantly shortened mean latency and increased the amplification percentage of the fEPSPs' amplitude and slope as compared with the progeny of rats with subclinical hypothyroidism.However,L-T4 treatment in the GD17 group showed only minimal effect on spatial learning of offspring.Conclusion Maternal subclinical hypothyroidism may impair spatial learning in the offspring; L-T4 treatment started early during pregnancy may alleviate this adverse effect.

Objective To explore whether maternal subclinical hypothyroidism gives rise to poor performance in the offspring and whether this is associated with the expression of several genes that are under the control of thyroid hormones. Methods Sixty female rats were divided into three groups ( each group n = 20): ( 1 )maternal subclinical hypothyroidism ( total thyroidectomy with T4 infusion), (2) maternal hypothyroidism ( total thyroidectomy without T4 infusion), and (3) control (sham operated). All rats were mated 10 days after the start of infusion. The infusion continued until 10 days postpartum. Pups were sacrificed at postnatal day 3, 7, and 21. The hippocampus was collected and tested for brain-derived neurotrophic factor (BDNF) and Rap1 protein expression by Western blotting and for BDNF and neural cell adhesion molecule ( NCAM ) mRNA expression by real-time polymerase chain reaction. On day 41-49, rat pups explored the Morris water maze. Time spent in the quadrant previously containing the plat form was recorded. Results The present study found decreases in BDNF mRNA (on day 3 ) and protein levels (on day 3 and 7 ) in hippocampi of pups from subclinical hypothyroidism dams (P＜0.05). No change was observed in the levels of NCAM mRNA, whereas at day 21, expression of Rap1 protein was higher than that of control offspring. In addition, pups of subclinical hypothyroidism dams showed a trend toward depression in short-term memory (P＞0.05), and long-term memory testing revealed a trend toward subclinical hypothyroidism group pups being less able to remember a fixed platform position than controls, spending less time in the proper quadrant ( P＜0. 05 ). Conclusion The long-term memory deficits of pups born to maternal subclinical hypothyroidism dams are likely related with decrease in BDNF expression as well as increase in Rap1 expression in hippocampi.

Objective To study the effect of maternal subclinical thyroid abnormalities [including subclinical hypothyroidism, hypothyroxinemia and positive anti-thyroid peroxidase antibody (TPOAb) with normal thyroid function] in women during 16-20 weeks of gestation on offspfing's intellectual development and motor function. Methods Sera from 1 268 women during 16-20 weeks of gestation (collected 2 years ago) were obtained and thyroid stimulating hormone (TSH), total thyroxine (TT4), free thyroxine (FT4) and TPOAb levels were measured. Pregnant specific thyroid function reference ranges were used to screen for subclinical hypothyroidism (18 cases), hypothyroxinemia (19 cases) and positive TPOAb (34 cases). From the same cohort, a total of 142 pregnant women who were euthyroid with negative TPOAb were selected as controls (a case: control ratio of 1 : 2). Intellectual and motor development score evaluations were performed in their children at 25-30 months of age. Results In the group of pregnant women with subclinical hypothyroidism, the offspring' s intelligence score was (109.89±13.81) points, which was 8.88 points lower than in the control group (P < 0.01). Similarly, the motor score of the offspring was (108.11±9.93) points, which was 9.98 points lower than in the control group (P < 0.01). In the pregnant women with hypothyroxinemia, the offspring's intelligence score was (112.32±15.10) points, 9.30 points lower than in the control group (P <0.01); the motor score was (112.21±12.26) points, 7.57 points lower than in the control group (P < 0.01). In the pregnant women with positive TPOAb and euthyroid function, the offspring's intelligence score was (112.70±20.64) points, 10.56 points lower than in the control group (P < 0.01); the motor score was (110.64±12.49) points, 9.03 points lower than in the control group (P < 0.01). Conclusion Maternal subclinical thyroid abnormality between 16-20 weeks of gestation adversely may affect offspring intellectual and motor development, suggesting the necessity for screening and treatment of maternal subclinical thyroid abnormality in the early stages of pregnancy.

