1.Protective effects of 7,8-DHF on the retina of diabetic rats and its mechanism
Aiping YANG ; Xinbao ZHENG ; Chunfeng CHEN ; Jiayu CHEN ; Jing XIA ; Mingfang LI ; Luyun WU ; Yongwang ZHAO
Recent Advances in Ophthalmology 2025;45(1):5-9
Objective To explore the protective effect of 7,8-dihydroxyflavone(7,8-DHF)on the retina of diabetic rats and its mechanism.Methods A total of 18 SPF-grade male Sprague-Dawley(SD)rats were selected and randomly divided into three groups:the normal group,the model group,and the experimental group,with six rats in each group.Rats in the normal group were fed with a normal diet,while those in the remaining two groups were fed with a high-fat emulsion through oral gavage continuously for 2 weeks to establish a diabetes model.Rats in the experimental group were provided with 7,8-DHF(5 mg?kg-1)by continuous intraperitoneal injection,while those in the normal and model groups were provided with an equal volume of normal saline.The rats in all groups received intervention once a day for 2 weeks.The changes in the body mass and fasting blood glucose(FBG)were observed before and after modeling.Besides,the changes in the retina of rats in each group were observed by fundus fluorescence angiography(FFA)after 2 weeks.Moreo-ver,the changes and apoptosis of retinal neuronal cells were detected by hematoxylin and eosin(HE)staining,CD31 im-munofluorescence,and terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)assays.Results After 2 weeks of continuous intervention,compared with the normal group,the body mass of rats in the model and experimental groups decreased(both P<0.05),and the FBG increased significantly(both P<0.05);compared with the model group,the experimental group showed an increase in the body mass(P<0.05)and a decrease in the FBG(P<0.05).The fundus photography and FFA of rats in the three groups did not reveal any fundus features of diabetic retinopathy.The HE staining results showed that the retina of rats in the normal and experimental groups was structurally intact,with neatly arranged cells and uniform thickness;the retinal structure of rats in the model group remained clear.However,the thickness of the inner layers of the retina of rats in the model group was thinner compared with the normal and experimental groups,exhibi-ting significant differences(both P<0.05).The CD31 immunofluorescence assay results indicated that the CD31 immuno-fluorescence intensity values of rats in the three groups were roughly comparable,without significant differences(all P>0.05).The TUNEL assay results suggested that the apoptosis of retinal neurons increased in rats in the model group com-pared with the normal group,exhibiting significant differences(P<0.001);compared with the model group,the apoptosis of retinal neurons of rats in the experimental group decreased significantly,displaying significant differences(P<0.001).Conclusion The apoptosis of retinal neurons in diabetic rats may precede vascular endothelial cell injury.7,8-DHF can improve the body mass,decrease the blood glucose level,and protect the retinal neurons in diabetic rats.
2.Effects of shared decision-making oriented vocational training on the social function of patients with schizophrenia
Chunyan JIANG ; Jiuhong SHUAI ; Hongyuan DENG ; Junhua ZHENG ; Chunfeng GOU ; Xiaoli YANG ; Deying TONG ; Hao FENG ; Xia HUANG ; Ru GAO
Sichuan Mental Health 2025;38(3):229-234
BackgroundAs a high prevalence disorder, schizophrenia has caused significant burden to family and society due to the impairment of occupational and social function. Currently, the dominant vocational training model in China follows a paternalistic, clinician-led decision-making approach. Although it improves patients' social function to some extent, it undermines their autonomy and treatment adherence. Therefore, it is urgently necessary to explore a new intervention method to enhance treatment compliance and social function in patients. ObjectiveTo explore the impact of shared decision-making oriented vocational training on social function in hospitalized schizophrenia patients, so as to provide references for rehabilitation interventions. MethodsA total of 68 patients diagnosed with schizophrenia according to the International Classification of Diseases, tenth edition (ICD-10) criteria were consecutively enrolled from January to June 2024 at The Third People's Hospital of Wenjiang Distric, Chengdu. Participants were randomly allocated into the research group (n=34) and the control group (n=34) using a random number table method. Both groups received routine rehabilitation training, while the research group received shared decision-making oriented vocational training for 12 weeks, 2 times a week for 2 hours each time. Before and at the 