MOR106 alleviates inflammation in mice with atopic dermatitis by blocking the JAK2/STAT3 signaling pathway and inhibiting IL-17C-mediated Tfh cell differentiation / 细胞与分子免疫学杂志

Objective To explore the significance of interleukin-17C(IL-17C)-mediated follicular helper T cell (Tfh) differentiation in atopic dermatitis (AD) model. Methods BALB/c mice were divided into control group, AD model group, low-dose MOR106 (anti-IL-17C huIgG1)(MDR106-L)treatment group and high-dose MOR106 (MOR106-H) treatment group, 8 mice in each group. Except for the control group, all the other groups were treated with 2, 4- dinitrochlorobenzene (DNCB) to establish AD models. The low-dose and high-dose MOR106 groups were treated with 5 mg/kg or 10 mg/kg MOR106 respectively. The differentiation of Tfh cell subsets in peripheral blood of mice was analyzed by flow cytometry, and the expression of Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3) signal pathway protein in skin tissue was detected by Western blot analysis. Results Compared with the control group, the dermatitis severity score, mass difference between two ears, spleen mass and spleen index of DNCB group increased significantly, while those of MOR106-L group and MOR106-H group decreased significantly. Compared with the control group, the Tfh subgroup of AD mice showed deregulated differentiation, resulting in a significant increase in the percentage of CD4+CXCR5+IFN-γ+Tfh1 cells, CD4+CXCR5+IL-17A+Tfh17 and CD4+CXCR5+IL-21+Tfh21 cells, and a significant decrease in the percentage of CD4+CXCR5+IL-10+Tfh10 cells and CD4+CXCR5+FOXP3+Tfr cells in peripheral blood. The protein levels of phosphorylated JAK2(p-JAK2) and p-STAT3 were significantly increased. MOR106 effectively reversed these changes of Tfh1, Tfh10, Tfh17, Tfh21 and Tfr cells in peripheral blood of AD mice. Compared with AD group, the levels of p-JAK2 and p-STAT3 protein in low-dose and high-dose MOR106 treatment groups decreased significantly. Conclusion MOR106 can reduce the inflammatory response of AD mice by blocking JAK2/STAT3 signaling pathway and inhibiting the differentiation of Tfh cells mediated by IL-17C.

Prevalence and risk factors of diabetic kidney disease in plain-sand areasand loess hilly areas of Gansu province / 中华全科医师杂志

Objective:To investigate the risk factors of diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM) patients in plain-sand areas and loess hilly areas of Gansu province.Methods:A total of 1 599 T2DM patients who participated in chronic disease and risk factors monitoring and basic public health service management were selected by multi-stage stratified random sampling method in the sandy plain areas and loess hilly areas of Gansu province. Questionnaire survey, physical measurement and laboratory tests were performed. Multivariate binary logistic model was used to analyze the influencing factors.Results:The prevalence of DKD was 22.1% (174/787) among T2DM patients in the sandy plain areas and 19.1%(155/812) in the loess hilly area, respectively. Hypertension ( OR=3.022), hyperuricemia ( OR=2.114) and HbA1c≥7%( OR=2.231) were the risk factors for DKD in the plain-sand areas, and the risk of DKD increased with age. In the loess hilly areas, female sex ( OR=0.379) was the protective factor for DKD; while duration of disease≥10 years ( OR=2.476), hyperuricemia ( OR=1.907), HbA1c≥7% ( OR=1.927) were the risk factors for DKD; and the risk of DKD increased with the increase of age, and decreased with the increase of per capita monthly income. Conclusions:The prevalence of DKD and its influencing factors are different between sandy plain areas and loess hilly areas in Gansu province. The prevention and treatment of hypertension should be given more attention in sandy plain areas. In addition, the screening of DKD should be conducted among T2DM patients, particularly for those with old age, hyperuricemia and HbA1c≥7% in both areas of the province.

Research progress on the relationship between subclinical hypothyroidism and depression / 中国临床药理学与治疗学

Subclinical hypothyroidism (SCH) is a mild impairment of thyroid function. Several existing studies suggest that SCH is associated with an increased risk of depression, but some studies have also found no correlation between SCH and depression. Therefore, whether there is an association between SCH and depression and the mechanism of interaction between the two remains controversial. Growing evidence suggested that SCH patients should not be routinely treated with levothyroxine, and the effect of the treatment of thyroid disease on various clinical psychiatric outcomes is also controversial. This article reviews the current research on the correlation between SCH and depression risk and whether drug intervention is needed.

