Neurodegenerative diseases are a group of chronic progressive diseases characterized by inflammation,degenera-tion and apoptosis.Chronic neuroinflammation is gradually becoming a potential pathogenic and predisposing factor.As a widely expressed non-histone nucleoprotein,HMGB1 participates in inflammatory process of human body through receptors of advanced glycation end products and Toll-like receptors while maintaining chromosome homeostasis.As a key factor of neuroinflammation,HMGB1 is widely involved in development of neurodegenerative diseases and may become a biomarker and a potential therapeutic target of neurodegenerative diseases.This article reviews the role of HMGB1 in neurodegenerative diseases and tries to provide ground-work for basic research and clinical application for targeting HMGB1 in the treatment of neurodegenerative diseases.

BACKGROUND:Remyelination in the central nervous system is a basic repair process triggered by demyelinating events,mainly through the proliferation,migration,and differentiation of oligodendrocyte precursor cells into oligodendrocytes.The process of remyelination is affected by many factors such as astrocytes,myelin debris,microglia,macrophages,endothelial cells,pericytes,T cells,and age.OBJECTIVE:Astrocytes play an important role in regulating synaptic activity,nutritional support,and tissue repair in the central nervous system.This review aims to provide potential therapeutic targets for demyelinating diseases of central nervous system by reviewing the role of astrocytes in remyelination.METHODS:A search was conducted on relevant literature collected from CNKI,PubMed,and Web of Science from 2014 tO 2024.The search terms were"astrocytes,oligodendrocyte precursor cells,remyelination"in both Chinese and English.Finally,66 articles were included after screening and summarized.RESULTS AND CONCLUSION:(1)The treatment of demyelinating diseases,such as multiple sclerosis,is limited to disease-modifying therapies,and there is no available method to overcome the failure of remyelination.Therefore,it is necessary to explore targets related to remyelination to promote myelin repair.(2)Remyelination is a process in which oligodendrocyte precursor cells proliferate,migrate,differentiate,and mature into oligodendrocytes,and the latter produce myelin to wrap axons to form myelin sheath.(3)Astrocytes regulate remyelination by phagocytosis of myelin debris,participating in inflammatory response,transforming into oligodendrocyte lineage cells,providing energy supply for oligodendrocyte lineage cells,releasing neurotrophic factors,and secreting extracellular matrix components.(4)The drugs screened in this paper use astrocytes and their derived factors as intervention targets to regulate the remyelination.Some drugs have satisfactory effects,but their effectiveness and safety still need more basic research and clinical trials to verify.(5)The mechanism of action of astrocytes in remyelination has not been fully elucidated,and the related molecular targets and signaling pathways can be further studied.

Objective:To analyze the efficacy of transjugular intrahepatic portosystemic shunt (TIPS) combined with main splenic artery embolization in the treatment of patients with portal hypertension upper gastrointestinal bleeding complicated with extensive portal vein thrombosis (PVT).Methods:This study was a prospective, single-center, open-label, single-arm clinical trial. In the first phase, 81 patients with portal hypertension upper gastrointestinal bleeding who were admitted to Beijing Shijitan Hospital, Capital Medical University from January 2018 to December 2018 were consecutively enrolled, including 57 males and 24 females, with the age of (51.3±10.4) years. During TIPS surgery, the pressure of the portal vein before and after the balloon blocking the splenic artery was measured to clarify the contribution of the splenic artery to portal hypertension. In the second stage, from January 2019 to December 2022, 104 patients with portal hypertension upper gastrointestinal bleeding complicated with extensive PVT were re-enrolled, including 71 males and 33 females, with the age of (50.9±12.5) years. TIPS combined with main splenic artery embolization was performed, and portal vein pressure was measured before and after embolization. Follow up on the postoperative esophageal and gastric varices of the patients in the second stage.Results:The portal vein pressures before and after the first stage of balloon occlusion of the splenic artery were (35.2±8.4) mmHg (1 mmHg=0.133 kPa) and (24.2±6.3) mmHg, respectively. The pressure after occlusion was lower than that before occlusion, and the difference was statistically significant ( t=10.54, P<0.001). The portal vein pressures before and after the second stage embolization were (36.1±9.5) mmHg and (21.1±4.7) mmHg respectively. The pressure after embolization was lower than that before embolization, and the difference was statistically significant ( t=13.47, P<0.001). In the second stage, among the 104 patients, the proportion of those whose varicose veins disappeared or improved 6 months after the operation was 43.3%(45/104) and 51.0%(53/104), respectively. There were no patients with aggravation or rebleeding due to rupture. One year later, 8 patients (7.7%) had aggravated or ruptured esophageal and gastric varices with bleeding. Two years later, 12 patients (11.5%) had aggravated or bleeding. Conclusion:TIPS combined with main splenic artery embolization can effectively reduce the portal vein pressure in patients with portal hypertension upper gastrointestinal bleeding complicated with extensive PVT, improve the degree of esophageal and gastric varices, and reduce the risk of gastrointestinal bleeding.

