1.Banxia Xiexin Tang Ameliorates Cognitive Dysfunction in Rat Model of Vascular Dementia via AGE/RAGE Pathway
Shuzhi LIANG ; Zhongmin ZHAO ; Suyu HOU ; Dandan LUO ; Yan ZHANG ; Xijian LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):10-21
ObjectiveTo explore the mechanism by which Banxia Xiexin Tang (BXT) regulates the advanced glycation end products (AGE)/receptor for advanced glycation end products (RAGE) signaling pathway to reduce neuroinflammatory responses and ameliorate cognitive dysfunction in the rat model of vascular dementia (VD). MethodsThe components of BXT were detected by ultra performance liquid chromatography-quadrupole -orbitrap-tandem mass spectrometry(UPLC-Q-Orbitrap-MS/MS), and the core components and key action pathways were screened out by network pharmacology and molecular docking. Sixty SPF-grade male SD rats were randomly allocated into the sham and modeling groups by the random number table method. The VD model was replicated by the modified bilateral occlusion of the common carotid arteries (2-VO) method. The successfully modeled rats were randomly allocated into the model, low-, medium-, and high-dose (3.748 5, 7.497, 14.994 g·kg-1) BXT (BXT-L, BXT-M, and BXT-H), and nimodipine (NMP, 0.002 7 g·kg-1) groups according to the random number table method. The rats in the drug intervention groups were administrated with corresponding drugs by gavage, and the sham and model groups received the same amount of normal saline for 14 consecutive days. The Morris water maze, Y-maze, and new object recognition experiments were conducted to evaluate the cognitive dysfunction of rats. Hematoxylin-eosin (HE) staining was used to evaluate the histopathological changes of the hippocampal tissue in rats. The mRNA levels of AGE, RAGE, and phosphorylated nuclear factor-kappa B p65 (p-NF-κB p65) in the hippocampal tissue of rats were determined by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). The expression of related proteins in the AGE/RAGE pathway in the hippocampal tissue of rats was determined by Western blot and immunohistochemistry (IHC). The levels of neurotransmitters and inflammatory mediators in the rat serum were measured by enzyme-linked immunosorbent assay (ELISA). ResultsThe chemical components of BXT were detected by UPLC-Q-Orbitrap-MS/MS. Network pharmacology and molecular docking identified the AGE/RAGE pathway as the key pathway. The results of the water maze, Y maze, and novel object recognition tests showed that compared with the sham group, the model group demonstrated prolonged successful latency and decreases in number of platform crossings, alternation rate, number of entries into the new arm, preference index, and discrimination index (P0.01). Compared with the model group, the BXT-H and BXT-M groups showed shortened successful latency (P0.01) and increases in number of platform crossings (P0.05), alternation rate (P0.01), number of entries into the new arm (P0.05), preference index (P0.01), and discrimination index (P0.01). HE results showed that compared with the sham group, the cells of model rats were loosely and disorderly arranged, and the nuclei were condensed. Compared with the model group, the pathological changes of the hippocampus in the BXT group were mitigated. Real-time PCR results showed that compared with the sham group, the model group presented up-regulated mRNA levels of AGE, RAGE, and p-NF-κB p65 in the hippocampus (P0.01), and compared with the model group, the BXT-H and BXT-M groups showcased down-regulated mRNA levels of AGE, RAGE, and p-NF-κB p65 (P0.01). Western blot results showed that compared with the sham group, the model group presented up-regulated expression of AGE, RAGE, p-NF-κB p65, and tumor necrosis factor-α (TNF-α) (P0.05), and compared with the model group, the BXT-H group presented down-regulated expression of AGE, RAGE, p-NF-κB p65, and TNF-α (P0.05). IHC results showed that compared with the sham group, the model group had increased expression of RAGE (P0.01), and compared with the model group, the BXT-H and BXT-M groups had reduced expression of RAGE (P0.01). ELISA results showed that compared with the sham group, the model group exhibited elevated levels of TNF-α and Interleukin-1β (IL-1β) and declined levels of acetylcholine (ACh) and dopamine (DA) in the serum (P0.01). Compared with the model group, the BXT-L, BXT-M, and BXT-H groups showed lowered levels of TNF-α and IL-1β in the serum (P0.05) and elevated levels of ACh and DA (P0.05). ConclusionBXT may ameliorate cognitive dysfunction in the rat model of VD by down-regulating the AGE/RAGE signaling pathway, reducing neuroinflammatory responses, and regulating neurotransmitter levels.
