Objective: To explore the longitudinal association between organophosphate esters (OPEs) exposure and blood pressure in children, so as to provide a reference for identifying the effects of OPEs exposure on child health. Methods: A total of 404 children from the Beijing Child Growth and Health Cohort (PROC) were enrolled using a case cohort study design, baseline physical examination, urine collection, questionnaires survey were administered in 2018 and follow up surveys in 2019-2020 and 2023. Participants were divided into case group ( n =140) and control group ( n =264) according to the observation of new onset of high blood pressure during the follow up period. High performance liquid chromatography tandem mass spectrometry was used to detect diethyl phosphate (DEP)，bis (2-chloroethyl) phosphate (BCEP)，bis (1-chloro-2-propyl) phosphate, (BCIPP), diphenyl phosphate(DPHP), dibutyl phosphate (DnBP), bis (1,3-dichloro-2-propyl) phosphate(BDCIPP), bis(2-butoxyethyl) phosphate(BBOEP), bis (2-butoxyethyl) 2-hydroxyethyl phosphate (BBOEHEP), 4-hydroxyphenyl diphenyl phosphate (4-OH-TPHP). Generalized linear mixed models and Quantile g computation models were developed to analyze the longitudinal associations between OPEs individual/mixed exposure and blood pressure in children. Results: The detection range of 9 OPEs metabolites,including DEP, BCEP, BCIPP, DPHP, DnBP, BDCIPP, BBOEP, BBOEHEP and 4-OH-TPHP at three time points (baseline, first follow up and second follow up) were 27.7%-92.1%, 24.0%-99.3% and 39.2%-90.9% respectively. Without adjustment for covariates such as gender, age, body mass index, Tanner stage, parental education, and monthly household income, and family history of hypertension, the increase of BDCIPP concentration and mixed exposure of OPEs may reduce children s systolic blood pressure( β= -0.85，-2.40，95%CI=-1.69--0.01，-3.30--1.50，P <0.05). After adjusting for the covariates, the longitudinal association of individual OPEs or mixed exposure with pediatric BP was not statistically significant ( P >0.05). Conclusion Children are commonly exposed to OPEs, and although no significant longitudinal associations are observed between exposure to OPEs and blood pressure among school aged children in Beijing, it is recommended that child exposure should be minimized whenever possible.

Objective: To explore sex difference in the cardiovascular health (CVH) status of 6-8 year old children in Beijing, so as to inform the early intervention of CVH related lifestyles. Methods: Based on the Beijing Children s Growth and Health Cohort (PROC), baseline physical examination, sequential questionnaire survey, and laboratory tests were conducted among 1 914 grade 1 students. Children s CVH and its subscales (health behaviors and health factors) scores were calculated according to the Life s Essential 8 (LE 8) index and categorized into high, moderate, and low CVH. CVH scores were reported as medians and interquartile ranges; sex differences were compared using the Chi square test and Wilcoxon test. Results: Among the 1 914 participants, the percentages of high, moderate, and low CVH were 35.7%, 63.5%, and 0.8%, respectively, and the percentages of high, moderate, and low health behavior scores were 25.9%, 67.5%, and 6.6%, respectively, with no statistically significant differences between sex ( χ 2=2.30, 0.07, P >0.05). The rates of high, moderate, and low health factor scores for boys and girls were 61.1%, 36.0%, 2.9% and 71.1%, 28.4%, 0.5%, respectively, with a statistically significant sex difference ( χ 2=31.88, P < 0.01). The overall CVH score was 76.0(70.0, 83.0), 76.0(69.0, 82.0) for boys, and 77.0(71.0, 83.0) for girls. Among the health behavior metrics, sleep scores were the best and physical activity scores were the worst[100.0(90.0,100.0), 40.0(20.0, 80.0 )]; among the health factor metrics, blood glucose scores were the best and lipid scores were the worst[100.0(100.0,100.0), 60.0(40.0,100.0)]. In respect to health factors, there were significant gender differences in body mass index, blood lipids, blood sugar, and blood pressure scores ( Z =-6.92, 3.01, -6.60, -2.30, <0.05), but there were no significant gender differences in diet, physical activity, nicotine exposure, or sleep scores with regards to health behaviors ( Z =0.99, 0.88, -0.13, 0.36, P > 0.05 ). Compared to boys, girls in the low and moderate CVH groups had high health factor scores despite low health behavior scores. Conclusion Most 6 to 8-year-old children in Beijing were found to have relatively good CVH, and optimization of children s CVH status can be achieved by promoting healthier lifestyles and monitoring health factors, especially among boys.

