Intracranial arterial dolichoectasia(IADE)is a major arterial disease characterized by artery elongation,dilatation,and curvature.Although the pathological mechanism of IADE is unclear,recent studies have suggested a close relationship with matrix metalloproteinases(MMPs).This review summarizes the possible pathological mechanism of IADE induced by MMPs in terms of MMPs activation and the occurrence and development of IADE,the correlation between MMPs activation and positive remodeling causing IADE,and the relationship between hemodynamic changes,MMPs activation and IADE and between IADE-associated diseases and MMPs,to provide potential therapeutic targets for the effective prevention and treatment of IADE.

"Upper deficiency leading to vertigo" is one of the representative discussions on deficiency vertigo in Huang Di Nei Jing, which has laid the foundation for the rich development of the theory of "deficiency causing vertigo" in later generations. The brain lymphatic system can remove metabolic wastes and provide nutrients for the brain, which is involved in the development of many brain diseases. This study believes that the broad definition of "upper deficiency leading to vertigo", that is to say, vertigo is triggered by abnormalities in the local physiological functions of the brain orifices, can be used as a platform for the pathogenesis of vertigo. Based on the findings of modern medicine on the lymphoid system, the authors discussed the possible interactions between the lymphoid system, phlegm, blood stasis, deficiency, and other pathological factors of vertigo. β-amyloid, neurotransmitters, inflammatory mediators and other "toxic pathogenic factors" may also be an important cause of vertigo. This article attempted to explain the pathogenesis of "upper deficiency leading to vertigo" with the help of lymphoid system, in order to provide new thinking direction for the development of TCM clinical diagnosis and treatment of vertigo.

