Objective This study aimed to investigate the correlation of cerebral perfusion and cognitive function status in patients with minor stroke(MS)or transient ischemic attack(TIA)complicated by severe intracranial arterial stenosis or occlusion(hereafter referred to as ICAS-MSTIA).Methods Retrospectively enrol consecutive ICAS-MSTIA patients admitted to the Department of Neurology,the First Affiliated Hospital of Xi'an Jiaotong University,from June 2023 to May 2024.In the meantime,healthy controls were openly recruited.The ICAS-MSTIA patients were divided into two groups based on the side of intracranial large artery stenosis or occlusion:the left intracranial large artery involvement group and the right intracranial large artery involvement group.All patients with intracranial large artery stenosis or occlusion underwent MR scanning within 2 weeks after the first episode of TIA or MS,while there was no specific time requirement for MR examination in the healthy control group.On the day of MR scanning,the Montreal cognitive assessment(MoCA)scale was used to evaluate the participants'global cognitive function and performance in various cognitive domains,including visuospatial/executive function,naming,attention,language,abstraction,delayed recall,and orientation.General information of all participants was collected,including age,sex,educational level,body mass index,and history of smoking and alcohol consumption.Clinical data were collected from both left and right intracranial large artery involvement groups,including cerebrovascular risk factors(such as,diabetes mellitus,hypertension,and hyperlipidemia),National Institutes of Health stroke scale(NIHSS)score at admission,responsible stenotic or occluded arteries(internal carotid artery,middle cerebral artery),degree of stenosis in the responsible vessel(severe stenosis[stenosis rate 70%-99%],occlusion[stenosis rate100%])and non-responsible vessel(no stenosis[0],mild stenosis[stenosis rate＞0-49%]),collateral circulation compensation(American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology[ASTIN/SIR]collateral circulation classification),and responsible events(TIA,MS).General data and MoCA scale scores were compared across the three groups,while clinical data were compared between the left and right intracranial large artery involvement groups.Statistical parametric mapping 12(SPM 12)was used to perform voxel-wise independent samples t-tests on cerebral blood flow(CBF)differences among the left ICAS-MSTIA group,right ICAS-MSTIA group,and healthy control group,with cluster-level family-wise error(FWE)correction applied for adjustment.Multiple linear regression analysis was conducted to evaluate the relationship between global CBF values and total MoCA scores in ICAS-MSTIA patients with left or right intracranial large artery involvement.Results A total of 33 ICAS-MSTIA patients and 33 healthy controls were enrolled in the study.Among the ICAS-MSTIA patients,21 had left intracranial large artery involvement and 12 had right involvement.(1)Among the three groups,statistically significant differences were observed in the proportions of individuals with reported smoking history(P=0.024)and alcohol consumption history(P=0.011).The left intracranial large artery involvement group had a higher NIHSS score(0[0,2]vs.0[0,0],P=0.044)and a higher proportion of patients with internal carotid artery involvement(13/21 cases vs.2/12 cases,P=0.027)compared with the right side group.No statistically significant differences were observed in other general or clinical data across the three groups or between the two non-control groups(all P＞0.05).(2)Statistically significant differences were found across the three groups in the MoCA scale total score and scores of visuospatial/executive function,attention,language,abstraction,delayed recall,and orientation cognitive domains(all P＜0.05),while no significant difference was noted in the naming score(P=0.063).The left intracranial large artery involvement group had lower total MoCA score and lower scores in visuospatial/executive function,attention,language,abstraction,delayed recall,and orientation in comparison to the healthy control group(all P＜0.016 7).The right intracranial large artery involvement group had significantly lower scores in language,abstraction,and orientation domains than the healthy control group(all P＜0.016 7).Additionally,the left side group had a lower attention domain score than the right side group(P＜0.016 7).No other statistically significant differences were found in pairwise comparisons(all P＞0.016 7).(3)Patients in both the left and right intracranial large artery involvement groups exhibited a significant decrease in CBF in extensive regions on the affected side,including the temporal lobe,dorsolateral prefrontal cortex,and occipital lobe.Furthermore,after correction,in the left involvement group CBF was higher in the contralateral lingual gyrus,cuneus,and calcarine sulcus compared with the healthy control group(P＜0.05).While in the right involvement group,no regions had increased CBF compared to the healthy control group.(4)Multiple linear regression showed positive correlation between CBF in ipsilateral precentral gyrus and superior temporal gyrus,and the total MoCA score in patients with left intracranial large artery involvement(FWE-corrected,P＜0.05).In contrast,there was no correlation between CBF and total MoCA score in patients with right intracranial large artery involvement.Conclusions ICAS-MSTIA patients exhibited various degrees of impairment in cerebral perfusion and cognitive function.A significant positive correlation is observed between these two impairments in patients with left intracranial large artery involvement.