Objective:To assess the association between short-term ambient air pollution exposure and arterial stiffness and whether obesity modifies these associations.Methods:A cross-sectional study was conducted based on Fangshan family cohort in Beijing. The 24 hours average air pollutant levels on the day cohort participants took baseline survey were calculated as short-term air pollution. A generalized additive model (GAM) with Gaussian links was used to estimate changes in typical carotid artery intima-media thickness (CIMT), brachial-ankle pulse wave velocity (BAPWV), pulse pressure (PP) and ankle-branchial index (ABI) after short-term exposure to each air pollution (PM 2.5, PM 10, SO 2, NO 2, CO). The cross-product terms of each air pollution, body mass index (BMI), and waist-to-hip ratio were included in the GAM model to test the interaction. Further, they conducted a stratified analysis to test their effects on the relationship between short-term exposure to each air pollution and the arterial stiffness indicators. Results:A total of 4 211 individuals were included in the analysis. Individuals' age was (58.9±8.7) years, of which 2 268 (53.9%) were female. Several covariates, including sociodemographic factors, lifestyle behaviors, and history of drugs, were included in the analysis. The results of the GAM analysis showed that an increase in PM 2.5 ( β=2.912×10 -4, 95% CI: 1.424×10 -4-4.400×10 -4, P<0.001), CO ( β=0.027, 95% CI: 0.011-0.043, P<0.001), SO 2 ( β=2.070×10 -3, 95% CI: 7.060×10 -4-3.430×10 -3, P=0.003), and NO 2 ( β=3.650×10 -4, 95% CI: 2.340×10 -5-7.060×10 -4, P=0.036) were associated with an increase in CIMT, while an increase in PM 10 ( β=0.018, 95% CI: 0.002-0.033, P=0.028) was associated with an increase in PP in the study population. Besides, the waist-to-hip ratio had an effect-modification on the correlation of short-term exposure of PM 2.5 (interaction P=0.015), NO 2 (interaction P=0.008), and CO (interaction P=0.044) with CIMT, and the correlation between short-term exposure of PM 2.5 (interaction P=0.002), NO 2 (interaction P=0.010), CO (interaction P=0.029), PM 10 (interaction P<0.001) with PP. The significant association between CIMT, PP, and air pollution concentrations was more visible in people with lower waist-to-hip ratios. Conclusions:Short-term ambient air pollution exposure was associated with arterial stiffness indicators, and there was an effect modification of waist-to-hip ratio on these associations, and lower waist-to-hip ratios may enhance the association between air pollution exposure and indicators.

