1.The effects of LncRNA KCNQ1OT1 on the migration and invasion of oral squamous cell carcinoma cells by regulating the miR-875-5p/ELK4 axis
Zihan MA ; Wanying SHI ; Jiang ZHU ; Teng XU ; Donghui SONG
Journal of Practical Stomatology 2025;41(3):365-371
Objective:To investigate the effects of long non coding RNA KCNQ1OT1(LncRNA KCNQ1OT1)on the migration and invasion of oral squamous cell carcinoma(OSCC)cells by regulating the microRNA-875-5p(miR-875-5p)/ETS like transcription factor 4(ELK4)axis.Methods:QRT-PCR was applied to detect the mRNA levels of LncRNA KCNQ1OT1,miR-875-5p,and ELK4 in OSCC cell lines(HSC-3,PE/CA-PJ15,HN13)and tissues.The dual luciferase assay was applied to detect the targeting relationship between LncRNA KCNQ1OT1 and miR-875-5p,and target relationship between miR-875-5p and ELK4.HSC-3 cells were used in control group,sh-NC group,sh-KCNQ1OT1 group,sh-KCNQ1OT1+anti-NC group,sh-KCNQ1OT1+anti-miR-875-5p group,miR-NC group,miR-875-5p mimic group,miR-875-5p mimic+pcDNA-NC group,and miR-875-5p mimic+ELK4 group.The migration and invasion abilities of HSC-3 cells were detected.Immunoblotting was applied to detect the protein expression of ELK4,MMP-2,MMP-9 and epithelial mesenchymal transition(EMT)(E-Cadherin,N-Cadherin,Vimentin).The nude mouse transplant tumor was applied to verify the effect of LncRNA KCNQ1OT1 on OSCC transplant tumors.Results:LncRNA KCNQ1OT1 and ELK4 mRNA expression increased in OSCC tissues and cancer cell lines,while miR-875-5p expression decreased(P<0.05).Database predictions show that miR-875-5p specifically bound to LncRNAs KCNQ1OT1 and ELK4,respectively.Compared with the sh-NC group,the numbers of cell migration and cell invasion,the expression of LncRNA KCNQ1OT1,ELK4,MMP-2,MMP-9,N-Cadherin,and Vimentin in the sh-KC-NQ1OT1 group were lower,while the expression of miR-875-5p and E-Cadherin was higher(P<0.05).Compared with the sh-KC-NQ1OT1+anti-NC group,the expression of miR-875-5p and E-Cadherin in the sh-KCNQ1OT1+anti-miR-875-5p group was lower,while the numbers of cell migration and cell invasion,the expression of ELK4,MMP-2,MMP-9,N-Cadherin,and Vimentin were higher(P<0.05).Compared with the miR-NC group,the expression of miR-875-5p and E-Cadherin in the miR-875-5p mimic group was higher,while the numbers of cell migration and cell invasion,the expression of ELK4,MMP-2,MMP-9,N-Cadherin,and Vim-entin were lower(P<0.05).Compared with the miR-875-5p mimic+pcDNA-NC group,the numbers of cell migration and cell inva-sion,the expression of ELK4,MMP-2,MMP-9,N-Cadherin,and Vimentin in the miR-875-5p mimic+ELK4 group were higher,while the expression of E-Cadherin was lower(P<0.05).The transplant tumor volume and weight of the sh-KCNQ1OT1 group were smaller than those of the sh-NC group,the mRNA and protein expression levels of LncRNA KCNQ1OT1,ELK4 were lower than those of the sh-NC group,and the expression level of miR-875-5p was higher than that of the sh-NC group(P<0.05).Conclusion:Inhibition of LncRNA KCNQ1OT1 can target the miR-875-5p/ELK4 axis to inhibit migration,invasion,and EMT of OSCC cells.
