Realgar is a mineral traditional medicine with definite efficacy. The function of realgar is detoxicating, insecticiding, eliminating dampness and phlegm, etc. It is widely applied in clinical practice by compatibility medicines. However, the safety and scientificalness of clinical application are questioned because of the toxic effect caused by arsenic compounds. At present, there are still many problems in the research of realgar, which are mainly manifested in three areas: the expression of main components and effective substances are inconsistent; the anti-tumor mechanism is difficult to explain at the molecular level; the mechanism of compatibility is not clear. As a result, realgar and realgar-containing Chinese patent medicines are frequently prohibited from entering the international market, and the reputation of traditional Chinese medicine is also damaged. This paper would analyze the research status of realgar at home and abroad as well as its problems from its main components, effective substances, anti-tumor mechanism and compatibility mechanism. In view of these difficulties, quantum chemical calculation method is proposed to solve them, so as to make up for the shortcomings and limitations of experimental technology and experimental conditions, reduce the cost of realgar research and improve research efficiency. Moreover, it provides inspiration for research of other mineral medicine.
Arsenicals ; pharmacology ; Medicine, Chinese Traditional ; Minerals ; Sulfides ; pharmacology

This study aims to establish a method for the determination of As B,As C,DMA,As( Ⅲ),MMA and As( Ⅴ) by using HPLC-ICP-MS. A Dioncx Ion PacTMAS7( 4 mm×250 mm) column was used for the HPLC-ICP-MS method. The mobile phase was 100 mmol·L-1 ammonium carbonate-1. 5 mmol·L-1 ammonium dibasic phosphate( gradient elution) at a flow rate of 1 m L·min-1. The injection volume was 10 μL. The linear relationships of As B,As C,DMA,As( Ⅲ),MMA,As( Ⅴ) were good with the concentration of10-500 μg·L-1. The average recovery rates( n = 6) were 105. 7%,100. 5%,102. 9%,105. 7%,100. 2%,92. 69%. The RSD were0. 50%,2. 4%,0. 93%,1. 3%,0. 89%,1. 5%. The precision and repeatability of this method were good. In this study,six forms of arsenic were separated effectively by this method. With methodological validation and sample determination,this method can be used to determine the morphological valence of arsenic in content determination.
Arsenic/analysis* ; Arsenicals/analysis* ; Chromatography, High Pressure Liquid ; Mass Spectrometry

Arsenic is a common metal-like element. Drinking arsenic-containing water and occupational exposure to arsenic are the main ways exposure to arsenic for population. Long-term exposure to arsenic can cause various organs dysfunction and cancer. After entering the body, inorganic arsenic is mainly methylated into monomethyl arsenic and dimethyl arsenic in the liver. Only a small part of inorganic arsenic is metabolized in the kidneys and lungs, and finally the metabolites of arsenic are excreted in the urine. understanding the biological characteristics of arsenic absorption, metabolism, and distribution in the body and formulating biological indicators related to occupational exposure to arsenic and can provide a scientific basis for the prevention and treatment of arsenic-related diseases. This article will review the biological monitoring indicators of occupational exposure to arsenic and the metabolic process of arsenic in the body.
Arsenicals ; Arsenic ; Occupational Exposure ; Drinking Water ; Liver/metabolism*

OBJECTIVES: This study was conducted to evaluate the cytotoxicity of gallium arsenide(GaAs), indium phosphide(InP) and indium arsenide(InAs) all of which are used as the semiconductor eletments in semiconductor industry. METHODS: Cytotoxicity in the alveolar macrophage was evaluated by the measurement of in vitro magnetometry, LDH release assay and histological examination. RESULTS: The relaxation curves by the in vitro magnetometry showed that GaAs has the cytotoxicity for the alveolar macrophage which is more significant in the higher dosages, while this cytotoxicity is not appeared in the groups added with InP or InAs or PBS. In the decay constant for two minutes after magnetization, GaAs-added groups showed a significant decrease with increasing doses, but both InP- and InAs-added groups did not show any significance. The LDH release assay showed a dose-dependent increasing tendency in the GaAs-, InP- and InAs-added groups. In terms of cellular morphological changes, GaAs-added groups revealed such severe cellular damages as prominent destructions in cell membranes and their morphological changes of nucleus, while InP- and InAs-added groups remained intact in intracellular structures, except for cytoplasmic degenerations. CONCLUSIONS: It is suggested that GaAs is more influential to cytotoxicity of alveolar macrophages than InP and InAs.
Arsenic* ; Arsenicals* ; Cell Membrane ; Cytoplasm ; Gallium ; Indium ; Macrophages* ; Macrophages, Alveolar ; Magnetometry ; Relaxation ; Semiconductors

