Reconstruction of "Public" Ethic in Health Care under the Strategy of Healthy China / 中国医学伦理学

The Healthy China Strategy launched by China is not only a practical policy, but also an ethical revolution in the field of health. Under the Healthy China Strategy, the health field and its sub-field health care are defined as areas with "public" ethics as the fundamental ethical principles. Reconstructing the health care with "public" ethics should get rid of the health care oriented market lead and technical lead, and return to its "public" nature. In terms of concrete realization, the state and the government need to be the power backing of the "public" ethics of the health and medical care, the reconstructing must be leaded by Chinese Communist Party, and the fundamental realization of the "public" ethics of the health and medical care should take the institutions as the fundamental approach.

Structure-based development of potent and selective type-II kinase inhibitors of RIPK1

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

Lead Toxicity in Children: Health Effects, Policies and Recommendations

Lead is a dangerous element that exists naturally in the Earth's crust. Any kind of lead causes a detrimental response in the human body. It is discharged into the environment during the manufacturing of batteries, foundries, ammunition, lead paint, water pipes, and other manufactured goods. It can enter the body through a variety of pathways, including those in the air, water, soil, food, and dust. Concern is raised since there is no amount of lead that is safe for the human body. The problem persists despite several prevention measures that the state and the federal governments have put in place. This review assesses the effects of lead exposure on children as well as suggested solutions to the issue.

Metal Exposure in Arica, Chile: Examining Toxic Elements / Análisis de exposición a metales en Arica, Chile: niveles de elementos tóxicos

BACKGROUND: Bioaccumulation of toxic metals in the population is associated with adverse health effects. Although some elements are essential for humans, high levels of exposure can be dangerous. OBJECTIVE: To describe the levels of Inorganic Arsenic (AsIn), Cadmium (Cd), Chromium (Cr), and Mercury (Hg) in urine, and Lead (Pb) in blood in the population of Arica, Chile. METHODOLOGY: Descriptive study. Beneficiaries of the Health Surveillance Program of Law 20.590 in sites of higher risk of exposure in the commune of Arica were considered eligible. The results of biological samples to measure their concentrations of AsIn, Cd, Cr, Hg in urine, and Pb in blood between August 2016 and May 2021 are described. RESULTS: 9520 samples from a population with a mean age of 40.5 years were studied. 4.21% of the adult population and 6.57% of the children had AsIn values above 35 μg/L, while at least 95 % of the total samples had levels below 33 μg/L. At least 90 % of the samples had Cd levels below 1.1 μg/L, and 8.44 % had Cd levels above 2 μg/L, higher in males (11.67%). There were no values above the reference in children. 99.77% and 99.33% had Cr and Pb values below the reference limit, respectively (using the lowest reference range established by Chile Ministry of Health (MINSAL) < 5 μg/L). Children did not present risk values for Cr, and 0.16% presented Pb concentrations between 5-10 μg/dL. All samples presented Hg concentrations below risk levels (< 10 μg/L). CONCLUSIONS: The results of this study suggest that a small percentage of the samples analyzed in the beneficiary population of Arica register metal concentration levels above national reference levels established by MINSAL, mainly AsIn, Cd, and Pb. It is essential to continue biomonitoring to reduce and prevent exposure to these metals, which can have harmful effects on human health.

ANTECEDENTES: La bioacumulación de metales en la población está asociada a efectos adversos y pueden ser peligrosos. OBJETIVO: Describir los niveles de Arsénico Inorgánico (AsIn), Cadmio (Cd), Cromo (Cr), Mercurio (Hg) y Plomo (Pb) en la población de Arica, Chile. MATERIALES Y MÉTODOS: Estudio descriptivo. Se incluyeron todas las personas beneficiarias del Programa de Vigilancia de Salud de la Ley 20.590 en sitios de riesgo de mayor exposición en la comuna de Arica entre agosto 2016 y mayo 2021. RESULTADOS: Se estudiaron 9.520 muestras provenientes de una población con una edad media de 40.5 años. 4.21% de la población adulta y el 6.57% de los niños presentaron valores de AsIn superiores a 35 μg/L y al menos el 95% de las muestras totales tenía niveles inferiores a 33 μg/L. Más del 90 % de las muestras tuvieron niveles de Cd menores a 1.1 μg/L y un 8.44% registró niveles de Cd superiores 2 μg/L. El 99.77% y 99.33% exhibieron valores normales de Cr y Pb, respectivamente. Todas las muestras presentaron concentraciones de Hg por debajo de los niveles de riesgo (< 10 μg/L). CONCLUSIONES: Los resultados sugieren que un porcentaje pequeño de la población de Arica registra niveles de concentración de metales por sobre niveles de referencia nacional establecidos por el Ministerio de Salud de Chile, principalmente de AsIn, Cd y Pb. Es importante continuar con la vigilancia para reducir y prevenir la exposición a estos metales, que pueden generar efectos nocivos en la salud humana.

