1.Research progress in neuropsychiatric diseases therapy using vagus nerves
Han NI ; Dujuan HE ; Jingyao DUAN ; Aibing CHEN ; Liming ZHANG
Chinese Journal of Pharmacology and Toxicology 2025;39(3):224-232
As the longest and most widely distributed pair of nerves in the brain,the vagus nerve is involved in the regulation of many systems and organs.Recent studies have found that the vagus nerve may be involved in the occurrence of a variety of neuropsychiatric diseases by regulating the release of neurotransmitters(such as norepinephrine,5-hydroxytryptamine,gamma-aminobutyric acid and acetylcholine)and regulating the immune system and gut-brain axis.This article focuses on the regulatory mechanisms of the vagus nerve on neurotransmitters,immune system function,and the gut-brain axis,as well the therapeutic advances in vagus nerve stimulation for neurological and psychi-atric diseases such as epilepsy,depression and anxiety disorders.
2.Peripheral blood inflammatory markers and cognitive impairment in patients with cerebral small vessel disease
Libin LIAO ; Xuan HE ; Dujuan SHA
International Journal of Cerebrovascular Diseases 2025;33(1):36-40
Cognitive impairment caused by cerebral small vessel disease (CSVD) can affect the quality of life of patients and impose a huge economic burden on the families and society. Inflammation is an important pathological mechanism of cognitive impairment in CSVD and its associated cognitive impairment. This article reviews the peripheral blood inflammatory markers of cognitive impairment in patients with CSVD.
3.Diagnostic value of three-dimensional arterial spin labeling in patients with isolated vertigo due to posterior circulation ischemia
Qian LIU ; Rongchao MA ; Luna WANG ; Xuan HE ; Dujuan SHA
International Journal of Cerebrovascular Diseases 2025;33(2):93-100
Objective:To investigate the predictive value of three-dimensional arterial spin labeling (3D-ASL) for posterior circulation ischemia (PCI) and posterior circulation stroke (PCS) in patients with isolated vertigo.Methods:Patients with isolated vertigo underwent 3D-ASL imaging at Drum Tower Hospital Affiliated to Nanjing University School of Medicine from January 1, 2022 to December 31, 2024 were included retrospectively. According to the imaging findings, the patients with isolated vertigo were divided into PCI group and non-PCI group. The PCI group was further divided into PCS group and non-PCS group. The baseline clinical data and laboratory examination data were collected. Cerebral blood flow (CBF) in different brain regions of the posterior circulation was obtained through 3D-ASL related parameters to evaluate the posterior circulation perfusion, including CBF at two post-labeling delay times (PLD) (1.5 s and 2.5 s), delayed perfusion CBF (ΔCBF), multisequence PLD (Multi-PLD) CBF, and CBF under arterial transit time (ATT). Multivariate logistic regression analysis was used to determine the association of different CBF values with PCI and PCS in patients with isolated vertigo. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of different CBF values for PCI and PCS. Results:A total of 81 patients with isolated vertigo were included, aged 63.0±12.1 years, 44 were males (54.3%); 58 (71.6%) had PCI and 27 (25.9%) had PCS. Multivariate logistic regression analysis showed that PLD 1.5 s-CBF (odds ratio [ OR] 1.372, 95% confidence interval [ CI] 1.169-1.611; P<0.001), ΔCBF ( OR 1.197, 95% CI 1.072-1.336; P=0.001), and Multi-PLD-CBF ( OR 2.099, 95% CI 1.257-3.504; P=0.005) were the independent predictive factors of PCI. ROC curve analysis showed that the area under the curve for predicting PCI using the above three parameters alone and in combination were 0.962 (95% CI 0.915-1.000), 0.683 (95% CI 0.543-0.823), 0.944 (95% CI 0.985-1.000), and 0.999 (95% CI 0.997-1.000), respectively. Multivariate logistic regression analysis showed that the PLD 1.5 s-CBF ( OR 1.246, 95% CI 1.030-2.089; P=0.002), ΔCBF ( OR 1.153, 95% CI 1.038-1.281; P=0.008), and multi-PLD-CBF ( OR 1.388, 95% CI 1.219-1.689; P=0.001) in cerebellar region were the independent predictors of PCS. ROC curve analysis showed that the area under the curve for predicting PCS using the above three parameters alone and in combination were 0.956 (95% CI 0.911-1.00), 0.802 (95% CI 0.685-0.920), 0.972 (95% CI 0.923-1.000), and 0.977 (95% CI 0.937-1.00), respectively. Conclusion:3D-ASL can predict PCI and PCS early, and combining multiple parameters can improve the predictive ability for PCI and PCS.
