Objective To explore the effects of Dushu pills on cognitive ability and mitochondrial dynamics related proteins in mouse model of Alzheimer's disease(AD)based on network pharmacology.Methods The corresponding targets of Dushu pills and its related targets with AD were predicted using TCMSP database.The intersection targets of Dushu pills and AD were obtained by Venny website.The protein interaction network and drug-disease-target network were mapped using String database and Cytoscape software,respectively.GO and KEGG enrichment analysis were performed for intersection targets using David database.The mouse model of AD was established by injecting Aβ25-35 into bilateral ventricles.The learning and memory ability of the mice was detected by behavioral tests,the mitochondrial damage of neurons in the hippocampus was observed by transmission electron microscopy,and the expression of proteins related to mitochondrial dynamics was detected by Western blot.Results A total of 311 intersection targets related to drugs and diseases were screened out from the database.GO and KEGG analysis showed that the relevant targets were concentrated in mitochondria and other components,and concentrated in the pathways of ATP binding and positive regulation of MAPK activity.Compared with the normal group,the learning and memory ability of the model group was decreased(P<0.05),mitochondrial ridges appeared swelling and fracture(P<0.0001),decreased expression of MAPK,Mfn2 and OPA1 proteins in hippocampus(P<0.01),the expression of DRP1 protein increased(P<0.01).Compared with the model group,the learning and memory ability of mice in the medium and high dose groups of Dushu pills was improved(P<0.05),mitochondrial damage was significantly improved(P<0.01),increased expression of MAPK,Mfn2 and OPA1 in the hippocampus(P<0.01),DRP1 protein expression decreased(P<0.01).Conclusion Dushu pills can reduce mitochondrial damage,maintain mitochondrial homeostasis,and improve the cognitive and memory ability of AD mice.

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.

Non-peptide macrocyclic drugs possess unique structural advantages that allow them to target various biomolecules of interest and thus show therapeutic potential against various diseases such as cancer, infectious diseases, etc. This review article examines 34 non-peptide macrocyclic drugs approved between 2000 and 2024, with a particular focus on the optimization process of representative macrocyclic drugs such as natural macrocycles, natural product-inspired macrocycles, and de novo-designed macrocycles. We discuss their structural characteristics, highlighting how conformational rigidity and enhanced target specificity contribute to their efficacy. Design details of these new macrocyclic drugs are illustrated through successful examples, offering insights for optimizing macrocycles. Of note, macrocyclization of U-shaped lead structures represents a novel molecular skeleton editing strategy in de novo macrocycle drug design.

Objective To explore the effects of Dushu pills on cognitive ability and mitochondrial dynamics related proteins in mouse model of Alzheimer's disease(AD)based on network pharmacology.Methods The corresponding targets of Dushu pills and its related targets with AD were predicted using TCMSP database.The intersection targets of Dushu pills and AD were obtained by Venny website.The protein interaction network and drug-disease-target network were mapped using String database and Cytoscape software,respectively.GO and KEGG enrichment analysis were performed for intersection targets using David database.The mouse model of AD was established by injecting Aβ25-35 into bilateral ventricles.The learning and memory ability of the mice was detected by behavioral tests,the mitochondrial damage of neurons in the hippocampus was observed by transmission electron microscopy,and the expression of proteins related to mitochondrial dynamics was detected by Western blot.Results A total of 311 intersection targets related to drugs and diseases were screened out from the database.GO and KEGG analysis showed that the relevant targets were concentrated in mitochondria and other components,and concentrated in the pathways of ATP binding and positive regulation of MAPK activity.Compared with the normal group,the learning and memory ability of the model group was decreased(P<0.05),mitochondrial ridges appeared swelling and fracture(P<0.0001),decreased expression of MAPK,Mfn2 and OPA1 proteins in hippocampus(P<0.01),the expression of DRP1 protein increased(P<0.01).Compared with the model group,the learning and memory ability of mice in the medium and high dose groups of Dushu pills was improved(P<0.05),mitochondrial damage was significantly improved(P<0.01),increased expression of MAPK,Mfn2 and OPA1 in the hippocampus(P<0.01),DRP1 protein expression decreased(P<0.01).Conclusion Dushu pills can reduce mitochondrial damage,maintain mitochondrial homeostasis,and improve the cognitive and memory ability of AD mice.

