Significance of high expression of C5orf46 in gastric cancer and potential intervention of tarditional Chinese medicine based on bioinformatics, molecular docking, and cell experiments / 中国中药杂志

This study aims to investigate the expression, prognosis, and clinical significance of C5orf46 in gastric cancer and to study the interaction between the active components of C5orf46 and tarditional Chinese medicine. The ggplot2 package was utilized for differential expression analysis of C5orf46 in gastric cancer tissues and normal tissues. The survival package was used for survival analysis, univariate regression analysis, and multivariate regression analysis. Nomogram analysis was used to assess the connection between C5orf46 expression in gastric cancer and overall survival. The abundance of tumor-infiltrating lymphocytes was calculated by GSVA package. Coremine database, Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) database, and PubChem database were used to search the potential components corresponding to C5orf46 gene and tarditional Chinese medicine. Molecular docking was performed to explore the binding affinity of potential components to C5orf46. Cell experiments were performed to explore the expression of C5orf46 gene in cells of the blank group, model group, and drug administration groups. As compared with normal tissues, C5orf46 expression was higher in gastric cancer tissues, which had more significant predictive effects in the early stages(T2, N0, and M0). The more advanced the tumor node metastasis(TNM) stage, the higher the C5orf46 expression and the lower the probability of survival of patients with gastric cancer. The expression of C5orf46 positively correlated with the helper T cells1 in gastric cancer and the macrophage infiltration level in gastric cancer, and negatively correlated with B cells, central memory T cells, helper T cells 17, and follicular helper T cells. Seven potential components of C5orf46 were obtained, and three active components were obtained after the screening, which matched five tarditional Chinese medicines, namely, Sojae Semen Nigrum, Jujubae Fructus, Trichosanthis Fructus, Silybi Fructus, and Bambusae Concretio Silicea. Molecular docking revealed that sialic acid and adeno-sine monophosphate(AMP) had a good binding ability to C5orf46. The results of real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot showed that, as compared with the model group, the mRNA and protein expression levels of C5orf46 were significantly lower in the drug administration groups. The lowest expression level was found at the concentration of 40 μmol·L~(-1). The results of this study provide ideas for the clinical development of traditional Chinese medicine compounds for the treatment of gastric cancer as well as other cancers.

Expression of thyroid-stimulating hormone receptor in mammary gland tissue of lactating rats / 中国地方病学杂志

Objective To observe the protein and mRNA expression of thyroid-stimulating hormone receptor (TSHR) in mammary gland tissue of lactating rats,and to explore iodine uptake mechanism.Methods Eighty adult Wistar rats (60 female and 20 male),weighting 210-250 g were selected.All female Wistar rats were randomly divided into 6 groups according to their body mass:normal non-pregnant group,lactating for 5-,10-,15-and 20-day groups and weaning for 5 days group,10 rats in each group.All rats were fed with conventional fodder and tap water freely.In addition to the normal non-pregnant group,other five groups of female and male rats were mated at 3 ∶ 1,respectively.Then the rats in all groups were killed on the 5th,10th,15th and 20th day after lactation and on the 5th day after weaning to get the mammary gland tissue.The protein and mRNA expression of TSHR were determined by immunohistochemical staining and real-time quantitative PCR.Results TSHR protein was expressed in mammary acinar and ductal epithelial cytoplasm.The expression of TSHR in mammary gland showed significant differences between groups (x2 =14.612,P ＜ 0.05),the staining intensity of mammary gland tissue in normal non-pregnant rats(weak,n =4; moderate,n =6) was weaker than that of lactating for 5 days(weak,n =2; moderate,n =3; strong,n =5) and 10 days groups(barely detectable,n =1;moderate,n =4; strong,n =5; x2 =4.113,5.250,all P＜ 0.05).The expression of TSHR mRNA in mammary gland showed significant differences between groups(F=20.488,P ＜ 0.05); the expression of TSHR mRNA in lactating for 10 days group(0.31 ± 0.06) was higher than that of lactating for 5 days group(0.22 ± 0.04,P ＜ 0.01),and the expression of lactating for 15 days group (0.16 ± 0.08) was significantly lower than that of lactating for 5 days group (P ＜ 0.05).Conclusions TSHR is widely expressed in mammary gland of lactating rats.The iodine uptake of mammary gland is enhanced in early lactation period when the body may be more susceptible to iodine deficiency,therefore iodine should be supplemented reasonably.

The effect of different levels of iodine nutrition on rat maternal thyroid function during pregnancy / 中国地方病学杂志