4.Research progress in the relationship between anxiety,fear and immune inflammatory responses
Dujuan HE ; Meikui ZHANG ; Han NI ; Jingyao DUAN ; Liming ZHANG
Military Medical Sciences 2025;49(3):227-232
Anxiety and fear,as common symptoms of psychiatric disorders,remain inadequately understood in terms of their pathogenesis.Changes in immune inflammation are considered to play a significant role in both the pathological and physiological processes associated with these mental illnesses.In recent years,it has been demonstrated that stress can regulate immune inflammation through multiple pathways,including the regulation of the autonomic nervous system,the hypothalamic-pituitary-adrenal axis,indoleamine 2,3-dioxygenase and its metabolite kynurenine,and the gut-brain axis.These pathways are implicated in the onset and treatment of anxiety and fear-related mental illnesses.This article focuses on the relationships between anxiety and fear-related mental illnesses and immune inflammatory responses.
5.Research progress in neuropsychiatric diseases therapy using vagus nerves
Han NI ; Dujuan HE ; Jingyao DUAN ; Aibing CHEN ; Liming ZHANG
Chinese Journal of Pharmacology and Toxicology 2025;39(3):224-232
As the longest and most widely distributed pair of nerves in the brain,the vagus nerve is involved in the regulation of many systems and organs.Recent studies have found that the vagus nerve may be involved in the occurrence of a variety of neuropsychiatric diseases by regulating the release of neurotransmitters(such as norepinephrine,5-hydroxytryptamine,gamma-aminobutyric acid and acetylcholine)and regulating the immune system and gut-brain axis.This article focuses on the regulatory mechanisms of the vagus nerve on neurotransmitters,immune system function,and the gut-brain axis,as well the therapeutic advances in vagus nerve stimulation for neurological and psychi-atric diseases such as epilepsy,depression and anxiety disorders.
6.Role of dipeptidyl peptidase-4 inhibitors in the prevention and treatment of ischemic stroke
Jingxuan ZHANG ; Xuan HE ; Dujuan SHA
International Journal of Cerebrovascular Diseases 2024;32(5):369-373
Diabetes is an important risk factor for ischemic stroke, and stress hyperglycemia after ischemic stroke will aggravate ischemic brain damage. Dipeptidyl peptidase-4 (DPP-4) inhibitors, as newly developed hypoglycemic drugs in recent years, have become one of the important research directions of type 2 diabetes drugs. Although the existing clinical trial data have not clearly confirmed the effectiveness of DPP-4 inhibitors in preventing ischemic stroke in patients with diabetes, animal model studies have shown that DPP-4 inhibitors can exert protective effects during ischemic brain injury through mechanisms such as anti-inflammatory, anti-apoptotic and promoting neurogenesis and angiogenesis. This article reviews the role and possible mechanisms of DPP-4 inhibitors in the prevention and treatment of ischemic stroke.
7.Associations of triglyceride-glucose index and remnant cholesterol with carotid intima-media thickness in non-diabetic population
Yunzhi SHEN ; Xiaoqiong DU ; Rongchao MA ; Xuan HE ; Dujuan SHA
International Journal of Cerebrovascular Diseases 2024;32(9):674-680
Objectives:To investigate associations of triglyceride glucose (TyG) index and remnant cholesterol (RC) with carotid intima-media thickness (cIMT) in non-diabetes population, and to evaluate the predictive value of TyG combined with RC for cIMT.Methods:Non-diabetes adult subjects underwent physical examination in Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University from January 2021 to December 2021 were included retrospectively. According to the findings of carotid ultrasound examination, they were divided into cIMT thickening group (≥1 mm) and non-cIMT thickening group. Multivariate logistic regression analysis was used to identify the independent risk factors for cIMT thickening. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of TyG index combined with RC for cIMT thickening. Results:A total of 1 109 subjects were enrolled, including 640 males (57.7%), aged 56.44±14.58 years, and 626 (56.4%) had cIMT thickening. The age and male proportion of the cIMT thickening group were significantly higher than those of the non-cIMT thickening group, and there were significant differences in the quartiles distribution of RC and TyG index between the two groups (all P<0.001). Multivariate logistic regression analysis showed that RC (odds ratio 1.601, 95% confidence interval 1.162-2.207; P=0.004) and TyG index (odds ratio 1.807, 95% confidence interval 1.302-2.508; P<0.001) were the independent risk factors for cIMT thickening. ROC curve analysis showed that the area under the curve of TyG index combined with RC to predict cIMT thickening was 0.717 (95% confidence interval, 0.687-0.747), indicating higher diagnostic efficacy than TyG index and RC alone. Conclusion:TyG index and RC are associated with cIMT thickening in the non-diabetes population, and the combination of them had good predictive value for cIMT thickening.
