ObjectiveTo investigate the anti-Alzheimer's disease （AD） effect of Dipsacus asper（DA） in the Caenorhabditis elegans model， and decipher the underlying mechanism via the peroxisome proliferator-activated receptor α （PPARα）/transcription factor EB （TFEB） pathway. MethodsFirst， transgenic AD C. elegans individuals were assigned into the blank control， model， positive control （WY14643， 20 µmol·L^-1）， and low-， medium-， and high-dose （100， 200， and 400 mg·L^-1， respectively） DA groups. The amyloid β-42 （Aβ₄₂） formation in the muscle cells， the paralysis time， and the deposition of amyloid β-protein （Aβ） in the head were detected. The lysosomal autophagy in the BV2 cell model was examined by Rluc-LC3wt/G120A. The expression levels of lysosomal autophagy-related proteins LC3Ⅱ， LC3I， LAMP2， and TFEB were detected by Western blot. Real-time quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of autophagy-related genes beclin1 and Atg5 and lysosome-related genes LAMP2 and CLN2 downstream of PPARα/TFEB. A reporter gene assay was used to detect the transcriptional activities of PPARα and TFEB. Immunofluorescence was used to detect the fluorescence intensity of PPARα， and the active components of the ethanol extract of DA were identified by UPLC-MS. RCSB PDB， Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， and Autodock were used to analyze the binding between the active components and PPARα-ligand-binding domain （LBD）. ResultsCompared with the model group， the positive control group and 200 and 400 mg·L^-1 DA groups showed prolonged paralysis time （P<0.05）， and all the treatment groups showed decreased Aβ deposition in the head （P<0.01）. DA within the concentration range of 50-500 mg·L^-1 did not affect the viability of BV2 cells. In addition， DA enhanced the autophagy flux （P<0.05）， up-regulated the mRNA levels of beclin1， Atg5， LAMP2， and CLN2 （P<0.05， P<0.01）， promoted the nuclear translocation of TFEB （P<0.05）， increased LAMP2 expression and autophagy flux （P<0.05， P<0.01）， and enhanced the transcriptional activities of PPARα and TFEB （P<0.01）. The positive control group and 200 and 400 mg·L^-1 DA groups showed enhanced fluorescence intensity of PPARα in the BV2 nucleus （P<0.01）. UPLC-MS detected nine known compounds of DA， from which 8 active components of DA were screened out. The docking results suggested that a variety of components in DA could bind to PPARα-LBD and form stable hydrogen bonds. ConclusionDA may reduce the pathological changes in AD by regulating the PPARα-TFEB pathway.

