1.Thyroid Hormone Network Regulation in MASLD: Mechanisms and Targeted Therapies
Wen-Ping XIAO ; Yang MA ; Heng GUAN ; Sha WAN ; Wen HAN ; Bing-Bing LUO ; Wu-Feng WANG ; Fang LIU
Progress in Biochemistry and Biophysics 2026;53(3):643-661
Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most prevalent chronic liver disease worldwide, affecting approximately 32%-38% of the adult population and posing a growing public health burden. MASLD represents a continuous disease spectrum ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH), progressive hepatic fibrosis, cirrhosis, and ultimately hepatocellular carcinoma (HCC). The pathological core of MASLD lies in disruption of hepatic lipid metabolic homeostasis, characterized by an imbalance among de novo lipogenesis, fatty acid β-oxidation, and very-low-density lipoprotein (VLDL)-mediated lipid export. This metabolic disequilibrium subsequently drives inflammatory injury and fibrotic progression. Among the multiple regulatory pathways involved, thyroid hormone (TH) signaling has emerged as a central regulator of hepatic metabolic homeostasis. The liver is a major peripheral target organ of TH action, where TH predominantly exerts its metabolic effects through thyroid hormone receptor β (TRβ). Large-scale epidemiological studies and meta-analyses have demonstrated that hypothyroidism is significantly associated with increased MASLD prevalence, more severe histological injury, and advanced hepatic fibrosis, suggesting that dysregulation of TH signaling may participate throughout the entire MASLD disease spectrum. At the molecular level, TH regulates hepatic lipid metabolism by coordinating suppression of lipogenesis, enhancement of mitochondrial fatty acid oxidation, and promotion of VLDL assembly and secretion through integrated genomic actions of the T3-TRβ axis and non-genomic signaling pathways. Across different stages of MASLD, TH signaling exerts stage-dependent protective effects. In the steatosis stage, TH improves metabolic flexibility by modulating insulin sensitivity, glucose metabolism, and lipid droplet clearance, thereby alleviating early lipotoxic stress. During progression to MASH, TH attenuates inflammatory amplification by improving mitochondrial homeostasis, suppressing activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, and modulating the gut-liver axis microenvironment. In advanced stages, TH signaling influences hepatic stellate cell activation and extracellular matrix deposition, partly through interaction with the transforming growth factor-β (TGF-β)/SMAD pathway, while alterations in intrahepatic TH availability, mediated by dynamic changes in iodothyronine deiodinase 1 (DIO1), contribute to fibrosis progression and hepatocellular dedifferentiation. In hepatocellular carcinoma, coordinated downregulation of TRβ and DIO1 establishes a tumor-associated hypothyroid state that promotes metabolic reprogramming and tumor progression. The clinical relevance of TH signaling in MASLD has been underscored by the recent approval of Resmetirom, a liver-targeted TRβ‑selective agonist, for the treatment of non-cirrhotic MASH with moderate-to-severe fibrosis (F2-F3). This approval represents a landmark transition from mechanistic understanding to metabolism-centered precision therapy in MASLD. Clinical trials have demonstrated that Resmetirom not only improves key histological endpoints, including MASH resolution and fibrosis regression, but also favorably modulates atherogenic lipid profiles, highlighting the therapeutic potential of selectively targeting hepatic TH pathways. This review systematically summarizes the multidimensional regulatory roles of TH across the MASLD disease spectrum and discusses emerging diagnostic and therapeutic implications of TH-based interventions, aiming to inform future mechanistic research and optimize clinical management strategies.
