Evidence remains limited regarding the cumulative multi-system health effects of nitrogen dioxide (NO2) exposure and its lag–response patterns. This study aimed to evaluate the associations between short-term NO₂ exposure and multi-system healthcare utilization, with particular emphasis on lagged effects. Daily data on ambient air pollution, meteorological factors, and healthcare utilization across multiple disease systems were collected from 2023 to 2024 in four subtropical humid monsoon cities in China. Using a time-series design, distributed lag non-linear models (DLNMs) were applied to examine lagged and exposure–response associations between short-term NO2 exposure (lag 0–7 days) and daily healthcare visits. Stratified analyses by sex, age, healthcare utilization type, and season, as well as sensitivity analyses, were conducted. Significant positive associations between NO2 exposure and healthcare utilization were consistently observed across all four cities, with relative risks (RRs) ranging from 1.016 (95

We previously found low-level heavy metals lead (Pb), cadmium (Cd), and mercury (Hg) co-exposure impairs cognition even at their respective no observed adverse effect levels. However, the underlying mechanisms and complex interactions within mixture remain poorly understood from neurobiological basis perspective. Therefore, following low-level Pb, Cd, and Hg co-exposure, we systematically investigated the effects of that on synaptic efficiency, excitation/inhibition (E/I) balance, active neurons, and cognitive behavior impairment using electrophysiology, c-Fos active neuron labeling, and cognitive behavioral tests. In vitro factorial design experiments indicated that very low-level Pb, Cd, and Hg co-exposure specifically disrupted hippocampal synaptic transmission mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, potentially serving as a neurobiological basis for cognitive impairment following that exposure. This synaptic dysfunction may further shift E/I balance toward hyperexcitability, with increasing baseline hippocampal neuronal activity and inducing mice risk-taking behavior in resting state. Paradoxically, with mild stimulation by foot-shock, co-exposure attenuated both neuronal and behavioral responsiveness. Further analysis showed that while baseline active excitatory neurons and vGluT1 expression (particularly in dentate gyrus) were elevated, their stimulus-evoked plasticity was impaired, following low-level Pb, Cd, and Hg co-exposure. Overall, our findings suggest that AMPA receptor-associated E/I imbalance from low-level Pb, Cd, and Hg co-exposure was linked to altered neuronal activity patterns and impaired cognitive behavioral regulation. This study provides valuable insights for researchers and managers in revising safety thresholds, exploring mechanisms, and searching interventions for low-level heavy metal exposure.

Lead (Pb), an ancient metallic environmental pollutant, has received widespread attention and has been strictly controlled, but current findings have found the hazards of Pb to be much higher than previously estimated. Pb exposure can lead to memory impairment. However, the underlying molecular mechanisms have not been fully elucidated. Dynamic changes in dendritic spines form the structural basis of memory, and MEF2C, a key regulator of dendritic plasticity, plays an important role in hippocampus-dependent learning and memory. This study focused on the role of ERK-induced MEF2C phosphorylation in Pb-induced learning and memory impairments. A rat model of Pb exposure from the embryo to adolescence and the model of Pb exposure in PC12 cells were established. The results showed that Pb exposure reduced the phosphorylation level of MEF2C in the rat hippocampus by affecting the expression of ERK5. In addition, it reduced the expression of MEF2C at the translation stage, which affected its transcriptional ability and led to abnormal expression of the downstream factor ARC, causing alterations in neuronal dendritic plasticity and affecting its memory ability. Further experiments showed that regulating the phosphorylation level of MEF2C could affect neurite growth in PC12 cells exposed to Pb. Our findings demonstrate that Pb exposure may contribute to memory impairment by affecting MEF2C and its phosphorylation levels, resulting in altered dendritic plasticity.

