Effect of Notch-Hes1 signaling blockade by a γ-secretase inhibitor on the expression of γδT17 cells in a mouse model of psoriasis-like skin inflammation / 中华皮肤科杂志

Objective@#To evaluate the effect of Notch-Hes1 signaling blockade by a γ-secretase inhibitor on the expression of γδT17 cells in a mouse model of psoriasis-like skin inflammation.@*Methods@#Forty-five healthy specific pathogen-free (SPF) male BALB/c mice were randomly divided into control group, model group and intervention group by simple random sampling. The model group and intervention group were both topically treated with imiquimod 5% cream (62.5 mg once a day) on the shaved back, the intervention group were then intraperitoneally injected with the γ-secretase inhibitor DAPT (10 mg/kg once a day) immediately after topical application of imiquimod, and the control group were topically treated with equivalent amount of vaseline once a day. After 6-day treatment, psoriasis area and severity index (PASI) was used to evaluate changes of skin lesions. On day 7, blood samples were obtained from all the mice through heart puncture after anesthetization, and spleen and skin tissues were acquired to prepare single cell suspension. Spleen index was compared among the 3 groups. Skin tissues on the mouse back were resected and subjected to hematoxylin-eosin staining to observe histopathological changes. Flow cytometry was performed to determine the percentage of γδT17 cells in the spleen and skin tissues, real-time reverse transcription (RT) -PCR to measure the mRNA expression of Hes1 in single cell suspension of the spleen, and enzyme-linked immunosorbent assay (ELISA) to determine the serum level of interleukin (IL) -17A. Statistical analysis was carried out by using one-way analysis of variance and repeated measures analysis of variance for comparison of indices among groups, and Pearson correlation analysis for evaluating the correlation between different indices.@*Results@#Twenty-four hours after the final treatment, the intervention group showed milder psoriasis-like skin inflammation, lower PASI score, and milder degree of epidermal thickening and dermal inflammatory cell infiltration compared with the model group. The model group showed significantly increased spleen index (12.534 ± 1.636) , proportions of γδT17 cells in the spleen (24.659% ± 4.603%) and skin tissues (22.127% ± 5.670%) , mRNA expression of Hes1 in the spleen (4.867 ± 0.543) , and serum level of IL-17A ([22.478 ± 2.776] ng/L) compared with the control group (all P < 0.01) . However, the above indices were significantly lower in the intervention group (9.449 ± 1.040, 14.966% ± 5.770%, 13.631% ± 5.946%, 2.541 ± 0.347, [18.639 ± 1.816] ng/L) than in the model group (all P < 0.01) . In the model group and intervention group, there were positive correlations between the proportions of γδT17 cells in the spleen and serum levels of IL-17A (r = 0.56, 0.53 respectively, both P < 0.05) , between the proportions of γδT17 cells in skin lesions and PASI scores (r = 0.56, 0.52 respectively, both P < 0.05) , as well as between the mRNA expression of Hes1 in the spleen and the proportions of γδT17 cells (r = 0.61, 0.58 respectively, both P < 0.05) or serum levels of IL-17A (r = 0.60, 0.54 respectively, both P < 0.05) .@*Conclusion@#Notch-Hes1 signaling blockade by γ-secretase inhibitor can markedly inhibit the expression of γδT17 cells, and effectively alleviate the severity of psoriasis-like skin inflammation in mouse models.

Association between macrophage migration inhibitory factor (MIF) -173G/C gene polymorphism and susceptibility to immune-related diseases in Chinese Han population: a meta-analysis / 中华微生物学和免疫学杂志