2.Nutritional insufficiency and appropriate catch-up growth in extremely preterm infants within 24 months of corrected age: a retrospective cohort study
Xiaoli QU ; Chunjin PENG ; Yixue ZHAO ; Yulan YANG ; Na LUO ; Ping WANG
Chinese Journal of Pediatrics 2026;64(1):68-76
Objective:To assess the status of undernutrition and appropriate catch-up growth in extremely preterm infants within 24 months of corrected age (CA).Methods:A retrospective cohort study was conducted. A total of 422 extremely preterm infants born at Shenzhen Maternity and Child Healthcare Hospital, Women and Children's Medical Center, Southern Medical University from January 2017 to December 2022 and followed up until 24 months of CA were enrolled. The extremely preterm infants were grouped by gestational age at birth (<25, 25-26, 27 weeks), birth weight (<500, 500-749, 750-999,≥1 000 g), weight for gestational age (large for gestational age (LGA), appropriate for gestational age (AGA), small for gestational age (SGA)) and sex. Weight data within 24 months of CA were collected every 3 months. Nutritional insufficiency, growth rate, and achievement of adequate catch-up growth were analyzed during the period from 0 to 24 months of CA. Z-score method was used to analyze data. Fenton 2013 preterm growth charts (Fenton 2013) were used before 40 weeks of corrected gestational age, and World Health Organization child growth standards (2009) fitted Z-scores were applied from 40 weeks of CA. Changes in weight Z-scores of extremely preterm infants from 0 to 24 months of CA were observed and compared, the occurrence of moderate to severe malnutrition and growth retardation was determined, nutritional insufficiency was assessed, and growth rate as well as the achievement of appropriate catch-up growth were analyzed. The Lambda-mu-sigma method combined with the Z-score fitting model was used to fit and analyze the distribution characteristics of weight percentiles in extremely preterm infants. The Chi-square test was used to compare differences among groups.Results:A total of 422 extremely preterm infants were included, with a gestational age at birth of 26.3(25.4, 27.2) weeks and a birth weight of (880±177) g. Among them, 238 were males and 184 were females; 36 cases (8.5%) were LGA, and 16 cases (3.8%) were SGA. During follow-up within 24 month of CA, 89 cases (21.1%) developed moderate to severe malnutrition. When compared separately among different birth weight and gestational age at birth groups, there had both statistically differences in the incidence of moderate to severe malnutrition ( χ2=42.94 and 9.17, both P<0.05). The incidence was the highest in the birth weight of CA<500 g group and the <25 weeks gestational age at birth group, while it was the lowest in the birth weight of CA≥1 000 g group and the 27 weeks gestational age at birth group in their respective groups. Growth retardation occurred in 5.2% (22/422). However, there had statistically differences in the incidence of growth retardation among different birth weight and gestational age at birth groups, in each grouped time interval ( χ2=21.61 and 4.30, both P<0.05). The proportions of rapid growth were relatively high in the 0-3 months and 3-6 months of CA groups, which were 96 cases (27.4%) and 98 cases (26.6%), respectively. Overall, appropriate catch-up growth was achieved in 341 cases (80.8%) from 0 to 24 months of CA. There had statistically differences in the completion rate of appropriate catch-up growth among different birth weight and gestational age at birth groups ( χ2=23.65 and 7.08, both P<0.05). The completion rate was the highest in the birth weight of CA<500 g group and the <25 weeks of gestational age at birth group, while it was the lowest in the birth weight of CA≥1 000 g group and the 27 weeks of gestational age at birth group. Conclusions:The lower the birth weight and gestational age of extremely preterm infants, the higher the incidence of moderate to severe malnutrition and the lower the achievement rate of adequate catch-up growth within 24 months of CA. The period of 0-6 months of CA is the critical window for catch-up in extremely preterm infants.
3.Perioperative immune dynamics and clinical outcomes in patients undergoing on-pump cardiac surgery
Zhiyuan CHENG ; Xinyi LIAO ; Juan WU ; Ping YANG ; Tingting WANG ; Qinjuan WU ; Wentong MENG ; Zongcheng TANG ; Jiayi SUN ; Jia TAN ; Jing LIN ; Dan LUO ; Hao WANG ; Chaonan LIU ; Jiyue XIONG ; Liqin LING ; Jing ZHOU ; Lei DU
Chinese Journal of Blood Transfusion 2026;39(1):31-43
Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10
/L vs preoperative 3.07×10
/L, P<0.001), with significant upregulation of CD11b (7.30×10
/L vs preoperative 3.05×10
/L, P<0.001) and CD54 (7.15×10
/L vs preoperative 2.99×10
/L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10
/L vs preoperative 1.12×10
/L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10
/L vs preoperative 1.12×10
/L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.
