Syl948 is a synthesized selective S1P1 agonist with novel structure. HTRF-IP1 test indicated that Syl948-P, the active form of Syl948 in vitro, has strong activity against S1P1 (EC50: 83 +/- 16 nmol x L(-1)), but its effect on S1P3 was very weak (EC50: 1 026 +/- 90 nmol x L(-1)). In SD rats, oral administration of Syl948 10 mg x kg(-1) significantly decreased the peripheral blood lymphocytes (PBL), with the maximal PBL inhibition rate of 63%, which was as similar as equal dose of fingolimod (FTY720). Oral administration of Syl948 10 mg x kg(-1) had no effect on heart rate of SD rats, which was better than FTY720. Daily oral administration with Syl948 (2 or 4 mg x kg(-1)) significantly prolonged the survival time of the allografts of skin slice on mice. In summary, the above results demonstrated that Syl948 has great selectivity in vitro and good activity in vivo, which indicated its potential use as an anti-rejection drug in skin transplantation.

Aim To determine the effect of SYL934 , a novel immunosuppressant, on skin allograft rejec-tion. Methods HTRF-IP1 assay was used to evaluate the agonistic activity of SYL934-P, the active form of SYL934 in vivo, on S1P1 and S1P3 in vitro. SD rat peripheral blood lymphocytes ( PBL ) test and heart rate test was used to assess the in vivo immunosuppres-sive effect and heart rate effect of SYL934 . Mice skin graft transplantation experiment was used to observe the effect of SYL934 on skin allograft refection. ResultsSYL934-P selectively activated S1 P1 but not S1 P3 in vitro. Single orally administration of SD rats with
SYL934 decreased the PBL significantly and played an obviously immunosuppressant role, but did not affect the heart rate. Daily orally administration of mice with SYL934 significantly increased the survival rate of al-lografts of skin slice in mice. Conclusion SYL934 has great selectivity in vitro and good activity in vivo, which indicated it potential use as an anti-rejection drug in skin transplantation.

Objective:To explore the evaluation of dual-parameter three dimension arterial spin labelling(3D-ASL)perfusion imaging on blood-supply situation of patients with chronic middle cerebral artery occlusion(CMCAO)and the relationship between that and cerebral infarction area.Methods:A total of 112 patients with unilateral CMCAO admitted to Handan Central Hospital from April 2019 to December 2021 were selected,and all of them were divided into a compensatory group(50 cases)with anterior cerebral artery(ACA)leptomeningeal anastomoses(LMA)and an uncompensated group(62 cases)according to the results of digital subtraction angiography(DSA)examination.The results of diffusion weighted imaging(DWI),magnetic resonance angiography(MRA)and dual-parameter 3D-ASL detection were respectively analyzed,and the clinical data,3D-ASL parameters and the incidence of cerebral infarction between the two groups were compared.The influence factors of compensation were further analyzed.The receiver operating characteristics(ROC)curve of LMA diagnostic value of CMCAO patients was drawn according to cerebral blood flow values[post label delay(PLD)=1.5 s,2.5 s)].The 3D-ASL parameters of patients with different cerebral infarction areas were compared,and the relationship between 3D-ASL parameters and cerebral infarction area was compared.Results:The apparent diffusion coefficient(ADC)at the side of lesion of CMCAO patients was(0.31±0.10),and cerebral blood flow values at 1.5s and 2.5s were respectively(25.67±4.25)and(54.09±4.49),which were significantly lower than those at the side of healthy,and the differences were statistically significant(t=27.591,34.210,3.913,P<0.05),respectively.The differences of cerebral blood flow values(1.5s and 2.5s)between compensatory group and uncompensated group were significant(t=5.584,4.090,P<0.05),respectively.The results of logistic regression analysis showed that age,stroke,cerebral infarction area and cerebral blood flow values(1.5 s and 2.5 s)were influencing factors on LMA compensation of CMCAO patients(OR=4.187,6.604,0.482,5.681,5.807,P<0.05),respectively.The ROC values showed that the area under curve(AUC)of 3D-ASL were respectively 0.720 and 0.812 in diagnosing LMA when PLD were respectively 1.5s and 2.5s.The proportion of normal and lacunar infarctions in the compensatory group was significantly higher than that in the uncompensated group,while the proportions of middle and small infarction,and large area infarctions of the compensatory group were significantly lower than those of the uncompensated group,and the difference was statistically significant(t=28.062,P<0.05).The difference in cerebral blood flow values(1.5s)among patients with different infarct areas was statistically significant(t=0.202,P<0.05).The cerebral blood flow value(1.5s)of 3D-ASL was negatively correlated with the area of cerebral infarction(r=-0.261,P<0.05).Conclusion:Dual parameter 3D-ASL can non-invasively and visually assess the compensatory status of LMA of patients with unilateral CMCAO.The blood flow perfusion of middle cerebral artery(MCA)at the side of lesion is related to the area of cerebral infarction.When the PLD is 1.5s,the sensitive response can be conducted on this,so as to provide objective and reliable basis for clinical diagnosis and treatment and curative effect.

