Study on the mechanism of astragalus glycyrrhiza decoction regulating SIRT1 / FOXO1 pathway to prevent QT interval prolongation induced by arsenic trioxide based on metabolomics / 中国临床药理学与治疗学

AIM: To explore the protective effect of astragalus glycyrrhiza decoction (AGD) on arsenic trioxide (ATO)-induced QT interval prolongation and its mechanism based on metabonomics. METHODS: The model of ATO-induced QT interval prolongation in rats was established, and ECG, blood routine, and metabonomics were detected, and the key targets were collected combined with network pharmacology. The possible candidate genes and pathways for the protective effect of AGD were screened by GO and KEGG enrichment analysis and then verified by experiments in vitro. RESULTS: AGD could significantly alleviate the ATO-induced QT interval of SD rats. GO enrichment analysis was mainly related to inflammatory response, reactive oxygen species, oxidative stress, inner cell vesicles, folds, inner cell vesicles, SMAD binding, R-SMAD binding, and signal receptor activator activity. KEGG analysis showed that it was mainly concentrated in the PI3K-Akt signal pathway, lipid and arteriosclerosis, FOXO signal pathway, TNF signal pathway, HIF-1, and other signal pathways. Through the H9c2 cell model in vitro, it was verified that AGD could reverse the expression of SIRT1 and FOXO1 proteins. CONCLUSION: AGD may improve the ATO-induced QT interval prolongation and reduce the cardiotoxicity of ATO by regulating the SIRT1 / FOXO1 signal pathway.

Research progress on roles and mechanisms of DNA hydroxymethylation in health effects induced by arsenic exposure / 环境与职业医学

Arsenic, a naturally occurring metal-like chemical element, is one of the 10 chemicals of major public concerns listed by the World Health Organization as harmful to the environment and human health. It can enter the human body through breathing, intaking food, drinking water, skin exposure, and other ways, and long-term exposure to arsenic can cause cancer of multiple organs and impaired function of multiple systems. Epigenetic mechanisms play an important role in arsenic-induced health effects, and research suggested that the carcinogenicity of arsenic may be associated with epigenetic changes. Previous studies focused on the effects of arsenic on DNA methylation modification. In recent years, research showed that 5-hydroxymethylcytosine (5-hmC), an intermediate of active demethylation of DNA, can act as a sensitive epigenetic mark and play a crucial role as a "bridge" between arsenic exposure and health effects. Based on the latest research progress on the role of DNA hydroxymethylation in the health effects associated with arsenic exposure, this article briefly described the relationship between the health effects of arsenic exposure and DNA hydroxymethylation, summarized the possible mechanisms of DNA hydroxymethylation in the health effects associated with arsenic exposure, and provided a scientific basis for preventing and treating the health effects associated with arsenic exposure.

Correlation Between Expression of HIF-1α and Prognosis of Arsenic-containing Chinese Herbal Compound in Treatment of Myelodysplastic Syndrome / 中国实验方剂学杂志

ObjectiveMyelodysplastic syndromes （MDS） is a group of clonal hematopoietic stem cell disorders，and this study aims to investigate the expression of hypoxia-inducible factor-1α（HIF-1α） in the bone marrow cells of patients with MDS and its correlation with the clinical features of MDS，the therapeutic efficacy of arsenic-containing Chineseherbal compound，and the survival prognosis. MethodAccording to the inclusion and exclusion criteria，27 MDS patients treated with arsenic-containing Chinese herbal compound in the Department of Hematology，Xiyuan Hospital，China Academy of Chinese Medical Sciences from January 2022 to September 2022 were included，and their bone marrow samples were collected by myelotomy. HIF-1α expression level in bone marrow cells was detected by real-time polymerase chain reaction （PCR） to analyze its correlation with clinical features，and logistic and Cox regression was used to analyze the risk factors affecting the efficacy and prognostic survival of MDS patients. ResultThe HIF-1α mRNA expression level was lower in bone marrow cells of MDS patients than in healthy subjects. HIF-1α was positively correlated with the degree of myelodysplasia（r=0.384，P<0.05） and bone marrow granulocytic system%（G%）（r=0.560，P<0.01）. Logistic regression showed that HIF-1α was a risk factor for the prognosis in the follow-up of the efficacy of treatment（P<0.05）and Cox regression showed that HIF-1α was an independent factor affecting the survival prognosis of MDS patients ［odds ratio（OR）=398.968，95% confidence interval（CI）（1.281，116 858.743），P<0.05］. ConclusionThe level of HIF-1α expression in bone marrow cells of MDS patients was closely related to the degree of clinical myelodysplasia and G%，and HIF-1α was a risk factor for the efficacy for and survival prognosis of MDS patients.

