Genetic polymorphisms of apolipoprotein E in nonarteritic anterior ischemic optic neuropathy.

PURPOSE: To elucidate the potential role of genetic polymorphisms of apolipoprotein E (APOE) in nonarteritic anterior ischemic optic neuropathy (NAION) and the association between APOE and NAION-induced ocular impairments. METHODS: A total of 73 NAION patients and 73 sex- and age-matched healthy controls were recruited for the study. Genomic DNA was isolated from peripheral blood samples. The alleles and genotypes of APOE were explored. The interaction between APOE and medical comorbidities was assessed by the multifactor dimensionality reduction (MDR) method. Among 81 affected eyes of NAION patients, an additional association study of APOE isoforms with visual impairments was carried out. RESULTS: The allele and genotype frequencies for APOE showed significant differences when comparing NAION cases and controls. Multivariate analysis adjusted for age, sex, hypertension, dyslipidemia, diabetes mellitus, cardiovascular disease, and cerebrovascular disease revealed that the ε3/ε4 genotype (OR = 3.86, 95% CI = 1.13-13.25, p = 0.032) and ε4 allele (OR = 3.55, 95% CI = 1.05-11.99, p = 0.041) were strong independent risk factors for NAION. Compared to eyes with the ε3/ε3 + ε2/ε4 genotype, individuals with the ε4/ε4 + ε3/ε4 genotype had worse visual field defects (VFDs) and thinner macular ganglion cell complex (mGCC) thicknesses with larger focal loss of volume (FLV) and general loss of volume (GLV). Compared to ε4 noncarriers, ε4 carriers also tended to have more serious VFD and mGCC loss. CONCLUSIONS: APOE polymorphisms conferred a significant risk of NAION and were significantly related to ocular impairments caused by NAION.

25-hydroxyvitamin D levels are inversely related to metabolic syndrome risk profile in northern Chinese subjects without vitamin D supplementation.

BACKGROUND: The comparatively low 25 hydroxyvitamin D [25(OH)D] levels have been reported in patients with metabolic syndrome (MetS). Herein we investigated the cross-sectional and longitudinal relationships between serum 25(OH)D levels and MetS risk profile in northern middle-aged Chinese subjects without vitamin D supplementation. METHODS: A cohort of 211 participants including 151 MetS patients and 60 controls at 20-69 years of age were enrolled from suburban Beijing, China. The recruited MetS patients were subjected to diet and exercise counselling for 1-year. All subjects at baseline and MetS patients after intervention underwent clinical evaluations. RESULTS: Serum 25(OH)D levels were significantly decreased in MetS patients. 25(OH)D levels were inversely related to MetS score, fasting blood glucose (FBG) and triglyceride-glucose index (TyG) after adjusting for cofounders (all P < 0.05). Participants in the lowest tertile of 25(OH)D levels had increased odds for MetS (P = 0.045), elevated FBG (P = 0.004) in all subjects, and one MetS score gain in MetS patients (P = 0.005). Longitudinally, the metabolic statuses as well as 25(OH)D levels of MetS patients were significantly improved (all P < 0.05), and the increase of 25(OH)D levels were inversely related to MetS scores, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), FBG, and TyG, while positively related to high-density lipoprotein cholesterol (HDL-C) after adjusting for confounders. CONCLUSIONS: 25(OH)D levels were significantly decreased in MetS patients, and it was negatively associated with metabolic dysfunctions at baseline and 1-year after. Metabolic aberrations of MetS patients were significantly ameliorated with 1-year follow-up counselling accompanying by notably elevated 25(OH)D levels.

Exploring the Impact of Corporate Social Responsibility Communication through Social Media on Banking Customer E-WOM and Loyalty in Times of Crisis.

Previous studies have largely explored corporate social responsibility (CSR) for organization-centric outcomes to achieve organizational performance, organizational commitment, or organizational citizenship behavior. However, the importance of CSR to achieve customer-centric outcomes is underexplored to date. Contemporary researchers have recently turned their attention toward CSR from the viewpoint of customer-centric outcomes. Therefore, the present study attempts to test the influence of CSR communication on social media and customer loyalty in the banking sector of a developing economy in times of crisis. This study also investigates the mediating effect of electronic word of mouth (E-WOM) with this relationship. The data of the present study were collected from different banking customers using a self-administered questionnaire. The empirical findings of this study validated that the CSR communication of a bank on social media increases customer loyalty, and E-WOM partially mediates this relationship. This study will be helpful for the banking sector to understand the importance of CSR communication to increase customer loyalty, which is very important for every bank in times of crisis.