Objective To evaluate the relationship between triglyceride-glucose index(TyG)and intensive care unit(ICU)mor-tality in patients with non-diabetic sepsis.Methods The retrospective cohort study analyzed the data from sepsis patients admitted to the Second Hospital & Clinical Medical School,Lanzhou University between January 2018 and December 2023.The patients were divided into three groups based on the terartiles of the TyG index:group T1,group T2 and group T3,with ICU mortality as the primary endpoint.Multivariate COX regression analysis and restricted cubic spline(RCS)modeling were performed to investigate the potential non-linear relationship between the TyG index and ICU mortality of patients with sepsis,and subgroup analysis were conducted to further explore these relationships.Results This study included 578sepsis patients,with an ICU mortality of 16.96％.The Kaplan-Meier survival curve analysis indicated that the ICU mortality in the group T3 was significantly higher than that in the group T1.The RCS analysis re-vealed a linear relationship between the TyG index and ICU mortality,for every 1-unit increase in the TyG index,the risk of ICU mortal-ity increased by approximately 54％.Subgroup analysis demonstrated consistent effect directions across different subgroups,with no sub-group-specific effects,indicating the robustness of the results.Conclusion TyG index may serve as a potential biomarker for predicting ICU mortality in non-diabetic sepsis patients.

Objective This study aimed to investigate the correlation of cerebral perfusion and cognitive function status in patients with minor stroke(MS)or transient ischemic attack(TIA)complicated by severe intracranial arterial stenosis or occlusion(hereafter referred to as ICAS-MSTIA).Methods Retrospectively enrol consecutive ICAS-MSTIA patients admitted to the Department of Neurology,the First Affiliated Hospital of Xi'an Jiaotong University,from June 2023 to May 2024.In the meantime,healthy controls were openly recruited.The ICAS-MSTIA patients were divided into two groups based on the side of intracranial large artery stenosis or occlusion:the left intracranial large artery involvement group and the right intracranial large artery involvement group.All patients with intracranial large artery stenosis or occlusion underwent MR scanning within 2 weeks after the first episode of TIA or MS,while there was no specific time requirement for MR examination in the healthy control group.On the day of MR scanning,the Montreal cognitive assessment(MoCA)scale was used to evaluate the participants'global cognitive function and performance in various cognitive domains,including visuospatial/executive function,naming,attention,language,abstraction,delayed recall,and orientation.General information of all participants was collected,including age,sex,educational level,body mass index,and history of smoking and alcohol consumption.Clinical data were collected from both left and right intracranial large artery involvement groups,including cerebrovascular risk factors(such as,diabetes mellitus,hypertension,and hyperlipidemia),National Institutes of Health stroke scale(NIHSS)score at admission,responsible stenotic or occluded arteries(internal carotid artery,middle cerebral artery),degree of stenosis in the responsible vessel(severe stenosis[stenosis rate 70%-99%],occlusion[stenosis rate100%])and non-responsible vessel(no stenosis[0],mild stenosis[stenosis rate＞0-49%]),collateral circulation compensation(American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology[ASTIN/SIR]collateral circulation classification),and responsible events(TIA,MS).General data and MoCA scale scores were compared across the three groups,while clinical data were compared between the left and right intracranial large artery involvement groups.Statistical parametric mapping 12(SPM 12)was used to perform voxel-wise independent samples t-tests on cerebral blood flow(CBF)differences among the left ICAS-MSTIA group,right ICAS-MSTIA group,and healthy control group,with cluster-level family-wise error(FWE)correction applied for adjustment.Multiple linear regression analysis was conducted to evaluate the relationship between global CBF values and total MoCA scores in ICAS-MSTIA patients with left or right intracranial large artery involvement.Results A total of 33 ICAS-MSTIA patients and 33 healthy controls were enrolled in the study.Among the ICAS-MSTIA patients,21 had left intracranial large artery involvement and 12 had right involvement.