Objective:To explore the effect and possible mechanism of Zexie Tang(ZXT)regulate the balance of M1/M2 polarization in macrophage cells.Methods:Lipid metabolism disorder mouse model was induced by Western diet(WD)in vivo,RAW264.7 cell M1/M2 macrophage model was induced by LPS/IL-4 in vitro,set up blank group,model group and ZXT group.The flu-orescence intensity of M1 and M2 macrophage markers in adipose tissue and RAW264.7 cells was observed by immunofluorescence staining;protein levels of p-AKT,AKT and COX-2 were measured by Western blot;levels of macrophage marker gene mRNAs of M1 and M2 were analysed by qPCR;IL-1β and IL-10 were measured by ELISA;content of NO was detected by Griess;binding of active components of Alismatis Rhizoma and Atractylodes Macrocephala with PI3K protein was analyzed by Docking.Results:Compared with WD group,expression of CD11c was significantly decreased in ZXT group,while expression of CD206 was significantly up-regulated;ZXT reversed LPS-induced increased in CD80 expression,down-regulated mRNA levels of M1 macrophage marker gene iNOS,etc,decreased the expression of COX-2 protein,and inhibited the secretion of IL-1β(P<0.001);ZXT promoted IL-4-induced CD206 expression,up-regulation of M2 macrophage marker gene Arg-1 and other mRNAs levels and secretion of IL-10;ZXT reversed the LPS-induced increased in NO release;p-AKT/AKT protein level increased in vivo and in vitro after ZXT administration;Docking re-sults show that many active ingredients in Alismatis Rhizoma and Atractylodes Macrocephala could form hydrogen bonds stably with PI3K protein.Conclusion:ZXT regulates the M1/M2 polarization balance of macrophages,and its mechanism may be related to the regulation of PI3K/AKT pathway.

Objective To investigate the effects and mechanisms of five-element music on the social behavior of the children of mothers with fear stress during pregnancy and provide a basis for the early prevention and treatment of clinical fetogenic affective disorders.Methods Forty-five pregnant mice were randomly divided into three groups:a control group,model group,and five-element music group.The model and five-element music group models were established using the bystander electric shock method.Additionally,the five-element music group was exposed to Palace Tune five-element music daily from 17:00 to 19:00 during pregnancy.On the 19th day of pregnancy,ELISA was employed to assess the levels of adrenocorticotropin(ACTH)and cortisol(CORT)in the serum of pregnant mice in each group for modeling evaluation.The offspring were subsequently grouped with their mother and underwent an 8-week-old three-box social experiment to observe their social behavior.We used the immunofluorescence double-labeling method to detect glutamatergic neuron activity in the medial prefrontal cortex(mPFC)of the offspring.High-performance liquid chromatography was employed to measure the total glutamate(Glu)content in the mPFC,while Gorky staining was used to observe changes in the dendritic spines of mPFC neurons in the offspring.Results Compared to those in the blank group,pregnant mice in the model group exhibited a significant increase in the levels of ACTH and CORT in their serum,and there was a significant decrease in the social interaction time and social novelty preference index of their offspring.There was also a significant decrease in glutamate neuron activity,glutamate content,and neuronal dendritic spine density.In contrast,compared with those in the model group,pregnant mice in the five-element music group demonstrated a reduction in the levels of ACTH and CORT in the serum,and there were improvements in the social behavior,glutamate neuron activity,glutamate content,and condition of neuronal dendritic spines in the offspring.Conclusions Intervention with five-element music effectively ameliorated the offspring's social behavior disorder result ing from prenatal fear stress;the mechanism was potentially linked to enhanced glutamate neuron activity in the mPFC region.

Aim To explore the related influencing factors of stroke in middle-aged and elderly population in China,and to construct a nomogram prediction model to provide more personalized reference for the prevention and treat-ment of stroke.Methods This study included 13 063 participants from the China Health and Retirement Tracking Survey project.This project conducted a cross-sectional survey in 2011 using a multi-stage sampling method,targeting in-dividuals aged 45 and above from 150 counties and 450 communities(villages)in 28 provinces(autonomous regions and municipalities).Detailed data were collected on participants'socio-demographic characteristics,physical measurements,health status,healthcare utilization,household income,and expenditure.The study participants were followed up to as-sess stroke in 2013,2015,and 2018.Univariate and multivariate Cox regression analyses were employed to identify the factors associated with stroke incidence and to construct a nomogram predictive model.Results During the follow-up,774 participants developed to stroke.Multivariate Cox regression results showed that older age(HR=1.028,95％CI:1.019-1.038),being single(HR=1.295,95％CI:1.031-1.626),smoking(HR=1.264,95％CI:1.074-1.489),abnormal body mass index(HR=1.204,95％CI:1.020-1.420),hypertension(HR=2.200,95％CI:1.855-2.609)and diabetes(HR=1.483,95％CI:1.117～1.970)were the risk factors affecting the incidence of stroke,high levels of annual per capita expenditure(HR=0.783,95％CI:0.642-0.953)are antagonistic factors in the incidence of stroke.The nomogram constructed based on the above factors had good predictive performance,and its area under the curve(AUC)was about 0.700.Conclusion Old age,being single,smoking,abnormal body mass index,history of hypertension and diabetes are independent risk factors for stroke,the nomogram constructed based on these factors can help predict the incidence rate of stroke.

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)