OBJECTIVE: To compare inhibition of cell growth and apoptosis in human cervical cancer cell lines (CaSki) by paclitaxel, cisplatin, arsenic trioxide and tetraarsenic oxide. METHODS: Inhibition of cell growth was determined by the water-soluble tetrazolium salts (WSTs) -1 assay. For apoptosis analysis in CaSki cell line treated with single or combination of two agents, CaSki cell line treated with each agent was stained with annexin-V/PI and flow cytometry was performed. RESULTS: Progression of apoptosis in CaSki cell line treated with paclitaxel, cisplatin, arsenic trioxide, and tetraarsenic oxide was time dependent. Inhibition of cell growth in CaSki cell line by paclitaxel, cisplatin, arsenic trioxide, and tetraarsenic oxide was dose and time dependent. Especially, tetraarsenic oxide was more effective in inhibition of CaSki cell growth compared to arsenic trioxide. Group treated with combination of cisplatin and tetraarsenic oxide showed more progressive apoptosis compared to other combination group. CONCLUSION: Tetraarsenic oxide has more potent anti-tumor effects than other agents on CaSki cell line. We need to consider further study about antitumor effect of tetraarsenic oxide through clinical study.
Apoptosis ; Arsenic ; Arsenicals ; Cell Line ; Cisplatin ; Flow Cytometry ; Humans ; Oxides ; Paclitaxel ; Tetrazolium Salts ; Uterine Cervical Neoplasms

BACKGROUND: Bowen's disease(BD) is an in situ squamous cell carcinoma(SCC) of the skin, which clinically presents as a scaly slightly elevated erythematous plaque. Approximately two thirds of patients with BD have solitary lesions, whereas the remaining patients have multiple lesions. Lesions of BD have a wide distribution covering both sun-exposed and covered skin. Chronic sunlight exposure is an important etiological factor in many patients, and inorganic arsenicals can cause lesions on unexposed skin. If untreated, 3-5% of BD cases evolve into invasive carcinoma including SCC, basal cell carcinoma(BCC), and sebaceous carcinoma(SC), although the precise mechanism is not yet clear. OBJECTIVE: The purpose of this study was to investigate the factors which may be involved in the development of BD and progression to invasive carcinoma. METHODS: We performed immunohistochemical analysis using monoclonal antibodies for p53, mdm-2, and bcl-2 in 7 cases of multiple BD with invasive carcinoma. RESULTS: In four of 6 cases of SCC immunopositive for p53, at least one lesion of each BD was positive for p53. Among them, two cases showed the consistency of p53 staining between BD and its SCC and the localization of the lesions on sun-exposed areas. On the other hand, two cases of SCC and the associated BD were immunonegative for p53 and positive for mdm-2 and all the lesions developed on the UV-nonexposed areas. In one particular case which had a history of arsenic ingestion, SC was immunopositive for p53, whereas the associated SCC and BD were immunonegative for p53. In one case associated adenoid BCC, BD was immunopositive for p53 and negative for bcl-2, whereas BCC was immunonegative for p53 and strongly positive for bcl-2. CONCLUSION: These results suggest that UV light may play a role in the development of BD and its progression to SCC and in addition to p53, some additional factor or conditions are required in the progression towards these invasive carcinomas from BD.
Adenoids ; Antibodies, Monoclonal ; Arsenic ; Arsenicals ; Bowen's Disease* ; Eating ; Hand ; Humans ; Skin ; Sunlight ; Ultraviolet Rays

OBJECTIVETo investigate the effect of ATO on the proportion of Treg in the peripheral blood of patients with severe aplastic anemia (SAA) in vitro.

METHODSThe peripheral blood of 20 newlydiagnosed patients were collected, and the peripheral blood monomuclear cells (PBMNC) were extracted. After the PBMNC were treated with ATO of different concentrotions (0, 1, 2.5 and 5 µmol/L) for 96 hours, the proportion of CD44 CD25CD127 regulatatory T cells (Treg) were detected by flow cytometry. The expression levels of Foxp3 mRNA were detected by RT-PCR, and the levels of IFN-γ,IL-4,IL-17 and TGF-β1 were detected by ELTSA to verify the results of flow cytomery.

RESULTSATO significantly increased the proportion of Treg (P<0.01) at the concentration of 2.5 and 5 µmol/L, and the rising degree of Treg proportion improved with the increasing ATO concentration(r= 0.524). Treg proportion increased at a concentration of 1 µmol/L, but without statistical significance (P>0.05). At 1(P<0.05), 2.5(P<0.01) and 5 µmol/L(P<0.01), ATO significantly up-regulated the expression of Foxp3 mRNA, and the increase of Foxp3 mRNA positively and linearly correlated with the increase of Treg cell-frequency(r=0.523). ATO significantly reduced the levels of IFN-γ (at ATO 1,2.5 and 5 µmol/L, P<0.01), IL-4 (at ATO 2.5 µmol/L, P<0.01; at ATO 5 µmol/L, P<0.01) and IL-17(at ATO 2.5 µmol/L, P<0.05; at ATO 5 µmol/L, P<0.01). ATO had no significant effect on TGF-β1 at 1(P>0.05) and 2.5 µmol/L (P>0.05), but significantly reduced TGF-β1 level at 5 µmol/L (P<0.05).

