Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

The chemical constituents were systematically separated from the roots of Berberis polyantha by various chromatographic methods, including silica gel column chromatography, HP20 column chromatography, polyamide column chromatography, reversed-phase C_(18) column chromatography, and preparative high-performance liquid chromatography. The structures of the compounds were identified by physicochemical properties and spectroscopic techniques(1D NMR, 2D NMR, UV, MS, and CD). Four phenylpropanoids were isolated from the methanol extract of the roots of B. polyantha, and they were identified as(2R)-1-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone-O-β-D-glucopyranoside(1), methyl 4-hydroxy-3,5-dimethoxybenzoate(2),(+)-syringaresinol(3), and syringaresinol-4-O-β-D-glucopyranoside(4). Compound 1 was a new compound, and other compounds were isolated from this plant for the first time. The anti-inflammatory activity of these compounds was evaluated based on the release of nitric oxide(NO) in the culture of lipopolysaccharide(LPS)-induced RAW264.7 macrophages. At a concentration of 10 μmol·L~(-1), all the four compounds inhibited the LPS-induced release of NO in RAW264.7 cells, demonstrating potential anti-inflammatory properties.
Plant Roots/chemistry* ; Animals ; Mice ; Berberis/chemistry* ; RAW 264.7 Cells ; Macrophages/immunology* ; Drugs, Chinese Herbal/isolation & purification* ; Nitric Oxide/metabolism* ; Molecular Structure ; Anti-Inflammatory Agents/isolation & purification*

Objective We made a bidirectional two-sample Mendelian randomization(MR)analysis to investigate the causal connection between metabolites and atopic dermatitis(AD).Methods Single nucleotide polymorphic(SNP)sites associated with metabolites were extracted from the aggregated data of a genome-wide association study(GWAS)as instrumental variables.Causal association between six metabolites and AD was analyzed using the TwoSampleMR package in R software.The primary methods employed included inverse variance weighted(IVW),MR Egger,and weighted median.Heterogeneity testing was conducted using Cochran's Q statistics.MR Egger intercept was employed to test for level pleiotropy.Additionally,sensitivity analysis was carried out using the"leave-one-out"approach.Results The IVW analysis results indicated that ascorbic acid(OR=0.861,95％CI:0.751-0.987),arachidonic acid(OR=0.363,95％CI:0.193-0.683),and cortisone(OR=0.447,95％CI:0.221-0.906)were negatively correlated with the occurrence of AD,while uridine(OR=3.473,95％CI:1.043-11.562),serotonin(OR=1.896,95％CI:1.007-3.571),and 2-hydroxyglutaric acid(OR=2.158,95％CI:1.186-3.924)were positively correlated with the occurrence of AD,and the differences were statistically significant.Conclusion There is no significant evidence supporting a causal association between AD and metabolic disorder,but this study identified potential evidence for a causal effect of six metabolic factors on an increased risk of AD.

Objective:To analyze the clinical curative effects of wire-to-port drainage and put-aside drainage after incision and hanging on perianal abscess.Methods:Eighty-two patients with perianal abscess admitted to Anqing Municipal Hospital between November 2019 and November 2022 were enrolled. The patients were divided into group A (41 cases, incision and hanging wire-to-port drainage) and group B (41 cases, incision and hanging put-aside drainage) by random digits table method. The clinical curative effect, operation time, wound healing time, postoperative recovery time and hospitalization time in the two groups were compared. The pain and anal function were evaluated by visual analogue score (VAS) and Wexner continence grading score (Wexner score) before surgery and 1, 7 d after surgery. The occurrence of complications within 1 month after surgery was statistically analyzed.Results:There was no significant difference in total clinical response rate between group A and group B ( P>0.05). There was no significant difference in operation time between the two groups ( P>0.05). The wound healing time, postoperative recovery time and hospitalization time in group A were significantly shorter than those in group B: (21.34 ± 2.21) d vs. (27.86 ± 2.84) d, (23.12 ± 2.42) d vs. (28.36 ± 2.91) d, (8.12 ± 0.83) d vs. (13.25 ± 1.47), P<0.05. At 1 and 7 d after surgery, the VAS and Wexner score in group A were lower than those in group B: (6.11 ± 0.62) points vs. (6.54 ± 0.67) points, (2.39 ± 0.25) points vs. (3.21 ± 0.33) points, (7.54 ± 0.77) points vs. (8.96 ± 0.91) points, (4.22 ± 0.43) points vs. (5.68 ± 0.58) points, P<0.05. There was no significant difference in total incidence of complications between the two groups within 1 month after surgery ( P>0.05). Conclusions:Compared with incision and hanging put-aside drainage, incision and hanging wire-to-port drainage can promote wound healing, shorten hospitalization time, relieve postoperative pain and improve anal function in patients with perianal abscess, with certain safety.

Objective This study aims to assess the role of DNA methylation changes in tongue cancer through a comprehensive analysis of global DNA methylation alterations during experimental lingual carcinogenesis.Methods C57BL/6J mice were subjected to 16-week oral administration of 4-nitroquinoline-1-oxide(4NQO,50 mg/L).Lingual mucosa samples,being representative of normal tissue(week 0)and early(week 12)and advanced(week 28)tumorigen-esis,were harvested for microarray and methylated DNA immunoprecipitation sequencing(MeDIP-Seq).The mRNA and promoter methylation of transforming growth factor-beta-signaling protein 1(SMAD1)were evaluated with real-time quantitative reverse transcription polymerase chain reaction and Massarray in human lingual mucosa and tongue cancer cell lines.Results The cytosine guanine island(CGI)methylation level observed at 28 weeks surpassed that of both 12 weeks and 0 weeks.The promoter methylation level at 12 weeks exceeded that at 0 weeks.Notably,208 differentially expressed genes were negatively correlated to differential methylation in promoters among 0,12,and 28 weeks.The mRNA of SMAD1 was upregulated,con-current with a decrease in promoter methylation levels in cell lines compared to normal mucosa.Conclusion DNA methylation changed during lingual carcinogenesis.Overexpression of SMAD1 was correlated to promoter hypomethyl-ation in tongue cancer cell lines.

Frontotemporal dementia (FTD) is a group of dementia diseases mainly characterized by progressive mental-behavioral abnormalities, executive dysfunction, and language impairment. A small number of FTD patients also present with movement disorders at certain disease course. Here the clinical and multimodal positron-emission tomography (PET) imaging manifestations in a patient with frontotemporal lobe dementia and parkinsonian syndrome are reported. 18F-fluorodopa PET showed reduced uptake in the head of the caudate nucleus. 18F-AV-45 PET showed negative amyloid deposition. 18F-AV-1451 PET showed tau deposition in the neocortex. The clinical and neuroimaging features support the underlying frontotemporal lobar degeneration-tau pathology.