BKMR

BKMR
  • 文章类型: Journal Article
    背景:中风是所有人类死亡的第二大原因,对人类健康构成严重威胁。环境暴露于金属混合物可能与中风的发生和发展有关,但是中国人口的证据还没有定论。
    目的:这项研究评估了中风风险与13种金属之间的关系方法:通过ICP-MS测量了100例中风患者和100例对照的全血样品中的金属浓度。使用三种统计模型研究了混合金属对卒中风险的累积影响。BKMR,WQS和QGC。
    结果:病例组的镁浓度较高,Mn,Zn,Se,Sn,和Pb高于对照组(p<0.05)。BKMR模型表明中风风险与接触混合金属之间存在相关性。WQS模型表明,Mg(27.2%),硒(25.1%)和锡(14.8%)与卒中风险呈正相关(OR=1.53;95%Cl:1.03-2.37,p=0.013)。QGC模型显示Mg(49.2%)与卒中风险呈正相关,而Ti(31.7%)与卒中风险呈负相关。
    结论:镁可能是混合金属暴露对卒中风险累积影响的最大因素,金属之间的相互作用需要更多的关注。这些发现可以为通过管理环境中的金属有效预防中风提供科学依据。
    BACKGROUND: Stroke is the second leading cause of death for all human beings and poses a serious threat to human health. Environmental exposure to a mixture of metals may be associated with the occurrence and development of stroke, but the evidence in the Chinese population is not yet conclusive.
    OBJECTIVE: This study evaluated the association between stroke risk and 13 metals METHODS: Metal concentrations in whole blood samples from 100 stroke cases and 100 controls were measured by ICP-MS. The cumulative impact of mixed metal on stroke risk was investigated by using three statistical models, BKMR, WQS and QGC.
    RESULTS: The case group had higher concentrations of Mg, Mn, Zn, Se, Sn, and Pb than the control group (p<0.05). BKMR model indicated a correlation between the risk of stroke and exposure to mixed metals. WQS model showed that Mg (27.2 %), Se (25.1 %) and Sn (14.8 %) were positively correlated with stroke risk (OR=1.53; 95 %Cl: 1.03-2.37, p=0.013). The QGC model showed that Mg (49.2 %) was positively correlated with stroke risk, while Ti (31.7 %) was negatively correlated with stroke risk.
    CONCLUSIONS: Mg may be the largest contributor to the cumulative effect of mixed metal exposure on stroke risk, and the interaction between metals requires more attention. These findings could provide scientific basis for effectively preventing stroke by managing metals in the environment.
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  • 文章类型: Journal Article
    已报道过和多氟烷基物质(PFAS)具有肝毒性作用。然而,目前尚不清楚它们是否与非酒精性脂肪性肝病(NAFLD)相关.这项巢式病例对照研究的重点是PFAS与NAFLD患病率之间的流行病学联系。我们从2014年至2019年的金昌队列人群中选择了476例新的NAFLD病例和952例年龄和性别匹配的对照。使用高效液相色谱-串联质谱法(HPLC-MS/MS)测量PFAS的血清浓度。仅纳入检出率≥90%的PFAS进行分析,其中包括PFPeA,PFOA,PFNA,PFHxS,全氟辛烷磺酸,和9Cl-PF3ONS。使用条件逻辑回归评估单次和共同暴露于PFAS与NAFLD发生之间的关系,分位数g计算(QgC),和贝叶斯核机回归(BKMR)模型。Logistic回归表明PFPeA,PFOA,和9Cl-PF3ONS在校正混杂因素后与NAFLD的发生率呈正相关,优势比(OR)和95%置信区间(CI)为3.13(95%CI:2.53,3.86),1.39(95%CI:1.12,1.73),和1.41(95%CI:1.20,1.66),分别。PFNA,PFHxS,和全氟辛烷磺酸与NAFLD的发病率呈非线性负相关,OR(95%CI)为0.53(0.46,0.62),0.83(0.73,0.95),和0.52(0.44,0.61),分别。QgC显示PFAS对NAFLD发病有显著的联合作用(OR:1.52,95%CI:1.24,1.88)。BKMR在PFAS混合物和NAFLD发生率之间显示出微弱的积极趋势。正相关主要由PFPeA和9Cl-PF3ONS驱动,而负相关主要受PFNA和PFOS的影响。BKMR模型还表明,PFOS和PFNA以及其他四种PFAS化合物之间存在相互作用。总之,我们的研究结果表明,个体和共同暴露于PFAS与NAFLD发病风险相关.
