Objective To investigate the kinetic changes of inflammatory cell infiltration and thyroid autoantibodies in the development of iodine-induced autoimmune thyroiditis in NOD.H-2~(h4)mice.Methods Either 128 five-week-old NOD.H-2~(h4)mice or 128 Kunming mice were randomly divided into two groups,and received plain water or water containing 0.05% sodium iodide.At the time points of 1,2,4,8,12,16,and 24 week after receiving iodinated water,mice were anesthetized by diethyl ether and bled from eye socket vein,and their thyroid glands were collected.Indirect ELISA method was used to measure the levels of serum thyroglobulin autoantibodies (TgAb)and thyroid hormone.After being fixed with paraformaldehyde and embedded in paraffin,thyroid sections were stained with HE and used for morphometrieal analysis.Results In the iodine treated group of NOD.H-2~(h4) mice,autoimmune thyroiditis was observed as early as 1 week after they began receiving indinated water.The prevalence as well as the degree of autoimmune thyroiditis reached the maximum at 12 weeks and remained until 24 weeks.Serum TgAb level increased after 8 weeks of iodine ingestion in NOD.H-2~(h4) mice,then increased steadily throughout the 24 weeks of experiment.On the contrary,serum TgAb was not increased in the control group of Kunming mice.Conclusion Iodine may induce and exacerbate lymphocytic infiltration of the thyroid in genetically susceptible NOD.H-2~(h4) mice,and serum TgAb is just a marker of autoimmune thyroiditis.

OBJECTIVETo assess the relationships between iodine biological exposure and subclinical thyroid dysfunctions.

METHODSThe cross-sectional survey was performed to obtain the epidemiologic data of population in three communities with different iodine biological exposure: mild iodine deficiency [median urinary iodine concentration (MUI) of 50-99 microg/L], more than adequate iodine intake (MUI of 200-299 microg/L), and excessive iodine intake (MUI over 300 microg/L). Univariate and multivariate analysis (logistic regression analysis) were used to analyze the risk factors of subclinical hypothyroidism and subclinical hyperthyroidism.

RESULTSLogistic regression analysis with sex and age controlled suggested that more than adequate iodine intake (OR = 3.172, P = 0.0004) and excessive iodine intake (OR = 6.391, P = 0.0001) increased the risk of subclinical hypothyroidism, while excessive iodine intake decreased the risk of subclinical hyperthyroidism (OR = 0.218, P = 0.0001). Logistic regression analysis including interaction of iodine intake and antibodies [thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb)] suggested that excessive iodine intake was an independent risk factor of subclinical hypothyroidism (OR = 6.360, P = 0.0001), but independent protect factor of subclinical hyperthyroidism (OR = 0.193, P = 0.0001). More than adequate iodine intake and it's interaction with TgAb increased the risk of subclinical hypothyroidism independently, in addition, it decreased the risk of subclinical hyperthyroidism at the present of TPOAb.

CONCLUSIONBoth excessive iodine intake and more than adequate iodine intake could increase risk of subclinical hypothyroidism, supplement of iodine should be controlled to ensure MUI within the safe range.

Adult ; Autoantibodies ; blood ; China ; Cross-Sectional Studies ; Dose-Response Relationship, Drug ; Female ; Humans ; Hyperthyroidism ; chemically induced ; epidemiology ; metabolism ; Hypothyroidism ; chemically induced ; epidemiology ; metabolism ; Iodide Peroxidase ; immunology ; Iodine ; administration & dosage ; adverse effects ; urine ; Male ; Multivariate Analysis ; Risk Factors ; Surveys and Questionnaires ; Thyroglobulin ; immunology

OBJECTIVE: To evaluate the sub-acute oral effect of titanium dioxide (TiO₂) nanoparticles on the oxidation/antioxidation biomarkers and inflammatory cytokines in blood, liver, intestine, and colon in rats. METHODS: Twenty four 4-week-old clean-grade Sprague Dawley (SD) rats were randomly devided into 4 groups by body weight (n=6, control, low, middle, and high), in which the rats were orally exposed to TiO₂ nanoparticles at doses of 0, 2, 10 and 50 mg/kg body weight/day for 28 consecutive days separately. Food intake, body weight and abnormal behaviors during the experiment were recorded. The rats were euthanized on the 29th day. The blood was collected via abdominal aortic method and centrifuged to collect the serum. Tissues from liver, intestine and colon were collected and homogenated. Then enzyme-linked immunosorbent assay (ELISA) and microwell plate methods were used to detect oxidation/antioxidation biomarkers including superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-Px), total mercapto (T-SH), glutathione disulfide (GSSG), malomdialdehvde (MDA) and inflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in the serum, liver, intestine and colon in the rats. RESULTS: Compared with the control group, no significant differences in body weight, food intake and organ coefficients were observed in all the three groups after TiO₂ gavage. No significant changes in GSH, GSH-Px, T-SH, and IL-6 were observed. Compared with the control group, significant increase of SOD activity in serum in high dose group, signi-ficant increase of GSSG concentration in intestine in middle and high dose group and significant increase of MDA concentration in liver in low and high dose group were observed. Compared with the control group, a significant increase of TNF-α in liver in middle and high dose group was observed. CONCLUSION TiO₂ nanoparticle can increase antioxidant enzymes activities in blood, increase oxidative biomarkers in liver and intestine, increase inflammatory cytokines in liver in rats after a 28-day sub-acute orally administration. Among blood, liver, intestine, and colon, liver is most sensitive to the toxicity induced by TiO₂ nanoparticles, followed by intestine, blood, and colon in sequence.
Animals ; Antioxidants ; Biomarkers ; Cytokines ; Nanoparticles ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley ; Titanium