Objective@#To investigate the association between macrophage migration inhibitory factor (MIF) -173G/C gene polymorphism and the susceptibility to immune-related diseases in Chinese Han population.@*Methods@#Databases of Wanfang, China National Knowledge Infrastructure (CNKI), PubMed, Excerpta Medica dataBASE (EMbase) and Web of Science (WOS) were comprehensively searched for pertinent articles published in Chinese and English. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used as effect size measures. Publication bias was examined by Brgge′s funnel plots and Egger′s test. Revman 5.3 and STATA 12.0 software were used for statistical analysis.@*Results@#Nine articles were included in this meta-analysis and the studied immune-related diseases included UC (ulcerative colitis), CD (Crohn′s disease), RA (rheumatoid arthritis), PS (psoriasis), asthma, BD (Behçet′s disease), VKH (Vogt-Koyanagi-Harada syndrome), AOSD (adult-onset Still′s disease) and AD (atopic dermatitis). The overall result of the meta-analysis showed that the MIF 173G/C gene polymorphism could increase the susceptibility to immune-related diseases in Chinese Han people (recessive genetic model: OR=1.92, 95%CI: 1.44-2.58; dominant genetic model: OR=1.44, 95%CI: 1.28-1.61; allele model: OR=1.34, 95%CI: 1.22-1.34; homozygote model: OR=1.98, 95%CI: 1.51-2.60; heterozygote model: OR=1.24, 95%CI: 1.11-1.40; all P<0.01). In addition, a subgroup analysis of the North and South of China showed that except for the heterozygote model in the North group, the recessive model (OR=2.03, 95%CI: 1.24-3.31), dominant genetic model (OR=1.51, 95%CI: 1.24-1.83), allele model (OR=1.37, 95%CI: 1.22-1.54) and homozygote model (OR=2.08, 95%CI: 1.31-2.30) all had statistical significance. All of the five models in the South group showed statistical significance (recessive model: OR=1.88, 95%CI: 1.31-2.69; dominant genetic model: OR=1.40, 95%CI: 1.22-1.61; allele model: OR=1.29, 95%CI: 1.10-1.52; homozygote model: OR=1.93, 95%CI: 1.38-2.71; heterozygote model: OR=1.19, 95%CI: 1.08-1.31; all P<0.05).@*Conclusion@#The polymorphism of MIF -173G/C gene may be a susceptible gene to immune-related diseases in Chinese Han people.

Effect of Notch1 signaling pathway on the differentiation and function of Th17 cells in peripheral blood of patients with psoriasis / 中华皮肤科杂志

Objective To evaluate the effect of Notch 1 signaling pathway on the differentiation and function of Th17 cells in peripheral blood of patients with psoriasis.Methods Peripheral blood samples were obtained from 35 patients with psoriasis and 32 healthy controls.Flow cytometry was performed to determine the proportion of Th17 cells in CD4+ T cells in peripheral blood mononuclear cells (PBMCs),real-time RT-PCR to measure the mRNA expression of retinoic acid receptor-related orphan receptor γt (RORγt),interleukin (IL)-17,Notch 1 and hairy-and-enhancer-of-split-1 (Hes-1),and enzymelinked immunosorbent assay (ELISA) to detect levels of IL-17 in the serum and culture supernatant of PBMCs stimulated with phorbol ester,calcium ionophore and brefeldin A.The correlation of Notch 1 mRNA expression with psoriasis area and severity index (PASI) was analyzed,so were its correlation with the proportion of Th17 cells,mRNA expression of RORγt,and mRNA and protein expression of IL-17.PBMCs isolated from the patients with psoriasis were divided into 5 groups to be treated with γ-secretase inhibitor N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butyl ester (DAPT) at different concentrations of 0(control group),2.5,5.0,10.0 and 20.0μmol/L,respectively,so as to evaluate the effects of blocking the Notch1 signaling pathway by DAPT on the proportion of Th17 cells in PBMCs,levels of RORγt and IL-17.Results Compared with the healthy controls,patients with psoriasis showed a significant increase in the proportion of Th17 cells in CD4+ T cells in PBMCs (2.863％ ± 0.969％ vs.0.604％ ± 0.124％,P ＜ 0.01),mRNA expression of RORγt (5.255 ± 0.998 vs.1.530-± 0.485,P ＜ 0.01),Notch1 (6.743 ± 1.756 vs.1.731 ± 0.456,P ＜ 0.01),Hes-1 (6.384 ± 1.665 vs.1.627 ± 0.485,P ＜ 0.01) and IL-17 (6.944 ± 1.626 vs.1.698 ± 0.329,P ＜ 0.01),and serum level of IL-17 ([36.444 ± 5.936] ng/L vs.[11.762 ± 2.260] ng/L,P ＜ 0.01).Among the patients with psoriasis,the mRNA expression of Notch1 was positively correlated with PASI scores,proportion of Th17 cells,mRNA expression of RORγt and IL-17,and serum level of IL-17 (r =0.584,0.544,0.518,0.549 and 0.511,respectively,all P ＜ 0.05).There were significant differences in the proportion of Th17 cells,mRNA expression of RORγt and IL-17,and level of IL-17 in the culture supematant among the control group,2.5-,5.0-,10.0-and 20.0-μmol/L DAPT groups (F =79.527,82.239,78.086 and 80.558,respectively,all P ＜ 0.01).The above indices were significantly lower in the 2.5-,5.0-,10.0-and 20.0-μmol/L DAPT groups than in the control group (all P ＜ 0.05),and decreased along with the increase of DAPT concentrations.Conclusion Notch1 signaling pathway can promote the differentiation of Th17 cells and the expression of RORγt,IL-17 and Hes-1 in the peripheral blood of patients with psoriasis.