2.Protective Effect of Schisandrol A on Hydrogen Peroxide Induced Injury in HK-2 Cell
Ziping ZHAO ; Yi WANG ; Nanqi ZHANG ; Wanying LI ; Mingjie SONG ; Yingping WANG
Herald of Medicine 2025;44(7):1021-1027
Objective To investigate the protective effect and mechanism of schisandrin A(SA)on hydrogen peroxide(H2O2)-induced oxidative stress injury in renal tubular epithelial cells(HK-2).Methods HK-2 cells were cultured in vitro and divided into five groups:blank control group,model control group(treated with 600 μmol·L-1 H2O2 for 2 h),low-dose SA group(0.125 μmol·L-1 SA,24 h pretreatment+H2O2),medium-dose SA group(0.5 μmol·L-1 SA,24 h pretreatment+H2 O2),high-dose SA group(0.75 μmol·L-1 SA,24 h pretreatment+H2O2).The cell survival was assessed by CCK-8 assay;apoptosis level was tested by Annexin V-FITC/PI double staining;cell cycle distribution was detected by propidium iodide staining;oxidative markers(ROS,SOD,MDA,GSH,LDH)was determined with commercial kits;and apoptosis-related proteins(Bax,Bcl-2,Caspase-3,Cytochrome C)was evaluated by Western blot.Results Compared with the blank control,the model group reduced in cell viability and increased in apoptosis(P<0.01),elevated in the ratio of G0/G1-phase cells and decreased in S-phase cells(P<0.05),decreased in SOD activity and GSH content(P<0.01),and increased in the levels of ROS,LDH,and MDA levels(P<0.01).In all SA dose,cell apoptosis reduced(P<0.01).In medium/high dose groups,the G0/G1-phase arrest reduced(P<0.05).In high dose group,the S-phase cells ratio increased(P<0.05).And in medium/high dose groups,ROS(P<0.01)decreased in a dose-dependent manner.The SOD activity increased non-significantly in all SA groups.In SA medium/high dose groups,the LDH activity decreased in a dose-dependent manner.In all SA groups,GSH increased(P<0.01)and MDA decreased,both in a dose-dependent manner.The Bax/Bcl-2 ratio significantly decreased(P<0.05)in all SA groups.The caspase-3 activity decreased in medium/high dose group(P<0.05);and Cytochrome C reduced in all SA groups(P<0.05).Conclusion SA protects HK-2 cells against H2O2-induced oxidative injury by modulating oxidative stress,inhibiting apoptosis,and ameliorating cell cycle arrest.
3.Characterization of cortical morphology and structural covariance network features in post-stroke patients with visuospatial neglect
Wanying ZHAO ; Lei CAO ; Weiqun SONG ; Linlin YE
Chinese Journal of Cerebrovascular Diseases 2025;22(7):474-486
Objective To investigate cortical morphological changes and structural covariance network(SCN)topological features in patients with visuospatial neglect(VSN)after stroke.Methods A retrospective analysis was conducted on acute stroke patients admitted consecutively to the Department of Rehabilitation Medicine,Xuanwu Hospital,Capital Medical University,from December 2023 to February 2025.General and clinical data were collected and compared,including age,sex,stroke type(hemorrhagic or ischemic),and time from stroke onset to first brain MRI.All patients were assessed for VSN using the line bisection task,line cancellation test,and star cancellation test.Patients with VSN were assigned to the VSN group,and those without VSN to the non-VSN group.Brain MRI was used to collect patients' brain structural images.T1-weighted MRI data were processed using Freesurfer for whole-brain segmentation.Based on the Desikan-Killiany atlas,the cortex was parcellated into 68 regions per hemisphere,total intracranial volume and cortical parameters were extracted,including cortical area(CA),mean cortical curvature(CC),cortical thickness(CT),and cortical volume(CV).A region-specific asymmetry index(AI)was calculated for cortical parameters of each brain regions using(left-right)/(left+right)to assess cortical lateralization.Analyze the SCN of each cortical parameters through covariance matrix to reflect covariation pattern of each brain region's structural morphological alternations.SCN were constructed separately for each cortical parameter based on inter-regional Pearson correlation coefficients(absolute values),with intracranial volume,age,and sex controlled via linear regression.The resulting 68×68 SCN matrices were transformed into binary networks across a sparsity range of 0.1 to 0.4(in 0.01 steps),and graph theoretical analysis were performed.Permutation tests were used to compare the global and local graph theoretical metrics of cortical SCN