Objective To observe the effect of different levels of iodine nutrition on rat maternal thyroid function during pregnancy.Methods A total of 225 Wistar rats one month after weaning were involved in the study(female 165,male 60,body mass 80 to 100 g).Female rats were randomly divided into six groups by body mass:control group(NI group),iodine deficiency 1 and 2 groups(LI1,LI2 groups),iodine excess 1 and 2 groups (HI1,HI2 groups),and the control of not pregnant group(NNI group).There were 30 rats in 1-5 groups and 15 rats in group 6.LI1,LI2 groups:low iodine diet + deionized water of no iodine or iodine-containing 5 μg/L; HI1,HI2 groups:normal diet + deionized water of iodine 3000,10 000 μg/L; NI,NNI groups:normal diet + deionized water of iodine-containing 50 μg/L.After 12 weeks,the females(except group 6) mated the male by 2 ∶ 1,and then each pregnant female rat was fed in a single cage.The female mice were sacrificed in the first(5 ± 2)d,the second (12 ± 2)d and the third trimesters of pregnancy (17 ± 2)d,respectively,and there blood samples and thyroid were obtained.Serum total thyroxine(TT4),free thyroxine(FT4),total triiodothyronine (TT3),free triiodothyronine (FT3) and thyroid stimulating hormone(TSH) were determined by radioimmunoassay and serum thyroglobulin(TG) and thyroid-binding globulin (TBG) were determined by enzyme-linked immunosorbent assay.Results ①Thyroid absolute quality and relative quality was compared among groups,and the differences were statistically significant (F =16.55,24.25,F ＜ 0.01 or ＜ 0.05).②At the first,the second and the third trimesters of pregnancy,the differences of maternal serum TT4 and FT4 between groups were statistically significant(F =5.02,13.41,17.39,41.89,23.72,48.64,P ＜ 0.01 or ＜ 0.05).Female rats in NI,HI1 and HI2 groups in different pregnant periods among inner groups were compared,and the differences of serum TT4 and FT4 were statistically significant(F=3.27,6.98,8.22,8.65,29.68,7.90,P ＜ 0.01 or ＜ 0.05).③ In the first and the third trimesters of pregnancy,maternal serum TT3 was compared among groups,and the differences were statistically significant(F=3.59,8.22,P ＜ 0.05 or ＜ 0.01) ; in the second and the third trimesters of pregnancy,maternal serum FT3 was compared among groups,and the difference was statistically significant(F =3.86,4.26,P ＜ 0.05 or ＜ 0.01).Female rats in NI,LI1 and HI1 groups in different pregnant periods among inner groups were compared,and the differences of maternal serum TT3 were statistically significant(F =8.77,7.11,6.28,P ＜ 0.01 or ＜ 0.05).④At the first,the second and the third trimesters of pregnancy,the differences of maternal serum TG and TBG were compared in groups,and the differences were statistically significant(F =5.47,3.62,9.35,4.15,13.16,22.78,P ＜ 0.01 or ＜ 0.05).The differences of maternal serum TG of HI1 group and of serum TBG of NI group in different pregnant periods among inner groups were statistically significant (F =3.18,7.94,P ＜ 0.05).⑤At the first,the second and the third trimesters of pregnancy,the differences of maternal serum TSH in groups were statistically significant(F =4.83,7.08,6.52,P ＜ 0.01); the differences of maternal serum TSH of all the 5 groups in different pregnant periods among inner groups were statistically significant (F =3.26,8.89,11.45,4.04,3.78,P ＜ 0.05).Conclusions Different levels of iodine nutrition can cause changes in thyroid function in rats maternal thyroid function during pregnancy; serum TT4,FT4 level decreases when iodine deficiency,and increase with iodine excess.Serum TT3,FT3 level of does not changed significantly due to compensatory regulation of the body.

Therapeutic efficacy of hyperbaric oxygen on traumatic brain injury in the rat and the underlying mechanisms / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the effects of hyperbaric oxygen (HBO) treatment on the activation of astrocytes and the expression of glia-derived neurotrophic factor (GDNF) and nerve growth factor (NGF) in the brain after traumatic brain injury (TBI).</p><p><b>METHODS</b>54 male SD rats were randomly divided into three groups (n = 18): sham-operated, TBI and HBO treatment groups. TBI was induced with Feeney's method, bone window was opened without strike on the brain tissue in the sham-operated group. HBO group rats received HBO treatment for 60 min in the hyperbaric chamber containing O2 100% at 3 ATA. When neurological functions were measured 48 h after TBI, rats were decapitated, the brain water content of 18 rats was measured, 18 brains were sliced for the morphological observation after Nissl staining and for the immunohistochemistry staining of astrocyte markers glial fibrillary acidic protein (GFAP), vimentin and S100, and the other 18 brains of injured side were used for Western blot analysis of GDNF and NGF.</p><p><b>RESULTS</b>HBO treatment reduced the neurological deficit, brain water content and hippocampal neuronal loss. In the observed cortex and hippocampal area astrocytes were activated, the cell number of positive expression of astrocyte markers GFAP, vimentin and S100 was increased, and the expression of GDNF and NGF was elevated after TBI. However, these indices were all enhanced further after the HBO treatment.</p><p><b>CONCLUSION</b>It is suggested that HBO may be an effective therapy for TBI and upregulation of the expression of GDNF and NGF may underly the effect of HBO.</p>

Effective dose and time window of ginseng total saponins treatment in rat after traumatic brain injury / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the neuroprotective effect, effective dose and time window of ginseng total saponins (GTS) treatment in rat after traumatic brain injury (TBI).</p><p><b>METHODS</b>The modified Feeney's method was used to establish TBI model in rat. GTS was treated intraperitoneally. The neurological function and histological morphology of brain tissue were observed.</p><p><b>RESULTS</b>Different doses of GTS were used 6 h after TBI. The neurological and histological results showed that: compared with the TBI group, significant efficacy was observed 2 - 14 days after injury with GTS treatment at 10, 20, 40, 60 and 80 mg/kg (P < 0.05); The effects of GTS at 20, 40, and 60 mg/kg were better than those of GTS at 10 and 80 mg/kg. During the research on the time window of GTS intervention, GTS (20 mg/kg) showed significant effect when used at 3 h and 6 h after TBI; however 12 h, 24 h after TBI, application of GTS did not exert any significant effect.</p><p><b>CONCLUSION</b>GTS intervention after TBI could reduce brain damage and promote recovery of the neurological function. Among doses of GTS 5 - 80 mg/kg, 20 - 60 mg/kg is the best dose limit. The effective time window of GTS is 6 h after TBI.</p>

Different levels of iodine intake and thyroid morphological changes of lactating rats and their newborns / 中国地方病学杂志