Role of Notch-Dll4 signaling pathway in autoimmune damage of Hashimoto thyroiditis / 中华内分泌代谢杂志

Forty patients with Hashimoto thyroiditis ( HT) and 20 healthy subjects with matched age-and sex-features ( NC) were selected. The patients with HT were further divided into normal thyroid function ( HT-A) and hypothyroidism ( HT-B) groups. Real-time PCR was performed to evaluate the expressions of Notch1, Dll4, and retinoid-related orphan receptor ( ROR )-γt mRNA. Flow-cytometry was used to detect the percentage of Th17 cells. Thyroid function, thyroid peroxidase antibody ( TPOAb) , and thyroglobulin antibody ( TgAb) were detected by electrochemiluminescence immunoassaies. The results showed that the Notch1, Dll4, ROR-γt mRNA levels and Th17 cell percentage were significantly increased in HT group compared with NC group (all P<0.01), especially in HT-B group. In HT patients, Notch1 and Dll4 mRNA expression levels were positively correlated with Th17 cell percentage and its transcription factor ROR-γt ( all P<0.01) . Besides, there were significantly positive correlations of Notch1 and Dll4 mRNA expressions with TPOAb and TgAb titers (P<0.05 or P<0.01). These results suggest that Notch1-Dll4 signaling pathway might be involved in the pathogenesis of thyroid-specific autoimmune damage by regulating Th17 cells in HT patients.

Notch1 signaling pathway regulates Th17 cell differentiation and function in murine psoriasis model / 中国免疫学杂志

Objective:To determine the effect of Notch1 signaling pathway on the differentiation and function of Th17 cells in murine psoriasis model.Methods: BALB/c mice were randomly divided into psoriasis model group and control group.Murine psoriasis model was established by topical 5% imiquimod application in combination with intraperitoneal injection of α-2b interferon.The CD4+ T lymphocytes were isolated by magnetic activated cell sorter (MACS).Flow cytometric analysis (FCM) was performed to detect the percentage of Th17 cells.Real-time RT-PCR was employed to measure the mRNA levels of RORγt,IL-17A,Notch1 and Hes-1.The CD4+ T lymphocytes were then divided into γ-secretase inhibitor DAPT groups and control group,and the expression differences of Notch1 signaling molecule and its target gene Hes-1 mRNA levels,Th17 cell percentage,RORγt and IL-17A mRNA levels,and IL-17A concentrations in cell-free supernatant were detected.Results: The expression levels of Th17 cell percentage and RORγt,IL-17A,Notch1 and Hes-1 mRNA in CD4+ T lymphocytes of murine psoriasis model were significantly higher than control mouse[(2.97±0.86)% vs.(0.65±0.11)%,t=15.083;(5.75±0.61) vs.(1.57±0.43),t=21.630;(7.83±0.97) vs.(1.63±0.31),t=25.348;(7.10±1.37) vs.(1.47±0.34),t=17.386;(7.30±1.15) vs.(1.67±0.48),t=18.840,respectively,all P<0.01].Compared with control group,Th17 cell percentage,mRNA expression levels of Notch1,Hes-1,RORγt and IL-17A,and IL-17A concentrations in cell-free supernatant from cultured CD4+ T lymphocytes of murine psoriasis model were dramatically decreased in DAPT treated groups in a dose-dependent way (F=74.368,89.719,126.572,94.558,124.323 and 123.231 respectively,all P<0.01).Conclusion: Notch1 signaling pathway can regulate the differentiation and function of Th17 cells in murine psoriasis model,and may have potential value for the target immunotherapy of psoriasis.