under each cortical parameters with different sparsity.Global metrics included clustering coefficient,path length,small-worldness parameters(normalized clustering coefficient[Gamma],normalized path length[Lambda],and small-world index[Sigma]),global efficiency,and average local efficiency.Local metrics included nodal degree,betweenness centrality,and nodal efficiency.Results(1)A total of 109 acute stroke patients were included(81 males,28 females,aged 30-80 years,mean[64±9]years),with 54 in the VSN group and 55 in the non-VSN group.No significant differences were found in age,sex,stroke type,or time from stroke onset to MRI between two groups(all P>0.05).(2)Comparison of cortical features(of different brain regions)between two groups showed significantly larger CA in the right insular surface area in the VSN group(2 466.50[2 143.75,2 662.50]mm2 vs.2 128.00[1 961.00,2 479.00)]mm2,P=0.037).No significant differences were observed in other regions or metrics(all P>0.05).The VSN group has significantly lower AI values for CT in the right isthmus cingulate gyrus(-0.01[-0.05,0.03]vs.0.02[-0.01,0.06],P=0.028)and postcentral gyrus(-0.02[-0.04,0.00]vs.0.00[-0.02,0.02],P=0.026).No significant AI differences were observed in other regions or metrics(all P>0.05).(3)For global network metrics:in the CA-based VSN,compared with the non-VSN group,Sigma values were significantly higher in the VSN group across multiple sparsity thresholds and at the average sparsity level(P<0.01).In the CT-based SCN,Lambda values were significantly higher in the VSN group at most sparsity thresholds and at the average level(P=0.004).In the CC-based SCN,clustering coefficient and average local efficiency were significantly lower in the VSN group across most sparsity thresholds and average sparsity(P<0.01).No significant differences were found in global metrics within the CV-based SCN.(4)For local metrics:in the CV-based SCN,compared with the non-VSN group,the VSN group showed significantly lower nodal efficiency in the left inferior temporal gyrus at most sparsity thresholds and at the average level(0.35[0.29,0.50]vs.0.65[0.51,0.72],P<0.01).No significant differences in local metrics were observed in other SCN between the two groups.Conclusions Patients with VSN exhibit abnormal cortical morphology and SCN topology,characterized by reduced overall integration efficiency and weakened local connectivity,alongside enhanced small-worldness and possible compensatory reorganization.The conclusions of this study require further validation in multicenter,large-scale,prospective studies.
4.Development and validation of the rapid health aging assessment scale for the Chinese population
Bingqi YE ; Jialu YANG ; Jianhua LI ; Wunong CHEN ; Jianhua YE ; Xiaotao ZHOU ; Yong WANG ; Siqi LI ; Qi ZHANG ; Wanying ZHAO ; Jiayi SONG ; Chun WANG ; Yan LIU ; Min XIA
Chinese Journal of Preventive Medicine 2025;59(7):1078-1083
Objective:To develop a rapid assessment scale for healthy aging suitable for the Chinese population.Methods:Based on existing healthy aging assessment scales, national standards, and expert consensus, an initial Healthy Aging Rapid Assessment Scale was drafted through two rounds of expert consultation. A pre-survey was conducted with 3 220 subjects recruited from Guangzhou between July 2023 and July 2024. Items were screened through item analysis and exploratory factor analysis to form the final scale. Reliability and validity of the final scale were validated across five cities: Guangzhou, Dongguan, Shenzhen, Baoding, and Chuxiong.Results:The initial version comprised 36 items, while the finalized scale contained 18 items across three dimensions: metabolic health, mental health, and cognitive health. Test-retest reliability ranged from 0.71 to 0.81 across all study sites. The Spearman-Brown coefficient varied between 0.91-0.96, Cronbach′s α between 0.77-0.83, comparative fit index (CFI) between 0.90-0.98, goodness-of-fit index (GFI) between 0.90-0.99, and root-mean-square error of approximation (RMSEA) between 0.03-0.09. For the three dimensions, reliability and validity metrics demonstrated consistency: Spearman-Brown coefficients 0.87-0.99, Cronbach′s α 0.77-0.83, CFI 0.90-0.98, GFI 0.90-0.99, and RMSEA 0.03-0.09 across four regions.Conclusion:The developed Healthy Aging Rapid Assessment Scale for the Chinese population exhibits robust reliability and validity.