ObjectiveTo study the morphological and functional changes of thyroid in lactating rats and their offspring in iodine deficiency and iodine excess animal models.MethodsOne hundred and twenty Wistar rats(30 males and 90 females) were selected.Based on their body weight,the 90 females were stratified and randomly divided into five groups( 18 in each group):low iodine group 1 and group 2(fed with low iodine feed and deionized water containing iodine of 0,5 μg/L) ; high iodine group 1,group 2 and control group(feed with normal diet and deionized water containing iodine of 3000,10 000,50 μg/L).After fed for 3 month,all female rats were mated with males in a ratio of 3 ∶ 1.After birth for 10 days,8 female rats and their offspring in each group were sacrificed.Changes of thyroid were observed by naked eyes.The thyroid weight was measured and pathological changes of thyroids were observed under light microscope.Results①Absolute and relative weight of lactating rats thyroid in low iodine group 1 and group 2 [ (92.02 ± 24.40 ),(77.11 ± 23.32 )mg,(0.509 ± 0.072),(0.384 ± 0.089) mg/kg] were much higher than that of control group[ (17.41 ± 9.25)mg,(0.102 ± 0.016)mg/kg,all P＜ 0.05].Absolute and relative weight of lactating rats thyroid in high iodine group 1 and group 2[(8.22 ± 0.41 ),(9.42 ±0.43)mg,(0.047 ± 0.006),(0.035 ± 0.005)mg/kg] were lower than that of control group(all P ＜ 0.05).Absolute and relative weight of lactating rats and their offspring thyroid was decreased with increase of iodide intake in the diet.②Thyroid enlargement of lactating rats in low iodine group 1 and group 2 was evident,but that of high iodine group 1 and group 2 was not.③Epithelial cell hyperplasia and smaller follicular cavity were observed in low iodine group 1 and group 2 under light microscope.Epithelial cell deformation and mostly flat were observed in high iodine group 1 and group 2.ConclusionsThyroid morphology is changed with iodide intake in the lactating rats and their offspring,and the changes are consistent between female rats and their newborns.

Influence of iodine on mRNA expression of iodide transporter, insulin-like growth factor Ⅰ and transforming growth factor beta in thyroid and mammary glands of lactating rats / 中国地方病学杂志

ObjectiveTo observe the influence of iodine on mRNA expression of iodide transporter (NIS),insulin-like growth factor Ⅰ (IGF- Ⅰ ) and transforming growth factor beta(TGF-β) in thyroid and mammary glands of lactating rats and to explore the role of NIS,IGF- Ⅰ and TGF-β mRNA in iodine uptake in thyroid and mammary glands of lactating rats.MethodsOne hundred and one Wistar rats(80 female and 21 male),weighting 8 - 100 g were selected.These female rats were randomly divided into five groups according to their body weight:control group(NI,normal feed,drank deionized water containing iodine 50 μg/L) ; low iodine group 1 and 2(LI-1,LI-2,low iodine feed,drank deionized water containing iodine 0 and 5 μg/L,respectively); high iodine group 1 and 2(HI-1,HI-2,normal feed,drank deionized water containing iodine 3000 and 10 000 μg/L,respectively),16 rats in each group.After feeding for 3 months,the female and male rates were mated 3:1.The female rats in each group were sacrificed at the fifth and tenth day after postpartum.Thyroid and mammary glands were taken.The mRNA levels of NIS,IGF- Ⅰ and TGF-β in thyroid and mammary glands of lactating rats were determined by real time quantitative PCR.ResultsThe fifth days after postartum,NIS,IGF- Ⅰ and TGF-β mRNA expression levels of thyroid and lactating mammary glands were different between groups,and the differences were statistically significant ( NIS:F =631.46,64.91,all P ＜ 0.01 ; IGF- Ⅰ:F =11.45,6.56,all P ＜ 0.01 ; TGF-β:F =291.83,304.53,all P ＜ 0.01).Compared with control group [NIS:0.0066 ± 0.0023, (0.1481 ± 0.0711 ) × 10-2; IGF- Ⅰ:0.0419 ± 0.0062,0.0542 ± 0.0044; TGF-β:0.1416 ± 0.0277,0.1670 ± 0.0499],regardless of thyroid or mammary gland,the NIS,IGF- Ⅰ and TGF-β mRNA expression of LI-1 [NIS:0.0447 ± 0.0110,(0.3030 ± 0.1831) × 10-2;IGF- Ⅰ:0.0662 ± 0.0078,0.0902 ± 0.008; IGF- Ⅰ:0.5514 ± 0.0508,0.6942 ± 0.0367],LI-2[NIS:0.0317 ±0.0081,(0.3017 ± 0.1601) × 10-2; IGF-I:0.0645 ± 0.0054,0.0894 ± 0.0093; TGF-β:0.5292 ± 0.0332,0.6704 ± 0.0277 ] was significantly increased (all P ＜ 0.01 ); the NIS mRNA expression of HI-1 [0.0043 ± 0.0011,(0.1233 ± 0.0954) × 10-2],HI-2[0.0037 ± 0.0017,(0.1058 ± 0.0854) × 10-2] was decreased(all P ＜ 0.05),while the expression of IGF-Ⅰ mRNA [0.0521 ± 0.0910,0.0715 ± 0.0026; 0.0516 ± 0.0078,0.0697 ± 0.0038] and TGF-β mRNA [0.2087 ± 0.0425,0.2361 ± 0.0425; 0.1971 ± 0.0237,0.2257 ± 0.0752 ] was increased (all P ＜ 0.05 ).The tenth days after postpartum,the mRNA expression levels of NIS,IGF- Ⅰ and TGF-β of thyroid and lactating mammary gland in rats were different between groups,and the differences were statistically significant (NIS:F =103.55,116.32,all P ＜ 0.01; IGF-Ⅰ:F =67.67,11.98,all P ＜ 0.01; TGF-β:F =74.30,381.30,all P ＜0.01 ).Compared with the control group[NIS:0.0069 ± 0.0011,(0.1337 ± 0.0599) × 10-2; IGF-Ⅰ:0.0390 ±0.0071,0.0534 ± 0.0056; TGF-β:0.1351 ± 0.0336,0.1534 ± 0.0320],the mRNA expression levels of NIS,IGF- Ⅰ and TGF-β of LI-1 [ NIS:0.0432 ± 0.0165,(0.2962 ± 0.0985 ) × 10-2; IGF- Ⅰ:0.0643 ± 0.0088,0.0873 ± 0.0055 ; TGF-β:0.5042 ± 0.0912,0.6408 ± 0.0420],LI-2[NIS:0.0287 ± 0.0111,(0.2873 ± 0.0862) × 10-2; IGF- Ⅰ:0.0621 ± 0.0094,0.0862 ± 0.0038; TGF-β:0.4893 ± 0.0504,0.6372 ± 0.0389] were significantly increased(all P ＜ 0.01 ); the NIS mRNA levels of HI-1 [ 0.0042 ± 0.0029,(0.1006 ± 0.0909) × 10-2],HI-2[0.0035 ± 0.0020,(0.0890 ± 0.0119) × 10-2] were decreased(all P＜ 0.05),while the expression of IGF-Ⅰ mRNA[0.0516 ± 0.0078,0.0668 ± 0.0071; 0.0508 ± 0.0089,0.0621 ± 0.0064] and TGF-β mRNA[0.2007 ± 0.0546,0.2175 ± 0.0370;0.1959 ± 0.0393,0.2097 ± 0.0425] were increased(all P ＜ 0.05 ).In thyroid and mammary glands,the comparisons of NIS,IGF,TGF-β mRNA expression of the fifth and tenth day after postartum,between each group were not statistically significant(all P ＜ 0.05).ConclusionsThere are regulatory mechanisms of thyroid and mammary glands of lactating rats in response to low or high iodine conditions.In low iodine,the expressions of NIS,IGF- Ⅰ and TGF-β mRNA in thyroid and mammary glands increase and iodide uptake ability is enhanced to meet the body needs.In high iodine,the expression of NIS mRNA decreases in thyroid and mammary glands.Due to the reduced ability of iodine uptake,iodine intake is reduced,thereby reducing the hazards of high iodine in filial rats.

