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.

Aim To investigate the mechanism of ligu aged 2 months of the same strain were used as the constilide (LIG) in delaying the senescence of auditory trol (Ctrl) group. Auditory brainstem response test was cortex and treating central presbycusis. Methods used to detect the auditory threshold of mice before and Forty C57BL/6J mice aged 13 months were randomly di after treatment. Levels of serum MDA and activity of vided into ligustilide low-dose(L-LIG) group, ligustil serum SOD were detected to display the level of oxidative ide medium-dose (M-LIG) group, ligustilide high-dose stress. The pathological changes of auditory cortex were (H-LIG) group and aging (Age) group, and 10 mice observed by HE staining. Ferroptosis was observed by

Aim To screen and study the expression of long non-coding RNA (IncRNA) in rats with middle cerebral artery occlusion (MCAO) with MCAO treated with Tao Hong Si Wu decoction (THSWD) and determine the possible molecular mechanism of THSWD in treating MCAO rats. Methods Three cerebral hemisphere tissue were obtained from the control group, MCAO group and MCAO + THSWD group. RNA sequencing technology was used to identify IncRNA gene expression in the three groups. THSWD-regulated IncRNA genes were identified, and then a THSWD-regu-lated IncRNA-mRNA network was constructed. MCODE plug-in units were used to identify the modules of IncRNA-mRNA networks. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) were used to analyze the enriched biological functions and signaling pathways. Cis- and trans-regulatory genes for THSWD-regulated IncRNAs were identified. Reverse transcription real-time quantitative pol-ymerase chain reaction (RT-qPCR) was used to verify IncRNAs. Molecular docking was used to identify IncRNA-mRNA network targets and pathway-associated proteins. Results In MCAO rats, THSWD regulated a total of 302 IncRNAs. Bioinformatics analysis suggested that some core IncRNAs might play an important role in the treatment of MCAO rats with THSWD, and we further found that THSWD might also treat MCAO rats through multiple pathways such as IncRNA-mRNA network and network-enriched complement and coagulation cascades. The results of molecular docking showed that the active compounds gallic acid and a-mygdalin of THSWD had a certain binding ability to protein targets. Conclusions THSWD can protect the brain injury of MCAO rats through IncRNA, which may provide new insights for the treatment of ischemic stroke with THSWD.

Objective:To explore the rehabilitation effect of multi-factor intervention based on the Finnish model of prevention of cognitive impairment in the elderly on patients with cognitive impairment after first-episode stroke, and to provide reference for rehabilitation nursing of cognitive impairment after stroke.Methods:The quasi-experiment research scheme was adopted and convenience sampling method was used to select participants with first-episode stroke cognitive impairment hospitalized in the General Hospital of Tianjin Medical University Airport Site. The 50 patients admitted from January to June 2022 were selected as the control group, and 50 patients admitted from July to December 2022 were selected as the intervention group. The control group received routine rehabilitation nursing and health education, and the intervention group received the Finnish model of prevention of cognitive impairment in the elderly on patients before discharge on the basis of the control group. The Mini-Mental State Examination (MMSE) and Health Education Compliance Assessment Scale for Stroke Patients were used to evaluate the changes of overall cognitive function and rehabilitation compliance before intervention, 3 and 6 months after intervention.Results:The final control group included 49 cases, including 35 males and 14 females, aged (64.67 ± 7.47) years old; the intervention group included 50 cases, 32 males and 18 females, aged (66.68 ± 8.75) years old. Before intervention, there were no significant differences in overall cognitive function and compliance of rehabilitation score ( P>0.05). At 3 and 6 months after intervention, the overall cognitive function score, the total score on compliance of rehabilitation, dimension scores of diet compliance, exercise rehabilitation compliance and health behavior compliance of the intervention group were (26.36±2.36) , (125.96 ± 13.80) , (23.30 ± 5.26) , (27.72 ± 4.46) , (43.66 ± 6.80) and (27.26 ± 3.71) , (152.44 ± 9.06) , (30.12 ± 6.42) , (33.32 ± 3.02) , (52.36 ± 4.70) , respectively. They were higher than the control group (24.04 ± 4.50) , (116.67 ± 10.26) , (19.31 ± 3.95) , (25.29 ± 3.45) , (40.59 ± 4.33) and (24.27 ± 4.33) , (138.92 ± 16.71) , (24.20 ± 4.48) , (30.00 ± 5.53) , (47.65 ± 8.03) , and the differences had statistical significance ( t values were -5.31- -2.67, all P<0.05). According to the variance analysis of repeated measurement, intergroup and time factor, the interaction between groups and time had significant impact on general cognitive function score, the total score of rehabilitation compliance, the dimension scores of diet, exercise rehabilitation and health behavior compliance ( Fgroup values were 8.33-18.08, Ftime values were 135.71-944.69, Finteraction values were 5.46-27.30, all P<0.05) . Time factor had significant impact on patient medication adherence score ( Ftime=206.23, P<0.05) . Conclusions:Multi-factor intervention based on the Finnish model of prevention of cognitive impairment in the elderly can improve the overall cognitive function and rehabilitation compliance of patients with cognitive impairment after first-episode stroke.