4th and 12th week of intervention, two groups were evaluated by General Self-Efficacy Scale (GSES), Stigma Scale for Mental Illness (SSMI), Scale of Social function of Psychosis Inpatients (SSFPI) and Inpatient Psychiatric Rehabilitation Outcome Scale (IPROS). ResultsA total of 63 participants completed the study, with 30 cases in the research group and 33 cases in the control group. Repeated measures ANOVA revealed statistically significant time effects and interaction effects in both groups for GSES, SSMI, SSFPI and IPROS scores (F=20.451, 16.022; 26.193, 12.944; 23.957, 5.023; 11.776, 3.985, P<0.05 or 0.01), while no significant group effects were observed (F=0.188, 0.742, 1.878, 0.474, P>0.05). At the 12th week of intervention, there were statistically significant differences in GSES, SSMI, SSFPI and IPROS scores between the two groups. ConclusionShared decision-making oriented vocational training may help to improve social function in patients with schizophrenia. [Funded by 2023 Chengdu Medical Research Project (number, 2023468)]
3.Meta-analysis of anterior cervical decompression and fusion ROI-CTM self-locking system in treatment of degenerative cervical spondylosis
Yanjie ZHOU ; Chunfeng CAO ; Zhongzu ZHANG ; Xiong NIU ; Xin WANG ; Zaihai YANG ; Liang ZHOU ; Bo LI
Chinese Journal of Tissue Engineering Research 2025;29(3):617-627
OBJECTIVE:Anterior cervical decompression and fusion is a classic surgical method for the treatment of degenerative cervical spondylosis.The use of nail plates increases the fusion rate and stability and indirectly leads to adjacent vertebral degeneration and postoperative dysphagia.In this paper,the clinical results and complications of ROI-CTM self-locking system and traditional cage combined with screw-plate internal fixation in the treatment of degenerative cervical spondylosis were compared by meta-analysis to provide evidence-based support for the selection of internal fixation methods in anterior cervical decompression and fusion. METHODS:CNKI,WanFang,VIP,PubMed,Cochrane Library,Web of Science,and Embase databases were searched for Chinese and English literature on the application of ROI-CTM self-locking system and fusion cage combined with screw plate internal fixation in the treatment of degenerative cervical spondylosis.The retrieval time range was from inception to July 2023.Two researchers selected the literature strictly according to the inclusion and exclusion criteria.The Cochrane bias risk tool was used to evaluate the quality of randomized controlled trials.Newcastle-Ottawa Scale was used to assess the quality of cohort studies.Meta-analysis was performed using RevMan 5.4 software.Outcome indicators included operation time,intraoperative blood loss,Japanese Orthopaedic Association score,Neck Disability Index,C2-C7 Cobb angle,fusion rate,incidence of adjacent vertebral degeneration,cage subsidence rate,and incidence of dysphagia. RESULTS:Thirteen articles were included,including eleven retrospective cohort studies and two randomized controlled trials,with 1 136 patients,569 in the ROI-C group,and 567 in the cage combined with the nail plate group.Meta-analysis results showed that the operation time(MD=-15.52,95%CI:-18.62 to-12.42,P<0.000 01)and intraoperative blood loss(MD=-24.53,95%CI:-32.46 to-16.61,P<0.000 01)in the ROI-C group and the fusion device combined with nail plate group.Postoperative adjacent segment degeneration rate(RR=0.40,95%CI:0.27-0.60,P<0.000 01)and postoperative total dysphagia rate(RR=0.18,95%CI:0.13-0.26),P<0.000 01)were statistically different.The two groups had no significant difference in Japanese Orthopaedic Association score,Neck Disability Index,C2-C7 Cobb angle,fusion rate,or cage subsidence rate(P≥0.05). CONCLUSION:Applying an ROI-CTM self-locking system and traditional cage combined with plate internal fixation in anterior cervical decompression and fusion can achieve satisfactory clinical results in treating degenerative cervical spondylosis.The operation of the ROI-CTM self-locking system is more straightforward.Compared with a cage combined with plate internal fixation,the ROI-CTM self-locking system can significantly reduce the operation time and intraoperative blood loss and has obvious advantages in reducing the incidence of postoperative dysphagia and adjacent segment degeneration.The ROI-CTM self-locking system is recommended for patients with skip cervical spondylosis and adjacent vertebral disease.However,given its possible high settlement rate,using a fusion cage combined with screw-plate internal fixation is still recommended for patients with degenerative cervical spondylosis with multiple segments and high-risk factors of fusion cage settlement,such as osteoporosis and vertebral endplate damage.