Lead (Pb), mercury (Hg), and cadmium (Cd), prevalent neurotoxic heavy metals in the environment, are commonly detected at low concentrations in the blood of the general population. Our previous studies demonstrated that Pb, Hg, and Cd mixture induced neurodevelopmental toxicity even at very low levels. However, the long-term effects of low-level Pb, Hg, Cd exposure on brain aging remain unclear. In this study, female rats were exposed to a mixture of 10 mg/L Pb(CH3COO)2, 0.05 mg/L HgCl2, and 3.5 mg/L CdCl2 via drinking water from mating until offspring weaning. Offspring continued to exposed to heavy metal mixture (3.5 mg/L Pb(CH3COO)2, 0.015 mg/L HgCl2, and 0.5 mg/L CdCl2) for 32 weeks. At 52 weeks of age, brain aging was comprehensively evaluated through behavioral testing, histopathological examination, and telomere assessment. The results revealed that prolonged low-level exposure to the Pb, Hg, and Cd mixture compromised telomeric function by shortening telomere length, inhibiting telomerase activity, and induced neuronal loss in the hippocampal CA1 and CA3 regions. Additionally, Golgi staining revealed disrupted dendritic spines in the hippocampus and altered spine-related signaling pathways (Snk-SPAR pathway). Furthermore, behavioral testing showed that exposure to this mixture impaired spatial memory and social cognition. In conclusion, prolonged exposure to low levels of Pb, Hg, and Cd accelerated brain aging by causing hippocampal telomere dysfunction, neuronal loss, dendritic degeneration, and cognitive decline in rats. These findings offer novel insights into the potential neurotoxic effects of chronic exposure to low-level of Pb, Hg, and Cd mixtures on neurological health.

Metabolic-dysfunction associated fatty liver disease (MAFLD) is a widespread chronic liver condition that has been steadily increasing among adolescents and young adults in recent years, posing a major global public health concern. This study aims to conduct an in-depth analysis of the Global Burden of Disease (GBD) 2021 data on MAFLD, focusing on prevalence, incidence, and disability-adjusted life years (DALY) for individuals aged 15-39, spanning the period from 1990 to 2021. This research examines data from the GBD study covering 1990 to 2021 to assess the prevalence, incidence, and DALYs associated with of MAFLD in adolescents and young adults aged 15-39. The analysis is broken down by socioeconomic status, geographic regions, and specific countries. Advanced statistical methods, including the estimated annual percentage change (EAPC) and Bayesian age-period-cohort (BAPC) modeling, were used to deliver the most current and thorough epidemiological assessment of MAFLD in this demographic. In 2021, the estimated global cases of non-alcoholic fatty liver disease among adolescents and young adults reached approximately 423 million, representing a 75.31% increase from 1990. The age-standardized prevalence rate (ASPR) was 14,221.32 cases per 100,000 population, and the age-standardized incidence rate (ASIR) was 977.61 cases per 100,000 population in 2021. Between 1990 and 2021, the ASPR, ASIR, age-standardized DALY rate, and age-standardized mortality rate showed a continuous upward trend, with EAPC of 0.84, 0.79, 0.65, and 0.81, respectively. Regions with Middle and Low-middle Socio-Demographic Index (SDI), as well as High-middle SDI, emerged as "hotspots" for MAFLD prevalence, particularly in North Africa, the Middle East, East Asia, and South Asia. Males exhibited higher prevalence rates compared to females, and the rates continued to increase across all adolescents and young adult age groups. By 2050, the ASPR for MAFLD among this population is projected to reach 16,101 cases per 100,000, signaling an alarming trend. Over the last 30 years, the burden of metabolic-dysfunction associated fatty liver disease has significantly increased among adolescents and young adults worldwide. To counter this rising global health concern, it is crucial to develop and implement targeted and effective interventions tailored to socio-economic settings.