    Per- and poly-fluoroalkyl substances (PFAS) have been reported to have hepatotoxic effects. However, it is unclear whether they are linked to non-alcoholic fatty liver disease (NAFLD). This nested case-control study focused on the epidemiological links between PFAS and the prevalence of NAFLD. We selected 476 new cases of NAFLD and 952 age- and sex-matched controls from the Jinchang cohort population between 2014 and 2019. Serum concentrations of PFAS were measured using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Only PFAS with a detection rate of ≥90 % were included for analysis, which included PFPeA, PFOA, PFNA, PFHxS, PFOS, and 9Cl-PF3ONS. The relationship between single and co-exposure to PFAS and the occurrence of NAFLD was evaluated using conditional logistic regression, Quantile g-computation (QgC), and Bayesian kernel machine regression (BKMR) model. Logistic regression indicated that PFPeA, PFOA, and 9Cl-PF3ONS were positive correlation with the incidence of NAFLD after adjusting for confounders, with odds ratios (OR) and 95 % confidence interval (CI) of 3.13 (95 % CI: 2.53, 3.86), 1.39 (95 % CI: 1.12, 1.73), and 1.41 (95 % CI: 1.20, 1.66), respectively. PFNA, PFHxS, and PFOS were nonlinearly and negatively associated with the incidence of NAFLD, with OR (95 % CI) of 0.53 (0.46, 0.62), 0.83 (0.73, 0.95), and 0.52 (0.44, 0.61), respectively. QgC showed a significant joint effect of PFAS mixture on NAFLD onset (OR: 1.52, 95 % CI: 1.24, 1.88). BKMR showed a weak positive trend between PFAS mixtures and NAFLD incidence. Positive correlations were primarily driven by PFPeA and 9Cl-PF3ONS, while negative correlations were mainly influenced by PFNA and PFOS. The BKMR model also suggested that there was an interaction between PFOS and PFNA and other four PFAS compounds. In conclusion, our findings suggest that individual and co-exposure to PFAS is associated with a risk of NAFLD onset.
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  • 文章类型: Journal Article
    金属污染会导致女性生育能力下降,然而,以前的研究更多地集中在单一金属对生育能力的影响上。在这项研究中,我们基于嵌套病例对照样本评估了金属混合物对女性生育力的影响.通过电感耦合等离子体质谱仪(ICP-MS)测定了来自180名女性的22种金属元素的血浆水平。最小绝对收缩和选择操作者(LASSO)惩罚回归选择对临床后果影响最年夜的金属。使用Logistic回归分析单金属与生育力之间的相关性,同时使用贝叶斯核函数回归(BKMR)模型分析混合金属的影响。八种金属(钙(Ca),铬(Cr),钴(Co),铜(Cu),锌(Zn),铷(Rb),通过LASSO回归选择锶(Sr)和锆(Zr)用于后续分析。在调整协变量后,Logistic模型显示,Cu(比值比(OR):0.33,95%CI:0.13-0.84)和Co(OR:0.38,95%CI:0.15-0.94)导致生育率显着降低,并确定了锌对生育能力的保护作用(OR:2.96,95%CI:1.21-7.50)。趋势测试表明,Cr的增加,Cu,Rb水平与生育率降低有关。BKMR模型表明,Cr,Co,Cu,当控制其他金属的浓度时,Rb与肥力下降呈非线性关系,表明Cu和Cr可能对肥力产生影响。分析表明Cu,Cr,Co,Rb,和生育能力,锌与肥力呈正相关。此外,我们发现了Cu和Cr之间相互作用的证据。我们的发现需要进一步验证,并可能在未来确定新的机制。
    Metal pollution can cause a decline in female fertility, however, previous studies have focused more on the effect of a single metal on fertility. In this study, we evaluated the effect of metal mixtures on female fertility based on nested case-control samples. The plasma levels of 22 metal elements from 180 women were determined by an inductively coupled plasma mass spectrometer (ICP-MS). Minimum absolute contraction and selection operator (LASSO) penalty regression selected metals with the greatest influence on clinical outcome. Logistic regression was used to analyze the correlation between single metals and fertility while a Bayesian kernel function regression (BKMR) model was used to analyze the effect of mixed metals. Eight metals (Calcium (Ca), Chromium (Cr), Cobalt (Co), Copper (Cu), Zinc (Zn), Rubidium (Rb), Strontium (Sr) and Zirconium (Zr)) were selected by LASSO regression for subsequent analysis. After adjusting for covariates, the logistic model showed that Cu (Odds Ratio(OR):0.33, 95% CI: 0.13 - 0.84) and Co (OR:0.38, 95% CI: 0.15 -0.94) caused a significant reduction in fertility, and identified the protective effect of Zn (OR: 2.96, 95% CI:1.21 -7.50) on fertility. Trend tests showed that increased Cr, Cu, and Rb levels were associated with reduced fertility. The BKMR model showed that Cr, Co, Cu, and Rb had a nonlinear relationship with fertility decline when controlling for the concentrations of other metals and suggested that Cu and Cr might exert an influence on fertility. Analysis showed a negative correlation between Cu, Cr, Co, Rb, and fertility, and a positive correlation between Zn and fertility. Furthermore, we found evidence for the interaction between Cu and Cr. Our findings require further validation and may identify new mechanisms in the future.
