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.

AbstractObjectivesAs people across the world suffer from coronavirus disease 2019 (COVID-19), further studies are needed to facilitate evaluating the severity and prognosis of COVID-19 patients. In the study, we aimed to dissect the dynamic profile and clinical implications of hematological findings in hospitalized patients with COVID-19.MethodsWe retrospectively analyzed the hematological findings of 72 patients with COVID-19 admitted from January 21 to February 17, 2020. The final date of follow-up was March 20, 2020. Dynamic profile of vital hematological parameters in severe and non-severe patients was presented at different time points (day 1, 5, 7, 9, 11, 13, 15 after admission), and the correlation of hematological parameters with hospitalization time was indicated.ResultsOf 72 patients with COVID-19, lymphopenia and leukopenia occurred in 39 (54.2%) and 20 (27.8%) patients with COVID-19, respectively. Fifteen (20.8%) patients were defined as severe cases and 57 (79.2%) were non-severe cases. Compared to non-severe patients, leukocyte count, neutrophil count and neutrophil-to-lymphocyte ratio (NLR) were significantly higher, whereas lymphocyte count was declined in severe patients at each time point. A growing trend in platelet count was found in non-severe patients over the follow-up period. In addition, a positive correlation of NLR with hospitalization time was detected from day 5 after admission.ConclusionsDynamic changes in vital hematological parameters from severe and non-severe patients had been characterized in the course of hospitalization. During hospitalization, NLR was found to have certain relevance to the hospitalization days and a role in forecasting disease prognosis for patients with COVID-19.

DNA methylation is being increasingly recognized to play a role in regulation of hepatitis B virus (HBV) gene expression. The aim of this study was to compare the CpG island distribution among different HBV genotypes. We analyzed 176 full-length HBV genomic sequences obtained from the GenBank database, belonging to genotypes A through J, to identify the CpG islands in the HBV genomes. Our results showed that while 79 out of 176 sequences contained three conventional CpG islands (I–III) as previously described, 83 HBV sequences harbored only two of the three known islands. Novel CpG islands were identified in the remaining 14 HBV isolates and named as CpG island IV, V, and VI. Among the eight known HBV genotypes and two putative genotypes, while HBV genomes containing three CpG islands were predominant in genotypes A, B, D, E, and I; genotypes C, F, G, and H tended to contain only two CpG islands (II and III). In conclusion, the CpG islands, which are potential targets for DNA methylation mediated by the host functions, differ among HBV genotypes, and these genotype-specific differences in CpG island distribution could provide new insights into the understanding of epigenetic regulation of HBV gene expression and hepatitis B disease outcome.

Preeclampsia is associated with developmental delay in infants and with an increased risk of various diseases in adulthood, including hypertension and epilepsy. It has been reported that several organs show developmental retardation and functional deficiency in offspring of preeclamptic rats. However, the developmental and functional changes in brains of the offspring of preeclamptic rats remain unknown. Here, we established a preeclampsia-like rat model induced using Nω-nitro-l-arginine methyl ester (l-NAME) to analyze the developmental and functional changes in brains of the offspring. Body and brain weights were decreased in the l-NAME group at postnatal day 0 (P0). However, there were no significant differences between the l-NAME and control groups in brain and body weights at P56. Upon further analysis, we detected a deficiency in neurogenesis, but not in apoptosis, which contributed to the smaller brains of the offspring in the l-NAME group at P0. Additionally, we observed an increase in gliogenesis to compensate for the brain weights of the offspring at P56. Although the weight and laminar structure of the brains were essentially normal at P56, spatial learning and memory were severely impaired. We also found that adult hippocampal neurogenesis was disrupted in the offspring from preeclampsia-like rats, which may explain the cognitive deficiency. Moreover, qRT-PCR revealed a reduced expression of neurogenesis-related genes in the offspring. Overall, we have described the deleterious effects of preeclampsia on the brains of offspring, providing clues to the cellular and molecular mechanisms involved in this pathogenesis, which may aid in the development of therapeutic approaches.Electronic supplementary materialThe online version of this article (doi:10.1007/s12035-014-9060-7) contains supplementary material, which is available to authorized users.