Lead (Pb), mercury (Hg), and cadmium (Cd) are prevalent and persistent environmental contaminants, causing detrimental effects on millions of individuals worldwide. Our previous research demonstrated that early-life exposure to low-level Pb, Hg, and Cd mixtures may lead to cognitive impairments. However, the association and interaction among low levels of Pb, Hg, or Cd exposure remains unclear. In this study, a two-level full factorial design (5.481, 0.036, and 2.132 mg/L for Pb, Hg, and Cd respectively) was conducted to assess the interplay among maternal Pb, Hg, and Cd exposure on offspring cognition. Following exposure during pregnancy and lactation, a competitive absorption among Pb, Hg, and Cd was observed. Maternal exposure to each metal alone resulted in higher blood and brain concentrations of Pb, Hg, and Cd in offspring compared to co-exposure at equivalent levels. However, behavioral experiments conducted in the Morris water maze and novel object recognition test revealed maternal Pb, Hg, and Cd exposure synergistically impaired offspring's spatial cognition and recognition memory. Importantly, this dysfunction persisted into middle age even without exposure after adulthood. Moreover, the open field test and elevated plus maze indicated maternal low-level Pb, Hg, and Cd co-exposure triggered risk-taking behavior in weaning offspring, with a significant main effect for Pb exposure. No long-lasting effect on risk-taking behavior was detected in middle-aged offspring. Further investigation into molecular mechanisms showed that the dysregulation of corticosterone reaction and immune response might be the potential mechanism underlying Pb, Hg, and Cd co-exposure-induced cognitive impairments. Our study highlights the synergistic and long-lasting effects of multiple heavy metal exposures,underscoring the urgency to prevent exposure to metal mixtures among children and women of childbearing age.

The heavy metals lead (Pb), cadmium (Cd), and mercury (Hg) that cause neurocognitive impairment have been extensively studied. These elements typically do not exist alone in the environment; they are often found with other heavy metals and can enter the body through various routes, thereby impacting health. Our previous research showed that low Pb, Cd, and Hg levels cause neurobehavioral impairments in weaning and adult rats. However, little is known about the biomarkers and mechanisms underlying Pb, Cd, and Hg mixture-induced neurological impairments. A combined analysis of metabolomic and proteomic data may reveal heavy metal-induced alterations in metabolic and protein profiles, thereby improving our understanding of the molecular mechanisms underlying heavy metal-induced neurological impairments. Therefore, brain tissue and serum samples were collected from rats exposed to a Pb, Cd, and Hg mixture for proteomic and metabolomic analyses, respectively. The analysis revealed 363 differential proteins in the brain and 206 metabolites in serum uniquely altered in the Pb, Cd, and Hg mixture exposure group, compared to those of the control group. The main metabolic impacted pathways were unsaturated fatty acids biosynthesis, linoleic acid metabolism, phenylalanine metabolism, and tryptophan metabolism. We further identified that the levels of arachidonic acid (C20:4 n-3) and, adrenic acid (C22:4 n-3) were elevated and that kynurenic acid (KA) and quinolinic acid (QA) levels and the KA/QA ratio, were decreased in the group exposed to the Pb, Cd, and Hg mixture. A joint analysis of the proteome and metabolome showed that significantly altered proteins such as LPCAT3, SLC7A11, ASCL4, and KYAT1 may participate in the neurological impairments induced by the heavy metal mixture. Overall, we hypothesize that the dysregulation of ferroptosis and kynurenine pathways is associated with neurological damage due to chronic exposure to a heavy metal mixture.

Exposure to essential and toxic metals occurs simultaneously as a mixture in real-life. However, there is no consensus regarding the effects of co-exposure to multiple metal(loid)s (designated hereafter metals) on blood lipid levels. Thus, blood concentrations of six human essential metals and five toxic metals in 720 general populations from southeastern China were simultaneously determined as a measure of exposure. In addition, quantile g-computation, Bayesian kernel machine regression, elastic net regression, and generalized linear model were used to investigate both the joint and individual effects of exposure to this metal mixture on human blood lipid levels. The significant positive joint effect of exposure to this metal mixture on serum total cholesterol (TC) levels, rather than on serum triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, Castelli risk index I, Castelli risk index II, atherogenic coefficient, and non-HDL-C levels, was found. In addition, the positive effect may be primarily driven by selenium (Se), lead (Pb), and mercury (Hg) exposure. In addition, on the effect of TC levels, the synergistic effect between Pb and Hg and the antagonistic effect between Se and Pb were identified. Our finding suggests that combined exposure to this metal mixture may affect human blood lipid levels. Therefore, reducing exposure to heavy metals, such as Pb and Hg, should be a priority for the general population. In addition, Se supplementation should also be considered with caution.

