Abstract: Objective To analyze the plasma metabolomics of patients with occupational silicosis, and screen the differential Methods metabolic pathways in different stages of silicosis. Thirty patients with occupational silicosis were selected as silicosis group by judgment sampling method, including 10 patients in each subgroups with silicosis at stages Ⅰ, Ⅱ, and Ⅲ. Another 10 healthy individuals without occupational dust exposure history were selected as the control group. Plasma of each patientwascollected.Themetabolitesfromtheirplasmasampleswerecollectedandidentifiedbyuntargetedmetabolomicsusing----ultraperformanceliquidchromatographyquadrupoletimeofflightmassspectrometry.Principalcomponentanalysisandpartial least square discriminant analysis were used to compare the differentially expressed metabolites. The metabolic pathways Results enrichment analysis was performed using MetaboAnanlyst 5.0 and other metabolic analysis software. There were significantlydifferentmetabolicprofilesamongtheplasmaofthesilicosissubgroupsandthecontrolgroup.Inthepositivemode,--149differentmetaboliteswerescreened,amongwhich99metaboliteswereupregulatedand50metabolitesweredown regulated. Sphingolipids metabolism, arginine and ornithine metabolism, and fatty acid degradation are the main metabolic pathwaysinsilicosissubgroupswithstagesⅠandⅡcomparedwiththecontrolgroup.Themetabolicpathwaysofsilicosisstage Ⅲ are arginine and proline metabolism, glycerol metabolism, glyoxylic acid and dicarboxylic acid metabolism, and glycine, Conclusion serine and threonine metabolism. The plasma metabolic profile of patients with silicosis in different stages changed significantly. Sphingolipid metabolism is the main metabolic pathway in the early and middle stages of silicosis. In - silicosisterminalstage,thechangeofarginineandproline basedmetabolicpathwayresultinginfibrosisaggravation.

Background The production and consumption of high polar pesticides in China are the largest in the world. Therefore, it is urgent to develop a method with fast analysis, large flux, and high accuracy to determine the residues of these pesticides in food. Objective To establish a method for the determination of eight highly polar pesticides [chlormequat, paraquat, difenzoquat, cyromazine, propamocarb, glyphosate, (aminomethyl)-phosphonic acid, and glufosinate] in vegetables and fruits by ultra-performance liquid chromatography-tandem mass spectrometry. Methods After comparing various types of hydrophilic interaction liquid chromatography (HILIC) columns, and optimizing pH value and buffer concentration of mobile phase, effective chromatographic retention and separation of selected eight pesticides were achieved. Based on the optimization of mass spectrometry under chromatographic conditions, a multiple reaction monitoring (MRM) channel of target compounds was established. In the sample pretreatment, through optimization of water content, extraction solvent, and purification method, a final MRM mode of ultra-performance liquid chromatography-tandem mass spectrometry was used for detection, and the isotope internal standard method was used for quantification. The accuracy and the precision of the method were evaluated using recovery and relative standard deviation. The established method was applied to detect 57 samples of retail vegetables and fruits to investigate the adaptability of the proposed method and the residual levels of selected high polar pesticides. Results For positive ion electrospray ionization (ESI⁺) detection, we chose Sielc Obelisc R as chromatographic column, and 20 mmol·L⁻¹ ammonium formate solution (pH=3±0.05) and acetonitrile as mobile phase; for negative ion electrospray ionization (ESI⁻) detection, we chose Shodex Asahipak NH2P-50 2D as chromatographic column, and 5 mmol·L⁻¹ ammonium acetate solution (pH=11±0.05) and acetonitrile as mobile phase to obtain good chromatographic separation and peak shape. Under the optimal conditions of sample water content standardization, using 2% acidified methanol as extraction solvent, and C18 dispersed solid phase extraction purification, the linearity ranges of five analytes (chlormequat, paraquat, difenzoquat, cyromazine, and propamocarb) and three analytes [glyphosate, (aminomethyl)phosphonic acid, and glufosinate] were 1.00-100 μg·L⁻¹ and 5.00-500 μg·L⁻¹ (both correlation coefficients>0.999) respectively, the detection limits were 0.002-0.010 mg·kg⁻¹, and the limits of quantification (LOQ) were 0.005-0.025 mg·kg⁻¹. At three spiked levels (LOQ, 2LOQ, and 5LOQ), the recoveries were in the range of 85.3%–113.2%, and the relative standard deviations were 1.5%–9.5% (n=6). Three target pesticides (chlormequat, cyromazine, and propamocarb) were detected in 57 samples of retail vegetables and fruits, and the residue of chlormequat in cowpea exceeded the maximum residue limit. Conclusion The established method of HILIC combined with ultra-performance liquid chromatography-tandem mass spectrometry and isotopic internal standard quantification has the characteristics of simplicity, stability, and easy operation, which is suitable for rapid screening and quantitative detection of selected eight high polar pesticide residues in large quantities of vegetables and fruits, and provides technical support for monitoring and risk assessment of high polar pesticide residues.