5.Epidemiological Characteristics of Malignant Tumors in Cancer Registration Areas of Heilongjiang Province in 2019 and the Trend from 2013 to 2019
Wanying WANG ; Huixin SUN ; Maoxiang ZHANG ; Haihan JIA ; Min ZHAO ; Guohong GAO ; Bingbing SONG
China Cancer 2025;34(5):368-376
[Purpose]To analyze the incidence and mortality of malignant tumors in cancer regis-tration areas of Heilongjiang Province in 2019 and the trend from 2013 to 2019.[Methods]The incidence and mortality data of malignant tumors reported by the Heilongjiang provincial cancer registries from 2013 to 2019 were collected,and the quality of data was assessed.The crude in-cidence/mortality rate,age-standardized incidence/mortality rate by Chinese standard population(ASIRC/ASMRC)and world standard population(ASIRW/ASMRW),0~74 years old cumulative rate were calculated.Joinpoint 4.6.0 software was used to calculate the average annual percentage change(AAPC)of ASIRC/ASMRC for the trend analysis from 2013 to 2019.[Results]In 2019,there were 16 732 new cases of malignant tumors in the cancer registration areas of Heilongjiang Province,including 8 639 males and 8 093 females.The crude incidence rate was 295.37/105,with an ASIRC and ASIRW of 167.10/105 and 164.18/105,respectively.There were 10 988 malig-nant tumor deaths,including 6 540 males and 4 448 females.The crude mortality rate was 193.97/105,with an ASMRC and ASMRW of 101.22/105 and 101.66/105,respectively.The inci-dence and mortality of malignant tumors increased rapidly after the age of 55,and the incidence and mortality of males were slightly higher than those of females.The top five malignant tumors of high incidence were lung cancer,female breast cancer,colorectal cancer,liver cancer and thy-roid cancer,and the top five malignant tumors of high mortality were lung cancer,liver cancer,colorectal cancer,stomach cancer and female breast cancer.From 2013 to 2019,the ASIRC of malignant tumors in cancer registration areas increased from 153.08/105 in 2013 to 167.10/105 in 2019,and the ASMRC increased from 92.22/105 in 2013 to 101.22/105 in 2019,but there was no statistical difference in the change trend.[Conclusion]The incidence and mortality of malignant tumors in Heilongjiang Province remain high.Lung cancer,female breast cancer,colorectal can-cer,liver cancer and stomach cancer should be the focus of cancer prevention and control.
6.Epidemiological Characteristics of Malignant Tumors in Cancer Registration Areas of Heilongjiang Province in 2019 and the Trend from 2013 to 2019
Wanying WANG ; Huixin SUN ; Maoxiang ZHANG ; Haihan JIA ; Min ZHAO ; Guohong GAO ; Bingbing SONG
China Cancer 2025;34(5):368-376
[Purpose]To analyze the incidence and mortality of malignant tumors in cancer regis-tration areas of Heilongjiang Province in 2019 and the trend from 2013 to 2019.[Methods]The incidence and mortality data of malignant tumors reported by the Heilongjiang provincial cancer registries from 2013 to 2019 were collected,and the quality of data was assessed.The crude in-cidence/mortality rate,age-standardized incidence/mortality rate by Chinese standard population(ASIRC/ASMRC)and world standard population(ASIRW/ASMRW),0~74 years old cumulative rate were calculated.Joinpoint 4.6.0 software was used to calculate the average annual percentage change(AAPC)of ASIRC/ASMRC for the trend analysis from 2013 to 2019.[Results]In 2019,there were 16 732 new cases of malignant tumors in the cancer registration areas of Heilongjiang Province,including 8 639 males and 8 093 females.The crude incidence rate was 295.37/105,with an ASIRC and ASIRW of 167.10/105 and 164.18/105,respectively.There were 10 988 malig-nant tumor deaths,including 6 540 males and 4 448 females.The crude mortality rate was 193.97/105,with an ASMRC and ASMRW of 101.22/105 and 101.66/105,respectively.The inci-dence and mortality of malignant tumors increased rapidly after the age of 55,and the incidence and mortality of males were slightly higher than those of females.The top five malignant tumors of high incidence were lung cancer,female breast cancer,colorectal cancer,liver cancer and thy-roid cancer,and the top five malignant tumors of high mortality were lung cancer,liver cancer,colorectal cancer,stomach cancer and female breast cancer.From 2013 to 2019,the ASIRC of malignant tumors in cancer registration areas increased from 153.08/105 in 2013 to 167.10/105 in 2019,and the ASMRC increased from 92.22/105 in 2013 to 101.22/105 in 2019,but there was no statistical difference in the change trend.[Conclusion]The incidence and mortality of malignant tumors in Heilongjiang Province remain high.Lung cancer,female breast cancer,colorectal can-cer,liver cancer and stomach cancer should be the focus of cancer prevention and control.
