AIM:To observe the changes of atrial fibrillation susceptibility,and the remodeling of atrial myo-cyte action potential,ultrarapid activation delayed rectifier potassium current(IKur)and transient outward potassium cur-rent(Ito)in elderly mice,and to explore the mechanism of atrial fibrillation from the single cell electrophysiological level.METHODS:The C57BL/6J mice were divided into old group(20 months old)and young group(4 months old).Atrial fi-brillation was induced by esophageal atrial pacing.The atrial myocytes were isolated,and action potential and ion currents were recorded with patch-clamp technique.The associated proteins were detected by Western blot technique.RE-SULTS:(1)Compared with young mice,the total incidence of atrial fibrillation was significantly increased in old mice(20.0%at 4 months old vs 60.0%at 20 months old,P<0.01).(2)The action potential duration of atrial myocytes in aged mice was shortened,and more significantly after stimulation.(3)The density of Ito and IKur in atrial myocytes of aged mice increased significantly,from(12.6±1.4)pA/pF to(21.7±1.1)pA/pF,and from(7.5±1.5)pA/pF to(13.3±2.1)pA/pF,respectively(P<0.01).After stimulation,the current increased more significantly,especially in older atrial cells.Compared with the young mice,the steady-state activation curve of Ito in the atrial myocytes of the aged mice shifted towards the depolarization,suggesting that activation of Ito channels in the aged mice increased at the same voltage stimula-tion.(4)Compared with young group,the expression of KV4.2(generating Ito)and KV1.5(generating IKur)proteins in the atrial tissue of the mice in old group was significantly increased,and the expression of caveolin-3 and end-binding protein 1(EB1)was up-regulated,suggesting that the increases in KV4.2 and KV1.5 total channel proteins and effective proteins in the cell membrane might contribute to the increase in the remodeling of potassium currents in the elderly atrial myo-cytes.CONCLUSION:The incidence of atrial fibrillation in elderly mice is significantly augmented,which may be related to the increases in Ito and IKur in atrial myocytes.The remodeling of potassium currents in elderly atrial myocytes is one of the electrophysiological bases leading to the shortening of action potential duration and the occurrence of atrial fibrillation.

AIM:To observe the changes of atrial fibrillation susceptibility,and the remodeling of atrial myo-cyte action potential,ultrarapid activation delayed rectifier potassium current(IKur)and transient outward potassium cur-rent(Ito)in elderly mice,and to explore the mechanism of atrial fibrillation from the single cell electrophysiological level.METHODS:The C57BL/6J mice were divided into old group(20 months old)and young group(4 months old).Atrial fi-brillation was induced by esophageal atrial pacing.The atrial myocytes were isolated,and action potential and ion currents were recorded with patch-clamp technique.The associated proteins were detected by Western blot technique.RE-SULTS:(1)Compared with young mice,the total incidence of atrial fibrillation was significantly increased in old mice(20.0%at 4 months old vs 60.0%at 20 months old,P<0.01).(2)The action potential duration of atrial myocytes in aged mice was shortened,and more significantly after stimulation.(3)The density of Ito and IKur in atrial myocytes of aged mice increased significantly,from(12.6±1.4)pA/pF to(21.7±1.1)pA/pF,and from(7.5±1.5)pA/pF to(13.3±2.1)pA/pF,respectively(P<0.01).After stimulation,the current increased more significantly,especially in older atrial cells.Compared with the young mice,the steady-state activation curve of Ito in the atrial myocytes of the aged mice shifted towards the depolarization,suggesting that activation of Ito channels in the aged mice increased at the same voltage stimula-tion.(4)Compared with young group,the expression of KV4.2(generating Ito)and KV1.5(generating IKur)proteins in the atrial tissue of the mice in old group was significantly increased,and the expression of caveolin-3 and end-binding protein 1(EB1)was up-regulated,suggesting that the increases in KV4.2 and KV1.5 total channel proteins and effective proteins in the cell membrane might contribute to the increase in the remodeling of potassium currents in the elderly atrial myo-cytes.CONCLUSION:The incidence of atrial fibrillation in elderly mice is significantly augmented,which may be related to the increases in Ito and IKur in atrial myocytes.The remodeling of potassium currents in elderly atrial myocytes is one of the electrophysiological bases leading to the shortening of action potential duration and the occurrence of atrial fibrillation.