4.Protective effects of 7,8-DHF on the retina of diabetic rats and its mechanism
Aiping YANG ; Xinbao ZHENG ; Chunfeng CHEN ; Jiayu CHEN ; Jing XIA ; Mingfang LI ; Luyun WU ; Yongwang ZHAO
Recent Advances in Ophthalmology 2025;45(1):5-9
Objective To explore the protective effect of 7,8-dihydroxyflavone(7,8-DHF)on the retina of diabetic rats and its mechanism.Methods A total of 18 SPF-grade male Sprague-Dawley(SD)rats were selected and randomly divided into three groups:the normal group,the model group,and the experimental group,with six rats in each group.Rats in the normal group were fed with a normal diet,while those in the remaining two groups were fed with a high-fat emulsion through oral gavage continuously for 2 weeks to establish a diabetes model.Rats in the experimental group were provided with 7,8-DHF(5 mg?kg-1)by continuous intraperitoneal injection,while those in the normal and model groups were provided with an equal volume of normal saline.The rats in all groups received intervention once a day for 2 weeks.The changes in the body mass and fasting blood glucose(FBG)were observed before and after modeling.Besides,the changes in the retina of rats in each group were observed by fundus fluorescence angiography(FFA)after 2 weeks.Moreo-ver,the changes and apoptosis of retinal neuronal cells were detected by hematoxylin and eosin(HE)staining,CD31 im-munofluorescence,and terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)assays.Results After 2 weeks of continuous intervention,compared with the normal group,the body mass of rats in the model and experimental groups decreased(both P<0.05),and the FBG increased significantly(both P<0.05);compared with the model group,the experimental group showed an increase in the body mass(P<0.05)and a decrease in the FBG(P<0.05).The fundus photography and FFA of rats in the three groups did not reveal any fundus features of diabetic retinopathy.The HE staining results showed that the retina of rats in the normal and experimental groups was structurally intact,with neatly arranged cells and uniform thickness;the retinal structure of rats in the model group remained clear.However,the thickness of the inner layers of the retina of rats in the model group was thinner compared with the normal and experimental groups,exhibi-ting significant differences(both P<0.05).The CD31 immunofluorescence assay results indicated that the CD31 immuno-fluorescence intensity values of rats in the three groups were roughly comparable,without significant differences(all P>0.05).The TUNEL assay results suggested that the apoptosis of retinal neurons increased in rats in the model group com-pared with the normal group,exhibiting significant differences(P<0.001);compared with the model group,the apoptosis of retinal neurons of rats in the experimental group decreased significantly,displaying significant differences(P<0.001).Conclusion The apoptosis of retinal neurons in diabetic rats may precede vascular endothelial cell injury.7,8-DHF can improve the body mass,decrease the blood glucose level,and protect the retinal neurons in diabetic rats.
