Objective To investigate the effect of N-myc downstream regulated gene 1(NDRG1)on ferroptosis in mouse brain microvascular endothelial cells(BMVEC)induced by oxygen-glu-cose deprivation(OGD).Methods After primary BMVEC were isolated and cultured from mice,electron microscopy was used to observe the mitochondrial morphology of the cells after OGD.bEnd.3 cells were cultured and divided into six groups:control group,model group(OGD),si-NC(negative control)group,si-NDRG1(NDRG1 interference RNA)group,OGD+si-NC(negative control modeling)group,and OGD+si-NDRG1(NDRG1 interference)group(n=3).The model group,OGD+si-NC group,and OGD+si-NDRG1 group were subjected to the OGD model.Si-NC transfection was performed in the si-NC and OGD+si-NC groups,while si-NDRG1 transfection was carried out in the si-NDRG1 and OGD+si-NDRG1 groups.Cell viability,MDA,glutathione,Fe2+,lipid peroxidation levels,and protein levels of NDRG1,glutathione peroxidase 4(GPX4),and acyl-CoA synthetase long-chain family member 4(ACSL4)were detected in each group.Results Compared with the control group,the model group showed a significant reduction in the number of cells adhering to the surface after OGD treatment,swollen cytoplasm and decrease in cell viability[(37.68±2.43)％vs(96.34±12.08)％,P＜0.05],down-regulation of GPX4 and up-regulation of ACSL4 and NDRG1 expression(0.78±0.02 vs 1.15±0.01,P＜0.01;1.45±0.04 vs 0.78±0.12,P＜0.01;1.22±0.01 vs 0.13±0.01,P＜0.01).In the si-NDRG1 group,the protein levels of GPX4 and NDRG1 were significantly lower,while the protein levels of ACSL4 and gluta-thione were significantly higher than the si-NC group(P＜0.05).The OGD+si-NC group showed significantly lower GPX4 expression and glutathione level,while obviously higher NDRG1,ACSL4 expression,MDA,and relative fluorescence intensities of Fe2+and oxidized lipid levels when compared to the si-NC and si-NDRG1 groups(P＜0.05).The OGD+si-NDRG1 group showed significantly lower GPX4 expression and glutathione level,and higher ACSL4 and relative fluorescence intensity of Fe2+than the si-NC group and the si-NDRG1 group,while lower NDRG1 expression than the si-NC group but higher than the si-NDRG1 group,and lower NDRG1,ACSL4,MDA,and relative fluorescence intensities of Fe2+and oxidized lipids when compared with the OGD+si-NC group(P＜0.05).Conclusion Knockdown of NDRG1 can alleviate OGD-induced ferroptosis in microvascular endothelial cells by improving iron metabolism and lipid per-oxidation.

