Aim To investigate the effect of oral itraconazole on pharmacokinetics of viaminate and under-stand the metabolism pathway of viaminate in healthy humans,as well as guide the reasonable medication for viaminate and itraconazole coadministration.Methods The study was conducted in a double-blind randomized and crossover manner with two phases of treatment with placebo-viaminate or itraconazole-viaminate.Eight healthy male subjects received an oral dose of 200 mg itraconazole(QD) or matched placebo for five consecutive days,and took an oral 100 mg dose of viaminate on day 4 after each treatment phase.The liquid chromatography-mass spectrometry(LC-MS) was established to measure the blood drug concentration of viaminate.Results Our results showed that the mean peak concentration of viaminate was increased with itraconazole [(21.21?11.65) ?g?L~(-1) vs(27.12?13.83) ?g?L~(-1),P0.05].Additionally,the mean elimination half life was prolonged [(2.71?0.38) h vs(4.43?0.93) h,P

Objective To explore the correlation among serum immunoglobulin G4 (IgG4),transforming growth factor-β1 (TGF-β1),connective tissue growth factor (CTGF) and Hashimoto thyroiditis (HT) thyroid fibrosis.Methods Case-control study.A total of 159 patients with HT visiting the Wuhan Union Hospital were collected from May 2013 to March 2015.All patients were divided into IgG4 HT group (IgG4≥1.35 g/L,n =39) and non-IgG4 HT group (IgG4 ＜ 1.35 g/L,n =120).The serum IgG4,TGF-β1 and CTGF were determined by enzyme-linked immunosorbent assays.The levels of serum thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb) were measured by electrochemiluminescence immunoassay.Meanwhile,ultrasound of the thyroid gland was performed.Statistical analysis was performed by use of SPSS 17.0 software.The Mann-Whitney U test was used to compare two independent samples of non-normal distribution data,Fisher's exact test was employed to analyze thyroid imaging differences,correlation test was performed to examine various correlations,multivariate Logistic regression analysis was used to evaluate thyroid fibrosis risk factors.Results Compared with that of non-IgG4 HT group,IgG4 HT group:TPOAb [(455.2 ± 169.7) vs.(186.5 ± 102.3),U =27.0,P=0.003],TgAb [(984.6±452.7) vs.(289.3 ±245.1),U=30.5,P=0.017],TGF-β1 [(1.45±0.97) vs.(0.30±0.22),U=119.0,P=0.035] andCTGF [(88.65±14.39) vs.(62.21± 8.76),U =69.0,P =0.039] were significantly higher,thyroid ultrasound showed obvious fibrosis (35/4 vs.32/88,x2 =48.03,P =0.000);significant positive linear correlation between IgG4 and TPOAb (r =0.719,P =0.000),CTGF and TGF-β1 (r =0.500,P ＜ 0.01) respectively.Logistic regression analysis indicated that all the serum IgG4,TPOAb,TGF-β1 and CTGF were independent risk factors of thyroid fibrosis [IgG4,odds ratio (OR) =1.968,P =0.014,95％ confidence interval (CI) =1.287-2.041;TPOAb,OR =2.537,P =0.012,CI =1.322-2.869;TGF-β1,OR =1.549,P =0.023,CI =1.105-1.498;CTGF,OR =1.185,P =0.046,CI =1.204-1.625].Conclusion The highlevel of circulating antibodies,IgG4,TGF-β1 and CTGF were significantly associated with thyroid fibrosis,and were independent risk factors of HT fibrosis.