Effects of different iodine intakes on rat iodine metabolism during pregnancy / 中国地方病学杂志

Objective To study the effects of different iodine intakes on rat iodine metabolism during pregnancy.Methods One hundred and fifty female Wistar rats (body weight 80-100 g) were randomly divided into five groups:control group(NI),lower iodine 1 and 2 groups(LI1 and LI2),High iodine 1 and 2 groups(HI1 and HI2) by weight,30 rats in each group.These rats were given deionized water containing different concentrations of iodine,50(NI),0 (LI1),5(LI2),3000(HI1) and 10000 μg/L(HI2),respectively.After 12 weeks,urine samples were collected before copulation.The rats were sacrificed at the first(6-7 days),second (12-13 days) and third trimesters(19-20 days),respectively,serum and amniotic fluid samples were collected.Urinary iodine and iodine level in the fetal amniotic fluid were measured by As3+-Ce4+ catalytic spectrophotometry.Serum iodine was measured by mild acid digestion method.Results The baseline medians of urinary iodine of LI1 and LI2 groups(5.96,15.92 μg/L) were significantly lower than that of the NI group(43.75 μg/L,all P ＜ 0.01),and the values of HI and HI2 groups(5263.96,20389.64 μg/L) were significantly higher than that of the NI group (all P ＜ 0.01).The median of urinary iodine during pregnancy was significantly lower than that of the baseline of no pregnancy(all P ＜ 0.01).The medians of urinary iodine of the NI group at the first and the second trimesters (28.97,34.34 μg/L) were significantly lower than that of the third trimester(42.31 μg/L,all P ＜ 0.01).The means of serum iodine of LI1 and LI2 groups[(3.68 ± 1.69),(10.45 ± 4.16) μg/L] were significantly lower than that of the NI group [(23.68 ± 3.85)μg/L,all P ＜ 0.05],and the means of serum iodine of HI1 and HT2 groups [(502.67 ± 97.03),(822.15 ± 139.45)μg/L] were significantly higher than that of the NI group (all P ＜ 0.01).Although the mean of serum iodine of HI group gradually decreased with the progression of gestation,the difference was not statistically significant(all P ＞ 0.05).The iodine levels in amniotic fluid of fetal rats at the second and the third trimesters in LI1 group(0.85,3.00 μg/L) were significantly lower than that of the NI group(3.56,7.91 μg/L,all P ＜ 0.01),but the difference was not statistically significant between the iodine level in amniotic fluid of fetal rats of the LI2 and the NI groups at the second and the third trimesters(all P ＞ 0.05).The iodine levels in amniotic fluid of fetal rats at the second and the third trimesters in the HI1 group(49.59,171.21 μg/L) were significantly higher than that of the NI group(all P ＜ 0.01).The iodine levels in amniotic fluid of fetal rats at the second and the third trimesters in HI2 group (98.76,544.77 μg/L) were significantly higher than that of the NI group(all P ＜ 0.01).The iodine level in amniotic fluid of fetal rats in the third trimester was significantly higher than that of the second trimester in all the groups (all P ＜ 0.01).The ratios of serum iodine and urinary iodine of the LI1 and the LI2 groups (1.29 ± 1.14,1.70 ± 1.01) were significantly higher than that of the NI group(0.51 ± 0.37,all P ＜0.01),and that of the HI1 and the HI2 groups(0.21 ± 0.07,0.11 ± 0.07) were significantly lower than that of the NI group (all P ＜ 0.01).The ratios of amniotic fluid iodine and serum iodine of the LI and the LI2 groups (0.19 ± 0.15,0.32 ± 0.17) were significantly higher than that of the NI group(0.13 ± 0.05,P ＜ 0.01),but the difference was not statistically significant between HI1 and HI2 groups(0.09 ± 0.03,0.11 ± 0.04) and NI group(all P ＞ 0.05).The ratio of amniotic fluid iodine and serum iodine of the third trimester was significantly higher than that of the second trimester(all P ＜ 0.05).Conclusions Different iodine intake leads to changes in the levels of maternal iodine metabolism in rats during pregnancy.There probably is a protection mechanism in the mother's body,which protects the mother and the fetal from injury by iodine excess or iodine deficiency.