Presence and the significance of Th9 cells in patients with hashimoto thyroiditis / 中华微生物学和免疫学杂志

Objective To investigate the presence and significance of Th9 cells and the related transcription factor ( PU.1 ) and cytokine ( IL-9 ) in peripheral blood of patents with hashimoto thyroiditis ( HT) .Methods Thirty patients with HT and thirty age/gender matched healthy subjects were recruited in this study.The peripheral blood and serum samples were collected from each subject.The percentages of Th9 cells and the transcriptional levels of PU.1 in peripheral blood mononuclear cells ( PBMCs) were meas-ured by flow cytometry analysis and real-time RT-PCR.The concentrations of IL-9, the functions of thyroid and the titers of thyroid-specific autoantibodies ( TPOAb and TgAb) in serum samples were detected by using enzyme-linked immunosorbent assay ( ELISA ) and electrochemiluminescence immunoassay analysis ( ECLIA) .Results Compared with healthy subjects, the percentages of Th9 cells and the expression of PU.1 at mRNA level in PBMCs and the concentrations of IL-9 in serum samples were all significantly in-creased in patients with HT [(1.49±0.68)%vs (0.87±0.24)%], 4.91±2.14 vs 1.66±0.52, (26.90± 7.74) pg/ml vs (16.71±5.87) pg/ml, all P<0.01).Serum concentrations of IL-9 were positively correla-ted with the percentages of Th9 cells (r=0.419, P=0.021).Moreover, the percentages of Th9 cells were positively correlated with the titers of TPOAb and TgAb in serum samples (r=0.394, P=0.032;r=0.457, P=0.011) of patients with HT.Conclusion The levels of Th9 cells and the related cytokine IL-9 were in-creased in the peripheral blood of patients with HT.A positive correlation was found between the percentage of Th9 cells and the titers of thyroid-specific autoantibodies.This study indicated that Th9 cells might be in-volved in the pathogenesis of autoimmune damage in thyroid.

Expression of miR-155 in peripheral blood and skin lesions from as well as its relationship with Th17 cells in patients with atopic dermatitis / 中华皮肤科杂志

Objective To detect the expressions of miR-155,T helper type 17 (Thl7) cells,and Th17 cellspecific transcription factor RORγt and effector cytokine interleukin (IL)-17 in peripheral blood and skin lesions from,and to evaluate their relationship in,patients with atopic dermatitis (AD).Methods Peripheral blood was obtained from 37 patients with AD and 33 age-and sex-matched healthy controls,and biopsy specimens from the lesional and perilesional skin of five patients with severe AD as well as from the normal skin of five healthy human controls.Real-time fluorescence-based reverse transcription (RT)-PCR was employed to measure the mRNA expression levels of miR-155,RORγt and IL-17 in peripheral blood mononuclear cells (PBMCs) and skin specimens,flow cytometry to detect the percentage of Th17 cells in PBMCs,enzyme-linked immunosorbent assay (ELISA) to determine the plasma concentration of IL-17.Statistical analysis was done using independent sample's t test,one-way analysis of variance followed by the least significant difference test,and linear correlation analysis.Results Compared with the healthy controls,the patients with AD showed a significant increase in Th17 cell percentage (1.78％ ± 0.52％ vs.0.47％ ± 0.15％,P＜ 0.01),mRNA expression levels of miR-155 (5.78 ± 1.78 vs.1.82 ± 0.46,P＜ 0.01),RORγt (6.08 ± 1.04 vs.1.64 ± 0.52,P＜ 0.01) and IL-17 (7.09 ± 1.75 vs.1.71 ± 0.46,P＜ 0.01),as well as in the plasma concentration of IL-17 ((2.51 ± 6.15) pg/ml vs.(11.80 ± 2.24) pg/ml,P＜ 0.01).There was a sequential decrease in the expression levels of miR-155,RORγt and IL-17 mRNA from lesional skin,perilesional skin to normal skin (F =41.803,17.040 and 37.064 respectively,all P ＜ 0.01).The miR-155 mRNA expression level in PBMCs was positively correlated with the SCORing Atopic Dermatitis (SCORAD) index,Th17 cell percentage,RORγt and IL-17 mRNA expression levels as well as IL-17 plasma concentration (r =0.405,0.426,0.402,0.410 and 0.408 respectively,all P ＜ 0.05).Similarly,the miR-155 expression level was positively correlated with RORγt and IL-17 mRNA expression levels in lesional and paralesional specimens (r =0.428 and 0.435 respectively,both P ＜ 0.05).Conclusion The up-regulated expression of miR-155,Th17 cells and their effector cytokine IL-17 may be associated with the development of AD.