AIM To investigate the effects of Ginkgo biloba extract on hearing function,cochlear morphology and autophagy-related protein expression in a rat model of presbycusis.METHODS Forty-five rats were randomly divided into the control group,the model group and the low,medium and high dose G.biloba extract groups(10,20 and 30 mg/kg),with 9 rats in each group.The rat model of presbycusis was established by intraperitoneal injection of 500 mg/kg D-galactose(D-gal).Eight weeks after the corresponding administration,the rats had their changes of hearing threshold detected by the auditory brainstem evoked potential(ABR);their morphological changes of cochlear hair cells,stria vascularis(SV)and spiral ganglion cells observed by HE staining;their number of hair cells inside and outside the cochlea detected by immunofluorescence staining;their ultrastructure changes of cochlear hair cells observed by transmission electron microscopy;and their expression of autophagy-related proteins in cochlea tissue detected by Western blot.RESULTS Compared with the control group,the model group displayed increased ABR threshold(P<0.01);more severely damaged inner and outer hair cells,spiral ganglion cells and SV,decreased SV thickness and numbers of spiral ganglion cells,inner and outer hair cells and autophagosomes(P<0.01);decreased protein expressions of Beclin1 and LC3 Ⅱ and ratio of LC3 Ⅱ/LC3 Ⅰ in cochlear tissue(P<0.01),and higher P62 protein expression(P<0.01).Compared with the model group,the medium and high dose G.biloba extract groups shared decreased ABR thresholds(P<0.01);improved morphology of inner and outer hair cells and SV in the cochlea,normalized,morphology of spiral ganglion cells,and increased SV thickness and the numbers of spiral ganglion cells,inner and outer hair cells and autophagosomes(P<0.05,P<0.01);increased protein expressions of Beclin1 and LC3 Ⅱ and the ratio of LC3 Ⅱ/LC3 Ⅰ in the cochlea(P<0.01),and decreased P62 protein expression(P<0.01).CONCLUSION The protective effects G.biloba extract on hearing function and cochlear cells in the rat model of presbycusis may be associated with the up-regulated expression of Beclin1 and LC3 Ⅱ proteins and down-regulated P62 protein expression in cochlear tissues.