Contenido de arsénico, conocimiento y actitud en el consumo del agua de pozo familiar / Arsenic content, knowledge and attitude in family well water consumption / Conteúdo de arsênico, conhecimento e atitude em relação ao consumo doméstico de água de poço

La contaminación por arsénico del agua de consumo humano, es un problema de salud pública, porque produce diversas enfermedades cancerígenas y de piel. Objetivo. Determinar niveles de arsénico en el agua de pozos, y evaluar el grado de conocimiento y actitud sobre el consumo del agua familiar. Materiales y métodos. Se utilizaron 96 muestras del agua de pozos del distrito de Juliaca. Las cuales se analizaron en laboratorio de Unidad de Servicios de Análisis Químicos de la Facultad de Química - Universidad Nacional Mayor de San Marcos-Lima, mediante la técnica Espectrofotometría de Absorción Atómica con Horno de Grafito. Los datos de arsénico fueron procesados estadísticamente mediante el diseño completamente al azar. Asimismo, la descripción del conocimiento y actitud del consumo de agua familiar se realizó aplicando la técnica de la encuesta y el instrumento fue un cuestionario de 11 ítems para la variable conocimiento y 7 para la variable actitud, con respuestas de alto, medio y bajo para conocimiento y buena, regular y mala calificadas con escala de Likert. Resultados. La concentración promedio fue 0.031 mg de As/L de agua y entre zonas hubo semejanza (p>0.05). En el grado de conocimiento sobre contaminación con arsénico en el agua de consumo humano respondieron el 40.81 % con calificación alta y el 59.19% están entre medio y bajo; en actitud, la calificación buena obtuvo menos del 50 % de encuestados y el resto están entre regular y mala. Conclusiones. El contenido arsenical en el agua de pozos supera los límites máximos permisibles según Organización Mundial de Salud y más del 50% se exponen al agua contaminada.

Arsenic contamination of drinking water is a public health problem, because it causes various carcinogenic and skin diseases. Objective. To determine arsenic levels in well water, and to evaluate the degree of knowledge and attitude about family water consumption. Materials and methods. Ninety-six samples of well water from the district of Juliaca were used. These were analyzed in the laboratory of the Chemical Analysis Services Unit of the Faculty of Chemistry - Universidad Nacional Mayor de San Marcos-Lima, using the technique Atomic Absorption Spectrophotometry with Graphite Furnace. The arsenic data were statistically processed using a completely randomized design. Likewise, the description of the knowledge and attitude of family water consumption was carried out by applying the survey technique and the instrument was a questionnaire of 11 items for the knowledge variable and 7 for the attitude variable, with answers of high, medium and low for knowledge and good, regular and bad rated with a Likert scale. Results. The average concentration was 0.031 mg As/L water and there was similarity between zones (p>0.05). In the degree of knowledge about arsenic contamination in drinking water, 40.81% responded with high qualification and 59.19% were between medium and low; in attitude, the good qualification obtained less than 50% of respondents and the rest were between regular and bad. Conclusions. The arsenic content in well water exceeds the maximum permissible limits according to the World Health Organization and more than 50% are exposed to contaminated water.

A contaminação da água potável por arsênico é um problema de saúde pública, pois causa várias doenças de pele e carcinogênicas. Objetivo. Determinar os níveis de arsênico na água de poço e avaliar o grau de conhecimento e atitude em relação ao consumo doméstico de água. Materiais e métodos. Foram utilizadas 96 amostras de água de poço do distrito de Juliaca. Elas foram analisadas no laboratório da Unidade de Serviços de Análises Químicas da Faculdade de Química da Universidade Nacional Mayor de San Marcos-Lima, usando a técnica de Espectrofotometria de Absorção Atômica com Forno de Grafite. Os dados sobre arsênico foram processados estatisticamente usando um desenho completamente aleatório. Da mesma forma, a descrição do conhecimento e da atitude do consumo familiar de água foi realizada aplicando a técnica de pesquisa e o instrumento foi um questionário de 11 itens para a variável conhecimento e 7 para a variável atitude, com respostas de alto, médio e baixo para o conhecimento e classificado como bom, regular e ruim em uma escala Likert. Resultados. A concentração média foi de 0,031 mg As/L de água e houve similaridade entre as zonas (p>0,05). Quanto ao grau de conhecimento sobre a contaminação por arsênico na água potável, 40,81% responderam com uma pontuação alta e 59,19% ficaram entre médio e baixo; quanto à atitude, a pontuação boa foi obtida por menos de 50% dos entrevistados e o restante ficou entre regular e ruim. Conclusões. O teor de arsênico na água de poço excede os limites máximos permitidos de acordo com a Organização Mundial da Saúde e mais de 50% estão expostos à água contaminada.

