Acteoside promotes autophagy and apoptosis of hepatoma cells by regulating JNK signaling pathway / 中国中药杂志

This study explored the molecular mechanism of acteoside against hepatoma 22(H22) tumor in mice through c-Jun N-terminal kinase(JNK) signaling pathway. H22 cells were subcutaneously inoculated in 50 male BALB/c mice, and then the model mice were classified into model group, low-dose, medium-dose, and high-dose acteoside groups, and cisplatin group. The administration lasted 2 weeks for each group(5 consecutive days/week). The general conditions of mice in each group, such as mental status, diet intake, water intake, activity, and fur were observed. The body weight, tumor volume, tumor weight, and tumor-inhibiting rate were compared before and after administration. Morphological changes of liver cancer tissues were observed based on hematoxylin and eosin(HE) staining, and the expression of phosphorylated(p)-JNK, JNK, B-cell lymphoma-2(Bcl-2), Beclin-1, and light chain 3(LC3) in each tissue was detected by immunohistochemistry and Western blot. qRT-PCR was performed to detect the mRNA expression of JNK, Bcl-2, Beclin-1, and LC3. The general conditions of mice in model and low-dose acteoside groups were poor, while the general conditions of mice in the remaining three groups were improved. The body weight of mice in medium-dose acteoside group, high-dose acteoside group, and cisplatin group was smaller than that in model group(P<0.01). The tumor volume in model group was insignificantly different from that in low-dose acteoside group, and the volume in cisplatin group showed no significant difference from that in high-dose acteoside group. Tumor volume and weight in medium-dose and high-dose acteoside groups and cisplatin group were lower than those in the model group(P<0.001). The tumor-inhibiting rates were 10.72%, 40.32%, 53.79%, and 56.44% in the low-dose, medium-dose, and high-dose acteoside groups and cisplatin group, respectively. HE staining showed gradual decrease in the count of hepatoma cells and increasing sign of cell necrosis in the acteoside and cisplatin groups, and the necrosis was particularly obvious in the high-dose acteoside group and cisplatin group. Immunohistochemical results suggested that the expression of Beclin-1, LC3, p-JNK, and JNK was up-regulated in acteoside and cisplatin groups(P<0.05). The results of immunohistochemistry, Western blot, and qRT-PCR indicated that the expression of Bcl-2 was down-regulated in the medium-dose and high-dose acteoside groups and cisplatin group(P<0.01). Western blot showed that the expression of Beclin-1, LC3, and p-JNK was up-regulated in acteoside and cisplatin groups(P<0.01), and there was no difference in the expression of JNK among groups. qRT-PCR results showed that the levels of Beclin-1 and LC3 mRNA were up-regulated in the acteoside and cisplatin groups(P<0.05), and the level of JNK mRNA was up-regulated in medium-dose and high-dose acteoside groups and cisplatin group(P<0.001). Acteoside promotes apoptosis and autophagy of H22 cells in mice hepatoma cells by up-regulating the JNK signaling pathway, thus inhibiting tumor growth.

Association between iron deficiency and prevalence of thyroid autoimmunity in pregnant and non-pregnant women of childbearing age: a cross-sectional study / 中华医学杂志(英文版)