Expression of macrophage migration inhibitory factor in peripheral blood of patients with Hashimoto's thyroiditis and its clinical significance / 中华内分泌代谢杂志

The levels of macrophage migration inhibitory factor (MIF) in peripheral blood mononuclear cell (PBMC) and serum in patients with Hashimoto's thyroiditis (HT) were detected by real-time PCR and ELISA,respectively.The results revealed that the expression of MIF mRNA in PBMC ( Z =-4.276,P＜0.01 ) and protein level in serum ( Z=-5.358,P＜0.01 ) were increased in HT patients,and positively correlated with thyroid specific autoantibodies and TSH levels.

Evaluation of balance between regulatory T cells and T helper 17 cells in patients with atopic dermatitis / 中华皮肤科杂志

[Objective] To assess the role of imbalance between regulatory T (Treg) cells and T helper 17 (Th17) cells in the pathogenesis of atopic dermatitis (AD).[Methods] Peripheral blood was obtained from 41 patients with AD and 38 age- and sex-matched healthy controls.Flow cytometry was performed to determine the percentage of Treg cells (CD4+CD25+Foxp3+ T cells) and Thl7 cells (CD4+ILl7+ T cells),real-time quantitative reverse transcription (RT)-PCR to detect the mRNA expressions of Foxp3 and RORγt,which are the specific transcription factors of Treg and Th17 cells respectively.Serum concentrations of transforming growth factor (TGF)-β,IL-17 and IL-23 were measured by enzyme linked immunosorbent assay(ELISA).Data were statistically assessed by independent-samples t test and Pearson correlation analysis.[Results] The patients with AD showed an obvious decrease in Treg cell percentage,transcription factor Foxp3 mRNA level and Treg/Th17 ratio (2.01％ ± 0.57％ vs.5.04％ ± 1.44％,t =12.47,P＜ 0.01; 0.65 ± 0.19 vs.1.71 ± 0.69,t=9.47,P＜0.01; 1.26 ± 0.61 vs.14.53 ± 5.77,t =14.11,P ＜ 0.01),but a significant increase in peripheral Th17 cell percentage and transcription factor RORγt mRNA level (1.77％ ± 0.55％ vs.0.39％ ± 0.15％,t =14.82,P ＜0.01; 5.97 ± 1.45 vs.1.49 ± 0.57,t =17.78,P ＜ 0.01 ) compared with the healthy controls.Further comparison revealed that Treg/Th17 ratio was significantly lower in patients with acute AD than in those with subacute AD (0.88 ± 0.04 vs.1.29 ± 0.11,t =4.02,P ＜ 0.01 ) and those with chronic AD (2.05 ± 0.24,t =4.83,P ＜ 0.01 ),statistically different between patients with subacute AD and chronic AD (t =2.89,P ＜ 0.05).There was no significant difference in the serum concentration of TGF-β between patients with AD and healthy controls ((15.28 ± 2.34) μg/L vs.(16.56 ± 3.27) μg/L,t =1.96,P＞ 0.05).A significant increase was observed in the serum levels of IL-17 and IL-23 in patients with AD compared with those in the healthy controls( (33.24 ± 7.06)ng/L vs.(11.68 ± 2.67) ng/L,t =17.96,P＜ 0.01; (56.35 ± 12.16) ng/L vs.(18.43 ± 3.90) ng/L,t =18.36,P＜ 0.01).In patients with moderate and severe AD,SCORing atopic dermatitis (SCORAD) index was negatively correlated with the percentage of Treg ceils (r =-0.40,P＜ 0.05 ),but positively correlated with that of Th17 cells (r =0.42,P ＜ 0.05 ).[Conclusion]s There exists a change in Treg/Th 17 ratio,mRN A expressions of RORγt and Foxp3,and serum levels of relevant cytokines in patients with AD,which may lead to immune imbalance and subsequently contribute to the development of AD.