Objective:To explore the serum IgG4 level in patients with IgG4-related Hashimoto thyroiditis(IgG4 HT),and its clinical implications.Methods:The serum IgG4 was determined in 129 patients with HT using enzyme-linked immunosorbent assays and classified into two subgroups based on IgG4 level:IgG4 HT group(IgG4≥135 mg/dl)and non-IgG4 HT group(IgG4<135 mg/dl).And the levels of serum thyroid hormone and thyroid peroxidase antibodies(TPOAb)and thyroglobulin antibodies(TgAb)were measured by electro-chemiluminescence immunoassay.Ultrasonic imaging of the thyroid gland were detected.Results:The TPOAb levels correlated significantly with both serum IgG4 levels(r=0.437 1,P=0.012 7)and IgG4/IgG ratios(r=0.396 2,P=0.023 5)in the patients with HT.Compared with that of non-IgG4 HT group(n=97),IgG4 HT group(n=32):①The mean age was lower(P=0.029 3);②Higher levels of serum TPOAb(P=0.002 1)and TgAb(P=0.012 8);③Ultrasound imaging:the more obvious thyroid nodule(P=0.022 6);④Logistic regression analysis showed that serum IgG4 and TPOAb were the risk factor for thyroid nodules(OR=1.672,P=0.021;2.549,P=0.014 ).Conclusion: IgG4 HT patients existed corresponding clinical characteristics.For the HT-patients with elevated serum IgG4,thyroid function and morphology should were more closely monitored.

Objective To investigate the value of CT perfusion imaging in quantitative monitoring on microcirculation hemodynamics,differences between tumor and normal tissues,differences between mass center and edge,and on tumour microvascular responses to anti-angiogenesis therapy. Methods Fifteen male New Zealand white rabbits were established to VX2 tumor-bearing model. The animals were divided into 2 groups,anti-angiogenesis therapy (n=11,TNP-470,20 to 30 mg/kg),and control (n=4). DEC-CT scanning (80 kV,120 mA,20 cm VOF) was performed at 1 week after tumor implantation,1 week after anti-angiogenesis therapy,and 2 week after anti-angiogenesis therapy. Perfusion parameters,including blood flow (BF),blood volume (BV),mean transit time (MTT),and permeability surface (PS) were calculated for tumor mass,tumor edge,tumor center and normal tissue. Results Significant differences of the average values were observed in BF,PS and MTT between tumor and normal tissue [149.32?30.99 vs 32.18?4.10 ml/(100 g?min),28.24?5.15 vs 11.88?0.71 ml/(100 g?min),2.79?0.66 vs 6.57?0.90 s,P

Established rat models with subclinical hypothyroidism (SCH) were divided into three groups:subclinical hypothyroid(SCH),SCH treated with levothyroxine (L-T4),and control group.The L-T4 group displayed lowered total cholesterol and endothelin levels compared with the SCH group[(1.29 ±0.05 vs 2.38 ±0.55) mmol/L,(98.54 ± 32.43 vs 160.62 ±37.25) nmol/L,both P＜0.05].Nitric oxide levels,left ventricular systolic pressure,and blood flow in abdominal aorta were significantly higher in the L-T4 group than those in the SCH group.The results of this study indicate that L-T4 treatment may improve endothclial dysfunction and hemodynamic changes in rats with SCH.

Objective To assess the influence of Rizatriptan on the cholecystokinin( CCK) expression in periaqueductal gray( PAG) of migraine model rat to investigate the possible mechanism by which Triptans treat mi?graine. Methods A total of 24 rats were randomly divided into four groups:normal control groups(A),migraine model groups(B),Rizatriptan control groups(C) and Rizatriptan treatment groups(D).C and D groups were intra?gastrically perfused with Rizatriptan,1 mg/kg per day. After 7 days,nitroglycerin was subcutaneously injected into the buttocks of the B and D group to induce migraine. Two hours after nitroglycerin injection,the trigeminal ganglia were isolated.CGRP expression in periaqueductal gray were determined using SYBR Green I real?time quantitative PCR and Immunohistochemistry. Results CCK mRNA levels ( target gene mRNA copies per 250 ng total RNA,× 106) in the rat midbrain of A,B,C,D groups were 1.25±0.41,1.71±0.93,0.17±0.12,0.22±0.07 respectively. CCK?8?immunoreactive positive cells in the rat PAG of each group were 37.17±12.62,40.17±11.09,27.33±7.71, 20.67±7.66 respectively. CCK mRNA expression in group C was significantly lower than that of group A(P<0.05) while the CCK mRNA expression in group D was lower than that of group B(P<0.05).The CCK?8?positive cells of the rat PAG in group D were lower than that in group B(P<0.05) . Conclusion Rizatriptan can down regulate the expression of CCK?8 in the PAG of the migraine rats and weaken the CCK?8 induced inhibition of the analgesic effects of opioid peptides.

