Purpose:To investigate the association between maternal pre-pregnancy body mass index (BMI) and astigmatism and corneal curvature in offspring. Patients and Methods:Corneal topography and an optical biometer were used to measure ocular parameters, while cycloplegic autorefraction was performed to assess cylindrical diopter and axis. Demographic, pregnancy, and offspring-related information was collected through questionnaires. Multiple linear regression analyses were conducted to evaluate the association. Results:A total of 213 mother-child pairs were included. Maternal pre-pregnancy BMI was categorized as underweight (11.3%), normal weight (66.7%), overweight (16.0%), and obese (6.1%). The mean age of the offspring was 6.80 ± 2.44 years (males 49.3%). Offspring born to mothers with overweight or obese pre-pregnancy BMI exhibited significantly higher steep corneal curvature, average corneal curvature, corneal astigmatism, and total astigmatism compared to those in the normal pre-pregnancy BMI group. In multiple linear regression analysis, after adjusting for relevant covariates, pre-pregnancy BMI was positively associated with steep corneal curvature (β=0.35, P=0.005), corneal astigmatism (β=0.21, P=0.001), and total astigmatism (β=0.22, P<0.001). Compared to normal pre-pregnancy BMI, pre-pregnancy obesity was positively associated with offspring steep corneal curvature (β=1.52, P=0.002) and those born to mothers with overweight or obese pre-pregnancy BMI had a significantly higher prevalence of corneal astigmatism (overweight: β=0.56, P=0.001; obese: β=0.55, P=0.038) and total astigmatism (overweight: β=0.47, P=0.002; obese: β=0.59, P=0.010). Conclusion:Offspring of mothers with overweight or obese pre-pregnancy BMI show higher prevalence of developing corneal and total astigmatism compared to the normal.

Background: Thyroid dysfunction plays an important role in the pathology of diabetes-associated cognitive dysfunction (DACD). However, thyroid hormone (TH) signaling and action changes in DACD brains remain unknown. This study evaluated the alternations in TH signaling and action in the brains of DACD mice and explored the beneficial effects of levothyroxine (L-T4) treatment.Methods: KK-Ay mice, serving as a spontaneous type 2 diabetes mellitus model, underwent intragastric administration of 10 ng/g and 20 ng/g of L-T4 solution or normal saline for 8 weeks. Age-matched C57BL/6J mice were used as normal controls. Cognitive and memory functions were examined through the open field and Morris water maze tests. Hippocampal TH signaling and pathogenic status were evaluated. The potential signaling pathways involved in the neuroprotective action of L-T4 were investigated through RNA sequencing and further verified through quantitative real-time PCR (qPCR), Western blotting (WB), immunofluorescence (IF), and fluorescent multiplex immunohistochemistry (mIHC) in vivo and vitro.Results: The expressions of hippocampal TH transporters (Mct8 and Oatp1c1), Dio2, and TH receptor were upregulated, whereas Dio3 as well as the TH-positive regulated genes MBP, Enpp2, and Klf9 were downregulated in DACD mice. Exogenous L-T4 partially alleviated cognitive and memory dysfunction and restored hippocampal neuronal activity by optimizing TH signaling. RNA sequencing provided insights into the role of type I interferon (IFN-I) signaling and necroptosis on the amelioration of hippocampal damage after L-T4 treatment. WB and qPCR further confirmed that the levels of key proteins for IFN-I signaling and necroptosis (p-STAT1, p-STAT2, IRF9, ZBP1, p-RIP3, and p-MLKL) were increased, but largely returned after L-T4 administration in vivo and T3 treatment in vitro. IF and mIHC revealed that IRF9 and p-MLKL colocalized in neurons, but not in astrocytes or microglia, of the hippocampus in DACD mice. The diabetes mellitus group had an increased number of IRF9+ p-MLKL+ NeuN+ cells, which decreased after L-T4 treatment. The elevated IFN-I signaling-mediated necroptosis in HT22 cells was also decreased by T3.Conclusion: We demonstrated abnormal hippocampal TH signaling and action in DACD. Promoting TH action with exogenous L-T4 ameliorated hippocampal impairment through inhibiting IFN-I signaling-induced necroptosis.

PurposeTo investigate the prevalence and body mass index (BMI) associations of congenital lower epiblepharon in children in China and the difference in the refractive errors between children with and without epiblepharon.MethodsChildren 6-12 years of age in Beichen District of Tianjin were screened for congenital epiblepharon from September to October 2017. All children underwent slit-lamp examination, strabismus screening, visual acuity examination and refraction. Weight and height were also recorded. The prevalence of lower epiblepharon in school-age children was evaluated, and its association with age, sex, BMI, and refractive error was analyzed.ResultsA total of 28,225 children were examined; 564 had epiblepharon. The prevalence of epiblepharon was found to be, for 6-year-olds, 2.50%; for 7-year-olds, 2.13%; for 8-year-olds, 2.10%; for 9-year-olds, 1.97%; for 10-year-olds, 1.85%; for 11-year-olds, 1.67%; and for 12-year-olds, 1.19% (P < 0.05). The prevalence of overweight and obesity in children with epiblepharon was found to be 16.7% and 47.2%, respectively. The prevalence and degree of astigmatism was higher than in nonepiblepharon children. We found a possible association between severity of astigmatism and severity of epiblepharon.ConclusionsIn our study, the prevalence of epiblepharon decreased with advancing age, and the majority of children with epiblepharon were found to be overweight or obese. Epiblepharon was associated with astigmatism.