Objective To investigate whether vertebrobasilar dolichoectasia(VBD)and three vascular endothelial injury factors correlate with white matter hyperintensity(WMH)and lacunar infarction(LI)in patients with cerebral small vessel disease(CSVD).Methods Patients with CSVD hospitalized at the Brain Disease Center of the First Affiliated Hospital of Henan University of Chinese Medicine from March 2023 to March 2024 were prospectively and consecutively included in this study.Baseline clinical data,including gender,age,body mass index,hypertension,diabetes mellitus,coronary artery disease,atrial fibrillation,hyperlipidemia,hyperhomocysteinemia,hyperuricemia,carotid plaque,history of previous stroke,smoking,alcohol consumption,and other vascular risk factors.The patients were categorized into CSVD with VBD group and CSVD without VBD group.Imaging assessments were performed within 24 h of enrollment,including evaluating the WMH severity using Fazekas scale score(mild WMH:1-2,moderate WMH:3-4,severe WMH:5-6),imaging characteristics of LI and vertebrobasilar artery parameters on three dimensional time of flight magnetic resonance angiography images(including bilateral vertebral artery diameters,basilar artery diameters,standard basilar artery length[BAL],and bending length of the basilar artery).A basilar artery diameter ≥4.5 mm or vertebral artery diameter ≥4.0 mm was defined as dilatation.BAL ≥29.5 mm was defined as elongation,and a basilar artery bending length ≥ 10.0 mm was defined as curvature.Patients meeting at least one of these criteria(dilatation,elongation,and curvature)were included in the CSVD with VBD group.Levels of interleukin-6(IL-6),soluble intercellular adhesion molecule-1(sICAM-1),and von Willebrand factor(vWF)levels were measured on the second day of enrollment.To analyze the influencing factors of VBD in CSVD patients and examine the correlation between vertebrobasilar artery imaging parameters,the levels of three vascular endothelial injury factors(IL-6,sICAM-1,vWF),and the severities of WMH and LI in patients with CSVD.Results A total of 88 patients with CSVD,aged 40-80 years,with a mean age of(64±10)years,were included in this study,with 50patients in the CSVD with VBD group and 38patients in the CSVD without VBD group.(1)Univariate analysis showed no statistically significant differences in clinical baseline data or the three endothelial injury factor levels between the two groups(all P＞0.05).After adjusting for age and gender,variables with P＜0.1 in the univariate analysis(male,smoking history)were further examined using multivariate Logistic regression analysis,which showed that neither male gender(OR,2.656,95％CI 0.647-10.907,P=0.175)nor smoking history(OR,0.992,95％CI 0.255-3.866,P=0.991)significantly increased the risk of VBD in CSVD patients.(2)There were no statistically significant differences in bilateral vertebral artery diameters or BAL among different severity of WMH or between patients with or without LI(all P＞0.05).The basilar artery bending length was significantly smaller in patients with mild and moderate WMH CSVD than those with severe WMH CSVD(2.49[1.60,4.58]mm,5.24[2.28,6.02]mm,6.99[5.19,8.93]mm,respectively;both P＜0.05).(3)Univariate analysis showed that IL-6,sICAM-1,and vWF levels were significantly higher in patients with moderate and severe WMH CSVD compared to patients with mild WMH CSVD(all P＜0.05).IL-6 and sICAM-1 levels were significantly higher in patients with severe WMH CSVD compared to patients with moderate WMH CSVD(both P＜0.05).The levels of IL-6,sICAM-1,and vWF were significantly higher in CSVD patients with LI than those in CSVD patients without LI(all P＜0.05).(4)After adjusting for confounders such as gender,age,and smoking history,the multifactorial Logistic ordered regression analysis,using patients with mild WMH CSVD as the reference indicated that high IL-6(OR,2.358,95％CI 1.268-4.387,P=0.007),sICAM-1(OR,2.077,95％CI 1.430-3.016,P＜0.01),and vWF(OR,1.437,95％CI 1.058-1.951,P=0.020)levels were significant risk factors for the occurrence of moderate WMH in patients with CSVD,as well as significant risk factors for severe WMH in patients with CSVD(IL-6[OR,5.340,95％CI 2.555-11.163,P＜0.01],sICAM-1[OR,16.004,95％CI3.692-69.379,P＜0.01],and vWF[OR,1.748,95％CI 1.267-2.412,P=0.001]);a long basilar artery bending length was an risk factor for the development of moderate(OR,1.287,95％CI 1.032-1.603,P=0.025)and severe(OR,1.639,95％CI 1.280-2.099,P＜0.01)WMH in CSVD patients.(5)After adjusting for confounding factors such as gender,age,and smoking history,multifactorial Logistic ordered regression analysis identified that high IL-6(OR,1.536,95％CI 1.074-2.198,P=0.019),sICAM-1(OR,2.066,95％CI 1.465-2.913,P＜0.01),vWF(OR,1.423,95％CI 1.078-1.879,P=0.013)levels are significant influential factors for the development of LI in CSVD patients.Conclusions Longer basilar artery bending length was associated with more severe WMH in patients with CSVD.Elevated levels of IL-6,sICAM-1,and vWF were associated with development of LI and more severe WMH in patients with CSVD.

