Background::The increasing burden of non-alcoholic fatty liver disease (NAFLD) worldwide imposes an emerging public health issue. We perform the current study to estimate the global prevalence, incidence, disease progression, and clinical outcomes of NAFLD.Methods::A systematic search was conducted in Medline, Embase, Web of Science, Google Scholar, and Cochrane CENTRAL that screened articles in English language published from January 2000 to December 2021. NAFLD prevalence, incidence, rate of disease progression, and outcomes were calculated with the DerSimonian-Laird random effects model with arcsine transformation.Results::Our search identified 59,156 records, of which 578 studies fulfilled our inclusion criteria. The overall prevalence of NAFLD was 29.38% (95% confidence interval [CI] 28.09–30.69) regardless of the diagnostic techniques. Looking at the group in which the diagnosis was made by ultrasound exclusively, the pooled prevalence was 30.49% (95% CI 29.55–31.43). NAFLD has become more prevalent during the year 2011–2021 (31.63%, 95% CI 30.23–33.04) compared with year 2000–2010 (27.94%, 95% CI 26.23–29.69). The pooled estimation of non-alcoholic steatohepatitis prevalence was 8.26% (95% CI 1.13–21.01), 46.49% (95% CI 35.93–57.20), and 46.72% (95% CI 37.57–55.98) in general population, NAFLD patients, and severe/morbidly obese patients, respectively. Based on a total of 110,142 newly developed NAFLD patients, the pooled incident rate was estimated as 46.24 cases per 1000 person-years (95% CI 43.21–49.30). In patients with NAFLD, the incident rate of hepatocellular carcinoma was 1.46 (95% CI 0.90–2.03) cases per 1000 person-years. The overall pooled estimate of NAFLD related mortality was 23.91 (95% CI 13.55–37.18) death per 1000 person-years.Conclusions::The prevalence of NAFLD is increasing globally. It is contributing to poor clinical outcomes including hepatocellular carcinoma and death. Rising awareness and urgent actions are warranted to control the NAFLD pandemic across the globe.Registration::PROSPERO, No. CRD42020171104.

Background and objective Targeted therapies are ineffective in lung squamous cancer(LUSC),and the low response rate of immunotherapy hampers its application in LUSC,so it is urgent to explore new strategies for LUSC treat-ment.Ferroptosis plays an important role in tumour suppression.The aim of this study was to investigate the role and mecha-nism of targeting 3-hydroxy-3-methylglutaryl-CoA synthase 1(HMGCS1)in regulating ferroptosis in LUSC cells,in order to provide a new research direction for LUSC therapy.Methods The expression of HMGCS1 in LUSC was analysed by The Cancer Genome Atlas(TCGA)and Clinical Proteomic Tumor Analysis Consortium(CPTAC)online databases;the relation-ship between HMGCS1 and survival time of lung cancer was analysed by the Kaplan-Meier Plotter online survival database;the expression level of HMGCS1 in LUSC tissues was verified by immunohistochemistry.After interfering with HMGCS1 expression by small interfering RNA(siRNA),cell activity and cell migration ability were detected by CCK8 and Transwell as-say;apoptosis was detected by flow cytometry after interfering with HMGCS1 or after treatment with the HMGCS1 inhibitor of hymeglusin;Fe2+,reactive oxygen species(ROS)and lipid peroxidation levels were detected by flow cytometry and high-content confocal fluorescence imaging systems,respectively in SKMES cells after inhibition of HMGCS1;and Western blot was performed to detect the expression of ACSL4,GPX4 and SLC7A11,which are markers of the ferroptosis pathway after in-hibition of HMGCS1.Results HMGCS1 mRNA and protein levels were significantly high in LUSC;siRNA interference with HMGCS1 expression inhibited the proliferative activity and migration ability of LUSC cells,but had no significant effect on apoptosis.Interference with HMGCS1 or treatment with the HMGCS1 inhibitor of hymeglusin significantly promoted intra-cellular Fe2+,ROS and lipid peroxidation levels in SKMES cells,and induced ferroptosis in LUSC cells;Western blot assay showed that inhibition of HMGCS1 significantly promoted the expression of ACSL4.Conclusion Inhibition of HMGCS1,a target of LUSC,promotes ferroptosis in lung cancer cells and provides a research basis for screening new therapeutic targets for LUSC.