Inactivated rotavirus vaccines (IRV) are an effective approach for providing protection against the virus. This double-blind, randomised, placebo-controlled, dose-escalation phase I trial evaluated the safety and immunogenicity of IRV in 288 healthy children aged 2–71 months without prior rotavirus vaccination or HIV infection. We stratified participants by age (7–71 months and 2–6 months) and schedule (2 or 3 doses), before randomising them 3:1 to receive one of three antigen doses (80, 160, or 320 ELISA Unit [EU]), or aluminium adjuvanted placebo. The primary endpoints included adverse reactions/events within 30 min post-dose, adverse reactions/events during days 0–7 and 8–28/30 post-dose, and serious adverse events (SAEs) 6 months after the full course. The secondary endpoints were neutralizing antibody (NTA) geometric mean titres (GMT) and seroconversion rates (≥4-fold rise) at day 28 post-final dose. IRV was well tolerated, with no vaccine-related SAEs in any of the cohorts; we observed clinically manageable transient mild-to-moderate fever in the high dose infant group. Dose-dependent increases in NTA and IgG antibody responses were observed across all cohorts. In the 3-dose infant group, the 320 EU dose yielded a GMT of 551.98 (95% CI 338.39 ~ 900.40) compared to 36.17 for placebo, and a seroconversion rate of 83.33% (vs. 10.00% for placebo); the 3-dose schedule outperformed the 2-dose regimen. Our findings confirm that IRV has a favourable safety and immunogenicity profile. This trial is registered with ClinicalTrials.gov (NCT04626856). This double-blind, randomized, placebo-controlled, dose escalation phase I trial evaluates the safety and immunogenicity of an inactivated rotavirus vaccine (IRV) in healthy young children and infants without prior rotavirus vaccination or HIV infection.

Benzene, toluene and xylenes (BTX) are common workplace volatile organic compounds, but evidence linking BTX exposure to biological aging is limited. We examined associations between urinary BTX metabolites and biological age acceleration, and explored biological plausibility using computational analyses (network toxicology and molecular docking). We enrolled 301 BTX-exposed workers and 741 unexposed controls (Henan, China, 2022-2023), and selected 301 matched controls using 1:1 propensity score matching. Biological age was estimated with the Klemera-Doubal method (KDM) from clinical biomarkers, and biological age acceleration (KDM-BA.Accel) was defined as biological age minus chronological age. Creatinine-adjusted urinary metabolites of benzene (S-phenylmercapturic acid [SPMA] and trans, trans-muconic acid [TTMA]), toluene (S-benzylmercapturic acid [SBMA]) and xylenes (2-methylhippuric acid [2MHA] and 3-/4-methylhippuric acids [3&4MHA]) were analyzed using generalized linear models, and mixture associations were assessed with Bayesian kernel machine regression (BKMR). In fully adjusted models, higher SPMA (β = 0.15, 95% CI: 0.07 to 0.24) and TTMA (β = 0.08, 95% CI: 0.01 to 0.14) were associated with higher KDM-BA.Accel, and xylene metabolites also showed positive associations. BKMR suggested a positive overall association of the BTX mixture with KDM-BA.Accel, with SPMA and TTMA contributing most prominently. Network toxicology prioritized eight hub genes (TP53, TNF, NFKB1, TGFB1, MAPK3, CTNNB1, FOS and JUN), and enrichment analyses were consistent with oxidative stress response, inflammatory signaling, and cell-cycle regulation pathways. Overall, higher urinary BTX metabolites, particularly benzene biomarkers SPMA and TTMA, was associated with higher biological age acceleration. Future work should include prospective cohorts with repeated biomonitoring and experimental studies to validate the associations and test the implicated mechanisms.