Objective:To explore the effects of short-term particulate matter(PM)exposure and the melatonin receptor 1B(MTNR1B)gene on triglyceride-glucose(TyG)index utilizing data from Fang-shan Family-based Ischemic Stroke Study in China(FISSIC).Methods:Probands and their relatives from 9 rural areas in Fangshan District,Beijing,were included in the study.PM data were obtained from fixed monitoring stations of the National Air Pollution Monitoring System.TyG index was calculated by fasting triglyceride and glucose concentrations.The associations of short-term PM exposure and rs10830963 polymorphism of the MTNR1B gene with the TyG index were assessed using mixed linear models,in which covariates such as age,sex,and lifestyles were adjusted for.Gene-environment inter-action analysis was furtherly performed using the maximum likelihood methods to explore the potential effect modifier role of rs10830963 polymorphism in the association of PM with TyG index.Results:A total of 4 395 participants from 2 084 families were included in the study,and the mean age of the study participants was(58.98±8.68)years,with 53.90％females.The results of association analyses showed that for every 10 μg/m3 increase in PM2.5 concentration,TyG index increased by 0.017(95％CI:0.007-0.027),while for per 10 μg/m3 increment in PM1o,TyG index increased by 0.010(95％CI:0.003-0.017).And the associations all had lagged effects.In addition,there was a positive association between the rs10830963 polymorphism and the TyG index.For per increase in risk allele G,TyG index was elevated by 0.040(95％CI:0.004-0.076).The TyG index was 0.079(95％CI:0.005-0.152)higher in carriers of the GG genotype compared with carriers of the CC genotype.The inter-action of rs10830963 polymorphism with PM exposure had not been found to be statistically significant in the present study.Conclusion:Short-term exposure to PM2.5 and PM10 were associated with higher TyG index.The G allele of rs10830963 polymorphism in the MTNR1B gene was associated with the elevated TyG index.

Objective:To delve into the intricate relationship between common genetic variations across the entire genome and the risk of non-syndromic cleft lip with or without cleft palate(NSCL/P).Methods:Utilizing summary statistics data from genome-wide association studies(GW AS),a thorough investigation to evaluate the impact of common variations on the genome were undertook.This involved assessing single nucleotide polymorphism(SNP)heritability across the entire genome,as well as within specific genomic regions.To ensure the robustness of our analysis,stringent quality control measures were applied to the GWAS summary statistics data.Criteria for inclusion encompassed the absence of missing values,a minor allele frequency≥1％,P-values falling within the range of 0 to 1,and clear SNP strand orientation.SNP meeting these stringent criteria were then meticulously included in our analy-sis.The SNP heritability of NSCL/P was calculated using linkage disequilibrium score regression.Addi-tionally,hierarchical linkage disequilibrium score regression to partition SNP heritability within coding re-gions,promoters,introns,enhancers,and super enhancers were employed,and the enrichment levels within different genomic regions using LDSC(v1.0.1)software were further elucidated.Results:Our study drew upon GWAS summary statistics data obtained from 806 NSCL/P trios,comprising a total of 2 418 individuals from the Chinese population.Following rigorous quality control procedures,490 593 out of 492 993 SNP were deemed suitable for inclusion in SNP heritability calculations.The observed SNP heritability of NSCL/P was 0.55(95％CI:0.28-0.82).Adjusting for the elevated disease pre-valence within our sample,the SNP heritability scaled down to 0.37(95％CI:0.19-0.55)based on the prevalence observed in the general Chinese population.Notably,our enrichment analysis unveiled significant enrichment of SNP heritability within enhancer regions(15.70,P=0.04)and super enhan-cer regions(3.18,P=0.03).Conclusion:Our study sheds light on the intricate interplay between common genetic variations and the risk of NSCL/P in the Chinese population.By elucidating the SNP heritability landscape across different genomic regions,we contribute valuable insights into the genetic basis of NSCL/P.The significant enrichment of SNP heritability within enhancer and super enhancer re-gions underscores the potential role of these regulatory elements in shaping the genetic susceptibility to NSCL/P.This paves the way for further research aimed at uncovering novel genetic pathogenic factors un-derlying NSCL/P pathogenesis.