BACKGROUND:Macrophage migration inhibitory factor(MIF)is a pleiotropic cytokine,which is secreted in different types of stem cells and can regulate the proliferation,differentiation and migration of various types of stem cells.Our previous research has confirmed that human embryonic stem cells secrete MIF and that its concentration in the culture medium is relatively stable.However,whether MIF is involved in the survival,proliferation and differentiation of human embryonic stem cells remains unclear. OBJECTIVE:To investigate the effects of MIF on survival,proliferation,and differentiation of human embryonic stem cells. METHODS:(1)Human embryonic stem cells H9 were cultured.The growth curve of cells was detected and plotted by CCK-8 assay.Enzyme-linked immunosorbent assay was used to determine the level of MIF in the medium.(2)To determine the effects of exogenous MIF on the survival and proliferation of human embryonic stem cells,different groups were established:the control group,which was cultured in stem cell medium without any modifications;the exogenous MIF group,which was treated with different concentrations(30,100,300 ng/mL)of MIF in the stem cell medium;the MIF inhibitor ISO-1 group,which was treated with different concentrations(2,7,21 μmol/L)of ISO-1 in the stem cell medium;and the MIF+ISO-1 group,which was treated with different concentrations of ISO-1 along with 100 ng/mL of MIF.Cell viability was assessed using the CCK-8 assay.(3)To further elucidate the effect of MIF gene on survival and proliferation of human embryonic stem cell,the MIF knockout H9 cell line was constructed by CRISPR-Cas 9 technology to observe the lineage establishment.(4)To determine the effect of high concentrations of MIF on human embryonic stem cell differentiation,100 ng/mL MIF and 100 ng/mL of CXCR4 neutralizing antibody were separately added to the normal stem cell culture medium.The expression levels of self-renewal factors(KLF4,c-MYC,NANOG,OCT4,and SOX2)and differentiation transcription factors(FOXA2,OTX2)were measured using real-time quantitative polymerase chain reaction,immunofluorescence staining,and western blot analysis. RESULTS AND CONCLUSION:(1)The logarithmic growth phase of H9 cells was between 3-6 days.Under normal growth conditions,human embryonic stem cells secreted MIF at a concentration of approximately 20 ng/mL,independent of cell quantity.(2)Compared to the control group,the addition of different concentrations of MIF had no effect on the proliferation of human embryonic stem cells(P>0.05).ISO-1 significantly inhibited the proliferation of human embryonic stem cells,with a stronger inhibition observed at higher concentrations of ISO-1(P<0.05).The addition of MIF in the presence of ISO-1 reduced the inhibitory effect of ISO-1(P<0.05).(3)Real-time quantitative polymerase chain reaction showed that knocking out 50%of the MIF gene resulted in a significant decrease in the growth vitality of human embryonic stem cells and failure to establish cell lines.(4)Adding 100 ng/mL exogenous MIF to the culture medium resulted in a decrease in the mRNA,protein,and fluorescence expression levels of the self-renewal transcription factor KLF4,while the mRNA,protein,and fluorescence expression levels of the differentiation factor FOXA2 increased.(5)When 100 ng/mL CXCR4 neutralizing antibody was added to the culture medium,the mRNA and protein expression levels of KLF4 increased,while the mRNA and protein expression levels of FOXA2 decreased,contrary to the expression trend observed in the MIF group.In conclusion,the endogenous secretion of MIF by human embryonic stem cells is essential for their survival.The addition of MIF to the culture medium does not promote the proliferation of human embryonic stem cells.However,it can lead to a decrease in the expression of the self-renewal factor KLF4 and an increase in the expression of the transcription factor FOXA2.This provides a clue for further investigation into the effects and mechanisms of MIF on the differentiation of human embryonic stem cells.The MIF-CXCR4 axis plays a regulatory role in this process.

Background: and Purpose Limited evidence exists on the effectiveness of endovascular treatment (EVT) for acute posterior circulation tandem lesion (PCTL). This study aimed to explore the role of extracranial vertebral artery (VA) stenting in patients with PCTL stroke undergoing EVT. Methods: Individual patient data were pooled from the BASILAR (EVT for Acute Basilar Artery Occlusion Study) and PERSIST (Posterior Circulation Ischemic Stroke) registries. Patients with PCTLs who underwent EVT were included in the present cohort and divided into the stenting and nonstenting groups based on the placement of extracranial VA stents. The primary efficacy outcome was the modified Rankin Scale (mRS) scores at 90 days and 1 year. Safety outcomes included 24-hour symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days and 1 year post-surgery. Results: A combined dataset of 1,320 patients with posterior circulation artery occlusion, including 263 (19.9%) with tandem lesions, of whom 217 (median age, 65 years; 82.9% male) met the inclusion criteria for the analysis. The stenting group had 84 (38.7%) patients, while the non-stenting group had 133 (61.3%). After adjustment for the potential confounders, extracranial VA stenting was associated with favorable shifts in mRS scores at both 90 days (adjusted common odds ratio [OR], 2.30; 95% confidence interval [CI], 1.23–4.28; P<0.01) and 1 year (adjusted OR [aOR], 2.04; 95% CI [1.05–3.97]; P=0.04), along with lower rate of mortality at both 90 days (aOR, 0.45; 95% CI [0.21–0.93]; P=0.01) and 1 year (aOR, 0.36; 95% CI [0.16–0.79]; P=0.01), with no significant difference in sICH incidence (aOR, 0.35; 95% CI [0.06–1.98]; P=0.24). Conclusion Extracranial VA stenting during EVT may improve functional outcomes and reduce mortality in patients with PCTL strokes.

