Antifungal Agents ; therapeutic use ; Fever ; Histiocytosis ; drug therapy ; etiology ; Humans ; Infant ; Lung Diseases, Fungal ; complications ; diagnosis ; drug therapy ; Male

Arthropathy, Neurogenic ; Child ; Coxa Vara ; Hand Deformities, Congenital ; Humans ; Male ; Synovitis

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.

OBJECTIVETo investigate the effects of schisandrin B (Sch-B) on expression of transforming growth factor-beta1 (TGF-beta1) and signal transduction molecule mRNA in rat lungs exposed to SiO2, and explore the intervention mechanism of Sch-B on pulmonary fibrosis induced by SiO2.

METHODSNinety six Wistar rats were randomly divided into control (normal saline) group, SiO2 group and SiO2 plus Sch-B group. The rats were exposed to SiO2 by direct tracheal instillation to establish the silicotic animal models. SiO2 group and SiO2 plus Sch-B group were treated with 1 ml SiO2 (50 mg/ml) for each rat From the first day after model establishment, SiO2 plus Sch-B group were orally given Sch-B (80 mg/kg) a day, control group and silica group were orally given olive oil. On the 3rd, 7th, 14th and 28th days after treatment, 8 rats in each group were sacrificed and samples were collected. The histo-pathological examination of lung was performed by HE staining. The expression levels of TGF-beta1, TGF-betaR II and Smad4 mRNA in the lung tissues were detected by RT-PCR.

RESULTSThe results of histo-pathological examination showed that in SiO2 group, lung tissues were injured obviously; the alveolar inflammation with alveolus interval edema and inflammation cell infiltration appeared on the 3rd and 7th days; the alveolus interval became thicker, became thicker, fibroblast and collagen matrix increased markedly on 14th day; the alveolar structure was damaged, alveolar wall thickened obviously, collagen aggravation and pulmonary fibrosis displayed on 28th day. The alveolar inflammation and pulmonary fibrosis in SiO2 plus Sch-B group were significantly less than those in SiO2 group. The expressions levels of TGF-beta1 TGF-betaR II and Smad4 mRNA (TGF-1beta: 1.03 +/- 0.31, 1.33 +/- 0.39,1.08 +/- 0.26, 0.82 +/- 0.16, TGF-betaR II: 0.65 +/- 0.11, 0.80 +/- 0.16, 0.83 +/- 0.24, 0.62 +/- 0.15, Smad4:0.87 +/- 0.15, 0.68 +/- 0.11, 0.78 +/- 0.19, 0.30 +/- 0.08) in SiO2 group were significantly higher than those in the control group (TGF-beta1:0.59 +/- 0.22, 0.55 +/- 0.25, 0.56 +/- 0.20, 0.55 +/- 0.12, TGR-betaR II :0.28 +/- 0.13, 0.31 +/- 0.15, 0.34 +/- 0.15, 0.27 +/- 0.09, Smad4:0.23 +/- 0.11, 0.40 +/- 0.12, 0.39 +/- 0.12, 0.18 +/- 0.06) (P < 0.01 or P < 0.05), but the expression level of TGF-beta1 mRNA was the highest on the 7th day. The expression levels of TGF-beta1 and Smad4 mRNA (TGF-beta1:0.68 +/- 0.28, 0.88 +/- 0.25, 0.75 +/- 0.11, 0.61 +/- 0.14,Smad4:0.25 +/- 0.12, 0.45 +/- 0.09, 0.44 +/- 0.07, 0.21 +/- 0.04) in SiO2 plus Sch-B group were significantly lower than those in SiO2 group (P < 0.01 or P < 0.05 ), but there were no significant differences of the TGFbetaR II mRNA expression levels between SiO2 group and SiO2 plus Sch-B group.

CONCLUSIONSch-B can reduce the pulmonary fibrosis induced by SiO2 through inhibition of the mRNA express of TGF-beta1 and Smad4 in the lung tissue, modulating the TGF-beta1/Smad4 signal transduction pathway and inhibiting the target gene activation.

Animals ; Cyclooctanes ; pharmacology ; Female ; Lignans ; pharmacology ; Lung ; drug effects ; metabolism ; pathology ; Male ; Polycyclic Compounds ; pharmacology ; RNA, Messenger ; genetics ; Rats ; Rats, Wistar ; Signal Transduction ; drug effects ; Silicosis ; metabolism ; pathology ; Smad4 Protein ; genetics ; metabolism ; Transforming Growth Factor beta1 ; genetics ; metabolism

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.

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.

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.

AIM To observe the clinical effects and safety of Zibei Zhike Granules (Asteris Radix et Rhizoma,Ardisiae japonicae Herba,Fritiliariae cirrhosae Bulbus,etc.) for acute broncho-bronchitis with remained toxicity lingering lung.METHODS A multi-center,randomized,double-blinded,double-simulation and positive drug parallel controlled trial was adopted.Two hundred and forty cases of patients with the 1 ∶ 1 ratio were assigned to treatment and control group.The treatment group were treated with Zibei Zhike Granules and the control group were treated with Zikebao Tablets (Asteris Radix et Rhizoma,Citri rubrum exocarpium,Platycodi Radix,etc.).The treatment course lasted five days.RESULTS The total effective rate of acute broncho-bronchitis in the treatment group was 73.04％,and 54.78％ in the control group.There was statistical significance between the total effective rate of the two groups (P ＜ 0.01).The total effective rate of traditional Chinese medicine syndrome in the treatment group was 73.91％ and 60.86％ in the control group,and there was statistical significance between the total effective rate of the two groups (P ＜ 0.05).The treatment group showed better clinical effects in improving individual symptoms of cough and spitting sputum.CONCLUSION Zibei Zhike Granules has good clinical effects on acute broncho-bronchitis.

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.