Objective To investigate whether vertebrobasilar dolichoectasia(VBD)and three vascular endothelial injury factors correlate with white matter hyperintensity(WMH)and lacunar infarction(LI)in patients with cerebral small vessel disease(CSVD).Methods Patients with CSVD hospitalized at the Brain Disease Center of the First Affiliated Hospital of Henan University of Chinese Medicine from March 2023 to March 2024 were prospectively and consecutively included in this study.Baseline clinical data,including gender,age,body mass index,hypertension,diabetes mellitus,coronary artery disease,atrial fibrillation,hyperlipidemia,hyperhomocysteinemia,hyperuricemia,carotid plaque,history of previous stroke,smoking,alcohol consumption,and other vascular risk factors.The patients were categorized into CSVD with VBD group and CSVD without VBD group.Imaging assessments were performed within 24 h of enrollment,including evaluating the WMH severity using Fazekas scale score(mild WMH:1-2,moderate WMH:3-4,severe WMH:5-6),imaging characteristics of LI and vertebrobasilar artery parameters on three dimensional time of flight magnetic resonance angiography images(including bilateral vertebral artery diameters,basilar artery diameters,standard basilar artery length[BAL],and bending length of the basilar artery).A basilar artery diameter ≥4.5 mm or vertebral artery diameter ≥4.0 mm was defined as dilatation.BAL ≥29.5 mm was defined as elongation,and a basilar artery bending length ≥ 10.0 mm was defined as curvature.Patients meeting at least one of these criteria(dilatation,elongation,and curvature)were included in the CSVD with VBD group.Levels of interleukin-6(IL-6),soluble intercellular adhesion molecule-1(sICAM-1),and von Willebrand factor(vWF)levels were measured on the second day of enrollment.To analyze the influencing factors of VBD in CSVD patients and examine the correlation between vertebrobasilar artery imaging parameters,the levels of three vascular endothelial injury factors(IL-6,sICAM-1,vWF),and the severities of WMH and LI in patients with CSVD.Results A total of 88 patients with CSVD,aged 40-80 years,with a mean age of(64±10)years,were included in this study,with 50patients in the CSVD with VBD group and 38patients in the CSVD without VBD group.(1)Univariate analysis showed no statistically significant differences in clinical baseline data or the three endothelial injury factor levels between the two groups(all P＞0.05).After adjusting for age and gender,variables with P＜0.1 in the univariate analysis(male,smoking history)were further examined using multivariate Logistic regression analysis,which showed that neither male gender(OR,2.656,95％CI 0.647-10.907,P=0.175)nor smoking history(OR,0.992,95％CI 0.255-3.866,P=0.991)significantly increased the risk of VBD in CSVD patients.(2)There were no statistically significant differences in bilateral vertebral artery diameters or BAL among different severity of WMH or between patients with or without LI(all P＞0.05).The basilar artery bending length was significantly smaller in patients with mild and moderate WMH CSVD than those with severe WMH CSVD(2.49[1.60,4.58]mm,5.24[2.28,6.02]mm,6.99[5.19,8.93]mm,respectively;both P＜0.05).(3)Univariate analysis showed that IL-6,sICAM-1,and vWF levels were significantly higher in patients with moderate and severe WMH CSVD compared to patients with mild WMH CSVD(all P＜0.05).IL-6 and sICAM-1 levels were significantly higher in patients with severe WMH CSVD compared to patients with moderate WMH CSVD(both P＜0.05).The levels of IL-6,sICAM-1,and vWF were significantly higher in CSVD patients with LI than those in CSVD patients without LI(all P＜0.05).(4)After adjusting for confounders such as gender,age,and smoking history,the multifactorial Logistic ordered regression analysis,using patients with mild WMH CSVD as the reference indicated that high IL-6(OR,2.358,95％CI 1.268-4.387,P=0.007),sICAM-1(OR,2.077,95％CI 1.430-3.016,P＜0.01),and vWF(OR,1.437,95％CI 1.058-1.951,P=0.020)levels were significant risk factors for the occurrence of moderate WMH in patients with CSVD,as well as significant risk factors for severe WMH in patients with CSVD(IL-6[OR,5.340,95％CI 2.555-11.163,P＜0.01],sICAM-1[OR,16.004,95％CI3.692-69.379,P＜0.01],and vWF[OR,1.748,95％CI 1.267-2.412,P=0.001]);a long basilar artery bending length was an risk factor for the development of moderate(OR,1.287,95％CI 1.032-1.603,P=0.025)and severe(OR,1.639,95％CI 1.280-2.099,P＜0.01)WMH in CSVD patients.(5)After adjusting for confounding factors such as gender,age,and smoking history,multifactorial Logistic ordered regression analysis identified that high IL-6(OR,1.536,95％CI 1.074-2.198,P=0.019),sICAM-1(OR,2.066,95％CI 1.465-2.913,P＜0.01),vWF(OR,1.423,95％CI 1.078-1.879,P=0.013)levels are significant influential factors for the development of LI in CSVD patients.Conclusions Longer basilar artery bending length was associated with more severe WMH in patients with CSVD.Elevated levels of IL-6,sICAM-1,and vWF were associated with development of LI and more severe WMH in patients with CSVD.