The survival impact of open esophagectomy (OE) versus thoracoscopic esophagectomy (TE) in patients with esophageal squamous cell carcinoma (ESCC) based on tumor location remains debated. This study employs energy balancing weights (EBW) to compare long-term survival between OE and TE across tumor locations. This ambispective cohort study analyzed 1778 patients with ESCC undergoing OE or TE at a tertiary hospital between January 2015 and December 2016. Primary endpoints were 5-year overall survival (OS) and disease-free survival (DFS); secondary endpoints included operative safety. EBW-adjusted Cox regression was used to compare long-term survival, with sensitivity analyses via inverse probability of treatment weighting and matching weight methods. The median survival times for upper, middle, and lower tumor locations were 60.06, 60.48, and 64.35 months, respectively. Compared with OE, the Cox regression analysis of TE showed that in the upper group, the HR was 0.45 (95

Background: Although integrase strand transfer inhibitor (INSTI)-based regimens are guideline-preferred, implementation in routine antiretroviral therapy (ART) programs remains gradual, and EFV-, NVP-, and PI-based regimens continue to contribute treatment exposure. Evidence is limited on long-term virological outcomes across ART anchor classes when regimen use changes over time and viral-load monitoring is clinically driven. Methods: We analyzed people living with HIV aged ≥15 years who initiated ART in Henan, China, during 2015-2024. ART class was categorized as EFV-, NVP-, INSTI-, or PI-based and assessed as initial and time-updated exposure. Outcomes were HIV RNA ≥200 copies/mL, HIV RNA ≥1000 copies/mL, and virological rebound after prior suppression. Cox models, IPTW MSMs, and joint IPTW-IIW MSMs were fitted, with joint IPTW-IIW MSMs prespecified as primary. Results: Among 44,746 participants, 8,399, 5,821, and 5,364 developed non-suppression, high-level viremia, and rebound, respectively. In primary joint MSMs, INSTI-based ART was associated with lower hazards across all outcomes in initial-regimen analyses (HRs, 0.56 [95% CI, 0.45-0.69], 0.42 [0.31-0.56], and 0.66 [0.50-0.87]) and time-updated analyses (0.54 [0.45-0.66], 0.40 [0.31-0.52], and 0.64 [0.51-0.81]). NVP-based ART was consistently associated with higher hazards. PI-based ART was also associated with higher hazards, particularly in time-updated analyses. Conclusions: During ART transition, INSTI-based regimens showed more favorable virological profiles, whereas NVP- and PI-based regimens were associated with higher virological risk. Accounting for both initial and changing regimen use, together with informative viral-load observation, improves real-world evaluation of regimen-class performance in care.

This study aimed to investigate the developmental trajectories and reciprocal relationship between social activities and cognition in middle-aged and elderly people with chronic diseases after controlling for the differences among individuals. The study used a representative sample of adults older than 45 years from the China Health and Retirement Longitudinal Study (CHARLS). The parallel latent growth curve models (LGCMs) were used to investigate the developmental trajectories and interactions between social activities and cognitive function from a dynamic perspective. The random-intercept cross-lagged panel models (RI-CLPMs) were conducted to examine the longitudinal bidirectional relationship between social activities and cognitive function. There were 4,174 over the age of 45 chronic disease patients with the mean age of 57.10 ± 7.57 years. The parallel LGCMs demonstrated that the rate of change in social activities positively predicted the rate of change in cognitive function (β (95

Disturbances in essential or toxic metal levels within the human body may disrupt thyroid homeostasis. However, existing studies on the associations between metal exposure and hypothyroidism have reported inconsistent findings, and the underlying mechanisms remain unclear. We aimed to evaluate the associations of multiple metal exposure with hypothyroidism and investigate the mechanisms using network toxicology analysis. Urinary concentrations of 13 metals were determined in 2916 participants using inductively coupled plasma mass spectrometry based on a cross-sectional study in Henan Province. The associations between metal exposure and hypothyroidism were assessed by generalized linear models, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) methods. Network toxicology analysis, including pathway enrichment and protein-protein interaction analyses, was conducted to identify potential hub genes and potential mechanistic pathways of metal-induced hypothyroidism. Urinary levels of Aluminum (Al) and Manganese (Mn) were significantly positively associated with hypothyroidism, while urinary levels of Selenium (Se) were negatively associated with hypothyroidism (all P < 0.05). In the WQS model, mixed metal exposure was positively associated with hypothyroidism (OR = 1.334, 95% CI: 1.086 ∼ 1.639), which was further supported by the BKMR model. Network toxicology analysis revealed Al, Mn, and Se-related hypothyroidism pathways, including lipid metabolism, PI3K-Akt signaling pathway, and apoptosis. Hub genes such as TNF, IL6, CASP3, and JUN were identified by Maximal clique centrality. Our findings suggest that exposure to Al, Mn, and Se was associated with hypothyroidism. The potential pathways involve lipid metabolism, the PI3K-Akt signaling pathway, and apoptosis.