Objective To estimate the critical value notification of emergency specimens in general laboratory whether a-chieved the desired goals,and to apply quality improvement measures to achieve quality improvement purposes.Methods Critical values of emergency specimens in general laboratory were monitored and collected in 2014.Statistical analysis was done for non-notification rates and sources of the critical values,and quality improvement began in July,2014 by training, continuing education and amonthly bulletin of notification data of critical values.Results Total number of Critical values of emergency specimens in general laboratory in 2014 was 2 648 and 1 950 of them had been reported by telephone.Total notifi-cation rate was 61.4% in the first 6 months,and was 81.4% from July to December.At last,Critical value notification rates increased to 97.72% in December.Conclusion Strengthening the management of critical value notification can help impro-ving the quality of laboratory service,as well as enhancing stuff responsibility and awareness of service for clinic.

OBJECTIVEAn optimal automatic selection method of permissible source region is proposed to reduce the ill-conditioned and ill-posed problems in the reconstruction of the light source in bioluminescence tomography.

METHODSThe 2D images captured by CCD are mapped into surface light irradiance distribution based on the light propagating model. The relation matrix between the source and light distribution is obtained by finite element method. Permissive source region is determined by using the automatic selection method proposed in this paper, and then Tikhonov regularization is applied to reconstruct the light source.

RESULTSThe center point distance between the optimal permissible source region and true source is 1.26 mm, and the center point error of the reconstructed light source and true source is 0.47 mm, the volume error is 9.13 mm3.

CONCLUSIONThe optimal permissive source region selection strategy is effective to locate the permissive source region close to the true source, and reduces the reconstructed error due to subjective orientation of permissible source region. This proposed method is the basis of high precision source reconstruction in bioluminescence tomography.

Objective To evaluate effects of a fusion protein LTβR-Fc, which can block the herpesvirus entry mediator ligand (LIGHT-HVEM)signaling pathway, on ovalbumin-induced dermatitis in a mouse model. Methods Thirty BALB/c mice were randomly and equally divided into 3 groups: blank control group treated with 100 μl of sodium chloride physiological solution, model group sensitized with 100 μl of sodium chloride physiological solution containing 100 μg ovalbumin, blocker group firstly blocked with 100 μl of sodium chloride physiological solution containing 100 μg LTβR-Fc followed by sensitization with 100 μl of sodium chloride physiological solution containing 100 μg ovalbumin at 24 hours after the blocking. Disease severity was evaluated by eczema area and severity index (EASI)score, and lesional size was measured on day 0, 4, 8, 12, 15, 20, 23, 27, 31 and 34 after the first sensitization. A total of three sessions of sensitization were carried out. At the end of treatment, all the mice were sacrificed after serum was obtained from their orbital cavities. Thereafter, tissue specimens were obtained from skin lesions, and single cell suspensions of the spleen were prepared. RT-PCR was performed to detect mRNA expressions of interferon γ (IFN-γ), interleukin 4 (IL-4)and IL-5 in murine lesions, ELISA to measure IFN-γ, IL-4 and IL-5 levels in culture supernatants of murine splenocytes, as well as ovalbumin-specific and total IgE and IgG1 levels in murine sera. Results LTβR-Fc significantly suppressed inflammatory response in the mouse model of dermatitis induced by ovalbumin. Compared with the model group, the blocker group showed significantly decreased lesion area and EASI score (both P < 0.05). In addition, a significant decrease was observed in the mRNA expressions of IL-4 (0.88 ± 0.25 vs. 1.81 ± 0.25, P < 0.05), IL-5 (0.75 ± 0.15 vs. 1.24 ± 0.26, P < 0.05)and IFN-γ (0.62 ± 0.09 vs. 1.11 ± 0.19, P < 0.05)in murine lesions, and in supernatant levels of IL-4 (9.58 ± 1.44 ng/L vs. 20.12 ± 5.39 ng/L, P < 0.05), IL-5 (11.37 ± 2.02 ng/L vs. 22.77 ± 4.07 ng/L, P < 0.05)and IFN-γ (16 167 ± 950.40 ng/L vs. 23 930 ± 44.20 ng/L, P < 0.05)in the blocker group compared with the model group. The serum levels of both total IgE and ovalbumin-specific IgE were significantly lower in the blocker group than in the model group(total IgE: 27 466.67 ± 2 052.64 μg/L vs. 32 277 ± 407.53 μg/L, P < 0.05; ovalbumin-specific IgE: 1 296.33 ± 32.72 μg/L vs. 2 323.33 ± 502.43 μg/L, P < 0.05), so were those of total IgG1 (0.46 ± 0.11 μg/L vs. 0.84 ± 0.11 μg/L, P < 0.05)and ovalbumin-specific IgG1 (0.62 ± 0.11 μg/L vs. 0.86 ± 0.07 μg/L, P < 0.05). Conclusion The fusion protein LTβR-Fc can alleviate symptoms of ovalbumin-induced dermatitis in the mouse model likely by suppressing the LIGHT-HVEM signaling pathway, suggesting that this signaling pathway may serve as a target for the treatment of dermatitis(such as atopic dermatitis).

