Objective This study aimed to identify differentially methylated genes (DMGs) associated with natural killer cells in patients with autoimmune thyroiditis (AIT),focusing on the influence of varying water iodine exposure levels. Methods Participants were divided into categories based on median water iodine (MWI) concentrations:iodine-fortified areas (IFA,MWI<10 μg/L),iodine-adequate areas (IAA,40 ≤ MWI ≤ 100μg/L),and iodine-excessive areas (IEA,MWI>300 μg/L). A total of 176 matched AIT cases and controls were recruited and divided into 89,40,and 47 pairs for IFA,IAA,and IEA,respectively. DMGs were identified using 850K BeadChip analysis for 10/10 paired samples. Validation of DNA methylation and mRNA expression levels of the DMGs was conducted using MethylTarget? and QRT-PCR for 176/176 paired samples. Results KLRC1,KLRC3,and SH2D1B were identified as significant DMGs. Validation revealed that KLRC1 was hypomethylated and highly expressed,whereas KLRC3 was hypermethylated and highly expressed in individuals with AIT. Furthermore,KLRC1 was hypomethylated and highly expressed in both IFA and IEA. Conclusion The DNA methylation status of KLRC1 and KLRC3 may play crucial roles in AIT pathogenesis. Additionally,DNA methylation of KLRC1 seems to be influenced by different iodine concentrations in water.

Objective To investigate the clinical application value of MRI Radiomics score(Radscore)combined with clinicopatho-logical features in predicting postoperative progression-free survival(PFS)of patients with endometrial cancer(EC).Methods A total of 127 patients with EC were selected.The radiomic features of the lesions were extracted from T2 WI,diffusion weighted imaging(DWI)and apparent diffusion coefficient(ADC)images.The features were screened by random forest model and Radscore was calcu-lated.Simultaneously,clinical and pathological characteristics of patients were collected and incorporated,and multivariate Cox regression analysis was used to screen the risk factors related to PFS.The MRI Radscore and clinicopathological features were mapped to the nomogram,and the performance of nomogram was evaluated by receiver operating characteristic(ROC)curve and calibration curve.Results Multivariate Cox regression analysis showed that progesterone receptor(PR),human epididymis protein 4(HE4)and MRI Radscore were independent risk factors for predicting PFS in patients with EC(P＜0.05).The area under the curve(AUC)of the predicted PFS at 1,3 and 5 years after surgery were 0.91,0.804 and 0.776,respectively.Calibration curves showed that nomogram had a good fit in predicting PFS in patients with EC 1,3 and 5 years after surgery.Conclusion The nomogram con-structed based on multi-sequence MRI Radscore and clinicopathological features has favorable accuracy and stability in predicting postoperative PFS in individuals diagnosed with EC.

Objective:To clarify the relationship between interleukin (IL)-6, IL-10 gene polymorphisms and autoimmune thyroid disease (AITD).Methods:Literature search was conducted through databases such as PubMed, Web of Science, CNKI, Embase, Wanfang Database and VIP.com, and domestic and foreign literatures related to IL-6, IL-10 gene polymorphisms and AITD were included in the study. The time limit was from the self-built of the databases to July 2021. Meta-analysis was performed with STATA 16.0 software, the odds ratio ( OR) and 95% confidence interval ( CI) were used as effect indicators, random-effect or fixed-effect model was selected according to the heterogeneity results, and the source of heterogeneity was explored through subgroup analysis. Publication bias was assessed using funnel plots and Egger's test. Results:Finally, 19 literatures were included, all in English. There were 12 studies on IL-6 genes and 11 studies on IL-10 genes, including 4 studies