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.

Arsenicals Review: Poison vis-a-vis Medicine

Arsenic tops the list of priority list of hazardous substances 2022. People are frequently exposed to the environmental pollutant metalloid arsenic through their food, water, air, and soil. Arsenic is famous for its toxic effects. However, arsenicals have recently gained attention due to promising clinical trials for the treatment of acute myeloid leukemia. Presently numerous studies on arsenic's anticancer effects have been done. So a review was conducted on the use of arsenicals as poison and medicine. Arsenical was used as a powerful medicine in the BC era. But arsenical became famous as "the King's Poison" and "the Poison of the King" due to its use as poison. But the development of Marsh’s Test in the 18th century led to a decrease in the use of arsenicals as poison. In the 18th century, arsenicals were used as medicine to treat a variety of diseases such as fever, rheumatism, psoriasis, and syphilis. The development of antibiotics, new, safer chemotherapeutic agents, and radiotherapy halted its use as medicine. The dose and form of arsenicals make them medicine or poison. Many literary works reveal that arsenic's journey as “medicine” and “poison” is still ongoing in the twenty-first century.

Arsenic Trioxide: Pharmacological Applications / Trióxido de Arsénico: Aplicaciones farmacológicas

Background: Arsenic trioxide is a chemical compound that has been used as a treatment for various diseases. Despite being potentially toxic, this compound has been used as a therapy to treat Acute Myeloid Leukemia and is being investigated as a possible treatment for different types of cancer. Objectives: The present review aims to describe the use and studies reported in the literature of Arsenic Trioxide as a possible therapeutic agent for Acute Myeloid Leukemia, Acute Promyelocytic Leukemia, Chronic Myeloid Leukemia, Multiple Myeloma, Myelodysplastic Syndrome, Hepatocellular Carcinoma, Lung Cancer, Neuroblastoma, Breast Cancer, Aplastic Hepatitis C, and HIV-1. Methods: A systematic review was conducted using databases (Elsevier, Google Scholar, PubMed) to compile documents published before December 2023. Results:Multiple pharmacological applications of arsenic trioxide have been reported to treat acute and chronic myeloid leukemia. Arsenic trioxide has been shown to inhibit angiogenesis, which helps treat multiple myeloma. Several studies have shown and suggested the effectiveness of arsenic trioxide as a treatment of hepatocellular carcinoma, lung cancer, neuroblastoma, prostate cancer, breast cancer, aplastic anemia, hepatitis C, and HIV-1. Conclusion: Despite potentially toxic effects, Arsenic compounds are therapeutic agents for multiple diseases, from syphilis to cancer. In recent years, more efficient ways have been investigated to deliver and find the specific dose to treat the disease, causing the fewest possible adverse effects.

Antecedentes: El trióxido de arsénico es un compuesto químico que se ha utilizado como tratamiento de diversas enfermedades. A pesar de ser potencialmente tóxico, este compuesto se ha utilizado como terapia para tratar la leucemia mieloide aguda y se está investigando como posible tratamiento para diferentes tipos de cáncer. Objetivos: La presente revisión pretende describir el uso del trióxido de arsénico como posible agente terapéutico para la leucemia mieloide aguda, la leucemia promielocítica aguda, la leucemia mieloide crónica, el mieloma múltiple, el síndrome mielodisplásico, el carcinoma hepatocelular, el cáncer de pulmón, el neuroblastoma, el cáncer de mama, la hepatitis C aplásica y el VIH-1. Métodos: Se realizó una revisión sistemática utilizando bases de datos (Elsevier, Google Scholar, PubMed) para recopilar documentos publicados antes de diciembre de 2023. Resultados: Se ha informado de múltiples aplicaciones farmacológicas del trióxido de arsénico para tratar la leucemia mieloide aguda y la leucemia mieloide crónica. Se ha demostrado que el trióxido de arsénico inhibe la angiogénesis, lo que resulta útil para el tratamiento del mieloma múltiple. Varios estudios han demostrado y sugerido la eficacia del trióxido de arsénico como tratamiento del carcinoma hepatocelular, el cáncer de pulmón, el neuroblastoma, el cáncer de próstata, el cáncer de mama, la anemia aplásica, la hepatitis C y el VIH-1. Conclusión: A pesar de tener un efecto potencialmente tóxico, los compuestos de arsénico destacan como agentes terapéuticos para múltiples enfermedades, desde la sífilis hasta el cáncer. En los últimos años, se han investigado formas más eficientes de administrar y encontrar la dosis específica para poder tratar la enfermedad, causando los menores efectos adversos posibles.