目的 探讨孕期生活饮食模式与足月新生低出生体质量儿及巨大儿发生风险的关系.方法 收集2018年4月-2019年2月在江西省某市人民医院分娩且符合纳入排除标准的2013对孕妇及其足月单胎新生儿作为研究对象,采用因子分析和结构方程模型相结合的方法研究母亲孕期生活饮食模式与新生低出生体质量儿、巨大儿的关系.结果 足月新生低出生体质量儿和巨大儿的发生率分别为3.7％和5.7％.因子分析和回归分析显示,孕期运动模式可降低新生儿低出生体质量发生风险(OR=0.89,95％CI:0.80～0.98);而孕期高盐高脂饮食模式则可增加巨大儿的发生风险(OR=1.07,95％CI:1.01～1.14).结构方程模型分析发现,孕期高盐高脂饮食对新生巨大儿的发生风险的总效应为0.069,其中直接效应为0.064,通过孕期增重过度的中介效应(0.061)而产生的间接效应为0.005;而孕期运动可降低新生儿低出生体质量的发生风险(直接效应为-0.058),但未发现孕期增重的中介效应.结论 孕期运动和高盐高脂饮食与足月新生儿出生体质量密切相关,孕期适量运动锻炼、控制高盐高脂及垃圾食品的摄入,对降低足月新生儿低出生体质量、巨大儿的发生风险具有重要意义.

Lead (Pb), cadmium (Cd), and mercury (Hg) are environmentally toxic heavy metals that can be simultaneously detected at low levels in the blood of the general population. Although our previous studies have demonstrated neurodevelopmental toxicity upon co-exposure to these heavy metals at these low levels, the precise mechanisms remain largely unknown. Dendritic spines are the structural foundation of memory and undergo significant dynamic changes during development. This study focused on the dynamics of dendritic spines during brain development following Pb, Cd, and Hg co-exposure-induced memory impairment. First, the dynamic characteristics of dendritic spines in the prefrontal cortex were observed throughout the life cycle of normal rats. We observed that dendritic spines increased rapidly from birth to their peak value at weaning, followed by significant pruning and a decrease during adolescence. Dendritic spines tended to be stable until their loss in old age. Subsequently, a rat model of low-dose Pb, Cd, and Hg co-exposure from embryo to adolescence was established. The results showed that exposure to low doses of heavy metals equivalent to those detected in the blood of the general population impaired spatial memory and altered the dynamics of dendritic spine pruning from weaning to adolescence. Proteomic analysis of brain and blood samples suggested that differentially expressed proteins upon heavy metal exposure were enriched in dendritic spine-related cytoskeletal regulation and axon guidance signaling pathways and that cofilin was enriched in both of these pathways. Further experiments confirmed that heavy metal exposure altered actin cytoskeleton dynamics and disturbed the dendritic spine pruning-related LIM domain kinase 1-cofilin pathway in the rat prefrontal cortex. Our findings demonstrate that low-dose Pb, Cd, and Hg co-exposure may promote memory impairment by perturbing dendritic spine dynamics through dendritic spine pruning-related signaling pathways.

