1.Protective Effect of Taohong Siwutang on Cerebral Ischemia-reperfusion Injury Based on A1/A2 Phenotype Transformation of Astrocytes Mediated by JAK2/STAT3 Pathway
Huifang WANG ; Xinru CHEN ; Mengyuan CHEN ; Xian ZHOU ; Lan HAN ; Weidong CHEN ; Zhaojie JI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):25-34
ObjectiveTo investigate whether the effect of Taohong Siwutang on cerebral ischemia-reperfusion (CIRI) injury in rats is related to the regulation of astrocyte polarization and explore the related mechanism. MethodsEighty-four male SD rats were randomly assigned to the following groups: A sham operation group, a model group, Taohong Siwutang treatment groups (low dose, medium dose, and high dose), ligustrazine phosphate tablet (LPT) group, and AG490 group. All groups, except for the sham operation group, underwent middle cerebral artery occlusion/reperfusion (MCAO/R) modeling and were treated for seven days. The neurological impairment was evaluated using the Longa score. The volume of cerebral infarction was assessed through 2,3,5-triphenyltetrazolium chloride (TTC) staining. Real-time fluorescent quantitative polymerase chain reaction (Real-time PCR) and Western blot analyses were performed to analyze the mRNA and protein expression levels of cortical complement 3 (C3), S100 calcium-binding protein A10 (S100A10), Janus kinase 2 (JAK2), and signal transducer and activator of transcription 3 (STAT3). Additionally, protein expression levels of vascular endothelial growth factor-A (VEGF-A) were assessed, and the mRNA expression levels of inflammatory factors, including interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α), were evaluated. Glial fibrillary acidic protein (GFAP) and C3, S100A10 and Co-localization was detected via immunofluorescence double staining. Lastly, VEGF expression levels were measured using enzyme-linked immunosorbent assay (ELISA). ResultsCompared with the sham operation group, the model group showed a significant increase in cerebral infarction volume and neurological impairment (P<0.01). C3 protein levels were elevated, while S100A10 levels were decreased. Pathway-related markers were significantly upregulated (P<0.05, P<0.01), and VEGF-A protein levels were significantly reduced (P<0.01). The mRNA expression of inflammatory factors was significantly upregulated (P<0.01). Co-localization analysis showed significantly increased GFAP and C3 fluorescence intensity (P<0.01) and greatly decreased GFAP and S100A10 fluorescence intensity (P<0.01). Additionally, VEGF content was significantly elevated (P<0.01). Compared with the model group, medium- and high-dose Taohong Siwutang and LPT groups exhibited a significant reduction in cerebral infarction volume and neurological impairment (P<0.01). Groups treated with low, medium, and high doses of Taohong Siwutang and LPT group exhibited a decrease in C3 protein expression levels and an increase in S100A10 expression levels (P<0.01). In the high-dose Taohong Siwutang and AG490 groups, both protein and mRNA expression of C3 and pathway-related markers were significantly downregulated (P<0.05, P<0.01), while S100A10 expression and VEGF-A protein levels were significantly increased (P<0.01). Additionally, the mRNA expression levels of inflammatory factors were significantly reduced (P<0.01). The co-localization fluorescence intensity of GFAP and C3 significantly decreased (P<0.01), while that of GFAP and S100A10 greatly increased (P<0.01). Furthermore, VEGF content exhibited a marked elevation (P<0.01). ConclusionTaohong Siwutang exerts a protective effect in rats with cerebral CIRI injury. The underlying mechanism is associated with the downregulation of the JAK2/STAT3 signaling pathway, promotion of A2-type astrocyte polarization, reduction of inflammatory factor release, and enhancement of VEGF production.