Effects of arsenic exposure on E2 and TRH and their receptor mRNA expressions in rats / 环境与职业医学

Background Arsenic can enter the hypothalamus to induce estrogen effect and interfere with the function of the neuroendocrine system. The thyroid endocrine system (hypothalamic-pituitary-thyroid axis) is one of the main endocrine systems, and the mechanism of arsenic-induced thyroid endocrine toxicity is still unclear. Objective To investigate the effects of different arsenic exposure levels on estradiol (E2), hypothalamic thyrotropin-releasing hormone (TRH), and their receptor (ERα, ERβ, and TRHR) mRNAs in rats and the possible hypothalamic toxic pathway and mechanism. Methods Seventy Wister rats were randomly divided a control group (sterile water); low-, medium-, and high-dose arsenic exposure groups [0.8, 4.0, and 20.0 mg·kg−1 sodium arsenite (NaAsO2)]; estrogen receptor inhibitor (ICI182780) intervention + low-, medium-, and high-dose arsenic exposure groups; with 10 animals in each group, half male and half female. Rats in the arsenic exposure groups were exposed to NaAsO2 by drinking water for 19 weeks, and rats in the intervention groups were injected with 0.5 mg·kg−1 ICI182780 via tail vein at week 9, 3 times a week. The levels of E2 and TRH in serum of rats were detected by ELISA. The expression levels of estrogen receptor α (ERα), estrogen receptor β (ERβ), and TRH receptor (TRHR) mRNAs in hypothalamus of rats were detected by real-time PCR (RT-PCR). Results (1) E2 and its receptor mRNA: Compared with the control group, the serum E2 level of female rats was increased in the low-dose and the medium-dose arsenic exposure groups (P<0.05), and the serum E2 level of male rats was increased in the low-dose, the medium-dose, and the high-dose arsenic exposure groups (P<0.05), and the change of female E2 was greater than that of male rats. Compared with the control group, the relative expression levels of ERα mRNA and ERβ mRNA in female rats were increased in the low-dose, the medium-dose, and the high-dose arsenic exposure groups (P<0.05), so were the relative expression levels of ERα mRNA in male rats (P<0.05). (2) TRH and its receptor mRNA: Compared with the control group, the serum TRH level of female rats was increased in the high-dose arsenic group (P<0.05), the relative expression level of TRHR mRNA was increased in the low-dose, the medium-dose, and the high-dose arsenic exposure groups (P<0.05). Results (1) and results (2) suggested that females were more likely than males to have abnormal changes in E2, TRH, and related receptor genes after arsenic exposure. (3) Compared with female rats in the medium-high dose arsenic exposure group, the expressions of TRH and TRHR induced by arsenic exposure were inhibited after the intervention of ICI182780 (P<0.05), suggesting that arsenic in the hypothalamus may have toxic effects on TRH and TRHR by inducing estrogen-like effects. Conclusion Arsenic exposure can induce estrogen-like effects in the hypothalamus, interfere with thyroid function, and show dose-dependent and sex differences. E2 and TRH and their receptors may be the toxic pathway of arsenic-related estrogen-like effect.

Osteonecrosis of the jaw induced by arsenic trioxide therapy in acute promyelocytic leukemia patient: a case report and literature review / 口腔疾病防治

Objective @#To investigate the etiology, clinical manifestations, treatment and prevention of jaw necrosis caused by arsenic trioxide to provide a reference for clinical diagnosis and treatment. @*Methods@#To analyze the clinical data and related literature of patients with jaw necrosis caused by acute promyelocytic leukemia treated with arsenic trioxide@*Results@#We report a case of jaw necrosis caused by the use of arsenic trioxide (10 mg once a day for one month) during the treatment of acute promyelocytic leukemia. About 20 days after treatment, the patient developed right maxillary pain accompanied by gingival redness and swelling and mucosal ulcer, 14-17 teeth had buccal and palatal alveolar bone exposed, gingival mucosa was missing, gingival tissue was damaged to the bottom of vestibular groove, and palatal soft tissue was damaged to 5-8 mm of palatal suture. Due to the unstable condition of acute promyelocytic leukemia, the patient was given conservative treatment such as oral vitamin and Kangfuxin liquid gargle to keep his mouth clean. Drug induced jaw necrosis reported in the literature can be caused by bisphosphonates. Arsenic trioxide can also cause local jaw necrosis. Clinically, it is often manifested as long-term wound nonunion, pus, alveolar bone or jaw bone exposure, dead bone formation, accompanied by pain, loose teeth, facial swelling and other symptoms. Anti inflammation, debridement and surgical removal of dead bone are commonly used treatment methods.@*Conclusion @# In clinical practice, we should be alert to drug-induced jaw necrosis and strengthen prevention.

