Objective To investigate the expression of peroxisome proliferator-activated receptors (PPARs) in epidermal keratinocytes of patients with psoriasis vulgaris and its significance.Methods Immunohistochemical method was used to examine the expression of PPARα,β/δand.γ in tissue specimens from the normal skin of 5 human controls,lesional and normal skin adjacent to the lesions of 17 patients with psoriasis vulgaris.A semi-quantitative analysis was carried out by image analyzer.Results Different levels of expression of the three PPAR isotypes were observed in the nuclei of epidermal keratinocytes of normal human controls.The expression intensity of PPAR α,β/δand γ was statistically higher in the epidermis of adjacent normal skin than that in psoriatic lesions(all P<0.01)and normal control skin(all P<0.01).Conclusions The decreased expression of PPARα may be associated with the overproliferation and parakeratosis of epidermal keratinocytes in psoriatic lesions,and PPAR β/δ and γ may display a synergistic effect on the maintenance of homeostatic proliferation and difierentiafion of epidermal cells.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized with multiple organ involvements.Acute acalculous cholecystitis (AAC) is an extremely rare manifestation of digestive system involvement in SLE.We reported a case of 32-year-old woman who complained skin rashes for two weeks and stomachache and oliguria for one day.She had rashes at onset,and developed fever,stomachache,hypotension and headache.Physical examination at admission indicated blood pressure 76/47mmHg(1 mmHg =0.133 kPa),heart rate 107 beats/min,warm acra.Murphy's sign was positive.Ultrasound suggested the enlarged gallbladder with surrounding hypoecho band yet no biliary calculi were found.A diagnosis of SLE was made,characteristic with distributive shock at the onset and AAC,complicated with neuropsychiatric lupus and lupus nephritis.She had an acute and severe course of disease,which had been relieved after treatment of high dose glucocorticoid and immunosuppressants.This case arouses clinicians to pay more attention to AAC as a rare form of disease flare in SLE.Early diagnosis of AAC is crucial to a favorable prognosis and in avoid of abdominal surgery.

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 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 current status of screening and management of thyroid diseases during pregnancy,and to provide evidence for further improvement of clinical management.Methods Clinical data of 5 981 pregnant women who delivered at Peking University First Hospital between September 1,2013 and September 30,2014 were analyzed retrospectively.Their average age was (30±4) years (18-47 years) and average gestational week was (39.2± 1.6) weeks (25.5-42.0 weeks).The reference range of thyroid stimulating hormone (TSH) was 0.1-2.5 mU/L recommended by the American Thyroid Association (ATA).The reference range of free thyroxine (FT4) was 11.48-22.70 pmol/L and the cut-off value of thyroid peroxidase antibody (TPOAb) was 34 U/ml both recommended by the kit.The specific reference range of TSH was obtained from normal pregnant women in this study (0.23-4.08 mU/L in the first trimester).Pregnant women with hypothyroidism were divided into two groups according to their TSH level at the first trimester:TSH ≥ 2.5-＜4.08 mU/L group and TSH ≥ 4.08 mU/L group.T test,Chi-square or Fisher's exact test were applied for statistical analysis.Results (1) Screening status:Of the 5 981 pregnant women,there were 13 cases (0.2％) of hyperthyroidism and 146 cases (2.4％) of hypothyroidism diagnosed before conception (133 cases of Hashimoto thyroiditis,eight cases after operation for thyroid cancer,and five cases after 131I therapy because of hyperthyroidism).Among the 5 822 cases requiring screening,4 044 cases (69.5％) received screening tests of TSH,FT4 and TPOAb during early pregnancy according to Chinese Guidelines,and 1 778 cases received neither standard screening nor screening test.(2) Treatment of hypothyroidism:Hypothyroidism treatment rate was only 61.5％ (107/174) according to the reference range recommended by the ATA,lower than that of 88.1％ (52/59) according to the reference range of this study (x2=14.430,P＜0.05).There were 60 cases receiving no treatment in TSH ≥ 2.5-＜4.08 mU/L group.Forty-three of these cases were reexamined,and one of them was abnormal,with a rate of 2.3％ (1/43).There were seven cases without treatment in TSH ≥ 4.08 mU/L group;six of them were reexamined among which one was abnormal,with a rate of 1/6.(3) Thyrotoxicosis:Among the 4 044 pregnant women,99 cases had TSH ＜0.1 mU/L,including 11 cases with FT4 ≥ 22.70 pmol/L (22.82-60.96 pmol/L).Only three cases were positive for thyrotrophin receptor antibody,and then diagnosed as hyperthyroidism and treated with propylthiouracil.(4) Thyroid cancer:Among the 5 981 pregnant women,six cases were diagnosed as thyroid cancer during pregnancy and lactation,with an incidence of 100.3/100 000.Of the six cases,five were diagnosed during pregnancy,and one at one month postpartum.All of the six cases underwent operation and were confirmed to be papillocarcinoma by pathology.Conclusions The screening rate of thyroid diseases during pregnancy is high,but the clinical management is not fully standardized.We suggested that each center should established its own normal reference range for thyroid function test.The incidence of thyroid cancer during pregnancy is increasing,thus attention should be paid to its diagnosis.