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Background Spontaneous bacterial peritonitis (SBP) is a serious complication and common cause of death in patients with liver cirrhosis. This study was conducted to compare the microbiological characteristics, drug resistance, and treatment outcomes for nosocomial SBP and community-acquired SBP. Methods A retrospective study was performed on 334 patients with culture-positive SBP at Beijing Youan Hospital, China, between January 2012 and December 2016. The medical records for these patients were reviewed, and their clinical and laboratory data were analyzed. Results A total of 155 (46.4%) patients with nosocomial SBP and 179 (53.6%) with community-acquired SBP were included in this study. From the patients’ ascitic fluids, 334 pathogenic strains, including 178 Gram-negative bacterial strains, 138 Gram-positive bacterial strains and 18 other microbial strains were isolated. E. coli was the major pathogen (24.3%), followed by Klebsiella pneumoniae (12.0%) and Enterococcus faecium (10.5%). The proportion of Enterococcus was significantly higher in the patients with nosocomial SBP (6.1% vs. 27.7%, P < 0.001) than in the patients with community-acquired SBP. The main pathogens isolated from the nosocomial infections were significantly more resistant to the first-line recommended drug. Compared with community-acquired SBP, nosocomial SBP had a poorer outcome (36.8% vs. 24.6%; P = 0.016). The independent predictors for 30-day mortality included nosocomial infection, Child-Pugh classification, hepatocellular carcinoma, renal failure and hepatic encephalopathy. Conclusion Gram-negative bacteria were the major pathogens involved in SBP in the cirrhotic patients. The strains isolated from the patients with nosocomial SBP displayed higher drug resistance than those isolated from patients with community-acquired SBP. Compared with community-acquired SBP, nosocomial SBP had a poorer outcome. When choosing drug treatments, the acquisition site of infection and the local epidemiological situation should be taken into account.

Purpose: To assess the potential role of amphiregulin as messenger molecule in ocular axial elongation. Methods: The experimental study included guinea pigs (total n = 78) (age: 3-4 weeks) which underwent bilateral lens-induced myopization and received 15 days later three intraocular injections in weekly intervals of amphiregulin antibody (doses:5 lg, 10 lg, 20 lg) into their right eyes, and three phosphatebuffered saline injections into their left eyes; and guinea pigs without lens-induced myopization and which received three unilateral intraocular injections of amphiregulin antibody (dose: 20 lg) or amphiregulin (doses: 1 ng; 10 ng; 20 ng) into their right eyes, and three phosphate-buffered saline injections into their left eyes. Seven days later, the animals were sacrificed. Intravitally, we performed biometry, and histology and immunohistochemistry post-mortem. Results: In animals with bilateral lens-induced myopization, the right eyes receiving amphiregulin antibody showed reduced axial elongation in a dose-dependent manner (dose: 5 lg: side difference: 0.14 AE 0.05 mm;10 lg: 0.22 AE 0.06 mm; 20 lg: 0.32 AE 0.06 mm; p < 0.001), thicker sclera (all p < 0.05) and higher cell density in the retinal nuclear layers and retinal pigment epithelium (RPE) (all p < 0.05). In animals without lens-induced myopia, the right eyes with amphiregulin antibody application (20 lg) showed reduced axial elongation (p = 0.04), and the right eyes with amphiregulin injections experienced increased (p = 0.02) axial elongation in a dosedependent manner (1 ng: 0.04 AE 0.06 mm; 10 ng: 0.10 AE 0.05 mm; 20 ng: 0.11 AE 0.06 mm). Eyes with lens-induced axial elongation as compared to eyes without lens-induced axial elongation revealed an increased visualization of amphiregulin upon immunohistochemistry and higher expression of mRNA of endogenous amphiregulin and epidermal growth factor receptor, in particular in the outer part of the retinal inner nuclear layer and in the RPE. Conclusion: Amphiregulin may be associated with axial elongation in young guinea pigs.