Intracranial arterial dolichoectasia(IADE)is a major arterial disease characterized by artery elongation,dilatation,and curvature.Although the pathological mechanism of IADE is unclear,recent studies have suggested a close relationship with matrix metalloproteinases(MMPs).This review summarizes the possible pathological mechanism of IADE induced by MMPs in terms of MMPs activation and the occurrence and development of IADE,the correlation between MMPs activation and positive remodeling causing IADE,and the relationship between hemodynamic changes,MMPs activation and IADE and between IADE-associated diseases and MMPs,to provide potential therapeutic targets for the effective prevention and treatment of IADE.

The core of diagnosing and treating diseases in traditional Chinese medicine lies in syndrome differentiation. The eight principles of syndrome differentiation serve as guidance for syndrome differentiation. As one of the eight principles of syndrome differentiation， the differentiation of deficiency and excess is the basic and critical method. Ischemic stroke is currently the leading cause harming the health of Chinese residents. Although the hypotheses about the cause of ischemic stroke have evolved from external wind to the later internal wind and to the modern theory of toxin damaging the brain collaterals， they all believe that this disease is rooted in internal deficiency and external excess. According to available studies， although stroke is characterized by complex pathogenesis and rapid progression of syndromes， the key cause evolution has a regularity， that is， from excess to deficiency. This article analyzes the historical evolution of the etiology， pathogenesis， and syndrome differentiation schemes of stroke. There are diverse schemes for the syndrome differentiation of stroke， which make it difficult to choose in clinical practice. In view of this problem， this paper puts forward a new approach of staging sequential treatment of ischemic stroke based on the differentiation of deficiency and excess according to the evolution law of the key cause of stroke. Furthermore， we conducted a randomized controlled study on 100 patients with ischemic stroke to evaluate this new approach. The results showed that the staging sequential treatment of ischemic stroke based on the differentiation of deficiency and excess demonstrated definite clinical efficacy. In addition， this article reviews the previous research results of our team and the research achievements of other teams to preliminarily explore the relationship between stroke syndromes and biomarkers， aiming to provide an objective basis for unveiling the pathogenesis of stroke. In summary， according to the key cause evolution （from excess to deficiency）， the treatment of ischemic stroke by stages based on differentiation of deficiency and excess can facilitate the rapid intervention and improve the clinical efficacy on ischemic stroke.

Vestibular migraine(VM)is a common vestibular disorder in which vertigo and migraine coexist,and visually induced vertigo is one of the typical vestibular symptoms of VM.The clinical manifestations of VM re-lated visual vertigo are various,which are affected by anxiety,motion sickness,age and other factors.Multiple mechanisms such as anatomical and physiological connections,gaze instability,visual vestibular integration defects,impaired sensory remodeling,sensitization of the central vestibular pathway,5-hydroxytryptamine and glutamate-glutamine cycle and other neurotransmitters may lead to VM-related visual vertigo.