Arsenic speciation and valence / 中国中药杂志

As arsenic widely exists in nature and has been used in the pharmaceutical preparations, the traditional Chinese medicine(TCM) with arsenic include realgar(As_2S_2 or As_4S_4), orpiment(As_2S_3), and white arsenic(As_2O_3). Among the above representative medicine, the TCM compound formulas with realgar are utilized extensively. Just in Chinese Pharmacopoeia(2020 edition), there are 37 Chinese patent medicines including realgar. The traditional element analysis focuses on the detection of the total amount of elements, which neglects the study on the speciation and valence of elements. The activity, toxicity, bioavailability, and metabolic pathways of arsenic in vivo are closely related to the existence of its form, and different forms of arsenic have different effects on organisms. Therefore, the study on the speciation and valence of arsenic is of great importance for arsenic-containing TCMs and their compound formulas. This paper reviewed four aspects of the speciation and valence of arsenic, including property, absorption and metabolism, toxicity, and analytical assay.

Mechanism of Learning and Memory Impairment in Rats Exposed to Arsenic and/or Fluoride Based on Microbiome and Metabolome / 生物医学与环境科学（英文）

OBJECTIVE@#Arsenic (As) and fluoride (F) are two of the most common elements contaminating groundwater resources. A growing number of studies have found that As and F can cause neurotoxicity in infants and children, leading to cognitive, learning, and memory impairments. However, early biomarkers of learning and memory impairment induced by As and/or F remain unclear. In the present study, the mechanisms by which As and/or F cause learning memory impairment are explored at the multi-omics level (microbiome and metabolome).@*METHODS@#We stablished an SD rats model exposed to arsenic and/or fluoride from intrauterine to adult period.@*RESULTS@#Arsenic and/fluoride exposed groups showed reduced neurobehavioral performance and lesions in the hippocampal CA1 region. 16S rRNA gene sequencing revealed that As and/or F exposure significantly altered the composition and diversity of the gut microbiome，featuring the Lachnospiraceae_NK4A136_group, Ruminococcus_1, Prevotellaceae_NK3B31_group, [Eubacterium]_xylanophilum_group. Metabolome analysis showed that As and/or F-induced learning and memory impairment may be related to tryptophan, lipoic acid, glutamate, gamma-aminobutyric acidergic (GABAergic) synapse, and arachidonic acid (AA) metabolism. The gut microbiota, metabolites, and learning memory indicators were significantly correlated.@*CONCLUSION@#Learning memory impairment triggered by As and/or F exposure may be mediated by different gut microbes and their associated metabolites.

Antagonism of Lentinan on sodium arsenite induced hepatotoxicity in mice / 公共卫生与预防医学

Objective To explore the intervention effects of lentinan on sodium arsenite (SA) induced hepatotoxicity in mice. Methods Healthy male C57BL/6 mice were used as experimental subjects and divided into 4 groups, namely control group, SA treatment group, lentinan intervention + SA exposure group, and lentinan intervention control group. The mice were given oral SA (10.0 mg/kg.bw, once every other day) for 14 days, and then the liver tissues and serum samples were collected. Hematoxylin-eosin (HE) was used to evaluate the characteristics of hepatic pathological damage. Enzyme-linked immunosorbent assay (ELISA), Flow Cytometry (FC) and Western-blotting (WB) were used to detect the levels of hepatic function, oxidative stress, CD4+ type 17 helper T cells (Th17), and inflammatory cytokines. Results Compared with the control group, the arsenic exposure group showed obvious hepatic pathological injury and increased levels of serum ALT (8.78±0.76 vs 5.47±0.49) and AST (12.42±1.87 vs 7.14±0.57), FC experiments showed that the Th17 content in liver tissues increased (67.70±4.94 vs 7.36±1.50), and ELISA showed that the antioxidant GSH content decreased (593.40±23.25 vs 730.94±30.81), and the levels of MDA (74.56±7.63 vs 49.90±6.42) and proinflammatory cytokines IL-17A (162.48±10.75 vs 118.53±7.92) and IL-1β (512.50±24.78 vs 462.48±22.15) increased in hepatic tissues (P < 0.05). Compared with the arsenic exposure group, the lentinan showed a significant antagonistic effect after intervention (P < 0.05). Compared to SA exposure group, WB analysis showed that compared with the arsenic exposure group, the expression levels of IL-17A (0.47±0.08 vs 0.89±0.11) and NLRP3 inflammasome (0.80±0.09 vs 1.09±0.16) in the liver tissues of the lentinan intervention group were significantly decreased (P < 0.05). Conclusion Lentinan alleviates SA-induced hepatic injury in mice, which may be mediated through the inhibition of Th17-IL-17A inflammatory signaling.