Reference Intervals for Thyroid-Associated Hormones and the Prevalence of Thyroid Diseases in the Chinese Population.

BACKGROUND: Thyroid diseases are highly prevalent worldwide, but their diagnosis remains a challenge. We established reference intervals (RIs) for thyroid-associated hormones and evaluated the prevalence of thyroid diseases in China. METHODS: After excluding outliers based on the results of ultrasound screening, thyroid antibody tests, and the Tukey method, the medical records of 20,303 euthyroid adults, who visited the Department of Health Care at Peking Union Medical College Hospital from January 2014 to December 2018, were analyzed. Thyroid-associated hormones were measured by the Siemens Advia Centaur XP analyzer. The RIs for thyroid-associated hormones were calculated according to the CLSI C28-A3 guidelines, and were compared with the RIs provided by Siemens. The prevalence of thyroid diseases over the five years was evaluated and compared using the chi-square test. RESULTS: The RIs for thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), total thyroxine (TT4), and total triiodothyronine (TT3) were 0.71-4.92 mIU/L, 12.2-20.1 pmol/L, 3.9-6.0 pmol/L, 65.6-135.1 nmol/L, and 1.2-2.2 nmol/L, respectively. The RIs of all hormones except TT4 differed significantly between males and females. The RIs of TSH increased with increasing age. The prevalence of overt hypothyroidism, overt hyperthyroidism, subclinical hypothyroidism, and subclinical hyperthyroidism was 0.5% and 0.8%, 0.2% and 0.6%, 3.8% and 6.1%, and 3.3% and 4.7% in males and females, respectively, which differed from those provided by Siemens. CONCLUSIONS: Sex-specific RIs were established for thyroid-associated hormones, and the prevalence of thyroid diseases was determined in the Chinese population.

Reference ranges for serum insulin-like growth factor I (IGF-I) in healthy Chinese adults.

PURPOSE: To determine serum insulin-like growth factor 1 (IGF-I) levels in healthy Chinese adults, establish reference ranges for serum IGF-I levels and observe the effects of age, sex, body mass index (BMI) and geographical region on serum IGF-I levels. METHODS: In total, 2791 healthy adults (1339 males and 1452 females) from the north (Beijing) and south (Guizhou Province) of China were recruited following a questionnaire survey, physical examination and laboratory examination. Both sexes were divided into 13 groups according to age (18, 19, 20-24, 25-29, 30-34, 35-39, 40-44, 45-49, 50-54, 55-59, 60-64, 65-69 and ≥70 years). The serum IGF-I levels were measured by performing a chemiluminescent assay (Immulite 2000®), and the LMS (Lambda-Mu-Sigma) method was applied to construct smooth centile curves of age-specific IGF-I levels. RESULTS: Serum IGF-I levels in the adults gradually decreased with increasing age from 18 to 70 years in both the male and female participants. Although the decrease in the level of IGF-1 was more pronounced in females than in males, no significant difference was observed between the sexes, except in the 60- to 64-year-old age group (P = 0.0329). The multiple linear regression model showed that there was an inverse relationship between the serum IGF-I level and BMI (P<0.001), and the serum IGF-I level in the Guizhou population was higher than that in the Beijing population (P<0.05). CONCLUSION: The normal reference ranges for age- and sex-specific serum IGF-I levels were established for the first time in a large sample of Chinese adults. The serum IGF-I levels were significantly influenced by age, BMI and geographical region.

A Novel Phenotype of Familial Hyperaldosteronism Type III: Concurrence of Aldosteronism and Cushing's Syndrome.