ObjectiveTo reveal the influence of Jianchangbang characteristic processing method on the change process of volatile components and the processing mechanism of reducing toxicity and increasing efficiency of Magnoliae Officinalis Cortex（MOC） by studying the changes in the composition and content of volatile components during the processing of ginger processed Xingpo pieces. MethodSamples of raw products， ginger juice moisturized products and stir-fried and heap moisturized products of MOC were taken according to the set time points， and headspace gas chromatography-mass spectrometry（HS-GC-MS） was used to determine the contents of volatile components in the samples， and the relative content of each component was obtained by peak area normalization. Principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were performed on the sample data using SIMCA 14.1 software， and the differential components during the processing were screened with variable importance in the projection（VIP） value>1 as the indicator. ResultA total of 68 volatile components were identified in the samples， among which some of the chemical components with similar structures showed similar trends of changes， and there was also the phenomenon of interconversion between compounds. Compared with the raw products， the contents of 42 components in ginger juice moisturized products increased， while the contents of 25 components decreased， 19 components were unique， and 4 components were unique to the raw products. Compared with ginger juice moisturized products， MOC in the early stage of piling had three unique components， and the contents of 11 components such as cyclosativene and （+）-α-pinene increased， and the contents of 5 components such as tricyclic terpene and α-curcumene decreased， and ginger juice moisturized products had four unique components. Compared with the early stage of piling， in the later stage， the contents of 8 components such as （+）-α-pinene and camphene significantly increased， while the contents of 6 components such as linalool and α-selinene significantly decreased. During the processing of MOC， there were significant changes in the chemical composition of the samples before and after 20 days. The differences between ginger juice moistening and the early stage of piling， the early stage and the later stage of piling could be clearly distinguished. ConclusionDuring the preparation process of ginger processed Xingpo pieces， the addition of ginger juice can reduce the contents of stimulating components， and the contents of active components continue to increase in several stages， such as the addition of ginger juice， frying and heap moisturizing， the quality of the decoction pieces may change significantly at about 20 d of processing. This study can provide a research basis for exploring the processing mechanism of ginger processed Xingpo pieces.

Objective To study the mechanism of the amelioration of renal injury in immunoglobulin A nephropathy(IgAN)rats by multi-glycosides of Tripterygium wilfordii(GTW)based on the sphingosine kinase 1(Sphk1)/sphingosine 1-phosphate receptor 2(S1PR2)signalling pathway.Methods An IgAN rat model was established by means of bovine serum albumin gavage+castor oil and carbon tetrachloride subcutaneous injection+lipopolysaccharide tail vein injection.The rats were randomly divided into the model,control and experimental groups,with 9 rats in each group,and 10 normal rats were taken as the blank group.In the control group,6.25 mg·kg-1·d-1 prednisone was given by gavage;in the experimental group,9.375 mg·kg-1·d-1GTW was given by gavage;and in the blank and model groups,0.5 mL·100 g-1·d-1 0.9％NaCl was given by gavage,and the drugs were administered to the rats once a day in each group.At the end of the 15th week,urine samples were collected and blood albumin(ALB),blood urea nitrogen(BUN),24 hour-urine protein quantification(24 h-UTP),and urine erythrocyte counts were determined in each group,and the expression levels of Sphk1/S1PR2 proteins in each group were detected by Western blotting.Results The renal pathological changes in the control and experimental groups were significantly reduced compared with those in the model group by hematoxylin-eosin staining and immunofluorescence.The levels of ALB in the blank,model,control and experimental groups were(32.49±2.23),(22.98±0.51),(26.01±1.33)and(26.53±1.92)g·L-1;the levels of BUN were(6.11±1.71),(13.75±2.96),(6.71±1.35)and(4.77±0.99)mmol·L-1;the levels of 24 h-UTP were(5.72±1.96),(9.12±2.15),(5.78±2.05)and(4.75±1.50)mg·24 h-1;the urine erythrocyte counts were(9.73±2.40),(14.62±2.60),(9.90±1.59)and(9.46±2.94)cell·μL-1;the relative expression levels of Sphk1 protein were 0.85±0.02,1.47±0.02,1.06±0.02 and 1.09±0.02;the relative expression levels of S1PR2 protein were 0.27±0.02,0.88±0.01,0.43±0.02,and 0.42±0.02,respectively.The above indexes in the model group were statistically significant when compared with those of the control group and the experimental group(all P＜0.01).Conclusion GTW may reduce the proliferation of mesangial cells by inhibiting the Sphk1/S1PR2 signalling pathway,thus attenuating kidney injury in IgAN rats.