BACKGROUND@#Thyroid autoimmunity (TAI) is prevalent among women of reproductive age and associated with adverse pregnancy outcomes. This study aimed to investigate the association between iron nutritional status and the prevalence of TAI in women during the first trimester of pregnancy and in non-pregnant women of childbearing age.@*METHODS@#Cross-sectional analysis of 7463 pregnant women during the first trimester of pregnancy and 2185 non-pregnant women of childbearing age nested within the sub-clinical hypothyroid in early pregnancy study, a prospective collection of pregnant and non-pregnant women's data, was conducted in Liaoning province of China between 2012 and 2015. Serum thyrotropin, free thyroxine, thyroid peroxidase antibodies (TPOAbs), thyroglobulin antibodies (TgAbs), serum ferritin, and urinary iodine were measured. Iron deficiency (ID) was defined as serum ferritin 150 μg/L. TPOAb-positive was defined as >34 U/mL and TgAb-positive was defined as >115 U/mL. Multilevel logistic regression was conducted to examine the association between TAI and different iron nutritional status after adjusting for potential confounders.@*RESULTS@#The prevalence of isolated TPOAb-positive was markedly higher in women with ID than those without ID, in both pregnant and non-pregnant women (6.28% vs. 3.23%, χ = 10.264, P = 0.002; 6.25% vs. 3.70%, χ = 3,791, P = 0.044; respectively). After adjusting for confounders and the cluster effect of hospitals, ID remained associated with TPOAb-positive in pregnant and non-pregnant women (odds ratio [OR]: 2.111, 95% confidence interval [CI]: 1.241-3.591, P = 0.006; and OR: 1.822, 95% CI: 1.011-3.282, P = 0.046, respectively).@*CONCLUSION@#ID was associated with a higher prevalence of isolated TPOAbs-positive, but not with isolated TgAb-positive, in both pregnant women during the first trimester of pregnancy and non-pregnant women of childbearing age, while IO was not associated with either isolated TPOAb-positive or isolated TgAb-positive.@*CLINICAL TRIAL REGISTRATION@#ChiCTR-TRC-13003805, http://www.chictr.org.cn/index.aspx.

Association between iron deficiency and prevalence of thyroid autoimmunity in pregnant and non-pregnant women of childbearing age: a cross-sectional study / 中华医学杂志(英文版)

Background@#Thyroid autoimmunity (TAI) is prevalent among women of reproductive age and associated with adverse pregnancy outcomes. This study aimed to investigate the association between iron nutritional status and the prevalence of TAI in women during the first trimester of pregnancy and in non-pregnant women of childbearing age.@*Methods@#Cross-sectional analysis of 7463 pregnant women during the first trimester of pregnancy and 2185 non-pregnant women of childbearing age nested within the sub-clinical hypothyroid in early pregnancy study, a prospective collection of pregnant and non-pregnant women’s data, was conducted in Liaoning province of China between 2012 and 2015. Serum thyrotropin, free thyroxine, thyroid peroxidase antibodies (TPOAbs), thyroglobulin antibodies (TgAbs), serum ferritin, and urinary iodine were measured. Iron deficiency (ID) was defined as serum ferritin <15 μg/L and iron overload (IO) was defined as ferritin >150 μg/L. TPOAb-positive was defined as >34 U/mL and TgAb-positive was defined as >115 U/mL. Multilevel logistic regression was conducted to examine the association between TAI and different iron nutritional status after adjusting for potential confounders.@*Results@#The prevalence of isolated TPOAb-positive was markedly higher in women with ID than those without ID, in both pregnant and non-pregnant women (6.28% vs. 3.23%, χ2 = 10.264, P = 0.002; 6.25% vs. 3.70%, χ2 = 3,791, P = 0.044; respectively). After adjusting for confounders and the cluster effect of hospitals, ID remained associated with TPOAb-positive in pregnant and non-pregnant women (odds ratio [OR]: 2.111, 95% confidence interval [CI]: 1.241–3.591, P = 0.006; and OR: 1.822, 95% CI: 1.011–3.282, P = 0.046, respectively).@*Conclusion@#ID was associated with a higher prevalence of isolated TPOAbs-positive, but not with isolated TgAb-positive, in both pregnant women during the first trimester of pregnancy and non-pregnant women of childbearing age, while IO was not associated with either isolated TPOAb-positive or isolated TgAb-positive.@*Clinical trial registration@#ChiCTR-TRC-13003805, http://www.chictr.org.cn/index.aspx.