Successful treatment of endodontic and periapical diseases requires the elimination of bacteria and micro-bial biofilms from root canals.Currently,the most preferred irrigation method involves the delivery of sodium hypochlo-rite via the combination of a syringe and ultrasonic activation.Calcium hydroxide is the main choice for intracanal medi-cament between endodontic appointments and treatment.However,conventional chemical disinfection of root canals is controversial due to drug permeability and drug resistance.New small biomolecule formulations with high penetrability and bioremediatory capacity,including antimicrobial peptides such as M33D and LL-37,antisense RNA ASwalR/ASvicR and nanoparticles such as silver nanoparticles,mesoporous calcium-silicate nanoparticles and chitosan nanoparticles,have effective antibacterial and antibiofilm properties for use in root canal systems and dentinal tubules,thereby promot-ing the healing of apical lesions.However,the in vivo drug stability,biosafety,and clinical efficacy of small biomolecule formulations need further investigation.Future research will still focus on the improvement and combination of tradition-al drugs,as new small molecule formulations and ideal disinfectant drugs need to be developed.In the present paper,we reviewed the development of new antibacterial agents and application of small biomolecule formulations for chemical disinfection of infected root canals.

Heart failure is the leading cause of death worldwide. Compound Danshen Dripping Pill (CDDP) or CDDP combined with simvastatin has been widely used to treat patients with myocardial infarction and other cardiovascular diseases in China. However, the effect of CDDP on hypercholesterolemia/atherosclerosis-induced heart failure is unknown. We constructed a new model of heart failure induced by hypercholesterolemia/atherosclerosis in apolipoprotein E (ApoE) and LDL receptor (LDLR) dual deficient (ApoE^-/-LDLR^-/-) mice and investigated the effect of CDDP or CDDP plus a low dose of simvastatin on the heart failure. CDDP or CDDP plus a low dose of simvastatin inhibited heart injury by multiple actions including anti-myocardial dysfunction and anti-fibrosis. Mechanistically, both Wnt and lysine-specific demethylase 4A (KDM4A) pathways were significantly activated in mice with heart injury. Conversely, CDDP or CDDP plus a low dose of simvastatin inhibited Wnt pathway by markedly up-regulating expression of Wnt inhibitors. While the anti-inflammation and anti-oxidative stress by CDDP were achieved by inhibiting KDM4A expression and activity. In addition, CDDP attenuated simvastatin-induced myolysis in skeletal muscle. Taken together, our study suggests that CDDP or CDDP plus a low dose of simvastatin can be an effective therapy to reduce hypercholesterolemia/atherosclerosis-induced heart failure.

Objective: This study aims to investigate the willingness and influencing factors of COVID-19 vaccination among Chinese middle school students, and to provide a reference for promoting the implementation of COVID-19 vaccination among middle school students. Methods: An online survey was conducted among middle school students in Beijing, Anqing of Anhui Province, Xi an of Shaanxi Province and Shenzhen of Guangdong Province, and 9 153 participants were enrolled in the present study. Single factor analysis and multinomial Logistic regression was used to determine the related factors of COVID-19 vaccination willingness. Results: The prevalence of vaccine acceptance, vaccine hesitancy and vaccine refusal among middle school students were 60.05%, 31.59% and 8.36%, respectively. The results of Chi square analysis showed there were significant difference of COVID-19 vaccination willingness among sex, school residence, grade, region, vaccination willingness of surrounding classmates, vaccination willingness of others, fear of SARS-CoV-2 and risk of SARS-CoV-2 infection( χ 2=8.43-1 059.43, P <0.05). Multinomial Logistic regression analysis presented that, compared to "vaccine acceptance" group, those girls, non resident in school, living in Beijing or Anqing, disagree or uncertain with influenced by peers, disagree or uncertain with influenced by others, uncertain with fear of SARS-CoV-2, disagree or uncertain with having risk of SARS-CoV-2 infection were more likely to show vaccine hesitancy( OR =1.22,1.21,1.49,1.69,1.75,2.54,1.41,2.32,3.32,1.99,2.38, P <0.05). And those non boarding in school, living in Beijing or Xi an, disagree or uncertainty influenced by peers, disagree or uncertainty influenced by others, disagree with fear of SARS- CoV- 2, disagree or uncertainty in having risk of SARS-CoV-2 infection were more likely to show vaccine refusal ( OR =1.27, 2.29 ,1.46,3.88,2.37,2.31,1.47,2.14,4.24,1.47, P <0.05). Conclusion The willingness of COVID-19 vaccination among middle school students in four cities is low, and targeted interventions should be advocated to form herd immunity.