2.Banxia Xiexin Tang Ameliorates Cognitive Dysfunction in Rat Model of Vascular Dementia via AGE/RAGE Pathway
Shuzhi LIANG ; Zhongmin ZHAO ; Suyu HOU ; Dandan LUO ; Yan ZHANG ; Xijian LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):10-21
ObjectiveTo explore the mechanism by which Banxia Xiexin Tang (BXT) regulates the advanced glycation end products (AGE)/receptor for advanced glycation end products (RAGE) signaling pathway to reduce neuroinflammatory responses and ameliorate cognitive dysfunction in the rat model of vascular dementia (VD). MethodsThe components of BXT were detected by ultra performance liquid chromatography-quadrupole -orbitrap-tandem mass spectrometry(UPLC-Q-Orbitrap-MS/MS), and the core components and key action pathways were screened out by network pharmacology and molecular docking. Sixty SPF-grade male SD rats were randomly allocated into the sham and modeling groups by the random number table method. The VD model was replicated by the modified bilateral occlusion of the common carotid arteries (2-VO) method. The successfully modeled rats were randomly allocated into the model, low-, medium-, and high-dose (3.748 5, 7.497, 14.994 g·kg-1) BXT (BXT-L, BXT-M, and BXT-H), and nimodipine (NMP, 0.002 7 g·kg-1) groups according to the random number table method. The rats in the drug intervention groups were administrated with corresponding drugs by gavage, and the sham and model groups received the same amount of normal saline for 14 consecutive days. The Morris water maze, Y-maze, and new object recognition experiments were conducted to evaluate the cognitive dysfunction of rats. Hematoxylin-eosin (HE) staining was used to evaluate the histopathological changes of the hippocampal tissue in rats. The mRNA levels of AGE, RAGE, and phosphorylated nuclear factor-kappa B p65 (p-NF-κB p65) in the hippocampal tissue of rats were determined by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). The expression of related proteins in the AGE/RAGE pathway in the hippocampal tissue of rats was determined by Western blot and immunohistochemistry (IHC). The levels of neurotransmitters and inflammatory mediators in the rat serum were measured by enzyme-linked immunosorbent assay (ELISA). ResultsThe chemical components of BXT were detected by UPLC-Q-Orbitrap-MS/MS. Network pharmacology and molecular docking identified the AGE/RAGE pathway as the key pathway. The results of the water maze, Y maze, and novel object recognition tests showed that compared with the sham group, the model group demonstrated prolonged successful latency and decreases in number of platform crossings, alternation rate, number of entries into the new arm, preference index, and discrimination index (P<0.01). Compared with the model group, the BXT-H and BXT-M groups showed shortened successful latency (P<0.01) and increases in number of platform crossings (P<0.05), alternation rate (P<0.01), number of entries into the new arm (P<0.05), preference index (P<0.01), and discrimination index (P<0.01). HE results showed that compared with the sham group, the cells of model rats were loosely and disorderly arranged, and the nuclei were condensed. Compared with the model group, the pathological changes of the hippocampus in the BXT group were mitigated. Real-time PCR results showed that compared with the sham group, the model group presented up-regulated mRNA levels of AGE, RAGE, and p-NF-κB p65 in the hippocampus (P<0.01), and compared with the model group, the BXT-H and BXT-M groups showcased down-regulated mRNA levels of AGE, RAGE, and p-NF-κB p65 (P<0.01). Western blot results showed that compared with the sham group, the model group presented up-regulated expression of AGE, RAGE, p-NF-κB p65, and tumor necrosis factor-α (TNF-α) (P<0.05), and compared with the model group, the BXT-H group presented down-regulated expression of AGE, RAGE, p-NF-κB p65, and TNF-α (P<0.05). IHC results showed that compared with the sham group, the model group had increased expression of RAGE (P<0.01), and compared with the model group, the BXT-H and BXT-M groups had reduced expression of RAGE (P<0.01). ELISA results showed that compared with the sham group, the model group exhibited elevated levels of TNF-α and Interleukin-1β (IL-1β) and declined levels of acetylcholine (ACh) and dopamine (DA) in the serum (P<0.01). Compared with the model group, the BXT-L, BXT-M, and BXT-H groups showed lowered levels of TNF-α and IL-1β in the serum (P<0.05) and elevated levels of ACh and DA (P<0.05). ConclusionBXT may ameliorate cognitive dysfunction in the rat model of VD by down-regulating the AGE/RAGE signaling pathway, reducing neuroinflammatory responses, and regulating neurotransmitter levels.
