Objective: To investigate the association between physical activity and the risk of mortality, so as to provide the basis for guiding the elderly to maintain appropriate levels of physical activity. Methods: A retrospective cohort study was adopted. Basic information, weekly physical activity items and duration of the elderly aged 50-71 years old was collected from the National Institutes of Health-American Association of Retired Persons Diet and Health Study database. With all-cause mortality risk as the main outcome indicator, controlling for demographic, dietary and disease factors, the association between the duration, metabolic equivalent and intensity of physical activity and all-cause mortality risk was analyzed using restricted cubic spline and multivariable Cox proportional risk regression model. Results: A total of 266 072 participants were included, with an mean age of (70.11±5.36) years old. There were 155 244 males (58.35%) and 110 828 females (41.65%), with a total of 36 006 deaths by December 31, 2011. The median duration of physical activity was 14.00 (interquartile range, 14.00) h/week and the median metabolic equivalents was 53.00 (interquartile range, 54.71) MET-h/week. Restricted cubic spline analysis indicated that the risk of all-cause mortality declined rapidly within the physical activity range of 0 to 15.0 h/week or 50.0 MET-h/week, but with the continuing increase in physical activity, the decline in the risk of all-cause mortality slowed down (all P<0.05). Multivariable Cox proportional risk regression analysis showed that compared with participants with no physical activity, participants with the duration of 0.1-<15.0 h/week, 15.0-<29.5 h/week, ≥29.5 h/week (HR=0.502, 0.386 and 0.368), or the metabolic equivalent of 0.1-<50.0 MET-h/week, 50.0-<110.8 MET-h/week and ≥110.8 MET-h/week (HR=0.511, 0.379 and 0.354) were associated with a reduced risk of all-cause mortality. The combination of mild (0.1-<5.0 h/week), moderate (≥5.0 h/week) and vigorous (≥1.3 h/week) activities had a lower risk of all-cause mortality (HR=0.320). Conclusions Moderate physical activity is associated with a reduced risk of mortality, and it is recommended to do 15.0 h or 50.0 MET-h of physical activity per week in combination with different intensities.

Objective:To explore the key genes and pathways that may play an important role in the pathogenesis of acne by bioinformatics analysis.Methods:GSE6475 and GSE53795 datasets were collected from GEO database, and 18 acne lesions tissues and 18 normal skin tissues were compared. David database was used to analyze the gene ontology (GO) and the key pathway (Kyoto Encyclopedia of genes and genomes, KEGG) of the differential genes, to establish the protein interaction network of the differential genes, and to obtain the most relevant key genes and important clusters.Results:A total of 314 up-regulated genes and 62 down-regulated genes were filtered from those GEO profiles. KEGG pathway analysis showed that these differential genes were mainly enriched in Staphylococcus aureus infection, osteoclast differentiation, pentose and glucuronate interconversions. In addition, 379 nodes and ten key genes (CXCL8, PTPRC, IL1B, ITGB2, CXCR4, ICAM1, CCR5, SELL, C3AR1 and PLEK) were screened out by protein interaction network.Conclusions:The key genes and pathways identified in this study may be new targets for intervention in the development of acne.

Objective To investigate the role and mechanism of SR8278,a synthetic antagonist of nuclear receptor subfamily 1 group D member 1(NR1D1),in alleviating the structural and functional impairment of the extraorbital lacrimal glands induced by jet lag in mice.Methods Totally 36 healthy wild C57BL/6J mice aged 8-10 weeks were randomly divid-ed into 3 groups(normal group,jet-lag group,and jet-lag+SR8278 group)after adapting to a circadian rhythm chamber under the 12 h light/12 h dark(12 h/12 h LD)cycle for 2 weeks,with 12 mice in each group.Mice in the normal group were fed in a circadian rhythm chamber in a 12 h LD cycle,mice in the jet-lag group were fed in a 12 h/12 h LD cycle with an 8-hour advanced LD schedule,and mice in the jet lag+SR8278 group were fed in a 12 h/12 h LD cycle with an 8-hour advanced LD schedule and received 25 mg·kg-1 SR8278.At the end of 5 days of intervention,locomotor activity,core body temperature and tear secretion of mice in each group were collected,and the weight of lacrimal gland tissues and size of lacrimal gland cells were measured.Immunohistochemical methods were used for histological evaluation of the extraor-bital lacrimal glands in mice.Lacrimal ribonucleic acid(RNA)was extracted for high-throughput RNA-sequencing analysis containing NR1D1,and the obtained transcriptomic data were used for KEGG and GO functional enrichment analysis.Re-sults Compared with the normal group,the jet-lag group had higher daytime activity,lower nighttime activity,higher daytime core body temperature,and lower nighttime core body temperature,with statistically significant differences(all P＜0.05).Compared with the jet-lag group,the jet-lag+SR8278 group had lower daytime activity,higher nighttime activi-ty,lower daytime core body temperature,and higher nighttime core body temperature,with statistically significant differ-ences(all P＜0.05).Compared with the normal group,the jet-lag group showed a decrease in lacrimal gland weight and tear secretion and an increase in size of lacrimal gland cells,with statistical significance(all P＜0.05);compared with the jet-lag group,the jet-lag+SR8278 group had an increase in lacrimal gland weight and tear secretion and a decrease in size of lacrimal gland cells,with statistical significance(all P＜0.05).Compared with the normal group,the jet-lag group showed a higher expression of NR1D1 in the lacrimal gland at night;compared with the jet-lag group,the jet-lag+SR8278 group showed a lower expression of NR1 D1 in the lacrimal gland at night(both P＜0.05).Bioinformatics analysis showed 947 significantly different genes in the jet-lag group and the jet-lag+SR8278 group,of which 43 are significantly upregulated genes,and 904 are significantly downregulated genes.The Notch signaling pathway has the most significant difference.Conclusion SR8278 effectively enhances the tear secretion function of jet-lagged mice by targeting NR1D1 inhibition.This process may be completed through the Notch signaling pathway.