on both IL-6 and IL-10 genes. In the whole population, the loci associated with AITD were IL-6 -174 G/C site (GG vs CC + GC: OR =1.94, 95% CI = 1.01 - 3.76), IL-6 -572 G/C site (GG + GC vs CC: OR = 0.49, 95% CI = 0.29 - 0.84; GG vs CC + GC: OR = 0.76, 95% CI = 0.60 - 0.96; GG + CC vs GC: OR = 0.63, 95% CI = 0.49 - 0.81), IL-10 -819 T/C site (TT + TC vs CC: OR = 1.84, 95% CI = 1.01 - 3.34; T vs C: OR = 1.59, 95% CI = 1.00 - 2.51), and IL-10 -1 082 A/G site (AA + AG vs GG: OR = 0.77, 95% CI = 0.64 - 0.92; AA vs GG + AG: OR = 2.03, 95% CI = 1.16 - 3.58; A vs G: OR = 0.76, 95% CI = 0.61 - 0.94). The results of subgroup analysis showed that in Asian population, the loci associated with AITD were IL-6 -174 G/C site (GG vs CC + GC: OR = 4.61, 95% CI = 1.11 - 19.23; G vs C: OR = 0.65, 95% CI = 0.44 - 0.97); IL-6 -572 G/C site (GG vs CC + GC: OR = 0.64, 95% CI = 0.41 - 0.99; GG + CC vs GC: OR = 0.60, 95% CI = 0.38 - 0.94); IL-10 -819 T/C site (TT + TC vs CC: OR = 2.51, 95% CI = 1.48 - 4.25; T vs C: OR = 1.91, 95% CI = 1.05 - 3.46); and IL-10 -1 082 A/G site (AA + AG vs GG: OR = 0.66, 95% CI = 0.52 - 0.84; AA vs GG + AG: OR = 2.83, 95% CI = 1.54 - 5.21; A vs G: OR = 0.66, 95% CI = 0.53 - 0.82). Conclusion:IL-6 -174 G/C, IL-6 -572 G/C, IL-10 -819 T/C and IL-10 -1 082 A/G polymorphisms are associated with the susceptibility to AITD, especially in Asians.

Objective:To observe the mRNA and protein expression levels of thyroid stimulating hormone receptor (TSHR), protein kinase A (PKA) and sodium iodine transporter (NIS) in mammary gland tissue of lactating rats with different iodine nutrition levels, and to explore the role of thyroid stimulating hormone (TSH)-THSR-cyclic adenosine monophosphate (cAMP)-PKA signal pathway in the process of mammary iodine uptake during lactation.Methods:Using a group design, according to body weight (80 - 100 g), 110 Wistar female rats were randomly divided into normal iodine (NI) group, severe iodine deficiency (SID) group, moderately iodine deficiency (MID) group, moderately iodine excess (MIE) group and severe iodine excess (SIE) group, with 22 rats in each group. Another 22 Wistar male rats were selected, and the feeding situation was consistent with that of NI group. After 3 months of feeding, 24-hour urine samples of female rats were collected, and the female rats were caged with the male rats (5 ∶ 1). After mating, each female rat was fed separately. At 10 days of childbirth, the lactating rats were sacrificed and thyroid and mammary gland tissues were taken. The urinary iodine was determined by arsenic cerium catalytic spectrophotometry. The morphological changes of thyroid and mammary gland tissues were observed by HE staining. The mRNA expression levels of TSHR, PKA and NIS in thyroid and mammary gland tissues were measured by real-time PCR; the protein expression levels of TSHR, PKA, phosphorylated PKA (p-PKA), and NIS in mammary gland tissue were measured by Western blotting.Results:Compared with NI group (162.59 μg/L), the median urinary iodine of female rats in SID and MID groups (3.16, 6.36 μg/L) was lower, and the median urinary iodine of female rats in MIE and SIE groups (2 356.27, 11 507.29 μg/L) was higher ( P < 0.01). HE staining showed that different levels of iodine uptake had different effects on thyroid follicles: most of the follicles in NI group were uniform round or oval; in MID group, the number of small follicles increased, the epithelial cells were monolayer columnar or cubic, the follicular cavity became smaller, and the glia decreased; the follicles in SID group became smaller, and the epithelial cells were columnar or high columnar, with reduced or absent glia in the follicular cavity; pleomorphic changes were found in thyroid follicles in SIE and MIE groups, with some follicles significantly enlarged and some small