Integridad Del ADN Espermático Y La Toxicidad Reproductiva Del Nitrato De Plomo En Ratones Machos Adultos

Introducción: La toxicidad del plomo se ha relacionado a diferentes patologías en humanos y varias evidencias sugieren una fuerte relación con el daño observado sobre la función reproductiva en humanos y roedores. Método: Se proporcionó a ratones una dosis única de nitrato de plomo (NP) (50mg/kg/pc), los cuales fueron eutanizados siete días postinyección con el objetivo de evaluar los espermatozoides que han salido de los túbulos seminíferos y están en tránsito por el epidídimo; además, se evaluó la fragmentación del ADN espermático mediante el ensayo tunel. Resultados: La disminución del peso corporal en ratones, tratados con NP (p 0,05); de igual manera, los valores fisiológicos como conteo y movilidad espermática no disminuyeron con el tratamiento (p > 0.05). El tránsito y maduración de los espermatozoides en el epidídimo no sería afectado por el NP, y al no observar aumento en la fragmentación del ADN espermático en el grupo tratado (p > 0,05), la protaminación espermática estaría cumpliendo su rol protector sobre el material genético murino, por lo que no hubo daños genotóxicos por el NP. Conclusión: La administración intraperitoneal de 50mg/kg/pc de NP, por siete días, no causa toxicidad sistémica ni efecto en la espermatogénesis en ratón.

Introduction: Lead toxicity has been linked to different diseases in humans and several evidences suggest a strong relationship with the observed damage on reproductive function in humans and rodents. Methods: Mice were given a single dose of lead nitrate (NP) (50mg/kg/bw), which were euthanized seven days post-injection with the aim of evaluating sperm to come out from the seminiferous tubules and are in transit through the epididymis. Also, the Tunel test was done to evaluate the sperm DNA fragmentation. Results: The decrease in body weight in mice treated with ln (p 0.05), in the same way physiological values such as sperm concentration and motility didn´t decrease with the treatment (p > 0.05). Transit and sperm maturation in the epididymis would not be affected by the ln, and because we did not observe increased sperm DNA fragmentation in the treated group (p > 0.05), sperm protamination would be fulfilling its protective role on murine genetic material avoiding genotoxic damage by ln. Conclusion: The intraperitoneal administration of 50mg/kg/pc of ln for seven days does not cause systemic toxicity or effect on spermatogenesis in mice.

Network-based Toxicogenomics Approach to Unraveling the Influence of Lead and Cadmium Mixture on the Development and Progression of Hypertension

Heavy metals, generally characterized by high densities and atomic weights, are ubiquitous in the environment and are a public health concern due to the several health issues they pose to humans. Of all heavy metals, lead and cadmium among others are known to be capable of inducing multiple health effects even at a low rate of exposure. Hypertension (HYP), a major cause of death and a risk factor for other cardiovascular diseases, is known to be caused by both lead and cadmium. While the mechanism underlying the development of HYP induced by independent exposure to lead and cadmium has been well studied, the mechanism underlying the induction and progression of HYP upon lead and cadmium co-exposure remains mildly explored. Hence, this study aimed to elucidate the mechanism using a toxicogenomic approach. The set of genes affected by both heavy metals was identified using the comparative toxicogenomics database (CTD) while HYP targets were retrieved from the Gene Cards database. The shared genes between the heavy metals and the disease were identified and subjected to further analysis. The results of our analysis revealed the signaling pathways that are dysregulated by lead and cadmium co-exposure while oxidative stress, inflammation, and endothelial dysfunction were revealed as processes pertinent to the induction and progression of HYP by lead and cadmium co-exposure. Biomarkers that could be used for prognosis evaluation were also identified. Ultimately, this study supports and advances the growing body of finding on the roles played by lead and cadmium co-exposure in inducing HYP.

Research progress of feature-based deep learning for predicting compound-protein interaction / 中国药科大学学报

@#The prediction of compound-protein interaction (CPI) is a critical technological tool for discovering lead compounds and drug repurposing during the process of drug development.In recent years, deep learning has been widely used in CPI research, which has accelerated the development of CPI prediction in drug discovery.This review focuses on feature-based CPI prediction models.First, we described the datasets, as well as typical feature representation methods commonly used for compounds and proteins in CPI prediction.Based on the critical problems in modeling, we discussed models for CPI prediction from two perspectives: multimodal features and attention mechanisms.Then, the performance of 12 selected models was evaluated on 3 benchmark datasets for both classification and regression tasks.Finally, the review summarizes the existing challenges in this field and prospects for future directions.We believe that this investigation will provide some reference and insight for further research on CPI prediction.