Objective:To follow up and observe the intellectual development of school children aged 8 to 10 in Baicheng County, Xinjiang Uygur Autonomous Region, which was a severe iodine deficiency disorders region in history, before and after effective control of the disease, in order to evaluate the impact of iodine supplementation on protection of children's intellectual development and provide a theoretical basis for scientific supplements of iodine.Methods:From 1989 to 2018, Combined Raven's Test for Rural in China (CRT-RC) was used to observe the intellectual development status of 660 Uyghur school children aged 8 to 10 in Baicheng County in 1989, 2002, 2006, 2012 and 2018, respectively. Children's intelligence quotient (IQ) was calculated using CRT-RC's 1987 normal sample of rural children in the same age group; the data of average iodized salt coverage rate (C-IS) and childhood goiter rate (GR) from multiple local surveys and the median urinary iodine (MUIC) of children were collected, combined with the "Criteria for Elimination of Iodine Deficiency Disorders" (GB 16006-2008) and the United Nations International Children's Emergency Fund (UNICEF) recommended standards, the status of iodine deficiency during children's growth (IDG) was divided into complete exposure to iodine deficiency, no exposure, and semi-exposed. The Flynn effect (FE) gain was calculated using norm samples of children aged 8 to 10 in 1987, 1996 and 2006 of CRT-RC, and the differences in children's intellectual development after FE correction before and after IDG reached the standard were compared.Results:The IQ of children were (81.67 ± 14.13), (83.26 ± 14.05), (89.68 ± 13.58), (98.50 ± 14.33) and (103.23 ± 15.25) points in Baicheng County in 1989, 2002, 2006, 2012 and 2018, respectively, the difference between different years was statistically significant ( F = 58.357, P < 0.01). The three indicators of C-IS, GR, and MUIC didn't meet the standards during the IDG evaluation period in the 1989, 2002, and 2006 groups, which were the complete exposure to iodine deficiency; in the 2012 group, only the MUIC met the standard, which was semi-exposed; in the 2018 group, three indicators all met the standard, which was no exposure. The FE gains of 1987 with 1996, 1996 with 2006 were 0.96 points/year and 0.74 points/year, respectively; after FE correction, the actual gains of IQ of 2002 and 2006 compared with 1989, 2012 and 2018 compared with 2006 were - 9.57, - 6.11, 4.38, and 4.67 points, respectively. Conclusions:In iodine deficiency areas, intermittent iodine supplementation (1989 - 2009) for children exposed to iodine deficiency during growth still cannot effectively protect children's intellectual development; continuous and effective iodine supplementation (2010 - 2018) with iodized salt as the core and covering children's growth period has obvious positive effects on protection of children's normal intellectual development. In the future, we will continue to observe the influence of IDG full-cycle suitable iodine nutrition on children's intellectual development.

In response to the recent interest in potassium iodate iodized (KIO 3) salt safety, we reviewed the background of KIO 3 in replacing of potassium iodine (KI) as salt fortificator and its effect in prevention and control of iodine deficiency disorders (IDD) or endemic goiter, the decision-making changes of fortificator of iodized salt in China, the research and progress of toxicology, and whether IO 3- exits in urine without decomposition or not. Our inclusions are: it is believed that the decision of the international organizations and agencies of national and local governments about the safety of KIO 3 in iodized salt is supported by adequate and scientific evidents. When it comes to the safety of KIO 3 added in iodized salt, it must be based on the trace amount of KIO 3 in salt which is limited while intaking. Reductive substances in food, cooking heating or reduction system of human body might quickly reduce trace IO 3- to I -, therefore, IO 3- might not be found in fresh urine.