follicles hyperplasia. Different levels of iodine intake had different effects on mammary duct: compared with NI group, the connective tissue around the mammary duct in SID and MID groups showed obvious fibrosis, while the fibrosis in MIE and SIE groups was significantly reduced. The results of real-time PCR showed that there were significant differences in the mRNA expression levels of TSHR, PKA and NIS in thyroid tissues of lactating rats with different levels of iodine nutrition ( F = 10.73, 92.37, 115.75, P < 0.01). There were statistically differences in the mRNA expression levels of TSHR, PKA and NIS in mammary gland tissues of lactating rats with different levels of iodine nutrition ( F = 40.25, 39.63, 14.92, P < 0.05). Western blotting results showed that there were significant differences in the protein expression levels of TSHR, PKA, p-PKA and NIS in mammary gland tissues of lactating rats with different levels of iodine nutrition ( F = 4.14, 6.73, 8.48, 4.51, P < 0.05). Among them, the protein expression level of TSHR in MIE and SIE groups was lower than that in NI group ( P < 0.05); the protein expression level of PKA in SID and MID groups was higher than that in NI group ( P < 0.05); the protein expression level of p-PKA in SID group was higher than that in NI group, but that in SIE group was lower than that in NI group ( P < 0.05), the protein expression level of NIS in SID group was higher than that in NI group ( P < 0.05). Conclusions:The mRNA and protein expression levels of TSHR are decreased in mammary gland tissues of lactating rats with high iodine intake, while the mRNA and protein expression levels of PKA and NIS are increased in low iodine intake. TSH-TSHR-cAMP-PKA signal pathway may be involved in the regulation of iodine intake in mammary gland tissue of lactating rats, which may protect itself and its offspring.

Objective:To verify the determination method of iodine in serum by inductively coupled plasma mass spectrometry (ICP-MS) and to evaluate the consistency between ICP-MS and As 3+-Ce 4+ catalytic spectrophotometry in determination of serum iodine. Methods:Serum iodine concentration was determined by ICP-MS, 187Re was used as an internal standard, and ralated parameters were optimized. Eighty-eight serum samples were simultaneously determined by ICP-MS and As 3+-Ce 4+ catalytic spectrophotometry, and the evaluation indexes included determination range of standard curve, detection limit, precision, accuracy. In addition, we also evaluated the consistency of the two methods through inter-group correlation analysis, intra-group correlation coefficient analysis, Passing-Bablok regression and Bland-Altman analysis. Results:The linear range of ICP-MS standard curve was 0 - 300 μg/L. There was a good linear correlation between iodine concentration value and iodine response value, and the correlation coefficient range was 0.999 8 to 0.999 9. The detection limit of the ICP-MS method was 1.96 μg/L. The relative standard deviation ( RSD) ranged from 0.2% to 1.4% and from 0.4% to 1.8% for intra and inter-batch precision tests of serum samples. The recovery rate ranged from 90.44% to 108.71%. The correlation analysis of 88 serum samples showed that there was a good correlation between the two methods ( r = 0.934, P < 0.05), and the intra-class correlation coefficient was 0.932. The results of Passing-Bablok regression showed that there was no significant difference between the two methods ( P > 0.05). Bland-Altman diagram suggested that the results of the two methods were consistent. Conclusions:ICP-MS method has low detection limit, high precision and accuracy. ICP-MS method is simple, rapid, easy and suitable for determination of iodine in large quantities of serum samples. The results of the two methods for determining serum iodine are consistent.