BACKGROUND:Remyelination in the central nervous system is a basic repair process triggered by demyelinating events,mainly through the proliferation,migration,and differentiation of oligodendrocyte precursor cells into oligodendrocytes.The process of remyelination is affected by many factors such as astrocytes,myelin debris,microglia,macrophages,endothelial cells,pericytes,T cells,and age.OBJECTIVE:Astrocytes play an important role in regulating synaptic activity,nutritional support,and tissue repair in the central nervous system.This review aims to provide potential therapeutic targets for demyelinating diseases of central nervous system by reviewing the role of astrocytes in remyelination.METHODS:A search was conducted on relevant literature collected from CNKI,PubMed,and Web of Science from 2014 tO 2024.The search terms were"astrocytes,oligodendrocyte precursor cells,remyelination"in both Chinese and English.Finally,66 articles were included after screening and summarized.RESULTS AND CONCLUSION:(1)The treatment of demyelinating diseases,such as multiple sclerosis,is limited to disease-modifying therapies,and there is no available method to overcome the failure of remyelination.Therefore,it is necessary to explore targets related to remyelination to promote myelin repair.(2)Remyelination is a process in which oligodendrocyte precursor cells proliferate,migrate,differentiate,and mature into oligodendrocytes,and the latter produce myelin to wrap axons to form myelin sheath.(3)Astrocytes regulate remyelination by phagocytosis of myelin debris,participating in inflammatory response,transforming into oligodendrocyte lineage cells,providing energy supply for oligodendrocyte lineage cells,releasing neurotrophic factors,and secreting extracellular matrix components.(4)The drugs screened in this paper use astrocytes and their derived factors as intervention targets to regulate the remyelination.Some drugs have satisfactory effects,but their effectiveness and safety still need more basic research and clinical trials to verify.(5)The mechanism of action of astrocytes in remyelination has not been fully elucidated,and the related molecular targets and signaling pathways can be further studied.

Objective:To analyze the efficacy of transjugular intrahepatic portosystemic shunt (TIPS) combined with main splenic artery embolization in the treatment of patients with portal hypertension upper gastrointestinal bleeding complicated with extensive portal vein thrombosis (PVT).Methods:This study was a prospective, single-center, open-label, single-arm clinical trial. In the first phase, 81 patients with portal hypertension upper gastrointestinal bleeding who were admitted to Beijing Shijitan Hospital, Capital Medical University from January 2018 to December 2018 were consecutively enrolled, including 57 males and 24 females, with the age of (51.3±10.4) years. During TIPS surgery, the pressure of the portal vein before and after the balloon blocking the splenic artery was measured to clarify the contribution of the splenic artery to portal hypertension. In the second stage, from January 2019 to December 2022, 104 patients with portal hypertension upper gastrointestinal bleeding complicated with extensive PVT were re-enrolled, including 71 males and 33 females, with the age of (50.9±12.5) years. TIPS combined with main splenic artery embolization was performed, and portal vein pressure was measured before and after embolization. Follow up on the postoperative esophageal and gastric varices of the patients in the second stage.Results:The portal vein pressures before and after the first stage of balloon occlusion of the splenic artery were (35.2±8.4) mmHg (1 mmHg=0.133 kPa) and (24.2±6.3) mmHg, respectively. The pressure after occlusion was lower than that before occlusion, and the difference was statistically significant ( t=10.54, P<0.001). The portal vein pressures before and after the second stage embolization were (36.1±9.5) mmHg and (21.1±4.7) mmHg respectively. The pressure after embolization was lower than that before embolization, and the difference was statistically significant ( t=13.47, P<0.001). In the second stage, among the 104 patients, the proportion of those whose varicose veins disappeared or improved 6 months after the operation was 43.3%(45/104) and 51.0%(53/104), respectively. There were no patients with aggravation or rebleeding due to rupture. One year later, 8 patients (7.7%) had aggravated or ruptured esophageal and gastric varices with bleeding. Two years later, 12 patients (11.5%) had aggravated or bleeding. Conclusion:TIPS combined with main splenic artery embolization can effectively reduce the portal vein pressure in patients with portal hypertension upper gastrointestinal bleeding complicated with extensive PVT, improve the degree of esophageal and gastric varices, and reduce the risk of gastrointestinal bleeding.

