BACKGROUND:The extracellular-regulated protein kinase 5(ERK5)signaling protein is essential for the survival of organisms,and resveratrol can promote osteoblast proliferation through various pathways.However,whether resveratrol can regulate osteoblast function through the ERK5 signaling protein needs further verification. OBJECTIVE:To explore the regulatory effect of ERK5 on the proliferation of MC3T3-E1 cells and related secreted proteins,and to further verify whether resveratrol can complete the above process by activating ERK5. METHODS:Mouse MC3T3-E1 preosteoblasts were treated with complete culture medium,XMD8-92(an ERK5 inhibitor),epidermal growth factor(an ERK5 activator),resveratrol alone,XMD8-92+EGF,and resveratrol+XMD8-92,respectively.Western blot assay was used to detect the expression of ERK5 and p-ERK5 proteins,proliferation-related proteins Cyclin D1,CDK4 and PCNA,and osteoblast-secreted proteins osteoprotegerin and receptor activator of nuclear factor-κB ligand in MC3T3-E1 cells of each group.The fluorescence intensity of ERK5,osteoprotegerin and receptor activator of nuclear factor-κB ligand in each group was detected by cell immunofluorescence staining,and cell proliferation was detected by EdU staining,respectively.The appropriate concentration and time of resveratrol intervention in MC3T3-E1 cells were determined by cell morphology observation and cell counting kit-8 assay. RESULTS AND CONCLUSION:The activation of ERK5 signaling protein could effectively promote the proliferation of MC3T3-E1 cells,up-regulate the osteoprotegerin/receptor activator of nuclear factor-κB ligand ratio.The appropriate concentration and time for resveratrol intervention in MC3T3-E1 cells was 5 μmol/L and 24 hours,respectively.Resveratrol could activate ERK5 signaling protein,thereby promoting osteoblast proliferation and up-regulating the osteoprotegerin/RANKL ratio.All these results indicate that resveratrol can promote the proliferation of MC3T3-E1 cells and up-regulate the osteoprotegerin/RANKL ratio by activating the ERK5 signaling protein.

Objective: To study the correlation between short sleep duration and screening myopia among primary and middle school students in Beijing, so as to provide a scientific basis for the comprehensive prevention and control of myopia among students. Methods: Using a stratified cluster random sampling, 25 593 primary and middle school students from 16 districts of Beijing were selected from September to November 2023. The National Common Diseases and Health Influencing Factors Monitoring Survey Questionnaire was used to conduct a questionnaire survey, and visual acuity was tested according to the Specification for the Screening of Refractive Error in Primary and Middle School Students. The reporting rates of short sleep duration and detection rates of screening myopia among primary and middle school students were compared using the Chi square test. Binary Logistic regression was used to analyze the correlation between short sleep duration and screening myopia. Results: About 68.63% of students reported short sleep duration. There was a statistically significant difference in the reporting rate of short sleep duration among students in different school stages ( χ 2=981.18, P <0.01), with the lowest reporting rate of vocational high school students (47.07%) and the highest reporting rate of ordinary high school students (76.17%). The detection rates of screening myopia among primary school students ( 57.09% ) and middle school students (76.53%) who reported short sleep duration were higher than those who reported enough sleep duration (52.65%, 71.94%), with satistically significant differences ( χ 2=14.83, 17.96, P <0.01). The results of binary Logistic regression analysis showed that primary and middle school students with short sleep duration had a higher risk of developing screening myopia, compared to students with enough sleep duration ( OR =1.25); after adjusting for confounding factors such as educational stage, gender, region, boarding situation, primary and secondary school students with short sleep duration still had a higher risk of screening myopia ( OR =1.26) ( P <0.01). The analysis results stratified by educational stage showed that primary school students from grades 4-6 and middle school students with short sleep duration had a higher risk of screening myopia ( OR=1.18, 1.20, P <0.01). Conclusions Primary and secondary school students in Beijing with short sleep duration sleep have a higher risk of developing screening myopia. Families, schools, and society should ensure enough sleep duration to reduce the occurrence of myopia among students.