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  • 文章类型: Journal Article
    先前关于金属与血脂异常之间关联的研究并不完全一致。很少有研究调查混合金属暴露与血脂异常之间的关系以及金属对社区老年人血脂异常的影响。评价社区老年人尿金属浓度与血脂异常风险的相关性及交互作用。我们设计了一项病例对照研究,以评估银川市老年人尿金属与血脂异常之间的相关性。13种金属的尿液水平,包括钙,钒,铁,钴,锌,铜,砷,硒,钼,镉,碲,和铊,采用电感耦合等离子体质谱(ICP-MS),采用血液生化分析仪对银川市4个不同地区的3384名老年人进行血脂检测。采用Logistic回归和限制性三次样条(RCS)探讨尿金属与血脂异常风险的相关性和剂量-反应关系。使用最小绝对收缩和选择算子(LASSO)回归来选择金属,然后使用加权分位数和(WQS)回归来探索混合金属中每种金属的重量。贝叶斯核机回归(BKMR)用于探讨金属与血脂异常风险的相互作用。(1)通过LASSO回归选择后,在多金属模型中,与最低四分位数相比,Fe的最高四分位数的调整OR(95CI)为0.47(0.37-0.60),锌1.43(1.13-1.83),1.46(1.11-1.92)硒为0.59(0.44-0.80),1.53(1.18-2.00)适用于Mo,Te为1.36(1.07-1.73)。(2)在WQS回归模型中,Fe和Mo在血脂异常的负效应和正效应中占最大权重,分别。(3)在BKMR模型中,Te和Se对血脂异常可能存在正相互作用。在混合金属中,Fe,As,Se,Mo,和Te与血脂异常的患病率有关,Fe和Mo贡献最大。Te和Se之间可能存在某些相互作用。
    Previous studies on the association between metals and dyslipidemia are not completely consistent. There are few studies investigating the relationship between mixed metal exposure and dyslipidemia as well as the effects of metals on dyslipidemia in community-dwelling elderly. To evaluate the correlations and interaction effect between the urinary concentrations of metals and the risk of dyslipidemia in community-dwelling elderly. We designed a case-control study to assess the correlation between urine metals and dyslipidemia in elderly people in the Yinchuan. The urinary levels of 13 metals, including calcium, vanadium, iron, cobalt, zinc, copper, arsenic, selenium, molybdenum, cadmium, tellurium, and thallium, were measured by inductively coupled plasma-mass spectrometry (ICP-MS), and the blood biochemical analyzer was used to measure the blood lipid levels of 3384 senior individuals from four different areas of Yinchuan city. Logistic regression and restricted cubic splines (RCS) were used to explore the correlation and dose-response relationship between urinary metals and the risk of dyslipidemia. Least absolute shrinkage and selection operator (LASSO) regression was used to select metals, and then weighted quantile sum (WQS) regression was used to explore the weight of each metal in mixed metals. Bayesian kernel machine regression (BKMR) was used to explore the interactions between metals on dyslipidemia risk. (1) After selection by LASSO regression, in the multi-metal model, compared with the lowest quartile, the adjusted ORs (95%CI) of the highest quartiles were 0.47 (0.37-0.60) for Fe, 1.43 (1.13-1.83) for Zn, 1.46 (1.11-1.92) for As, 0.59 (0.44-0.80) for Se, 1.53 (1.18-2.00) for Mo, and 1.36 (1.07-1.73) for Te. (2) In the WQS regression model, Fe and Mo accounted for the largest weight in the negative and positive effects of dyslipidemia, respectively. (3) In the BKMR model, there may be a positive interaction between Te and Se on dyslipidemia. Among the mixed metals, Fe, As, Se, Mo, and Te were associated with the prevalence of dyslipidemia, with Fe and Mo contributing the most. There may be certain interactions between Te and Se.