Neurodegenerative diseases are a group of chronic progressive diseases characterized by inflammation,degenera-tion and apoptosis.Chronic neuroinflammation is gradually becoming a potential pathogenic and predisposing factor.As a widely expressed non-histone nucleoprotein,HMGB1 participates in inflammatory process of human body through receptors of advanced glycation end products and Toll-like receptors while maintaining chromosome homeostasis.As a key factor of neuroinflammation,HMGB1 is widely involved in development of neurodegenerative diseases and may become a biomarker and a potential therapeutic target of neurodegenerative diseases.This article reviews the role of HMGB1 in neurodegenerative diseases and tries to provide ground-work for basic research and clinical application for targeting HMGB1 in the treatment of neurodegenerative diseases.

Objective: To explore the clinical efficacy of Xiaoshuan enteric-coated capsule (XSECC) in treating cerebral infarction and its potential mechanism of action. Methods: Patients with acute ischemic stroke (AIS) of the qi deficiency and blood stasis type were randomly assigned to the control and observation groups. They were evaluated using the National Institutes of Health Stroke Scale (NIHSS), Activities of Daily Living (ADL), Hachinskilnchemic Scale (HIS), Barthel Index (BI), clinical efficacy scores, and TCM syndrome scores on days 0, 14, 30, and 90. Furthermore, VEGF and BDNF levels were measured on days 30 and 90. Finally, we analyzed the changes in each scale score and vascular neurological factor in both groups. Results: After 14 days of treatment, the difference values in NIHSS, ADL, and BI were higher, and TCM syndrome and clinical efficacy scores were increased in the observation group compared with those of the control group (all P < .05). After 30 days, the NIHSS, ADL, HIS, and TCM syndrome scores were decreased compared with those of the control group, while BI and clinical efficacy scores were increased (all P < .05). After 90 days, the difference value in ADL was higher, and TCM syndrome score was increased in the observation group compared with that of the control group (P = .047, P = .005, respectively). The levels of VEGF and BDNF were higher in the observation group than in the control group on days 14, 30, and 90 (all P < .05). VEGF and BDNF levels on day 0 were associated with prognosis of patients with AIS; therefore, they have a predictive value for the prognosis of acute cerebral infarction. Conclusions XSECC therapy can improve clinical outcomes in patients with acute and recurrent cerebral infarctions. Its mechanism of action may be associated with the secretion of VEGF and BDNF.

BACKGROUND:Vascular regeneration,as one of the crucial repair processes after its onset,necessitates visual analysis between the two. OBJECTIVE:To analyze the literature on ischemic stroke and vascular regeneration in the past decade using bibliometrics and sort out the current status,hotspots,and future research trends in this field. METHODS:We used a bibliometric approach to search the Web of Science database for literature on ischemic stroke and vascular regeneration published between January 2011 and May 2023.The obtained data were systematically analyzed using the VOSviewer visualization software to identify the number of articles,countries,keywords,institutions,authors,citations,and trends. RESULTS AND CONCLUSION:We searched and selected 1 484 articles and found that the relationship between ischemic stroke and vascular regeneration has emerged as a research hotspot in the cerebrovascular field,with the number of published articles continuing to rise.Most of these articles were authored by institutions from China and the United States.Shanghai Jiao Tong University was the most cited institution.The most influential author was Hermann DM,whose article had been cited 1 003 times.The current hot research topics in the field include extracellular vesicles,microRNAs and mesenchymal stem cells,which are being studied for their correlations with relevant diseases.To conclude,the bibliometric analysis provides a visual analysis of ischemic stroke and vascular regeneration,which is found to be an emerging focus as well as a valuable reference for future trends and highlights in ischemic stroke and vascular regeneration.