3.Effects of recombinant human syntaxin-4(STX4) on lipopolysaccharide-induced islet β-cell INS-1 injury and underlying mechanism
Jianlin ZHAO ; Yufeng CHEN ; Suyu WU ; Jiangyan LI ; Chengyun XIONG ; Ying ZHANG ; Xiuqin GENG
Chinese Journal of Endocrinology and Metabolism 2021;37(8):738-744
Objective:To explore the effect of recombinant human syntaxin-4(STX4) on lipopolysaccharide(LPS)-induced injury in islet β-cells(INS-1).Methods:Pancreatic islet β-cells(INS-1) were divided into Control (blank control), LPS (LPS treatment), LPS+ NC (transfection of negative control vector, LPS treatment), and LPS+ STX4 (transfection of pcDNA-STX4, LPS treatment) groups. RT-qPCR and Western blot were used to detect STX4 mRNA and protein expression, flow cytometry to detect apoptosis, DCFHDA method to detect reactive oxygen species(ROS) level, xanthine oxidation method to detect superoxide orgotein dismutase(SOD) level, colorimetric method to detect glutathione peroxidase(GSH-Px) level, ammonium molybdate colorimetric method to detect catalase(CAT) level, thiobarbituric acid method to detect malonaldehyde(MDA) level, ELISA method to detect the level of interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and insulin secretion levels under glucose conditions secreted by cells, Western blot method to detect Cleared Caspase-3, Bcl-2 Associated X Protein(Bax), p65 protein expression. After treatment with NF-κB signaling pathway activator, STX4 up-regulated islet β-cell INS-1 was given LPS stimulation, and the same method was used to measure apoptosis, ROS, SOD, GSH-Px, CAT, MDA levels and secreted IL-1β, TNF-α, insulin levels and Cleaved Caspase-3, Bax, p65 protein levels.Results:Compared with the Control group, the expression of STX4 mRNA and protein in islet β cells of the LPS group decreased, the apoptosis rate, ROS level, and MDA levels increased, and the levels of SOD, GSH-Px, and CAT decreased, the levels of IL-1β, TNF-α increased, the level of insulin secreted by the cells decreased, and the expression levels of Cleaved Caspase-3, Bax, and p65 also increased. NF-κB pathway activator treatment reversed the effect of up-regulated STX4 on islet β-cell apoptosis, ROS, SOD, GSH-Px, CAT, MDA levels and secreted IL-1β, TNF-α levels, and Cleaved Caspase-3 , Bax and p65 protein levels.Conclusion:Up-regulation of STX4 alleviated LPS-induced islet β cell oxidative damage, apoptosis and inflammatory factor release. The underlying mechanism might be related to the inhibition of activated NF-κB signaling pathway.
