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.

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.

Objective:To investigate the impact of lesions in different nuclei of the subcortical basal ganglia on speech processing functions in patients with post-stroke dysarthria.Methods:From July 2022 to September 2023, a total of 20 patients with post-stroke dysarthria (patient group) and 22 healthy individuals (control group) were recruited. Brain imaging data, including structural magnetic resonance imaging(MRI) and diffusion-weighted imaging (DWI), as well as behavioral data of speech fluency task and picture association task were collected. Structural MRI data was analyzed using SPM12 software to perform voxel-based morphometry (VBM), measuring cortical thickness and gray matter volume (VGM) in specific nuclei of the basal ganglia. Behavioral metrics, such as reaction time (RT) and the number of valid responses were extracted for each task. Statistical analysis was conducted using SPSS 27.0 and R 4.0 softwares. Spearman correlation analysis was applied to examine relationships between neuroimaging parameters and behavioral performance indicators.Results:The patient group exhibited significantly smaller gray matter volumes in both left and right caudate nuclei((2.69±0.92)mm 3, (3.17±0.91)mm 3 ) and putamen (3.31±1.08)mm 3, (3.66±0.91)mm 3) compared to the control group (caudate nuclei (3.19±0.36)mm 3, (3.49±0.52)mm 3 putamen (4.52±0.54)mm 3, (4.72±0.64)mm 3), with statistically significant differences ( t=-2.83, 1.68; t=-3.59, 3.52, both P<0.05). Behavioral experiments revealed that the patient group exhibited significantly prolonged reaction time during picture association and naming tasks (1 910.50(1 214.25, 3 806.75) ms, 1 362.00(978.00, 2 297.00) ms) compared to the control group (1 618.00(1 162.75, 2 401.75) ms, 1 224.00(984.25, 1 661.50) ms; Z=-5.20, -4.61, both P<0.05). Gray matter volumes in the left caudate nucleus and left putamen exhibited negative correlations with reaction times during the picture naming task ( r=-0.52, -0.54, both P<0.05). Additionally, the gray matter volume of the left putamen demonstrated a positive correlation with the number of valid responses in speech fluency task-T2 ( r=0.46, P<0.05), whereas the left globus pallidus volume showed a negative correlation with speech fluency task-T1 ( r=-0.51, P<0.05) with the same measure. Conclusion:Lesions in the left subnuclei of the basal ganglia directly impair early-stage speech functions, including conceptual preparation and lexical selection, whereas right-side lesions exert less pronounced effects on linguistic performance compared to their left counterparts. Furthermore, the basal ganglia's involvement in higher-order linguistic processing may represent an indirect consequence of cognitive decline.

Objective:To investigate the impact of lesions in different nuclei of the subcortical basal ganglia on speech processing functions in patients with post-stroke dysarthria.Methods:From July 2022 to September 2023, a total of 20 patients with post-stroke dysarthria (patient group) and 22 healthy individuals (control group) were recruited. Brain imaging data, including structural magnetic resonance imaging(MRI) and diffusion-weighted imaging (DWI), as well as behavioral data of speech fluency task and picture association task were collected. Structural MRI data was analyzed using SPM12 software to perform voxel-based morphometry (VBM), measuring cortical thickness and gray matter volume (VGM) in specific nuclei of the basal ganglia. Behavioral metrics, such as reaction time (RT) and the number of valid responses were extracted for each task. Statistical analysis was conducted using SPSS 27.0 and R 4.0 softwares. Spearman correlation analysis was applied to examine relationships between neuroimaging parameters and behavioral performance indicators.Results:The patient group exhibited significantly smaller gray matter volumes in both left and right caudate nuclei((2.69±0.92)mm 3, (3.17±0.91)mm 3 ) and putamen (3.31±1.08)mm 3, (3.66±0.91)mm 3) compared to the control group (caudate nuclei (3.19±0.36)mm 3, (3.49±0.52)mm 3 putamen (4.52±0.54)mm 3, (4.72±0.64)mm 3), with statistically significant differences ( t=-2.83, 1.68; t=-3.59, 3.52, both P<0.05). Behavioral experiments revealed that the patient group exhibited significantly prolonged reaction time during picture association and naming tasks (1 910.50(1 214.25, 3 806.75) ms, 1 362.00(978.00, 2 297.00) ms) compared to the control group (1 618.00(1 162.75, 2 401.75) ms, 1 224.00(984.25, 1 661.50) ms; Z=-5.20, -4.61, both P<0.05). Gray matter volumes in the left caudate nucleus and left putamen exhibited negative correlations with reaction times during the picture naming task ( r=-0.52, -0.54, both P<0.05). Additionally, the gray matter volume of the left putamen demonstrated a positive correlation with the number of valid responses in speech fluency task-T2 ( r=0.46, P<0.05), whereas the left globus pallidus volume showed a negative correlation with speech fluency task-T1 ( r=-0.51, P<0.05) with the same measure. Conclusion:Lesions in the left subnuclei of the basal ganglia directly impair early-stage speech functions, including conceptual preparation and lexical selection, whereas right-side lesions exert less pronounced effects on linguistic performance compared to their left counterparts. Furthermore, the basal ganglia's involvement in higher-order linguistic processing may represent an indirect consequence of cognitive decline.