Changes of IL-21 and Its Mediated JAK/STAT Signaling Pathway in Patients with Immune Thrombocytopenia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the correlation between JAK/STAT signaling pathways and pathogenesis of immune thrombocytopenia(ITP).</p><p><b>METHODS</b>Twenty-six newly-diagnosed ITP patients was included in this study. They all meet the clinical and hematological criteria for the diagnosis of ITP, and patients with coronary heart disease, severe refractory hypertension, diabetes or with severe liver or kidney function incompetence were ruled out. 24 healthy control without autoimmune diseases, viral infectious diseases and with normal liver and kidney functions were also included. The expressions of Jak3, p-Jak3 mRNA, Stat3, and p-Stat3 were tested and the changes in levels of IL-21 mRNA, IL-21 cell secretion after DEX intervention and AG490 blockade were measured.</p><p><b>RESULTS</b>Compared with the healthy control, patients with ITP had significantly high expressions of Jak3, p-Jak3 mRNA, Stat3 and p-Stat3 protein, which significantly reduced after AG490 blocking (P<0.01). The expression of IL-21 mRNA and the secretion of IL-21 obviously decreased after DEX intervention, but increased after AG490 blocking(P<0.01).</p><p><b>CONCLUSION</b>The pathogenesis of ITP associates with the activation of JAK/STAT signaling pathways, and IL-21-mediated JAK/STAT signaling pathways play regulatory role in ITP.</p>

Quality regionalization study on Gentianae Macrophyllae Radix / 中国中药杂志

The 79 samples of Gentianae Macrophyllae Radix were collected based on the distributed information by document literature. Based on sample information, and using the regression model of Gentianae Macrophyllae Radix index component and environmental factors, and combined with the prediction results of ecological suitability by MaxEnt and principal component analysis results of index component, the space distribution of Gentianae Macrophyllae Radix was estimated with the spatial analysis function of ArcGIS. The results showed that it had a higher comprehensive quality in south of Shaanxi, south of Gansu, middle of Sichuan and southeast of Xizang. The study results were coinciding with the producing regions of Gentianae Macrophyllae Radix. It can provide reference for Gentianae Macrophyllae Radix resource conservation, development and utilization.

Berberine inhibits norepinephrine-induced apoptosis in neonatal rat cardiomyocytes via inhibiting ROS-TNF-α-caspase signaling pathway / 中国结合医学杂志

<p><b>OBJECTIVE</b>To determine the effect of berberine (Ber) on norepinephrine (NE)-induced apoptosis in neonatal rat cardiomyocytes.</p><p><b>METHODS</b>The cultured neonatal rat cardiomyocytes were treated with NE in the presence or absence of Ber. The activity of lactate dehydrogenase (LDH) in the culture medium was examined, and apoptosis of cardiomyocytes was assessed by Hoechst 33258, isothiocyanate (FITC)-conjugated annexin-V, and propidine iodide (PI) staining. In addition, the activities of caspases-2 and-3 were measured by a fluorescent assay kit. The level of secreted tumor necrosis factor α (TNF-α) and production of intracellular reactive oxygen species (ROS) were also determined.</p><p><b>RESULTS</b>NE at a concentration of 50 μ mol/L induced an obvious increase in the activity of LDH in the culture medium (P<0.05), which was inhibited by coincubation with 0.5, 1.0, or 2.0 μ mol/L Ber (P<0.05). Ber also significantly attenuated NE-induced apoptosis in a dose-dependent manner (P<0.01). Moreover, Ber at a dose of 2 μ mol/L markedly decreased the ROS and TNF-α productions (P <0.05) and inhibited the activation of caspases-2 and -3 in cardiomyocytes exposed to NE (P<0.05)h.</p><p><b>CONCLUSION</b>The present study suggested that Ber could reduce NE-induced apoptosis in neonatal rat cardiomyocytes through inhibiting the ROS-TNF-α-caspase signaling pathway.</p>

Epidemiological study of the effects of smoking cigarette on thyroid gland / 中华流行病学杂志