4.Exploring Intervention Effect of Atractylodis Macrocephalae Rhizoma Processed with Aurantii Fructus Immaturus Juice on Slow-transit Constipation and Its "Microbiota-Metabolism" Synergistic Regulation Mechanism Based on Theory of "Spleen Governing Transportation and Transformation"
Dan LI ; Xiaoxia LIU ; Xiaofen WANG ; Zuxin HE ; Junnan WEI ; Yanqing LIU ; Yuxuan GAO ; Ping LUO ; Fang WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):201-209
ObjectiveBased on the theory of "spleen governing transportation and transformation", this study investigates the efficacy of Atractylodis Macrocephalae Rhizoma processed with Aurantii Fructus Immaturus juice(AMR-AFI) in improving slow-transit constipation(STC), as well as the synergistic regulatory mechanism involving the microbiota-metabolism axis, thereby elucidating the scientific basis of its processing theory. MethodsAnimals were randomly divided into the control group, model group, positive drug(mosapride) group(3 mg·kg-1), and low-, medium-, and high-dose groups of AMR-AFI(3.9, 7.8, 15.6 g·kg-1). Except for the control group, the remaining five groups were induced with STC using loperamide hydrochloride. Following modeling, interventions were administered. All groups received continuous administration for 15 d, during which fecal samples, colon tissue, and serum were collected. Constipation improvement was assessed by measuring fecal moisture content and small intestinal propulsion rate, histological morphology of colonic tissue was observed via hematoxylin-eosin(HE) staining, and the levels of interleukin(IL)-6, tumor necrosis factor(TNF)-α, and IL-2 in serum were detected using enzyme-linked immunosorbent assay(ELISA). Furthermore, the microbial community structure in mouse feces was analyzed by 16S rRNA sequencing, while transcriptomic sequencing was employed to screen differentially expressed genes in colonic tissue, followed by gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses. Finally, Spearman correlation analysis was conducted to explore the association between differential microbiota and differential genes. ResultsCompared with the control group, the intestinal propulsion rate and fecal moisture content in the model group were significantly decreased(P<0.01), while serum levels of IL-6, TNF-α, and IL-2 were significantly elevated(P<0.01). HE staining showed damage and shedding of colonic mucosal epithelial cells, along with a reduction in goblet cells in the model group. In comparison with the model group, all treatment groups improved the pathological state of the colonic mucosa to varying degrees and reduced serum levels of IL-6, TNF-α, and IL-2(P<0.01). Among these, the high-dose group of AMR-AFI significantly increased the intestinal propulsion rate and fecal moisture content of rats(P<0.05, P<0.01). Further transcriptomic analysis revealed that a total of 104 differentially expressed genes were identified from comparisons between the model group and the control group, as well as between the model group and the high-dose group of AMR-AFI. These genes were mainly enriched in pathways closely related to STC pathogenesis, such as arachidonic acid metabolism and aldosterone-regulated sodium reabsorption. 16S rRNA sequencing results indicated that AMR-AFI reversed the structural imbalance of the gut microbiota in model mice, increased species richness, downregulated the relative abundance of pro-inflammatory bacteria such as Parasutterella, and enriched beneficial and butyrate-producing bacteria, including Lachnospiraceae_NK4A136_group, Ruminococcaceae, and Lachnospiraceae. Spearman correlation analysis further showed that the beneficial bacteria enriched in the AMR-AFI group were negatively correlated with genes involved in the arachidonic acid metabolic pathway and positively correlated with genes in the aldosterone-regulated sodium reabsorption pathway. In contrast, pro-inflammatory bacteria in the model group exhibited the opposite correlation trends. ConclusionAMR-AFI can effectively exert synergistic therapeutic effects on STC by regulating intestinal microbiota, arachidonic acid-mediated inflammatory metabolism, and aldosterone-regulated water-salt balance pathways.