(1)Among the three groups,statistically significant differences were observed in the proportions of individuals with reported smoking history(P=0.024)and alcohol consumption history(P=0.011).The left intracranial large artery involvement group had a higher NIHSS score(0[0,2]vs.0[0,0],P=0.044)and a higher proportion of patients with internal carotid artery involvement(13/21 cases vs.2/12 cases,P=0.027)compared with the right side group.No statistically significant differences were observed in other general or clinical data across the three groups or between the two non-control groups(all P＞0.05).(2)Statistically significant differences were found across the three groups in the MoCA scale total score and scores of visuospatial/executive function,attention,language,abstraction,delayed recall,and orientation cognitive domains(all P＜0.05),while no significant difference was noted in the naming score(P=0.063).The left intracranial large artery involvement group had lower total MoCA score and lower scores in visuospatial/executive function,attention,language,abstraction,delayed recall,and orientation in comparison to the healthy control group(all P＜0.016 7).The right intracranial large artery involvement group had significantly lower scores in language,abstraction,and orientation domains than the healthy control group(all P＜0.016 7).Additionally,the left side group had a lower attention domain score than the right side group(P＜0.016 7).No other statistically significant differences were found in pairwise comparisons(all P＞0.016 7).(3)Patients in both the left and right intracranial large artery involvement groups exhibited a significant decrease in CBF in extensive regions on the affected side,including the temporal lobe,dorsolateral prefrontal cortex,and occipital lobe.Furthermore,after correction,in the left involvement group CBF was higher in the contralateral lingual gyrus,cuneus,and calcarine sulcus compared with the healthy control group(P＜0.05).While in the right involvement group,no regions had increased CBF compared to the healthy control group.(4)Multiple linear regression showed positive correlation between CBF in ipsilateral precentral gyrus and superior temporal gyrus,and the total MoCA score in patients with left intracranial large artery involvement(FWE-corrected,P＜0.05).In contrast,there was no correlation between CBF and total MoCA score in patients with right intracranial large artery involvement.Conclusions ICAS-MSTIA patients exhibited various degrees of impairment in cerebral perfusion and cognitive function.A significant positive correlation is observed between these two impairments in patients with left intracranial large artery involvement.

Objective:Exploring the safety and efficacy of intermittent theta rhythm stimulation on cortical excitability and upper limb motor function in patients with stroke at recovery stage.Method:From January,2022 to April 2023,30 patients with stroke at recovery stage who received rehabilita-tion treatment were randomly divided into the experimental group(n=15)and the control group(n=15)using the random number method.Both groups were subjected to routine rehabilitation training.The experimental group was given additional intermittent theta rhythm stimulation on the basis of routine rehabilitation,and the control group added intermittent theta rhythm sham stimulation,5 times a week for 4 weeks.Neurophysiologic indexes were tested on both the healthy and affected sides of the patients in the 2 groups before and after the intervention,as well as the assessment of upper limb motor function.Result:After 4 weeks of intervention,there were no statistical differences in MEP maximum wave ampli-tude,MEP latency,CMCT value,CSP value and RMT value of the healthy side between before and after in-tervention and between the groups(P>0.05);MEP maximum wave amplitude of the affected side of the experi-mental group was higher than before intervention(P<0.05);the affected side of the experimental group had a low-er MEP latency,CSP value,and RMT value than before intervention and the control group(P<0.01,P<0.05).Fugl-Meyer upper limb function scores,MBI scores,grip strength on the affected side,and nine-hole post time spent in the experimental group improved after the intervention compared to before the intervention(P<0.01,P<0.05).Fugl-Meyer upper extremity function scores,MBI scores,and time spent on the affected side of the nine-hole column improved in the experimental group after the intervention compared to the control group(P<0.01,P<0.05).Conclusion:Intermittent theta rhythm stimulation combined with conventional rehabilitation training did not show significant effects on the cortical excitability of the healthy side of patients with stroke at recovery stage.However,it could improve the cortical excitability of the affected side of patients with stroke at recovery stage and improve the motor function of the upper limbs.