ObjectiveTo establish a mouse model of basilar artery dolichoectasia （BAD） and explore the mechanism of modified Tongqiao Huoxuetang （JTQHX） in regulating BAD via phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） pathway. MethodSixty C57/BL6 female mice were randomized into sham operation （injected with 10 U·mL^-1 inactivate elastase）， model， atorvastatin calcium tablets （2.6 mg·kg·d^-1）， and low- and high-dose （crude drug 3.4， 17 g·kg^-1·d^-1， respectively） JTQHX groups. The mouse model of BAD was established by injection with 10 U·mL^-1 elastase. After 14 days of modeling， the sham operation group and model group were administrated with equal volumes of pure water by gavage， and other groups with corresponding drugs for 2 months. The levels of interleukin-6 （IL-6） and calpain （LpA） in the serum were measured by enzyme-linked immunosorbent assay （ELISA）. Verhoeff 's Van Gieson （EVG） staining was employed to observe the pathological changes of blood vessels. Terminal-deoxynucleotidyl transferase mediated nick end labeling （TUNEL） was employed to examine the apoptosis rate of vascular smooth muscle cells （VSMCs）. Image Pro Plus was used to observe and calculate the curvature index， elongation length， percentage increase in vessel diameter， and curvature angle of the basilar artery vessels in mice. Western blot was employed to determine the expression levels of PI3K and Akt in the vascular tissue. ResultCompared with the sham operation group， the model group showed lowered IL-6 level （P<0.01）， no significant change in LpA level， increased apoptosis of VSMCs （P<0.01）， and increased curvature index， elongation length， percentage increase in vessel diameter， and curvature angle （P<0.01）. Furthermore， the modeling up-regulated the protein levels of PI3K and Akt in blood vessels （P<0.01） and aggravated the destruction of the inner elastic layer， atrophy of the muscular layer， and hyaline changes in the connective tissue of the medial membrane of the basilar artery wall. Compared with the model group， 2 months of treatment with JTQHX elevated the IL-6 level （P<0.01）， reduced the apoptosis of VSMCs （P<0.01）， decreased the curvature index， elongation length， percentage increase in vessel diameter， and curvature angle （P<0.05， P<0.01）， and down-regulated the protein levels of PI3K and Akt in blood vessels （P<0.01）. In addition， the treatment alleviated the destruction of the inner elastic layer， atrophy of the muscular layer， and hyaline changes in the connective tissue of the medial membrane of the basilar artery wall. ConclusionJTQHX inhibits the elongation， expansion， and curvature of basilar artery vessels and alleviates the pathological changes by reducing the apoptosis of VSMCs and down-regulating the expression of PI3K/Akt pathway.

The comorbidities of vertebrobasilar dolichoectasia（VBD） and cerebral small vessel disease（CSVD） increase the poor prognosis of patients，and elucidating the mechanism underlying their comorbidities helps to explore effective treatment strategies. Therefore，based on the collateral disease theory and combining with the pathogenesis and research progress of traditional Chinese and Western medicine on the understanding of the two，this study proposes that both the disease locations are in the brain collaterals and the pathogenesis is deficiency in foundation and excess in symptoms. The main pathogenesis roots in the deficiency of original Qi and the emptiness of brain collaterals，which corresponds to the dysfunction of endothelial cells and neuro-endocrino-immune networks in modern medicine. The symptoms are cerebral blood stasis，occlusion of cerebral arteries and toxic lesion of cerebral arteries，corresponding to cerebrovascular atherosclerosis，hemodynamic changes，hypoperfusion and toxic metabolites-induced injury of white matter in modern medicine. Based on the collateral disease theory，exploring the common pathogenesis of the VBD and CSVD is expected to facilitate the establishment of TCM treatment scheme including the principles，methods and medicines，and improve the clinical prognosis of patients.

Migraine with brainstem aura is one of the subtype of migraine with aura, with varied etiology and complex mechanism. Migraine with brainstem aura and transient loss of consciousness (TLOC) often occur together clinically, seriously affect the social life of the patients. At present, relation between migraine with brainstem aura and TLOC has not been elucidated, and clinical manifestations between TLOC and syncope is similar and easily confused by physicians. In order to deeply explore the complex relations between migraine with brainstem aura and TLOC, this article summarizes the clinical association, pathogenesis and differential diagnosis of migraine with brainstem aura associated with TLOC, so as to further optimize the clinical diagnosis strategies and provide new ideas for exploring comprehensive treatment measures for migraine with brainstem aura associated with TLOC.