Objective:Experimental autoimmune thyroiditis (EAT) rat model was establish to observe the effects of iodine excess on thyroid function, antibody and thyrotropin receptor (TSHR) gene expression in EAT rats, and to explore the role of TSHR gene in autoimmune thyroiditis.Methods:According to body weight (80 - 180 g), 48 rats (4-week-old female Lewis) were randomly divided into control group, thyroglobulin (TG) group, TG + high iodine Ⅰ(TG + HⅠ) group, and TG + high iodine Ⅱ (TG + HⅡ) group, 12 rats per group. The iodine concentration in drinking water given to each group was 50 μg/L, 50 μg/L, 20 mg/L and 200 mg/L, respectively. At the same time, rats in TG, TG + HⅠ and TG + HⅡ groups were immunized once every two weeks for three times using pTg and CFA as immunoreagent. Paraffin embedded sections of thyroid tissues were used to observe the pathological changes of rats. The serum levels of thyroglobulin antibody (TgAb), thyroperoxidase autoantibody (TPOAb), free triiodothyronine (FT 3) and free thyroxine (FT 4) in rats were determined by radioimmunoassay. Serum TSHR content in rats was determined by enzyme linked immunosorbent assay (ELISA). The expression of TSHR mRNA in whole blood and thyroid tissue of rats was determined by RT-PCR. The expression of TSHR protein in thyroid tissue of rats was determined by immunohistochemistry (IHC). Results:Hematoxylin-eosin (HE) showed that the thyroid follicles in control group were complete in structure and regular in shape, and no lymphocyte infiltration was observed. A small number of lymphocytes were observed in TG group and scattered in distribution. Follicular structure destruction, fusion and interfollicular infiltration were observed in TG + HⅠ group and TG + HⅡ group. There were significant differences in serum TgAb, TPOAb, FT 3 and FT 4 levels among all groups ( H = 30.28, 21.99, 12.87, 26.69, P < 0.05). Compared to the control group [6.89 (6.32, 7.27), 11.02 (7.60, 12.53), 5.05 (2.71, 7.99), 7.51 (6.50, 9.24) pmol/L], the levels of TgAb [34.99 (25.39, 41.35), 37.70 (29.06, 43.99), 46.41 (38.52, 55.26)], TPOAb [22.87 (13.65, 31.82), 22.22 (14.82, 28.33), 14.61 (12.95, 19.34)], FT 3 [57.74 (24.56, 64.27), 43.64 (5.69, 80.03), 38.56 (17.73, 47.59) pmol/L], and FT 4 [62.16 (41.22, 91.57), 60.61 (35.52, 103.31), 47.96 (31.84, 112.71) pmol/L] were significantly higher in TG group, TG + HⅠ group, and TG + HⅡ group ( P < 0.05). Compared with the control group [(249.37 ± 38.12) μU/L], TG group [(225.33 ± 41.28) μU/L], and TG + HⅠ group [(218.15 ± 65.51) μU/L], TSHR expression level in TG + HⅡ group [(154.26 ± 25.95) μU/L] were significantly decreased ( P < 0.05). The mRNA expression levels of TSHR gene in the whole blood (0.89 ± 0.19, 0.89 ± 0.30, 0.85 ± 0.24) and thyroid tissue(0.63 ± 0.25, 0.46 ± 0.16, 0.51 ± 0.25) of TG group, TG + HⅠ group and TG + HⅡ group were significantly lower than that of control group (1.00 ± 0.05, 1.13 ± 0.21, P < 0.05). IHC showed that the positive intensity of TSHR protein in control group was significantly higher than that in TG group, TG + HⅠ group and TG + HⅡ group. Conclusions:Long-term exposure to high iodine will eventually lead to the damage of iodine-uptake function in thyroid gland and thyroid diseases. Abnormal expression of TSHR gene may lead to antigenicity of thyrotropin binding site in extracellular receptor region and autoimmune thyroid disease.