Research progress of the screening and generation of lead compounds based on artificial intelligence model / 中国药科大学学报

@#Excellent lead compounds have a profound influence on drug development and can improve the success rate of product launch. It is expensive and time-consuming to discover lead compounds by traditional methods, yet artificial intelligence (AI) can discover good lead compounds efficiently.This article systematically summarizes the research progress of obtaining lead compounds through the screening and generation models of AI, classifies different models according to the type of information input, focuses on drug repurposing by screening model and multi-objective drug design by generation model, and discusses the development prospect of AI in the research field of lead compounds, aiming to provide new research ideas for the application of AI in lead compounds.

Effects of lead exposure on development of heart and spine in zebrafish embryos / 环境与职业医学

Background Lead is widely distributed. Lead exposure interferes with early life development in zebrafish, but the mechanisms by which lead exposure affects skeletal development and cardiac development are not clear as yet. Objective To investigate the molecular mechanisms of bone development and cardiac development toxicity induced by lead acetate exposure. Methods Zebrafish embryos were exposed to different concentrations of lead acetate (0, 6, 12, 24, and 48 μmol·L−1) for 3 h post-fertilization (3 hpf) until 5 d post-fertilization (5 dpf). The malformation phenotypes of 5 dpf were counted, and the mRNA expressions of spinal development-related genes (bmp2b, bmp4, bmp9, runx2a, runx2b) and heart development-related genes (nkx2.5, myh6, myh7) were detected by quantitative PCR (qPCR). Expressions of genes of development-related regulatory pathways including Wnt/β-catenin pathway (wnt5a, wnt8a, wnt10a, β-catenin) and TGF-β pathway (tgf-β1, tgf-β2) as well as key molecule eph of Eph-Ephrin signaling were analyzed. Results At 5 dpf, the zebrafish in the lead acetate treated groups showed deformed phenotypes including spinal curvature and pericardial sac edema compared to the control group. In the lead acetate groups at 24 and 48 μmol·L−1, the spinal curvature deformity rates reached 26.47% and 71.52% (P<0.01) respectively. The qPCR results revealed that the expression levels of spinal development-related genes bmp2b, bmp4, bmp9, runx2a, and runx2b were downregulated in the 48 μmol·L−1 exposure group compared to the control group by 82.8%, 58.0%, 88.7%, 85.5%, and 69.2%, respectively (P<0.05 or P<0.01); the expression levels of heart development-related genes myh6, myh7, and nkx2.5 were down-regulated by 63.7%, 58.9%, and 55.2%, respectively (P<0.01); the expression levels of wnt8a and β-catenin in the Wnt/β-catenin pathway were down-regulated by 71.5% and 47.3% (P < 0.05 or P < 0.01), respectively; the expression level of tgf- β1 in the TGF-β pathway was down-regulated by 67.5% (P<0.01); the expression level of eph was down-regulated by 86.9% (P<0.01). Conclusion Lead acetate exerts developmental toxic effects on zebrafish heart and bone by down-regulating the expressions of genes related to spinal development and heart development, as well as inhibiting development-related Wnt/β-catenin and TGF-β pathways and Eph-Ephrin signaling, causing malformed phenotypes such as spinal curvature and pericardial sac edema.

Characteristics and source analysis of heavy metal pollution in environment in Guizhou Province / 环境与职业医学

Heavy metal pollution poses a serious threat to the environment and human health. Guizhou is a province with apparent regional features of heavy metal pollution such as lead, zinc, mercury, and arsenic in agriculture and mining soils. The coefficient of variation results showed that heavy metal pollution in the soils of agricultural planting areas and mine caves was closely related to human activities, and arsenic and zinc were greatly affected by human activities. In the water environment, mercury pollution presents in mine cave water samples, and cadmium, mercury, and lead pollution present in scenic park water samples. The results of single-factor pollution index showed that mercury in mine cave water samples and cadmium, mercury, and lead in scenic park water samples were graded as severe pollution. The results of Nemero pollution index showed the highest comprehensive pollution level of heavy metals was in scenic park water samples. In atmospheric dust fall, cadmium, mercury, lead are the most prominent pollution. Potential risks to ecological environment were identified for cadmium and mercury in all study areas and lead in other areas outside Wanshan. The results of integrated potential ecological risk index indicated a high-risk level of heavy metal pollution in atmospheric dust fall in the current study area. At present, the heavy metal pollutants in the environment of Guizhou are mainly originated from natural factors such as geological background content and soil-forming parent material, and human activities such as mining, metal smelting, agricultural activities, and sewage irrigation. The analysis showed serious heavy metal pollution in the environment of Guizhou, which caused harm to the local environment. It is crucial that environmental protection measures be taken during human activities.