Objective: To establish a method for the determination ofsamarium oxide and lanthanum oxide by inductively coupled plasmamass spectrometryin the air of workplace. Methods: Samarium, lanthanum and their compounds in the air of workplace were collected through microporous filter. The samples were digested by nitricacid and perhydrol (V/V=4∶1) and detected by inductively coupled plasmamass spectrometry. Results: The linear range ofsamarium oxide and lanthanum oxide was 0-50.00 μg/L, Sm₂O₃: y=0.0119x, r=0.9999; La₂O₃: y=0.0617x, r=0.9998. The detection limits were less than 0.1 μg/L, and the minimum detection concentration were less than 1.52×10^-5 mg/m³. The sampling efficiency were 100%, the recovery rates were 95.70%-102.01%, and the precision were 0.78%-1.58%. Conclusion The indicators established in this study are conformed with the requirements of Chinese Occupational Standars of GBZ/T 210.4-2008, "The Guidelines for the Development of Occupational Hygiene StandarsMehods Part 4: Determination of Chemical Substances in the Air of Workplace".

Objective:To study the effect of samarium trioxide (Sm 2O 3) particles on rat lung tissue and compare it with the same dose of silica (SiO 2) particles, in order to find the reference index for early screening of pneumoconiosis. Methods:In October 2018, 72 SPF healthy male rats were randomly divided into control group, SiO 2 group and Sm 2O 3 group. The lungs of rats in each group were perfused with 2.0 ml/kg normal saline and 280 mg/kg SiO 2 and Sm 2O 3 particle suspension by one-time non exposed tracheal perfusion. The lungs of rats were stained with hematoxylin eosin (HE) staining, and the pathological changes of lung tissues were observed. The concentrations of SNAIL homologue 1 (SNAI1) , SNAIL homologue 2 (SNAI2) , and heat shock protein-27 (HSP-27) in rat serum were detected by enzyme-linked immunosorbent assay. 0.5 g of lung tissue from rats in Sm 2O 3 group and control group exposed to dust for 56 days was screened for long-chain noncoding RNA (lncRNA) and circular RNA (circRNA) . Results:After 7 days of dust exposure, the alveoli in SiO 2 group and Sm 2O 3 group were disordered, and lymphoid tissue aggregation and proliferation were observed around the bronchial wall. At 14 days, a large number of lymphocytes infiltrated in SiO 2 group, and a small number of macrophages containing Sm 2O 3 and fibrotic nodules scattered in Sm 2O 3 group. At 28 days, a small amount of lymphocyte infiltration appeared in SiO 2 group, and fibrotic nodules were seen in some areas of Sm 2O 3 group. At 56 days, there was a small amount of fibroblast proliferation in SiO 2 group, and a large number of fibrotic nodules containing gray black matter were seen in Sm 2O 3 group. There was no significant difference in lung organ coefficient among groups at different dust exposure time ( P>0.05) . After 14 days of dust exposure, the contents of SNAI1 and SNAI2 in serum of rats in SiO 2 group were lower than those in control group, the content of SNAI2 in serum of Sm 2O 3 group was lower than that in control group, and the contents of SNAI1 and SNAI2 in serum of Sm 2O 3 group were higher than those in SiO 2 group ( P<0.05) . The content of HSP-27 in SiO 2 group was lower than that in control group ( P<0.05) . After 56 days of dust exposure, the content of HSP-27 in Sm 2O 3 group was lower than that in control group ( P<0.05) . At 56 days, lncRNA in Sm 2O 3 group was up-regulated by 148 and down regulated by 725, circRNA was up-regulated by 16 and down regulated by 153. Conclusion:Sm 2O 3 can cause lung injury in rats, and the change of SNAI2 content can be detected in the early stage, which can be used as a reference index for early screening of pneumoconiosis. There are differences in the expression of lncRNA and circRNA after 56 days of dust exposure in rats, which may be related to the pathogenesis of pneumoconiosis.

