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INTRODUCTION: We investigated the impact of metabolic dysfunction-associated steatotic liver disease (MASLD) on cardiovascular structure development in children. METHODS: We followed 1,356 children with the mean age of 6.6 years for 4.5 years in Beijing, China. We assessed the association of MASLD with cardiovascular structure (carotid intima-media thickness and left ventricular mass) outcomes at baseline and follow-up. RESULTS: Over follow-up, 59 children had persistent MASLD, 109 had incident MASLD (progression), and 35 had normalization of liver health. Children with MASLD normalization showed a significantly lower mean development in carotid intima-media thickness (0.161 vs 0.188 mm) and left ventricular mass (4.5 vs 12.4 g) than children with persistent MASLD. DISCUSSION: The control of MASLD was associated with improved cardiovascular structure development.

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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.

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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.

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Background Life's Essential 8 (LE8) metrics for cardiovascular health (CVH) aid primordial prevention in US populations. Methods and Results We conducted a child cohort study (PROC [Beijing Child Growth and Health Cohort]) with baseline (2018-2019) and follow-up (2020-2021) assessments, enrolling disease-free 6- to 10-year-old children from 6 elementary schools in Beijing. We collected LE8-assessed components via questionnaire surveys and 3 cardiovascular structural parameters by 2-dimensional M-mode echocardiography: left ventricular mass (LVM), LVM index, and carotid intima-media thickness. Compared with 1914 participants (mean age, 6.6 years) at baseline, we saw lower mean CVH scores at follow-up (n=1789; 8.5 years). Among LE8 components, diet presented the lowest perfect-score prevalence (5.1%). Only 18.6% of participants had physical activity ≥420 min/wk, 55.9% had nicotine exposure, and 25.2% had abnormal sleep duration. Prevalence of overweight/obesity was 26.8% at baseline and 38.2% at follow-up. We noted optimal blood lipid scores in 30.7%, while 12.9% of children had abnormal fasting glucose. Normal BP was 71.6% at baseline and 60.3% at follow-up. LVM (g), LVM index (g/m2.7), and carotid intima-media thickness (mm) were significantly lower in children with high (56.8, 33.2, 0.35) or moderate CVH scores (60.6, 34.6, 0.36), compared with children with low CVH scores (67.9, 37.1, 0.37). Adjusting for age/sex, LVM (ß=11.8 [95% CI, 3.5-20.0]; P=0.005), LVM index (ß=4.4 [95% CI, 0.5-8.3]; P=0.027), and carotid intima-media thickness (ß=0.016 [95% CI, 0.002-0.030]; P=0.028) were higher in the low-CVH group. Conclusions CVH scores were suboptimal, declining with age. LE8 metrics indicated worse CVH in children with abnormal cardiovascular structural measurements, suggesting the validity of LE8 in assessing child CVH. Registration URL: https://www.chictr.org.cn/index.html; Unique identifier: ChiCTR2100044027.

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The "magic methyl effect" strategy was used to design a series of 5-alkyl-2-pyrazol-oxazolidin-4-one derivatives as novel hepatitis B virus (HBV) capsid assembly modulators. Most of these compounds exhibited potent HBV inhibitory activities with low cytotoxicities in HepG2.2.15 cells. The most promising compounds 9d and 10b had single-digit nanomolar IC50 values with a high selectivity index. Compared with the lead compound (3.0%), they caused 15% and 18% decreases in HBe antigen secretion at 1.0 µM, respectively. In addition, compounds 9d and 10b possessed good pharmacokinetic profiles with oral bioavailability values of 56.1% and 48.9%, respectively. These results indicated that the two compounds were potential therapeutic agents for HBV infection.