While air pollution may adversely affect acute upper respiratory infection (AURI), whether meteorological factors modify this effect rarely been studied. This study sought to examine the association of air pollution with the morbidity of AURI as well as the modification effects of temperature and relative humidity (RH). Daily AURI visits data were obtained from Zhengzhou university hospital from 2014 to 2019. Distributed lagged nonlinear model (DLNM) was used to assess the effect of air pollutants on AURI morbidity. The modification effects of temperature and RH on the association of air pollution with AURI morbidity was explored by DLNM with an interaction term of the cross-basis of air pollutants and the temperature or RH. During the study period, 87,186 college students sought medical care for AURI. The relative risk (RR) and 95

INTRODUCTION:The individual survival benefit of neoadjuvant therapy (NAT) for patients with triple-negative breast cancer (TNBC) remains uncertain. This study aimed to evaluate the individualized treatment effect (ITE) of NAT on event-free survival (EFS) in patients with TNBC using causal survival forests. METHODS:This study included 803 patients with TNBC from a retrospective clinical cohort at a tertiary hospital in Henan Province, China. The outcome was 3-year EFS. ITEs were estimated on the restricted mean survival time (RMST) scale. A positive ITE indicated predicted benefit from NAT. Model performance was evaluated using C-for-benefit, rank weighted average treatment effects, and calibration. Patients were grouped into ITE quartiles, and survival outcomes were compared according to predicted benefit group and treatment concordance. RESULTS:Among 803 patients, 250 received NAT. The average treatment effect was -1.62 months. The predicted ITEs ranged from -7.92 months favoring No NAT to 3.67 months favoring NAT, indicating substantial heterogeneity in treatment benefit. The model showed positive ranking performance with an AUTOC of 5.67 months and the C-for-benefit was 0.537. Tumor size, clinical axillary lymph node status, and clinical N stage were the main contributors to predicted ITEs. In the Q1 and Q4 groups, concordant treatment was associated with an average RMST gain of 5.23 months. CONCLUSIONS:Among patients with TNBC, CSF identified subgroups with different predicted directions and magnitudes of 3-year EFS benefit. Stratification based on ITEs may support individualized assessment of treatment benefit and provide a basis for future validation.

BACKGROUND:Occupational exposure to high ambient temperature may affect liver function, but pathways remain unclear. OBJECTIVE:To examine associations between high ambient temperature and liver enzymes among steelworkers, and to evaluate mediation by inflammatory cells and moderation by age. METHODS:In this cross-sectional study of 1111 steelworkers, high ambient temperature exposure was classified at the workshop level using wet-bulb globe temperature (WBGT) per Chinese standards (GBZ 2.2-2007): time-weighted average WBGT ≥ 25 °C (high-temperature) vs. <25 °C (control). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and inflammatory cell counts were measured from venous blood. Multivariable generalized linear models estimated associations; mediation (via lymphocytes) used bootstrap confidence intervals; age moderation was tested. RESULTS:Compared with controls, the high ambient temperature exposure group exhibited elevated levels of ALT and AST, as well as higher counts of white blood cells, lymphocytes, monocytes, and eosinophils (P < 0.05). High ambient temperature exposure emerged as independently associated with ALT (β = 0.384, 95%CI: 0.222, 0.546) and AST (β = 0.238, 95%CI:0.065, 0.410) levels. Lymphocyte counts statistically mediated the relationship between high ambient temperature exposure and elevated serum ALT (β = 0.062, 95%CI: 0.026, 0.104) and AST (β = 0.046, 95%CI:0.009, 0.092) levels. Additionally, age only moderated the path between high ambient temperature exposure and lymphocyte count (β = -0.192, 95%CI: -0.316, -0.067). SIGNIFICANCE:Occupational heat was associated with higher ALT/AST; lymphocyte-related indirect association was observed and attenuated with age. Longitudinal and mechanistic studies are needed to assess causality. IMPACT:Findings support WBGT-based heat monitoring, routine ALT and AST screening in hot posts, and targeted acclimatization hydration and work- rest protocols, especially for younger workers, while future studies test whether enhanced heat controls improve liver outcomes.