7.Development and validation of the rapid health aging assessment scale for the Chinese population
Bingqi YE ; Jialu YANG ; Jianhua LI ; Wunong CHEN ; Jianhua YE ; Xiaotao ZHOU ; Yong WANG ; Siqi LI ; Qi ZHANG ; Wanying ZHAO ; Jiayi SONG ; Chun WANG ; Yan LIU ; Min XIA
Chinese Journal of Preventive Medicine 2025;59(7):1078-1083
Objective:To develop a rapid assessment scale for healthy aging suitable for the Chinese population.Methods:Based on existing healthy aging assessment scales, national standards, and expert consensus, an initial Healthy Aging Rapid Assessment Scale was drafted through two rounds of expert consultation. A pre-survey was conducted with 3 220 subjects recruited from Guangzhou between July 2023 and July 2024. Items were screened through item analysis and exploratory factor analysis to form the final scale. Reliability and validity of the final scale were validated across five cities: Guangzhou, Dongguan, Shenzhen, Baoding, and Chuxiong.Results:The initial version comprised 36 items, while the finalized scale contained 18 items across three dimensions: metabolic health, mental health, and cognitive health. Test-retest reliability ranged from 0.71 to 0.81 across all study sites. The Spearman-Brown coefficient varied between 0.91-0.96, Cronbach′s α between 0.77-0.83, comparative fit index (CFI) between 0.90-0.98, goodness-of-fit index (GFI) between 0.90-0.99, and root-mean-square error of approximation (RMSEA) between 0.03-0.09. For the three dimensions, reliability and validity metrics demonstrated consistency: Spearman-Brown coefficients 0.87-0.99, Cronbach′s α 0.77-0.83, CFI 0.90-0.98, GFI 0.90-0.99, and RMSEA 0.03-0.09 across four regions.Conclusion:The developed Healthy Aging Rapid Assessment Scale for the Chinese population exhibits robust reliability and validity.
8.The effects of LncRNA KCNQ1OT1 on the migration and invasion of oral squamous cell carcinoma cells by regulating the miR-875-5p/ELK4 axis
Zihan MA ; Wanying SHI ; Jiang ZHU ; Teng XU ; Donghui SONG
Journal of Practical Stomatology 2025;41(3):365-371
Objective:To investigate the effects of long non coding RNA KCNQ1OT1(LncRNA KCNQ1OT1)on the migration and invasion of oral squamous cell carcinoma(OSCC)cells by regulating the microRNA-875-5p(miR-875-5p)/ETS like transcription factor 4(ELK4)axis.Methods:QRT-PCR was applied to detect the mRNA levels of LncRNA KCNQ1OT1,miR-875-5p,and ELK4 in OSCC cell lines(HSC-3,PE/CA-PJ15,HN13)and tissues.The dual luciferase assay was applied to detect the targeting relationship between LncRNA KCNQ1OT1 and miR-875-5p,and target relationship between miR-875-5p and ELK4.HSC-3 cells were used in control group,sh-NC group,sh-KCNQ1OT1 group,sh-KCNQ1OT1+anti-NC group,sh-KCNQ1OT1+anti-miR-875-5p group,miR-NC group,miR-875-5p mimic group,miR-875-5p mimic+pcDNA-NC group,and miR-875-5p mimic+ELK4 group.The migration and invasion abilities of HSC-3 cells were detected.Immunoblotting was applied to detect the protein expression of ELK4,MMP-2,MMP-9 and epithelial mesenchymal transition(EMT)(E-Cadherin,N-Cadherin,Vimentin).The nude mouse transplant tumor was applied to verify the effect of LncRNA KCNQ1OT1 on OSCC transplant tumors.Results:LncRNA KCNQ1OT1 and ELK4 mRNA expression increased in OSCC tissues and cancer cell lines,while miR-875-5p expression decreased(P<0.05).Database predictions show that miR-875-5p specifically bound to LncRNAs KCNQ1OT1 and ELK4,respectively.Compared with the sh-NC group,the numbers of cell migration and cell invasion,the expression of LncRNA