8.Neuronal function-related biomarkers and post-stroke cognitive impairment
Weiquan HUANG ; Xuan HE ; Dujuan SHA
International Journal of Cerebrovascular Diseases 2024;32(11):857-863
Post-stroke cognitive impairment (PSCI) is one of the common complications of stroke, which seriously affects the quality of life and survival rate of patients, and imposes a heavy burden on families and society. More and more studies have shown that blood biomarkers are closely associated with PSCI. This article reviews the peripheral blood neuronal function related biomarkers in PSCI.
9.Correlation between residual cholesterol and carotid intima-media thickness in non-diabetic population
Xiaoqiong DU ; Xinchen MA ; Xuan HE ; Ruijie YANG ; Dujuan SHA
International Journal of Cerebrovascular Diseases 2023;31(1):29-33
Objective:To investigate the correlation between residual cholesterol (RC) and carotid intima-media thickness (cIMT) in non-diabetic population.Methods:Non-diabetes population received health examination in Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School from January 1, 2018 to December 31, 2021 were retrospectively included. According to the carotid ultrasound results, they were divided into cIMT thickening group (≥1 mm) and non-thickening group (<1 mm). The RC level was calculated according to total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Multivariate logistic regression analysis was used to determine the correlation between RC and cIMT. Results:A total of 1 803 non-diabetes subjects, aged 58.3±15.6 years, including 1 100 males (61.0%), were enrolled. There were 916 patients (50.8%) in the cIMT thickening group and 887 (49.2%) in the non-cIMT thickening group. Compared with the non-cIMT thickening group, cIMT thickening group had significantly higher proportion of male, hypertension, hyperlipidemia, atrial fibrillation, past stroke history, smoking and alcohol consumption, as well as significantly higher age, blood glucose, triglyceride, RC, TC and LDL-C, and significantly lower HDL-C (all P<0.01). Multivariate logistic regression analysis showed that RC was independently associated with cIMT thickening ( Ptrend<0.001). Conclusion:RC is associated with cIMT thickening in non-diabetes population.
10.Homocysteine induces inflammatory polarization in mouse microglia by up-regulating Rap1a
Aijun WEI ; Dujuan HE ; Meikui ZHANG
Chinese Journal of Pathophysiology 2023;39(12):2242-2250
AIM:To investigate the impact of homocysteine(Hcy)on the inflammatory response mediated by BV2 mouse microglia,and to explore the mechanism of Ras-related protein 1a(Rap1a)in the Hcy-induced inflammatory response in BV2 cells.METHODS:Mouse microglial cell line BV2 was cultured in vitro,and Hcy intervention was used to establish a hyperhomocysteinemia cellular model.The cells were divided into 4 groups:blank control group,and 50 μmol/L,100 μmol/L and 150 μmol/L Hcy groups.The mRNA expression levels of M1 polarization markers,inflammatory factors IL-6,IL-1β and TNF-α,and Rap1a in BV2 cells were detected by RT-qPCR.Additionally,the levels of inflamma-tory factors IL-6,IL-1β and TNF-α in BV2 cells were measured using an ELISA kit.The protein expression level of Rap1a was detected by Western blot assay.To verify the function of Rap1a,viral transfection was employed for both over-expression and knockdown experiments.RESULTS:Under the intervention of Hcy concentration above 100 μmol/L,BV2 cells exhibited inflammatory polarization,as indicated by the increased mRNA expression of M1 polarization markers CD80 and CD86(P<0.05).The mRNA and protein expression levels of inflammatory factors IL-6,IL-1β and TNF-α were significantly up-regulated(P<0.05).Additionally,the mRNA and protein expression levels of Rap1a also showed a significant increase(P<0.05).Moreover,Rap1a mRNA level was positively correlated with CD80 mRNA,IL-1β content and TNF-α content(P<0.05).The multiplicities of infection of the viruses with Rap1a overexpression and Rap1a knock-down were both 80,and the effective transfection was observed through fluorescence microscopy.Overexpression of Rap1a exacerbated the inflammatory polarization of BV2 cells induced by Hcy(P<0.05),while knockdown of Rap1a attenuated this polarization(P<0.05).CONCLUSION:Hcy can promote M1 polarization of BV2 mouse microglia,leading to in-flammatory response,which indicates that Rap1a could potentially serves as a critical regulatory factor in the Hcy-induced inflammatory response of BV2 cells.

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