Objective To investigate the effect of treatment with levothyroxine in early maternal subclinical hypothyroidism (SCH) on the neural development of the progeny. Methods 75 thyroidectomized female Wistar rats were divided randomly into groups of hypothyroidism (CH), SCH, SCH treated with levothyroxine at embryonic day 10 (E10), E13, and E17. There were 15 sham operated controls. Body weight,thyroid function, and the development of progeny by morris water maze, immunohistochemistry, and Nissl's staining of progeny were made. Results Pups from SCH or CH group had significantly lower body weight than euthyroid group ( P＜0. 05 ). Pups from E10, E13 or E17 groups had normal body weight compared to pups of control (P＞0.05). The levels of TSH and total T4( TT4 ) of all pups were normal. The mean latencies were longer in pups from CH, SCH, and E17 group than the control (P＜0.05). The mean escape latencies did not differ between the control and E10 group pups and between the control and E13 pups (P＞0.05). There were changes in the cytoarchitecture of the barrel cortex and of the hippocampus ( toluidine blue-stained sections) in CH, SCH, and E17 pups. The barrel cortex of E10 or E13 pups was similar to that of control pups. The distribution of BrdUlabeled cells was more widespread in CH, SCH, and E17 pups than in control, E10, and E13 progeny.Conclusion Maternal SCH disturbs learning and memory performances, cytoarchitecture and cell migration of the pups. Treatment with levothyroxine in early maternal SCH before E13 improves the cell migration in the developing brain of the progeny.

Data were collected through questionnaire from 505 women enrolled during early pregnancy.Based on soy intake frequency,the subjects were divided into three groups:frequent (three or more times per week),conventional ( more than twice per month but less than three times per week),and occasional ( two or fewer times per month).Serum TSH and FT4 were measured by chemiluminescence immunoassay.The urinary concentrations of two primary isoflavones (daidzein and genistein) and creatinine were further assessed in 95 subjects from the three groups.The percentages of frequent,conventional,and occasional consumers were 18.6％,62.6％,and 18.8％,respectively.No difference was found in age,medical records,family history of thyroid diseases,serum FT4,TSH,and prevalence of thyroid dysfunctions among three groups. Both urinary daidzein and genistein levels were significantly higher in the frequent consumers compared with the other two groups.No correlations were found between urinary isoflavone levels and serum FT4 or TSH.These findings suggest that dietary soy consumption during early pregnancy seems not to be associated with the development of thyroid dysfunction.

Objective To investigate the associations ofa disintegrin and metalloproteinase with thrombospondin type 1 motifs (ADAMTS1) gene single nucleotide polymorphism (SNPs) with vulnerability of carotid plaque formation and atorvastatin lipid-efficacy in patients with cerebral infarction.Methods Seven hundred and seventy-eight patients with anterior circulation infarction,admitted to our hospital from June 2010 to June 2015,were divided into the following 3 groups according to their carotid ultrasound examination results:vulnerable plaque group (n=291),stable plaque group (n=286) and no plaque group (n=201).Atorvastatin was given in patients from the 3 groups and the low density lipoprotein cholesterin (LDL-C) level was detected to evaluate the atorvastatin lipid-efficacy in 151 patients from vulnerable plaque group 4 weeks after treatment.The SNPs of rs402007 (G/C) in ADAMTS1 gene of all patients were detected by PCR amplification and DNA sequencing.Results There were statistically significant differences in age,fibrinogen (FIB) level,homocysteine (HCY) level and percentage of patients having diabetes among the three groups (P＜0.05).The frequencies of GC+CC genotype and C allele in rs402007 (G/C) ofADAMTS1 gene in the vulnerable plaque group were significantly higher as compared with those in the no plaque and vulnerable plaque groups (P＜0.05).After adjusting risk factors (age,FIB,HCY and diabetes),GC+CC genotype was the independent risk factor of vulnerable plaque (OR=1.559,P=0.015,95％CI:1.089-2.232).There were no significant differences in LDL-C levels before and after atorvastatin treatment among the GG,GC,and CC genotypes in vulnerable plaque group (P＞0.05).Conclusion C allele in ADAMTS1 gene might increase the risk of plaque's instability;no correlation exists between A DAMTS1 gene polymorphisms and LDL-C lowing efficacy to atorvastatin.