Objective To investigate the predictive value of pan-immune-inflammation value(PIV),blood urea nitrogen to albumin ratio(BAR),collateral circulation and National Institutes of Health stroke scale(NIHSS)score for disease progression and short-term prognosis in patients with acute perforating artery cerebral infarction(APACI).Methods Patients with APACI admitted to the Neurology Department of Anhui NO.2 Provincial People's Hospital from January 2019 to October 2024 were retrospectively enrolled in this study.General and clinical data,including age,gender,previous history(hypertension,diabetes,hyperlipidemia,coronary heart disease,atrial fibrillation),smoking history,drinking history,NIHSS scores at admission were collected.Fasting venous blood samples were collected from the patients within 24 h after admission to detect levels of neutrophils,lymphocytes,monocytes,platelets,blood urea nitrogen,and serum albumin.PIV(PIV=neutrophils × platelets × monocytes/lymphocytes)and BAR were calculated.The location of lesions and Fazekas classification of white matter lesions were evaluated using head MRI and MR angiography at admission.Collateral circulation status was assessed based on CT angiography upon admission.Disease progression was defined through comparing the NIHSS score at 72-hour after admission to the score at admission(an increase of 2 or more points in NIHSS score indicating disease progression).The patients were divided into a progression group and a non-progression group based on the increase in NIHSS score,as aforementioned.Patients follow-up was conducted through phone call or outpatient visits at 90 d after discharge.The modified Rankin scale(mRS)was used to evaluate the prognosis,with a mRS score of 0-2 indicates good prognosis,and a 3-6 indicates poor prognosis.Factors with statistically significant differences in univariate analysis were included in a multivariate Logistic regression analysis to explore the influencing factors of disease progression and poor prognosis in patients with APACI.The receiver operating characteristic(ROC)curve was used to evaluate the predictive value of each indicator for disease progression and poor prognosis in patients with APACI.Results A total of 165 patients with APACI were enrolled in this study,including 121 males and 44 females,aged 27-86 years,with an average of(61±11)years.Among all patients enrolled,56 patients were included in the progression group and 109 patients in the non-progression group,124 patients showed good prognosis and 41 patients had poor prognosis.No statistically significant differences were found in age,gender,smoking history,drinking history,hypertension,diabetes,hyperlipidemia,coronary heart disease,atrial fibrillation,lesion location,and Fazekas classification of white matter lesions between the progression group and the non-progression group(all P＞0.05).While the NIHSS score at admission,proportion of poor collateral circulation,PIV and BAR in the progression group were significantly higher than those in the non-progression group(all P＜0.05).Multivariate Logistic regression analysis showed that high NIHSS score at admission(OR,1.177,95％CI 1.001-1.384,P=0.049),poor collateral circulation(OR,3.107,95％CI 1.216-7.939,P=0.018),high PIV(OR,1.006,95％CI 1.003-1.009,P=0.001),and high BAR(OR,1.610 × 109,95％CI 5.769 × 104-4.494 × 1013,P＜0.01)were independent risk factors of disease progression in patients with APACI.ROC curve analysis results showed that the area under the curve(AUC)of combination of PIV,BAR,collateral circulation and NIHSS score at admission for predicting disease progression in patients with APACI