5.Transcranial ultrasound imaging characteristics of 6-OHDA Parkinson's disease rats and their correlation with motor deficits and pathological changes
Ying ZHANG ; Qingyuan LIU ; Jian WU ; Min YANG ; Fen WANG ; Yingchun ZHANG ; Chunfeng LIU
Chinese Journal of Ultrasonography 2025;34(3):239-246
Objective:To analyze transcranial sonography(TCS)imaging characteristics of rats with 6-hydroxydopamine hydrochloride(6-OHDA)and explore the correlations between the imaging characteristics with motor deficits and pathological changes.Methods:Twenty-nine male SD rats were divided into 3 groups:8 in the no-treatment control(NC)group,10 in the Sham group and 11 in the 6-OHDA group. The model for Sham/Parkinson's disease(PD)was established by stereotacticly injecting saline/6-OHDA containing ascorbic acid to bilateral substantia nigra pars compacta(SNpc). After three weeks,the models were stable. At the fourth week and seventh week,the behavioral testing was accomplished. The TCS examination was performed weekly at the same time for four weeks. At the eighth week,the rats were sacrificed for pathology.Results:①Behavioral testing:6-OHDA group showed asymmetric motor deficits and the difference was significant compared with the NC group and Sham group(both P<0.001). ②TCS examination:compared with the NC and Sham group,there were asymmetric substantia nigra hyperechogenicity(SNH)in 6-OHDA group(both P<0.05);meanwhile the area of SNH in the left was significantly larger in the right side( P<0.05).No significant change in SNH area was found during the continuous observation period of weeks 4-7. For 6-OHDA group,the area of SNH was negatively correlated with the number of forelimb wall-touches( r=-0.825, P<0.001). ③Pathological examination:compared with NC group and sham group,the substantia nigra(SN)of 6-OHDA group showed a series of pathological events,including dopaminergic(DA)neurons asymmetrically decreasing,asymmetric ironion deposition and the number of active microglia increasing(all P<0.05). Correlation analysis showed that the area of SNH was negatively correlated with the number of DA neurons survivors( r=-0.689, P=0.013),while the activation of microglial and the deposition of iron were positively correlated with the area of SNH( r=0.915,0.735;all P<0.001). Conclusions:Asymmetric SNH of 6-OHDA PD rats is a representation of asymmetric motor deficits,and the mechanism is related to a catalogue of asymmetric pathological changes in SN,which comprise DA neurons decreasing,asymmetric iron ions deposition,microglial activating.
6.Changes of brain excitation/inhibition balance and gray matter volume and their correlations with clinical features in benign childhood epilepsy with centrotemporal spikes
Xinhe YAO ; Qiang XU ; Yiwen CHEN ; Qirui ZHANG ; Jianrui LI ; Zhaojie WANG ; Yuzhuo LI ; Fang YANG ; Yan HE ; Chunfeng WU ; Gang YANG ; Guangming LU ; Zhiqiang ZHANG
Chinese Journal of Neuromedicine 2025;24(4):378-384
Objective:To explore the changes of brain excitation/inhibition balance and gray matter volume (GMV) and their correlations with clinical features in benign childhood epilepsy with centrotemporal spikes (BECTS).Methods:A cross-sectional study was performed; 83 BECTS children enrolled from Department of Diagnostic Radiology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University from January 2015 to January 2024 were selected as BECTS group. During the same period, 101 age- and gender-matched healthy children were recruited as healthy control group through advertisements in local primary schools. Data of conventional MRI and resting-state functional MRI (rs-fMRI) of the two groups were collected. Whole brain GMV was analyzed by voxel-based morphometry (VBM), and Hurst index was calculated based on time series data of blood oxygen level dependent (BOLD) signal of rs-fMRI. Correlations of GMV and Hurst index with disease duration and onset age in children with BECTS were explored by Pearson correlation analysis.Results:Compared with the healthy control group, the BECTS group had significantly increased GMV and decreased Hurst index in the bilateral Rolandic region ( P<0.05). Pearson correlation analysis showed that in the BECTS group, GMV in bilateral Rolandic region was negatively correlated with onset age ( r=-0.267, P=0.015) and positively correlated with disease course ( r=0.267, P=0.015); Hurst index in bilateral Rolandic region was positively correlated with onset age ( r=0.323, P=0.003) and negatively correlated with disease course ( r=-0.240, P=0.029); Hurst index was negatively correlated with GMV in bilateral Rolandic region ( r=-0.328, P=0.003). Conclusion:BECTS children have excitation/inhibition imbalance in epilepsy-related regions and cortical structural delay, and both of them are related to onset age and disease course.