OBJECTIVETo investigate the effect of cigarette smoking on thyroid gland volume, thyroid function and thyroid autoantibodies in the areas with different iodine intakes.

METHODSA cross-sectional epidemiological study in Panshan (mild iodine-deficient area), Zhangwu (more than adequate iodine intake area) and Huanghua (iodine-excessive area) was conducted in 3761 subjects in 1999.80.2 % of them were followed up in 2004. Questionnaires, thyroid function, thyroid autoantibodies, urinary iodine concentration,and thyroid B ultrasound were performed.

RESULTSThe prevalence of goiter was higher in smokers than in non-smokers (15.1% vs. 11.5%, P< 0.05). The average thyroid volume was higher in smokers with phenomenon more obvious in Panshan and Huanghua areas. Data from logistic analysis showed that smoking cigarette was an independent risk factor of goiter. There was no difference in serum TSH and Tg level between smokers and non-smokers. The positive rate of TPOAb (>100 IU/ml) was higher in smokers than in non-smokers(10.8% vs. 9.0 % , P <0.05) and was especially obvious in Huanghua area. Smoking was a independent risk factor of increasing positive rate of TPOAb. During the prospective observation,it was found that the incidence of positive TPOAb(>,100 IU/ml) was 7.4% in the subjects that were from non-smokers turning to smokers and 2.9% in those whose smoking behavior did not change. Logistic analysis indicated that the shifting from non-smoking to smoking was independent risk factor for the increase on high incidence of positive TPOAb.

CONCLUSIONSmoking cigarette was a independent risk factor of goiter. Smoking was also a risk factor of increasing TPOAb positive rate. Shifting from not smoking to smoking was an independent risk factor of increasing high incidence of positive TPOAb.

Autoantibodies ; blood ; Cross-Sectional Studies ; Female ; Goiter ; blood ; epidemiology ; immunology ; physiopathology ; Humans ; Incidence ; Male ; Smoking ; adverse effects ; Thyroid Function Tests ; Thyroid Gland ; physiopathology ; Thyroid Hormones ; blood

Objective To investigate epidemiologieal characteristics of hypothyroidism and factors influencing its outcome in the areas with different iodine intakes.Methods An epidemiologic follow-up study of thyroid diseases was performed in Panshan (iodine deficient),Zhangwu [mild iodine deficiency before universal salt iodination (USI) and more than adequate iodine intakes after USI ] and Huanghua ( iodine excessive) in China.A total of 3 761 subjects were investigated in 1999,and 3 018 (80.2% ) of them were followed up in 2004.FT_4,FT_3,TSH,thyroid autoantibodies and urinary iodine concentration were determined and thyroid B ultrasound was performed in all participants.Results Five-year cumulative incidence of overt hypothyroidism was 0.23%,0.47% and 0.35% in Panshan,Zhangwu and Huanghua,respectively.Twenty patients with autoimmune- induced overt hypothyroidism did not comply with the physician's orders to take thyroxine.Thyroid function spontaneously turned to normal in 55% of them,turned to subclinical hypothyroidism in 20% and maintained overt hypothyroidism in 25%.Five-year cumulative incidence of subclinical hypothyroidism in Zhangwu (2.60%) and Huanghua (2.89%) were significantly higher than that in Panshan(0.23% ) (both P＜0.01 ).One hundred patients with subclinical hypothyroidism were followed up,and 5% of them developed overt hypothyroidism,66% turned to euthyroidism and 29% maintained subclinical hypothyroidism.Raised serum TSH (＞6 mU/L) in the original survey ( OR = 3.4),positive thyroid autoantibodies in the follow-up study ( OR = 5.3 ) and more than adequate iodine supplementation in the mild iodine-deficient population ( OR = 8.0) were risk factors influencing outcome of subclinical hypothyroidism.Conclusion More than adequate iodine supplementation among a population in the mildly iodine-deficient area may increase the incidence of overt and subolinical hypothyroidism, and also influence outcome of subclinical hypothyroidism.