<p><b>OBJECTIVE</b>To investigate the effect of cigarette smoking on thyroid gland volume, thyroid function and thyroid autoantibodies in the areas with different iodine intakes.</p><p><b>METHODS</b>A cross-sectional epidemiological study in Panshan (mild iodine-deficient area), Zhangwu (more than adequate iodine intake area) and Huanghua (iodine-excessive area) was conducted in 3761 subjects in 1999.80.2 % of them were followed up in 2004. Questionnaires, thyroid function, thyroid autoantibodies, urinary iodine concentration,and thyroid B ultrasound were performed.</p><p><b>RESULTS</b>The prevalence of goiter was higher in smokers than in non-smokers (15.1% vs. 11.5%, P< 0.05). The average thyroid volume was higher in smokers with phenomenon more obvious in Panshan and Huanghua areas. Data from logistic analysis showed that smoking cigarette was an independent risk factor of goiter. There was no difference in serum TSH and Tg level between smokers and non-smokers. The positive rate of TPOAb (>100 IU/ml) was higher in smokers than in non-smokers(10.8% vs. 9.0 % , P <0.05) and was especially obvious in Huanghua area. Smoking was a independent risk factor of increasing positive rate of TPOAb. During the prospective observation,it was found that the incidence of positive TPOAb(>,100 IU/ml) was 7.4% in the subjects that were from non-smokers turning to smokers and 2.9% in those whose smoking behavior did not change. Logistic analysis indicated that the shifting from non-smoking to smoking was independent risk factor for the increase on high incidence of positive TPOAb.</p><p><b>CONCLUSION</b>Smoking cigarette was a independent risk factor of goiter. Smoking was also a risk factor of increasing TPOAb positive rate. Shifting from not smoking to smoking was an independent risk factor of increasing high incidence of positive TPOAb.</p>

Determination of cut-off points of thyroid peroxidase antibody and thyroglobulin antibody and their clinical significance / 中华检验医学杂志

40 IU/ml were used as cut-off points.(4) TSH level was higher in subjects with positive thyroid autoantibodies than those without antibodies (P

Expression of tyrosine kinase receptor B in OVCAR-3 ovarian cancer cells and its significance / 中国癌症杂志

Background and purpose:TrkB,a neurotrophic tyrosine kinase receptor,serves as a potent and specific suppressor of anoikis of non-malignant epithelial cells,and induces high invasion capacity in these cells.TrkB over-expression has been associated with chemotherapy resistance and poor survival in neuroblastoma and some other highly aggressive cancers.However,the relationship of the expression of TrkB to anoikis resistance in ovarian cancer cells has rarely been reported in literature.This study investigated the expression and significance of anoikis- suppressor TrkB in OVCAR-3 ovarian cancer cells.Methods:The expression of TrkB and its ligand BDNF was evaluated in OVCAR-3 ovarian cancer cells under different culture conditions by RT-PCR and Western blot.Results: TrkB mRNA was overexpressed in multicellular spheroids(cell-spheroids,anchorage-independent culture,AIC)as compared to that in OVCAR-3 cells(adhesive-cells,adhesive culture,AC),(35.3?0.7)% versus(23.5?0.5)%;but BDNF mRNA expression was the opposite to the above situation,(41.4?0.6)% versus(32.24?0.7)%(P

Impact of iodine intake on thyroid diseases——A five-year prospective epidemiological study / 中华内分泌代谢杂志

