Objective To analyze the changes of thyroid function of healthy primipara before 20 weeks of gestation to establish normal gestational age-specific reference interval of thyroid hormones,and to investigate the prevalence of maternal thyroid disorders during the first half of pregnancy.Methods A total of 1605 healthy primipara without risk factors of thyroid diseases before 20 gestational weeks and 200 non-pregnant healthy women who accepted pre-conception care in Beijing Friendship Hospital from September 2010 to June 2011 were tested for serum thyroid stimulating hormone (TSH),free thyroxine (FT4) and thyroid peroxidase antihody (TPOAb) by chemiluminometric immunoanalysis.One thousand two hundred and fourty-three pregnant women among them with negative thyroid antibooly and without previons thyroid diseases were selected as the standard population for normal interval.Gestational age-specific percentile categories for TSH and FT4 were calculated.The prevalence of maternal thyroid disorders was examined by gestational agespecific intervals.Results (1) Compared with non-pregnant women,the median value of serum TSH in pregnant women decreased by 29.56％ to the value of 0.91 mU/L; while that of FT4 rose by 7.79％ to the value of 11.33 pmol/L before 12 weeks; and TSH increased while FT4 decreased during 13 to 20 weeks.(2) The median values and reference intervals (2.5th percentile,97.5th percentile) for TSH were 1.59 mU/L (0.15 mU/L,5.19 mU/L) in no-pregnant women,1.12 mU/L (0.03 mU/L,3.67 mU/L) at 8-12+6 gestational weeks,1.21 mU/L (0.05 mU/L,3.74 mU/L) at 13-16+6 gestational weeks,1.50 mU/L (0.31 mU/L,4.33 mU/L) at 17-19+6 gestational weeks; and the median values and reference intervals (2.5th percentile,97.5th percentile) for FT4 were 9.91 pmol/L (6.69 pmol/L,14.03 pmol/L),10.68 pmol/L (7.98 pmol/L,18.66 pmol/L),10.04 pmol/L (6.18 pmol/L,16.22 pmol/L),9.40 pmol/L (6.44 pmol/L,13.51 pmol/L) respectively.(3) According to gestational age-specific reference intervals,the general prevalence of maternal thyroid disorders,including hyperthyroidism,hypothyroidism,subclinical hypothyroidism and hypothyroinemia,was 3.55％ (57/1606).At 8-12+6 gestational weeks,13-16+6 gestational weeks and 17 19+6 gestational weeks,the occurrence of hyperthyroidism was 0.00％,0.13％ and 0.00％;that of hypothyroidism was 0.00％,0.13％ and 0.00％; the incidence of subclinical hypothyroidism was 3.60％,2.76％ and 3.00％; the occurrence of hypothyroxinemia was 0.16％,0.26％ and 0.86％,respectively.The positive rate of TPOAb at 8-12+6,13-16+6 and 17-19+6 gestational weeks were 22.91％ (140/611),16.56％ (126/761) and 15.45％(36/233),and the total positive rate of TPOAb was 18.82％ (302/1605).The median level of TPOAb was 38.90,41.87 and 39.10 mU/L,respectively.Conclusions Before 20 gestational weeks,specific changes occur in maternal thyroid function.TSH level decreases during 8 to 12 gestational weeks,and then increases gradually; while FT4 level increases during 8 to 12 weeks,and then decreases gradually.Thyroid dysfunction during pregnancy is common and subclinical hypothyroidisum is the leading problem in thyroid disorders.Screening for thyroid function during early pregnancy is suggested.

