Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents. Convallatoxin, a natural cardiac glycoside, exhibits potent anti-tumor activities. Literature has confirmed that PTHR1 is highly expressed in OS tissues and cells and downregulation of PTHR1 could decrease the invasion and growth of OS cells and increase tumor differentiation. In addition, PTHR1 could activate Wnt signaling pathway to promote the malignant functions of OS. In the present study, MG63 and U2OS cells were treated with 0, 12.5, 25, and 50 nM convallatoxin in order to elucidate the precise function of convallatox on the malignant behaviors of OS cells. Moreover, MG63 and U2OS cells treated with convallatoxin were transfected with Ov-PTHR1 or sh-DKK1, aiming to explore whether convallatoxin impeded the malignant progression of OS by modulating PTHR1 and Wnt/β-catenin pathway. CCK-8, wound healing and transwell assays were employed to assess the proliferation, migration, and invasion of OS cells. Differentiation markers (collagen 1, osteopontin, RANKL, Runx2, osteocalcin) were measured to evaluate OS cell differentiation. Results illuminated that convallatoxin suppressed proliferation, migration, and invasion as well as promoted osteogenic differentiation of OS cells. Besides, convallatoxin inhibited PTHR1 expression and inactivated Wnt/β-catenin pathway and PTHR1 overexpression activated Wnt/β-catenin pathway. Furthermore, PTHR1 overexpression or DKK1 knockdown reversed the suppressing effects of convallatoxin on OS cell proliferation, migration, and invasion, as well as the enhancing effect of convallatoxin on OS cell osteogenic differentiation. Collectively, convallatoxin may repress the malignant progression of OS by blocking PTHR1 and Wnt/β-catenin pathway.

Purpose. To probe the property of serum uric acid in evaluating the activity of patients with thyroid-associated ophthalmopathy. Methods. A total of 443 patients with TAO admitted to our hospital from March 2016 to February 2021 were selected for the observation group. Simultaneously, 443 healthy subjects were selected for the control group. The observation group was divided into the active group ( n = 254 ) and the inactive group ( n = 189 ) according to the clinical activity score (CAS). Besides, the patients were divided into mild group ( n = 201 ), moderate severe group ( n = 133 ) and extremely severe group ( n = 109 ) based on the severity of TAO. Serum uric acid, free triiodothyronine (FT3), free thyroid hormone (FT4), thyrotropin stimulating hormone (TSH) and glycosylated hemoglobin (HbA1c) levels were detected and analyzed in each group. Results. Serum UA, FT3, FT4, TSH and HbA1c in the active group were significantly enhanced than those in the other two groups ( P < 0.05 ), and there was no significant difference between the inactive group and the control group ( P > 0.05 ). In different disease severity groups, the serum UA level of patients in the active group was significantly promoted than that in the inactive group and control group ( P < 0.05 ) and was decreased successively in extremely severe group, moderate severe group and mild group, with statistical significance ( P < 0.05 ). Pearson’s analysis showed that UA was positively correlated with FT3, FT4, and HbA1c ( r = 0.652 , P = 0.031 ; r = 0.571 , P = 0.042 ; r = 0.737 , P = 0.024 ), while was reversely correlated with TSH level ( r = − 0.137 , P = 0.262 ). There was no correlation between UA and FT3, FT4, and HbA1c levels in the inactive group. UA detection showed the average sensitivity and specificity of TAO activity were 94.3% and 85.2%, respectively. There was no significant correlation between the severity of disease and serum UA in inactive patients ( P = 0.135 ). There was a positive correlation between the severity of disease and serum UA in active patients ( P = 0.005 ). Conclusion. UA may be used as a laboratory indicator for quantitative clinical diagnosis of thyroid-associated ophthalmopathy (TAO) and as a parameter for the presence of TAO activity.

Background: Gender and reproductive status differences exist in both non-alcoholic fatty liver disease (NAFLD) and body composition. Our purpose was to investigate the relationship between body composition and the severity of liver steatosis and fibrosis in NAFLD in different gender and reproductive status populations. Methods: This cross-sectional study included 880 participants (355 men, 417 pre-menopausal women, 108 post-menopausal women). Liver steatosis and fibrosis and body composition data were measured using FibroScan and a bioelectrical impedance body composition analyzer (BIA), respectively. Multiple ordinal logistic regression (MOLR) was used to analyze the correlation between body composition indicators and liver steatosis grade and fibrosis stage in different gender and menopausal status populations. Results: Men have higher waist circumference (WC), appendicular skeletal muscle mass (ASM), appendicular skeletal muscle mass index (ASMI), fat free mass (FFM), and fat free mass to fat mass ratio (FFM/FM) than pre- or post-menopausal women, while pre-menopausal women have higher percent body fat (PBF), visceral fat area (VFA), and fat mass (FM) than the other two groups (p < 0.001). Besides, men have greater controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) values (p < 0.001). For MOLR, after adjusting for confounding factors, WC (OR, 1.07; 95% CI, 1.02-1.12; P = 0.011) and FFM/FM (OR, 0.52; 95% CI, 0.31-0.89; P = 0.017) in men and visceral obesity (OR, 4.16; 95% CI, 1.09-15.90; P = 0.037) in post-menopausal women are independently associated with liver steatosis grade. WC, PBF, and visceral obesity are independently associated with liver fibrosis stage in men (OR, 1.05; 95% CI, 1.01-1.09, P = 0.013; OR, 1.08; 95% CI, 1.01-1.15; P = 0.018; OR, 3.92; 95% CI, 1.97-7.81; P < 0.001, respectively). Conclusions: Increased WC and low FFM/FM in men and visceral obesity in post-menopausal women are independent correlates of aggravated liver steatosis. In addition, increased WC, PBF, and visceral obesity are independent correlates of worsening liver fibrosis in men. These data support the gender- and reproductive status-specific management of NAFLD.