Objective To investigate the association of the polymorphism of the N-acetyltransferase 2 (NAT2 )gene with isoniazid-induced hepatotoxicity and anti-tuberculous treatment efficacy in Chinese Han patients with tuberculosis(TB).Methods A total of 108 TB patients who received initial anti-TB treatment were followed up prospectively.A polymerase chain reaction direct sequencing approach was used to detect genetic polymorphisms of the NAT2 gene.Associations between NAT2 genotype and isoniazid-induced hepatitis/early treatment were analyzed.Chi-square test was used for statistical analysis. Results Among the 108 TB patients, intermediate-acetylators (IA ) was the most frequent NAT2 genotype with the proportion of 54.63%(59/108).The proportion of rapid-acetylators(RA)was 33.33%(36/108),slow-acetylators (SA)was 10.19%(11/108)and super-rapid acetylators was 1 .85 % (2/108). Among the 20 patients who developed drug-induced hepatitis,2 were RA,5 were SA and 13 were IA. Regarding NAT2 genotype,RA patients had a lower incidence of hepatotoxicity (OR =0.176,95 %CI :0.038-0.809,P =0.014)and SA patients were more likely to developed drug-induced hepatic injury (OR=4.556,95 %CI :1 .231 -16.854,P =0.044 ).Statistical analysis revealed that the frequency of variant diplotypes,NAT2*4/*6A (OR=7.741 ,95 %CI :2.653-22.586,P <0.01 )and NAT2 *6A/*6A (OR=15 .353,95 %CI :1 .506 -156.552,P =0.020)were significantly increased in TB patients with hepatotoxicity.NAT2 *4/*4 was less likely to developed hepatic injury (OR =0.176,95 %CI :0.038-0.809,P =0.014).Among the 58 culture-positive patients,12(31 .03%)were persistent culture positive after 2 months standard therapy.Early treatment failure was observed with significantly higher incidence rate in RA than other genotypes (OR = 7.200, 95 % CI :1 .794-28.900, P = 0.008). Conclusions In Chinese Han TB patients,IA is the most frequent NAT2 genotype.The SA status of NAT2 is a risk factor of isoniazid-induced hepatotoxicity.The diplotype of NAT2 *6A has clearly high risk of isoniazid-induced hepatotoxicity.In contrast,NAT2 * 4/* 4 is protective diplotype.RA is associated with early treatment failure in culture-positive patients.