4.Clinical features and treatment outcome of extranodal nasal-type NK/T-cell lymphoma of the extra-upper aerodigestive tract
Yuting ZHAO ; Ying WANG ; Shunan QI ; Yong YANG ; Xia HE ; Yujing ZHANG ; Huiqiang HUANG ; Liling ZHANG ; Gang WU ; Baolin QU ; Liting QIAN ; Xiaorong HOU ; Fuquan ZHANG ; Xueying QIAO ; Hua WANG ; Gaofeng LI ; Yuan ZHU ; Jianzhong CAO ; Junxin WU ; Tao WU ; Suyu ZHU ; Mei SHI ; Liming XU ; Zhiyong YUAN ; Hang SU ; Yuqin SONG ; Jun ZHU ; Yexiong LI
Chinese Journal of Oncology 2021;43(7):787-794
Objective:To investigate the clinical features and prognosis of extranodal nasal-type NK/T-cell lymphoma of the extra-upper aerodigestive tract (extra-UADT NKTCL).Methods:The clinical data of 159 patients with extra-UADT NKTCL from the China Lymphoma Collaborative Group (CLCG) database between November 2001 and December 2015 were retrospectively analyzed. Kaplan-Meier survival analysis and Log-rank test were used to evaluate the prognosis. The Cox regression model is used for multi-factor analysis.Results:Extra-UADT NKTCL commonly occurs in skin and soft tissues (106/159, 66.7%) and gastrointestinal tract (31/159, 19.5%). The incidences of elevated lactate dehydrogenase (LDH) and Ann Arbor Ⅲ~Ⅳ stage were 47.8% (76/159) and 64.2% (102/159), respectively. The 3-year overall survival (OS) and progression-free survival (PFS) rates were 43.6% and 27.9%, respectively. The corresponding OS rates of primary skin/soft tissue site and gastrointestinal tract site were 41.0% and 59.4% ( P=0.281), while the PFS rates were 24.8% and 48.3%, respectively ( P=0.109). Combined modality treatment improved the 3-year OS of all the patients (58.4% vs 33.9%, P=0.001) and 3-year PFS (40.7% vs 20.7%, P=0.008) when compared with chemotherapy alone. LDH elevation, Ann Arbor synthesising and ≥2 junction external bits were intrusive as independent risk factors for total survival ( P<0.05), LDH elevation and ≥2 junction outer bits were intrusive as independent risk factors for progressionless survival( P<0.05). The distant extranodal dissemination was the primary failure patterns. Conclusions:Extra-UADT NKTCL appears to have distinct clinical characteristics and poor outcome. Compared with chemotherapy alone, combined modality treatment may improve the prognosis of patients with extra-UADT NKTCL.
5.Clinical features and treatment outcome of extranodal nasal-type NK/T-cell lymphoma of the extra-upper aerodigestive tract
Yuting ZHAO ; Ying WANG ; Shunan QI ; Yong YANG ; Xia HE ; Yujing ZHANG ; Huiqiang HUANG ; Liling ZHANG ; Gang WU ; Baolin QU ; Liting QIAN ; Xiaorong HOU ; Fuquan ZHANG ; Xueying QIAO ; Hua WANG ; Gaofeng LI ; Yuan ZHU ; Jianzhong CAO ; Junxin WU ; Tao WU ; Suyu ZHU ; Mei SHI ; Liming XU ; Zhiyong YUAN ; Hang SU ; Yuqin SONG ; Jun ZHU ; Yexiong LI
Chinese Journal of Oncology 2021;43(7):787-794
Objective:To investigate the clinical features and prognosis of extranodal nasal-type NK/T-cell lymphoma of the extra-upper aerodigestive tract (extra-UADT NKTCL).Methods:The clinical data of 159 patients with extra-UADT NKTCL from the China Lymphoma Collaborative Group (CLCG) database between November 2001 and December 2015 were retrospectively analyzed. Kaplan-Meier survival analysis and Log-rank test were used to evaluate the prognosis. The Cox regression model is used for multi-factor analysis.Results:Extra-UADT NKTCL commonly occurs in skin and soft tissues (106/159, 66.7%) and gastrointestinal tract (31/159, 19.5%). The incidences of elevated lactate dehydrogenase (LDH) and Ann Arbor Ⅲ~Ⅳ stage were 47.8% (76/159) and 64.2% (102/159), respectively. The 3-year overall survival (OS) and progression-free survival (PFS) rates were 43.6% and 27.9%, respectively. The corresponding OS rates of primary skin/soft tissue site and gastrointestinal tract site were 41.0% and 59.4% ( P=0.281), while the PFS rates were 24.8% and 48.3%, respectively ( P=0.109). Combined modality treatment improved the 3-year OS of all the patients (58.4% vs 33.9%, P=0.001) and 3-year PFS (40.7% vs 20.7%, P=0.008) when compared with chemotherapy alone. LDH elevation, Ann Arbor synthesising and ≥2 junction external bits were intrusive as independent risk factors for total survival ( P<0.05), LDH elevation and ≥2 junction outer bits were intrusive as independent risk factors for progressionless survival( P<0.05). The distant extranodal dissemination was the primary failure patterns. Conclusions:Extra-UADT NKTCL appears to have distinct clinical characteristics and poor outcome. Compared with chemotherapy alone, combined modality treatment may improve the prognosis of patients with extra-UADT NKTCL.