2.Protective Effect of Taohong Siwutang on Cerebral Ischemia-reperfusion Injury Based on A1/A2 Phenotype Transformation of Astrocytes Mediated by JAK2/STAT3 Pathway
Huifang WANG ; Xinru CHEN ; Mengyuan CHEN ; Xian ZHOU ; Lan HAN ; Weidong CHEN ; Zhaojie JI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):25-34
ObjectiveTo investigate whether the effect of Taohong Siwutang on cerebral ischemia-reperfusion (CIRI) injury in rats is related to the regulation of astrocyte polarization and explore the related mechanism. MethodsEighty-four male SD rats were randomly assigned to the following groups: A sham operation group, a model group, Taohong Siwutang treatment groups (low dose, medium dose, and high dose), ligustrazine phosphate tablet (LPT) group, and AG490 group. All groups, except for the sham operation group, underwent middle cerebral artery occlusion/reperfusion (MCAO/R) modeling and were treated for seven days. The neurological impairment was evaluated using the Longa score. The volume of cerebral infarction was assessed through 2,3,5-triphenyltetrazolium chloride (TTC) staining. Real-time fluorescent quantitative polymerase chain reaction (Real-time PCR) and Western blot analyses were performed to analyze the mRNA and protein expression levels of cortical complement 3 (C3), S100 calcium-binding protein A10 (S100A10), Janus kinase 2 (JAK2), and signal transducer and activator of transcription 3 (STAT3). Additionally, protein expression levels of vascular endothelial growth factor-A (VEGF-A) were assessed, and the mRNA expression levels of inflammatory factors, including interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α), were evaluated. Glial fibrillary acidic protein (GFAP) and C3, S100A10 and Co-localization was detected via immunofluorescence double staining. Lastly, VEGF expression levels were measured using enzyme-linked immunosorbent assay (ELISA). ResultsCompared with the sham operation group, the model group showed a significant increase in cerebral infarction volume and neurological impairment (P<0.01). C3 protein levels were elevated, while S100A10 levels were decreased. Pathway-related markers were significantly upregulated (P<0.05, P<0.01), and VEGF-A protein levels were significantly reduced (P<0.01). The mRNA expression of inflammatory factors was significantly upregulated (P<0.01). Co-localization analysis showed significantly increased GFAP and C3 fluorescence intensity (P<0.01) and greatly decreased GFAP and S100A10 fluorescence intensity (P<0.01). Additionally, VEGF content was significantly elevated (P<0.01). Compared with the model group, medium- and high-dose Taohong Siwutang and LPT groups exhibited a significant reduction in cerebral infarction volume and neurological impairment (P<0.01). Groups treated with low, medium, and high doses of Taohong Siwutang and LPT group exhibited a decrease in C3 protein expression levels and an increase in S100A10 expression levels (P<0.01). In the high-dose Taohong Siwutang and AG490 groups, both protein and mRNA expression of C3 and pathway-related markers were significantly downregulated (P<0.05, P<0.01), while S100A10 expression and VEGF-A protein levels were significantly increased (P<0.01). Additionally, the mRNA expression levels of inflammatory factors were significantly reduced (P<0.01). The co-localization fluorescence intensity of GFAP and C3 significantly decreased (P<0.01), while that of GFAP and S100A10 greatly increased (P<0.01). Furthermore, VEGF content exhibited a marked elevation (P<0.01). ConclusionTaohong Siwutang exerts a protective effect in rats with cerebral CIRI injury. The underlying mechanism is associated with the downregulation of the JAK2/STAT3 signaling pathway, promotion of A2-type astrocyte polarization, reduction of inflammatory factor release, and enhancement of VEGF production.
