Purpose: To estimate prevalence, associated factors, and time trends of myopia in Chinese children and adolescents. Methods: We searched PubMed, EMBASE, and Web of Science for studies examining the prevalence of myopia in children and adolescents aged 3 years to 19 years in China before October 2018. We pooled the prevalence and associated factors for myopia and estimated time trends. Results: In 22 eligible studies including 192,569 individuals, the pooled prevalence (95% confidence interval [CI]) of myopia and high myopia in the study period from 1998 to 2016 was 37.7% (95% CI: 23.5–52.0%) and 3.1% (95% CI: 1.2–5.0%), respectively, with higher odds for girls than boys (myopia: odds ratio: 1.29; 95% CI: 1.14–1.46; P < 0.001; high myopia: odds ratio: 1.37; 95% CI: 1.05–1.78; P = 0.02) and with higher prevalences for urban areas than rural regions (myopia: 48.8% [95% CI: 32.3–65.3] vs. 31.9% [95% CI: 20.4–43.3; P < 0.001]). The pooled prevalence of myopia and high myopia increased from 4.7% (95% CI: 2.5–6.9) and 0.2% (95% CI: 0.0–0.5), respectively, in <7-years-olds to 56.2% (95% CI: 29.8–82.5) and 15.1% (95% CI: 6.4–23.8), respectively, in 16- to 18-year-olds. Myopic refractive error increased with older age (P < 0.001), female gender (P < 0.001), and study year (P = 0.003). Studies performed after 2013 showed a prevalence of myopia and high myopia in the 16- to 18-year-olds of 84.8% (95% CI: 84.4–85.2%) and 19.3% (95% CI: 18.6–20.2%), respectively. Assuming a further linear relationship with the study year, myopia prevalence in 2050 among children and adolescents aged 3 years to 19 years would be estimated to be about 84%. Conclusion: The marked rise in high myopia prevalence among adolescents in China may be of importance for high myopia as risk factor for irreversible vision loss in Chinese adults in the future.
The persistence of hepatitis B virus (HBV) infection is maintained by the nuclear viral covalently closed circular DNA (cccDNA), which serves as transcription template for viral mRNAs. Previous studies suggested that cccDNA contains methylation-prone CpG islands, and that the minichromosome structure of cccDNA is epigenetically regulated by DNA methylation. However, the regulatory effect of each CpG island methylation on cccDNA activity remains elusive. In the present study, we analyzed the distribution of CpG methylation within cccDNA in patient samples and investigated the impact of CpG island methylation on cccDNA-driven virus replication. Our study revealed the following observations: 1) Bisulfite sequencing of cccDNA from chronic hepatitis B patients indicated that CpG island I was seldom methylated, 2) CpG island II methylation was correlated to the low level of serum HBV DNA in patients, and in vitro methylation studies confirmed that CpG island II methylation markedly reduced cccDNA transcription and subsequent viral core DNA replication, 3) CpG island III methylation was associated with low serum HBsAg titers, and 4) Furthermore, we found that HBV genotype, HBeAg positivity, and patient age and liver fibrosis stage were also relevant to cccDNA CpG methylation status. Therefore, we clearly demonstrated that the status of cccDNA methylation is connected to the biological behavior of HBV. Taken together, our study provides a complete profile of CpG island methylation within HBV cccDNA and new insights for the function of CpG methylation in regulating HBV cccDNA transcription.
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