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  • 文章类型: Journal Article
    背景:全氟烷基和多氟烷基物质(PFAS)是持久性合成化学物质,常见于日常用品中。PFAS与破坏葡萄糖稳态有关,然而,它们是否与妊娠期糖尿病(GDM)风险相关尚无定论.我们研究了妊娠期两次测量的PFAS浓度与GDM风险的前瞻性关联。
    方法:在PETALS妊娠队列中,我们进行了一项巢式病例对照研究,包括41例GDM病例和87例对照.在妊娠早期和中期收集的血清中测量PFAS分析物(平均值[SD]:13.9[2.2]和20.2[2.2]孕周,分别),通过曲线下面积(AUC)计算累积暴露量,以整合PFAS浓度和暴露时间。个体调整加权非条件逻辑回归模型检查了7个与GDM风险相关的PFAS。使用错误发现率(FDR)校正P值。用贝叶斯核机回归(BKMR)分析混合模型。
    结果:PFDA,在妊娠早期,PFNA和PFOA分别与每四分位数范围(IQR)较高的GDM风险相关(OR[95%CI]:1.23[1.09,1.38]),1.40[1.24、1.58]),和1.15[1.04,1.27],分别),怀孕中期(1.28[1.15,1.43],1.16[1.05,1.28],和1.20[1.09,1.33],分别),和累积暴露(1.23[1.09,1.38],1.21[1.07,1.37],和1.19[1.09,1.31],分别)。妊娠中期和累积暴露的全氟辛烷磺酸与GDM风险增加相关(1.41[1.17,1.71]和1.33[1.06,1.58],分别)。妊娠早期PFUnDA与较低的GDM风险相关(0.79[0.64,0.98]),而妊娠中期水平与较高风险相关(1.49[1.18,1.89]).PFHxS与妊娠早期和中期GDM风险降低相关(0.48[0.38,0.60]和0.48[0.37,0.63],分别)和累积暴露(0.49[0.38,0.63])。PFPeA与GDM无关。在BKMR模型中观察到类似的结论;然而,这些模型的总体关联无统计学意义.
    结论:始终观察到与PFDA相关的GDM风险较高,PFNA,和PFOA暴露在妊娠早期和中期。结果应在更大的基于人群的队列中得到证实,育龄个体应潜在地避免PFAS的已知来源。
    BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are persistent synthetic chemicals and are commonly found in everyday items. PFAS have been linked to disrupting glucose homeostasis, however, whether they are associated with gestational diabetes mellitus (GDM) risk remains inconclusive. We examined prospective associations of PFAS concentrations measured twice in pregnancy with GDM risk.
    METHODS: In the PETALS pregnancy cohort, a nested case-control study which included 41 GDM cases and 87 controls was conducted. PFAS analytes were measured in blood serum collected in both early and mid-pregnancy (mean [SD]: 13.9 [2.2] and 20.2 [2.2] gestational weeks, respectively), with cumulative exposure calculated by the area-under-the-curve (AUC) to integrate both the PFAS concentration and the timing of the exposure. Individual adjusted weighted unconditional logistic regression models examined seven PFAS in association with GDM risk. P-values were corrected using the false-discovery-rate (FDR). Mixture models were analyzed with Bayesian kernel machine regression (BKMR).
    RESULTS: PFDA, PFNA and PFOA were individually associated with higher GDM risk per interquartile range (IQR) in early pregnancy (OR [95% CI]: 1.23 [1.09, 1.38]), 1.40 [1.24, 1.58]), and 1.15 [1.04, 1.27], respectively), mid-pregnancy (1.28 [1.15, 1.43], 1.16 [1.05, 1.28], and 1.20 [1.09, 1.33], respectively), and with cumulative exposure (1.23 [1.09, 1.38], 1.21 [1.07, 1.37], and 1.19 [1.09, 1.31], respectively). PFOS in mid-pregnancy and with cumulative exposure was associated with increased GDM risk (1.41 [1.17, 1.71] and 1.33 [1.06, 1.58], respectively). PFUnDA in early pregnancy was associated with lower GDM risk (0.79 [0.64, 0.98]), whereas mid-pregnancy levels were associated with higher risk (1.49 [1.18, 1.89]). PFHxS was associated with decreased GDM risk in early and mid-pregnancy (0.48 [0.38, 0.60] and 0.48 [0.37, 0.63], respectively) and with cumulative exposure (0.49 [0.38,0.63]). PFPeA was not associated with GDM. Similar conclusions were observed in BKMR models; however, overall associations in these models were not statistically significant.
    CONCLUSIONS: Higher risk of GDM was consistently observed in association with PFDA, PFNA, and PFOA exposure in both early and mid-pregnancy. Results should be corroborated in larger population-based cohorts and individuals of reproductive age should potentially avoid known sources of PFAS.
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