Correlation between HLA-Cw*0602 and LCE3B_LCE3C-del allele interaction and psoriasis vulgaris in a population of Mongolian nationality in Inner Mongolia / 中国基层医药

Objective:To investigate the effect of HLA-Cw*0602 and LCE3B_LCE3C-del allele interaction on the risk of psoriasis vulgaris in a population of Mongolian nationality in Inner Mongolia. Methods:A total of 365 Mongolian patients with psoriasis vulgaris who received treatment in The Affiliated Hospital of Inner Mongolia Medical University from January 2006 to December 2015 (case group) and 284 healthy subjects who concurrently received physical examination in the same hospital (control group) were included in this study. After sex and age matching, and quality control, the correlations between HLA-Cw*0602 and LCE3B_LCE3C-del allele and psoriasis vulgaris in a population of Mongolian nationality were analyzed using SPSS 20.0 software. The interaction between HLA-Cw*0602 and LCE3B_LCE3C-del alleles (adjusting for potential confounders including age and sex) was analyzed using logistic regression. Results:Logistic regression interaction item Int of dominant inheritance mode HLA-Cw*0602 allele and recessive inheritance mode LCE3C_LCE3B-del allele revealed OR = 2.38, P = 0.033, and interaction index S = 1.21, indicating that there was a synergistic effect between the two alleles. Conclusion:The co-existence of HLA-Cw*0602 and LCE3B_LCE3C-del may increase the risk of psoriasis vulgaris in a population of Mongolian nationality in Inner Mongolia.

Research progress on Nrf2 in diabetic cardiomyopathy and intervention of traditional Chinese medicine / 中国临床药理学与治疗学

As a cardiovascular complication of diabetes, diabetic cardiomyopathy seriously affects the prognosis of patients with diabetes. The incidence and mortality of diabetic cardiomyopathy increase, and has emerged as a research hotspot in current years. The pathogenesis of diabetic cardiomyopathy is complex, involving a range of signaling pathways in its incidence and development. Nuclear factor NF-E2-related factor 2 (Nrf2), as a powerful antioxidant gene, enhances the capacity of the myocardium to withstand oxidative stress via interplay with different signaling elements and exerts anti-inflammatory response, anti-myocardial fibrosis, and anti-apoptosis effects. Researches have shown that certain ingredients of traditional Chinese medicine can alleviate the myocardial injury by affecting the relationship of Nrf2 with other signaling factors via enhancing the expression of Nrf2. Here we review the role of Nrf2 and therapy of traditional Chinese medicine in diabetic cardiomyopathy in hope of providing referential idea for the treatment of diabetic cardiomyopathy. A reference for the prevention and therapy of diabetic cardiomyopathy.

Research Progress of Molecular Regulatory Mechanism of Non-coding RNAs in Papillary Thyroid Carcinoma / 肿瘤防治研究

Papillary thyroid carcinoma is one of the most common thyroid cancer subtypes. Although papillary thyroid carcinoma can be treated effectively with excision, microwave ablation, radioactive iodine and hormone replacement therapy, these ways are inefficient in reducing its morbidity, mortality and recurrence rates. Therefore, it is very important to seek the molecular mechanism of the occurrence and development of papillary thyroid carcinoma, to provide effectively early diagnosis, accurate treatment and better long-term prognosis for papillary thyroid carcinoma patients. This paper summarizes the molecular regulatory mechanisms of non-coding RNAs and their related signaling pathways in the occurrence and development of papillary thyroid carcinoma, in order to provide evidence for continued research of biomarkers for papillary thyroid carcinoma.