Objective ToexploretheCTcharacteristicsofinvasivepulmonaryadenocarcinomapresentingaspuregroundglass nodule(pGGN)withthin-sliceCT,andtodifferentiateinfiltratingadenocarcinoma(IA)fromnon-IA.Methods 271patientswith pGGNconfirmedbysurgicalpathologywereenrolledinthisstudyforretrospectiveanalysis.Patientsweredividedinto4groups:18 atypicaladenomatoushyperplasias(AAH),114adenocarcinomasinsitu(AIS),82minimallyinvasiveadenocarcinomas(MIA)and 57IA.Allthepatientsunderwentthin-sliceCTscansin1weekbeforesurgery.ThemaximumdiameterandaverageCTvaluewere measured,andtheimagingcharacteristicsofallpGGN,includingpleuralinelentationandvacuolesignwererecorded.Results The maximumdiameter,averageCTvalue,age,vacuolesignandsmokinghistory weresignificantlydifferent (P<0.05)betweenIA groupandnon-IAgroup.Nosignificantstatisticaldifferenceswereobservedingenderandpleuralindentation.Thediagnosticefficacy ofthemaximumdiameterandaverageCTvalueweregoodandtheROCcurveswere0.876and0.802respectively.Conclusion Itis helpfultodifferentiateIAgroupfromnon-IAgroupusingthemaximumdiameter,theaverageCTvalue,age,vacuolesignandsmoking history.ThemaximumdiameterandaverageCTvalueofIAgrouparesignificantlyhigherthannon-IAgroup.

Objective To investigate G protein-coupled estrogen receptor(GPER)mediated neuroprotective effect and mechanism in an ischemic stroke model. Methods Bilateral ovariectomy (OVX)was used to establish a castrated model of adult SPF grade female SD rats. Enzyme-linked immunosorbent assay was used to detect serum estrogen level at 4 weeks after procedure.Middle cerebral artery occlusion(MCAO)was use to prepare a stroke model.The rats were randomly divided into sham operation(n=6),MCAO(n=7),MCAO+estrogen(MCAO+E2,n=8),MCAO+agonist(MCAO+G1,n=8)and MCAO +antagonist G15(MCAO +G15,n =7)groups. The neurological severity score (NSS),2,3,5-triphenyltetrazolium chloride(TTC)staining were used to measure the volume of cerebral infarction in order to assess the effects of different interventions.Western blot was used to detect the protein expression of hypoxia inducible factor-1α(HIF-1α),c-Jun N-terminal kinase(JNK),and Caspase-3 in the ischemic penumbra. Results (1)Estrogen level:after OVX,The level of serum estrogen in rats was significantly lower than that before castration(20 ± 9 ng/L vs. 73 ± 21 ng/L,P <0. 01).(2)NSS score:the NSS score of MCAO in each group was significant higher than that in the sham operation group (P<0.01);The NSS score of the MCAO+G1 group was significantly lower than that of the MCAO group and the MCAO+G15 group(6.0 ±1.8 vs.11.9 ±2.0 and 10.0 ±2.1).The difference was statistically significant (all P<0.05).(3)Cerebral infarct volume:there was significant difference in infarcted volume between the sham operation group and all other groups(all P<0.01);Compared with the MCAO group and the MCAO+G15 group,the infarct volume of the MCAO+E2 group and MCAO+G1 group was significantly reduced(19.8 ± 4.0%,14.0 ± 2.9%)vs.29.7 ± 5.8% and 27.6 ± 3.6%).The difference was statistically significant (all P<0.05).(4)Results of Western blot:the relative optical density values of HIF-1α,JNK,and Caspase-3 of the MCAO group were higher than those of the MCAO + G1 group(all P <0.01). Conclusions GPER mediates the neuroprotective effect of estrogen in the ischemic stroke model.This protective effect is associated with the regulation of the expression levels of HIF-1α,JNK,and Caspase-3.