Detection of macrophage migration inhibitory factor in peripheral blood mononuclear cells, sera and skin tissue fluid of patients with vitiligo vulgaris / 中华皮肤科杂志

ObjectiveTo detect the expression levels of macrophage migration inhibitory factor (MIF) in peripheral blood mononuclear cells (PBMCs),sera and skin tissue fluid from patients with vitiligo vulgaris,and to investigate their clinical significance.MethodsThirty-nine patients with vitiligo vulgaris and 31 age- and sex-matched normal human controls were recruited in this study.Real-time reverse transcription-PCR was employed to assess the expressions of MIF mRNA in PBMCs,enzyme-linked immunosorbent assay (ELISA) to detect the concentrations of MIF in sera and skin tissue fluid from these subjects.ResultsPatients with vitiligo vulgaris showed a significantly higher level of MIF mRNA in PBMCs (6.70 (2.64 - 8.65) vs.1.67 (1.24 - 2.45),Z=5.895,P＜ 0.05),MIF protein in sera (32.76 (10.67 - 40.98) μg/L vs.7.89 (6.13 - 9.54) μg/L,Z=5.936,P ＜ 0.05 ) and skin tissue fluid ( 167.80 ( 107.40 - 219.60) μg/L vs.42.44 (32.29 - 49.74) μg/L,Z =4.715,P ＜ 0.05) compared with the normal human controls.The expression levels of MIF mRNA in PBMCs,and MIF protein in sera and skin tissue fluid were also higher in patients with progressive vitiligo than in those with stable vitiligo (7.89 (3.89 - 9.12) vs.5.62 (2.23 - 7.29),Z=2.213,P＜ 0.05; 37.80 (29.50 - 45.70) μg/L vs.22.70 (9.36 - 37.78) μg/L,Z=2.141,P＜ 0.05; 211.50 (131.70 - 248.75) μg/L vs.144.65 (89.13 - 167.30) μg/L,Z =2.100,P ＜ 0.05).In addition,the vitiligo area severity index (VASI) score was positively correlated with the expression levels of MIF mRNA in PBMCs (r =0.486,P ＜ 0.05)and MIF protein in sera (r =0.453,P ＜ 0.05).ConclusionMIF might play a certain role in the pathogenesis of vitiligo vulgaris.

The Correlation between Thyrotropin and Dyslipidemia in a Population-based Study

This study investigated the relationship between serum thyrotrophin levels and dyslipidemia in subclinical hypothyroid and euthyroid subjects. A total of 110 subjects with subclinical hypothyroidism and 1,240 euthyroid subjects enrolled in this study. Patients with subclinical hypothyroidism had significantly lower high density lipoprotein cholesterol (HDL-C) levels than those who were euthyroid. The lipid profiles were each categorized and mean thyrotrophin levels were higher in subjects in the dyslipidemia subclasses than subjects in the normal subclasses. Thyrotrophin was positively associated with serum triglyceride and negatively associated with serum HDL-C in women. Thyrotrophin was also positively associated with total cholesterol (TC) in the overweight population along with TC and LDL-C in overweight women. In the euthyroid population, thyrotrophin was positively associated with TC in the overweight population. In conclusion, serum thyrotrophin was correlated with dyslipidemia in subclinical hypothyroid and euthyroid subjects; the correlation was independent of insulin sensitivity.

Relationship betweenserum TSH and dyslipidemia / 中华内分泌代谢杂志

Objective To investigate the relationship between serum thyrotrophin(TSH)and dyslipidemia in subclinical hypothyroid and euthyroid subjects. Methods An epidemiological study on diabetes and thyroid diseases was performed in Dadong community, Shenyang city, in 2007. 110 subjects with subclinical hypothyroidism(SCH)and 1 240 euthyroid subjects were enrolled in the study. Neither history of thyroid diseases nor administration of thyroid-related and lipid-regulating medicines were reported in these subjects. The levels of serum thyroid hormones, lipids, fasting plasma glucose(FPG), and insulin were determined. Results (1)Patients with SCH had significantly lower HDL-C levels than those who were euthyroid.(2)According to the guideline of treatment of adult dyslipidemia in China, the lipid profiles were each categorized. Mean TSH levels were higher in subjects in the dyslipidemia subclass than subjects in the normal subclass. The differences were significant in high LDL-C subclass in overweight individuals. In euthyroid overweight women, mean TSH levels were significantly higher in high LDL-C subclass. In the euthyroid population, TSH was positively associated with total cholesterol in overweight population. The association was not modified by the homestasis model assessment for insulin resistance(HOMA-IR)values.(3)TSH was associated positively with serum triglycerides and negatively with serum HDL-C in women. TSH was positively associated with total cholesterol in overweight population and positively associated with total cholesterol and LDL-C in overweight women after adjustment for age, sex, and body mass index. Conclusion Raised serum TSH seems to be a risk factor of dyslipidemia in subclinical hypothyroid and euthyroid subjects, which is independent of insulin sensitivity.