Effect of levothyroxine replacement therapy on adipocyte expression in subclinical hypothyroidism rats / 中华地方病学杂志

Objective To observe the changes of adiponectin (APN),chemerin and tumor necrosis factor-α (TNF-α) in subclinical hypothyroidism (SCH) rats,and to clarify the effect of L-thyroxine (L-T4) replacement therapy.Methods Sixty-five male Wistar rats were randomly divided into five groups via the random number table method:control group (n =10),SCH group A (n =15),SCH group B (n =15),SCH group C (n =15) and L-T4 treatment group (SCH + L-T4,n =10).Rats in groups SCH A,B and C were fed with 5,15 and 20 mg·kg-1·d-1 methimazole (MMI) once daily by gavage.The rats in SCH + L-T4 group were given 20 mg·kg-1·d-1 MMI once daily through gavage,after 8 weeks,6 μg·kg-1· d-1 of L-T4 was intragastrically added (50 μg/tablet) and the model was completed at the 16th week.The levels of serum APN,chemerin and TNF-α were measured via the enzyme linked immunosorbent assay (ELISA) method.The mRNA and protein levels of APN,chemerin and TNF-α in visceral adipose tissue of 5 groups were determined by real-time PCR (RT-PCR) and Western blotting,respectively.Results Compared with the control group [(202.20 + 17.27) ng/L,(143.70 ± 18.46) ng/L,(114.69 ± 4.18) μg/L],the serum chemerin levels in the SCH A,B,C groups were significantly higher [(314.33 ± 16.80),(355.00 ± 17.10),(365.00 ± 11.63) ng/L,P ＜0.05] and TNF-α levels also increased significantly [(222.60 ± 14.13),(279.20 ± 12.79),(288.30 ± 15.89) ng/L,P ＜0.05],and APN levels were significantly decreased [(77.21 ± 3.08),(68.58 ± 2.92),(59.45 ± 2.41) μg/L,P ＜0.05];but compared with SCH group C,the levels of chemerin and TNF-α in the SCH + L-T4 group were decreased [(260.07 ± 10.80),(178.40 ± 10.29) ng/L] and the level of APN [(102.35 ± 3.17) μg/L] was increased (P＜ 0.05).The mRNA and protein levels of APN in SCH A,B,C groups were significantly lower than those in the control group (P ＜0.05).The APN mRNA and protein levels in the SCH + L-T4 group were significantly higher than those in the SCH group C (P ＜ 0.05).The mRNA and protein levels of chemerin and TNF-α in the SCH A,B,C groups were higher than those in the control group (P ＜ 0.05).However,the mRNA and protein levels of chemerin and TNF-α in the SCH + L-T4 group were significantly lower than those in the SCH group C (P ＜ 0.05).Conclusion The expression levels of serum chemerin and TNF-α in SCH rats have increased,and APN levels decreased,but L-T4 can ameliorate these changes.

Vitamin D status and its associated risk factors among healthy adults in Gansu province / 中华临床营养杂志

Objective To investigate the prevalence of vitamin D deficiency and its associated metabolic risk factors in the healthy adults in Gansu Province, a western province of China.Methods Through stratified, multistage probability population sampling, 11 300 adults (4 740 men and 6 417 women aged 18-79 years) who had been living in their current residence for at least 5 years were arbitrarily chosen from seven representative geographical cities in Gansu Province from June 2014 to December 2015.The data obtained from a questionnaire-based survey, anthropometric and biochemical assessments, and areal bone mineral density measurement were collected and analyzed.Results The overall mean serum 25(OH)D was (16.07±9.40) μg/L.The prevalence of severe deficiency (0.05).Conclusions Vitamin D deficiency is highly prevalent among adult populations in Gansu, northwestern of China, and is largely attributed to younger age and female sex.The cumulative effects of factors including sun exposure, physical activity, and calcium supplementation play an influential role in maintaining vitamin D levels.

Prevalence and related risk factors of hypothyroidism in adults of Gansu province / 中华健康管理学杂志