Insomnia is a prevalent clinical condition that not only diminishes the patient's quality of life but also has the potential to give rise to further health complications.Traditional Chinese medicine(TCM)has been used to treat insomnia for thousands of years,with distinct advantages.TCM uses syndrome differentiation and therapy to achieve its therapeutic effects,by regulating the internal balance of the human body.To gain a deeper understanding of how TCM treats insomnia,it is crucial to create animal models that exhibit insomnia symptoms closely resembling those found in humans.This review summarizes the current disease-syndrome combination models,which can be classified into four categories:liver depression and Qi stagnation,heart-spleen deficiency,heart-kidney incompatibility,and Yin and blood deficiency.This paper focuses on specific modelling method ologies,assessment indicators,and model performances,with the aim of enhancing our understanding of the pathophysiology of insomnia in the context of TCM,and providing technical assistance for clinical efficacy evaluation and the creation of novel drugs.

Insomnia is a prevalent clinical condition that not only diminishes the patient's quality of life but also has the potential to give rise to further health complications.Traditional Chinese medicine(TCM)has been used to treat insomnia for thousands of years,with distinct advantages.TCM uses syndrome differentiation and therapy to achieve its therapeutic effects,by regulating the internal balance of the human body.To gain a deeper understanding of how TCM treats insomnia,it is crucial to create animal models that exhibit insomnia symptoms closely resembling those found in humans.This review summarizes the current disease-syndrome combination models,which can be classified into four categories:liver depression and Qi stagnation,heart-spleen deficiency,heart-kidney incompatibility,and Yin and blood deficiency.This paper focuses on specific modelling method ologies,assessment indicators,and model performances,with the aim of enhancing our understanding of the pathophysiology of insomnia in the context of TCM,and providing technical assistance for clinical efficacy evaluation and the creation of novel drugs.

Objective:To evaluate the safety and efficacy of intravenous tirofiban in stent-assisted embolization of acute ruptured intracranial aneurysms.Methods:A total of 286 patients with acute ruptured intracranial aneurysms who received stent-assisted embolization in Department of Neurosurgery, Linyi People's Hospital from January 2020 to September 2022 were enrolled. According to different preoperative antiplatelet regiments, they were divided into aspirin combined with double resistant group (preoperatively taking orally loading dose of aspirin and clopidogrel, n=167) and tirofiban group (intravenously injecting tirofiban, n=119). Propensity score matching (PSM) was used to adjust for potential differences in age, gender, Hunt-Hess grading, hypertension history, diabetes history, smoking history, aneurysm location, aneurysm neck, aneurysm body-neck ratio, and stent types; incidences of perioperative hemorrhagic and ischemic complications, and neurological recovery status at discharge (scores of modified Rankin scale [mRS]≤2 as good recovery) were compared between the two groups. Results:After 1:1 PSM, 96 patients were included in each group. No significant difference in incidence of hemorrhagic complications was noted between the double resistant group (2.1%) and tirofiban group (0.0%, P>0.05). No significant difference in incidence of ischemic complications was noted between the double resistant group (9.3%, including 8 with intraoperative thrombosis and 1 with postoperative infarction) and tirofiban group (7.2%, including 6 with intraoperative thrombosis and 1 with postoperative infarction, P>0.05). No significant difference in good recovery rate at discharge was noted between double resistant group (86.4%) and tirofiban group (90.6%, P>0.05). Conclusion:In stent-assisted embolization therapy for acute ruptured intracranial aneurysms, preoperative intravenous tirofiban enjoys the same safety and efficacy compared with preoperative oral loading dose of aspirin and clopidogrel.