was 0.914(95％ CI0.861-0.952,P＜0.01),which was greater than that of each indicator(all P＜0.05).No statistically significant differences were found in smoking,drinking,hypertension,hyperlipidemia,coronary heart disease,atrial fibrillation,lesion location,and BAR between the poor prognosis and the good prognosis group(all P＞0.05).Compared with the good prognosis group,the poor prognosis group had significantly older age and higher proportion of patients with diabetes,NIHSS score at admission,proportion of patients with poor collateral circulation,and PIV(all P＜0.05).Moreover,the proportion of men in the poor prognosis group was lower than that in the good prognosis group(P=0.039).There was a statistically significant difference between the good prognosis group and the poor prognosis group in the Fazekas classification of white matter lesions(P＜0.01).Multivariate Logistic regression analysis showed that high NIHSS score at admission(OR,1.345,95％CI 1.081-1.674,P=0.008),poor collateral circulation(OR,3.903,95％CI 1.061-14.355,P=0.040),and high PIV(OR,1.011,95％CI 1.005-1.017,P＜0.01)were independent risk factors of poor prognosis in patients with APACI.The AUC for predicting poor prognosis in patients with APACI through combining PIV,collateral circulation and NIHSS score at admission was 0.911(95％CI 0.857-0.950,P＜0.01),which is greater than using poor collateral circulation or NIHSS score at admission alone(both P＜0.05).However,there was no statistically significant difference in AUC between the PIV,collateral circulation and NIHSS score combined predictive model and the PIV(alone)predictive model(P＞0.05).Conclusions High PIV,high BAR,poor collateral circulation,and high NIHSS score at admission were independent risk factors of disease progression in patients with APACI.Combination of these four indices demonstrates relatively high predictive value for disease progression.In addition,high PIV,poor collateral circulation,and high NIHSS score at admission are independent risk factors of poor prognosis in patients with APACI.Joint detection of the three indices may assist in short-term prognosis evaluation of patients with APACI.

Objective To evaluate the relationship between triglyceride-glucose index(TyG)and intensive care unit(ICU)mor-tality in patients with non-diabetic sepsis.Methods The retrospective cohort study analyzed the data from sepsis patients admitted to the Second Hospital & Clinical Medical School,Lanzhou University between January 2018 and December 2023.The patients were divided into three groups based on the terartiles of the TyG index:group T1,group T2 and group T3,with ICU mortality as the primary endpoint.Multivariate COX regression analysis and restricted cubic spline(RCS)modeling were performed to investigate the potential non-linear relationship between the TyG index and ICU mortality of patients with sepsis,and subgroup analysis were conducted to further explore these relationships.Results This study included 578sepsis patients,with an ICU mortality of 16.96％.The Kaplan-Meier survival curve analysis indicated that the ICU mortality in the group T3 was significantly higher than that in the group T1.The RCS analysis re-vealed a linear relationship between the TyG index and ICU mortality,for every 1-unit increase in the TyG index,the risk of ICU mortal-ity increased by approximately 54％.Subgroup analysis demonstrated consistent effect directions across different subgroups,with no sub-group-specific effects,indicating the robustness of the results.Conclusion TyG index may serve as a potential biomarker for predicting ICU mortality in non-diabetic sepsis patients.