Objective To evaluate the relationship between iodine intake level and the occurrence and development of thyroid diseases.Methods During the period of 1999-2004,a cross-sectional survey in 1999 and a 5-year follow-up survey were conducted in the 3 communities with different iodine intake levels in China:Panshan (mild deficiency),Zhangwu (more than adequate) and Huanghua (iodine excess).A total of 3 761 subjects were included in 1999 and 80.24% of them participated in the 5-year follow-up survey in 2004.The levels of serum thyroid hormones and thyroid autoantibodies were measured,and thyroid B ultrasound was performed.Results (1) The prevalence of overt hypothyroidism in 1999 in Zhangwu and Huanghua was 3.5 and 7.3 times,and that of subclinical hypothyroidism was 3.2 and 6.6 times as high as in Panshan,respectively.The 5-year cumulative incidence of subclinical hypothyroidism was 11.3 and 12.6 times as high as in Panshan,but no difference of incidence of overt hypothyroidism was found.(2) The prevalence of autoimmune thyroiditis (AIT) in 1999 in Zhangwu and Huanghua was 3.8 and 6.2 times,and the S-year cumulative incidence of AIT was 4.4 and 5.5 times as high as in Panshan.(3) During the 5-year follow-up period,the incidences of hypothyroidism in subjects with positive thyroid peroxidase antibody and euthyreidism in Zhangwu and Huanghua were 4.2 and 10.3 times as high as in Panshan.(4) No significant differences in both prevalence in 1999 and 5-year cumulative incidence of overt hyperthyroidism were found in the 3 communities.(5) The incidence of thyroid cancer was 19.37/100 000 per year in Huanghua,and all of the cases were papillary thyroid cancer,and no thyroid cancer was found in Zhangwu and Huanghua.Conclusion More than adequate or excessive dietary iodine intake may induce and promote the occurrence and development of hypothyroidism and AIT,therefore,median urinary iodine excretion (MUI)more than 200?g/L in the population appears not safe.The observation that a higher incidence of thyroid cancer occurred in the iodine excessive areas with MUI 600?g/L deserves further investigation.

Thyroid autoantibodies In a five-year follow-up survey of populations with different Iodine intakes / 中华内分泌代谢杂志

Objective To perform a follow-up survey about thyroid disorders in three rural communities with different iodine intakes in China,observe the incidences and natural outcomes of positive thyroid autoantibodies in euthyroid population,and also explore the influence of iodine intakes on these outcomes and autoantibodies.Methods In 1999,a cross-sectional study on thyroid disorders was performed in three rural communities of Pansan ( mild iodine deficient area),Zhangwu ( more than adequate iodine intake area) and Huanghua (excessive iodine intake area) in China.The 5-year follow-up study was performed in 2004.Both in 1999 and 2004,serum levels of TSH,thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) were measured with the same method.Iodine in urine and B ultrasound on thyroid were also examined.Results Among the euthyroid subjects with normal TSH level in 1999,an increased prevalence of positive TPOAb in Zhangwu and an increased prevalence of positive TgAb in Hnanghua were observed in 2004 (both P＜0.05 ).Most of euthyroid subjects with positive TPOAb or positive TgAb in 1999 remained positive thyroid antibodies in 2004. The percentage was even higher in those with high levels of antibodies.Thyroid dysfunction was more frequent in subjects with positive TPOAb and/or TgAh than in those without thyroid antibodies (14.44% vs 3.11%,P＜0.01).For those with positive antibodies in 1999,the incidence of hypothyroidism in 2004 was 1.32%,8.46% and 15.38% in Pansan,Zhangwu and Huanghua,respectively (P＜0.05).The 5-year cumulative incidences of positive TPOAb (≥50 U/ml) and TgAb (≥40 U/ml) were 2.81% and 3.82%,respectively.The incidence of positive TPOAb was the highest in Zhangwu ( 3.84% ).The incidence of positive TgAb was the highest in Huanghua (5.07%),significantly higher than those in other two areas (P＜0.05).Conclusion The incidence of thyroid dysfunction is higher in subjects with positive antibodies than that in those with negative antibodies.The high iodine intake is a risk factor of hypothyroidism in subjects with positive thyroid antibodies.Sustained excessive iodine intake increases the incidence of positive thyroid antibodies.