ICP-MS establishes blood lead reference method expected to improve detection accuracy / 中华检验医学杂志

Lead poisoning severely threatens human health with its cumulation and durability in the body. The analysis of lead in blood is vital for screening, diagnosis, treatment, and prognostication of lead poisoning and for indirectly monitoring the level of lead in the environment. Although the detection programs are available throughout our country, the accuracy and comparability of the results cannot meet the expectation. A variety of factors can affect the accuracy of blood lead testing. To promote the application of blood lead analysis in clinical trials and reduce the bias of results, a better reference system for blood lead analysis should be established to evaluate the accuracy of traditional methods, promote the standardization of blood lead analysis and achieve accurate blood lead testing.

Research progress on the biological activity of pyrrole 1,2-α indole alkaloids / 中国基层医药

Pyrrole [1,2-α] indole is a novel fused heterocyclic skeleton, which is also the basic structural unit and synthetic intermediate of many natural active products and drugs. Pyrrole [1,2-α] indole heterocyclic derivatives have attracted much attention in organic synthesis and medicinal chemistry because of their extensive and marked biological activities. Plant extracts have always been an important source of active compounds. At present, the alkaloids based on the pyrrole [1,2-α] indole heterocyclic structure discovered and isolated from plant extracts include isatisine, isoborreverine, flinderoles, polyavolensin and yuremamine. This paper reviews the research progress on the biological activity of pyrrole [1,2-α] indole heterocyclic derivatives and has found that pyrrole [1,2-α] indole heterocyclic derivatives have a good development prospect in screening active compounds and developing candidate drugs.

The expression of adhesion molecules in Z310 cells induced by combined exposure to black carbon and lead / 中国职业医学

Objective: To investigate the effects of combined exposure to black carbon and lead on the expression of cell adhesion molecules and their regulating microRNAs (miRNAs) in the rat choroid plexus epithelial Z310 cells. Methods: i) Z310 cells were randomly divided into control group, black carbon exposure group, lead exposure group and combined exposure group. The lead exposure group and black carbon exposure group were treated with 10 μmol/L lead acetate and 10 mg/L black carbon, respectively, and the combined exposure group was treated with both in the above doses. After 12.0 hours, the expressions of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and mucosal vascular addressin cell adhesion molecule-1 (MAdCAM-1) in Z310 cells was detected by Western blotting. The expression of miR-326, miR-328-3p and miR-542-3p which regulated ICAM-1 was detected by real-time fluorescent quantitative polymerase chain reaction. ii) Z310 cells or Z310 cells transfected with miRNA-326 mimic were randomly divided into control group, miRNA-326 transfection control group, combined exposure group and miRNA-326 transfection combined exposure group. Cells in the two control groups were not treated. The two combined exposure groups were treated with 10 mg/L black carbon and 10 μmol/L lead acetate for 12.0 hours. The expression of ICAM-1 was detected by Western blotting. Results: i) The relative expression of ICAM-1, VCAM-1 and MAdCAM-1 in the cells of black carbon exposure group and ICAM-1 in the lead exposure group was higher than those in the control group (all P<0.05). The relative expression of ICAM-1 and MAdCAM-1 in the combined exposure group was higher than those in the other three groups (all P<0.05). The relative expression of VCAM-1 in cells of combined exposure group was higher than those in the control group and lead exposed group (all P<0.05). The relative expression of miR-326 in cells of the lead exposure group and black carbon exposure group was lower than those in the control group (all P<0.05). The relative expression of miR-326 in the combined exposure group was lower than that in the other three groups (all P<0.05). There was no significant difference between miR-328-3p and miR-542-3p in the four groups (all P>0.05). ii) The relative expression of ICAM-1 in cells of the miR-326 transfection control group cells was lower than that in the control group (P<0.05), while in the cells in the combined exposure and miRNA-326 transfection combined exposure group, it was higher than that in the control and miRNA-326 transfection control groups (all P<0.05), and lower in the miRNA-326 transfection combined exposure group than in the combined exposure group (P<0.05). Conclusion: Black carbon or lead exposure can upregulate the expression of ICAM-1, VCAM-1 and MAdCAM-1 in Z310 cells. Black carbon and lead combined exposure lead to a synergistic effect on upregulation of ICAM-1 and MAdCAM-1 expression, particularly ICAM-1. The combined exposure of black carbon and lead may upregulate the expression of ICAM-1 by downregulating the expression of miR-326.