Objective:Exploring the safety and efficacy of intermittent theta rhythm stimulation on cortical excitability and upper limb motor function in patients with stroke at recovery stage.Method:From January,2022 to April 2023,30 patients with stroke at recovery stage who received rehabilita-tion treatment were randomly divided into the experimental group(n=15)and the control group(n=15)using the random number method.Both groups were subjected to routine rehabilitation training.The experimental group was given additional intermittent theta rhythm stimulation on the basis of routine rehabilitation,and the control group added intermittent theta rhythm sham stimulation,5 times a week for 4 weeks.Neurophysiologic indexes were tested on both the healthy and affected sides of the patients in the 2 groups before and after the intervention,as well as the assessment of upper limb motor function.Result:After 4 weeks of intervention,there were no statistical differences in MEP maximum wave ampli-tude,MEP latency,CMCT value,CSP value and RMT value of the healthy side between before and after in-tervention and between the groups(P>0.05);MEP maximum wave amplitude of the affected side of the experi-mental group was higher than before intervention(P<0.05);the affected side of the experimental group had a low-er MEP latency,CSP value,and RMT value than before intervention and the control group(P<0.01,P<0.05).Fugl-Meyer upper limb function scores,MBI scores,grip strength on the affected side,and nine-hole post time spent in the experimental group improved after the intervention compared to before the intervention(P<0.01,P<0.05).Fugl-Meyer upper extremity function scores,MBI scores,and time spent on the affected side of the nine-hole column improved in the experimental group after the intervention compared to the control group(P<0.01,P<0.05).Conclusion:Intermittent theta rhythm stimulation combined with conventional rehabilitation training did not show significant effects on the cortical excitability of the healthy side of patients with stroke at recovery stage.However,it could improve the cortical excitability of the affected side of patients with stroke at recovery stage and improve the motor function of the upper limbs.

Objective To investigate the predictive value of pan-immune-inflammation value(PIV),blood urea nitrogen to albumin ratio(BAR),collateral circulation and National Institutes of Health stroke scale(NIHSS)score for disease progression and short-term prognosis in patients with acute perforating artery cerebral infarction(APACI).Methods Patients with APACI admitted to the Neurology Department of Anhui NO.2 Provincial People's Hospital from January 2019 to October 2024 were retrospectively enrolled in this study.General and clinical data,including age,gender,previous history(hypertension,diabetes,hyperlipidemia,coronary heart disease,atrial fibrillation),smoking history,drinking history,NIHSS scores at admission were collected.Fasting venous blood samples were collected from the patients within 24 h after admission to detect levels of neutrophils,lymphocytes,monocytes,platelets,blood urea nitrogen,and serum albumin.PIV(PIV=neutrophils × platelets × monocytes/lymphocytes)and BAR were calculated.The location of lesions and Fazekas classification of white matter lesions were evaluated using head MRI and MR angiography at admission.Collateral circulation status was assessed based on CT angiography upon admission.Disease progression was defined through comparing the NIHSS score at 72-hour after admission to the score at admission(an increase of 2 or more points in NIHSS score indicating disease progression).The patients were divided into a progression group and a non-progression group based on the increase in NIHSS score,as aforementioned.Patients follow-up was conducted through phone call or outpatient visits at 90 d after discharge.The modified Rankin scale(mRS)was used to evaluate the prognosis,with a mRS score of 0-2 indicates good prognosis,and a 3-6 indicates poor prognosis.Factors with statistically significant differences in univariate analysis were included in a multivariate Logistic regression analysis to explore the influencing factors of disease progression and poor prognosis in patients with APACI.The receiver operating characteristic(ROC)curve was used to evaluate the predictive value of each