KCNQ1OT1,ELK4,MMP-2,MMP-9,N-Cadherin,and Vimentin in the sh-KC-NQ1OT1 group were lower,while the expression of miR-875-5p and E-Cadherin was higher(P<0.05).Compared with the sh-KC-NQ1OT1+anti-NC group,the expression of miR-875-5p and E-Cadherin in the sh-KCNQ1OT1+anti-miR-875-5p group was lower,while the numbers of cell migration and cell invasion,the expression of ELK4,MMP-2,MMP-9,N-Cadherin,and Vimentin were higher(P<0.05).Compared with the miR-NC group,the expression of miR-875-5p and E-Cadherin in the miR-875-5p mimic group was higher,while the numbers of cell migration and cell invasion,the expression of ELK4,MMP-2,MMP-9,N-Cadherin,and Vim-entin were lower(P<0.05).Compared with the miR-875-5p mimic+pcDNA-NC group,the numbers of cell migration and cell inva-sion,the expression of ELK4,MMP-2,MMP-9,N-Cadherin,and Vimentin in the miR-875-5p mimic+ELK4 group were higher,while the expression of E-Cadherin was lower(P<0.05).The transplant tumor volume and weight of the sh-KCNQ1OT1 group were smaller than those of the sh-NC group,the mRNA and protein expression levels of LncRNA KCNQ1OT1,ELK4 were lower than those of the sh-NC group,and the expression level of miR-875-5p was higher than that of the sh-NC group(P<0.05).Conclusion:Inhibition of LncRNA KCNQ1OT1 can target the miR-875-5p/ELK4 axis to inhibit migration,invasion,and EMT of OSCC cells.
9.Protective Effect of Schisandrol A on Hydrogen Peroxide Induced Injury in HK-2 Cell
Ziping ZHAO ; Yi WANG ; Nanqi ZHANG ; Wanying LI ; Mingjie SONG ; Yingping WANG
Herald of Medicine 2025;44(7):1021-1027
Objective To investigate the protective effect and mechanism of schisandrin A(SA)on hydrogen peroxide(H2O2)-induced oxidative stress injury in renal tubular epithelial cells(HK-2).Methods HK-2 cells were cultured in vitro and divided into five groups:blank control group,model control group(treated with 600 μmol·L-1 H2O2 for 2 h),low-dose SA group(0.125 μmol·L-1 SA,24 h pretreatment+H2O2),medium-dose SA group(0.5 μmol·L-1 SA,24 h pretreatment+H2 O2),high-dose SA group(0.75 μmol·L-1 SA,24 h pretreatment+H2O2).The cell survival was assessed by CCK-8 assay;apoptosis level was tested by Annexin V-FITC/PI double staining;cell cycle distribution was detected by propidium iodide staining;oxidative markers(ROS,SOD,MDA,GSH,LDH)was determined with commercial kits;and apoptosis-related proteins(Bax,Bcl-2,Caspase-3,Cytochrome C)was evaluated by Western blot.Results Compared with the blank control,the model group reduced in cell viability and increased in apoptosis(P<0.01),elevated in the ratio of G0/G1-phase cells and decreased in S-phase cells(P<0.05),decreased in SOD activity and GSH content(P<0.01),and increased in the levels of ROS,LDH,and MDA levels(P<0.01).In all SA dose,cell apoptosis reduced(P<0.01).In medium/high dose groups,the G0/G1-phase arrest reduced(P<0.05).In high dose group,the S-phase cells ratio increased(P<0.05).And in medium/high dose groups,ROS(P<0.01)decreased in a dose-dependent manner.The SOD activity increased non-significantly in all SA groups.In SA medium/high dose groups,the LDH activity decreased in a dose-dependent manner.In all SA groups,GSH increased(P<0.01)and MDA decreased,both in a dose-dependent manner.The Bax/Bcl-2 ratio significantly decreased(P<0.05)in all SA groups.The caspase-3 activity decreased in medium/high dose group(P<0.05);and Cytochrome C reduced in all SA groups(P<0.05).Conclusion SA protects HK-2 cells against H2O2-induced oxidative injury by modulating oxidative stress,inhibiting apoptosis,and ameliorating cell cycle arrest.