Objective: To analyze the incidence of statutory and keymonitored infectious diseases among school students in Beijing from 2016 to 2020, so as to provide a reference for developing the prevention and control of infectious diseases in schools. Methods: A descriptive statistical analysis was conducted on student cases aged 6-22 years in Beijing from 2016 to 2020 selected from the China Disease Surveillance Information Reporting Management System. Rate comparisons were performed using the 2 test and trend 2 test. Results: From 2016 to 2020, the overall incidence of statutory and keymonitored infectious diseases among students in Beijing showed an upward trend (χ2trend=582.42), the incidence rates of Category B and other infectious diseases exhibited a downward trend (χ2trend=82.71, 18.34), while Category C infectious diseases demonstrated a significant upward trend (χ2trend=911.75) (P<0.01). Among Category B infectious diseases, scarlet fever, bacillary dysentery, tuberculosis, and HIV/AIDS were predominant, with annual average incidence rates of 61.33/100 000, 35.38/100 000, 13.88/100 000, and 3.78/100 000, respectively. Except for HIV/AIDS, the reported incidence rates of other infectious diseases showed a declining trend. Among Category C infectious diseases, influenza, other infectious diarrhea, hand-foot-mouth disease, and mumps were predominant, with annual average incidence rates of 956.13/100 000, 114.39/100 000, 111.37/100 000, and 28.24/100 000, respectively. Influenza showed a significant upward trend (χ2trend=1 508.30), while the other infectious diarrhea, hand-foot-mouth disease, and mumps exhibited a downward trend (χ2trend=13.84, 25.78, 6.13) (P<0.05). Among other infectious diseases, varicella was predominant (χ2trend=17.47, P<0.05). Scarlet fever, influenza, hand-foot-mouth disease, and mumps had higher incidence rates among primary and middle school students; other infectious diarrhea and varicella were more prevalent among high school students; tuberculosis and bacillary dysentery were more common among high school and college students; and HIV/AIDS had higher incidence rates among college and high school students. Conclusion From 2016 to 2020, the incidence of Category B infectious diseases among students in Beijing showed a declining trend, while influenza, a Category C infectious disease, exhibited a significant upward trend.

Objective: To explore the association between CDKAL1 rs35261542, FAIM2 rs 3205718, and VGLL4 rs 2574704 polymorphisms with childhood obesity and related metabolic phenotypes to provide evidence for personalized prevention and management strategies. Methods: Based on the 2023 Long term Nutritional Health Effects of Early Childhood Nutrition Package Intervention project, the study enrolled 1 078 children aged 5-7 years from four counties in Henan (Songxian and Ruyang countries) and Guizhou (Guiding and Fuquan countries) provinces. Using BMI Z scores, 87 overweight and obese(OVOB) children were selected and matched by sex, age, and BMI Z score with 117 normal weight controls. Participants were further stratified into four metabolic phenotype groups: metabolically healthy normal weight (MHNW, n =51), metabolically unhealthy normal weight (MUNW, n =66), metabolically healthy obesity (MHO, n =31) and metabolically unhealthy obesity (MUO, n =56) based on four conventional cardiometabolic risk factor (CR) criteria. Data were collected through questionnaires, anthropometric measurements, serum biochemical tests, and KASP genotyping. The distribution of three genetic polymorphisms ( CDKAL1 rs35261542, FAIM2 rs3205718, VGLL4 rs 2574704) across metabolic subgroups was analyzed. Multivariate Logistic regression models assessed associations between these polymorphisms and obesity/metabolic phenotypes. Results: Multivariate Logistic regression analysis showed that Homozygous mutant AA genotype of CDKAL1 rs 35261542 was positively associated with OVOB( OR =3.63), MHO ( OR =11.04), MUO ( OR = 4.88 ) ( P <0.05). Homozygous TT genotype of FAIM2 rs 3205718 increased OVOB risk ( OR =4.44, P <0.05) but showed no association with metabolic phenotypes ( P >0.05). Homozygous mutant TT of VGLL4 rs 2574704 reduced the risks of MHO and MUO ( OR = 0.30, 0.24， P <0.05). Cumulative genetic effects analysis demonstrated carriers of 1 or 2 risk genotypes of rs 35261542 and rs 3205718 had progressively higher OVOB risk ( OR =2.53, 20.79), and the combination of rs 35261542 and rs 2574704 increased risks for both MHO ( OR =8.50) and MUO ( OR =5.00) ( P <0.05). Conclusions The AA genotype of rs 35261542 ( CDKAL1 ) positively correlates with childhood obesity and metabolic abnormalities. The TT genotype of rs 3205718 ( FAIM 2) increases obesity risk but not metabolic phenotypes. The TT genotype of rs 2574704 ( VGLL 4) shows protective effects against metabolic dysfunction. Risk genotypes exhibit dosedependent cumulative effects on obesity and metabolic outcomes.