Association between combined exposure of heavy metals and biomarkers of early renal damage in occupational population / 中国职业医学

Objective: To investigate the effect of combined exposure to four heavy metals (lead, cadmium, arsenic, mercury) on early kidney injury in occupational population. Methods: A total of 384 workers exposed to combined heavy metals in a non-ferrous metal smelting plant in Guangdong Province were selected as the research subjects using judgment sampling method. The levels of blood lead, urinary cadmium and urinary arsenic were detacted by inductively coupled plasma mass spectrometry, while urinary mercury levels were measured using cold atomic absorption spectroscopy (acidic tin chloride reduction method). The levels of biomarkers such as urinary β2-microglobulin (β2-MG), kidney injury molecule-1 (Kim-1) and neutrophil gelatinase-associated lipocalin (NGAL) were detected by enzyme-linked immunosorbent assay. Spearman correlation analysis, linear regression, weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) models were used to analyze the association between the exposure to the four heavy metals and early kidney injury biomarkers. Results: The median of blood lead, urinary cadmium, urinary arsenic and urinary mercury were 0.47 μmol/L and 4.450, 27.790 and 0.520 μg/gCr, respectively. The median of urinary β2-MG, Kim-1 and NGAL were 62.960, 1.130 and 18.150 μg/gCr, respectively. Spearman correlation analysis showed that urinary levels of β2-MG, Kim-1, and NGAL were weakly correlated with blood lead and urinary mercury levels (all P<0.01), but not correlated with urinary cadmium and urinary arsenic (all P>0.05). The results of multiple linear regression analysis showed that urinary mercury was positively correlated with urinary β2-MG, Kim-1 and NGAL (all P<0.01), urinary arsenic was positively correlated with urinary β2-MG level (P<0.01), and blood lead was negatively correlated with urinary β2-MG and Kim-1 (all P<0.05). The WQS regression analysis showed that the combined effect of the four heavy metals was positively correlated with urinary β2-MG, Kim-1 and NGAL (all P<0.01), with mercury having the highest impact and lead the lowest. BKMR model analysis showed the increasing trend in urinary β2-MG, Kim-1 and NGAL with the increasing levels of the combined exposure to the four heavy metals. Urinary β2-MG, Kim-1 and NGAL decreased when urinary mercury level increased from the 25th percentile to the 75th percentile and the other metals were correspondingly fixed at a certain level. When the blood exposure levels of other metals remained at the corresponding median levels, urinary β2-MG, Kim-1 and NGAL levels were positively correlated with urinary arsenic level, but no significant linear dose-response relationship was observed with the other three heavy metals. Conclusion: sLead, arsenic, and mercury are independently associated with early kidney injury biomarkers in occupational population from non-ferrous metal smelting. The four heavy metals had positive combined effects on urinary β2-MG, Kim-1 and NGAL, with mercury having the greatest impact.

Association between exposure to lead, cadmium, and arsenic and blood pressure in workers from a smelter / 环境与职业医学