ObjectiveTo investigate the effects of aconitine, mesaconitine and hypaconitine on calcium release in isolated adult rat cardiac myocytes.MethodsThe left ventricular cardiac myocytes isolated from adult Sprague-Dawley rats were perfused withacnitine, mesaconitine and hypaconitine at 0.3 μmol/L, 1μmol/L, 3 μmol/L for 12 min. The spontaneous calcium release (SCR) rate, the end-diastolic[Ca2+](F0) and the calcium transient amplitude (ΔF) were detected 4 min, 8 min and 12 min after the perfusion. 12 min after the perfusion with acnitine, mesaconitine and hypaconitine at 0.3 μmol/L, the changes of systolic dynamics and calcium transient were detected for the positive inotropic effect. Results Any of aconitine, mesaconitine and hypaconitine induced SCR, mesconitine-induced SCR rate was highest at low concentration (0.3 μmol/L), and aconitine-induced SCR rate highest at high concentration (3 μmol/L). Compared with the control, 12 min after the perfusion with acnitine, mesaconitine and hypaconitine at 3 μmol/L elevated F0 (1.459 ± 0.379, 1.585 ± 0.493, 1.213 ± 0.254vs.1.079 ± 0.108, allP<0.05) and ΔF(1.615 ± 0.455, 2.210 ± 0.756, 1.528 ± 0.422vs. 1.036 ± 0.125, allP<0.05), mesaconitine with ΔF higher than aconitine and hypaconitine. At low concentration (0.3 μmol/L), compared with control, aconitine, mesaconitine and hypaconitine increased ΔF (0.409 ± 0.127, 0.423 ± 0.107, 0.414 ± 0.118vs.0.260 ± 0.065;P<0.05 orP<0.01) and contraction amplitudes (5.464% ± 2.239%, 7.449% ± 2.548%, 5.524% ± 1.645%vs.3.428% ± 0.911%;P<0.05 orP<0.01), prolonged the time to peak of calcium transient (0.041 ± 0.016 s, 0.039 ± 0.009 s, 0.038 ± 0.011 svs.0.032 ± 0.007 s;P<0.05 or P<0.01); compared with aconitine, mesaconitine and hypaconitine decreased calcium transient time constant (0.301 ± 0.054 s, 0.324 ± 0.064 svs.0.361 ± 0.076 s;P<0.05 orP<0.01) and diastolic t50 (0.124 ± 0.035 s, 0.126 ± 0.040 svs.0.157 ± 0.056 s;P<0.05 orP<0.01).ConclusionsAconitine, mesaconitine and hypaconitine reveal the positive inotropic effects couple with the toxic effects. Increased[Ca2+]in cardiac myocytes is the key factor for the positive inotropic effects, but also the risk factor for SCR.

A rapid analytical method for the determination of dezocine and pethidine in hair samples using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was established.After cleaned hair was extracted by grinding with methanol and ultrasonic, the final solution was analyzed by UPLC-MS/MS.The targets were gradient eluted on a Waters Acquity BEH C18 (2.1 mm × 100 mm, 1.7 μm) column with 0.1% formic acid-water and methanol as mobile phase at a flow rate of 0.4 mL/min.The ESI+ ion source and multiple reaction monitoring (MRM) were used to select the qualitative and quantitative ion pairs of dezocine and pethidine.Dezocine and pethidine showed good linearity in the range of 0.01-8 ng/mg, with the limit of detection of 0.005 ng/mg and the LOQs of 0.01 ng/mg.The accuracy, precision, matrix effect, extraction recovery, and stability all met the requirements.The established method is simple, rapid, and accurate for the qualitative and quantitative determination of dezocine and pethidine in hair, which can be applied in the case analysis of dezocine and/or pethidine abuse.

Objective:To determine the effects of TPS on peripheral blood Tregs in sepsis mouse induced by burn plus P.aeruginosa infection.Methods: The experimental mice were separated into five groups randomly ,including sham burn group ,burn plus P.aeruginosa infection group ,burn plus P.aeruginosa infection with TPS (50,100,200 mg/kg) treatment group.Peripheral blood Tregs were isolated with Magnetic Microbeads and cultured in vitro from the day after burn (PBD0) to 4 days after burn(PBD4).IL-10, IFN-γ,IL-4 levels in Tregs culture supernatants were determined by sandwich enzyme-linked immunosorbent assays ( ELISA ) . Purification of CD4+CD25high Tregs and CD4+T cells in C57BL/6 mice were administrated by magnetic beads sorting .Tregs and CD4+T cells were cultured in vitro after joining TPS to without TPS cells as a control .The phenotypes of Tregs were analyzed by flow cytometry , and cytokines were measured by ELISA .Results:Vis-a-vis the results of the untreated group ,TPS could markedly decrease IL-4 and IL-10 secretion level and significantly increase the secretion of IFN-γ,and the secretion of IL-10 level and concentration of TPS dose effect.Vis-a-vis the results of the untreated group ,in vitro experiment ,without stimulation of TPS ,CD4+T cell proliferation and IFN-γwere significantly reduced ( P<0.05 ) and IL-4 levels increased significantly;CD4+T cell proliferation and IFN-γwere significantly increased and IL-4 levels were significantly reduced in the group of TPS with antibody-1;there was no significant difference in CD 4+T cell proliferation and the levels of IFN-γand IL-4 in the group of TPS with antibody-2.Conclusion:TPS could inhibit the abnormal ac-tivities of CD4+CD25highTregs in burn with P.aeruginosa infection mice,at least in part via inhibiting IL-10 secretion,and trigger a shift of Th2 to Th1 with activation of CD4+T cells in burn with P.aeruginosa infection mice.