Objective To investigate the prevalence and epidemiological characteristics of hypothyroidism, possible related lifestyle and metabolic risk factors of hypothyroidism in adults of Gansu province, and to provide scientific evidence for the prevention of hypothyroidism. Methods Stratified multi-stage cluster sampling with probability proportionate to size method was used to collect data from 10071 residents aged 18 to 79 years and who had lived in the local area for more than 5 years. All participants were asked to fill in the questionnaire, and to take physical examination including anthropometric measurements and venous blood samples. Risk factors of hypothyroidism were analyzed by Chi-square test and multivariate logistic regression analysis. Result The prevalence of hypothyroidism was 10.1％ (overt hypothyroidism: 1.5％, subclinical hypothyroidism: 8.7％). Female (12.1％) had a higher percentage when compared to male (7.5％). In addition to the increased odds with older age and female gender, current or previous smoking history (OR: 0.467, 95％CI: 0.289-0.754, P=0.002), salty taste preference (OR:0.355, 95％CI:0.162-0.776, P=0.022) and a frequent seafood intake (OR:0.148, 95％CI:0.057-0.385, P<0.001) were tended to be associated with reduced risk of hypothyroidism. Logistic regression analysis showed that positive thyroid peroxidase antibodies (OR:1.976, 95％CI:1.037-3.768, P=0.039), positive thyroglobulin antibodies (OR:2.419, 95％CI:1.160-5.043, P=0.018) and triglycerides (OR:1.241, 95％CI:1.044-1.474, P=0.014) were associated with increased risk of hypothyroidism. Conclusion The prevalence of hypothyroidism in Gansu province was high, affecting approximately one in ten adults, and majority of which were SCH. Both lifestyle factors and metabolic factor were associated with hypothyroidism. Developing a healthy lifestyle at work and home, and paying attention to the control of blood lipids are conducive to the prevention of hypothyroidism.

Association of insulin-like growth factor 1 receptor gene rs2229765 polymorphism with osteoporosis in postmenopausal women / 中国组织工程研究

BACKGROUND: Insulin-like growth factor 1(IGF-1) plays an important role in regulating osteocyte function and bone metabolism. The association of insulin-like growth factor 1 receptor (IGF-1R) gene polymorphisms with osteoporosis in postmenopausal women has not yet been reported.OBJECTIVE: To investigate the correlation between IGF-1R gene rs2229765 single nucleotide polymorphism and osteoporosis in postmenopausal women.METHODS: IGF-1R gene rs2229765 SNPs were detected using PCR-RFLP in 218 patients with postmenopausal osteoporosis and 270 postmenopausal women with normal bone mineral density. The bone mineral density of the lumbar spine, femoral neck and forearm was determined by dual-energy X-ray absorptiometry. Serum IGF-1 level was investigated by ELISA.RESULTS AND CONCLUSION: The AA genotype (29% vs. 17%, P=0.001) and A allele (51% vs. 40%, P=0.000)distributions of the rs2229765 polymorphism in the osteoporosis group were significantly higher than those in the control group. Compared with GG genotype of rs2229765, AA genotype was significantly associated with an increased risk of osteoporosis (OR=2.12, 95%CI=1.27-3.54, P=0.004). The analysis of serum IGF-1 showed that osteoporotic women with rs2229765AA (P=0.007) and GA (P=0.016) genotype were found to have a lower serum IGF-1 level than osteoporotic women with GG genotype. Our results indicate that the IGF-1R gene rs2229765 polymorphism capable of regulating serum IGF-1 level is associated with postmenopausal osteoporosis.

Association of serum uric acid level with the prevalence of metabolic syndrome / 实用医学杂志

Objective To investigate the correlation of serum uric acid (SUA) level with the prevalence of metabolic syndrome (MS). Methods A random, multi-stage cross-sectional study was performed in 2364 resuden, aged from 20 to 74, in Lanzhou, Gansu province.The resudents were divided into groups according to the level of SUA or 4 components of MS. The relationship between SUA and MS was analyzed. Results The overall morbidity of MS was 20.13 % in Lanzhou , and the morbidity of MS was higher in female than that in male (23.22% vs. 17.37%, P < 0.05);The prevalences of MS was higher in the hyperuricemia (HUA) people than that in the healthy people (32.40 % vs. 17.70 %,P < 0.05); With the increase of SUA level, the morbidity rates of MS and its components increased;The risk of MS showed a gradual increase with the SUA level, the risk of MS(odds ratio,95%CI)in sex-specific quartiles of SUA was 2.33(1.45 ~ 3.71),2.33(1.45 ~3.71),2.44(1.53 ~ 3.89)in male;and 1.58(0.97~2.56),2.54(1.60 ~ 4.00),5.29(3.41 ~ 8.22)in female. The more the components of MS , the higher the SUA level was found for both the male and the female subjects , with the higher rate of HUA morbidity(P < 0.05). Conclusion There is a significant association between SUA level and MS, as well as the MS components. Comprehensive prevention and control should be taken for the reduction of the risk factors, and much attention should be paid to monitor the SUA level.