AIMS:This study aims to examine the effect of relative muscle strength (RMS) on the progression to diabetes or regression to normoglycemia in individuals with prediabetes. METHODS:Data were sourced from the China Health and Retirement Longitudinal Study (CHARLS), which followed 3250 individuals aged ≥45 years with prediabetes. RMS was calculated as the ratio of grip to appendicular skeletal muscle mass (ASM). Multinomial logistic regression was used to assess the association of RMS with subsequent glycemic transitions, including regression to normoglycemia, persistence of prediabetes, and progression to diabetes. Mediation analysis explored the role of inflammation and lipid profiles in this association. RESULTS:During the follow-up period, 1953 participants remained in the prediabetes stage, 698 reverted to normoglycemia, and 599 progressed to diabetes. Participants regressing to normoglycemia exhibited significantly higher RMS than those remaining prediabetic [M (IQR): 2.25 (1.85, 2.62) vs. 2.16 (1.78, 2.55)], whereas those who progressed to diabetes showed lower RMS [1.97 (1.61, 2.32)]. Compared to the low RMS group, the OR (95% CI) for the high RMS group was 0.49(0.38, 0.64). Mediation analysis showed that high-density lipoprotein (HDL), triglycerides (TG), and C-reactive protein (CRP) partially mediated the effect between RMS and prediabetes progression, accounting for 14.47%, 4.41%, and 0.21% of the overall effect, respectively. CONCLUSIONS:Higher RMS independently protects against prediabetes progression and may aid regression, mediated by HDL, TG, and CRP.

To investigate the association between atmospheric temperature and embryonic development and pregnancy outcomes in women undergoing IVF/ICSI, and to evaluate the interaction between temperature and PM2.5. This study included 3747 patients undergoing IVF/ICSI treatment at one tertiary hospital in Henan Province from January 2015 to August 2023. Daily mean temperature, relative humidity, and PM2.5 concentrations were sourced from publicly available datasets. Temperature exposure was evaluated across seven time windows, with average levels calculated for each. Outcome measures encompassed oocyte and embryo quality indicators and pregnancy outcomes. Compared with the reference temperature range, exposure to low temperature dTimes New Romanuring Period C (from the start of gonadotropin treatment to oocyte retrieval) was associated with − 2.95 (95