Rat insulin-like growth factor- Ⅰ and transforming growth factor-β1 mRNA expression in thyroid and placenta with different iodine intakes during pregnancy / 中国地方病学杂志

ObjectiveTo study the mRNA expression of rat Insulin-like growth factors- Ⅰ (IGF- Ⅰ ) and Transforming growth factor-β1 (TGF-β1) in thyroid and placenta with different iodine intakes during pregnancy.MethodsOne hundred and fifty female Wistar rats,weighting 80 - 100 g,were randomly divided into five groups according to body weight,30 rats in each group.Each group was given deionized water containing different concentrations of iodine,50 μg/L(control group,NI),0 μg/L(iodine deficiency 1 group,LI1 ),5 μg/L(iodine deficiency 2 group,LI2),3000 μg/L(iodine excess 1 group,HI1 ),and 10 000 μg/L(iodine excess 2 group,HI2),respectively.After feeding for 12 weeks,the female rats were mated with male rats.The female rats were sacrificed at first(6,7 days),trimester( 12,13 days),and third trimesters( 19,20 days),respectively,then their thyroid and placenta were collected.The mRNA expressions of IGF- Ⅰ and TGF-1 in thyroid and placenta were detected by real-time quantitative PCR.Results①The actual thyroid weights of LI1 and LI2 groups[ (12.17 ± 5.41 ) × 10-2 g,(3.54 ± 1.21) × 10-2 g] were significantly higher than that of NI group[ (2.05 ± 0.50) × 10-2 g,all P ＜ 0.05] ;actual weights of HI1 and HI 2 groups[ (1.64 ± 0.27) × 10-2 g,(1.66 ± 0.29) × 10-2 g] were compared with that of NI group,the difference was not statistically significant(all P ＞ 0.05).②The mRNA expression of IGF- Ⅰ: at the first trimester,LI1 and LI2 groups(l.98 ± 0.35,1.47 ± 0.22) were all higher than that of NI group(1.01 ± 0.18,all P＜ 0.01 ),HI1 and HI2 groups(0.68 ± 0.16,0.75 ± 0.09) were lower than that of NI group(all P ＜ 0.01 );at the second trimester,HI2 group( 1.14 ± 0.17) was lower than that of NI group( 1.58 ± 0.33,P ＜ 0.01 ) ; at the third trimester,LI2 and HI2 groups(1.47 ± 0.20,1.45 ± 0.35) were lower than that of NI group(2.20 ± 0.37,all P＜0.01).The mRNA expression of IGF- I level in NI group at the first,second,and third trimesters(1.01 ±0.18,1.58 ±0.33,2.20 ± 0.37) was up regulated gradually,pairwise comparisons were statistically significant(all P ＜ 0,01 ).③The mRNA expression of TGF-β1: at the first trimester,LI1 group (1.37 ± 0.13) was higher than NI group (1.05 ±0.18,P ＜ 0.01 ),HI1 and HI2 groups(0.50 ± 0.09,0.44 ± 0.11) were lower than NI group(all P＜ 0.01); at the second trimester,LI1 and HI2 groups(1.39 ± 0.28,1.17 ± 0.12) were higher than NI group(0.63 ± 0.22,all P ＜0.01 ) ; at the third trimester,LI1 and LI2 groups ( 1.57 ± 0.30,1.23 ± 0.20) were higher than NI group ( 0.68 ± 0.17,all P＜ 0.01).TGF-β1 mRNA expressions of NI group at the second (0.63 ± 0.22) and third trimesters(0.68 ± 0.17) were lower than that of the first trimester (1.05 ± 0.18,all P ＜ 0.01).④ Rats' IGF-Ⅰ mRNA expression in placental: at the second trimester HI1 group,HI2 group( 1.48 ± 0.16,1.45 ± 0.25) were all higher than the NI group ( 1.00 ± 0.10,all P ＜ 0.01 ) ; at third trimester,HI1 group ( 1.75 ± 0.15 ) were higher than the NI group ( 1.54 ± 0.29,P＜ 0.05),HI2 group(l.94 ± 0.31) were higher than the NI group(P ＜ 0.01 ).IGF- Ⅰ mRNA expression in placental of NI group at the third trimester was higher than the second trimester(P＜ 0.01).⑤ Rats' TGF-β1 mRNA expression in the placenta: at the second trimester and the third trimester of pregnancy there were no significant difference between the five groups(all P ＞ 0.05) ; NI group at the third trimester(0.83 ± 0.16) was lower than the second trimester(0.98 ± 0.20,P ＜ 0.05).Conclusions During pregnancy,IGF- I mRNA expression increases in thyroid under the conditions of iodine deficiency,and this effect is particularly significant in the first trimester; at the same time,TGF-β1 mRNA expression is increased,and this inhibition becomes clear with the deepening of iodine deficiency.Under the condition of iodine excess,the functions of IGF- Ⅰ and TGF-β1 in thyroid above-mentioned were relatively weak.With the development of gestational period,promoting tissues growth and differentiation effect of placenta's IGF- Ⅰ was more significant gradually,but,inhibited effect of TGF-β1 was weaken.

Effect of different levels of iodine nutrition on secretion of placental hormone in pregnant rats / 中国地方病学杂志