CONTEXT: To date, all the familial hyperaldosteronism type III (FH-III) patients reported presenting with typical primary aldosteronism (PA), without showing other adrenal hormone abnormalities. OBJECTIVE: This study characterized a novel phenotype of FH-III and explored the possible pathogenesis. PATIENTS AND METHODS: A male patient presented with severe hypertension and hypokalemia at the age of 2 years and developed Cushing's syndrome at 20 years. He was diagnosed with PA and Cushing's syndrome on the basis of typical biochemical findings. He had massive bilateral adrenal hyperplasia and underwent left adrenalectomy. KCNJ5 was sequenced, and secretion of aldosterone and cortisol were observed both in vivo and in vitro. RESULTS: A heterozygous germline p.Glu145Gln mutation of KCNJ5 was identified. ARMC5, PRKAR1A, PDE8B, PDE11A, and PRKACA genes and ß-catenin, P53 immunoactivity were normal in the adrenal. CYP11B2 was highly expressed, whereas mRNA expression of CYP11B1, CYP17A1, and STAR was relatively low in the hyperplastic adrenal, compared with normal adrenal cortex and other adrenal diseases. In the primary cell culture of the resected hyperplastic adrenal, verapamil and nifedipine, two calcium channel blockers, markedly inhibited the secretion of both aldosterone and cortisol and the mRNA expression of CYP11B1, CYP11B2, CYP17A1, and STAR. CONCLUSIONS: We presented the first FH-III patient who had both severe PA and Cushing's syndrome. Hypersecretion of cortisol might be ascribed to overly large size of the hyperplastic adrenal because CYP11B1 expression was relatively low in his adrenal. Like aldosterone, synthesis and secretion of cortisol in the mutant adrenal may be mediated by voltage-gated Ca2+ channels.

[Construction of Zinc-alpha2-glycoprotein expression plasmid and its expression in 3t3-l1 preadipocytes].

OBJECTIVE: To construct mouse Zinc-alpha2-glycoprotein (mZAG) eucaryotic expression plasmid and identify its expression in 3T3-L1 preadipocytes. METHODS: The total RNA from mouse liver tissue was extracted. The reverse-transcript(RT)-PCR method was used to amplify the complete domain sequence of mZAG, and the confirmed PCR products was inserted into expression plasmid by DNA ligation. The mZAG expression plasmids with various concentrations (0, 0.4, 0.8, and 1.6 microg) were transfected into 3T3-L1 preadipocytes, and ZAG expression in mRNA and protein level was determined by real-time fluorescence quantitative PCR and Western blot, respectively. RESULTS: DNA sequencing confirmed the right sequence of mZAG expression plasmid pcDNA3.1(-)-mZAG. After the mZAG expression plasmid with different concentrations were transfected into 3T3-L1 preadipocytes, mZAG mRNA level significantly increased and reached 2.58 folds (P=0.002), 3.67 folds (P=0.000 and 5.19 folds (P=0.001) of that in the control group (no mZAG transfection). mZAG protein level also significantly increased and reached 2.75 folds of that in the control group (P=0.017). Treating 3T3-L1 cells with small interfering RNA (siRNA) sequence siRNA 1 and siRNA 4 resulted in a decrease of mZAG mRNA to 49% and 41% of those in the control group(no siRNA sequence transfection) (P=0.002P=0.000)and a decrease of mZAG protein to 55% and 62% of that in the control group (P=0.004,P=0.025). CONCLUSIONS: mZAG expression plasmid pcDNA3.1(-)-mZAG was successfully established in this study. This plasmid can be well expressed in 3T3-L1 preadipocytes. siRNA 1 and siRNA 4 can effectively inhibit the expression of mZAG in these cells.

[Effect of bodyweight on the onset of puberty of female children and adolescents].

OBJECTIVE: To investigate the possible effects and roles of bodyweight on the puberty onset in adolescent girls. METHODS: Totally 288 Chinese female children and adolescent girls aged 5 to 16 were followed up yearly for four consecutive years. The height, bodyweight, fat percentage, sexual characteristics, and the serum levels of leptin and insulin-like growth factor-1 (IGF-1) were studied to analyze the influential factors of puberty onset and age of menarche. RESULTS: The serum level of leptin elevated significantly from age 13 [(9.23 +/- 1.25) microg/L] and reached peak at age 16 [(13.19 +/- 1.45) microg/L]. IGF-1 significantly correlated with the timing of puberty onset (r = 0.292, P = 0.016). BMI and fat percentage had no significant effects on the onset of puberty, but were negatively correlated with the age of menarche (r = -0.323, P = 0.037, r = -0.298, P = 0.038 respectively). CONCLUSION: Bodyweight may have effect on puberty onset in female adolescents.

[Puberty development of the healthy adolescent girls of Daqing city, Heilongjiang province].