The reference range of serum thyrotropin in iodine-sufficient areas: An epidemiological study / 中华内分泌代谢杂志

Objective To verify the criteria proposed by National Academy of Clinical Biochemistry(NACB)guidelines in investigating the factors that affect serum TSH determination, and to determine the reference range of serum TSH in iodine-sufficient areas of China. Methods In 2007, 5 348 inhabitants were enrolled from 3 iodine-sufficient areas of Liaoning Province, and were asked to fulfill the questionnaire. Serum TSH, thyroid peroxidase antibody(TPOAb), and thyroglobulin antibody(TgAb)were determined, and thyroid ultrasonography was carried out. Results The distribution of TSH levels was skewed in healthy people and closely fit the curve of Gaussian distribution after logarithmic transformation. The levels of TSH in subjects of 12-19 years of age were significantly higher than those of other age groups(P＜0.01), and no significant difference was found among the latter groups. TSH level in females [(1.68±1.90)mIU/L] was higher than in males[(1.45±1.92)mIU/L, P＜0.01]. The reference range of TSH was 0.43-4.74 mIU/L in males, and 0.48-5.39 mIU/L in females. Family history of thyroid disease, abnormal thyroid ultrasonography, and positive thyroid antibodies were the factors that influenced TSH level. Conclusion The reference range of serum TSH in iodine-sufficient areas of China is established.

Caregivers of Elderly with Dementia in Shanghai / 中国康复理论与实践

@#ObjectiveTo analyze burden and tolerance of caregivers of elders with dementia in Shanghai.MethodsOn the basis of surveyed before, total 1271 caregivers of elders with dementia were investigated with the questionnaire that concerned the demographic characteristics, influence on body, psychology, life and tolerance.ResultsNearly 60% of the caregivers felt stress, nearly 40% of the caregivers thought that mental pressure had a negative impact on their health as a result of caring patients. Most of the caregivers responded with tolerance to non-adaptive behavior.ConclusionDementia caregivers are old, the burden is heavy. It is necessary to establish a social support system for elderly with dementia as soon as possible.

Evaluation of Behavioral and Psychological Symptoms in Elderly with Dementia in Shanghai / 中国康复理论与实践

@# ObjectiveTo evaluate probability and severity of behavioral and psychological symptoms in dementia (BPSD) in elderly with dementia in Shanghai.MethodsOn the basis surveyed before, total 1271 elderly with dementia were investigated with the international neuropsychiatric inventory (NPI) to evaluate BPSD.ResultsThe proportion of elderly with dementia that had BPSD was 50.95% , it was 32.17% for clinical significant disturbance (CSD). The symptoms had greatest impact on the caregivers were paranoia (2.32±1.48), followed by abnormal motor behavior (2.30±1.31) and hallucinations (2.16±1.25). The severity rating included mild 620 cases, moderate 238 cases, and severe 406 cases.ConclusionThe incidence rate of BPSD in elderly with dementia was high. The standard of severity grading should be selected with purposes.

A Cross-Sectional Study of Senile Dementia in Shanghai / 中国康复理论与实践

@#ObjectiveTo investigate the epidemiology of senile dementia in Shanghai.Methods15158 residents aged 65 or over were selected by stratified random cluster sampling from 3 districts in Shanghai. Two stages was carried to ascertain dementia: in the first stage, Mini Mental State Examination (MMSE) and Activity of Daily Living Scale (ADL) were used as screening tools; in the second stage, DSM-Ⅳ criteria for dementia was applied to diagnosis.ResultsScreening positive rate of MMSE and ADL are both 9.9%. 1271 cases of elderly with dementia were identified. The crude and age-standardized prevalence in residents aged 65 or over was 8.1% and 6.1%. The female, older age, lower education and worse marriage seemed to be more susceptible to senile dementia(P<0.01).ConclusionSenile dementia has become one of major diseases harmful to elderly's health.