Objective To observe and compare the different orthotopic models of papillary thyroid cancer ( PTC) cell lines of RET/PTC1 rearrangement and BRAFV600E mutation in nude mice. Methods Human PTC cell lines TPC-1, BHP5-16 and BHP2-7 were used. The genotypes of RET/PTC1 rearrangement and BRAFV600E mutation were determined by realtime-PCR and DNA sequencing analysis. The cells(2×105) were injected into the thyroid gland of nude mice. The nude mice were executed at 4th, 12th week, and then their thyroid tumors were removed and weighed. The levels of thyroid hormone were detected using chemiluminescent immunoassay. Results Both TPC-1 and BHP2-7 cells were identified as RET/PTC1 rearrangement by real time-PCR, and the expression of RET/PTC1 rearrangement in BHP2-7 cell was higher than that of TPC-1 cell. BRAFV600E mutation was found in BHP5-16 cell by DNA sequencing analysis, but was not found in TPC-1 and BHP2-7 cells. There were different characteristics in three orthotopic nude model groups. Tumorigenic rates of TPC-1 and BHP5-16 groups were 100%, but the growth of tumor was more rapid in BHP5-16 group than that in TPC-1 group, with more weight tumor. The changes of thyroid hormone levels in BHP5-16 group and TPC-1 group were the same, which were normal at 4th week and sharply decreased at 12 th week(P<0. 05). However, the tumorigenic rate of BHP2-7 group was only 6. 25%. Compared with normal control group, there was no statistical difference in the levels of thyroid hormone in BHP2-7group(P>0. 05). Conclusions It showed difference in the orthotopic models of PTC cell lines of RET/PTC1 rearrangement and BRAFV600E mutation in nude mice. BRAFV600E mutation has obvious impacts on increasing tumorigenic rate and promotion of tumor growth in the orthotopic model. It should not be ignored that advanced thyroid tumor will lead to the destruction of thyroid function.

Objective To observe the implementation of national food safety standard for “Iodine Concentration in Edible Salt”(GB 26878-2011) and its effectiveness on iodine nutritional status of key populations. Methods Information of iodine concentration in edible iodized salt of various provinces (autonomous regions and municipalities, including Xinjiang Production and Construction Corps) was collected using Baidu Searching Engine through the establishment of key words. Sal t samples were collected in Tianjin City and Aksu Region of Xinjiang , and the salt iodine concentration in both places was 30 mg/kg. In Tianjin, Hongqiao, Tanggu and Hangu, Beichen were selected as representatives of the downtown areas, the coastal areas and the suburbs, respectively and counties of Baodi and Ji were iodine deficiency areas in history. Sampling work was carried out from August 2012 to March 2013 in Tianjin. In Aksu, Yatuoer Township and Charqi Town in Baicheng County, Aotebeixi and Aketuohai Townships in Wushen County were chosen as iodine deficiency areas, and the survey was carried out from January to September 2013 . Random urine samples of school-age children ( 8 - 10 years old ) , pregnant women and lactating women were collected; urinary iodine was measured following the Method for Determination of Iodine in Urine by As3+-Ce4+ Catalytic Spectrophotometry(WS/T 107-2006) and iodine in edible iodized salt was measured following the General Test Method in Salt Industry Determination of Iodideion ( GB/T 13025 . 7-1999 ) . Results Fourteen of the provinces(autonomous regions and municipalities, including the Corps of Xinjiang) chose 25 mg/kg as their iodine concentration in edible iodized salt and 13 provinces chose 30 mg/kg. Besides, there were another 5 provinces providing 30 mg/kg particularly for pregnant women and lactating women while 25 mg/kg for other populations. In Tianjin, the medians of iodine concentration in edible iodized salt were ranged from 24.4 - 32.1 mg/kg in retail stores and 26.4 mg/kg at households. The household coverage rate of iodized salt and the proportion of households using adequately iodized salt were 78.5%(168/214) and 62.6%(134/214), respectively. The median ranges of urinary iodine were 178.2 - 183.9 μg/L in school children, 124.3 - 130.9 μg/L in pregnant women and 72.7 - 109.5 μg/L in lactating women. In Aksu, the medians of iodine concentration in edible iodized salt were 27.1 and 26.5 mg/kg in retail stores and households, respectively. The household coverage rate of iodized salt and the proportion of households using adequately iodized salt were 100.0% (363/363) and 98.9%(359/363), respectively. The median ranges of urinary iodine were 174.8 - 293.0, 154.9 - 230.0 and 135.8 - 239.3 μg/L among school children, pregnant women and lactating women, respectively. The median of iodine concentration in a special edible iodized salt sample reached 49.1 mg/kg, and qualified rate was 0(0/11) in Aksu. Conclusions All provinces , municipalities and autonomous regions ( including the Corps of Xingjiang ) in China have adjusted the iodine content in edible iodized salt in accordance with GB 26878-2011. However, in Tianjin the household iodine concentration in edible salt is lower than the local standards; the household coverage rate of iodized salt and the proportion of households using adequately iodized salt are lower than the national standards; pregnant women and lactating women are at risk of mild iodine deficiency.