CONCLUSIONATO can mediate the immune regulation through up-regulating the proportion of Treg in peripheral blood of patients with SAA and reducing the levels of IFN-γ, IL-4 and IL-17.

OBJECTIVETo investigate the effects of arsenic trioxide (AsO) on Cdc20 and Mad2 in process of AML HL-60 cell proliferation.

METHODSThe proliferation of HL-60 cells was detected by CCK-8 method at different concentrations of arsenic trioxide for 24, 48 and 72 hours. The cell morphological changes were observed by inverted microscopy. The expressions of Mad2 and Cdc20 mRNA and protein in HL-60 cells treated with AsO for 48 h were detected by real-time PCR and Western blot respectively.

RESULTSArsenic trioxide significantly inhibited the HL-60 cell proliferation and displayed a good time-dose correlation. RT-PCR and Western blot showed that the expression of Mad2 was up-regulated and the expression of Cdc20 was down-regulated in HL-60 cells treated with arsenic trioxide of different concentration (4,8,10 µmol/L).

CONCLUSIONArsenic trioxide can inhibit the human acute myeloid leukemia HL-60 cell proliferation, and its mechanism may be related with up-regulation of Mad2 expression and down-regulation of Cdc20 expression.

OBJECTIVETo analyze the correlation of ATO therapeutic dose with the relapse of patients with acute promyelocytic leukemia (APL) and to investigate the optimal dose and courses of ATO.

METHODSThe clinical data of 102 patients with APL from January 2008 to June 2015 were analyzed retrospectively. The clinical characteristics of APL patients in relapsed group and maintained remission group were compared. According to ATO dose in 2 years recommended in chinese guideline as criteria of grouping, the patients were divided into ATO high and low dose groups, then the relapse rate in groups was compared. The cut-off value of ATO dose was analyzed by ROC curve.

RESULTSUnivariate analysis showed that the relapse rate in high ATO and low ATO groups on 2 year treatment was 2.5% and 17.7% respectively (P<0.05); multiple variate analysis demonstrated that the ATO dose>22.4 mg/kg on 2 year treatment was independent preventive factor for the relapse of APL (OR=0.119, P<0.05). The ROC curve showed that the cut-off value of ATO dose on 2 year treatment was 8.765 mg/kg. The relapse rate of APL in group of ATO dose >8.765 mg/kg group was significantly lower than that in group of ATO dose <8.765 mg/kg.

CONCLUSIONThe relapse of APL relates with used ATO dose, sufficient use of ATO dose can decrease the relapse rate of APL.

OBJECTIVETo investigate the effects of arsenic trioxide (As2O3) on the proliferation, differentiation and apoptosis of HL-60 cells in vitro and explore the underlying mechanisms.

METHODSAfter HL-60 cells were treated with different concentration of As2O3, the cell proliferation was determined by MTS/PES method, the differentiation state was detected by the nitroblue tetrazolium (NBT) reduction test; flow cytometry was used to analyze the apoptosis and expression of CD11b. In addition, SYBR Green real-time RT-PCR was used to measure the mRNA levels of C-FES, BCL-2, BAX, survivin , P21 and P27.

RESULTSAs2O3 could obviously inhibit the proliferation of HL-60 cells, and the effect was in dose- and time-dependent manners (r=-0.967; r=-0.954). Low concentration (0.1, 0.5 and 1.0 µmol/L) of As2O3 could significantly promote the differentiation of HL-60 cells, the cells exhibited a higher NBT-reducing ability and expressed far more CD11b antigens. High concentration (2.5 and 5.0 µmol/L) of As2O3 induced HL-60 cell apoptosis, but the ability of promoting differentiation decreased. The expression of C-FES mRNA significantly increased after being treated with As2O3 at the concentrations 1.0 and 5.0 µmol/L, and the former is more obvious, which confirmed that C-FES mRNA level paralleled the cell differentiation degree. Also, the expression of BCL-2 and survivin significantly decreased, while the expression of BAX, P21 and P27 was significantly upregulated in HL-60 cells after being treated with 5.0 µmol/L As2O3.

CONCLUSIONAs2O3 can significantly suppress cell proliferation, promote the differentiation and induce the apoptosis in HL-60 cells, and the mechanism of As2O3 anti-tumor activity may be involved in the regulation of C-FES, cell cycle and apoptosis-related genes.