Objective To study the effect of different levels of iodine nutrition on secretion of placental hormone in pregnant rats.Methods Two hundred and twenty five Wistar rats (165 female,60 male),weighing about 80 - 100 g were used in the study.Female rats were randomly divided into five groups according to their body weights:low iodine group Ⅰ(LⅠ),low iodine group Ⅱ (LⅡ),adequate iodine(control) group(Al),high iodine group Ⅰ ( HⅠ ),and high iodine group Ⅱ (H Ⅱ ),and 33 rats in each group.Animals in the low iodine groups were fed low-iodine diet,the iodine content was 13.46 μg/kg,in addition,these rats drank deionized water which containing potassium iodated,the dose was 0 and 5 μg/L,respectively.The rats of adequate and the two high iodine groups were fed normal diet,the iodine content was 22.00 μg/kg,they also drank deionized water,containing potassium iodated 50,3000,and 10000 μg/L,respectively.The rats mated after 3 months of feeding,and were respectively sacrificed at early pregnancy(5 ± 2)d,second trimester( 12 ± 2)d,and third trimester of pregnancy(17 ± 2)d,and then their serum was taken.Serum human chorionic gonadotropin(HCG),human chorionic thyrotropin(HCT),and progesterone were measured by enzyme-linked immunosorbent assay (ELISA).Results In the third trimester,the serum levels of rat HCG were significantly different between groups(F =4.16,P ＜ 0.05).The means of rats serum HCG of the two low iodine groups [ (16.08 ± 4.45),(17.43 ± 2.70)U/L] were significantly higher compared with that of AI group[ (13.68 ± 3.52)U/L] in the third trimester(all P ＜ 0.01 ).In the second and third trimester,the levels of rats serum HCT were significantly different between groups(F =3.59,3.40,all P ＜ 0.05).The means of rats serum HCT of HI group [(70.11 ± 10.97)μU/L] in the second trimester and HII group[(74.93 ± 13.22)μU/L] in the third trimester were higher than those of AI group[ (57.14 ± 12.56),(58.17 ± 8.54)μU/L] significantly(all P ＜ 0.01 ).There were statistical differences of the means of serum progesterone among trimester of pregnancy(F =4.06,4.43,all P ＜ 0.05).The level of serum progesterone of the third trimester[ ( 1462.80 ± 286.48 )pmoL/L] compared to those of the first[ (1929.93 ± 158.37) pmol/L] and the second trimester[ (1856.44 ± 542.08)pmol/L] was decreased significantly(all P ＜ 0.05) in LI group.In the control group,the level of serum progesterone of the second trimester [ (2046.45 ± 475.67)pmol/L ] was significantly higher than the first trimester[ (1714.39 ± 461.71 )pmol/L,P ＜ 0.05 ].Conclusions During pregnancy,placenta could promote HCG secretion under iodine-deficient conditions.In addition,the placenta increases the secretion of HCT under conditions of excess iodine.In the condition of severe iodine deficiency,the secretion of serum progesterone decreases,and further decreases with prolongation of pregnancy,but it is opposite to the change of HCG during pregnancy.This phenomenon could lead to harmful pregnant outcomes easily.

The inhabitant's iodine nutrition status of some coastal areas in China: a cross-sectional study / 中国地方病学杂志

Objective To study whether the measure of consumption of iodized salt to prevent iodine deficiency disorders could lead to residents excessive iodine intake in the coastal areas in China.Methods A large population-based cross-sectional study was carried out in four typical costal provinces along the coastline from north to south,including Liaoning,Shanghai,Zhejiang and Fujian.In addition to survey all of its area of Shanghai,the other three provinces' investigation was carried out at urban and rural levels,respectively,including 5 costal cities,5 costal villages and 3 inland rural areas(as a control point) in each province.In each investigated spot,the local water iodine,residents qualified iodized salt consumption rate,per capita daily intake of salt and urinary iodine levels in different populations were investigated.Results A total of 7552 copies of drinking water samples,7996 salt samples and 9873 urine samples of different populations(adults,lactating women,pregnant women and children) were collected from the 4 provinces.Except the coastal cities and counties of Zhejiang province,the qualified iodized salt consumption rates at household were all greater than 90％ in the investigated spots.The median urinary iodine(MUI) of adults and children investigated in the costal areas were in the range of 100 - 299μg/L.The MUIs of lactating women of all investigated areas were all greater than 100 μg/L.The MUI of pregnant women was at an insufficient iodine level which was lower than 150 μg/L in Shanghai,the costal cities of Zhejiang and the coastal counties of Fujian.Conclusions The overall level of iodine nutrition of coastal residents is appropriate; and it is insufficient among pregnant women in some coastal areas; coastal areas should adhere to the salt iodization measures to control iodine deficiency disorders.

Effect of tumor necrosis factor-α with different levels of iodine on expression of Na+/I- symporter in cultured lactating mammary cells / 中国地方病学杂志

Objective To observe the expression of Na+/I- symporter(NIS) in cultured lactating mammary cells with different levels of iodine and the effect of tumor necrosis factor-α(TNF-α). Methods Original generation of mouse lactating mammary cells cultured in vitro were divided into low iodine group Ⅰ (LI-Ⅰ), low iodine group Ⅱ (LI-Ⅱ), adequate iodine group(AI), high iodine group Ⅰ(HI-Ⅰ), and high iodine group Ⅱ(HI-Ⅱ). Cells were cultured in DEME/F12 culture medium for 24 h with different concentrations of iodine (0,5,50,3000 and 10 000 μg/L, respectively), and TNF-α( 10-2 mg/L) was added to some of cultured cells for 24 h. The expression of NIS mRNA of lactating mammary cells was determined by real-time quantitative PCR and the expression of NIS protein was detected by In-Cell Western. Results In iodine alone group, the expression of NIS mRNA in LI-Ⅰ group [ (64.66 ± 14.99) x 10-4] was higher than that of AI group[ (22.76 ± 7.36) × 10-4, P ＜ 0.01 ]; HI-I group[ (10.18 ±3.53) × 10-4] and HI-Ⅱ group[ (8.59 ± 2.89) × 10-4] were lower than that of AI group(all P ＜ .0.05); With increased iodine concentration, the expression of NIS mRNA decreased. The expression of NIS mRNA in LI-Ⅰ group [(2.72 ± 0.45) × 10-4], LI-Ⅱ group[ (2.69 ± 0.68) × 10-4] and AI group[(1.80 ± 0.67) × 10-4] with iodine plus TNF-o were all lower than that of LI-Ⅰ group, LI-Ⅱ group[ (29.82 ± 4.47 ) × 10-4], and AI group without TNF-α (all P ＜ 0.01). In iodine plus TNF-α, the expression of NIS mRNA in HI-Ⅰ group[(6.58 ± 2.87) × 10-4] and HI-Ⅱ[(7.04 ± 1.36) × 10-4] group were all higher than that of AI group(all P ＜ 0.05); With increased iodine deficiency or iodine excess, the expression of NIS mRNA increased. With increased iodine concentration, the expression of NIS protein decreased in iodine alone group. The expression of NIS protein in iodine plus TNF-α was all lower than that in iodine alone group. In iodine plus TNF-α, the expression of NIS protein increased in both iodine deficiency and iodine excess conditions. Conclusions Iodine may decrease the expression of NIS mRNA and protein of lactating mammary cells. The expression of NIS mRNA and protein of lactating mammary cells was inhibited by TNF-α under different levels of iodine.