Background Occupational exposure to lead, cadmium, or arsenic is a potential risk factor for blood pressure elevation. Current studies mainly focus on the relationship between a single metal and blood pressure. However, mixed metal exposure often exists in the actual working environment, and the interactive effects of polymetallic interactions on blood pressure and the dose-effect relationship remain unclear yet. Objective To explore the influence proportion of occupational exposure to lead, cadmium, or arsenic on blood pressure and their interactive effects. Methods From January to December 2021, workers from a smelter in southern China were selected. Demographic characteristics, height, weight, and blood pressure of workers were collected through questionnaire and physical examination. At the same time, their urine samples were collected and the levels of urinary lead, urinary cadmium, and urinary arsenic were detected by inductively coupled plasma mass spectrometry, and corrected by urinary creatinine (Cr). Linear regression and logistic regression were used to analyze the relationship between urinary lead, cadmium, and arsenic and blood pressure. Weighted quantile sum (WQS) regression was applied to evaluate the dose-effect relationship between urinary lead, cadmium, and arsenic exposures and blood pressure and the effect weight of each metal on blood pressure. Generalized linear regression and additive/multiplicative scaling were used to identify interactive effects of the three metals on blood pressure. Results A total of 1075 workers were included in this study, with a mean age of (44.68±5.11) years and mean working seniority of (24.66±5.23) years. There were 891 males (88.9%) and 184 were females (17.1%); 24.7% workers were drinkers and 45.7% workers were smokers; 302 workers (28.1%) reported hypertension and 37 of them were taking antihypertensive drugs. The P50 (P25, P75) levels of urinary lead, urinary cadmium, and urinary arsenic were 6.11 (3.71, 11.08), 3.88 (2.68, 5.44), and 26.04 (19.99, 35.11) μg·g−1, respectively. After adjusting for gender, age, working seniority, body mass index, smoking, drinking, and the usage of antihypertensive drugs, systolic and diastolic blood pressure increased by 0.772 and 0.418 mmHg respectively for 10% increase in lead, cadmium, and arsenic mixed exposure. Urinary cadmium, among the three single exposures, had the greatest effect on systolic and diastolic blood pressure, weight (w)=0.523 and 0.551 respectively. The interaction of urinary lead and urinary cadmium was positively correlated with the occurrence of hypertension, multiplicative interaction OR (ORint)=1.88 (95%CI: 1.09, 3.63), attributable proportion due to interaction (AP)=1.19 (95%CI: 0.40, 8.18). Conclusion This study shows that mixed exposure to lead, cadmium, and arsenic has a positive relationship with blood pressure, in which cadmium plays a major role. Co-exposure to lead and cadmium has a positive interactive effect on hypertension development and systolic blood pressure elevation.

Impact of lead oxide nanoparticle exposure on the polarization of microglia cells in mouse hippocampus / 中国职业医学

Objective To investigate the effect of exposure to lead oxide nanoparticles (PbO NPs) on the polarization of microglia in mouse hippocampus. Methods i) Specific pathogen-free male C57 mice were randomly divided into control group, low-, medium- and high-dose groups, with 10 mice in each group. Mice in these three dose groups were intraperitoneally injected with PbO NPs suspension at doses of 5, 10 and 20 mg/kg per day, respectively, and mice in the control group were intraperitoneally injected with the same volume of 0.9% sodium chloride solution, five days per week for four weeks. ii) BV-2 cells were treated with PbO NPs at doses of 0.0, 2.5, 5.0 and 10.0 mg/L for 24 hours. iii) BV-2 cells were randomly divided into control group, PbO NPs group and triggering receptor expressed on myeloid cells 2 (TREM2) high expression + PbO NPs group. The cells in the control group received no treatment. The cells in PbO NPs group were exposed to 10.0 mg/L PbO NPs suspension for 24 hours. Cells in TREM2 high expression + PbO NPs group were transfected with Trem2 high expression plasmid, and then exposed to 10.0 mg/L PbO NPs suspension for 24 hours. iv) The mRNA expression of M1 markers ［nitric oxide synthase (iNos), cyclooxygenase 2 (Cox2), chemokine receptor 7 (Ccr7)］, M2 markers ［arginin-1 (Arg-1), transforming growth factor-β (Tgf-β), chemokine receptor 2 (Ccr2)］ and Trem2 of microglia was detected by real-time fluorescent quantitative polymerase chain reaction. The protein expression of iNOS, ARG-1 and TREM2 was detected by Western blotting. Results i) During the experiment, there was no significant difference in body weight of mice among these four groups (P>0.05). The relative expression of Cox2 and Ccr7 mRNA in the hippocampus of the mice increased in the low-dose group and the iNos, Cox2 and Ccr7 mRNA increased in the medium- and high-dose groups, compared with the control group (all P<0.05). The relative mRNA expression of Tgf-β in the hippocampus of the mice of low-dose group and Arg-1, Tgf-β and Ccr2 in the medium- and high-dose groups was decreased compared with the control group (all P<0.05). The mRNA relative expression of iNos, Cox2 and Ccr7 was increased (all P<0.05), while the mRNA relative expression of Arg-1, Tgf-β and Ccr2 was decreased (all P<0.05) in the hippocampus of the mice of high-dose group compared with the low-dose group. The relative expression of Trem2 mRNA and TREM2 protein in the hippocampus of mice of the medium- and high-dose groups was lower than those in the control group (all P<0.05). The relative expression of Trem2 mRNA and TREM2 protein in the hippocampus of mice of the high dose group was lower than those in the low- and the medium-dose groups (all P<0.05). With the increase of PbO NPs exposure dose, the relative expression of iNOS protein in hippocampus tissues of mice increased (P<0.01), and the relative expression of ARG-1 protein decreased (P<0.01). ii) With the increase of PbO NPs exposure dose, the relative expression of iNOS protein increased (P<0.01), and the relative expression of ARG-1 protein decreased (P<0.01) in BV-2 cells. The relative expression of iNOS protein in BV-2 cells of PbO NPs group and TREM2 high expression + PbO NPs group was increased (all P<0.05), and the relative expression of ARG-1 protein decreased (all P<0.05) compared with the control group. The relative expression of iNOS protein decreased (P<0.05), and the relative expression of ARG-1 protein increased (P<0.05) in BV-2 cells of TREM2 high expression + PbO NPs group compared with the PbO NPs group. Conclusion Exposure to PbO NPs could increase the M1 polarization and decrease the M2 polarization of microglia, with a dose-effect relationship. The M1 polarization of microglia decreased and M2 polarization increased after overexpression of Trem2 gene. The regulation of microglia polarization by TREM2 may be involved in the neurotoxic effects of PbO NPs.