Objective To explore the effects and related mechanism of Exendin-4 on secretion of extracellular matrix in high glucose-induced glomerular mesangial cells(GMCs). Methods GMCs were incubated in medium with glucose or Exendin-4 for the four groups: normal glucose group(NG group): cells were treated in medium with 5.6 mmol/L glucose; NG with Exendin-4 treatment group(NGE group): cells were treated with 5.6 mmol/L glucose and Exendin-4; high glucose group(HG group): cells were cultured with 30 mmol/L glucose; HG with Exendin-4 treatment group(HGE group): cells were treated with 30 mmol/L glucose and Exendin-4 at concentration of 3, 5, 10, 15, 30 nmol/L separately, which were cultured for 12, 24, 48 hours. GMCs treated with Exendin-4 were determined by assessing proliferation using a CCK8 method. The levels of fibronectin(FN), collagen type Ⅳ(Col-Ⅳ)in the cell supernatant were measured using enzyme-linked immunosorbent assay(ELISA). The gene levels of Col-Ⅳ, FN, and expression of inflammatory mediators including monocyte chemotactic protein 1(MCP-1), tumor necrosis factor-α(TNF-α), intercellular cell adhesion molecule-1(ICAM-1), transforming growth factor-β1(TGF-β1)were evaluated using reverse transcription PCR(RT-PCR); The expression of nuclear transcription factor-κB(NF-κB), glucagon-like peptide-l receptor(GLP-1R), and phosphorylation levels of mitogen-activated protein kinases(MAPKs)were evaluated by Western blot. Results(1)After treatment with 10 nmol/L Exendin-4 for 24 hour, the proliferation rate of GMCs was significantly decreased compared with 3 nmol/L, 5 nmol/L Exendin-4 treatment(P<0.05), while there was no difference compared with 15 nmol/L, 30 nmol/L Exendin-4 treatment(both P>0.05). (2)The gene expression of FN, Col-Ⅳ and the inflammatory mediators, MCP-1, TNF-α, ICAM-1, TGF-β1 in HG group were significantly increased compared with the NG group,(all P<0.05). After treatment with Exendin-4, the levels of FN, Col-Ⅳ and the gene expression of TNF-α, MCP-1, ICAM-1, TGF-β1 were decreased(all P<0.05). (3)Compared with NG group, the expression of NF-κB and the phosphorylation of extracellular regulated protein kinases(p-Erk1/2), Jun N-terminal kinase(p-JNK)and, p38MAPK(p-p38MAPK)in the group of HG group were increased significantly, accompanied by the decrease of GLP-1R protein level(all P<0.05). Importantly, Exendin-4 treatment significantly reduced protein expression of p-Erk1/2, p-JNK, and NF-κB(all P<0.05), and the level of GLP-1R protein increased(P<0.05). Furthermore, specific Erk1/2, JNK or NF-κB inhibitors markedly blocked Exendin-4-mediated decrease in the levels of FN, Col-Ⅳ. Conclusion Exendin-4 treatment inhibits the secretion of extracellular matrix potentially through Erk1/2, JNK/NF-κB signaling in higher glucose induced GMCs.

Objective To explore the effects of Levoeitirize dihydrochloride on interleukin-13(IL-13)and interleukin-18(IL-18)in the serum of the patients with cough variant asthma(CVA).Methods 70 cases with CVA were randomly devided into control group of 35 cases and treatment group of 35 cases.Control group was given Chlort rimeton and the treatment group was given Levocitirize dihydroehloride.The levels of IL-13 and IL-18 in the serum were measured before and after treatment.Results After treatment,the concentrations of IL-13 and IL-18 in patients in the treatment group were(46.7±17.3)ng/L and(145.2±27.1)ng/L，and those in the control group were(98.5±30.7)ng/L and(179.6±30.5)ne/L，which were significantly improved.Conclusion The treatmem of Levoeitirize dihydrochloride could improve the CVA through improving the production of IL-13 and IL-18.