Background: and Purpose Limited evidence exists on the effectiveness of endovascular treatment (EVT) for acute posterior circulation tandem lesion (PCTL). This study aimed to explore the role of extracranial vertebral artery (VA) stenting in patients with PCTL stroke undergoing EVT. Methods: Individual patient data were pooled from the BASILAR (EVT for Acute Basilar Artery Occlusion Study) and PERSIST (Posterior Circulation Ischemic Stroke) registries. Patients with PCTLs who underwent EVT were included in the present cohort and divided into the stenting and nonstenting groups based on the placement of extracranial VA stents. The primary efficacy outcome was the modified Rankin Scale (mRS) scores at 90 days and 1 year. Safety outcomes included 24-hour symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days and 1 year post-surgery. Results: A combined dataset of 1,320 patients with posterior circulation artery occlusion, including 263 (19.9%) with tandem lesions, of whom 217 (median age, 65 years; 82.9% male) met the inclusion criteria for the analysis. The stenting group had 84 (38.7%) patients, while the non-stenting group had 133 (61.3%). After adjustment for the potential confounders, extracranial VA stenting was associated with favorable shifts in mRS scores at both 90 days (adjusted common odds ratio [OR], 2.30; 95% confidence interval [CI], 1.23–4.28; P<0.01) and 1 year (adjusted OR [aOR], 2.04; 95% CI [1.05–3.97]; P=0.04), along with lower rate of mortality at both 90 days (aOR, 0.45; 95% CI [0.21–0.93]; P=0.01) and 1 year (aOR, 0.36; 95% CI [0.16–0.79]; P=0.01), with no significant difference in sICH incidence (aOR, 0.35; 95% CI [0.06–1.98]; P=0.24). Conclusion Extracranial VA stenting during EVT may improve functional outcomes and reduce mortality in patients with PCTL strokes.

Background: and Purpose Limited evidence exists on the effectiveness of endovascular treatment (EVT) for acute posterior circulation tandem lesion (PCTL). This study aimed to explore the role of extracranial vertebral artery (VA) stenting in patients with PCTL stroke undergoing EVT. Methods: Individual patient data were pooled from the BASILAR (EVT for Acute Basilar Artery Occlusion Study) and PERSIST (Posterior Circulation Ischemic Stroke) registries. Patients with PCTLs who underwent EVT were included in the present cohort and divided into the stenting and nonstenting groups based on the placement of extracranial VA stents. The primary efficacy outcome was the modified Rankin Scale (mRS) scores at 90 days and 1 year. Safety outcomes included 24-hour symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days and 1 year post-surgery. Results: A combined dataset of 1,320 patients with posterior circulation artery occlusion, including 263 (19.9%) with tandem lesions, of whom 217 (median age, 65 years; 82.9% male) met the inclusion criteria for the analysis. The stenting group had 84 (38.7%) patients, while the non-stenting group had 133 (61.3%). After adjustment for the potential confounders, extracranial VA stenting was associated with favorable shifts in mRS scores at both 90 days (adjusted common odds ratio [OR], 2.30; 95% confidence interval [CI], 1.23–4.28; P<0.01) and 1 year (adjusted OR [aOR], 2.04; 95% CI [1.05–3.97]; P=0.04), along with lower rate of mortality at both 90 days (aOR, 0.45; 95% CI [0.21–0.93]; P=0.01) and 1 year (aOR, 0.36; 95% CI [0.16–0.79]; P=0.01), with no significant difference in sICH incidence (aOR, 0.35; 95% CI [0.06–1.98]; P=0.24). Conclusion Extracranial VA stenting during EVT may improve functional outcomes and reduce mortality in patients with PCTL strokes.