10.Characterization of cortical morphology and structural covariance network features in post-stroke patients with visuospatial neglect
Wanying ZHAO ; Lei CAO ; Weiqun SONG ; Linlin YE
Chinese Journal of Cerebrovascular Diseases 2025;22(7):474-486
Objective To investigate cortical morphological changes and structural covariance network(SCN)topological features in patients with visuospatial neglect(VSN)after stroke.Methods A retrospective analysis was conducted on acute stroke patients admitted consecutively to the Department of Rehabilitation Medicine,Xuanwu Hospital,Capital Medical University,from December 2023 to February 2025.General and clinical data were collected and compared,including age,sex,stroke type(hemorrhagic or ischemic),and time from stroke onset to first brain MRI.All patients were assessed for VSN using the line bisection task,line cancellation test,and star cancellation test.Patients with VSN were assigned to the VSN group,and those without VSN to the non-VSN group.Brain MRI was used to collect patients' brain structural images.T1-weighted MRI data were processed using Freesurfer for whole-brain segmentation.Based on the Desikan-Killiany atlas,the cortex was parcellated into 68 regions per hemisphere,total intracranial volume and cortical parameters were extracted,including cortical area(CA),mean cortical curvature(CC),cortical thickness(CT),and cortical volume(CV).A region-specific asymmetry index(AI)was calculated for cortical parameters of each brain regions using(left-right)/(left+right)to assess cortical lateralization.Analyze the SCN of each cortical parameters through covariance matrix to reflect covariation pattern of each brain region's structural morphological alternations.SCN were constructed separately for each cortical parameter based on inter-regional Pearson correlation coefficients(absolute values),with intracranial volume,age,and sex controlled via linear regression.The resulting 68×68 SCN matrices were transformed into binary networks across a sparsity range of 0.1 to 0.4(in 0.01 steps),and graph theoretical analysis were performed.Permutation tests were used to compare the global and local graph theoretical metrics of cortical SCN under each cortical parameters with different sparsity.Global metrics included clustering coefficient,path length,small-worldness parameters(normalized clustering coefficient[Gamma],normalized path length[Lambda],and small-world index[Sigma]),global efficiency,and average local efficiency.Local metrics included nodal degree,betweenness centrality,and nodal efficiency.Results(1)A total of 109 acute stroke patients were included(81 males,28 females,aged 30-80 years,mean[64±9]years),with 54 in the VSN group and 55 in the non-VSN group.No significant differences were found in age,sex,stroke type,or time from stroke onset to MRI between two groups(all P>0.05).(2)Comparison of cortical features(of different brain regions)between two groups showed significantly larger CA in the right insular surface area in the VSN group(2 466.50[2 143.75,2 662.50]mm2 vs.2 128.00[1 961.00,2 479.00)]mm2,P=0.037).No significant differences were observed in other regions or metrics(all P>0.05).The VSN group has significantly lower AI values for CT in the right isthmus cingulate gyrus(-0.01[-0.05,0.03]vs.0.02[-0.01,0.06],P=0.028)and postcentral gyrus(-0.02[-0.04,0.00]vs.0.00[-0.02,0.02],P=0.026).No significant AI differences were observed in other regions or metrics(all P>0.05).(3)For global network metrics:in the CA-based VSN,compared with the non-VSN group,Sigma values were significantly higher in the VSN group across multiple sparsity thresholds and at the average sparsity level(P<0.01).In the CT-based SCN,Lambda values were significantly higher in the VSN group at most sparsity thresholds and at the average level(P=0.004).In the CC-based SCN,clustering coefficient and average local efficiency were significantly lower in the VSN group across most sparsity thresholds and average sparsity(P<0.01).No significant differences were found in global metrics within the CV-based SCN.(4)For local metrics:in the CV-based SCN,compared with the non-VSN group,the VSN group showed significantly lower nodal efficiency in the left inferior temporal gyrus at most sparsity thresholds and at the average level(0.35[0.29,0.50]vs.0.65[0.51,0.72],P<0.01).No significant differences in local metrics were observed in other SCN between the two groups.Conclusions Patients with VSN exhibit abnormal cortical morphology and SCN topology,characterized by reduced overall integration efficiency and weakened local connectivity,alongside enhanced small-worldness and possible compensatory reorganization.The conclusions of this study require further validation in multicenter,large-scale,prospective studies.

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