indicator for disease progression and poor prognosis in patients with APACI.Results A total of 165 patients with APACI were enrolled in this study,including 121 males and 44 females,aged 27-86 years,with an average of(61±11)years.Among all patients enrolled,56 patients were included in the progression group and 109 patients in the non-progression group,124 patients showed good prognosis and 41 patients had poor prognosis.No statistically significant differences were found in age,gender,smoking history,drinking history,hypertension,diabetes,hyperlipidemia,coronary heart disease,atrial fibrillation,lesion location,and Fazekas classification of white matter lesions between the progression group and the non-progression group(all P＞0.05).While the NIHSS score at admission,proportion of poor collateral circulation,PIV and BAR in the progression group were significantly higher than those in the non-progression group(all P＜0.05).Multivariate Logistic regression analysis showed that high NIHSS score at admission(OR,1.177,95％CI 1.001-1.384,P=0.049),poor collateral circulation(OR,3.107,95％CI 1.216-7.939,P=0.018),high PIV(OR,1.006,95％CI 1.003-1.009,P=0.001),and high BAR(OR,1.610 × 109,95％CI 5.769 × 104-4.494 × 1013,P＜0.01)were independent risk factors of disease progression in patients with APACI.ROC curve analysis results showed that the area under the curve(AUC)of combination of PIV,BAR,collateral circulation and NIHSS score at admission for predicting disease progression in patients with APACI was 0.914(95％ CI0.861-0.952,P＜0.01),which was greater than that of each indicator(all P＜0.05).No statistically significant differences were found in smoking,drinking,hypertension,hyperlipidemia,coronary heart disease,atrial fibrillation,lesion location,and BAR between the poor prognosis and the good prognosis group(all P＞0.05).Compared with the good prognosis group,the poor prognosis group had significantly older age and higher proportion of patients with diabetes,NIHSS score at admission,proportion of patients with poor collateral circulation,and PIV(all P＜0.05).Moreover,the proportion of men in the poor prognosis group was lower than that in the good prognosis group(P=0.039).There was a statistically significant difference between the good prognosis group and the poor prognosis group in the Fazekas classification of white matter lesions(P＜0.01).Multivariate Logistic regression analysis showed that high NIHSS score at admission(OR,1.345,95％CI 1.081-1.674,P=0.008),poor collateral circulation(OR,3.903,95％CI 1.061-14.355,P=0.040),and high PIV(OR,1.011,95％CI 1.005-1.017,P＜0.01)were independent risk factors of poor prognosis in patients with APACI.The AUC for predicting poor prognosis in patients with APACI through combining PIV,collateral circulation and NIHSS score at admission was 0.911(95％CI 0.857-0.950,P＜0.01),which is greater than using poor collateral circulation or NIHSS score at admission alone(both P＜0.05).However,there was no statistically significant difference in AUC between the PIV,collateral circulation and NIHSS score combined predictive model and the PIV(alone)predictive model(P＞0.05).Conclusions High PIV,high BAR,poor collateral circulation,and high NIHSS score at admission were independent risk factors of disease progression in patients with APACI.Combination of these four indices demonstrates relatively high predictive value for disease progression.In addition,high PIV,poor collateral circulation,and high NIHSS score at admission are independent risk factors of poor prognosis in patients with APACI.Joint detection of the three indices may assist in short-term prognosis evaluation of patients with APACI.

Objective To investigate the role of lupeol in mitigating chondrocyte senescence in osteoarthritis(OA)by regulating autophagy through the sirtuin 3(SIRT3)/mechanistic target of rapamycin kinase(mTOR)pathway.Methods Knee articular chondrocytes from primary-generation mice were isolated and divided into different groups,including a control group,a lupeol group(given 2.5,5,10,20,and 40 μmol/L lupeol),a tert-butyl hydrogen peroxide(TBHP)group(receiving 50 μmol/L TBHP),TBHP+lupeol group,TBHP+lupeol+chloroquine(CQ)group(receiving 20 μmol/L CQ,an autophagy inhibitor),TBHP+lupeol+si-NC group,and TBHP+lupeol+si-SIRT3 group.Cell proliferation,reactive oxygen species(ROS)levels,and apoptosis were determined