Objective To investigate the difference between self-perceived risk and objective risk of stroke in the elderly population in Haikou area and explore the related factors in order to deter-mine the role of stroke knowledge in self-perceived risk.Methods A cross-sectional questionnaire survey was conducted on 584 elderly patients who were selected by convenience sampling from those taking physical examination in the First Affiliated Hospital of Hainan Medical College from September 2022 to April 2023.According to the accuracy of self-perceived risk of stroke,they were divided into an under-estimation group(170 cases),an accurate-estimation group(329 cases)and an over-estimation group(85 cases).Their self-perceived risk of stroke was assessed with the Stroke Risk Perception Questionnaire,and the objective risk of stroke was assessed with the Screening Criteria of Stroke High-Risk Group Screening Intervention Project of National Health Commission.Multivariate logistic regression model was used to analyze the factors related to the accuracy of self-perceived risk of stroke.One-way ANOVA was used to analyze the correlation be-tween the accuracy of self-perceived stroke risk and stroke knowledge.Results The participants with low,moderate,and high self-perceived risk of stroke accounted for 75.5％,20.5％and 3.9％,respectively.Compared with the objective risk assessment,the percentages of the participants with self-perceived stroke risk were 29.1％,56.3％and 14.6％,respectively,in the under-,accurate-and over-estimation groups.Significant differences were observed in gender,education level,smoking,drinking,exercise,fatty diet,fruit,overweight or obesity,and dyslipidemia among all groups(P＜0.05,P＜0.01).Multivariate logistic regression analysis showed that smoking,regular exercise,overweight or obesity and dyslipidemia were associated with accuracy of stroke risk perception in the accurate and the over-estimation groups when the under-estimation group was regarded as control(P＜0.01).The total score of stroke knowledge was 6.81±3.63,7.17±3.47 and 8.07± 3.24,respectively in the 3 estimation groups.The accuracy of self-perceived stroke risk was corre-lated with stroke knowledge(F=3.756,P=0.024).Conclusion Targeted health education should be implemented to make the elderly establish correct awareness of stroke risk,promote healthy behaviors and habits,and achieve the goal of early stroke prevention.

Objective To compare the safety and efficacy of emergency balloon dilation angioplasty with emergency stent implantation in treating patients with acute anterior tandem occlusion caused by atherosclerosis at the starting segment of the internal carotid artery.Methods A total of 91 patients with stroke caused by acute anterior tandem occlusion,who were admitted to the First Affiliated Hospital of Hainan Medical College and the Third Affiliated Hospital of Guangzhou Medical University of China within 24 hours after disease onset to receive treatment from January 2018 to October 2022,were enrolled in this study.The patients were divided into balloon dilation angioplasty group(balloon dilation group,n=51)and stent implantation group(stenting group,n=40).The basic clinical data were compared between the two groups.The modified thrombolysis in cerebral infarction(mTICI)grade 2b-3 was defined as a good recanalization.The postoperative 90-day modified Rankin scale(mRS)score of 0-2 points was defined as a good clinical prognosis.Results The good recanalization rate and postoperative 90-day good clinical prognosis rate in the stenting group were 70％and 60％respectively,which were higher than 60％and 52％respectively in the balloon dilation group,and the differences between the two groups were not statistically significant(P=0.361 and P=0.391 respectively).The incidences of symptomatic intracranial hemorrhage(sICH),asymptomatic intracranial hemorrhage(aSICH),and mortality in the stenting group were 10％,32.5％,and 22.5％respectively,which in the balloon dilation group were 11.8％,41.2％,and 17.7％respectively,and the differences between the two groups were not statistically significant(P=1.000,P=0.396,and P=0.564 respectively).Conclusion For the treatment of patients with acute anterior tandem occlusion caused by atherosclerosis at the starting segment of the internal carotid artery,both emergency balloon dilation angioplasty or stent implantation are clinically safe and effective.(J Intervent Radiol,2024,33:593-598)

Objective:To explore the molecular mechanism through which repetitive transcranial magnetic stimulation (rTMS) promotes nerve regeneration after ischemic stroke.Methods:The miRNA expression profile in rats after rTMS was downloaded from the GEO database. Differentially-expressed miRNAs were identified using R software, and their corresponding mRNAs were predicted using the online database in order to construct miRNA-mRNA regulatory networks and identify the key miRNAs. The protein interaction network encoded by each gene was constructed by functional enrichment analysis, and the core mRNAs in the network were identified. Twenty-four male Sprague-Dawley rats of a specific pathogen-free grade were randomly divided into a sham operation group, a model group and a magnetic stimulation group, each of 8, and a stroke model was induced in the model and magnetic stimulation groups. The magnetic stimulation group then received rTMS for 7 consecutive days, while the other 2 groups did not. Modified neural function scores (mNSSs) were used to quantify neural function deficits before the experiment and 1, 3 and 7 days after the modeling. Eight days after the modeling, brain tissues were sampled for hematoxylin-eosin and Nishin staining to observe tissue loss and neuron morphology. Real-time fluorescence quantitative polymerase chain reactions were employed to verify the differential gene expression in the ischemic cortex.Results:A total of 167 different miRNAs were screened, and 25 mRNAs were predicted. Enrichment analysis showed that those genes are related to the positive regulation of cell migration and the positive regulation of neurotrophic factor receptor signaling pathways, including adenylate-activated protein kinase, the neurotrophic factor pathway, and rat sarcoma signaling pathways. The miRNA-mRNA regulatory network highlighted miR-206-3p, miR-378a-3p, miR-107-3p, miR-92a-3p and miR-29b-3p as key miRNAs. Integrin subunit β1, aquaporin 4, brain-derived nerve growth factor (BDNF), and member 4 of solutes vector family 2 were identified as key mRNAs by the protein interaction network analysis. Seven days after the modeling, the average mNSS score of the magnetic stimulation group was significantly lower than the model group′s average. Compared with the model group, the expression of miR-206-3p in the right cortex of the magnetic stimulation group had decreased significantly, while BDNF expression had increased significantly.Conclusions:miR-206-3p-BDNF pathways play an important role in neural repair promoted by rTMS.