Objective To analyze the relationship between different iodine intakes and epidemiological features of hyperthyroidism in 3 communities with different iodine intake levels,as well as to explore the risk factor for the pathogenesis of hyperthyroidism.Methods A cohort study was performed in 3 Chinese rural communities with long-term stable iodine nutrition status defined as mild deficient (Panshan),more than adequate (Zhangwu, previously mild iodine deficiency and salt iodization lasting 8 years until 2004) and excessive (Huanghua).A total of 3 761 (934 males,2 827 females) inhabitants aged above 13 participated in the original investigation in 1999 and 3 018(709 males,2 309 females) of them received identical examinations after 5 years.Results Median urinary iodine concentration of school-aged children was 87.61zg/L in Panshan,213.9?g/L in Zhangwu and 633.5?/L in Huanghua (P＜0.05) at fallowing up,and no statistic significance was found when comparing the corresponding data from original survey (83.5?g/L,242.9?g/L and 650.9?g/L).The accumulative incidence of hyperthyroidism was 13.6/1 000,9.4/1 000 and 8.1/1 000 (P＞0.05),being 16.4/1 000,11.2/1 000 and 9.1/1 000 (P＞0.05) in female,respectively in Panshan,Zhangwu and Huanghua.In original healthy subjects (without history of thyroid disease and overt thyroid dysfunction) merely with either positive thyroid peroxidase antibody (TPOAb＞50 IU/ml) or thyroglobulin antibody (TgAb＞40 IU/ml),the accumulative incidence of newly diagnosed hyperthyroidism was not significantly different among 3 communities in follow-up survey.TSH＜0.3 mIU/L,positive TPOAb or goiter in original healthy participants were associated with the occurrence of overt hyperthyroidism in 5 years [ Logistic Regression,OR = 5.7 (95% CI 2.1-15 ),OR = 3.8 (95% CI 1.7-8.7 ) and OR = 3.1 (95% CI 1.4-6.8) respectively].Conclusion Iodine supplementation in mild iodine deficient area does not increase the incidence of overt hyperthyroidism ultimately.Long-term excessive iodine intake does not affect the incidence and pattern of hyperthyroidism.TSH＜0.3 mIU/L,positive TPOAb and goiter in healthy individuals are the risk factors for hyperthyroidism.

Objective To perform a follow-up survey about thyroid disorders in three rural communities with different iodine intakes in China,observe the incidences and natural outcomes of positive thyroid autoantibodies in euthyroid population,and also explore the influence of iodine intakes on these outcomes and autoantibodies.Methods In 1999,a cross-sectional study on thyroid disorders was performed in three rural communities of Pansan ( mild iodine deficient area),Zhangwu ( more than adequate iodine intake area) and Huanghua (excessive iodine intake area) in China.The 5-year follow-up study was performed in 2004.Both in 1999 and 2004,serum levels of TSH,thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) were measured with the same method.Iodine in urine and B ultrasound on thyroid were also examined.Results Among the euthyroid subjects with normal TSH level in 1999,an increased prevalence of positive TPOAb in Zhangwu and an increased prevalence of positive TgAb in Hnanghua were observed in 2004 (both P＜0.05 ).Most of euthyroid subjects with positive TPOAb or positive TgAb in 1999 remained positive thyroid antibodies in 2004. The percentage was even higher in those with high levels of antibodies.Thyroid dysfunction was more frequent in subjects with positive TPOAb and/or TgAh than in those without thyroid antibodies (14.44% vs 3.11%,P＜0.01).For those with positive antibodies in 1999,the incidence of hypothyroidism in 2004 was 1.32%,8.46% and 15.38% in Pansan,Zhangwu and Huanghua,respectively (P＜0.05).The 5-year cumulative incidences of positive TPOAb (≥50 U/ml) and TgAb (≥40 U/ml) were 2.81% and 3.82%,respectively.The incidence of positive TPOAb was the highest in Zhangwu ( 3.84% ).The incidence of positive TgAb was the highest in Huanghua (5.07%),significantly higher than those in other two areas (P＜0.05).Conclusion The incidence of thyroid dysfunction is higher in subjects with positive antibodies than that in those with negative antibodies.The high iodine intake is a risk factor of hypothyroidism in subjects with positive thyroid antibodies.Sustained excessive iodine intake increases the incidence of positive thyroid antibodies.

OBJECTIVETo evaluate the application of dual-probe chromogenic in situ hybridization (dual-probe CISH) in analysis of HER2 gene status of breast cancer patients by comparison with fluorescence in situ hybridization (FISH). The potential impact of chromosome 17 polysomy in the determination of HER2 status was also studied.