5.Exploring Intervention Effect of Atractylodis Macrocephalae Rhizoma Processed with Aurantii Fructus Immaturus Juice on Slow-transit Constipation and Its "Microbiota-Metabolism" Synergistic Regulation Mechanism Based on Theory of "Spleen Governing Transportation and Transformation"
Dan LI ; Xiaoxia LIU ; Xiaofen WANG ; Zuxin HE ; Junnan WEI ; Yanqing LIU ; Yuxuan GAO ; Ping LUO ; Fang WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):201-209
ObjectiveBased on the theory of "spleen governing transportation and transformation", this study investigates the efficacy of Atractylodis Macrocephalae Rhizoma processed with Aurantii Fructus Immaturus juice(AMR-AFI) in improving slow-transit constipation(STC), as well as the synergistic regulatory mechanism involving the microbiota-metabolism axis, thereby elucidating the scientific basis of its processing theory. MethodsAnimals were randomly divided into the control group, model group, positive drug(mosapride) group(3 mg·kg-1), and low-, medium-, and high-dose groups of AMR-AFI(3.9, 7.8, 15.6 g·kg-1). Except for the control group, the remaining five groups were induced with STC using loperamide hydrochloride. Following modeling, interventions were administered. All groups received continuous administration for 15 d, during which fecal samples, colon tissue, and serum were collected. Constipation improvement was assessed by measuring fecal moisture content and small intestinal propulsion rate, histological morphology of colonic tissue was observed via hematoxylin-eosin(HE) staining, and the levels of interleukin(IL)-6, tumor necrosis factor(TNF)-α, and IL-2 in serum were detected using enzyme-linked immunosorbent assay(ELISA). Furthermore, the microbial community structure in mouse feces was analyzed by 16S rRNA sequencing, while transcriptomic sequencing was employed to screen differentially expressed genes in colonic tissue, followed by gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses. Finally, Spearman correlation analysis was conducted to explore the association between differential microbiota and differential genes. ResultsCompared with the control group, the intestinal propulsion rate and fecal moisture content in the model group were significantly decreased(P<0.01), while serum levels of IL-6, TNF-α, and IL-2 were significantly elevated(P<0.01). HE staining showed damage and shedding of colonic mucosal epithelial cells, along with a reduction in goblet cells in the model group. In comparison with the model group, all treatment groups improved the pathological state of the colonic mucosa to varying degrees and reduced serum levels of IL-6, TNF-α, and IL-2(P<0.01). Among these, the high-dose group of AMR-AFI significantly increased the intestinal propulsion rate and fecal moisture content of rats(P<0.05, P<0.01). Further transcriptomic analysis revealed that a total of 104 differentially expressed genes were identified from comparisons between the model group and the control group, as well as between the model group and the high-dose group of AMR-AFI. These genes were mainly enriched in pathways closely related to STC pathogenesis, such as arachidonic acid metabolism and aldosterone-regulated sodium reabsorption. 16S rRNA sequencing results indicated that AMR-AFI reversed the structural imbalance of the gut microbiota in model mice, increased species richness, downregulated the relative abundance of pro-inflammatory bacteria such as Parasutterella, and enriched beneficial and butyrate-producing bacteria, including Lachnospiraceae_NK4A136_group, Ruminococcaceae, and Lachnospiraceae. Spearman correlation analysis further showed that the beneficial bacteria enriched in the AMR-AFI group were negatively correlated with genes involved in the arachidonic acid metabolic pathway and positively correlated with genes in the aldosterone-regulated sodium reabsorption pathway. In contrast, pro-inflammatory bacteria in the model group exhibited the opposite correlation trends. ConclusionAMR-AFI can effectively exert synergistic therapeutic effects on STC by regulating intestinal microbiota, arachidonic acid-mediated inflammatory metabolism, and aldosterone-regulated water-salt balance pathways.
6.Current status and associated factors of sleep problems among preschool children in Hainan Province
Chinese Journal of School Health 2026;47(4):517-521
Objective:
To understand the current status and associated factors of sleep problems among preschool children in Hainan Province, so as to provide scientific evidence for improving sleep health in this population.
Methods:
From January 2021 to June 2022, a total of 4 105 preschool children aged 3-6 years from 62 kindergartens in Hainan Province were selected using stratified cluster random sampling method. Demographic information and lifestyle habits were collected through the Hainan Province Child Growth and Development Survey Questionnaire. The Children s Sleep Habits Questionnaire (CSHQ) was employed to assess sleep status. Unconditional binary Logistic regression model was applied to investigate the associated factors of sleep problems among preschool children.
Results:
The overall CSHQ score for children was 58.03±18.84, with 80.95% of preschool children exhibiting sleep related issues. The top three most prevalent sleep problem domains were bedtime resistance (72.42%), sleep anxiety ( 54.88 %), and parasomnias (38.86%). Logistic regression analysis revealed that higher family annual income ( OR=0.60, 95%CI = 0.45-0.79), higher maternal education level ( OR=0.53, 95%CI =0.32-0.89), regular or daily vitamin D supplementation ( OR=0.77, 95%CI =0.60-0.99), and fully self initiated eating behavior ( OR=0.71, 95%CI =0.59-0.85) were negatively related with children s sleep problems; in addition, screen exposure ( OR=1.27, 95%CI =1.06-1.51) and picky eating ( OR= 1.47 , 95%CI =1.21-1.78) were positively related to children s sleep problems (all P <0.05).
Conclusion
The high detection rate of sleep problems among preschool children in Hainan Province is multifactorially associated with family environment, dietary habits, and lifestyle behaviors.