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BACKGROUND AND AIM: Conflicting results suggest a link between serum uric acid and diabetes and previous studies ignored the effect of continuous exposure of serum uric acid on diabetes risk. This study aims to characterize hyperuricemia trajectories in middle-aged adults and to examine its potential impact on diabetes risk, considering the role of obesity, dyslipidemia, and hypertension. METHODS AND RESULTS: The cohort included 9192 participants who were free of diabetes before 2013. The hyperuricemia trajectories during 2009-2013 were identified by latent class growth models. Incident diabetes during 2014-2018 was used as the outcome. Modified Poisson regression models were used to assess the association of trajectories with diabetes. Furthermore, marginal structural models were used to estimate the mediating effects of the relationship between hyperuricemia trajectories and diabetes. We identified three discrete hyperuricemia trajectories: high-increasing (n = 5794), moderate-stable (n = 2049), and low-stable (n = 1349). During 5 years of follow-up, we documented 379 incident diabetes cases. Compared with the low-stable pattern, the high-increasing pattern had a higher risk of developing diabetes (RR, 1.42; 95% CI: 1.09-1.84). In addition, the percentages of total effect between the high-increasing hyperuricemia pattern and diabetes mediated by obesity, dyslipidemia, and hypertension were 24.41%, 18.26%, and 6.29%. However, the moderate-stable pattern was not associated with an increased risk of diabetes. CONCLUSIONS: These results indicate that the high-increasing hyperuricemia trajectory is significantly associated with an increased risk of diabetes. Furthermore, obesity, dyslipidemia, and hypertension play mediating roles in the relationship between the high-increasing hyperuricemia pattern and increased diabetes risk.

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Background: Hypoxia-inducible factor 1-alpha (HIF-1α) stability and transcriptional action are reduced by the hypoxia-inducible factor 1-alpha subunit suppressor (HIF1AN). Its inappropriate expression is associated with the development of cancer and immune control. It is yet unknown how HIF1AN, clinical outcomes, and immune involvement in breast cancer (BC) are related. Methods: Using the GEPIA, UALCAN, TIMER, Kaplan-Meier plotter, and TISIDB datasets, a thorough analysis of HIF1AN differential expression, medical prognosis, and the relationship between HIF1AN and tumor-infiltrating immune cells in BC was conducted. Quantitative real-time PCR (qRT-PCR) analysis of BC cells were used for external validation. Results: The findings revealed that, as compared to standard specimens, BC cells had significantly lower levels of HIF1AN expression. Good overall survival (OS) for BC was associated with higher HIF1AN expression. Additionally, in BC, the expression of HIF1AN was closely associated with the chemokines and immune cell infiltration, including neutrophils, macrophages, T helper cells, B cells, Tregs, monocytes, dendritic cells, and NK cells. A high correlation between HIF1AN expression and several immunological indicators of T-cell exhaustion was particularly revealed by the bioinformatic study. Conclusions: HIF1AN is a predictive indicator for breast tumors, and it is useful for predicting survival rates.

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2-Oxazolidinone is well known as a pharmacophore for antibacterial agents represented by two marketed medicines, Linezolid and Tedizolid. On the other hand, there are growing reports on the various biological activities of 2-oxazolidinones beyond antibacterial activities. Therefore, in this review, we provide an overview of the progress of this untraditional area of 2-oxazolidinones in the past 10 years (2011-2021).

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Influenza vaccination rates among Chinese middle school students are low. This study aims to explore the influencing factors of vaccination among middle school students and promote vaccination. We conducted a mixed-methods study, integrating a questionnaire survey among 9145 middle school students in four cities in China and semi-structured interviews with 35 middle school students to understand their attitudes and perceptions toward vaccination based on the Health Belief Model. We found the overall vaccination rate was 38.2% (3493/9145), with students in Beijing, boarding at school, or senior high school showing higher values than their counterparts (p < 0.05). Multiple logistic regression results showed that non-boarding (OR = 0.46, 95%CI: 0.42−0.51) and perceived barriers (OR = 0.97, 95%CI: 0.96−0.98) were unfavorable factors for influenza vaccination, whereas perceived susceptibility (OR = 1.07, 95%CI: 1.05−1.08), perceived benefits (OR = 1.02, 95%CI: 1.01−1.04), cues to action (OR = 1.08, 95%CI: 1.05−1.11), and self-efficacy (OR = 1.04, 95%CI: 1.02−1.07) were facilitators. Qualitative results indicated that positive health beliefs, school, and the home environment contribute to vaccination. In conclusion, the influenza vaccination rate among middle school students remains low. The concerns about the safety and potential side effects of vaccines are the main barriers to vaccination, underscoring the need for strengthening communication, education, and information among students and their teachers/parents.