Epidemiological research progress in the effects of metal exposure on kidney / 中南大学学报(医学版)

Chronic kidney disease (CKD) is suffered progressive loss of kidney function lasting more than 3 months and is classified according to the degree of kidney damage (level of proteinuria) and the decreased glomerular filtration rate (GFR). The most severe form of CKD is end-stage renal disease. The prevalence of CKD is high with fast growth rate and the disease burden has become increasingly serious. CKD has become an important public health problem threatening human health. The etiology of CKD is complex. In addition to genetic factors, environmental factors are an important cause of CKD. With the development of industrialization, environmental metal pollution has become increasingly severe, and its impact on human health has received widespread attention. A large number of studies have shown that metals such as lead, cadmium, and arsenic can accumulate in the kidney, which can cause damage to the structure and function of the kidney, and play an important role in the development of CKD. Therefore, summarizing the epidemiological research progress in the relationship between arsenic, cadmium, lead, and other metal exposures and kidney diseases can provide new ideas for the prevention and control of kidney diseases caused by metal exposure.

Arsenic Content in Cordyceps： A Review / 中国实验方剂学杂志

Cordyceps， a unique precious Chinese herbal medicine in China， has the effects of tonifying the kidney and lungs， stopping bleeding， and resolving phlegm. It has definite clinical effects on diabetes， respiratory diseases （such as chronic obstructive pulmonary disease）， chronic kidney diseases， slow arrhythmia， and hyperlipidemia. We searched China National Knowledge Infrastructure （CNKI）， Wanfang Data， VIP， SpringerLink （Biomedical Sciences）， Embase， Proquest （Life Sciences）， PubMed， Cochrane Library， and SinoMed for the research on the arsenic content in Cordyceps. According to statistical analysis， arsenic in Cordyceps mainly exists in the non-toxic or low-toxic form. The arsenic-containing compounds in Cordyceps may be an arsenic-sugar compound with anticancer effect. The inorganic arsenic content in Cordyceps is lower than the arsenic standard stipulated by the State Food and Drug Administration. It remains uncertain whether different measurement methods can affect the results. The total arsenic content varies in Cordyceps from different producing areas， and the general rule of total arsenic content in Cordyceps produced in different provinces， districts， and counties cannot be obtained from the results of the existing studies. The arsenic content in Cordyceps is mainly concentrated in the insect part， which is significantly different from that in stroma， and no arsenic is detected in the mycelia. The soil arsenic content in the growing areas is generally high， which may be a main reason for the high arsenic content in Cordyceps. As a valuable medicinal material for tonifying and nourishing， Cordyceps still plays an irreplaceable role in disease prevention， health care， chronic disease management， and rehabilitation.

A survey on the prevalence and associated factors of arsenic poisoning-related skin lesions in an arsenic tailing area in Hunan Province, China / 中华皮肤科杂志

Objective:To investigate epidemiological characteristics of arsenic poisoning-related skin lesions in an arsenic tailing area in Hunan Province.Methods:A cross-sectional study was conducted. From October 2016 to January 2017, all residents aged over 18 years (except pregnant women) were enrolled from 3 villages in Baiyun Town, Shimen County, Hunan Province by using a cluster-sampling method. Demographic information was collected through a face-to-face questionnaire interview. All residents received skin examination performed by professional dermatologists, and blood, urine, and hair samples were collected for the measurement of arsenic levels. Non-conditional logistic regression analysis was performed to analyze factors associated with arsenic poisoning-related skin lesions.Results:A total of 1 092 eligible residents in the arsenic tailing area were recruited in this study, and 756 (69.2%, 95% CI: 66.5%, 72.0%) presented with arsenic poisoning-related skin lesions, including hyperkeratosis, hypo- or hyper-pigmentation. The median ( Q1, Q3) arsenic levels were 0.31 (0.14, 0.74) μg/g in hair samples ( n = 1 079), 0.84 (0.67, 1.10) μg/L in blood samples ( n =1 091), and 60.31 (41.71, 91.52) μg/L in urine samples ( n =1 092). Multivariable analysis showed that the occurrence of arsenic poisoning-related skin lesions was associated with age, residential location, and occupational arsenic exposure history, but was not associated with gender, ethnicity, education levels, migration history, arsenic levels in hair, blood, or urine. Compared with the group aged 18 - 39 years, the group aged 40 - 59 years and the group aged over 60 years showed significantly higher risks of arsenic poisoning-related skin lesions (adjusted OR = 11.34, 95% CI: 5.98, 21.50, P < 0.001; adjusted OR = 71.82, 95% CI: 35.81, 144.05, P < 0.001, respectively). Compared with the residents in the Wangyangqiao village, residents in the Heshan village and Huangchang village showed significantly higher risks of arsenic poisoning-related skin lesions (adjusted OR = 2.89, 95% CI: 2.05, 4.08, P < 0.001; adjusted OR = 4.13, 95% CI: 1.94, 8.78, P < 0.001, respectively). The risk of arsenic poisoning-related skin lesions was significantly higher in residents with occupational exposure history than in those without (adjusted OR = 1.99, 95% CI: 1.04, 3.83, P = 0.039) . Conclusion:Nearly 70% of the residents presented with arsenic poisoning-related skin lesions in an arsenic tailing area in Hunan Province, and the duration and previous degree of arsenic exposure were associated with the risk of arsenic poisoning-related skin lesions.