Effects of different levels of iodine concentration on insulin-like growth factors Ⅰ mRNA expression of thyroid and breast in lactating rats / 中国地方病学杂志

Objective To study the effects of different levels of iodine concentration on insulin-like growth factors Ⅰ (IGF-1) mRNA expression of thyroid and breast in lactating rats. Methods Thirty Wistar female rats, having been weaned for 1 month, were randomly divided into three groups according to their body weights, i. e. :low iodine(LI) group,adequate iodine(AI) group, high iodine(HI) group, 10 rats in each group. Synthetic fodder and deionized water containing iodine of 0,150,3000 μg/L was respectively fed to these rats. After fed for 3 months, the rats mated and had offspring. Their mammary glands, thyroids and serum were sampled at lactation day 5. The serum iodine of lactating rats were determined by moderate acid digestion method, level of T3 and T4 were determined by radioimmunoassay method, and the expressions of IGF-1 mRNA of mammary glands and thyroids were determined by real-time fluorescence quantitative PCR assay. Results The value of serum iodine of LI group [(17.38±3.27) μg/L] was lower than that of AI group [(43.42±6.92) μg/L, P<0.05], and the value of serum iodine of HI group[(350.10±38.46)μg/L] was higher than that of AI group (P<0.05). The level of T3 of LI group and HI group[ (1.11±0.25), (1.61±0.33)μg/L] reduced obviously compared with that of AI group[(2.18±0.46) μg/L, P<0.05]. The mean of T4 of LI group and HI group[(33.40±11.11),(56.54±10.38)μg/L] had no statistical significance compared with AI group(44.02±12.51)μg/L, P>0.05), but the level of T4 of LI group was lower than that of HI group(P<0.05). The level of IGF-1 mRNA expression of thyroid in LI group and HI group (0.34±0.08, 0.23±0.08) was higher than that of AI group(0.15±0.03, P<0.05). The level of IGF-1 mRNA expression of lactating mammary in LI group(0.59±0.18) was higher than that of AI group(0.40±0.10, P<0.05). The level of IGF-1 mRNA expression of thyroid was lower than that of breast between the same group(t=3.54, 6.44,2.62, all P<0.05). Conclusion Iodine could affect IGF-1 mRNA expression of thyroid and lactating mammary, and IGF-1 mRNA expression of lactating mammary was stronger than that of the thyroid.

Study on the effects of different vitamin A levels on thyroid cell apoptosis and related gene expression of mice taking excessive iodine / 中国地方病学杂志

Objective To explore the effects of different vitamin A(VA) levels on thyroid cells apoptosis and its gene expression of mice taking excessive iodine. Methods Kunming mice were randomly divided into 6 groups according to body weight 3 weeks after born: normal control(NI) group, high iodine(HI) group, low vitamin (LVA) group, high iodine plus low vitamin A(HI+LVA) group, high iodine plus vitamin A1 (HI+VA1) group, high iodine plus vitamin A2(HI+VA2) group. The VA was given in food(4000,4000,0,0,8000,16 000 U/kg), and the iodine was given as potassium iodate in water (I-:50,3000,50,3000,3000,3000 μg/L). The apoptosis was tested using in situ end labehng(TUNEL) method. Reverse transcription polymerase chain reaction (RT-PCR) were used to measure the level of mRNA of apoptosis gene(Fas, FasL, Bcl-2) in tissues. Results Apoptotic index measured by TUNEL method was rising along with the mice age. Compared to NI group[(14.09±5.68)%], apoptotic index was significantly increased in HI[(20.91±9.57)%], HI+LVA[(20.29±9.90)%]and HI+VA2 [(19.51±8.25)%]groups in the three months(P < 0.05). Compared to NI group[(16.80±9.90)%], apoptotic index was significantly increased(P < 0.05) in HI[(23.22±8.58)%],LVA[(22.56±6.17)%],HI+LVA [(25.99±9.62)%],HI+VA1 [(21.65±7.74)%]groups in the six months. Compared with the NI group(Fas: 1.29±0.25,1.27±0.26; FasL: 1.60±0.13,1.65±0.13), the mRNA levels of Fas and FasL in HI group(Fas: 1.57±0.36,1.49±0.35; FasL: 1.85±0.46,1.84±0.32) were increased, but the differences were not remarkable(P > 0.05) in the three and six months. Compared with the HI group, the mRNA levels of Fas in HI+ VA1, HI+VA2(1.33±0.35, 1.30±0.26) groups were decreased to the level in NI group in the six months. The mRNA levels of Fas and FasL were not different (P > 0.05) between HI+LVA(I.60±0.27,1.88±0.46) and HI groups in the three months. The mRNA levels of Bcl-2 were not remarkably differences in the three months (1.05±0.19,0.96±0.33,0.95±0.26,1.18±0.27,1.10±0.19,0.98±0.36, all P > 0.05), and in the six months (1.35±0.28,1.60±0.25,1.48±0.18,1.71±0.26,1.66±0.29,1.56±0.35, all P > 0.05). Conclusions Excessive iodine can cause thyroid cells apoptosis in mice. Supplementation of suitable amount of VA can regulate the levels of the apoptosis-related genes expression, and partly antagonize the apoptosis caused by high iodine.