BACKGROUND:Ischemic stroke is a highly prevalent disease associated with apoptosis.Neuronal death occurs after cerebral ischemia,including necrosis and apoptosis.The ischemic core region is dominated by necrosis,while delayed neuronal death in the penumbra is dominated by apoptosis.The penumbra has become a target for the treatment of ischemic stroke.This bibliometric analysis was used to identify the characteristics,hotspots,and frontiers of global scientific output related to apoptosis in ischemic stroke over the past 5 years. OBJECTIVE:To analyze the role of apoptosis and its mechanisms in the pathological process of ischemic stroke through a bibliometric approach. METHODS:A total of 927 relevant literature records from 2018 to 2022 were retrieved from Science Citation Index Expanded(SCI-Expanded)and Social Science Citation Index Expanded(SSCI-Expanded)of the Web of Science Core Collection.Research trends and hotspots of apoptosis in ischemic stroke were visualized using Citespace,VOSviewer and Bibliometrix. RESULTS AND CONCLUSION:From 2018 to 2020,the number of papers on the role of apoptosis in ischemic stroke showed an upward trend,but in 2020,the number of papers began to reduce.China had the largest number of publications,and the United States ranked the second.Capital Medical University and BRAIN RESEARCH BULLETIN were the institutions and journals with the most articles,respectively.In recent years,the two keywords"expression"and"oxidative stress"have appeared more frequently.The bibliometric study showed that in the past 5 years,most of the studies focused on basic research,in which research on the role of apoptosis in ischemic stroke has gradually decreased in the last 3 years,showing a downward trend.On the contrary,nerve regeneration has gradually become a research hotspot,especially the regulation of neurotrophic factors under the influence of different mechanisms,and the research on angiogenesis and glial cell repair is on the rise.At the same time,apoptosis in nerve regeneration is a potential point of discovery.

Objective:To investigate the expression and clinical significance of microRNA-124(miR-124)and microRNA-1976(miR-1976)in the serum of patients with Parkinson's disease(PD).Methods:A total of 58 patients with PD were selected from September 2020 to June 2022 and categorized as the PD group.The Unified Parkinson's Disease Rating Scale(UPDRS)score was used to divide the PD patients into two groups: those with a UPDRS score≤60(25 patients)and those with a UPDRS score >60(33 patients). The Hoehn-Yahr grading scale was used to grade the PD patients.Additionally, 30 healthy individuals who had undergone a physical examination during the same period were selected as the control group.After collecting the subjects' serum, we performed real-time fluorescent quantitative PCR(qRT-PCR)to detect the expressions of miR-124 and miR-1976 in the serum.Logistic regression analysis was employed to analyze the influencing factors, and the diagnostic significance of serum miR-124 and miR-1976 in PD patients was evaluated using the receiver operating characteristic(ROC)curve.To predict the target genes of miR-1976, we utilized several software including TargetScan and Mirtarbase.Results:Compared to the control group, the PD group showed a significant down-regulation of serum miR-124 expression[(1.49±0.36) vs.(1.02±0.32)]( t=8.85, P<0.001), while miR-1976 expression was sharply up-regulated[(0.98±0.30) vs.(1.33±0.37)]( t=6.92, P<0.001). The low expression of serum miR-124 and the overexpression of miR-1976 were identified as independent risk factors for PD( OR>1, P<0.05). The Hoehn-Yahr rating of PD patients with a UPDRS score above 60 was higher than that of patients with a UPDRS score below 60[(3.42 ± 0.73) vs.(2.16 ± 0.42)]( t=3.05, P<0.05). However, there was no significant difference in serum miR-124 and miR-1976 expression between groups with different UPDRS scores[miR-124: (1.09±0.26) vs.(0.98±0.38)( t=0.89, P>0.05); miR-1976: (1.42±0.43) vs.(1.23±0.68)( t=0.62, P>0.05)]. The ROC analysis results demonstrated that miR-124 and miR-1976 had area under the curve(AUC)values of 0.832 and 0.797, respectively, in diagnosing PD.The corresponding cutoff values were 1.205 and 1.196, respectively.The sensitivity for miR-124 was 74.1%, while for miR-1976 it was 51.8%.The specificity for miR-124 was 77.8%, and for miR-1976 it was 90.1%.When both miR-124 and miR-1976 were combined in the diagnosis of PD, the AUC was 0.912, with a sensitivity of 76.4% and a specificity of 93.2%.Furthermore, it was found that miR-1976 targeted the PINK1 gene, suggesting its potential as a target gene in PD. Conclusions:The expression of miR-124 was found to be decreased in PD patients, while the expression of miR-1976 was increased.Both miR-124 and miR-1976 showed some reference value in PD diagnosis, and their combined diagnostic value was higher.This suggests that further study on their significance is warranted.However, it should be noted that the expressions of miR-124 and miR-1976 were not found to be correlated with the UPDRS score of PD patients.