BACKGROUND:The temporal directional relationship between sleep duration and depressive symptoms remains unclear. This study explored their dynamic links among middle-aged and older Chinese adults using a panel vector autoregressive framework. METHODS:We used nationally representative longitudinal data from the China Health and Retirement Longitudinal Study (CHARLS, 2011-2020). Analyses included participants with ≥3 repeated measurements of sleep duration and depressive symptoms to compute inter-wave change scores. Sleep duration was self-report. Depressive symptoms were measured by the 10-item CES-D scale. A panel vector autoregressive (PVAR) model was applied to examine the dynamic bidirectional association between sleep duration and depressive symptoms across multiple survey waves. RESULTS:12,747 participants were included in this study. An initial change in sleep duration was negatively associated with subsequent changes in sleep duration (β= -0.340, 95% CI: -0.358, -0.322). Similarly, an initial change in depressive symptoms was associated with subsequent reductions in depressive symptoms (β = -0.329, 95% CI: -0.346, -0.311). No significant association was observed between initial changes in depressive symptoms and subsequent changes in sleep duration (β = -0.001, 95% CI: -0.007, 0.005). In contrast, longer sleep duration significantly showed a directional lagged association with subsequent reductions in depressive symptoms (β = -0.064, 95% CI: -0.110, -0.018). CONCLUSIONS:Sleep duration was associated with lower subsequent depressive symptoms, while depressive symptoms did not predict sleep duration. These results indicate a directional temporal association and suggest that sleep duration may be a potential intervention target for improving mental health in middle-aged and older adults.

OBJECTIVES:To compare associations of antiretroviral therapy (ART) strategies with all-cause mortality and assess whether first opportunistic infection (OI) occurrence and time partly explain survival differences. METHODS:We analyzed 38,692 people with HIV in Henan Province (2015-2024). ART initiation timing and regimen were assessed, with early initiation defined as CD4+ T cell counts ≥500 cells/μL. Cox regression estimated associations with all-cause mortality and first OI. Multistate models characterized transitions to first OI and death, and time-to-event mediation analyses quantified the contribution of OI occurrence and time. RESULTS:During a median follow-up of 5.07 years, 2868 deaths occurred. Compared with late ART initiation, early initiation was associated with lower all-cause mortality (HR: 0.46; 95% CI: 0.41-0.52), and a lower transition hazard from OI to death (HR: 0.47; 95% CI: 0.27-0.81). Compared with PI-based regimens, INSTI- and NNRTI-based regimens showed lower observed all-cause mortality risks, with HRs (95% CI) of 0.51 (0.35-0.73) and 0.60 (0.50-0.72), respectively. At 5 years, early ART initiation and INSTI-based therapy were associated with absolute reductions in cumulative mortality risk of 8.51% and 4.76%, respectively, with residual disparity close to the total effect and a small shifting distribution effect (< 0.30%) attributable to first OI occurrence and time. CONCLUSIONS:Earlier ART initiation, especially at CD4+T cell counts ≥500 cells/μL, was associated with better survival. INSTI- and NNRTI-based regimens showed more favorable observed mortality outcomes than PI-based regimens. OI occurrence and time explained only a limited proportion of survival differences.

BACKGROUND/OBJECTIVES:To evaluate the associations between sedentary behavior and physical activity (PA) with biological aging and the effect on biological aging of replacing sedentary behavior with an equal amount of time spent on different PA. METHODS:A total of 301,603 U.K. adults (aged 38-73 years) were included. Sedentary behavior was quantified by summing up the time spent on watching TV, using computer, and driving every day. PA was quantified by the duration and frequency of light, moderate, and vigorous PA. Biological aging was estimated by PhenoAge algorithms based on clinical traits. Linear regression and isotemporal substitution model were used to test the relationships of sedentary behavior and PA with biological aging. RESULTS:Compared with individuals with sedentary behavior ≤3 hr/day, those with sedentary behavior of 3-5, 5-8, and >8 hr/day were associated with higher biological age acceleration, respectively. Consistently, PA was associated with lower biological age acceleration (p < .001). The isotemporal substitution model suggested that replacing sedentary behavior with PA (in hours per day) can delay biological age acceleration (light PA: β = -0.12, 95% CI [-0.14 to -0.09]; moderate PA: β = -0.22, 95% CI [-0.25 to -0.18]; vigorous PA: β = -0.21, 95% CI [-0.28 to -0.14). Multiplicative interactions were observed between sedentary behavior and all type of PA on biological age acceleration (p for interaction <.001). CONCLUSION:Based on UK Biobank cohort, sedentary behavior and lack of PA were associated with accelerated biological aging, while replacing sedentary behavior with PA was linked to slower biological aging. Significance/Implications: To delay biological aging, the population should replace sedentary behaviors with PA.