Periodontal disease is a risk factor for many systemic diseases such as Alzheimer's disease and adverse pregnancy outcomes. Cleft palate (CP), the most common congenital craniofacial defect, has a multifaceted etiology influenced by complex genetic and environmental risk factors such as maternal bacterial or virus infection. A prior case-control study revealed a surprisingly strong association between maternal periodontal disease and CP in offspring. However, the precise relationship remains unclear. In this study, the relationship between maternal oral pathogen and CP in offspring was studied by sonicated P. gingivalis injected intravenously and orally into pregnant mice. We investigated an obvious increasing CP (12.5%) in sonicated P. gingivalis group which had inhibited osteogenesis in mesenchyme and blocked efferocytosis in epithelium. Then glycolysis and H4K12 lactylation (H4K12la) were detected to elevate in both mouse embryonic palatal mesenchyme (MEPM) cells and macrophages under P. gingivalis exposure which further promoted the transcription of metallopeptidase domain17 (ADAM17), subsequently mediated the shedding of transforming growth factor-beta receptor 1 (TGFBR1) in MEPM cells and mer tyrosine kinase (MerTK) in macrophages and resulted in the suppression of efferocytosis and osteogenesis in palate, eventually caused abnormalities in palate fusion and ossification. The abnormal efferocytosis also led to a predominance of M1 macrophages, which indirectly inhibited palatal osteogenesis via extracellular vesicles. Furthermore, pharmacological ADAM17 inhibition could ameliorate the abnormality of P. gingivalis-induced abnormal palate development. Therefore, our study extends the knowledge of how maternal oral pathogen affects fetal palate development and provides a novel perspective to understand the pathogenesis of CP.
Animals ; Female ; Porphyromonas gingivalis ; Pregnancy ; Mice ; Cleft Palate/etiology* ; Glycolysis

Objective: To analyze high myopia and dioptre changes in middle school students in Beijing from 2019 to 2022, so as to provide a basis for formulating preventive and control measures. Methods: Using stratified cluster random sampling, 16 districts of Beijing were divided into four groups, each of which was respectively composed of 83, 83, 84, and 84 middle schools, in order to examine non cycloplegic auto refraction among the senior grades 1 to 3 students from September to October in each year (from 2019 to 2022). Finally, the dataset results of each of the four groups (21 589, 21 161, 21 561, 21 123) were compared by the Chi square test and trend Chi square test. Trend changes were evaluated by annual percentage change (APC). Results: The rates of high myopia were higher in female students than in males from 2019 to 2022 (15.60%,14.59%; 15.33%, 14.44%; 14.65 %, 14.17%; 14.63%,13.84%), and the difference in 2019 was statistically significant ( χ 2=4.93, P <0.05). The rates of high myopia in middle school students in urban areas were significantly higher than those in rural areas(16.45%, 13.78%; 16.81 %, 13.00%; 15.84%, 13.06%; 15.85%, 12.72%), and the differences were statistically significant ( χ 2=30.18, 60.43, 33.92 , 42.23, P <0.05). With the increase of grade, the rates of high myopia increased ( χ 2 trend =674.56, 608.38, 655.21, 676.89, P <0.05), with junior grade 3 students being the most robust. The rate of high myopia in middle school students from 2019 to 2022 decreased from 15.09 to 14.22%, with an average annual rate of 2.08% ( APC=-2.08, t=-7.99, P ＜0.05). The refractive error of high myopia middle school students in 2019 and 2022 were -7.44(-10.25, -6.00) and -7.38(-10.00, -6.00)D, respectively, with no statistically significant difference ( H=4.30, P >0.05). Conclusions The rate of high myopia in middle school students in Beijing shows a decreasing trend, but it remains at a high level. It is necessary to classify the prevention and control strategy, and standardize the measures in order to manage early onset, high incidence rates, and severe myopia.

Objective: To explore the association between parental myopia and extracurricular activities before school age with myopia among lower grade students, so as to provide evidence for myopia prevention on low grade students. Methods: From November 2020 to June 2022, a total of 8 368 students of grade 1-3 were selected from Beijing, Liaoning, Zhejiang, Henan, Chongqing, Shaanxi Province by the stratified cluster random sampling and probability sampling methods, and were administered with a questionnaire survey and eye examinations. Multivariate Logistic regression was used to analyze the association between parental myopia and extracurricular activities before school age with myopia among lower grade students. Results: The prevalence of myopia in grade 1-3 was 23.7% in 6 provinces in China. Students who in central area, grade 3, boarding at school, doing homework/reading/writing time ≥1 h/d after school, extracurricular activities ≥1 h in the past week, extracurricular activities before school age, parental myopia, poor reading and writing posture, sleeping time <10 h/d, less exercise time because of homework or extracurricular activities, having annual vision examination had a higher myopia detection rate, with statistically significant differences ( χ 2=36.41, 487.72, 15.97, 21.35, 43.95, 15.33, 54.04, 6.67, 3.88, 20.02, 20.06, P <0.05). After adjusted for the confounding factors, there was a significant interaction between parental myopia and extracurricular activities before school age with myopia ( P interaction <0.01). After adjusting for confounding factors, Logistic regression analysis showed that those having extracurricular activities before school age had a higher risk of myopia ( OR=1.33, 95%CI =1.19-1.56), compared with those who did not. Compared with children without nearsighted parents, children with nearsighted parents had higher prevalence of myopia ( OR=1.64, 95%CI = 1.45- 1.84) ( P <0.05); and the values of indicators ( RERI, API, Index S ) for interaction between parental myopia and extracurricular activities before school age were 0.35, 0.27, 1.37, respectively. Conclusion Both parental myopia and extracurricular activities before school age are associated with myopia among lower grade students, with interactive effects.