Analysis and cross-study of the organizations and teams of the endemic disease prevention and control in China / 中国地方病学杂志

Objective To know the current conditions of institution set-up,personnels allocated and equipment supplied in county-,city-and country-level in endemic disease prevention and control.Methods Questionnaires,regarding institution set-up,personnels allocated and equipment supplied,was performed among staffs from administrative apartment and professional apartment.Results There were 31 institutions for endemic disease prevention and control in province level of our country(except Hainan Province),with one institution in each province.There were 308 institutions for endemic disease prevention and control in city level,and 23 cities did not have one.There were 2340 institutions for endemic disease prevention and control in county level,none in 502 counties.There were 20 provinces which had the professional crew of the endemic disease administration,but other provinces did not.The proportion of high-grade professional staff of province,city,county level was 24.84% (310/1248),17.05%(481/2821),5.31%(598/11 256)respectively.The averaged size of wdrking place at province-,city-and county-level was 2603.9,324.6,1227 m2.The averaged area of laboratory of province,city,county level was 1093.8,147.4 and 46.6 m2 respectively.The average quantity of equipments valued over ten thousand yuan at province-,city-and county-level is 15.5,2.2,0.6 respectively.Conclusions After the innovation of organizations for endemic disease prevention and control,the number of personnels devoting to this work has been curtailed,working place and equipment is insufficient,which hinders the prevention and control.

Relationship among sexual differences of susceptibility to motion sickness, AVP levels of plasma and pituitary and V1b receptor expression of pituitary in rats / 中国应用生理学杂志

<p><b>AIM</b>To investigate the relationship among sexual differences of motion sickness (MS), AVP levels of plasma and pituitary and the expression of pituitary V1b receptors for further understanding of the MS mechanisms.</p><p><b>METHODS</b>The conditioned taste aversion (CTA) of 0.15% saccharin sodium solution (SSS) was served as MS model. 98 (49 male and 49 female) rats were used in this experiment, 50 for the detection of the AVP level in plasma and pituitary with radioimmunoassay (RIA), 12 for the observation of the number of V1b receptor-positive neurons in the pituitary with the fluorescence immunohistochemistry method, the rest for the evaluation of the expression of V1b receptor in the pituitary by Western blot.</p><p><b>RESULTS</b>With regard to male rats, decrease of the drinking volume of 0.15% SSS was greater in female rats after rotatory stimulation. The plasma AVP concentration of female rats was significantly higher than that of males under normal conditions, but reduced significantly after rotatory stimulation. However, no significant change was found in male rats. In addition, the pituitary AVP level of the female rats was significantly higher than that of the male rats under normal conditions, but decreased at 8 h and significantly at 24 h after rotation. Similarly, the pituitary AVP level of male rats also decreased significantly at 8 h after rotation, but this decrease was not comparable to that of the females. At 24 h after rotation the pituitary AVP level almost recovered in male rats. In the pituitary, which was related to the stress response, the V1b receptor-positive neurons and the expression level of V1b receptor in female rats were significantly higher than those of the male rats, but they decreased significantly after rotation, while no apparent change was detected in the male rats.</p><p><b>CONCLUSION</b>The changes of plasma and pituitary AVP and V1b receptor level of the pituitary after rotatory stimulation are different between male and female rats and the AVP secretion of the pituitary may be involved in the sexual difference in susceptibility to motion sickness.</p>

Effects and mechanisms of ginsenoside Rb3 on glutamate excitotoxic injury in cultured neurons of rat hippocampus / 中国应用生理学杂志

<p><b>AIM</b>To observe protective effects of ginsenoside Rb3 on glutamate excitotoxic injury in cultured hippocampal neurons and involved mechanisms.</p><p><b>METHODS</b>On cultured rat hippocampal neurons treated with glutamate at toxic concentration, we made the following investigations: by using MTT assay, LDH leakage detection, tests of total NOS, iNOS and cNOS activity, and the protective effects of ginsenoside Rb3.</p><p><b>RESULTS</b>Ginsenoside Rb3 can enhance the hippocampal neuronal viability, decrease the LDH leakage, elevate the viability of cNOS, and in the same time weaken iNOS's viability.</p><p><b>CONCLUSION</b>Ginsenoside Rb3 has the significant protective effects on glutamate excitotoxic injury. The involved mechanism may include antagonizing the injury of neuron membrane, inhibiting the viability of iNOS, and increasing the activity of cNOS.</p>

Protective effects of ginsenoside RB3 on hypoxic/ischemic brain injury and involved mechanisms / 中国应用生理学杂志

<p><b>AIM</b>To observe protective effects and involved mechanism of ginsenoside Rb3 on hypoxic/ischemic brain injury, using cultured hippocampal neurons, rat hippocampal slices and intact animals.</p><p><b>METHODS</b>(1) Mice were tightly closed in glasses of 150 ml, and then survival time of them was observed. (2) During simulated ischemia and after reoxygenation, changes of orthodromic population spikes (OPS) in the area CA1 of hippocampal slice were investigated. (3) By using histochemistry, the expressions of NOS in CA1 area of rat hippocampus after hypoxic exposure were observed. (4) Using LDH detection, tests of total NOS, iNOS and cNOS activity, the protective effects of ginsenoside Rb3 were investigated on cultured hippocampal neurons treated with hypoxia.</p><p><b>RESULTS</b>(1) Given ginsenoside Rb3 (10 mmol/L), mice survived significantly longer than that of control group. (2) The occurrence of HIP (hypoxic injury potentials) decreased after administration of ginsenosides Rb3 (60 micromol/L) in many slices, while the recovery rate and amplitude of OPS after reoxygenation were significantly higher than those of the control group. (3) In CA1 area of rat hippocampus, NOS-positive neurons increased at the end of 24 h hypoxia and further 24 h reoxygenation, while the number of NOS-positive neurons decreased after treatment with ginsenoside Rb3. (4) The LDH leakage rate of cultured rat hippocampal neurons increased at the end of hypoxia, while it decreased after treatment with Rb3. Moreover the total NOS, especially iNOS activity of these neurons also decreased.</p><p><b>CONCLUSION</b>Ginsenoside Rb3 has a significant protective effect on hypoxic-ischemic injury of neurons, and this involves the stabilization of the cell membrane, the inhibition of the expression and activity of NOS, especially iNOS activity.</p>