7.Transcranial ultrasound imaging characteristics of 6-OHDA Parkinson's disease rats and their correlation with motor deficits and pathological changes
Ying ZHANG ; Qingyuan LIU ; Jian WU ; Min YANG ; Fen WANG ; Yingchun ZHANG ; Chunfeng LIU
Chinese Journal of Ultrasonography 2025;34(3):239-246
Objective:To analyze transcranial sonography(TCS)imaging characteristics of rats with 6-hydroxydopamine hydrochloride(6-OHDA)and explore the correlations between the imaging characteristics with motor deficits and pathological changes.Methods:Twenty-nine male SD rats were divided into 3 groups:8 in the no-treatment control(NC)group,10 in the Sham group and 11 in the 6-OHDA group. The model for Sham/Parkinson's disease(PD)was established by stereotacticly injecting saline/6-OHDA containing ascorbic acid to bilateral substantia nigra pars compacta(SNpc). After three weeks,the models were stable. At the fourth week and seventh week,the behavioral testing was accomplished. The TCS examination was performed weekly at the same time for four weeks. At the eighth week,the rats were sacrificed for pathology.Results:①Behavioral testing:6-OHDA group showed asymmetric motor deficits and the difference was significant compared with the NC group and Sham group(both P<0.001). ②TCS examination:compared with the NC and Sham group,there were asymmetric substantia nigra hyperechogenicity(SNH)in 6-OHDA group(both P<0.05);meanwhile the area of SNH in the left was significantly larger in the right side( P<0.05).No significant change in SNH area was found during the continuous observation period of weeks 4-7. For 6-OHDA group,the area of SNH was negatively correlated with the number of forelimb wall-touches( r=-0.825, P<0.001). ③Pathological examination:compared with NC group and sham group,the substantia nigra(SN)of 6-OHDA group showed a series of pathological events,including dopaminergic(DA)neurons asymmetrically decreasing,asymmetric ironion deposition and the number of active microglia increasing(all P<0.05). Correlation analysis showed that the area of SNH was negatively correlated with the number of DA neurons survivors( r=-0.689, P=0.013),while the activation of microglial and the deposition of iron were positively correlated with the area of SNH( r=0.915,0.735;all P<0.001). Conclusions:Asymmetric SNH of 6-OHDA PD rats is a representation of asymmetric motor deficits,and the mechanism is related to a catalogue of asymmetric pathological changes in SN,which comprise DA neurons decreasing,asymmetric iron ions deposition,microglial activating.
8.Changes of brain excitation/inhibition balance and gray matter volume and their correlations with clinical features in benign childhood epilepsy with centrotemporal spikes
Xinhe YAO ; Qiang XU ; Yiwen CHEN ; Qirui ZHANG ; Jianrui LI ; Zhaojie WANG ; Yuzhuo LI ; Fang YANG ; Yan HE ; Chunfeng WU ; Gang YANG ; Guangming LU ; Zhiqiang ZHANG
Chinese Journal of Neuromedicine 2025;24(4):378-384
Objective:To explore the changes of brain excitation/inhibition balance and gray matter volume (GMV) and their correlations with clinical features in benign childhood epilepsy with centrotemporal spikes (BECTS).Methods:A cross-sectional study was performed; 83 BECTS children enrolled from Department of Diagnostic Radiology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University from January 2015 to January 2024 were selected as BECTS group. During the same period, 101 age- and gender-matched healthy children were recruited as healthy control group through advertisements in local primary schools. Data of conventional MRI and resting-state functional MRI (rs-fMRI) of the two groups were collected. Whole brain GMV was analyzed by voxel-based morphometry (VBM), and Hurst index was calculated based on time series data of blood oxygen level dependent (BOLD) signal of rs-fMRI. Correlations of GMV and Hurst index with disease duration and onset age in children with BECTS were explored by Pearson correlation analysis.Results:Compared with the healthy control group, the BECTS group had significantly increased GMV and decreased Hurst index in the bilateral Rolandic region ( P<0.05). Pearson correlation analysis showed that in the BECTS group, GMV in bilateral Rolandic region was negatively correlated with onset age ( r=-0.267, P=0.015) and positively correlated with disease course ( r=0.267, P=0.015); Hurst index in bilateral Rolandic region was positively correlated with onset age ( r=0.323, P=0.003) and negatively correlated with disease course ( r=-0.240, P=0.029); Hurst index was negatively correlated with GMV in bilateral Rolandic region ( r=-0.328, P=0.003). Conclusion:BECTS children have excitation/inhibition imbalance in epilepsy-related regions and cortical structural delay, and both of them are related to onset age and disease course.