OBJECTIVE: To investigate the process of puberty development of healthy adolescent girls in Northern China. METHODS: 288 adolescent girls of Daqing city, Heilongjiang province, aged 5 to 16, were studied and followed up yearly for four years. The height, weight, fat percentage, second sex characteristics, and the blood levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E(2)) were examined. RESULTS: The mean age of puberty onset of these healthy adolescent girls was 8.5 years +/- 1.1 years. The blood levels of FSH, LH and E(2) were 0.2 mIU/L, 1.1 mIU/L and 0.06 nmol/L respectively (the 95 percentiles were 2.5 mIU/L, 2.3 mIU/L and 0.12 nmol/L respectively). Their mean age of menarche was 12.4 years +/- 1.2 years. The mean age of breast development was 8.8 years +/- 1.1 years. CONCLUSION: The girls in Northern China begin their puberty development at younger ages than reported before.

[Mechanism of interleukin-1beta increasing growth hormone expression in rat pituitary GH3 cells].

OBJECTIVE: To investigate the effect(s) of interleukin-1beta (IL-1beta) on the activity of human growth hormone (hGH) gene promoter in rat pituitary GH3 cells and the molecular mechanism. METHODS: The method of luciferase reporter gene was used. We firstly established stable GH3 cell line which contains hGH gene promoter -484-30 bp and luciferase reporter gene. After treating these cells with IL-1beta or IL-1beta plus various signaling transduction inhibitors, the concentration of GH in the medium and lysate of GH3 cells and luciferase activities in GH3 cells were measured to reflect the effect of IL-1beta on secretion and synthesis of GH and the promoter activity of the hGH gene and the molecular mechanism. Results IL-1beta (10-10(4)U/ml) increased secretion and synthesis of GH. IL-1beta at levels of 10(2)-10(4) U/ml promoted the luciferase expression in stable GH3 cells, and the maximal action was 1.61 times of the control (P < 0.001). Among the inhibitors of intracellular signaling transduction pathways, mitogen-activated protein kinases (MAPK) inhibitor PD98059 (40 micromol/L) and p38 MAPK inhibitor SB203580 (5 micromol/L) completely blocked the stimulatory effect of IL-1beta, and phosphoinositide 3-kinase (PI3-K) inhibitor LY294002 (10 micromol/L) partly blocked the induction of IL-1beta. Neither overexpression of Pit-1 nor inhibiting Pit-1 expression affected IL-1beta induction of hGH promoter activity. The stimulatory effect of IL-1beta was abolished following deletion of the -196 to -132 bp fragment. CONCLUSIONS: IL-1beta increases the activity of hGH gene promoter in rat pituitary GH3 cells. This stimulatory effect of IL-1beta appears to require the intracellular MAPK, p38 MAPK, and PI3-K dependent signaling pathways. The effect of IL-1beta requires the promoter sequence that spans the -196 to -132 bp fragment of the gene, but it is unrelated to Pit-1 protein.

[The Effect of Cytokines on Expression of Growth Hormone Gene in Rat Pituitary GH(3) Cells].

To study the effect of interleukin-11(IL-11), ciliary neurotropic factor (CNTF) and transforming growth factor-beta (TGF-beta) on the hGH gene promoter activity in rat pituitary GH(3) cells and the interaction with pituitary-specific transcription factor Pit-1, firstly the stable transformed GH(3) cell line which contained hGH gene promoter 484-30 bp and luciferase reporter gene was established, then the concentration of GH in the medium and lysate of GH(3) cells and luciferase activities in GH(3) cells were measured, after treating these cells with the above cytokines, the effects of cytokines on secretion and synthesis of GH, and the promoter activity of the hGH gene were observed. The results of our experiments showed that IL-11(20 nmol/L), CNTF(10 nmol/L) and TGF-beta(5 nmol/L) regulated secretion and synthesis of GH, and the luciferase expression in stable-transformed GH(3) cells. IL-11 and CNTF had a stimulatory effect, whereas TGF-beta had an inhibitory one. Neither overexpression of Pit-1 nor inhibition of Pit-1 expression could affect the regulatory role of these cytokines. In conclusion, IL-11, CNTF and TGF-beta regulated the GH production in pituitary GH(3) cell line by regulating the hGH gene promoter activity, while Pit-1 might not be involved in the roles.