Objective:To study the effect of samarium trioxide (Sm 2O 3) particles on rat lung tissue and compare it with the same dose of silica (SiO 2) particles, in order to find the reference index for early screening of pneumoconiosis. Methods:In October 2018, 72 SPF healthy male rats were randomly divided into control group, SiO 2 group and Sm 2O 3 group. The lungs of rats in each group were perfused with 2.0 ml/kg normal saline and 280 mg/kg SiO 2 and Sm 2O 3 particle suspension by one-time non exposed tracheal perfusion. The lungs of rats were stained with hematoxylin eosin (HE) staining, and the pathological changes of lung tissues were observed. The concentrations of SNAIL homologue 1 (SNAI1) , SNAIL homologue 2 (SNAI2) , and heat shock protein-27 (HSP-27) in rat serum were detected by enzyme-linked immunosorbent assay. 0.5 g of lung tissue from rats in Sm 2O 3 group and control group exposed to dust for 56 days was screened for long-chain noncoding RNA (lncRNA) and circular RNA (circRNA) . Results:After 7 days of dust exposure, the alveoli in SiO 2 group and Sm 2O 3 group were disordered, and lymphoid tissue aggregation and proliferation were observed around the bronchial wall. At 14 days, a large number of lymphocytes infiltrated in SiO 2 group, and a small number of macrophages containing Sm 2O 3 and fibrotic nodules scattered in Sm 2O 3 group. At 28 days, a small amount of lymphocyte infiltration appeared in SiO 2 group, and fibrotic nodules were seen in some areas of Sm 2O 3 group. At 56 days, there was a small amount of fibroblast proliferation in SiO 2 group, and a large number of fibrotic nodules containing gray black matter were seen in Sm 2O 3 group. There was no significant difference in lung organ coefficient among groups at different dust exposure time ( P>0.05) . After 14 days of dust exposure, the contents of SNAI1 and SNAI2 in serum of rats in SiO 2 group were lower than those in control group, the content of SNAI2 in serum of Sm 2O 3 group was lower than that in control group, and the contents of SNAI1 and SNAI2 in serum of Sm 2O 3 group were higher than those in SiO 2 group ( P<0.05) . The content of HSP-27 in SiO 2 group was lower than that in control group ( P<0.05) . After 56 days of dust exposure, the content of HSP-27 in Sm 2O 3 group was lower than that in control group ( P<0.05) . At 56 days, lncRNA in Sm 2O 3 group was up-regulated by 148 and down regulated by 725, circRNA was up-regulated by 16 and down regulated by 153. Conclusion:Sm 2O 3 can cause lung injury in rats, and the change of SNAI2 content can be detected in the early stage, which can be used as a reference index for early screening of pneumoconiosis. There are differences in the expression of lncRNA and circRNA after 56 days of dust exposure in rats, which may be related to the pathogenesis of pneumoconiosis.