Objective:To explore influence on physical development of children aged 18 months from HIV-positive mothers for prevention mother to child transmission of HIV (PMTCT) in Guangxi Zhuang autonomous region, and provide evidence for the improvement PMTCT program.Methods:This retrospective case control study was conducted in 554 HIV negative infants aged 18 months whose HIV positive mothers had received PMTCT services reported through PMTCT system database from January 1, 2010 to December 31, 2017 and 1 109 healthy infants born in 2017, whose mothers were healthy, in Lingshan, Luzhai, and Hengxian counties, ranking top three counties with high HIV infection prevalence, in Guangxi. PMTCT data and physical development data such as height, weight and head circumference of children aged 18 months were collected. The physical dysplasia in the infants was defined as at least one of the three main indicators of height, weight and head circumference below the normal range.Results:The number of HIV-positive mother and their infants in the case group were 667 and 554 respectively, and the PMTCT rates were 91.15 % (608/667) and 96.57 % (535/554) respectively. HIV positive rate, mortality rate and mother to child transmission rate of the infants aged 18 months were 1.44 % (8/554), 3.07 % (17/554) and 1.91 % (8/418) respectively, and the physical examination results of the infants aged 18 months showed that the physical dysplasia rate was 30.51 % (169/554). Among the 1 109 infants in the control group, the physical dysplasia rate was 9.83 % (109/1 109). The difference between the case group and the control group was significant ( P<0.01). Conclusion:The PMTCT rates of HIV positive mother and their children were more than 90.00 %, respectively. However, poor physical development rate of infants aged 18 months were more than 30.00 %. The possible influence of PMTCT on physical development of the infants aged 18 months of HIV positive mother’s needs to be further studied.

Objective :To explore rehabilitative effect of low—frequency (1Hz ,LF) repetitive transcranial magnetic stimulation (rTMS) combined functional electrical stimulation (FES) on lower limb spasm and motor function in pa—tients with subacute ischemic stroke (SAIS).Methods : A total of 92 SAIS patients with lower limb spasm and motor dysfunction hospitalized in our department were randomly divided into sham stimulation + FES group (sham stimu—lation group ,n＝45) and low—frequency rTMS + FES group (LF—rTMS group ,n＝47) ,both groups were continu—ously treated for three weeks .Lower limb motor function and spasm severity were assessed by Fugl—Meyer motor as—sessment (FMA) and modified Ashworth scale (MAS) respectively before and after treatment ,and motor evoked potential (MEP) was detected .Results : Compared with before treatment ,there was significant rise in FMA score , and significant reductions in MAS score and MEP in two groups after three—week treatment , P＝ 0.001 all ;com—pared with sham stimulation group ,there was significant rise in FMA score [16. 0 (13.0 ,23. 5 ) scores vs. 19. 0 (16.0 ,27.0) scores] ,and significant reductions in MAS score [1. 5 (1. 3 ,1.5) scores vs. 1. 0 (0. 5 ,1. 5) scores] and MEP [ (24.64 ± 0. 39) ms vs. (24.43 ± 0.31) ms] in LF—rTMS group after treatment , P＜0.05 or ＜ 0. 01 . Conclusion : Compared with sham stimulation + FES ,LF—rTMS + FES can more significantly improve lower limb spasm and motor function in patients with subacute ischemic stroke .