7.Nutritional insufficiency and appropriate catch-up growth in extremely preterm infants within 24 months of corrected age: a retrospective cohort study
Xiaoli QU ; Chunjin PENG ; Yixue ZHAO ; Yulan YANG ; Na LUO ; Ping WANG
Chinese Journal of Pediatrics 2026;64(1):68-76
Objective:To assess the status of undernutrition and appropriate catch-up growth in extremely preterm infants within 24 months of corrected age (CA).Methods:A retrospective cohort study was conducted. A total of 422 extremely preterm infants born at Shenzhen Maternity and Child Healthcare Hospital, Women and Children's Medical Center, Southern Medical University from January 2017 to December 2022 and followed up until 24 months of CA were enrolled. The extremely preterm infants were grouped by gestational age at birth (<25, 25-26, 27 weeks), birth weight (<500, 500-749, 750-999,≥1 000 g), weight for gestational age (large for gestational age (LGA), appropriate for gestational age (AGA), small for gestational age (SGA)) and sex. Weight data within 24 months of CA were collected every 3 months. Nutritional insufficiency, growth rate, and achievement of adequate catch-up growth were analyzed during the period from 0 to 24 months of CA. Z-score method was used to analyze data. Fenton 2013 preterm growth charts (Fenton 2013) were used before 40 weeks of corrected gestational age, and World Health Organization child growth standards (2009) fitted Z-scores were applied from 40 weeks of CA. Changes in weight Z-scores of extremely preterm infants from 0 to 24 months of CA were observed and compared, the occurrence of moderate to severe malnutrition and growth retardation was determined, nutritional insufficiency was assessed, and growth rate as well as the achievement of appropriate catch-up growth were analyzed. The Lambda-mu-sigma method combined with the Z-score fitting model was used to fit and analyze the distribution characteristics of weight percentiles in extremely preterm infants. The Chi-square test was used to compare differences among groups.Results:A total of 422 extremely preterm infants were included, with a gestational age at birth of 26.3(25.4, 27.2) weeks and a birth weight of (880±177) g. Among them, 238 were males and 184 were females; 36 cases (8.5%) were LGA, and 16 cases (3.8%) were SGA. During follow-up within 24 month of CA, 89 cases (21.1%) developed moderate to severe malnutrition. When compared separately among different birth weight and gestational age at birth groups, there had both statistically differences in the incidence of moderate to severe malnutrition ( χ2=42.94 and 9.17, both P<0.05). The incidence was the highest in the birth weight of CA<500 g group and the <25 weeks gestational age at birth group, while it was the lowest in the birth weight of CA≥1 000 g group and the 27 weeks gestational age at birth group in their respective groups. Growth retardation occurred in 5.2% (22/422). However, there had statistically differences in the incidence of growth retardation among different birth weight and gestational age at birth groups, in each grouped time interval ( χ2=21.61 and 4.30, both P<0.05). The proportions of rapid growth were relatively high in the 0-3 months and 3-6 months of CA groups, which were 96 cases (27.4%) and 98 cases (26.6%), respectively. Overall, appropriate catch-up growth was achieved in 341 cases (80.8%) from 0 to 24 months of CA. There had statistically differences in the completion rate of appropriate catch-up growth among different birth weight and gestational age at birth groups ( χ2=23.65 and 7.08, both P<0.05). The completion rate was the highest in the birth weight of CA<500 g group and the <25 weeks of gestational age at birth group, while it was the lowest in the birth weight of CA≥1 000 g group and the 27 weeks of gestational age at birth group. Conclusions:The lower the birth weight and gestational age of extremely preterm infants, the higher the incidence of moderate to severe malnutrition and the lower the achievement rate of adequate catch-up growth within 24 months of CA. The period of 0-6 months of CA is the critical window for catch-up in extremely preterm infants.
8.Research progress on quality control methods for monitoring illicit drugs use in wastewater
Yue XIAO ; Shuai YUAN ; Ruxin LUO ; Ruiqin ZHU ; Bin DI ; Ping XIANG
Journal of China Pharmaceutical University 2025;56(2):139-147
The use of wastewater analysis, or wastewater-based epidemiology, to assess and monitor the situation of drug abuse is now widely used at home and abroad. However, there is currently a lack of effective evaluation methods and effective ways of comparison, supervision and standardization, which is not conducive to the analysis and comparisons of data in different countries and regions. Quality control techniques can control the laboratory's analytical errors, safeguard the consistency and comparability of identification conclusions, and promote the further improvement of the level and capacity of urban drug governance, thus playing significant roles. This paper provides an overview of sample collection, sample preservation and transportation, laboratory analysis, back-calculation of drug use and external laboratory quality control in the process of wastewater analysis, with a view to exploring more comprehensive scientific and objective methods and approaches suitable for examining and evaluating qualitative and quantitative analysis of drugs in wastewater among laboratories.
