Background: The relationship between TSH and the lipid profile is contradictory because few studies have excluded the potential influence of the thyroid hormones (TH). The aim of the present study was to evaluate the relationship between serum TSH levels and the lipid profile independent of TH. Methods: 1302 CHD patients diagnosed by coronary angiography were retrospectively studied. The prevalence and distribution of thyroid dysfunction were analyzed first. To assess the impact of TSH on serum lipids, Pearson’s correlation analysis was performed after adjustments for classic factors and TH. To calculate the extent of the effect of TSH on the serum cholesterol level, the partial least squares method and additional statistical methods were used. Results: After the exclusions, a total of 568 patients (270 males and 298 females with a mean age of 63.56 ± 11.376 years) were selected. The prevalence of thyroid dysfunction among the patients was 18.66%, and the prevalence of hypothyroidism (15.32%) was higher than that of hyperthyroidism (3.34%). Even after adjusting for confounding factors, such as sex, age, smoking status, fasting plasma glucose levels and TH, a significant positive impact of TSH on the serum total cholesterol (TC) level was revealed (r = 0.095, p = 0.036). Each 1 mIU/L increase in the TSH level might be linked to a 0.015580712 mmol/L elevation of the serum TC value. Conclusions: TSH can increase the TC level in CHD patients independent of TH. The present study suggests a potential physiological role of TSH and the importance of maintaining an appropriate TSH level in CHD patients.

Osteopetrosis (OMIM: 611497), literally “stone bone,” is a group of inherited bone disorders characterized by increased skeletal mass due to defective osteoclast function. A patient who reported a history of frequent fractures, weakness and fatigue was admitted to our hospital in 2011. The patient presented with the typical features of osteopetrosis: fractures after minor trauma, early tooth loss, anemia, hepatosplenomegaly, and a generalized increase in bone mineral density (BMD). Aside from his father's complaint of excessive tooth loss, his mother, two sisters, son, and daughter were healthy. Blood samples of the family members were drawn for genetic analyses. The entire coding region and adjacent splice sites of the pleckstrin homology domain–containing family M (with RUN domain) member 1 (PLEKHM1) gene were sequenced. One mutation, a heterozygous deletion mutation in exon 11 (c.3051_3052delCA), was identified in the patient but not in his relatives. The mutation leads to a translation product with a highly impaired Rubicon homology domain. Co‐immunoprecipitation and immunofluorescence analyses using HEK293 cells showed that overexpression of a PLEKHM1 CA‐deletion mutant resulted in a dramatic decrease in the interaction between PLEKHM1 and the small GTPase Rab7 compared to wild‐type PLEKHM1. The normal processes of endocytosis and autophagy were disturbed in cells expressing the mutant (transfected HEK293 and U937 cells), as indicated by epidermal growth factor receptor (EGFR) degradation and an altered LC3‐I/II ratio, respectively, which may lead to a defect in osteoclast function. A four‐year follow‐up study of the patient showed that the PLEKHM1‐dependent osteopetrosis was relatively malignant, with significant symptoms of pancytopenia and hepatosplenomegaly. © 2016 American Society for Bone and Mineral Research.

Subclinical hypothyroidism (SCH) is becoming a global health problem due to its increasing prevalence and potential deleterious effects. However, the molecular mechanisms underlying the lipid metabolic disorders in SCH have not been fully clarified. Additionally, progress in elucidating the exact pathogenesis of SCH has been hampered by the lack of optimized mouse models. Methimazole (MMI) was applied to construct a noninvasive SCH mouse model. Eight-week-old C57BL/6 mice were administrated MMI through the drinking water. After 12 weeks, the MMI-treated mice showed the diagnostic criteria for SCH: increased serum thyrotropin (TSH) levels with constant thyroid hormone levels that persisted for approximately 8 weeks. Notably, SCH mice presented evident lipid metabolic disturbances, including dyslipidemia and hepatic lipid accumulation. Further analysis showed that hepatic endoplasmic reticulum stress (ER stress) was induced in the SCH mice or by the elevation of TSH in vitro, likely via the IRE1α/XBP-1 pathway. Interestingly, when we used 4-phenyl butyric acid to repress ER stress in SCH mice for 4 weeks, dyslipidemia and hepatic lipid accumulation were both significantly alleviated. Our findings indicate that an optimized SCH mouse model could be established using MMI and ER stress may play a pivotal role in the lipid metabolic abnormalities in SCH.

Osteogenesis imperfecta (OI) is a connective tissue disorder affecting the skeleton and other organs, which has multiple genetic patterns, numerous causative genes, and complex pathogenic mechanisms. The previous classifications lack structure and scientific basis and have poor applicability. In this paper, we summarize and sort out the pathogenic mechanisms of OI, and analyze the molecular pathogenic mechanisms of OI from the perspectives of type I collagen defects(synthesis defects, processing defects, post-translational modification defects, folding and cross-linking defects), bone mineralization disorders, osteoblast differentiation and functional defects respectively, and also generalize several new untyped OI-causing genes and their pathogenic mechanisms, intending to provide the evidence of classification and a scientific basis for the precise diagnosis and treatment of OI.