Objective:To screen differential proteins in the serum of workers with rare earth samarium oxide pneumoconiosis, in order to provide new ideas for finding its early diagnostic biomarkers.Methods:In April 2019, three male workers diagnosed with samarium oxide pneumoconiosis at a rare earth factory in Baotou City, Inner Mongolia Autonomous Region were selected as the observation group, and three male workers who were not exposed to dust were selected as the control group. The serum was sequenced using the Label-free proteomic method to screen for differentially expressed proteins, followed by cluster of orthologous groups of proteins (COG) annotation, gene ontology (GO) enrichment analysis, and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis. The interaction gene library retrieval tool database and Cytoscape 3.9.1 software were used to draw protein-protein interaction networks. CytoHubba plugin was used to screen for differentially expressed proteins with high scores, and real-time fluorescence quantitative polymerase chain reaction (RT/q-PCR) was used to validate the proteomic sequencing results.Results:A total of 45 up-regulated differentially expressed proteins and 5 down-regulated differentially expressed proteins were screened out in the serum of workers with rare earth samarium oxide pneumoconiosis. In the COG functional classification, post-translational modifications, protein turnover, and chaperones were the most numerous. GO enrichment included 25 entries for biological processes such as complement activation (classical pathways), 15 entries for cellular components such as extracellular recombinants, and 10 entries for molecular functions such as protein binding. The pathways identified by KEGG enrichment analysis mainly included infectious diseases, immune system, signal transduction, and immune related diseases. The top 10 scoring proteins were haptoglobin, complement C1r subcomponent, complement C1s subcomponent, apolipoprotein C-Ⅲ, apolipoprotein A-Ⅱ, prothrombin, afamin, complement component C8 gamma chain, complement component C6, complement component C7. The RT/q-PCR validation results showed that the mRNA expression levels of haptoglobin, prothrombin and complement C1s subcomponent in the observation group were significantly higher than those in the control group, and the differences were statistically significant ( P<0.05) . Conclusion:Ten differentially expressed proteins in the serum of workers with rare earth samarium oxide pneumoconiosis are screened, which provides a good idea for the screening of biomarkers for early diagnosis of samarium oxide pneumoconiosis.

Objective:To screen differential proteins in the serum of workers with rare earth samarium oxide pneumoconiosis, in order to provide new ideas for finding its early diagnostic biomarkers.Methods:In April 2019, three male workers diagnosed with samarium oxide pneumoconiosis at a rare earth factory in Baotou City, Inner Mongolia Autonomous Region were selected as the observation group, and three male workers who were not exposed to dust were selected as the control group. The serum was sequenced using the Label-free proteomic method to screen for differentially expressed proteins, followed by cluster of orthologous groups of proteins (COG) annotation, gene ontology (GO) enrichment analysis, and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis. The interaction gene library retrieval tool database and Cytoscape 3.9.1 software were used to draw protein-protein interaction networks. CytoHubba plugin was used to screen for differentially expressed proteins with high scores, and real-time fluorescence quantitative polymerase chain reaction (RT/q-PCR) was used to validate the proteomic sequencing results.Results:A total of 45 up-regulated differentially expressed proteins and 5 down-regulated differentially expressed proteins were screened out in the serum of workers with rare earth samarium oxide pneumoconiosis. In the COG functional classification, post-translational modifications, protein turnover, and chaperones were the most numerous. GO enrichment included 25 entries for biological processes such as complement activation (classical pathways), 15 entries for cellular components such as extracellular recombinants, and 10 entries for molecular functions such as protein binding. The pathways identified by KEGG enrichment analysis mainly included infectious diseases, immune system, signal transduction, and immune related diseases. The top 10 scoring proteins were haptoglobin, complement C1r subcomponent, complement C1s subcomponent, apolipoprotein C-Ⅲ, apolipoprotein A-Ⅱ, prothrombin, afamin, complement component C8 gamma chain, complement component C6, complement component C7. The RT/q-PCR validation results showed that the mRNA expression levels of haptoglobin, prothrombin and complement C1s subcomponent in the observation group were significantly higher than those in the control group, and the differences were statistically significant ( P<0.05) . Conclusion:Ten differentially expressed proteins in the serum of workers with rare earth samarium oxide pneumoconiosis are screened, which provides a good idea for the screening of biomarkers for early diagnosis of samarium oxide pneumoconiosis.