Aim To introduce an improved method of Langendorff perfusion of the isolated rat heart that is easy to determine the termination of digestion.Methods Hearts were excised quickly from anesthetized SD rats.After the perfusate was free of blood,the solution was changed to perfusion buffer(0.6% Collagenase B,0.6% BSA,30 ?mol?L-1 Ca2+ in Tyrode solution)at 37℃.Hearts were isolated by traditional and improved Langendorff perfusion.Individual myocardial cell was measured by video-based motion edge-detection system(IonOptix,USA).Results One group of heart was digested by traditional Langendorff perfusion for 13~16 min.The termination of digestion could not be judged properly by this method.The nature and quality of the cardiocytes were various.The cardiocytes could not keep their survival and viability when exposed to Tyrode Solution with 1.8 mmol?L-1 Ca2+.Another group was digested by improved Langendorff perfusion.More than 80% survival cardiac ventricle myocytes could be obtained by improved Langendorff perfusion.Moreover,about 50% cardiac myocytes exposed to Tyrode solution with 1.8 mmol?L-1 Ca2+ could retain rod-shaped and be used to contraction research.The contraction of cardiocyte was stabile within 1 000 s.Conclusion Cardiac myocytes disassociated from improved Langendorff perfusion can be used in these studies of detecting contraction and relaxation.This method is economical and easy to control.The beginners are able to acquire the technological method over a short-term practice.

Case-based teaching (CBT) on the basis of treatment guidelines was carried out to develop standard medical behavior, improve learning efficiency and students' ability of solving clini-cal problems. In clinical internship teaching, guidelines for common and frequently-occurring respira-tory diseases and CBT were organically combined. Cases were carefully selected and questions were meticulously set. Guidelines were thoroughly analyzed and teaching was reasonably evaluated. There-fore, students' learning interests were initiated and learning efficiency was improved. It not only trained evidence-based medicine thinking of intern students, but also improved the teaching ability of clinical teachers.

Objective:To investigate the effects of Xiaoyu-Jiangzhi capsules on blood lipid, carotid artery atherosclerosis (CAA) and plaque in apolipoprotein E knockout (ApoE -/-) mice. Methods:The ApoE -/- mice were fed with high-fat food to establish carotid atherosclerosis model. The ApoE -/- mice were randomly by weight divided into model group, Atorvastatin group, low- and high-dose Xiaoyu-Jiangzhi capsules group. The C57BL/6cnc mice were used as control group and fed with normal diet. The Atorvastatin group was given atorvastatin suspension 1.3 mg/kg, low and high dose groups were given Xiaoyu-Jiangzhi capsule suspension 325 and 975 mg/kg, and the control group and model group were given equal volume of distilled water. The mice were gavaged with 0.1 ml/10 g body weight, once a day, and the weight of mice was recorded weekly. After 12 weeks of continuous intragastric administration, the blood lipid and liver /body weight index of the mice were measured. Carotid arteries were sliced to conduct oil red O staining and VG staining for the pathological analysis. Results:After 12 weeks of drug administration, the weight of mice in the high-dose group was significantly lower than the model group. The level of TC (25.92 ± 4.21 mmol/L vs. 30.39 ± 4.67 mmol/L) and LDL-C (7.97 ± 2.14 mmol/L vs. 10.26 ± 1.97 mmol/L) in the high-dose group significantly decreased ( P<0.05), the level of HDL-C in the low and high-dose group significantly increased ( P<0.05). The pathological results showed that after 12 weeks of administration, the carotid artery lipid deposition blockage rate in the Atorvastatin group and the high dose group were significantly smaller than the model group( P<0.05), and no vascular plaque has been formed. Conclusion:The Xiaoyu-Jiangzhi capsules could reduce LDL-C, increase HDL-C levels, reduce the constriction of arterial stenosis and slow down the formation process of carotid plaque.

Objective: To explore possible the mental health difference between freshmen upgrading from junior college and ordinary freshmen,to provide valuable reference for the targeted mental health educaiton and service. Methods: A comparative analysis of the results of University Personality Inventory (UPI) 2016-2019 among freshmen upgrading from junior college and ordinary freshmen in one university in Nanjing was carried out . Results: Among 11 955 freshmen, the detection rate of severe mental health problems (class Ⅰ) was 22.58%, scores of four indicators(physical symptoms, neurosis, depression, schizophrenia) and prevalence of class Ⅰ problems among freshmen upgrading from junior college were significantly lower than those of ordinary freshmen(P<0.05). Longitudinal comparison showed that there were significant differences in the proportion of class Ⅰ and the scores of the four indicators in each freshmen group in four years(P<0.05). After group interview with class Ⅰ, the proportion of type A and type B among freshmen upgrading from junior college were significantly higher than that of ordinary freshmen(χ2=4.12，9.23, P<0.05). Conclusion Mental health level of freshmen upgrading from junior college is higher than that of ordinary freshmen. Mental health of ordinary freshmen shows improving trend, while freshmen upgrading from junior college shows a non-linear decreasing trend,with high proportion of mental problems, which worth further attention.