by CCK-8,DCFH-DA probe,and flow cytometry.Cell senescence was evaluated by β-gal staining.Western blot was used to determine the expressions of SIRT3,mTOR,senescence marker proteins(p21 and p16),extracellular matrix(ECM)degradation-related proteins(aggrecan,collagen Ⅱ,ADAMTS5,and MMP13),and autophagy-related proteins(LC3B Ⅰ,LC3BⅡ,and P62).RT-qPCR was used to determine the mRNA levels of senescence-associated secretory phenotypes(SASP),including IL-6,Cxcl10,MCP1,and MMP3.The expression of LC3 was detected by immunofluorescence.Autophagosomes were observed by transmission electron microscopy.A total of 30 male wild-type C57BL/6 mice were divided into different groups(n=10),including a Sham group,an OA group,and an OA+lupeol group receiving 50 mg/(kg·d)lupeol via gastric gavage.Cartilage damage was evaluated by safranin O-fast green staining.Results Based on the results of cell viability assay,20 μmol/L lupeol treatment for 24 h was identified as the optimal intervention concentration and duration.Compared with that in the TBHP group,cell viability was elevated in the TBHP+lupeol group(P＜0.05);ROS production,the proportion of β-gal-positive cells,the protein expression levels of p21 and p16,and the mRNA levels of SASP were decreased(P＜0.05);the protein levels of aggrecan and collagen Ⅱ were elevated and the protein levels of ADAMTS5 and MMP13 were decreased(P＜0.05);apoptosis was reduced(P＜0.05);P62 protein levels were reduced and the LC3B Ⅱ/LC3B Ⅰ ratio,the intensity of LC3B fluorescence spots,and the number of autophagosomes were increased(P＜0.05);the expression level of SIRT3 was elevated and the level of mTOR phosphorylation was reduced(P＜0.05)in the TBHP+Lupeol group.CQ treatment effectively abolished the promotion effects of lupeol on cell viability and autophagy,and the inhibitory effects of lupeol on ROS level,cell senescence,ECM degradation,and apoptosis(P＜0.05).Silencing of SIRT3 reversed the inhibitory effect of lupeol on mTOR phosphorylation level and the promotion effect of lupeol on autophagy(P＜0.05).In the in vivo experiment,compared with the OA group,the OA+lupeol group showed reduced cartilage degeneration and lower scores for the Osteoarthritis Research Society International grading system(P＜0.05).The OA+lupeol group also showed up-regulated SIRT3 expression,reduced mTOR phosphorylation level,increased LC3B Ⅱ/LC3B Ⅰ ratio,reduced MMP13 protein level,and reduced mRNA level of SASP(P＜0.05).Conclusion Lupeol alleviates chondrocyte senescence in osteoarthritis by regulating autophagy through the SIRT3/mTOR pathway.

Objective To elucidate the regulatory effects of Glycerol Kinase(GLPK)on the inflammatory response induced by lipopolysaccharide(LPS)in mouse Raw264.7 macrophages.Methods Raw264.7 macrophages were cultured in vitro,and an inflammatory model was established through LPS induction.The transcriptional levels of inflammatory cytokines NF-κB,TNF-α,IL-6,and IL-1β were quantified using RT-qPCR.The expression and localization of GLPK were examined via Western blot and immunofluorescence.Additionally,Western blot analysis was employed to detect the levels of cellular pan-succinylation and H3K23su expression.ChIP-qPCR was utilized to assess the enrichment of H3K23su modification at the IL-10 promoter.The total reactive oxygen species production was measured using DCFH-DA probes,while mitochondrial ROS levels were determined with Mito-SOX probes.Mitochondrial membrane potential changes,indicative of mitochondrial dysfunction,were evaluated using JC-1 fluorescent probes.Furthermore,GLPK overexpression plasmids were transfected into cells to investigate the effects of GLPK on inflammatory responses,mitochondrial function,and epigenetic modifications.Results LPS treatment led to mitochondrial dysfunction,inflammatory responses exacerbation,succinylation modifications reduction,and GLPK protein expression decrease in Raw264.7 cells.Overexpression of GLPK in LPS-treated cells improved mitochondrial function and reduced the transcription of pro-inflammatory cytokines.ChIP-qPCR analysis revealed that GLPK overexpression could reverse the LPS-induced suppression of H3K23su modification at the IL-10 promoter,thereby attenuating the inflammatory response.Conclusion LPS mediates inflammatory responses in Raw264.7 macrophages through a GLPK-dependent H3K23 succinylation modification mechanism.