Objective To investigate the effect of N-myc downstream regulated gene 1(NDRG1)on ferroptosis in mouse brain microvascular endothelial cells(BMVEC)induced by oxygen-glu-cose deprivation(OGD).Methods After primary BMVEC were isolated and cultured from mice,electron microscopy was used to observe the mitochondrial morphology of the cells after OGD.bEnd.3 cells were cultured and divided into six groups:control group,model group(OGD),si-NC(negative control)group,si-NDRG1(NDRG1 interference RNA)group,OGD+si-NC(negative control modeling)group,and OGD+si-NDRG1(NDRG1 interference)group(n=3).The model group,OGD+si-NC group,and OGD+si-NDRG1 group were subjected to the OGD model.Si-NC transfection was performed in the si-NC and OGD+si-NC groups,while si-NDRG1 transfection was carried out in the si-NDRG1 and OGD+si-NDRG1 groups.Cell viability,MDA,glutathione,Fe2+,lipid peroxidation levels,and protein levels of NDRG1,glutathione peroxidase 4(GPX4),and acyl-CoA synthetase long-chain family member 4(ACSL4)were detected in each group.Results Compared with the control group,the model group showed a significant reduction in the number of cells adhering to the surface after OGD treatment,swollen cytoplasm and decrease in cell viability[(37.68±2.43)％vs(96.34±12.08)％,P＜0.05],down-regulation of GPX4 and up-regulation of ACSL4 and NDRG1 expression(0.78±0.02 vs 1.15±0.01,P＜0.01;1.45±0.04 vs 0.78±0.12,P＜0.01;1.22±0.01 vs 0.13±0.01,P＜0.01).In the si-NDRG1 group,the protein levels of GPX4 and NDRG1 were significantly lower,while the protein levels of ACSL4 and gluta-thione were significantly higher than the si-NC group(P＜0.05).The OGD+si-NC group showed significantly lower GPX4 expression and glutathione level,while obviously higher NDRG1,ACSL4 expression,MDA,and relative fluorescence intensities of Fe2+and oxidized lipid levels when compared to the si-NC and si-NDRG1 groups(P＜0.05).The OGD+si-NDRG1 group showed significantly lower GPX4 expression and glutathione level,and higher ACSL4 and relative fluorescence intensity of Fe2+than the si-NC group and the si-NDRG1 group,while lower NDRG1 expression than the si-NC group but higher than the si-NDRG1 group,and lower NDRG1,ACSL4,MDA,and relative fluorescence intensities of Fe2+and oxidized lipids when compared with the OGD+si-NC group(P＜0.05).Conclusion Knockdown of NDRG1 can alleviate OGD-induced ferroptosis in microvascular endothelial cells by improving iron metabolism and lipid per-oxidation.

Objective To investigate the relationship between brain structural networks and gut micro-biota in patients with mild cognitive impairment associated with Parkinson's disease(PD-MCI),and the impact on cognitive function by neuroimaging and intestinal microbiology techniques.Methods 29 cases of patients with PD-MCI and 17 cases of PD patients with normal cognitive function(PD-NC)were enrolled.MRI T1-weighted and diffusion tensor imaging were collected for graph theory analysis,and fecal samples were analyzed using 16s DNA sequencing.Partial correlation analysis assessed relationships among differential bacteria,structural network prop-erties,and cognitive scale scores,finally followed by mediation effect analysis.Results In PD patients,the abundance of Prevotellaceae,Alloprevotella,and UCG-10 bacteria was positively correlated with language and memory cognitive domains,while the abundance of UCG-010 showed a negative correlation with executive function.Additionally,the gut microbiota also was associated with several distinct brain structural network node characteristics.Mediation analysis indicated that Prevotellaceae's effect on logical memory was mediated by the node degree in the right opercular inferior frontal gyrus(IE=0.074,95%CI:0.21～0.001,P=0.046).Conclusions PD-MCI patients showed distinct gut microbiota and brain network features compared to PD-NC patients.The association and the me-diation analysis of gut microbiota with brain networks and cognitive impairment suggests a role for Prevotellaceae in brain network alterations related to MCI,highlighting the gut-brain axis's potential influence on cognition.

Objective To investigate the relationship between brain structural networks and gut micro-biota in patients with mild cognitive impairment associated with Parkinson's disease(PD-MCI),and the impact on cognitive function by neuroimaging and intestinal microbiology techniques.Methods 29 cases of patients with PD-MCI and 17 cases of PD patients with normal cognitive function(PD-NC)were enrolled.MRI T1-weighted and diffusion tensor imaging were collected for graph theory analysis,and fecal samples were analyzed using 16s DNA sequencing.Partial correlation analysis assessed relationships among differential bacteria,structural network prop-erties,and cognitive scale scores,finally followed by mediation effect analysis.Results In PD patients,the abundance of Prevotellaceae,Alloprevotella,and UCG-10 bacteria was positively correlated with language and memory cognitive domains,while the abundance of UCG-010 showed a negative correlation with executive function.Additionally,the gut microbiota also was associated with several distinct brain structural network node characteristics.Mediation analysis indicated that Prevotellaceae's effect on logical memory was mediated by the node degree in the right opercular inferior frontal gyrus(IE=0.074,95%CI:0.21～0.001,P=0.046).Conclusions PD-MCI patients showed distinct gut microbiota and brain network features compared to PD-NC patients.The association and the me-diation analysis of gut microbiota with brain networks and cognitive impairment suggests a role for Prevotellaceae in brain network alterations related to MCI,highlighting the gut-brain axis's potential influence on cognition.