Objective:Placental iodide transport is necessary for maintaining an adequate iodide supply to the developing fetus. We hypothesized that compounds from the placental barrier can compensate for decreases in maternal iodine intake and normalize fetal iodine levels. Methods:Pregnant rats administered different amounts of iodine (1.24, 2.5, 5, or 10 mu g/day) were evaluated on gestational day (gd) 16 and 20. The iodine levels in maternal blood, amniotic fluid (AF), and placental tissue were estimated using As-Ce catalytic spectrophotometry. The protein and/or messenger RNA (mRNA) levels of sodium iodide symporter (NIS), pendrin, alpha-smooth muscle actin (alpha-SMA), and CD31 in the placental labyrinth, trophoblast cells isolated using laser capture microdissection (LCM), and/or fetomaternal thyroid were detected using immunoblotting, real-time polymerase chain reaction, and/or immunohistochemistry. Results:When iodine intake was reduced, iodine levels in maternal blood gradually decreased; however, placental iodine levels were not significantly different between groups on gd16 and gd20. Minimal changes were observed in AF iodine levels on gd16, and a mild decreasing trend was observed (iodine dose, 10 to 1.24 mu g/day) on gd20. NIS protein, which was linearly distributed along the basolateral membrane of maternal-fetal thyroid follicles, gradually increased with decreasing iodine levels. Regarding iodine deficiency in the placental labyrinth on gd16 and gd20, pendrin and glycosylated NIS proteins were significantly upregulated in a dose-dependent manner. However, the mRNA levels were unchanged. Furthermore, the conversion of NIS protein from the nonglycosylated to the glycosylated form increased. In trophoblast cells isolated using LCM,PDSmRNA levels increased in the 1.24-mu g/day group on gd16 but notNISmRNA levels. There was a smaller alpha-SMA(+)area in the labyrinth zone on gd16 and gd20; however, the proportional CD31(+)area increased on gd16 and reduced on gd20 with decreased iodine levels. Conclusions:All mechanisms upregulating the expression of iodine transporters and changes in villous stroma and microvessel area in the placental labyrinth can promote iodide transfer from mother to fetus in iodine deficiency, especially before the onset of fetal thyroid function. Compensatory NIS protein regulation in the placenta against decreased iodine intake mainly occurs during translation and glycosylation modification after translation. Pendrin may be more important than NIS in the mediation of placental iodide transport.

Objective To investigate the expression of MCT8,DCX,SHH and ARC/ARG3. 1 in brain neurons of neonatal rats exposed to thyroid dysfunction in uterus.Methods Wistar pregnant rats were randomly divided into control group and experimental groups in which rats were drunk water with 1, 3, or 5 ppm propylthiouracil

目的 探讨肾上腺皮质癌(ACT)潜在致病机制,并筛选出可能作为相关生物靶标的基因.方法 从基因表达数据库Gene Expression Omnibus (GEO)中选取儿童ACT相关RNA芯片数据集(GSE75415),利用R语言的相关函数包对其中的18个ACT组织样本(实验组)以及7个正常肾上腺皮质组织样本(对照组)中的mRNA表达数据进行预处理差异表达分析,对ACT各分级(stage1～4)的差异表达基因(DEGs)和重合差异基因(OLDEGs),采用功能富集分析(GO功能富集和KEGG通路),并筛选出中心基因.同时对TCGA数据库包括79个ACT样本的二代测序数据进行分析,筛选出对ACT患者生存时间有影响的基因.结果 Stage1～4分别有248、334、315和561个基因发生了差异表达,各分级样本组间存在73个重合基因(OLDEGs),中心基因HSPA13、GARS、STXBP1、AKIRIN1、TUBB3在各分级中均表达上调,中心基因ADH1B、DCN、RASSF2、PDGFRA、PLAT、C3、FOS在各分级中均表达下调,它们通过影响免疫反应、细胞周期、磷酸化、凝血及相应的信号通路,对ACT的发生与发展发挥作用.另外,OLDEGs在79个TCGA数据库ACT样本生存期分析发现,基因XPO1、RACGAP1、PDGFD、NR4A2、MXRA5、VPS51、TMED3、NDFIP1和CDKN1C与ACT的生存期密切相关.结论 在各级中均差异表达的基因和生存期相关基因可以作为ACT治疗的新靶点,这将有助于进一步理解肾上腺皮质癌的病因和预后治疗.