INTRODUCTION:To compare the mortality effects of dynamic antiretroviral therapy (ART) regimens among people with HIV (PWH), while accounting for time-varying CD 4+ T cell counts and HIV viral loads. METHODS:Leveraging data from 32 713 ART-naïve individuals (2015-2024) in Henan, China, we compared three approaches: baseline, time-fixed Cox model that classified participants by ART class at initiation, time-varying Cox model that updated ART class over follow-up; and marginal structural model (MSM) to address time-varying confounding. ART regimens were classified as nonnucleoside reverse transcriptase inhibitor (NNRTI)-, integrase strand transfer inhibitor (INSTI)-, or protease inhibitor (PI)-based regimens (reference: NNRTI). Outcomes included all-cause mortality and AIDS-related mortality. RESULTS:Effect estimates shifted from the baseline time-fixed model toward stronger protective associations after incorporating time-updated ART exposure and further adjusting for time-varying confounding. In the MSM, compared with NNRTI-based regimens, INSTI- and PI-based regimens were associated with lower all-cause mortality [INSTI: hazard ratio (HR) = 0.38, 95% confidence interval (CI): 0.29-0.49; PI: HR=0.69, 95% CI: 0.52-0.91] and lower AIDS-related mortality (INSTI: HR = 0.31, 95% CI: 0.17-0.57; PI: HR = 0.47, 95% CI: 0.25-0.89). Secondary exploratory cumulative exposure analyses yielded patterns broadly consistent with lower mortality for INSTI exposure, whereas estimates for PI exposure were closer to the null and should be interpreted cautiously. CONCLUSION:Accounting for time-updated ART exposure and time-varying confounding, INSTI-based regimens were associated with lower all-cause and AIDS-related mortality than NNRTI-based regimens. These findings underscore the need to account for dynamic ART exposure and time-varying confounding in observational comparative effectiveness studies of ART regimens.

OBJECTIVE:This study investigated the associations of intrinsic capacity, a multidomain measure of functional health, with the incidence and progression of ischemic heart disease, and the mediation of such associations by indices related to insulin resistance (IR). METHODS:We included 386,462 adults from the UK Biobank who were free of ischemic heart disease and its associated complications, including heart failure and arrhythmia, at baseline. Associations were estimated using Cox models, and multistate models for transitions. Mediation by IR-related indices was quantified in a counterfactual framework. RESULTS:Over a median 13.68 years of follow-up, 29,994 ischemic heart disease events occurred. Hazard ratios (95% confidence intervals) for ischemic heart disease were 1.15 (1.11-1.18), 1.38 (1.33-1.43), 1.68 (1.61-1.75), and 2.24 (2.12-2.37) for intrinsic capacity scores of 1, 2, 3, and ≥4 versus 0. Estimates from the multistate model for the transition from baseline to ischemic heart disease were consistent with the Cox results. Hazard ratios (95% confidence intervals) for transition from ischemic heart disease to death were 1.32 (1.14-1.53) for intrinsic capacity score 3 and 1.46 (1.21-1.74) for intrinsic capacity score ≥ 4, and 1.30 (1.09-1.56) from complications to death for intrinsic capacity score ≥ 4. IR-related indices accounted for 6.77-22.40% of the association between intrinsic capacity and ischemic heart disease, 5.38-24.24% for complications, and 2.22-10.04% for death. CONCLUSIONS:Lower intrinsic capacity was associated with higher risks of ischemic heart disease and its progression, partly through IR-related pathways, supporting metabolic dysfunction as a modifiable target for early risk stratification.