Levothyroxine treatment for subclinical hypothyroidism during pregnancy and the subsequent neuropsychological development of the offspring: a prospective epidemiological study / 中华内分泌代谢杂志

Objective To prospectively observe the effect of levothyroxine treatment on neuropsychological development in offspring of pregnant women with subclinical hypothyroidism. Methods Twenty-three pregnant women with subclinical hypothyroidism received levothyroxine therapy (SCH+LT4 group) and 17 who did not receive levothyroxine ( SCH group) were enrolled; 24 pregnant women with normal thyroid function were referred as controls (C group). All the subjects underwent the planned thyroid tests regularly. Serum TSH, TT4, FT4, TT3,FT3, TPOAb, and TgAb levels were determined. Their 14-30 month-old children underwent the tests relating to intelligence and motor activity with the Bayley scale. Results In SCH group, SCH+LT4 group, and C group, the MDI were 115. 12, 118.56, and 117.63, respectively. And the PDI were 115.47, 120.65, and 117.50,respectively. The MDI and PDI were the highest in SCH+LT4 group and were the lowest in SCH group. Serum TSH levels remained above 2.0 mIU/L during the whole course of pregnancy in SCH group and higher than that in C group at all time points ( P＜0.05 ). Serum TT4 and FT4 levels were lower in SCH group than in C group at all time points except G28 and G32. The baseline TSH level in SCH+LT4 group was the highest ( P＜0.01 ), their TT4 and FT4 levels were the lowest among the three groups. In SCH + LT4 group, serum TSH, TT4, and FT4 levels were similar to C group after L-T4 treatment. Conclusion The prompt L-T4 treatment can maintain normal TSH levels in pregnant women with subclinical hypothyroidism during the whole course of pregnancy, and impairment of neuropsychological development in infants may be avoided.

Impact of maternal subclinical hypothyroidism during the first trimester on brain development of the offspring: a prospective study / 中华内分泌代谢杂志

Objective To assess the effects of maternal subclinical hypothyroidism (SCH) during the first trimester on neuropsychological development of the offspring by 20-30 months. Methods In this study, 1 761 pregnant women from 10 hospitals with about 8 weeks of gestation were enrolled. Urinary iodine excretion and serum thyrotropin ( TSH ), free thyroxine ( FT4 ), and thyroid peroxidase antibody ( TPOAb ) levels were determined in all subjects. Pregnant women with SCH (TSH≥2.5 mIU/L) were divided into two subgroups using trimester-specific thyroid function reference: group A (2.5 mIU/L≤TSH＜3.93 mIU/L, 18 cases), and group B (TSH ≥3.93 mIU/L, 20 eases). Thirty euthyroid and TPOAb-negative women from the same cohort were selected as controls. Intellectual and motor development score evaluations were performed in the children by 20-30 months of age. Results Children of women with SCH and subgroups A and B had lower mean intelligence scores 6.55,3.39, and 9.40 points compared with those of the control group (P=0. 001, P=0. 125, and P＜0. 001 ); the respective mean motor scores were 6.31,4.35, and 8.07 points being lower than that of the control ( P=0. 003,P=0. 070, and P=0. 001 ). Intelligence scores and motor scores were negatively correlated with TSH levels (r=-0.425, P＜0. 001 and r=-0. 394, P=0. 001 ). Multiple group comparisons revealed that differences of TSH affected intelligence and motor scores (F=9. 277, P＜0. 001 and F=5. 909, P=0. 004). Ordinal logistic regression analysis showed that possibilities for the reduction of filial mental development index ( MDI ) and psychomotor development index ( PDI ) scores in SCH with maternal TSH levels≥3.93 mIU/L were 8.66 and 6.27 times that of controls ( OR = 8.66,95% CI 2.72-27.57, OR =6.27,95% CI 2.03-19.34 ). Conclusion Maternal elevated TSH levels diagnosed by trimester-specific reference during early gestation are independently associated with lowered filial neurodevelopment scores by 20-30 months.