6.Meta-analysis for the Efficacy and Safety of Right Ventricular Septum Pacing and Right Ventricular Apical Pacing in Chinese Population
Ming BAI ; Jun PANG ; Qiang LI ; Tao WANG ; Aiyun DENG ; Changyuan CHEN ; Cunrui ZHAO ; Shijie WANG ; Suyu YAO ; Junbo GE ; Yuejin YANG ; Zheng ZHANG
Chinese Circulation Journal 2015;(8):766-770
database until 2015-01, and all randomized controlled trials (RCT) upon (RVS) pacing and (RVA) pacing in Chinese population were enrolled. According to Cochrane Handbook 5.0.2 quality evaluation criteria, the publications were selected by 2 independent researchers and Meta-analysis was conducted with RevMan5.0 software.
Results: A total of 16 RCT articles including 1199 patients were enrolled in this study. The research was divided into 2 groups: RVS group,n=602 and RVA group,n=597. Meta-analysis indicated that the following indexes in RVS group were better than those in RVA group: the differences between post-and pre-operation for the combination value in LVEF (MD=1.90, 95% CI 0.75-3.05,P=0.001), stroke volume (MD=7.08, 95% CI 2.39-11.76,P=0.003), QRS wave width (MD=29.13, 95% CI 5.71-52.54,P=0.01), LVESV (MD=2.04, 95% CI -4.22 to 8.31,P<0.00001), LVEDV (MD=2.64, 95% CI 1.80-3.49, P<0.00001), BNP (MD=68.00, 95% CI 57.57-78.43,P<0.00001), inter ventricular septum and left ventricular posterior wall motion delay time (SPWMD) (MD=22.68, 95% CI 16.91-28.45,P<0.00001), E/A (MD=0.49, 95% CI 0.41-0.57, P<0.00001), LRVPEI (MD=14.06, 95% CI 12.36-15.75,P<0.00001), resistance of electrode (MD=-67.02, 95% CI -119.96 to -14.08,P=0.01) and pacing threshold (MD=0.09, 95% CI 0.00-0.18,P=0.04). The time of operation in RVS group was longer than that in RVA group, (MD=-11.76, 95% CI -14.69 to -8.82,P<0.00001). The differences between post- and pre-operation in LVEDD, Tei index and X-ray exposure time were similar between 2 groups,P>0.05.
Conclusion: RVS is a relatively feasible pacing method in Chinese population.
7.Analysis on 7 417 ADR Reports Induced by Antineoplastic Drugs from 91 Hospitals
Weilan WANG ; Suyu ZHAO ; Daihong GUO ; Chao CHEN ; Liang MA ; Yuanjie XU ; Pengzhi ZHAO ; Liang ZHAO
China Pharmacy 2015;(20):2784-2786,2787
OBJECTIVE:To investigate characteristics and regularity of ADR induced by antineoplastic drugs and provide ref-erence for the safe drug use. METHODS:7 417 ADR reports induced by antineoplastic drugs from 91 hospitals from 2009 to 2013 were collected in the ADR monitoring center of PLA. According to the classification in national ADR monitoring cencer,Excel soft-ware was performed to statistically analyze the data. RESULTS:Among 7 417 ADR reports,1 475 were severe ADR(19.89%), 196 were the new and general ADR(2.64%),and 44 were new and severe ADR(0.59%);the elderly patients aged from 45-59 years accounted for the highest proportion (41.01%);intravenous administration was the main administration route causing ADR (88.96%);the incidence of antineoplastic drugs was higher in plant-derived drugs(26.55%),platinum drugs(24.86%)and an-ti-metabolism drugs (19.46%);ADR mostly manifested as lesions of digestive system (38.80%),blood system (16.53%) and general system(12.79%);43.60%ADR occurred within 12 hours after administration. CONCLUSIONS:Highly poisonous,nar-row-range security antineoplastic drugs could easily induce ADR. Risk prevention of antineoplastic drugs should be strengthened to undertake monitoring for high-risk patients and antineoplastic drugs,and severe ADR. More attention should be attached to the reac-tions after 12 h administration to reduce ADR incidence as much as possible.

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