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.

OBJECTIVE To investigate the cytotoxicity of cyflumetofen for SH-SY5Y cells and the mechanism. METHODS SH-SY5Y cells treated with cyflumetofen 0.03, 0.06, 0.125, 0.25, 0.5, 1, 2, 2.6, 4, 6, 8 and 16 mmol·L-1 for 48 h. Cell survival was measured with MTT assay. The reactive oxygen species (ROS) was determined with the DCFH- DA probe, and mitochondrial membrane potential (MMP) was detected by JC-1 staining. The morphological changes in cell nuclei were observed with Hoechst33258 staining. Cell cycle and apoptosis were determined by flow cytometry. The protein levels of phosphorylated Jun Kinase (p-JNK) and p-P38 were measured by Western blotting. RESULTS Compared with solvent (DMSO) control group, cyflumetofen (≥0.06 mmol · L- 1) inhibited the proliferation of SH- SY5Y cells obviously (P<0.05), and the IC50 was 2.6 mmol·L-1. MMP declined and ROS levels increased significantly in cyflumetofen 1, 2, 4 and 6 mmol·L- 1 groups (P<0.01). Cyflumetofen 2, 4 and 6 mmol·L- 1 induced nucleic accumulation, nuclear shrinkage and disintegration in SH-SY5Y cells. Apoptosis rates of cyflu? metofen 2, 4 and 6 mmol·L- 1 groups increased from (0.7±0.1)% in DMSO control group to (6.7±0.1)%, (72.4±8.6)% and (90.7±3.2)% (P<0.01). Cyflumetofen 4 and 6 mmol·L- 1 induced G1 phase cell cycle arrest (P<0.01). In addition, Western blotting showed that cyflumetofen 4 and 6 mmol·L-1 up-regulated the expression of p-JNK (P<0.01), while the level of p-P38 in SH-SY5Y cells was increased in cyflumetofen 6 mmol · L- 1 group (P<0.01). CONCLUSION Cyflumetofen induces cell damage, apoptosis and G1 phase cell cycle arrest in SH- SY5Y cells. The mechanism may be associated with oxidative damage, and activation of P38 and JNK stress-response pathways.