Objective:By establishing a rat model of experimental autoimmune thyroiditis(EAT), to investigate the effects of different iodine intake on the hippocampal morphology, monoamine neurotransmitters and ethology of the offspring of EAT rats.Methods:A total of 60 female and 20 male Lewis rats with a body weight of 50 - 60 g were selected. Female rats were divided into 4 groups (15 rats in each group) with random number table method according to their body weight: control group (NI group), thyroglobulin group (Tg group), Tg + high iodine Ⅰ group (Tg + HⅠ group), and Tg + high iodine Ⅱ group (Tg + HⅡ group), and the latter three groups were model groups. The contents of iodine in drinking water of the 4 groups were 100 μg/L, 100 μg/L, 20 mg/L and 200 mg/L, respectively. Rats in the model groups were immunized with porcine thyroglobulin (PTg) subcutaneously at multiple sites, and the NI group was injected with normal saline, once every 2 weeks, 3 times in total. The rats in each group were mated in cages according to the ratio of 3 : 1 between female and male. After experiment of the offspring, the urine samples of mother rats were collected within the previous week, urinary iodine concentration was determined by As 3+-Ce 4+ catalytic spectrophotometry; then the mother rats were killed, HE staining was used to observe the changes of thyroid histomorphology and the infiltration of inflammatory cells; serum thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb) of mother rats were determined by radioimmunoassay. Brain tissues were collected from 7 days old offspring, hippocampal morphology of 7 days old offspring was observed by toluidine blue staining; the contents of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) in brain tissues of 7 days old offspring were measured by enzyme-linked immunosorbent assay (ELISA); 30 and 60 days old offspring were used for water maze-location navigation test and open field test. Results:The levels of urinary iodine increased significantly of mother rats in Tg + HⅠ and Tg + HⅡ groups than that in NI group (median, μg/L: 35 380.18, 236 847.16 vs 221.43, P < 0.05). HE staining showed that the thyroid tissue of mother rats in Tg, Tg + HⅠ and Tg + HⅡ groups had different degrees of destruction and inflammatory cells infiltration, and the degree of destruction and infiltration increased with the increase of iodine intake. Compared with NI group, the contents of TgAb and TPOAb in serum of mother rats in Tg, Tg + HⅠ and Tg + HⅡ groups were significantly increased(2.118 4 ± 0.675 1, 2.103 0 ± 0.714 1, 2.783 6 ± 1.084 3 vs 0.790 1 ± 0.101 0, P < 0.05; 1.015 8 ± 0.252 8, 1.019 5 ± 0.202 0, 0.936 6 ± 0.183 4 vs 0.692 2 ± 0.111 9, P < 0.05), and the content of TgAb in Tg + HⅡ group was significantly higher than that in Tg and Tg + HⅠ groups ( P < 0.05). Compared with NI group, the number of hippocampal neurons decreased and relative damage occurred in Tg, Tg + HⅠ and Tg + HⅡ groups of the offspring. Compared with NI group, the NE contents in brain tissues of the offspring in Tg, Tg + HⅠ and Tg + HⅡ groups decreased (pg/ml: 1 232.01 ± 253.45, 1 197.64 ± 222.46, 1 074.40 ± 366.38 vs 1 733.67 ± 158.12, P < 0.05); there were no significant differences in DA and 5-HT contents in brain tissues of offspring in each group ( P > 0.05). In the water maze-location navigation test, the latency of the Tg + HⅡ group on the 4th day of the 30 days old offspring reaching the platform was significantly longer than that of the NI and Tg groups ( P < 0.05). In the open field test, there was no significant difference in 30 and 60 days old offspring in the latency of moving the original quadrant ( P > 0.05). Conclusions:With the increase of iodine intake, the degrees of thyroid tissue destruction and inflammatory cells infiltration in EAT rats increase, and the levels of TgAb in serum increase significantly. Iodine has certain effects on the hippocampal morphology and the level of monoamine neurotransmitters in the brains of the offspring of EAT rats. The effects of different iodine-induced EAT rats on their offspring's learning, memory and spatial exploration are mainly shown in childhood.

Objective To analyze clinicopathological characteristics and the potential risk-related factors of female breast hyperplasia in different age groups.Method From Jan 2015 to Dec 2016,patients diagnosed with breast hyperplasia in 12 hospitals were evaluated.All patients completed the self-designed questionnaires on women'health,including basic demographic information,clinic examination information,radiologic information and pathologic results.The patients were divided into a young group (＜ 45 years old) and an elderly group (from 45 to 75 years old).Results There were 3 684 cases of breast hyperplasia,including 2 291 cases in young group and 1 393 cases in elder group,respectively Clinically breast pain type were most commonly observed in both young and older groups (50.3％ vs.42.7％,P ＜ 0.001).While pathological research based on biopsy showed that breast adenopathy were the most common changes in both groups (67.9％ vs.61.7％,P ＜0.001).More breast cancer cases were identified in elder group than that in young group,especially in clinically lump type patients (9.4％ vs.4.2％,P ＜ 0.001).Compared with elder group,patients in young group have different distribution characteristics regarding to fertility factors,lifestyle factors and psychology scale including anxiety and depression.Conclusion Distributions of clinicopathological characteristics and risk factors of female breast hyperplasia differ across different age groups.