Parkinson′s disease (PD) is the most common age-related neurodegenerative disease, which has the effects on the patients′ quality of life and brings a huge burden to the society and family. The pathological feature of PD is the abnormal accumulation of alpha-synuclein (α-syn) in the brain of substantia nigra-striatum, mediating the death of dopaminergic neurons. However, further studies have found that α-syn mediates the abnormal function of astrocytes leading to the destruction of the blood-brain barrier and the release of inflammatory factors caused by microglia, which are related to the pathogenesis of PD. Therefore, neurons, glial cells, and blood vessels as a whole named neurovascular unit can better reflect the pathophysiological environment of PD and reveal the PD pathogenesis. Studies have detected the ways of α-syn transmission, such as prion-like, tunneling nanotubes, exosomes, are connected with the pathogenesis and progression of PD. The Braak stage and the prospective cohort of early PD provide a view that the peripheral α-syn to the central nervous system may be an another important way to mediate the pathogenesis and progression of PD. The research about the abnormal aggregation and spread of α-syn can provide the new theory for the pathogenesis of PD and the new disease modifying therapy of PD. This article reviews the role of abnormal aggregation and transmission of α-syn in the pathogenesis of PD.

Objective To explore the improvement of cognitive impairment in patients with mild and moderate vascular cognitive impairment( VCI) treated with cerebralcare granule ( CG) and basic treat-ment.Methods From October in 2014 to December in 2016 year,143 cases of VCI patients were admitted from six hospitals in some areas of Hebei Province as the research objects,and divided into CG treatment group (experimental group,n=98) and conventional treatment group (control group,n=66).Three months and six months after treatment,the score of mental state examination ( MMSE) ,the Montreal cognitive assess-ment scale ( MoCA) and the daily living capacity scale( ADL) of the two groups were compared after 3 and 6 moths of treatment.Results ①The total score of MMSE in the experimental group was higher than that of the control group for six months after treatment, and the difference was statistically significant ( ( 23. 76 ± 4.02) vs (21.52±5.13),P<0.05).②Six months after treatment,the total score of MoCA ((21.06±4.66) vs (18.32±5.20)) and visual spatial/executive function((3.05±1.37) vs (2.42±1.66)),calculation force ((2.24±0.84) vs (1.83±1.05)) and orientation ability((5.20±1.12) vs (4.06±1.35)) scores in the ex-perimental group were significantly higher than those in the control group (P<0.05) .③Six months after treat-ment,the ADL score in the experimental group was lower than that before treatment,and the difference was statistically significant((24.96±8.74) vs (29.20±11.55),P<0.05);while there was no significant difference in the ADL score between the experimental group and the control group after 6 months (P>0.05).Conclusion CG can improve cognitive function in mild to moderate VCI patients,mainly in visual space/execution func-tion,calculation ability and orientation ability,and with the extension of treatment time,the curative effect is more obvious.

OBJECTIVE:To investigate the composition and medication regularities of prescriptions for Treatise on Febrile Dis-eases. METHODS:The prescriptions included in Treatise on Febrile Diseases were collected and inputted into TCM inheritance platform system(V2.5)software,and prescription database was established. The medication and the compatibility regularity of pre-scriptions were excavated using the function of software integration. RESULTS & CONCLUSIONS:83 kinds of TCM involved in 112 prescriptions ranked by frequency,among which 24 ingredients were used more than 4 times. Commonly used TCM groups were summarized to evolve 16 key groups and 8 new prescriptions. Four properties of TCM are mainly the property of“Wen and Han”,and five tastes mostly are“Sweet,Bitter,Spicy”. TCM with the property of“Wen and Sweet”taste are more than those with the property of“Wen and Spicy”,and TCM acting on spleen are more than those acting on lung.