Objective To observe the effects of different iodine intake on the thyroid tumor growth and thyroid function in the orthotopic nude mice model of human papillary thyroid carcinoma (PTC) cell line TPC-1.Methods Human PTC cell line TPC-1 (2 × 105) was injected into the left thyroid gland of nude mice.After the operation,the nude mice were randomly divided into three groups:low iodine group (LI),normal iodine group (NI),and high iodine group(HI,50 folds of normal iodine) based on the iodine levels contained in their diet.4 and 12 weeks later,the nude mice were executed,then their thyroid tumors were removed and weighted.The levels of urinary iodine were measured with As3+-Ce4+ catalytic spectrophotometry using ammonium persulfate digestion method.The thyroid hormone level was detected using chemiluminescent immunoassay.The morphology and structure of thyroid tumor tissue was observed by microscope.Results The iodine intervention feeding was successful according to urinary iodine level of LI,NI,and HI groups,paralleled to their iodine intakes.However,the difference of the weight of thyroid tumor in three groups had no statistical significance(P＞0.05).At 4 weeks,compared with control group,the levels of thyroid hormones were normal in NI group,while lower T4 and normal T3 were found in LI group.However,T4 was higher and T3 was lower in HI group (P＜0.05).At 12 weeks,the levels of thyroid hormones all were decreased due to the enlargement of thyroid gland tumor in NI,LI and HI groups.T4 and T3 in LI group were the lowest among three groups,even T4 was below detection limit.T4 was normal and T3 was lower in HI group as compared to control group.Conclusion Iodine intake may not significantly affect tumor growth in the orthotopic nude mice model of human PTC cell line TPC-1,but it has a significant effect on the synthesis of thyroid hormones.

Objective To set up the reference range for thyroid hormones and thyrotropin (TSH) of 8-10 years old school children in certain regions of China to provide reference criteria for diagnosis,treatment,and monitoring of thyroid diseases and related research.Methods A cross-sectional survey was conducted in primary school children aged 8-10 years from six iodine sufficient areas.664 normal school children were selected for establishing reference ranges of thyroid hormones and TSH after crucial screening through questionnaire and laboratory investigation.The serum hormone levels were determined by using chemiluminescent immunoassay (Bayer's reagents),and the reference range of each hormone was displayed as its 95％ central interval.Results The reference ranges of TSH,FT4,FT3,TT4,and TT3 were 1.03-8.42 mIU/L,13.44-20.59 pmol/L,4.75-6.96pmol/L,75.29-152.66 nmol/L,and 1.76-3.35 nmol/L,respectively.There was no significant difference in hormone levels between boys and girls.The eight years old group had slightly higher TT4 level compared with the other age groups.The rural children had higher TSH and TT3 levels and lower FT4 level than the urban children.Conclusion The thyroid hormone and TSH levels are substantially different between school children and adults.Therefore,it is necessary to establish the reference range of thyroid function indices for normal school children in order to diagnose,treat,and monitor thyroid diseases.