Humans are commonly exposed to the representative neurotoxic heavy metals lead (Pb), cadmium (Cd), and mercury (Hg). These three substances can be detected simultaneously in the blood of the general population. We have previously shown that a low-dose mixture of these heavy metals induces rat learning and memory impairment at human exposure levels, but the pathogenic mechanism is still unclear. LIM kinase 1 (LIMK1) plays a critical role in orchestrating synaptic plasticity during brain function and dysfunction. Hence, we investigated the role of LIMK1 activity in low-dose heavy metal mixture-induced neurobehavioral deficits and structural synaptic plasticity disorders. Our results showed that heavy metal mixture exposure altered rat fear responses and spatial learning at general population exposure levels and that these alterations were accompanied by downregulation of LIMK1 phosphorylation and structural synaptic plasticity dysfunction in rat hippocampal tissues and cultured hippocampal neurons. In addition, upregulation of LIMK1 phosphorylation attenuated heavy metal mixture-induced structural synaptic plasticity, dendritic actin dynamics, and cofilin phosphorylation damage. The potent LIMK1 inhibitor BMS-5 yielded similar results induced by heavy metal mixture exposure and aggravated these impairments. Our findings demonstrate that LIMK1 plays a crucial role in neurobehavioral deficits induced by low-dose heavy metal mixture exposure by suppressing structural synaptic plasticity.

Environmental exposure to heavy metal mixture of lead (Pb), cadmium (Cd), and mercury (Hg) would induce hazardous health effects. However, there is a paucity of data on how exposure to heavy metal mixture alters the metabolic dynamics of individual metals. Considering that the dose plays a key role in determining the toxicity of heavy metals, we performed a factorial design with three heavy metals (Pb, Cd, and Hg) at low exposure levels. Female rats were exposed to Pb, Cd, and (or) Hg from successful mating until pup weaning. Their concentrations in maternal blood, breast milk, and postnatal day 0 (PND0) and PND21 offspring blood and whole brain were measured. Using ANOVA analysis, Pearson correlation, and structural equation model, we demonstrated the complex interactions among heavy metals during their absorption, mother-offspring transport, and target organ accumulation. Among all the explored samples, almost all the highest Pb, Cd, and Hg levels were observed in their respective single heavy metal exposure groups. In addition, Hg was found could antagonize the transport of Pb or Cd, when they cross the placental barrier and blood-brain barriers (BBB). However, the effect of Hg no longer presented when they are absorbed through the digestive system. The antagonistic effect of Pb on Cd was observed when they cross the placental barrier. In addition, Cd was also found to compete the transport pathway of Pb when they cross the BBB after birth. Compared to Pb and Hg, we found that the transport efficiency of Cd in the digestive system was lower, whereas the chelation of Cd by the placental barrier was better. This preliminary information may help researchers to explore the mechanism underlying the hazardous effects of heavy metal mixture exposure, or for regulatory agencies to revise guidelines for heavy metal exposure.

Contaminated water and food are the main sources of lead, cadmium, and mercury in the human body. Long-term and low-level ingestion of these toxic heavy metals may affect brain development and cognition. However, the neurotoxic effects of exposure to lead, cadmium, and mercury mixture (Pb + Cd + Hg) at different stages of brain development are rarely elucidated. In this study, different doses of low-level Pb + Cd + Hg were administered to Sprague-Dawley rats via drinking water during the critical stage of brain development, late stage, and after maturation, respectively. Our findings showed that Pb + Cd + Hg exposure decreased the density of memory- and learning-related dendritic spines in the hippocampus during the critical period of brain development, resulting in hippocampus-dependent spatial memory deficits. Only the density of learning-related dendritic spines was reduced during the late phase of brain development and a higher-dose of Pb + Cd + Hg exposure was required, which led to hippocampus-independent spatial memory abnormalities. Exposure to Pb + Cd + Hg after brain maturation revealed no significant change in dendritic spines or cognitive function. Further molecular analysis indicated that morphological and functional changes caused by Pb + Cd + Hg exposure during the critical phase were associated with PSD95 and GluA1 dysregulation. Collectively, the effects of Pb + Cd + Hg on cognition varied depending on the brain development stages.

线上教学正在逐步应用到医学教学实践中.文章通过对我国医学院校线上教学中存在的问题进行梳理,发现主要问题集中在教学目标、教学设计、课程评价、教学氛围、教学方式等方面,并提出应对策略,为医学线上教学的发展和改革提供参考.

