Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver disorders that is featured by the extensive deposition of fat in the hepatocytes. Current treatments are very limited due to its unclear pathogenesis. Here, we investigated the function of circ_0057558 and miR-206 in NAFLD. High-fat diet (HFD) feeding mouse was used as an in vivo NAFLD model and long-chain-free fatty acid (FFA)-treated liver cells were used as an in vitro NAFLD model. qRT-PCR was used to measure levels of miR-206, ROCK1 mRNA, and circ_0057558, while Western blotting was employed to determine protein levels of ROCK1, p-AMPK, AMPK, and lipogenesis-related proteins. Immunohistochemistry were performed to examine ROCK1 level. Oil-Red O staining was used to assess the lipid deposition in cells. ELISA was performed to examine secreted triglyceride (TG) level. Dual-luciferase assay was used to validate interactions of miR-206/ROCK1 and circ_0057558/miR-206. RNA immunoprecipitation was employed to confirm the binding of circ_0057558 with miR-206. Circ_0057558 was elevated while miR-206 was reduced in both in vivo and in vitro NAFLD models. miR-206 directly bound with ROCK1 3’-UTR and suppressed lipogenesis and TG secretion through targeting ROCK1/AMPK signaling. Circ_0057558 directly interacted with miR-206 to disinhibit ROCK1/AMPK signaling. Knockdown of circ_0057558 or overexpression of miR-206 inhibited lipogenesis, TG secretion and expression of lipogenesis-related proteins. ROCK1 knockdown reversed the effects of circ_0057558 overexpression. Injection of miR-206 mimics significantly ameliorated NAFLD progression in vivo. Circ_0057558 acts as a miR-206 sponge to de-repress the ROCK1/AMPK signaling and facilitates lipogenesis and TG secretion, which greatly contributes to NAFLD development and progression.

Background: To assess the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) used as an adjunct to insulin therapy in adults with type 1 diabetes.Methods: A search of electronic databases (Medline, Embase, and the Cochrane Central Register of Controlled Trials) from 1 January 1950 to 23 May 2021 was conducted to find randomized controlled trials. The primary outcome was the change in HbA1c. Eight efficacy and six safety secondary endpoints were evaluated via meta-analysis. Weighted mean difference (WMD) and odds ratio (OR), alongside 95% confidence interval (CI), were calculated using the random effects model.Results: Among 1,379 candidate studies, 11 trials comprising 2,856 participants satisfied the inclusion criteria. Overall, GLP-1 RA adjunctive therapy reduced HbA1c by −0.21% (95% CI, −0.33 to −0.10), weight by −4.04 kg (−4.8 to −3.27), systolic pressure by −2.57 mmHg (−4.11 to −1.03), and diastolic blood pressure by −1.02 mmHg (−1.99 to −0.06). In addition, there was a decrease in prandial insulin dose (WMD, −4.23 IU; 95% CI, −5.26 to −3.20), basal insulin dose (−2.40 IU; −3.93 to −0.87), and total insulin dose (−5.73 IU; −10.61 to −0.86). Moreover, GLP-1 RAs did not increase the incidence of severe hypoglycemia, diabetic ketoacidosis, or severe adverse events. However, GLP-1 RAs increased the incidence of gastrointestinal adverse events (OR, 2.96; 95% CI, 2.33–3.77).Conclusion: Our meta-analysis of randomized clinical trials suggests moderate beneficial effects of GLP-1 RAs on the metabolic profile in patients with type 1 diabetes, without an increased risk of serious adverse events.Clinical Trial Registration:https://www.crd.york.ac.uk/PROSPERO; Identifier: CRD 42020199840.

Background: Aromatase excess syndrome (AEXS) is a rare autosomal dominant disorder caused by CYP19A1 overexpression. Clinical manifestations of AEXS include pre- or peri-pubertal gynecomastia, advanced bone age and compromised adult height. Case presentation: Here we report an 8-year-old boy diagnosed with AEXS by chromosomal array that revealed a 1.1 Mb novel de novo duplication at 15q21.2, with a predicted final height of 157.4 cm. We prescribed letrozole and growth hormone (GH) to maximize his linear growth. Without further bone age advancement, his height increased from 137.7 cm to 144 cm after an 8-month treatment period. Conclusions: We identified a novel duplication at 15q21.2 in AEXS, and found that aromatase inhibitor (AI) plus GH might provide a better growth-promoting approach for AEXS patients.