METHODSOne hundred and forty-six cases of paraffin-embedded breast cancer tissues were retrieved. Analysis of HER2 gene and chromosome 17 copy numbers using CE-approved commercial kits of dual-probe FISH (for 146 cases) and dual-probe CISH (for 73 cases) were carried out. The results were interpreted according to ASCO/CAP, 2007 either HER2 gene copy number or the ratio of HER2/centromere 17 (CEN17).

RESULTSOf the 73 cases analyzed by both FISH and dual-probe CISH, the concordance rates for negative and positive results was 91.7% (33/36) and 97.4% (37/38) respectively, while the overall concordance rate between the two methods was 95.9% (70/73). Of the 146 cases analyzed by FISH, 13 cases were interpreted as equivocal if only HER2 copies were counted, compared with 8 equivocal cases by calculating the ratio of HER2/CEN 17. Moreover, 3 cases (4.8%) of the 63 HER2-positive cases determined by HER2 copies turned out to be HER2-negative when determined by the ratio of HER2/CEN 17; while using dual-probe CISH, 1 (3.0%) of the 33 positive cases turned out to be negative. In addition, when using FISH, there were more chromosome 17 polysomy cases (63.5%, 40/63) in the HER2-positive subgroup than HER2-negative subgroup (37.3%, 28/75) (P = 0.002).

CONCLUSIONSDual-probe CISH can achieve similar results as compared to FISH, indicating that this technology is a reliable alternative to FISH in HER2 testing. The accuracy can further be improved when HER2 and chromosome 17 are simultaneously tested and counted.

Breast Neoplasms ; genetics ; Carcinoma, Ductal, Breast ; genetics ; Chromosomes, Human, Pair 17 ; genetics ; Gene Dosage ; Genes, erbB-2 ; genetics ; Humans ; In Situ Hybridization ; methods ; In Situ Hybridization, Fluorescence ; Paraffin Embedding ; Polyploidy

OBJECTIVETo introduce Back-propagation (BP) neural network and genetic algorithm for multi-objective optimization of extraction technology of Cortex Fraxini.

METHODBP neural network was established and optimized with uniform design. Genetic algotithm was used for multi-objective optimization of extraction technology of cortex fraxini.

RESULTthe optimization of extraction was as follows: extraction temperature was 99 degrees C, concentration of EtOH was 50%, liquid-solid ratio was 7, extraction time was 94 min. The proportional error between predictive value and practical measured value was just -1.16% and -5.14%.

CONCLUSIONBack-propagation neural network and genetic algorithm for multi-objective optimization of extraction technology of cortex fraxini is advisable.

Algorithms ; Drugs, Chinese Herbal ; chemistry ; Neural Networks (Computer)

Objective of this study was to investigate the correlation of body-carried inherited paternal antigens (IPA) in one mother after delivery with pregnancy thrombocytopenia. The changes of platelet (Plt) count in the mother who delivered 2 years ago and her child who is now one year's old were detected, routine tests included Helicobacter pylori, CMV, EBV, parvovirus and other herpes virus's infection were carried out. Eight insertion or deletion sites (InDel) SNP with strong polymorphisms in Chinese population was selected to detect IPA from a genomic library, then primers were designed, the nested PCR and real-time quantitative PCR were used to detect 54 healthy mother-child pairs, the obtained average value was taken as the control, finally two InDel polymorphism sites between mother and child were used to identify the mother/child microchimerism. The IPA of the mother were examined at 4 time points. The results showed that the Plt level of the mother who had suffered thrombocytopenia since 20 weeks after pregnancy reduced to 10 × 10(9)/L. After using gamma globulin, the Plt count increased gradually, but the Plt count decreased rapidly when withdrawal. This patient did not have the infections of virus and Helicobacter pylori. IPA average value of 54 cases were from 10(-5) to 10(-4). At 67 d after delivery, the Plt count of the mother was 14 × 10(9)/L, IPA was 3.45 × 10(-3), which was 30 times higher than the normal. In one month after treatment the IPA was 1.3 × 10(-4) (Plt 256 × 10(9)/L), 5 months later it was 1.2 × 10(-4) (Plt 158 × 10(9)/L), and 6 months later it was 1.5 × 10(-4) (Plt 325 × 10(9)/L). When IPA reached the normal level, the Plt count returned to normal. Her child suffered thrombocytopenia (4 × 10(9)/L) one month after he was born, then recovered after high-dose gamma globulin therapy. It is concluded that abnormal high level IPA may lead to pregnancy thrombocytopenia.
Antigens ; genetics ; Chimerism ; Fathers ; Female ; Humans ; Infant, Newborn ; Male ; Pregnancy ; Pregnancy Complications, Hematologic ; genetics ; Thrombocytopenia ; etiology ; genetics