Abstract Biomarkers could improve the understanding of the causes of obesity and its association with chronic diseases for people. The purpose of the review is to summarize recent advances in transcriptomic, proteomic, and metabolomic phenotypic biomarkers of obesity in order to deepen the understanding of the etiology of obesity and its metabolic consequences. In the precise prevention and control of childhood obesity, different groups of biomarkers can improve the accuracy of the word "obesity" and help early detection of specific biomarkers with risk characteristics, so as to realize the transformation of childhood obesity from a one size fits all prevention and control strategy to a personalized prevention and control plan during the development of obesity.

Abstract Childhood obesity is one of the major global public health challenges and has a profound impact on the physical and mental health of children and adolescents. The article summarizes the establishment of gut microbiota in early life and the influences of early nutritional status and feeding patterns, maternal and infant microbiota transmission, delivery methods and the use of antibiotics on gut microbiota and childhood obesity. The paper focuses on the possibility of using the structural characteristics of gut microbiota (gene richness and evenness, relative abundance ratio and key indicator bacteria) as potential interventional targets and predictors of intervention effects in childhood obesity, and introduces the application of probiotics and other biological agents, as well as fecal microbiota transfer for the childhood obesity intervention, and briefly describes the latest progress in the mechanism of gut microbiota and childhood obesity, so as to provide the reference for the precise prevention and control of childhood obesity.

Background Pesticide exposure may impact the reproductive health of women undergoing assisted reproductive technology (ART). However, data on pesticide exposure levels in women undergoing ART in China are scarce, and current research on influencing factors is limited. Objective To evaluate the preconceptional pesticide exposure levels and identify potential determinants among women undergoing ART. Methods This study was designed as a cross-sectional survey and recruited 508 women undergoing ART from July 2017 to December 2018 at the fertility clinic of the International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. Gas chromatography/liquid chromatography-tandem mass spectrometry was used to determine the metabolite concentrations of organophosphate pesticides (OPs), pyrethroid pesticides (PYRs), and neonicotinoid pesticides (NEOs) in urine. The sum of molar concentrations of the three pesticide classes (∑₂OPs, ∑₂PYRs, and ∑₂NEOs) were calculated. A questionnaire was used to collect demographic characteristics, dietary habits, and behavioral information. Multiple linear regression was employed to analyze the associations of demographic characteristics, dietary habits, and behavioral variables with the concentrations of pesticide metabolites in urine among the participants. Results The median creatinine-adjusted concentrations of ∑₂OPs, ∑₂PYRs, and ∑₂NEOs in this study were 419.77, 2.95, and 20.36 nmol·g⁻¹, respectively. The multiple linear regression results showed that the urinary concentration of ∑₂OPs was 42.88% higher in the participants with daily vegetable intake than in those who consumed vegetables ≤3 d per week (P<0.05), and the urinary concentration of ∑₂PYRs was 37.24% higher in the participants with daily fruit intake than in those who consumed fruits ≤3 d per week (P<0.01). Similarly, the urinary concentrations of ∑₂NEOs were 24.51% and 29.30% higher in the participants who consumed fruits daily and 4-6 d per week, respectively, than in those who consumed fruits ≤3 d per week (P<0.05). Besides, we also found that the urinary concentration of ∑₂PYRs was negatively correlated with body mass index (BMI) in the participants (P<0.05). Furthermore, the urinary concentration of ∑₂NEOs was not only positively correlated with age (P<0.05), but also significantly associated with pet ownership and infertility causes among the participants. Specifically, the participants who continued to own pets after conception had a 30.11% higher urinary concentration of ∑₂NEOs than those who never owned pets (P<0.05), and the participants with infertility due to female factors had a 24.10% lower urinary concentration of ∑₂NEOs than those who received ART treatment for infertility caused by male factors (P<0.05). Conclusion The women undergoing ART in Shanghai are widely exposed to pesticides. Age, BMI, frequency of vegetable and fruit intake, pet ownership, and infertility causes may be related to the pesticide exposure levels in this population. However, more human data are needed to confirm these findings.