Relationship of TSH with atherosclerosis-related factors in subclinical hypothyroidism / 中华内分泌代谢杂志

Two hundred and fifty patients with subclinical hypothyroidism ( SCH) and 120 euthyroid volunteers were recruited for the study, SCH patients were stratified into 2 groups according to TSH levels(group A:TSH10 mIU/ L). All subjects were examined for clinical characteristics, thyroid profile, lipid profile, and biomarkers of early atherosclerosis. Patients in group B received L-thyroxine replacement treatment to achieve euthyroidism. After 6 months of stable euthyroidism all measurements were repeated. SCH patients had higher levels of total cholesterol(TC), low-density lipoprotein-cholesterol(LDL-C), asymmetric dimethyl arginine (ADMA), carotid artery intima media thickness(CIMT), thromboxane B2(TXB2), and C-reactive protein(CRP) but with lower nitric oxide(NO) level compared with euthyroid subjects. Levels of TC, LDL-C, CIMT, TXB2, and ADMA decreased, and NO level increased significantly after 6 months of euthyroidism. TSH was positively correlated with TC, LDL-C, CIMT, ADMA, and TXB2; and negatively correlated with NO. Based on multivariate regression analysis, TSH was an independent influential factor of CIMT and NO. We conclude that raised TSH is an important risk factor of atherosclerosis in SCH.

Changes in endothelial function in rats with subclinical hypothyroidism after levothyroxine treatment / 中华内分泌代谢杂志

Established rat models with subclinical hypothyroidism (SCH) were divided into three groups:subclinical hypothyroid(SCH),SCH treated with levothyroxine (L-T4),and control group.The L-T4 group displayed lowered total cholesterol and endothelin levels compared with the SCH group[(1.29 ±0.05 vs 2.38 ±0.55) mmol/L,(98.54 ± 32.43 vs 160.62 ±37.25) nmol/L,both P＜0.05].Nitric oxide levels,left ventricular systolic pressure,and blood flow in abdominal aorta were significantly higher in the L-T4 group than those in the SCH group.The results of this study indicate that L-T4 treatment may improve endothclial dysfunction and hemodynamic changes in rats with SCH.

The effects of TSH on human vascular endothelial cells and smooth muscle cells / 中华内分泌代谢杂志

Objective To study the effect of thyroid-stimulating hormone (TSH) on human vascular endothelial cells and smooth muscle cells and to explore the roles of TSH in the development of atherosclerosis.Methods Human vascular endothelial cells and smooth muscle cells were cultured in vitro.MTT method was used to assay the effect of TSH on cell viability.Real-time PCR was used to determine the levels of endothelial nitric oxide synthase (eNOS),prostacyclin(PGI2),endothelin-1 (ET-1),plasminagen activator inhibitor(PAI-1) (mRNA) in endothelial cells and the phenotype transition of smooth muscle cells.The effect of TSH to the cycle of smooth muscle cells was detected by using flow cytometry.Immunocytochemistry and Western blot were used to investigate the expression of the cell cyclin A,D1,and the expression of endothelial cell associated factors eNOS and ET-1.Results Compared with the control group,eNOS and PGI2 mRNA levels decreased while ET-1 and PAI-1 mRNA levels increased when different concentrations of TSH were applied to endothelial cells(P＜0.05).The level of eNOS protein was decreased gradually while the level of ET-1 protein was gradually increased(P＜0.05).Different concentrations of TSH applied to smooth muscle cells could promote the transition of cell cycle phase G2 to phase M and increase the expression of cell cyclin A and D1.Conclusion TSH may damage the function of vascular endothelial cells and promote the proliferation of smooth muscle cells.

The role of TSH in cholesterol synthesis / 中华内分泌代谢杂志

Thyroid diseases are often accompanied with dyslipidemia.In me past,low level of myroid hormone(TH) was considered a main factor in causing elevated level of blood cholesterol in hypothyroid patients.However,some clinical features can not be explained by this traditional theory. For example,in subclinical hypothyroid cases,both levels of thyroid-stimulating hormone (TSH) and serum total cholesterol (TC) increase,while TH level remains normal.From this phenomenon,we speculate that in case with hypothyroidism,not only there is a relationship between serum TC and TH levels,but also serum TC level change is related to TSH in some way,which has not been noticed.The purpose of this paper is to review the new and most advanced progress in the research of TSH and cholesterol.