Objective To observe prolactin (PRL) and estradiol (E2) levels in lactating women in different iodine nutrition areas.Methods According to the recent national water-borne high iodine area survey and the monitoring results of iodine deficiency disorders,the following places were selected,including Nankang,Xinggang and Yingpan towns of Beihai City,Guangxi (water iodine ≤ 10 μg/L,low iodine areas),Yangcheng Township and Jiajiazhuang Township of Fenyang City,Shanxi (water iodine 50-100 μg/L,adaptive iodine areas),Pingyao County and Jicun Town of Fenyang City,Shanxi (water iodine ≥300 μg/L,high iodine areas),and urinary and blood samples were collected in lactating women (n =100,97,123) from the three regions.The urinary iodine concentration was tested by arsenic cerium catalytic spectrophotometry.Serum levels of PRL and E2 were determined by chemiluminescence immunoassay.Results The urinary iodine medians of lactating women were 51.42,283.62,842.31 μg/L,respectively,in the three regions,the difference between the regions was statistically significant (x2 =241.09,P ＜ 0.05);the iodine levels of lactating women in low iodine areas,adaptive iodine areas and high iodine areas were in the state of iodine deficiency (＜ 100 μg/L),sufficient or adequate (200-299 μg/L) and iodine excess status (≥ 300 μg/L),respectively.Serum PRL and E2 levels of lactating women in the three types of areas were 38.81,20.98,16.41 μg/L and 29.57,43.70,45.51 ng/L,respectively.The differences between the regions were statistically significant (x2 =41.54,24.03,P ＜ 0.05).Conclusion With the increase of iodine nutrition level,PRL in lactating women has presented a gradually decreasing trend,E2 is increased.

Objective To understand the effects of different water iodine level on iodine nutrition and thyroid function in pregnant women,and provide a reference for prevention and treatment of iodine deficiency disorders in the future.Methods According to the background material of water iodine in provinces given non-iodized salt,the administrative villages with water iodine content ＜ 10,10-49,50-99,100-299 and ≥ 300 μg/L were selected as survey sites in Shandong,Shanxi,Hebei,Henan,Jiangsu and Anhui provinces.Urine,blood,drinking water and salt samples were collected from pregnant women at the site of investigation,and urinary iodine,serum iodine,thyroid function and antibody index,water iodine,and salt iodine were measured;thyroid volume was also examined.Results A total of 575 pregnant women were investigated.The medians urinary iodine of pregnant women with water iodine ＜ 10,10-49,50-99,100-299 and ≥300 μg/L groups were 175.55,180.90,139.70,330.15 and 817.70 μg/L,respectively,and the differences were statistically significant in different water iodine groups (H =152.593,P ＜ 0.01).The levels of serum iodine and free thyroxine (FT4) were significantly different among pregnant women in different water iodine groups (H =82.843,F =3.070,P ＜ 0.01 or ＜ 0.05).However,there was no significant difference in serum thyroid stimulating hormone (TSH) levels (H =1.774,P ＞ 0.05).And with the increase of water iodine levels,the abnormal rate of TSH showed the phenomenon of middle low and both ends high ("U" type,x2 =16.729,P ＜ 0.01).There were no significant differences in the positive rates of serum thyroid peroxidase antibody (TPOAb),thyroglobulin antibody (TgAb),any antibody and double antibodies in pregnant women among different water iodine groups (P ＞ 0.05).And there was a statistically significant difference in the detection rate of subclinical hypothyroidism (x2 =11.869,P ＜ 0.05).The rates of goiter in pregnant women among different water iodine groups were less than 5％.The difference in detection rates of thyroid nodules was statistically significant (x2 =13.591,P ＜ 0.05),and the rate was the highest in water iodine ≥300 μg/L group (21.33％,16/75).Conclusions In water iodine ≥300 μg/L group,urinary iodine level of pregnant women is in the level of iodine excess,and serum iodine level,FT4 level,thyroid nodules detection rate are higher.The abnormal rate of serum TSH and the detection rate of hypothyroidism show a "U" curve that increases at iodine deficiency and iodine excess.