9.Association between urinary metal mixtures and mild cognitive impairment among elderly residents in Guangdong compounds
Chuijia KONG ; Ying ZHANG ; Zhenkun TAN ; Junjiao PING ; Haibo ZHANG ; Jiali LUO ; Xinxia LIU
Journal of Environmental and Occupational Medicine 2025;42(8):893-899
Background Environmental metal exposure is closely associated with the onset and progression of mild cognitive impairment (MCI) in the elderly. Effectively identifying hazardous metal exposure and assessing their interaction effects have significant public health implications. Objective To explore the relationship between urinary single metal and metal mixture exposure and MCI in elderly compound residents. Methods This study included 391 elderly individuals aged 60 and above from residential compounds in Zhongshan City, Guangdong Province. Concentrations of iron (Fe), copper (Cu), selenium (Se), arsenic (As), cadmium (Cd), manganese (Mn), chromium (Cr), nickel (Ni), vanadium (V), cobalt (Co), antimony (Sb), thallium (Tl), zinc (Zn), calcium (Ca), and magnesium (Mg) in urine were measured using inductively coupled plasma mass spectrometry. Cognitive function in the elderly was assessed using the Chinese version of the Mini-Mental State Examination (MMSE). Logistic regression was used to explore the relationship between single metal exposure level and MCI. LASSO regression and multi-metal logistic regression models were used to identify key metal ions associated with MCI. Bayesian kernel machine regression (BKMR) was employed to analyze the relationship between key metal ion mixtures and MCI, as well as the interactions between metals. Age, gender, education level, occupation, and body mass index were adjusted as covariates. Results A total of 78 among the 391 elderly individuals surveyed (19.94%) were diagnosed with MCI (MCI group), and the other 313 individuals were controls. The levels of Se, Cd, Mn, and As in the urine of the MCI group were significantly higher than those in the control group (P < 0.05). In the single-metal model, after adjusting for covariates and using the first quartile (Q1) of each metal concentration as the reference, the OR for MCI in the elderly in the Q4 group of Se was 2.190 (95%CI: 1.017, 4.716); for Cd, the OR was 2.345 (95%CI: 1.041, 5.283) in the Q3 group and 2.371 (95%CI: 1.043, 5.393) in the Q4 group; for Mn, the OR was 2.355 (95%CI: 1.038, 5.344) in the Q2 group; for As, the OR was 3.377 (95%CI: 1.442, 7.908) in the Q3 group and 2.886 (95%CI: 1.227, 6.788) in the Q4 group; for Sb, the OR was 2.779 (95%CI: 1.234, 6.257) in the Q2 group. When urinary metal concentrations were ln-transformed and included as continuous variables in the single-metal model, Cd concentration was positively correlated with MCI (OR=1.377; 95%CI: 1.008, 1.882; P=0.044). Cd, Se, Mg, Ca, Mn, As, Cr, Co, Tl, and Sb were selected by the LASSO regression model and included in the multi-metal model. In the multi-metal model, compared with Q1, the OR for MCI in the elderly was 0.395 (95%CI: 0.164, 0.953) in the Q2 group of Co and 0.390(95%CI: 0.167,0.911) in the Q3 group of Co; for Mn, the OR in the Q2 group was 2.636 (95%CI: 1.053, 6.596); for Sb, the OR in the Q2 group was 2.640 (95%CI: 1.047, 6.658). As continuous variables, Mg (OR=0.472; 95%CI: 0.248, 0.899; P=0.022) and Co (OR=0.857; 95%CI: 0.737, 0.996; P=0.044) concentrations were negatively correlated with MCI. The BKMR mixture analysis suggested that Mg and Co exhibited a synergistic negative correlation with MCI, while Mn and Sb exhibited a synergistic positive correlation with MCI. Mg and Co attenuated the positive correlation of Mn and Sb with MCI, whereas Mn weakened the protective effects of Mg and Co. Conclusion Elevated levels of Se, Cd, As, Mn, and Sb in urine may increase the risk of MCI in the elderly, while Mg and Co have protective effects. Potential synergistic or antagonistic interactions may be found among Mn, Sb, Mg, and Co, which should not be overlooked in terms of their impact on the cognitive function of the elderly.


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