Objectives To discuss the characteristics of late gadolinium enhancement (LGE) magnetic resonance (MR) imaging in patients with hypertrophic cardiomyopathy (HCM) and left ventricular apical aneurysm (LVAA) and its related prognostic value. Methods Thirty HCM patients with LVAA were collected from August 2004 to August 2013. All cases with coronary artery diseases were ruled out, and all patients underwent LGE derived by cardiac MR (CMR). Five cases of LVAA were pathological confirmed. Atrial and ventricular diameters, apical aneurysm diameters and left ventricular ejection fraction were measured, and apical aneurysm LGE was evaluated. All patients were then followed up. Comparisons in continuous parameters between patients with or without LGE were performed by independent t test. A Cox proportional hazard model was used to estimate the hazard rate for adverse cardiovascular events. Results LGE was identified in 21 LVAAs and non-LGE in 9 LVAAs. Between two groups, there was no significant difference in the size of LVAA [(16.4 ± 11.5) mm vs. (20.3 ± 9.8) mm, P=0.63]. In particular, the complete transition from non-LGE to LGE LVAA was recorded during follow-up in one patient. Pathological findings confirmed that LGE indicated fibrous tissue in LVAA, and LVAA without LGE indicated viable myocardium. The follow-up suggested that the patterns and the size of LVAA were associated with the adverse events in these patients (LGE of LVAA, HR=7.94, P=0.064; the size of LVAA, HR=1.08, P=0.009). Conclusions LGE-MR had important clinical significance in HCM patients with LVAA. LGE in LVAA corresponded with the fibrous tissue and was associated with the prognosis.

Objective To investigate the influence of murine cytomegalovirus on the expansion of CD+CD25+ Foxp3+ regulatory T cell (Treg) and the activation of CD4+ CD25+Foxp3 - effector T cell (TE) in vivo. Methods Forty-two BALB/c mice were intraperitoneally inoculated with appropriate amount ofMCMV Smith strain for establishing the model of infection, another 42 mice served as mocked-infected con-trois. Day 28 post MCMV infection was determined to be the demarcation point of the acute and chronic in- fection based on the viral load of major visceral organs. On day 1,3, 7, 14, 28, 45 and 60 post infection, splenocytes were prepared by means of routine method. The proportions of CD4+CD25+ Foxp3+Treg and CD4+CD25+Foxp3- activated TE in T lymphocyte were measured by flow cytometry. Results The propor- tion of CD+CD25+ Foxp3+ T cells in T lymphocytes was persistently suppressed since day 7 post infection, and fell to the lowest level on day 28 post infection (P <0.01), then zoomed and reached the peak value on day 60 post infection (P < 0.05). CD4+CD25+ Foxp3 - TE proportion was up to the highest on day 3 post infection(P < 0. 01), then suppressed and in significantly lower level since day 45 post infection (P < 0.05). Treg/CD+TE ratio was in lower level on day 3 to 14 post infection(P <0.05) ; but on day 45 and day 60 post infection Treg/CD+ TE ratio was markedly increased (P < 0.05). Conclusion MCMV infec- tion can increase the CD+CD25+Foxp3+ Treg proportion, and inhibit CD4+T cells activation in chronic in- fection phase, which is likely to suppress the function of antiviral immunity in the infected host to cause a persistent latent infection.

Background To report quality control methods and baseline reproducibility data of the ultrasound measurements of carotid artery intima-media thickness in the project of Establishment of an Integrated System for Coronary Heart Disease Prevention and Treatment.Methods Standard ultrasound scanning and measuring protocols were established by the study group.All sonographers and readers were trained by the carotid ultrasound core lab and all digital ultrasound images were centrally read.Ten subjects were scanned twice (with 1 week interval) by 2 sonographers independently and images were read by a single reader to evaluate the sonographer variability.Twenty subjects' images were read twice (with 1 week interval) by a single reader to assess the reader variability and the reproducibility of IMT measured at different carotid segments.Results The intraclass correlation (ICC) of intra-and inter-sonographer and intrareader for mean IMT measurements was 0.99,0.98 and 0.97 respectively; while for max IMT,it was 0.97,0.99 and 0.95 respectively.Among different carotid segments and sites,ICC for mean IMT measurements of common carotid (CCA),carotid artery bulb (Bulb),internal carotid artery (ICA),overall near wall and overall far wall was 0.97,0.99,0.89,0.93 and 0.98 respectively.Conclusion The reproducibility of IMT measurements according to our protocol is acceptable,although better reproducibility is found when measuring the mean IMT than max IMT,CCA and Bulb IMT than ICA IMT,and far wall IMT than near wall IMT.