This study aimed to examine the reciprocal associations between socioeconomic status (SES) and cognitive function by disentangling between-person and within-person effects, and further examined potential heterogeneity across six specific subgroups: age, gender, residence, ever smoking, ever drinking, night sleep duration, and depressive symptoms. The data analyzed were drawn from the China Health and Retirement Longitudinal Study (CHARLS) during 2011–2018. Cognitive function was assessed by intelligence and episodic memory. SES was operationalized using annual per-capita household expenditure, occupation, education level, and health insurance. Adjusted random intercept cross-lagged panel models (RI-CLPMs) and multiple group RI-CLPMs were used to determine the reciprocal relationship between cognitive function and SES. Among 9,322 participants, at the between-person level, middle-aged and older adults showed positive association between SES and cognitive function over an eight-year period after adjusting covariates (β = 0.545, P < 0.001). At the within-person level, SES and cognitive function exhibited reciprocal positive cross-lagged effects across wave 2 to 4 (β = 0.032–0.063, P < 0.050). Using multi-group RI-CLPMs, we identified differences in the longitudinal effect of SES on cognitive function, particularly when comparing groups based on the residence and depressive symptoms (P < 0.050). An increase in individual socioeconomic status was a positive predictor of cognitive function. Likewise, improvements in cognitive function were found to positively predict short-term gains in socioeconomic status. These findings suggest that tailored interventions should be developed to prevent cognitive aging, taking into account the heterogeneity of different population.

To explore the association between comprehensive living environment and depression trajectories and examine the potential mediating role of sleep duration. This study included 7,773 middle-aged and older participants based on the China Health and Retirement Longitudinal Study. Living environment was assessed using outdoor PM2.5 level, solid fuel use, water type, room type and room temperature. Depression trajectories were identified using Latent Class Trajectory Model. Multinomial logistic regression and mediation analysis was used for analysis. Three depression trajectories were identified: low-rising (63.99

Background: Influenza is a serious contagious disease caused by influenza virus. It is particularly dangerous for children, potentially leading to severe and even fatal complications. The aim of this study was to evaluate the safety and immunogenicity of two candidate quadrivalent influenza subunit vaccines in children aged 6-35 months. Methods: The subjects were randomly divided into three groups at a 1:1:1 ratio and received the corresponding vaccines: QIV-Sub-HD (Quadrivalent Influenza Subunit Vaccine, High Dose), QIV-Sub-LD (Quadrivalent Influenza Subunit Vaccine, Low Dose) and QIV-Split-LD (Quadrivalent Influenza Split-Virion Vaccine, Low Dose). Adverse events were recorded at 30 min, 0-7 days and 8-28 and 30 days after each dose of immunization. Serious adverse events (SAEs) were collected and reported within 6 months after the full vaccination. Blood samples were collected before the first dose and on 28 days, 3 months and 6 months after full vaccination for antibody detection to evaluate the immunogenicity and duration of immune responses. Results: The results showed that the relative and absolute criteria met the goals set by the clinical trial protocol, indicating that both vaccines are immunogenic. From the first dose to 30 days after full vaccination, the total incidence of adverse reactions in the QIV-Sub-HD, QIV-Sub-LD and QIV-Split-LD groups was 29.64%, 33.33% and 29.64%, respectively. The main symptoms were fever, cough, diarrhea and vomiting. No new safety concerns were identified. Conclusions: The quadrivalent influenza subunit vaccines candidate, manufactured by Ab&B Bio-tech Co., Ltd. JS., are safe and immunogenic in children aged 6-35 months.

Atherosclerosis have been implicated in cardiovascular disease (CVD) risks, and whether frailty played a mediating role in this association was unclear. This study aimed to assess the associations of cumulative atherosclerosis index of plasma (CumAIP) exposure with incidence of CVD and evaluate the mediating role of frailty. The study analyzed data from the China Health and Retirement Longitudinal Study (CHARLS) cohort. Triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) were extracted to calculate the CumAIP. Frailty was assessed using the frailty index (FI). CVD events were confirmed based on medical history. Cox proportional hazards, linear regression, and restricted cubic spline (RCS) models were employed, along with mediation analysis. Increased atherosclerosis was associated with increased risks of CVD. In the fully adjusted Cox model, compared to the CumAIP Q1 group, the HR and 95