The Outline of the “Healthy China 2030” Plan clearly proposes to strengthen health education in schools. Health education should be integrated into the national education system and become an important part of quality education at all stages of education. The COVID-19 pandemic has affected the physical and mental health of college students to varying degrees and posed new challenges to health education in universities. Firstly, this paper expounds the present situation and the value of health education for college students in the new ear, analyzes the current problems of health education in colleges and universities, and explores the optimization path, in order to promote the health education in colleges and universities and promote the comprehensive physical and mental healthy development of college students.

The heavy metals, namely lead (Pb), cadmium (Cd), and mercury (Hg), have been studied extensively in various independent studies. It has been seen that these metals are usually detected simultaneously in the human blood at low levels. However, it is unknown whether exposure to these heavy metal mixtures (MM) can induce neurological damages at these low levels. Therefore, we investigated the influence of the Pb, Cd, and Hg mixture on the nervous system in rats at exposure doses equivalent to those normally found in the human blood. After pregnant rats being exposed to MM via drinking water throughout the gestation and lactation, their offspring were followed-up till adulthood. MM caused cognitive deficits and impairments in a dose-dependent manner. Furthermore, MM disrupted dendritic spines, the structural basis of learning and memory, and induced changes in spine-related pathways. Meanwhile, we explored an early and safe way to remedy these impairments through a postnatal enriched environment. The enriched environment ameliorated MM-impaired cognitive function, synaptic plasticity, and spine-related pathways. This study demonstrated that low-dose co-exposure to Pb, Cd, and Hg can cause cognitive and synaptic plasticity deficits and timely intervention through the enriched environment has a certain corrective effect.

Heavy metals such as lead (Pb), cadmium (Cd), and mercury (Hg) are representative neurotoxicological contaminants that can evoke cognitive dysfunctions. Low levels of these contaminants can be detected simultaneously in the human blood. In our previous study, behavioral performances were markedly impaired by exposure to these heavy metal mixtures (MM) at low levels. However, the aspects of cognitive functions involved are not well understood. Here, we further analyzed search strategies using a new algorithm named Morris water maze-unbiased strategy classification (MUST-C). Rat pups were co-exposed to low doses of Pb, Cd, and Hg during the embryonic and lactation stage. MM exposure at low doses, similar to those found in the general population, impaired search strategies even though their latency and path length were not affected in the Morris water maze task. MM-exposed rats preferred to use more directionless repetition strategies and less target orientation strategies than did vehicle-exposed animals in a dose-dependent manner. In addition, thionine staining and electron microscopy further revealed that MM exposure induced dose-dependent search strategy related place cell injures in the hippocampal CA1 and CA3 regions. These results demonstrate that the use of suboptimal search strategies underlies the early cognitive deficits in rats exposed to low doses of MM. The current study determined that search strategy analysis might be a novel sensitive assessment method for evaluating in the neurobehavioral toxicity.

We conducted a meta-analysis to evaluate the association between prenatal cadmium (Cd) exposure and birth weight. PubMed, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang databases were searched for studies published before March 2019. We used a model-based method, standardizing effect size from linear regression models to include a maximum number of studies during our quantitative evaluations. As a result, 11 articles from the general population, containing 10 birth cohorts and one cross-sectional study, were included. Our meta-analysis demonstrated that a 50% increase of maternal urine Cd (UCd) would be associated with a 6.15 g decrease in neonatal birth weight (beta= -6.15 g, 95% CI: -10.81, -1.49) as well as a 50% increase of maternal blood Cd (BCd) would be associated with an 11.57 g decrease (beta = -11.57 g; 95% CI: -18.85, -4.30). Stratified analysis of UCd data indicated that the results of female newborns were statistically significant (beta=-8.92 g, 95% CI: -17.51, -0.34), as was the first trimester (beta = -11.34 g, 95% CI: -19.54, -3.14). Furthermore, increased UCd levels were associated with a higher rate of low birth weight (LBW) risk (OR = 1.12, 95% CI: 1.03, 1.22). This meta-analysis demonstrated that elevated maternal Cd levels are associated with decreased birth weight and higher LBW risk. (C) 2019 Elsevier Ltd. All rights reserved.