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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.

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PURPOSE: To assess the radiolucent lines (RLLs) around both tibial and femoral components in patients following lateral unicompartmental knee arthroplasty (UKA). METHODS: We performed a retrospective review of the records of a consecutive series of patients who had undergone lateral UKA. The RLLs were assessed with standard anteroposterior and lateral radiographs post-operatively. The patient-reported outcome measures included the Hospital for Special Surgery (HSS) score and Oxford knee score (OKS). The femoral component position (FCP) and femoral-tibial angle (FTA) were also recorded. RESULTS: A total of 198 UKAs that had appropriate radiographs and outcome scores were reviewed with a median follow-up of 33 (range, 12-71) months. The results suggested that 69 cases (34.8%) had RLLs on the standard radiographs. The incidence rates of femoral and tibial physiological RLLs were 11.6% (23/198) and 26% (52/198), respectively, of which 3% (6/198) concerned both components. All RLLs were considered "physiologic lines" that developed within one year after surgery. There were no significant differences among the types of RLLs in any of the outcome measures. No differences in FCP (P = .359) or FTA (P = .111) at the last follow-up were seen. CONCLUSIONS: It was found that one-third of UKAs had RLLs on radiographs following lateral UKA. All RLLs developed within one year after surgery. As a clinical consequence, the development of RLLs does not affect the short-term outcomes after lateral UKA.

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Increasing evidence indicates that altered expression of microRNAs (miRNAs) is associated with osteoarthritis (OA) progression. In our study, we demonstrated that miR-377-3p is underexpressed in OA-affected cartilage and IL-1ß-treated chondrocytes. Overexpression of miR-377-3p enhanced chondrocyte proliferation and restrained apoptosis and signs of cartilage matrix degradation and of an inflammatory response. Furthermore, ITGA6 was identified as a target gene of miR-377-3p. The latter was found to directly bind to the 3' untranslated region (3'UTR) of ITGA6 mRNA and downregulate ITGA6. In addition, ITGA6 expression was high in OA-affected tissues and negatively correlated with miR-77-3p expression. Overexpression of ITGA6 reversed the effects of miR-377-3p on IL-1ß-caused chondrocyte apoptosis, cartilage matrix degradation, and the inflammatory response. Moreover, bioinformatic analysis and a luciferase assay indicated that miR-377-3p expression is regulated by long noncoding RNA NEAT1, which binds to miR-377-3p and inactivates it. We showed that NEAT1 was highly expressed in OA-affected cartilage, negatively correlated with miR-377-3p levels, and positively correlated with ITGA6 levels. These findings provide information for the development of future treatments of OA, suggesting that miR-377-3p may be a therapeutic target in OA.

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MicroRNAs (miRNAs, miRs) are frequently dysregulated in osteoarthritis (OA), but the role of specific miRNAs in OA remains unclear. In this study, we found that miR-93-5p is underexpressed in human and rat OA-affected cartilage (compared with normal cartilage) as well as in IL-1ß-treated chondrocytes. Overexpression of miR-93-5p promoted chondrocyte viability, suppressed chondrocyte apoptosis, and maintained the balance between anabolic and catabolic factors of the extracellular matrix in vitro. Similarly, injection of a miR-93-5p-expressing lentivirus alleviated the destruction of articular cartilage in a rat model of OA (anterior cruciate ligament transection). Furthermore, TCF4 was identified as a direct target gene of miR-93-5p. miR-93-5p directly targeted the 3' untranslated region (3'-UTR) of TCF4 mRNA and repressed TCF4 expression. Overexpression of TCF4 attenuated the effects of miR-93-5p on chondrocyte apoptosis and functions. Finally, analyses of miR-93-5p and TCF4 in OA-affected cartilage tissues revealed that miR-93-5p expression inversely correlated with TCF4 expression. Altogether, these findings indicate that miR-93-5p slows OA progression partially by suppressing TCF4 expression, and this phenomenon may provide novel insights into the function of miRNA in OA.

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