A method of automatic determination of salt iodine by iodine element detector / 中华地方病学杂志

Objective:To establish a method for automatic determination of iodine level in salt by arsenic-cerium catalytic spectrophotometry using an iodine element detector (hereinafter referred to as this method), and to provide reference for in-depth study of salt iodine detection technology.Methods:This method was used to determine the iodine level in salt, and the linear range, detection limit, precision, and accuracy (determination of salt iodine standard substance GBW10006y and GBW10007y, and addition recovery experiment) of this method were determined. The iodine level of 35 salt samples was determined by this method and redox titration method recommended by the national standard, and the results were compared.Results:This method had a good linear relationship within the range of 50 - 600 μg/L standard curve, the absolute value of the correlation coefficients was > 0.999 0, and the detection limit was 5.0 mg/kg. The relative standard deviation of iodine concentration in salt samples with low, medium and high iodine concentrations were all < 6.0%. The determination results of salt iodine standard substance GBW10006y and GBW10007y were within the given value ranges; three iodine concentrations (6.0, 10.0 and 30.0 mg/kg) were added to the salt samples, with an average recovery rate of 96.7% to 105.0%, and a total average recovery rate of 100.9%. The method comparison experiment showed that there was no statistically significant difference between the salt iodine determination results of this method and the redox titration method ( t = - 1.54, P = 0.132). Conclusion:This method has the advantages of high accuracy, good precision and wide linear range in determining salt iodine, and is suitable for the detection of large quantities of samples in salt iodine monitoring.

A preliminary study on the effect of arsenic exposure on necroptosis of mouse myocardial cells / 中华地方病学杂志

Objective:To study the effects of arsenic exposure on necroptosis pathway and inflammatory response of mouse myocardial cells.Methods:Sixty male C57BL/6J mice were randomly divided into control group (group C) and low, medium, and high dose arsenic exposure groups (groups L, M, H) based on body weight using a random number table method. Each group had 15 mice, and they drank 0.00, 0.15, 1.50, and 15.00 mg/L arsenic trioxide (As 2O 3) solution prepared with deionized water. The exposure period was 12 weeks. Hematoxylin-eosin (HE) staining and Masson trichrome staining of paraffin-embedded heart tissues were used to observe the histopathology changes of the heart. Transmission electron microscopy (TEM) was used to evaluate the ultrastructural changes of myocardial cells. The quantitative real-time PCR (qRT-PCR) was used to detect the mRNA expression of inflammatory genes [tumor necrosis factor (TNF)-α and interleukin(IL)-6] and the genes involved in necroptosis pathway [receptor-interacting protein (RIP) 1, RIP3 and mixed-lineage kinase domain-like protein (MLKL)]. Protein expressions of RIP1 and RIP3 in the heart were assessed by western blotting. Results:Histopathological examination results showed there were myocardial necrosis, inflammatory cells infiltration and fibroblasts hyperplasia and other changes in groups M and H. TEM analysis revealed marked ultrastructural changes in groups M and H, including fractured myofibril, fractured Z lines of sarcomere, and swollen mitochondria with fractured cristae. Compared with group C (1.00 ± 0.00), the mRNA expression of RIP1 in group H was significantly up-regulated (1.41 ± 0.06, P < 0.05); the mRNA expressions of RIP3 (1.29 ± 0.14, 1.56 ± 0.08), MLKL (1.23 ± 0.05, 1.36 ± 0.07), TNF-α (2.20 ± 0.10, 2.23 ± 0.18) and IL-6 (1.87 ± 0.16, 1.63 ± 0.15) were significantly up-regulated in groups M and H ( P < 0.05). The protein expressions of RIP1 (0.43 ± 0.04, 0.50 ± 0.04) and RIP3 (0.68 ± 0.02, 0.84 ± 0.05) in groups M and H were higher than those in group C (0.25 ± 0.01, 0.45 ± 0.04, P < 0.05). Conclusion:Subchronic arsenic exposure induces histopathological changes such as myocardial necrosis and fibrosis in mice, inducing necroptosis and inflammatory reactions in myocardial cells.