Objective To analyze the median urinary iodine(MUI)level in normal pregnant women based on World HeMth Organization(WHO) recommended criterion,and to provide the MUI reference values for monitoring and evaluating iodine nutrition during pregnancy and related studies.Methods Total 604 normal pregnant and 192 non-pregnant women(as a comparison)were selected from a cross-sectional survey.These women were all healthy,iodine sufficient,with normal thyroid function,and negative anti-thyroid antibodies.The iodine content in drinking water,edible salt,and urine was determined by standard methods,and serum TSH,FT4,FT3,thyroid peroxidaseantibody(TPOAb),and thyroglobulin antibody(TgAb)were measured using chemiluminescent immunoassay.Resuits (1)The iodine in drinking water was 3.0μg/L indicating such small amount of iodine could be neglected for daily iodine intake.(2)All women consumed iodized salt with the median iodine in salt of 31.7 mg/kg.The daily iodine intake of at least 240 μg could be roughly estimated if an average of 10 g salt was taken per person per day and further subtracted by 20%iodine lost during cooking,which could meet the iodine needs during pregnancy.(3)The MUI of 173.1μg/L was calculated from 604 pregnant women having 174.5,167.0,and 180.7 μg/L during the first,second,and third trimesters,respectively,reaching the optimal level of 150-249 μg/L recommended by WHO for pregnant women.However,our data showed relatively lower levels,not reaching 200μg/L.The MUI of 240.2μg/L was calculated from 192 non-pregnant women,reaching the level of"above requirement"(200-299μg/L) recommended by WHO for adults.(4)All women were euthyroid and antibody-negative,but the TSH level in pregnant women was lower than that in non-pregnant women,in particular during the first trimester,while FT4 and FT3 were considerably decreased compared with the non-pregnant(with an exception of FT4 in the first trimester),and both gradually declined with the gestational age.Conclusions The optimal MUI level of 150-249 μg/,L recommended by WHO can be applied to pregnant Chinese women,but our data provided a relatively low range of 150-200μ/L throughout pregnancy.The higher MUI of 240.2μg/L in non-pregnant women indicated that iodized salt with different contents should be supplied on market to meet the requirement of different groups of population.

Objective To study mother and infant's iodine metabolism and thyroid function during lactation with different iodine intakes. Methods Wistar rats were randomly assigned to four groups with severe iodine deficiency (SID), mild iodine deficiency (MiID), normal iodine (NI), and excessive iodine (ExI) intake respectively. All rats were fed on an iodine deficient food and drinking water with different quantities of potassium iodide for 3 months until mating. The urinary iodine, milk iodine, blood iodine, and thyroid hormones (TH) were detected in lactating mother and the offspring rats 14 days after birth. Thyroid weight of mother rats was determined. Thyroid morphology of mother and their offsprings was observed. Results ( 1) Iodine contents in urine, milk, and blood of lactating rats and the offsprings were increased with the increase of iodine supplied in diet. But the change in amplitude between groups was decreased in the other; urine iodine > milk iodine > blood iodine. (2) Serum TT4[ (16. 7±12. 0 vs 36.4±15. 0) nmol/L, P<0.05] was significantly decreased, but TSH [(5.73±2.90vs 1. 38±0.30)mIU/L, P<0.01]and TT3/TT4(6.6±2.7 vs 2. l±0.3,P<0.01) were increased in lactating rats of SID group compared with NI, so as TT4( 10.6±2. 3 vs 16.4±4. 7) nmol/L, P<0.05 ] of offspring rats in SID, but were not in MiID and ExI groups. (3 ) Histological studies showed that small follicular thyroid nodules with follicular hyperplasia occurred in both lactating rats and their offsprings in the SID group, mild swelling in MiID group and polymorphism changes appeared in mother rats of ExI group, but no significant difference appeared in offsprings compared with NI group. Conclusions Severe iodine deficiency will lead to hypothyroidism in mother and infant, but normal iodine nutrition and thyroid function in mother and offspring were maintained through the compensatory action of mother and child in mild iodine deficiency and iodine excess.