Objective:To investigate the effect of melatonin (MT) on hypoxia-induced injury of PC12 cells and its mechanism.Methods:PC12 cells cultured in vitro were divided into the control, the hypoxic, and three groups of hypoxic cells combined with different doses (low, medium, and high) of MT at 12.5, 25, and 50 μmol/L, respectively. Cell viability was measured by MTT. The expression of cysteine-containing aspartate 3 (cleaved caspase-3) and SOX2 proteins was detected by Western blot. The expression of SOX2 mRNA was detected by real-time fluorescence quantitative polymerase chain reaction (PCR). The activity of superoxide dismutase (SOD) and content of malondialdehyde (MDA) were detected by the kit. The combined treatment group with the most significant effect was selected as the hypoxia+MT group, and then the effects of hypoxia+MT, hypoxia+siRNA-NC, hypoxia+siRNA-SOX2, hypoxia+MT+pcDNA, and hypoxia+MT+pcDNA-SOX2 on cell viability, apoptosis, protein expression level of cleaved-caspase-3, protein and mRNA levels of SOX2, SOD activity, and MDA levels, respectively, were investigated.Results:Compared with the control group, cell survival rate and SOD activity in the hypoxia group were significantly decreased, while cell apoptosis rate, cleaved caspase-3 protein expression level, MDA content, SOX2 mRNA, and protein expression level were significantly increased (all P<0.05). The effects of low, medium, and high levels of MT and the low expression of SOX2 could ameliorate the above changes induced by hypoxia (all P<0.05), while the overexpression of SOX2 could alleviate the effects of MT on the viability, apoptosis, and oxidative stress of hypoxia-induced PC12 cells (all P<0.05). Conclusions:MT can reduce hypoxia-induced injury to PC12 cells by inhibiting the expression of SOX2.

Objective To explore the application effects and evaluation of scenario pedagogy on hierarchical first aid training for nurses. Methods A total of 160 nursing staffs, who took part in the first aid training from July 2013 to June 2014, were selected and averagely divided into observation group ( scenario pedagogy) and control group ( traditional pedagogy) by random number table. We compared basic theory of first aid, operant skill of first aid and comprehensive ability. Results After the training, the theory, operant skill and comprehensive ability were (96. 25 ± 8. 31), (93. 64 ± 7. 48), (95. 24 ± 7. 65), that were all higher than those of the control group (t=3. 265, 2. 985, 2. 988;P<0. 01);in the observation group after the training, the N0, N1, N2 level of nursing staffs′comprehensive ability were (94. 41 ± 8. 22), (96. 24 ± 7. 43), (98. 21 ± 7. 46) higher than those of the control group (t=2. 982, 3. 041, 3. 215;P<0. 01). Conclusions Scenario pedagogy method can significantly mobilize the study enthusiasm of nurses at all levels, and increase all level nurses′basic emergency theory, emergency operation skills and comprehensive abilities.

Parkinson's disease (PD) is a common degenerative disease of the central nervous system, but no drug has been found to be surely able to protect neurons so far, delay onset or slow progression of the disease. Currently there are a variety of Chinese formulas, single herb medicines, active fractions and monomers showed prophylactic and therapeutic effect on PD animal models. The mechanisms include protection of substantia nigra cells, improvement of neurotransmitter content, anti-oxidation, immune regulation, enhancement of Western medicine efficacy, reduction of side effects, etc. All these mechanisms may play integrated effect and slow disease progression. In particular, Chinese medicine compound may have some advantages in neuroprotective treatment of PD, because a variety of active ingredients can exert multi-links, multi-levels and multi-targets integrated regulation effect on human body. However, the level and standard of Chinese medicine studies on PD animal still need to be improved.
Animals ; Antioxidants ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; methods ; Neuroprotective Agents ; pharmacology ; Parkinson Disease ; drug therapy ; immunology ; Substantia Nigra ; drug effects ; metabolism