ObjectiveTo investigate the effect of arsenic trioxide (As2O3) on the metastasis capability of Ewing's sarcoma ceils. MethodsMTT assays were performed to choose appropriate concentrations of As2O3 (＜ 2 μmol/L) for the experiments.Migration and invasion assays were performed to assess the effect of As2O3 on the metastasis of Ewing's sarcoma cells. Changes in matrix metalloproteinase(MMP)-9 expressions were detected by gel zymography assay and the phosphoinositide 3-kinase/AKT(PI3K-AKT)pathway was investigated using Western blot. ResultsThe amount of Ewing's sarcoma cells across basal membrane of Transwell in migration and invasion assay decreased gradually with the increase in As2O3 concentration. The average quantities of A-673 across the membrane after treatment by gradual concentrations accounted for 54.3 ％,49.0 ％ and 17.0 ％ of that of untreated group respectively in migration assay (F=112.78,P ＜ 0.01), while 52.7 ％, 32.3 ％ and 10.3 ％ in invasion assay(F =183.76, P ＜ 0.01). Similarly, the percentage of RD-ES was 46.0 ％,39.0 ％ and 8.0 ％ in migration assay (F =408.25,P ＜ 0.01) and 58.7 ％,22.3 ％ and 9.0 ％ in invasion assay (F =373.25, P ＜ 0.01)respectively. The difference had statistics significance.The expression of MMP-9 was suppressed by As2O3 treatment according to gel zymography assay.Western blot assay showed that PI3K-AKT pathway was inhibited and nuclear factor kappa B(NF-κB)was inactivated.ConclusionLow-concentration As2O3 may inhibit metastasis capability of Ewing's sarcoma cells.

ObjectiveTo assess the clinical efficacy and safety of donepezil in treating the mild to moderate cognitive impairment of vascular dementia.Methods60 patients with vascular dementia were randomly divided into therapy group (donepezil 5 mg/d for 4 weeks, and then increased to 10 mg/d) and control group (piracetan 800 mg,3/d). All patients were assessed with Mini Mental State Examination (MMSE), Wechsler Adult Intelligence Revised in China (WAIS-RC), Activities of daily living (ADL), and Clinical Global Impression (CGI), before and 12 weeks after treatment. ResultsMMSE scores improved significantly in both groups after the treatment. The therapy group produced significantly better scores than the control groups on the MMSE(P<0.05). WAIS-RC scores improved significantly in the therapy groups(P<0.01), but there was no significant difference for control groups(P>0.05), before and after treatment. Severity Improvement(SI) score of ADL and CGI in the both groups decreased. The total efficiencies of donepezil and piracetan groups were 86% and 56% respectively. There was no significant difference in adverse effects between two groups. ConclusionDonepezil can improve the cognitive function of patients with vascular dementia, which seems better than that of piracetan, and it is fairly safe for vascular dementia patients to take donepezil 10 mg a day.

Objective To study the drifting law of floats and potential risks of Oncomelania hupensis diffusion in the water diversion rivers of the east route of South?to?North Water Diversion Project. Methods The O. hupensis snails in the river chan?nels were monitored by the salvage method and snail luring method with rice straw curtains,and the diffusion possibility of snails along with water was assessed through the drift test of floats with GPS. Results In the flood seasons from 2006 to 2013, totally 8 338.0 kg of floats were salvaged,and 2 100 rice straw curtains were put into water in the Li Canal and Jinbao shipping channel,but no Oncomelania snails were found. The drift test of floats with GPS before water diversion showed that the flow ve?locity on water surface(northbound)was 0.45 m/s,the average drift velocity of the floats was 0.56-0.60 m/s,and the average drift distances each time were 999.70- 1 995.50 m in the Gaoshui River section,while there were no obvious drift in Jinbao shipping channel section. During the water diversion period,the flow velocity on water surface(northbound)was 0.45 m/s,the average drift velocity of the floats was 0.35-0.41m/s,and the average drift distances each time were 1 248.06-1 289.44 m in the Gaoshui River,while in Jinbao shipping channel section,the flow velocity on water surface was 0.28 m/s,the average drift velocity of the floats was 0.25- 0.27 m/s,and the average drift distances each time were 477.76- 496.38 m. The drift test showed that the floats gradually closed to the river bank as affected by water flow,wind direction and ship waves,when blocked by the reeds,water plants or other obstacles,and they would stopped and could not continue to drift without outside help. Con?clusions There are no Oncomelania snails found in the river channels of the east route of South?to?North Water Diversion Proj?ect. The drifting distance of the floating debris along with the water is restricted by the flow rate and shore environment.

Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment.Oral squamous cell carcinoma(OSCC),a representative hypoxic tumor,has a heterogeneous internal metabolic environment.To clarify the relationship between different metabolic regions and the tumor immune microenvironment(TME)in OSCC,Single cell(SC)and spatial transcriptomics(ST)sequencing of OSCC tissues were performed.The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data.The metabolic activity of each spot was calculated using scMetabolism,and k-means clustering was used to classify all spots into hyper-,normal-,or hypometabolic regions.CD4T cell infiltration and TGF-β expression is higher in the hypermetabolic regions than in the others.Through CellPhoneDB and NicheNet cell-cell communication analysis,it was found that in the hypermetabolic region,fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts(iCAFs),and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12.The secretion of CXCL12 recruits regulatory T cells(Tregs),leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment.This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC,ST and TCGA bulk data,and highlights potential targets for therapy.

Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment.Oral squamous cell carcinoma(OSCC),a representative hypoxic tumor,has a heterogeneous internal metabolic environment.To clarify the relationship between different metabolic regions and the tumor immune microenvironment(TME)in OSCC,Single cell(SC)and spatial transcriptomics(ST)sequencing of OSCC tissues were performed.The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data.The metabolic activity of each spot was calculated using scMetabolism,and k-means clustering was used to classify all spots into hyper-,normal-,or hypometabolic regions.CD4T cell infiltration and TGF-β expression is higher in the hypermetabolic regions than in the others.Through CellPhoneDB and NicheNet cell-cell communication analysis,it was found that in the hypermetabolic region,fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts(iCAFs),and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12.The secretion of CXCL12 recruits regulatory T cells(Tregs),leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment.This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC,ST and TCGA bulk data,and highlights potential targets for therapy.

Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment.Oral squamous cell carcinoma(OSCC),a representative hypoxic tumor,has a heterogeneous internal metabolic environment.To clarify the relationship between different metabolic regions and the tumor immune microenvironment(TME)in OSCC,Single cell(SC)and spatial transcriptomics(ST)sequencing of OSCC tissues were performed.The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data.The metabolic activity of each spot was calculated using scMetabolism,and k-means clustering was used to classify all spots into hyper-,normal-,or hypometabolic regions.CD4T cell infiltration and TGF-β expression is higher in the hypermetabolic regions than in the others.Through CellPhoneDB and NicheNet cell-cell communication analysis,it was found that in the hypermetabolic region,fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts(iCAFs),and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12.The secretion of CXCL12 recruits regulatory T cells(Tregs),leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment.This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC,ST and TCGA bulk data,and highlights potential targets for therapy.

Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment.Oral squamous cell carcinoma(OSCC),a representative hypoxic tumor,has a heterogeneous internal metabolic environment.To clarify the relationship between different metabolic regions and the tumor immune microenvironment(TME)in OSCC,Single cell(SC)and spatial transcriptomics(ST)sequencing of OSCC tissues were performed.The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data.The metabolic activity of each spot was calculated using scMetabolism,and k-means clustering was used to classify all spots into hyper-,normal-,or hypometabolic regions.CD4T cell infiltration and TGF-β expression is higher in the hypermetabolic regions than in the others.Through CellPhoneDB and NicheNet cell-cell communication analysis,it was found that in the hypermetabolic region,fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts(iCAFs),and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12.The secretion of CXCL12 recruits regulatory T cells(Tregs),leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment.This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC,ST and TCGA bulk data,and highlights potential targets for therapy.

Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment.Oral squamous cell carcinoma(OSCC),a representative hypoxic tumor,has a heterogeneous internal metabolic environment.To clarify the relationship between different metabolic regions and the tumor immune microenvironment(TME)in OSCC,Single cell(SC)and spatial transcriptomics(ST)sequencing of OSCC tissues were performed.The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data.The metabolic activity of each spot was calculated using scMetabolism,and k-means clustering was used to classify all spots into hyper-,normal-,or hypometabolic regions.CD4T cell infiltration and TGF-β expression is higher in the hypermetabolic regions than in the others.Through CellPhoneDB and NicheNet cell-cell communication analysis,it was found that in the hypermetabolic region,fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts(iCAFs),and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12.The secretion of CXCL12 recruits regulatory T cells(Tregs),leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment.This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC,ST and TCGA bulk data,and highlights potential targets for therapy.

Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment.Oral squamous cell carcinoma(OSCC),a representative hypoxic tumor,has a heterogeneous internal metabolic environment.To clarify the relationship between different metabolic regions and the tumor immune microenvironment(TME)in OSCC,Single cell(SC)and spatial transcriptomics(ST)sequencing of OSCC tissues were performed.The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data.The metabolic activity of each spot was calculated using scMetabolism,and k-means clustering was used to classify all spots into hyper-,normal-,or hypometabolic regions.CD4T cell infiltration and TGF-β expression is higher in the hypermetabolic regions than in the others.Through CellPhoneDB and NicheNet cell-cell communication analysis,it was found that in the hypermetabolic region,fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts(iCAFs),and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12.The secretion of CXCL12 recruits regulatory T cells(Tregs),leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment.This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC,ST and TCGA bulk data,and highlights potential targets for therapy.

Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment.Oral squamous cell carcinoma(OSCC),a representative hypoxic tumor,has a heterogeneous internal metabolic environment.To clarify the relationship between different metabolic regions and the tumor immune microenvironment(TME)in OSCC,Single cell(SC)and spatial transcriptomics(ST)sequencing of OSCC tissues were performed.The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data.The metabolic activity of each spot was calculated using scMetabolism,and k-means clustering was used to classify all spots into hyper-,normal-,or hypometabolic regions.CD4T cell infiltration and TGF-β expression is higher in the hypermetabolic regions than in the others.Through CellPhoneDB and NicheNet cell-cell communication analysis,it was found that in the hypermetabolic region,fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts(iCAFs),and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12.The secretion of CXCL12 recruits regulatory T cells(Tregs),leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment.This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC,ST and TCGA bulk data,and highlights potential targets for therapy.