Thyroid hormone analogues belong to a novel class of agents,which exert thyromimetic actions by selectively binding to thyroid hormone receptors,especially in the aspects of lipid lowering and calorigenesis.This review focuses on the research and application of selective thyroid hormone analogues in animal experiments and clinical trials.

Objective To explore the trend of Th_1/Th_2 bias in Hashimoto thyroiditis(HT)and their effects on the pathogenesis of HT.Methods The proportion and mean fluorescence intensity(MFI)of CCR5 and CD30 were examined on peripheral T lymphocytes by flow cytometry in patients with Hashimoto thyroiditis(HT)(n=21)and healthy controls(n=45).Results The proportion of both CD4~+CCR5~+and CD~+4 CD30~+ cells were significantly increased in HT group(P

A total of 1151 subjects were enrolled in this study.Metabolic syndrome (MS) was diagnosed according to the International Diabetes Federation (IDF) criteria.Significant differences in waist circumference,body mass index(BMI),diastolic blood pressure(DBP),systolic blood pressure(SBP),fat mass,Fat％ in different serum TSH levels were found.There were positive relation between fasting plasma glucose,DBP,SBP,and serum FT4 levels,between high density lipoprotein-cholesterol,DBP,SBP,waist circumference,fat mass,Fat％,and serum FT3 levels,even after adjustment for age and sex.Serum FT3 and FT4 levels were higher in the MS group than those in the control group.

Objective To investigate whether chlorophyllin could protect human umbilical vein endothelial cell (HUVEC) against oxidative damage by inducing the expression of heme oxygenase-1 (HO-1) and to explore the underlying mechanism.Methods The cellular protection of chlorophyllin against oxidative damage was detected by cell-survival assay with flow cytometry.The level of free radicals was detected directly by electron spin resonance spectra.The induced expression of HO-1 was shown by RT-PCR,Western blot,immunofluorescence confocal laser microscopy and enzymatic activity test.Whether the activation of PI3K/Akt pathway was involved was detected by Western blot.Results Chlorophyllin could protect HUVEC against oxidative damage caused by H2O2 via scavenging the excessive free radicals.Chlorophyllin treatment could induce expression of HO-1 in a dose- and time-dependent manner.The activation of PI3K/Akt pathway was required in the induction of HO-1.LY294002,the specific inhibitor of PI3K,could suppress the activation of PI3K/Akt and the induced expression of HO-1 in a dose-dependent manner.Conclusions Chlorophyllin shows cellular protection against oxidative damage by counteracting the excessive free radicals.Up-regulation of HO-1 expression plays a pivotal role in the protection of chlorophyllin,while the activation of PI3K/Akt signaling pathway is required in the induction of HO-1.

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.

OBJECTIVETo investigate the plasma level of extracellular histones in patients with silicosis, and to explore the role of extracellular histones in the pathogenesis of pulmonary fibrosis in silicosis.

METHODSSixty-two patients with silicosis were enrolled as the silicosis group, consisting of 23 patients with stage I silicosis, 25 with stage II silicosis, and 14 with stage III silicosis; sixty workers who had a history of occupational exposure to silica dust for more than 2 years and had not been diagnosed with silicosis were enrolled as the silica dust exposure group; sixty-five healthy workers without a history of occupational exposure to dust were enrolled as healthy controls. Enzyme-linked immunosorbent assay was applied to measure the plasma levels of plasma extracellular histone (H4) and transforming growth factor-β(TGF-β).

RESULTSCompared with healthy controls [(0.82±0.67) μg/ml], the silica dust exposure group[(4.14±2.85) μg/ml] and silicosis group[(9.50±5.04) μg/ml] had significant increases in plasma level of H4 (P<0.01). The plasma level of H4 was significantly correlated with the stage of silicosis(r=0.8955, P=0.0388). The silicosis group had a significantly higher plasma level of TGF-β than the silica dust exposure group and healthy controls(P <0.05). In the patients with silicosis, the plasma level of H4 was significantly correlated with that of TGF-β(r=0.5375, P<0.01).

CONCLUSIONThe plasma level of extracellular histones increases significantly in the pathogenesis of silicosis, and extracellular histones may play an important role in the progression of fibrosis in silicosis.