Inhibition of lead-induced hepatic inflammation by inhibiting neutrophil granule protein in mice / 中国职业医学

Objective To explore the beneficial effects and mechanisms of neutrophil elastase (NE) and myeloperoxidase (MPO) on lead-induced hepatic inflammation in mice. Methods The specific pathogen free male C57BL/6 mice were randomly divided into four groups： control group, lead-exposed group, NE inhibitor group, and MPO inhibitor group, with three mice in each group. The mice in lead-exposed group, NE inhibitor group, and MPO inhibitor group were intraperitoneally injected with a dose of 10 mg/kg body mass of lead acetate solution, while the mice of control group received an equal volume of 0.9% saline three times per week for four weeks. In the last seven days, mice in both inhibitor groups were intraperitoneally injected with a dose of 40 mg/kg NE inhibitor sivelestat sodium or MPO inhibitor 4-aminobenzoic acid hydrazide (4-ABAH) once per day. Mouse body weight and liver histopathological changes were observed. The mRNA expression of genes associated with inflammation, such as tumor necrosis factor-α (Tnfa), interleukin-1β (Il1b), interleukin-6 (Il6), and nucleotide-binding oligomerization domain-like receptor protein 3(Nlrp3), apoptosis-associated speck-like protein (Asc) and cysteinyl aspartate specific proteinase (Caspase1) in the mouse liver tissues was detected by real-time quantitative polymerase chain reaction. The protein expression of NLRP3, ASC, and CASPASE-1 was detected using Western blotting. Results The activities of mice in all four groups were generally normal, and there was no significant difference in body weight (P>0.05). The results of hematoxylin-eosin staining showed that the cell size of hepatocytes varied in the lead-exposed mice, with indistinct cell boundaries, indicating early inflammatory responses in liver tissues. After intervention with NE or MPO inhibitors, the early inflammatory responses improved in the liver tissues of the mice in both inhibitor groups, with a better improvement observed in MPO inhibitor group compared with the NE inhibitor group. The mRNA expression of Tnfa, Il1b, Il6, Nlrp3, Asc, and Caspase1, as well as the protein expression of ASC, and CASPASE-1 in the livers of mice in the lead-exposed group was higher compared with those in the control group (all P<0.05). Compared with the lead-exposed group, the relative mRNA expression of Tnfa, Il1b, Il6, Nlrp3 and Asc was decreased in the liver tissues of mice in the NE inhibitor group (all P<0.05), while the relative expression of mRNA of Tnfa, Il1b, Il6, Caspase1 and the protein expression of ASC and CASPASE-1 were decreased in the liver tissues of mice in the MPO inhibitor group (all P<0.05). Conclusion Lead induce hepatic inflammation in mice by activating NLRP3 inflammasome. The inhibition of NE or MPO improve the lead-induced hepatic inflammatory responses in mice by alleviating NLRP3 inflammasome activation.

Effects of lead and manganese combined exposure on neurodevelopmental toxicity and JNK expression in zebrafish / 环境与职业医学