9.Latest research progress in application of single-cell transcriptome sequencing technology in autoimmune diseases
Jinmei SUN ; Chunwei SHI ; Guilian YANG ; Wentao YANG ; Chunfeng WANG
Chinese Journal of Immunology 2024;40(10):2219-2222,2228
Single-cell RNA sequencing technology takes a single cell as research object,counts and analyzes the gene expres-sion level of each transcript and heterogeneity between cells.This technology makes up for the defects of traditional sequencing techno-logy to some extent.Autoimmune disease is the damage or dysfunction of autotissue cells caused by autoimmune tolerance or abnormal regulation of autoimmunity cells.In this paper,the research results on application of single-cell RNA sequencing technology in autoim-mune disease in recent years are reviewed,which provides valuable clues for early realization of precise medical treatment.
10.Correlation study of transcranial sonography combined with serum biomarkers and cognitive status in patients with Parkinson′s disease
Hai WANG ; Yingchun ZHANG ; Changwei DING ; Caishan WANG ; Yujing SHENG ; Xiaofang CHEN ; Ying ZHANG ; Min YANG ; Pan MAO ; Yong YANG ; Ping FENG ; Chengjie MAO ; Jing CHEN ; Chunfeng LIU
Chinese Journal of Ultrasonography 2024;33(6):512-518
Objective:To explore the correlation between transcranial sonography (TCS) combined with serum homocysteine (Hcy), blood glucose, blood lipids, the cognitive status of Parkinson′s disease (PD) patients, and to analyze the clinical application value of these parameters in assessing the cognitive status of PD patients.Methods:A total of 152 PD patients admitted to the Second Affiliated Hospital of Soochow University from January 2020 to June 2023 were retrospectively collected as the PD group, and 101 healthy examinees matched for age and gender during the same period were selected as control group. Clinical data [age, gender, duration of illness, Montreal Cognitive Assessment (MoCA) score, Mini-Mental State Examination (MMSE) score, Unified Parkinson′s Disease Rating Scale Part Ⅲ (UPDRS-Ⅲ) score, Hoehn-Yahr (H-Y) stage, etc.], serum tests (Hcy, blood glucose, total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein concentration), and TCS examination results (third ventricular width, midbrain area, peak systolic velocity of bilateral middle cerebral arteries, bilateral middle cerebral artery resistance index, bilateral substantia nigra hyperechoic area) were collected. The two groups were divided into pure PD group and PD group with elevated Hcy, pure control group and control group with elevated Hcy, based on an Hcy concentration threshold of ≥15 μmol/L. The differences in the above parameters among the four groups were compared. The correlation between Hcy and cognitive status (MoCA score, MMSE score) of PD patients and the above parameters were analyzed.Results:The MoCA score and MMSE score of the PD group with elevated Hcy were lower than those of the pure PD group, and the UPDRS-Ⅲ score and H-Y stage were higher than those of the pure PD group (all P<0.001). The order of Hcy concentration from high to low was PD group with elevated Hcy, pure Hcy elevation group, pure PD group, and pure control group. The differences in serum data and TCS data among the four groups were statistically significant (all P<0.001). Spearman correlation analysis showed: ①In the PD group, the concentration of Hcy was positively correlated with glucose concentration, H-Y stage, low-density lipoprotein concentration, right middle cerebral artery resistance index, UPDRS-Ⅲ score, total cholesterol concentration, triglyceride concentration, left middle cerebral artery resistance index, third ventricular width, and age ( rs=0.422, 0.350, 0.348, 0.334, 0.325, 0.300, 0.293, 0.283, 0.221, 0.164, all P<0.05); Hcy concentration was negatively correlated with midbrain area, MMSE score, MoCA score, peak systolic velocity of right middle cerebral artery, peak systolic velocity of left middle cerebral artery, and high-density lipoprotein concentration ( rs=-0.328, -0.282, -0.245, -0.229, -0.224, -0.192, all P<0.05). ②Clinical data, serum data, and TCS data of PD patients were all correlated with MoCA score and MMSE score, with midbrain area showing the largest positive correlation ( rs=0.524, 0.516; both P<0.05) and H-Y stage showing the largest negative correlation( rs=-0.490, -0.468; both P<0.05). Conclusions:PD patients with elevated Hcy have lower cognitive scores than pure PD patients. The correlation between Hcy concentration and blood glucose concentration is the highest in PD patients, followed by H-Y stage. The cognitive scores of PD patients are most correlated with midbrain area and unrelated to substantia nigra hyperechoic area. Lowering serum Hcy concentration in PD patients may be one of the ways to delay cognitive impairment.

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