Case-Control Studies ; Disease Progression ; Dust ; Histones ; blood ; Humans ; Occupational Exposure ; Silicon Dioxide ; Silicosis ; blood ; pathology ; Transforming Growth Factor beta ; blood

Objective: In order to explore the role of heparan sulfate (HS) during the pathogenesis of acute respiratory distress syndrome (ARDS) , the protective effect of HS and its fragments against extracellular histones was compared. Methods: Calf thymus histones (CTH) were injected via femoral vein to induce ARDS in rats. HS, HS fragments or saline was intraperitoneally injected (10mg/kg, Q6h, 24h) to test the protective effect against CTH. The ratio of wet/dry lung weight, protein content in bronchoalveolar lavage fluid (BALF) , total leukocyte and neutrophil count in BALF were measured. Results: After CTH injection, the ratio of wet/dry lung weight (5.7±0.95) was much higher than the saline control group (3.1±0.15). The protein content (0.47±0.086mg/ml) , total leukocyte[ (97.4±15.6l) ×10⁴/ml] and neutrophil (18±3.4/LPF) in BALF were obviously increased compared with the saline control group. The intervention of HS evidently decreased ratio of wet/dry lung weight (4.2±0.41) , protein content[ (0.26±0.019) mg/ml], leukocyte[ (61.3±5.74) ×10⁴/ml] and neutrophil (12±1.8/LPF) in BALF. HS fragments also decreased ratio of wet/dry lung weight, protein content, leukocyte and neutrophil count in BALF though the strength was much less than HS. Conclusion HS and its fragments could provide protection against extracellular histones during the pathogenesis of ARDS. For the protective effect full length HS was much better than HS fragments.

Objective: Practice of setting up campus clinics in school,to explore adolescent outpatient service mode to better meet the diversified demands of teenagers,and to promote more effective implementation of adolescent health care. Methods: Campus-based adolescent outpatient clinics were established in 2 universities in Chongqing,a questionnaire survey was conducted among 136 students who participated in the consultation, campus-based outpatient services and adolescents’ satisfaction towards the services were analyzed. Hospital adolescent outpatient services were compared before and after the establishment of campus adolescent clinic. Results: Most of adolescent outpatient clinic in hospitals offered disease-based treatment instead of consultation. The overall satisfaction rate was 94.85%, and the satisfaction towards service ability, communication skills, outpatient time arrangement, and privacy protection was 96.32%, 96.32%, 88.97% and 94.12%, respectively. After the establishment of campus adolescent outpatient clinics, adolescent outpatient services in hospital increased dramatically including consultation. Conclusion It is necessary to offer adolescent outpatient services in schools, which are more helpful for the diversified demands of teenagers.

Objective: To explore the role of lysophosphatidic acid, vascular endothelial growth facor and endothelin in the pathogenesis of pulmonary fibrosis in coal workers’pneumoconiosis patients, the relationship of lysophosphatidic acid, VEGF and ET in serum was studied. Methods: Sixty two pneumoconiosis patients were selected as cases group, which included 23 cases of stage Ⅰ, 25 cases of stageⅡand 14 cases of stageⅢ. Twenty workers were selected as dust exposure group who exposed to coal dust for more than 2 years and had not been diagnosed as pneumoconiosis. Ten healthy people who had no occupational dust exposure were simultaneously selected as the control group. The serum levels of LPA, VEGF and ET were measured by ELISA. Results: The serum levels of VEGF and ET in coal dust exposed group and pneumoconiosis group were much higher than in the control group. The differences were statistically significant among the three groups (P<0.01) . The serum levels of LPA increased in the dust exposed group, stage Ⅰand stage Ⅱgroup. The serum levels of LPA correlated positively with the levels of VEGF and ET (P<0.05) . Conclusions The serum levels of LPA, VEGF and ET had evident correlation with the pulmonary fibrosis caused by coal dust, which indicate that LPA, VEGF and ET may play a pivotal role in the process of pulmonary fibrosis. The study will throw light on both pathogenesis and early intervention for pneumoconiosis.

Objective To determine the factors that influence the development of abnormal thyrotropin (TSH) level in an euthyroid population.Methods We conducted a follow-up study in 3 communities with different iodine status.Of the 3403 euthyroid subjects at baseline screened in 1999,80.1% ( n = 2727 ) was visited and sampled in 2004 for measuring TSH,thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb).Results Iodine status in the 3 communities were stable.Decreased TSH level( <0.3 mU/L) developed in 2.5% (n =68) of sampled subjects,while raised TSH level( > 4.8 mU/L) in 2.4% (n = 64).A logistic analysis showed that risk factors for developing decreased TSH level included positive conversion of TPOAb (OR = 5.5 ),positive TPOAb both in 1999 and in 2004 ( OR = 4.0),positive TgAb in 2004 ( OR = 3.7) and TSH < 1.0 mU/L in 1999 ( OR = 2.6).Risk factors involved in developing raised TSH level included iodine status of Zhangwu community ( OR = 4.1 ),iodine status of Huanghua community ( OR = 3.9),positive TgAb in 2004 ( OR = 3.7 ),positive TPOAb both in 1999 and 2004 (OR =3.6),positive conversion of TPOAb (OR =2.7) and TSH > 1.9 mU/L in 1999 (OR = 2.6 ).Conclusions Exposure to long-term iodine excess imposes danger of developing hypothyroidism.The risk will be even higher when exposing to iodine adequacy after correction of iodine deficiency.An interval between 1.0 and 1.9 mU/L of TSH level was optimul with the least probability of developing abnormal TSH level.