Background Lead and manganese are heavy metal pollutants widely existing in the environment, which can accumulate in the human body through the food chain, exert neurotoxicity, and cause neurodegenerative disorders. Especially in early childhood, the developing blood-brain barrier and nervous system are highly susceptible to environmental chemical pollutants. Most of the previous studies focused on the toxic effects of single heavy metal such as lead or manganese, while the studies on combined toxic effect are still scarce, and involved mechanisms are still unclear. c-Jun N-terminal kinase (JNK) is involved in neuronal development and regeneration, and some studies have found that JNK is involved in lead or manganese induced neurotoxicity. Its role in the toxicity of combined lead and manganese is unknown. Objective To understand the neurodevelopmental toxicity mechanism and to observe changes of JNK expression in zebrafish induced by combined lead and manganese exposure at environmentlly low concentrations. Methods Zebrafish embryos within 2 h post fertilization (hpf) were divided into four groups: control group, lead exposure group (0.1 mg·L−1 lead acetate), manganese exposure group (0.3 mg·L−1 manganous chloride), and lead-manganese combined exposure group (0.1 mg·L−1 lead acetate +0.3 mg·L−1 manganous chloride) and exposed to lead or/and manganese at designed levels for 7 d. Spontaneous movements and motor locomotion were observed, and mortality rate were calculated. The changes of JNK mRNA expression in zebrafish were evaluated. Results The experimental results showed that no significant effect of lead or/and manganese on spontaneous movements and mortality rate was found in zebrafish compared with the control group (P＞0.05). The results of locomotion analysis showed that compared with the control group, the activity counts and activity distance of zebrafish in the manganese exposure group were slightly increased (P＜0.01); the activity counts and activity distance of zebrafish in the lead exposure group were reduced by 50% and those in the lead-manganese exposure group were reduced by 80% (P＜0.01). Compared with the lead exposure group, the activity counts and activity distance of zebrafish in the lead-manganese combined exposure group decreased significantly by 60% (P＜0.05). The real-time quantitative PCR results showed that the JNK mRNA expression level was significantly increased in the lead-manganese combined exposure group compared with the control group(P＜0.01). Conclusion Lead exposure combined with manganese exposure at environmentlly low concentration can induce neurodevelopmental toxicity to zebrafish. JNK may be involved in neurodevelopmental toxicity induced by the combined exposure to lead and manganese.

Monte Carlo design and preliminary test of X-ray protective rubber / 中国辐射卫生

@#<b>Objective</b> To complete the Monte Carlo design and preliminary test of X-ray protective rubber. <b>Methods</b> According to the characteristics of X-ray energy spectrum for interventional therapy, the shielding effects of lead rubber, tungsten and bismuth composite rubber, and gadolinium and bismuth composite rubber samples were calculated by Monte Carlo simulation. The variation law of lead equivalent of lead-free rubber and lead rubber with X-ray peak tube voltage was obtained through actual measurement. <b>Results</b> Within the peak tube voltage range of 60-110 kV, lead-free rubber effectively replaced lead rubber. <b>Conclusion</b> The shielding and attenuation effect of the existing lead-free protective rubber on low-energy stray X-rays is better than that of lead rubber. Considering the inherent defects of lead rubber, flexible X-ray protective materials with thermoplastic elastomer as filler will have broad development prospects.

Risk assessment of dietary lead exposure in Shanghai residents over 15 years old / 上海预防医学

ObjectiveTo investigate the risk of dietary lead exposure in residents aged 15 years and above in Shanghai. MethodsBased on the dietary consumption survey of residents aged 15 years and above in spring 2012 and the monitoring data of food lead contamination in Shanghai from 2020 to 2021， the dietary exposure level was assessed using the point assessment method and compared with the provisional weekly tolerable intake （PTWI） to assess the exposure risk. ResultsThe overall detection rate of lead in 9 commonly consumed food categories by residents in Shanghai was 56.82%， with a total excess rate of 0.23%. The average weekly dietary lead exposure （by body weight） of residents was 2.979 4 μg·kg⁻¹. The top three dietary lead contributing factors were vegetables （30.69%）， cereals （28.88%）， and aquatic products （11.12%）. The average weekly dietary lead exposure （by body weight） of residents in urban， suburban， and rural areas were 3.282 5， 2.979 5 and 2.478 0 μg·kg⁻¹， respectively. The food with the highest contribution rate of dietary lead exposure in these regions was vegetables， with contribution rates of 33.65%， 29.69%， and 25.22%， respectively. The average weekly dietary lead exposure （by body weight） of male and female residents was 3.077 7 and 2.881 5 μg·kg⁻¹， respectively， with vegetables being the main source of dietary lead， contributing 30.03% and 31.39%， respectively. The average weekly dietary lead exposure （by body weight） of residents aged 15‒， 45‒， and ≥60 years old was 3.084 2，3.009 9 and 2.874 4 μg·kg⁻¹， respectively. The food with the highest contribution rate of dietary lead exposure in these groups was vegetables， contributing 27.12%， 32.10%， and 32.26%， respectively. ConclusionThe dietary lead exposure of Shanghai residents aged 15 years and above is at an acceptable level， and the vegetables， cereals， and aquatic products with high contribution rates need to be supervised more closely.