Incidences of hyperthyroidism in communities with different iodine intake levels:a five-year prospective and comparative epidemiological survey / 中华内分泌代谢杂志

Objective To analyze the relationship between different iodine intakes and epidemiological features of hyperthyroidism in 3 communities with different iodine intake levels,as well as to explore the risk factor for the pathogenesis of hyperthyroidism.Methods A cohort study was performed in 3 Chinese rural communities with long-term stable iodine nutrition status defined as mild deficient (Panshan),more than adequate (Zhangwu, previously mild iodine deficiency and salt iodization lasting 8 years until 2004) and excessive (Huanghua).A total of 3 761 (934 males,2 827 females) inhabitants aged above 13 participated in the original investigation in 1999 and 3 018(709 males,2 309 females) of them received identical examinations after 5 years.Results Median urinary iodine concentration of school-aged children was 87.61zg/L in Panshan,213.9?g/L in Zhangwu and 633.5?/L in Huanghua (P＜0.05) at fallowing up,and no statistic significance was found when comparing the corresponding data from original survey (83.5?g/L,242.9?g/L and 650.9?g/L).The accumulative incidence of hyperthyroidism was 13.6/1 000,9.4/1 000 and 8.1/1 000 (P＞0.05),being 16.4/1 000,11.2/1 000 and 9.1/1 000 (P＞0.05) in female,respectively in Panshan,Zhangwu and Huanghua.In original healthy subjects (without history of thyroid disease and overt thyroid dysfunction) merely with either positive thyroid peroxidase antibody (TPOAb＞50 IU/ml) or thyroglobulin antibody (TgAb＞40 IU/ml),the accumulative incidence of newly diagnosed hyperthyroidism was not significantly different among 3 communities in follow-up survey.TSH＜0.3 mIU/L,positive TPOAb or goiter in original healthy participants were associated with the occurrence of overt hyperthyroidism in 5 years [ Logistic Regression,OR = 5.7 (95% CI 2.1-15 ),OR = 3.8 (95% CI 1.7-8.7 ) and OR = 3.1 (95% CI 1.4-6.8) respectively].Conclusion Iodine supplementation in mild iodine deficient area does not increase the incidence of overt hyperthyroidism ultimately.Long-term excessive iodine intake does not affect the incidence and pattern of hyperthyroidism.TSH＜0.3 mIU/L,positive TPOAb and goiter in healthy individuals are the risk factors for hyperthyroidism.

A five-year follow-up study of hypothyroidism in areas with different iodine intakes / 中华内分泌代谢杂志

Objective To investigate epidemiologieal characteristics of hypothyroidism and factors influencing its outcome in the areas with different iodine intakes.Methods An epidemiologic follow-up study of thyroid diseases was performed in Panshan (iodine deficient),Zhangwu [mild iodine deficiency before universal salt iodination (USI) and more than adequate iodine intakes after USI ] and Huanghua ( iodine excessive) in China.A total of 3 761 subjects were investigated in 1999,and 3 018 (80.2% ) of them were followed up in 2004.FT_4,FT_3,TSH,thyroid autoantibodies and urinary iodine concentration were determined and thyroid B ultrasound was performed in all participants.Results Five-year cumulative incidence of overt hypothyroidism was 0.23%,0.47% and 0.35% in Panshan,Zhangwu and Huanghua,respectively.Twenty patients with autoimmune- induced overt hypothyroidism did not comply with the physician's orders to take thyroxine.Thyroid function spontaneously turned to normal in 55% of them,turned to subclinical hypothyroidism in 20% and maintained overt hypothyroidism in 25%.Five-year cumulative incidence of subclinical hypothyroidism in Zhangwu (2.60%) and Huanghua (2.89%) were significantly higher than that in Panshan(0.23% ) (both P＜0.01 ).One hundred patients with subclinical hypothyroidism were followed up,and 5% of them developed overt hypothyroidism,66% turned to euthyroidism and 29% maintained subclinical hypothyroidism.Raised serum TSH (＞6 mU/L) in the original survey ( OR = 3.4),positive thyroid autoantibodies in the follow-up study ( OR = 5.3 ) and more than adequate iodine supplementation in the mild iodine-deficient population ( OR = 8.0) were risk factors influencing outcome of subclinical hypothyroidism.Conclusion More than adequate iodine supplementation among a population in the mildly iodine-deficient area may increase the incidence of overt and subolinical hypothyroidism, and also influence outcome of subclinical hypothyroidism.