3.Study on influencing factors for cerebral small vessel disease in type 2 diabetes mellitus
Chenye XIE ; Zhaojie JI ; Zhen CHEN ; Liang JIN ; Zhou MEI
Chinese Journal of Diabetes 2025;33(5):350-353
Objective To explore the influencing factors forcerebral small vessel disease(CSVD)in patients with type 2 diabetes mellitus(T2DM).Methods A total of 160 patients with T2DM admitted to the Department of Endocrinology our hospital were enrolled in this study from January 2024 to March 2024,and divided into simple T2DM group(n=107)and T2DM combined with CSVD(CSVD,n=53)group according to the combination of CSVD.The general information and biochemical indicators were compared between the two groups.Logistic regression analysis was used to analyze the influencing factors for CSVD in patients with T2DM,and ROC curve was used to evaluate the diagnostic efficacy of CSVD markers.Results The CSVD group showed significantly higher values than the T2DM group(P<0.05)in the following parameters:DM duration,serum uric acid,cystatin C(CysC),neutrophils,monocytes,C-RP,monocyte-to-high-density lipoprotein cholesterol ratio(MHR),and PAC-1 levels.Conversely,the CSVD group had significantly lower levels of LDL-C,lymphocytes,and albumin-to-globulin ratio(A/G)compared to the T2DM group(P<0.05).Logistic regression analysis indicated that A/G,CysC,MHR,and DM duration were influencing factors for T2DM complicated with CSVD.Receiver operating characteristic(ROC)curveanalysis demonstrated that the combined prediction model incorporating A/G,CysC,MHR,and DM duration yielded an area under the curve of 0.88,indicating good predictive performance.Conclusions A/G,CysC,MHR,and duration are independent risk factors for CSVD in patients with T2DM.Early identification of these items may facilitate the prevention of CSVD in patients with T2DM.
4.Analyzing the dysfunction of the mesial temporal lobe epilepsy glymphatic system based on diffusion tensor imaging analysis along the perivascular space index
Zhaojie WANG ; Qiang XU ; Yuzhuo LI ; Jianrui LI ; Yiwen CHEN ; Fang YANG ; Chenxi SHEN ; Xiangjun JI ; Gang YANG ; Guangming LU ; Zhiqiang ZHANG
Chinese Journal of Radiology 2025;59(2):168-176
Objective:To investigate the differences of the glymphatic system (GS) function between patients with mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE-HS) and healthy controls and between different seizure types by using diffusion tensor imaging along perivascular space (DTI-ALPS), and to analyze the correlation between GS function and the course of disease, as well as the efficacy of predicting the surgical outcome.Methods:This study was a cross-sectional study. A total of 171 patients with mTLE-HS (mTLE-HS group) and 75 healthy volunteers (HC group) were retrospectively enrolled from July 2009 to July 2021 at Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University. The general information of all subjects, such as seizure type (partial seizure, secondary generalized seizure), surgical outcome, etc., was analyzed. The 3D magnetization prepared rapid gradient echo T 1WI and DTI sequence images were collected. The VBM analysis method was used to segment cerebrospinal fluid and calculate the volume. The ALPS index of the bilateral brain was calculated using the Atlas-based DTI-ALPS method. Independent sample t-test or paired t test were used to compare the ALPS index between the mTLE-HS group and HC group, and between patients with different seizure types. Pearson correlation analysis was used to analyze the correlation between bilateral ALPS index and disease duration in mTLE-HS group. The predictive value of the ALPS index for surgical outcomes was evaluated by receiver operating characteristics curve and area under the curve. Results:Among the 171 mTLE-HS patients, 98 patients were mTLE with left-side HS (mTLE-LHS) and 73 patients were mTLE with right-side HS (mTLE-RHS); 37 patients underwent surgical treatment, including 27 with good prognosis and 10 with poor prognosis. Compared with the HC group, the left-side ALPS index of mTLE-LHS and mTLE-RHS were both decreased ( P<0.05). The right-side ALPS index in mTLE-RHS was lower than that in the HC group ( P<0.001). There was no significant difference in the right-side ALPS index between mTLE-LHS and HC group ( P=0.080). The ALPS index on the affected side of patients with secondary generalized seizures was significantly lower than that of patients with only partial seizures (all P<0.05), but the difference in ALPS index on the healthy side was not statistically significant( P>0.05). The left-side and right-side ALPS index in mTLE-LHS were negatively correlated with disease duration ( r=-0.272, P=0.007; r=-0.307, P=0.002), but no significant correlation was found between the left-side or right-side ALPS index in mTLE-RHS (all P>0.05). The DTI-ALPS index on the affected side in mTLE-HS patients exhibited good diagnostic accuracy for surgical outcome classification, with an area under the curve of 0.778. Conclusions:The patients with mTLE-HS exhibit dysfunction of the GS, and the degree of impairment is related to the type of seizure and the course of epilepsy. The ALPS index, which characterizes the function of GS, demonstrates good diagnostic accuracy for classifying surgical outcomes.