Distribution characteristics and health risk assessment of elements in drinking water from endemic fluorosis areas with water improvement in Xi'an City / 中华地方病学杂志

Objective:To analyze the types and distribution characteristics of elements in drinking water from endemic fluorosis areas with water improvement in Xi'an City, understand the relationship between fluoride and various elements, and conduct health risk assessment on potential high-risk elements.Methods:From May to June 2017, one endemic fluorosis area with water improvement (Gaoling District, Huyi District, Lintong District) was selected according to the northeast, the southwest and the due east directions of Xi'an City as the survey area. Sixteen endemic fluorosis villages were selected from each endemic area, and 2 water samples were collected from each endemic village to detect fluoride and 12 elements such as chromium, manganese, ferrum, copper, zinc, arsenic, selenium, molybdenum, cadmium, antimony, barium, and lead. Hygienic evaluation was conducted according to national standards, and the potential high-risk elements (arsenic, molybdenum) were assessed for health risk through the health risk assessment model recommended by the National Environmental Protection Agency of the United States.Results:The water samples from the endemic fluorosis areas in Xi'an City mainly contained seven elements: barium, ferrum, molybdenum, arsenic, zinc, manganese, and chromium. The content of copper and selenium was relatively low, while the content of cadmium, antimony, and lead was extremely low. The fluoride content in water samples from Gaoling District and Lintong District was relatively high, and the fluorine, arsenic, molybdenum elements was pairwise positively correlated ( P < 0.05). The molybdenum element in water samples from Lintong District exceeded 9.38% (3/32). The fluoride in the water samples of Huyi District was relatively low, and the arsenic, molybdenum elements was positively correlated ( r = 0.84, P < 0.001), and the arsenic element exceeded the standard by 25.00% (8/32). The main health risk of drinking water in endemic fluorosis areas with water improvement in Xi'an City was arsenic exposure, with children at a higher risk than adults, and the areas of Huyi District, Lintong District, and Gaoling District declined, the risk of cancer (CR) of Gaoling District was < 10 -4 and hazard quotient (HQ) was < 1. However, in the areas of Huyi District and Lintong District (except HQ of adults), there was a higher risk (CR > 10 -4, HQ > 1). Children in one endemic fluorosis village in Lintong District had a higher non carcinogenic risk of molybdenum (HQ > 1). Conclusions:The drinking water in endemic fluorosis areas with water improvement in Xi'an City mainly contains 7 elements, especially arsenic and molybdenum, which need to be regularly monitored. Some areas have high health risks of arsenic in water, and monitoring, management, and related epidemiological investigations need to be strengthened. At the same time, it is necessary to actively monitor other toxic and harmful substances that may be introduced during the water improvement process to prevent the occurrence of secondary health problems.

Research progress on the ferroptosis role in liver injury induced by inorganic arsenic / 中华地方病学杂志

Inorganic arsenic (iAs) is a common carcinogen that exists in the environment. Liver, as the main target organ of arsenic metabolism, long-term exposure to iAs can ultimately lead to carcinogenesis through two stages: liver fibrosis and cirrhosis. Ferroptosis is a type of programmed cell death caused by the accumulation of iron dependent lipid peroxides that affects the normal function of mitochondria. It has been found that ferroptosis occurs during liver fibrosis. Liver fibrosis caused by iAs has been a global health problem for a long time, but so far there is no effective treatment. The discovery of ferroptosis provides a new way to solve this problem. Therefore, this article will review the research progress of the mechanism of liver injury caused by iAs and ferroptosis.

Investigation results of drinking-water-borne endemic arsenic poisoning in Henan Province in 2019 / 中华地方病学杂志

Objective:To learn about the progress of prevention and control of drinking-water-borne endemic arsenic poisoning in Henan Province, and provide scientific basis for achieving the goal of eliminating high arsenic hazards as scheduled.Methods:From July to August 2019, in accordance with the requirements of the National Monitoring Program for Drinking-water-borne Endemic Arsenic Poisoning, a general survey was carried out in 26 high-arsenic villages in 6 counties of Henan Province to investigate the water improvement situation and the operation of water improvement projects, and the arsenic content in drinking water of households was measured, meanwhile, the arsenic poisoning status of permanent residents in high-arsenic villages was investigated.Results:All 26 villages with high arsenic content in the province had undergone water improvement, with a water improvement rate of 100.00%. A total of 18 water improvement projects were investigated in 26 high-arsenic villages, all of which were operating normally. Twenty-six water samples were collected, and the arsenic content in the household water was < 0.01 mg/L, which met the sanitary standards for drinking water. No patient of endemic arsenic poisoning was found during the survey.Conclusion:In Henan Province, the drinking-water-borne endemic arsenic poisoning has been effectively controlled, and the prevention and control achievements should continue to be consolidated in the future.