5.Study on influencing factors for cerebral small vessel disease in type 2 diabetes mellitus
Chenye XIE ; Zhaojie JI ; Zhen CHEN ; Liang JIN ; Zhou MEI
Chinese Journal of Diabetes 2025;33(5):350-353
Objective To explore the influencing factors forcerebral small vessel disease(CSVD)in patients with type 2 diabetes mellitus(T2DM).Methods A total of 160 patients with T2DM admitted to the Department of Endocrinology our hospital were enrolled in this study from January 2024 to March 2024,and divided into simple T2DM group(n=107)and T2DM combined with CSVD(CSVD,n=53)group according to the combination of CSVD.The general information and biochemical indicators were compared between the two groups.Logistic regression analysis was used to analyze the influencing factors for CSVD in patients with T2DM,and ROC curve was used to evaluate the diagnostic efficacy of CSVD markers.Results The CSVD group showed significantly higher values than the T2DM group(P<0.05)in the following parameters:DM duration,serum uric acid,cystatin C(CysC),neutrophils,monocytes,C-RP,monocyte-to-high-density lipoprotein cholesterol ratio(MHR),and PAC-1 levels.Conversely,the CSVD group had significantly lower levels of LDL-C,lymphocytes,and albumin-to-globulin ratio(A/G)compared to the T2DM group(P<0.05).Logistic regression analysis indicated that A/G,CysC,MHR,and DM duration were influencing factors for T2DM complicated with CSVD.Receiver operating characteristic(ROC)curveanalysis demonstrated that the combined prediction model incorporating A/G,CysC,MHR,and DM duration yielded an area under the curve of 0.88,indicating good predictive performance.Conclusions A/G,CysC,MHR,and duration are independent risk factors for CSVD in patients with T2DM.Early identification of these items may facilitate the prevention of CSVD in patients with T2DM.
6.Analyzing the dysfunction of the mesial temporal lobe epilepsy glymphatic system based on diffusion tensor imaging analysis along the perivascular space index
Zhaojie WANG ; Qiang XU ; Yuzhuo LI ; Jianrui LI ; Yiwen CHEN ; Fang YANG ; Chenxi SHEN ; Xiangjun JI ; Gang YANG ; Guangming LU ; Zhiqiang ZHANG
Chinese Journal of Radiology 2025;59(2):168-176
Objective:To investigate the differences of the glymphatic system (GS) function between patients with mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE-HS) and healthy controls and between different seizure types by using diffusion tensor imaging along perivascular space (DTI-ALPS), and to analyze the correlation between GS function and the course of disease, as well as the efficacy of predicting the surgical outcome.Methods:This study was a cross-sectional study. A total of 171 patients with mTLE-HS (mTLE-HS group) and 75 healthy volunteers (HC group) were retrospectively enrolled from July 2009 to July 2021 at Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University. The general information of all subjects, such as seizure type (partial seizure, secondary generalized seizure), surgical outcome, etc., was analyzed. The 3D magnetization prepared rapid gradient echo T 1WI and DTI sequence images were collected. The VBM analysis method was used to segment cerebrospinal fluid and calculate the volume. The ALPS index of the bilateral brain was calculated using the Atlas-based DTI-ALPS method. Independent sample t-test or paired t test were used to compare the ALPS index between the mTLE-HS group and HC group, and between patients with different seizure types. Pearson correlation analysis was used to analyze the correlation between bilateral ALPS index and disease duration in mTLE-HS group. The predictive value of the ALPS index for surgical outcomes was evaluated by receiver operating characteristics curve and area under the curve. Results:Among the 171 mTLE-HS patients, 98 patients were mTLE with left-side HS (mTLE-LHS) and 73 patients were mTLE with right-side HS (mTLE-RHS); 37 patients underwent surgical treatment, including 27 with good prognosis and 10 with poor prognosis. Compared with the HC group, the left-side ALPS index of mTLE-LHS and mTLE-RHS were both decreased ( P<0.05). The right-side ALPS index in mTLE-RHS was lower than that in the HC group ( P<0.001). There was no significant difference in the right-side ALPS index between mTLE-LHS and HC group ( P=0.080). The ALPS index on the affected side of patients with secondary generalized seizures was significantly lower than that of patients with only partial seizures (all P<0.05), but the difference in ALPS index on the healthy side was not statistically significant( P>0.05). The left-side and right-side ALPS index in mTLE-LHS were negatively correlated with disease duration ( r=-0.272, P=0.007; r=-0.307, P=0.002), but no significant correlation was found between the left-side or right-side ALPS index in mTLE-RHS (all P>0.05). The DTI-ALPS index on the affected side in mTLE-HS patients exhibited good diagnostic accuracy for surgical outcome classification, with an area under the curve of 0.778. Conclusions:The patients with mTLE-HS exhibit dysfunction of the GS, and the degree of impairment is related to the type of seizure and the course of epilepsy. The ALPS index, which characterizes the function of GS, demonstrates good diagnostic accuracy for classifying surgical outcomes.
7.Clinical characteristics and prognosis analyses of metastatic sites symptom as the first manifestation in esophageal carcinoma patients with stage T 1 and T 2
Jingna JI ; Xiaomin WANG ; Fujun ZHAO ; Anping ZHENG ; Zhaojie SHENG ; Qingshan ZHU
Cancer Research and Clinic 2021;33(2):129-133
Objective:To explore the clinical characteristics and prognosis of metastatic sites symptom as the first manifestation in esophageal carcinoma patients with stage T 1 and T 2, and to provide a reference for clinical practice. Methods:The clinical data of 50 esophageal carcinoma patients with stage T 1 and T 2 who had lymph node or distant metastasis as the first symptom in Anyang Tumor Hospital of Henan Province from November 2007 to December 2019 were retrospectively analyzed. Survival analysis was performed by using Kaplan-Meier method. Univariate analysis was performed by using log-rank test. Results:Among 50 patients with esophageal carcinoma, lymph node metastases as the first symptom were found in 42 cases and distant organ metastases as the first symptom were found in 8 cases. The 1-, 3-, 5-year overall survival rates of patients with stage Ⅰ-Ⅱ and stage Ⅲ-Ⅳ were 58.7%, 49.0%, 16.3% and 56.1%, 12.2%, 0, respectively, and there was no statistically significant difference in OS of both groups ( P = 0.094). The 1-, 3-, 5-year overall survival rates of patients with stage N 1 and stage N 2-N 3 were 63.5%, 34.7%, 17.3% and 52.2%, 11.9%, 0, respectively, and there was no statistically significant difference in OS of both groups ( P = 0.083). The 1-, 3-, 5-year overall survival rates were 64.6%, 30.5%, 18.3%, respectively in radiotherapy group and 38.2%, 0, 0, respectively in non-radiotherapy group, and there was a statistically significant difference in OS of both groups ( P = 0.008); the progression-free survival in radiotherapy group was better than that in non-radiotherapy group ( P = 0.028). The 1-, 3-, 5-year overall survival rates were 70.8%, 35.5%, 21.3% and 33.3%, 0, 0 and 35.4%, 0, 0, respectively in concurrent chemoradiotherapy group, radiotherapy group and chemotherapy group, and there was a statistically significant difference in overall survival among three groups ( P = 0.004). The results of univariate analysis showed that radiotherapy ( χ2 = 7.112, P = 0.008) and concurrent chemoradiotherapy ( χ2 = 10.940, P = 0.004) were the main factors affecting the prognosis. Conclusions:Lymph node and distant metastasis could occur in esophageal carcinoma patients with stage T 1 and T 2. Radiotherapy can prolong the progression-free survival time and concurrent chemoradiotherapy could benefit overall survival of these patients.

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