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.

Lipoprotein lipase (LPL) is a key enzyme in lipid and lipoprotein metabolism. LPL mainly hydrolyzes triglyceride-rich lipoproteins and provides free fatty acid (FFAs) for metabolic tissues. LPL acts as a molecular bridge between lipoproteins and cell surface lipoprotein receptors, facilitating lipoprotein uptake. Recent studies have shown that LPL is widely expressed in tissues. LPL has a variety of physiological functions, Lipoprotein lipase (LPL) is a key enzyme in lipid and lipoprotein metabolism. LPL mainly hydrolyzes triglyceride-rich lipoproteins and provides free fatty acid (FFAs) for metabolic tissues. LPL acts as a molecular bridge between lipoproteins and cell surface lipoprotein receptors, facilitating lipoprotein uptake. Recent studies have shown that LPL is widely expressed in tissues. LPL has a variety of physiological functions, which regulates lipid metabolism and energy balance in the brain. Besides, it is closely related to Alzheimer's disease. This paper mainly reviews the latest research progress of LPL in the nervous system and provides new targets for the treatment and prevention.

Objective To study the effects of microemulsion/ethosomes on transdermal absorption properties and efficacy of Huoxue Zhitong Cataplasm. Methods The improved Franz diffusion cells were used for the in-vitro permeation experiment with rat skins as the barriers, which was used to evaluate the transdermal absorption properties. In the erxeriment, the contents of paeonol, eugenol and methyl salicylate were used as markers, and detected by ultra performance liquid chromatography to evaluate the transdermal absorption effects. The anti-inflammatory and analgesia activity were evaluated through the writhing plate experiments. Results The cumulative release rate of paeonol in Huoxue Zhitong Cataplasm, Microemulsion Huoxue Zhitong Cataplasm and Ethosomes Huoxue Zhitong Cataplasm were, in order, 65.30%, 61.30%and 60.20%in 24 h;eugenol were, in order, 51.08%, 54.71% and 55.66% in 24 h; methyl salicylate were, in order, 49.20%, 65.17% and 72.15% in 24 h. Furthermore, Microemulsion Huoxue Zhitong Cataplasm high-dose group and Ethosomes Huoxue Zhitong Cataplasm medium-dose group had good effects on reducing the inflammatory exudate of peritoneal capillary and capillary permeability (P<0.05) in animal models. Conclusion Huoxue Zhitong Cataplasm based on microemulsion/ethosomesnano-technology has good transdermal absorption properties and efficacy.

Objective To optimize refinement of water extract from Bushen Yangxue Granules by chitosan flocculation.Methods According to the content of icariin detected by HPLC, the waters amount, extraction time and extraction times were evaluated by orthogonal design. The effects of the solution concentration, clarifying temperature and the amount of clarifying agent on the flocculation clarification processes were optimized with the content of icariin and polysaccharides.Results The optimum water extraction processes A2B1C3 were follows: 10 times amount of water, three times extraction and 1 h for each extraction process. The optimized flocculation clarification processes A1B2C3 were as follows: solution concentration was 0.4 g/mL, the clarifying temperature was 40℃ and the addition of chitosan was 0.1%.Conclusion The optimized refining process is stable and feasible.

Objective To explore the Effects of nursing model on anxiety and sleep of laparoscope cholecystectomy ( LC) patients based on story theory. Methods Totally 50 cases of LC patients were divided into the observation group and the control group according to convenience sampling method, with 25 cases in each group. Patients in the control group received routine nursing care, while patients in the observation group received nursing intervention based on the the story theory. Self-rating Anxiety Scale ( SAS) and Pittsburgh Sleep Quality Index ( PSQI ) were used to evaluate patients′ anxiety and sleep status before and after the intervention. The plasma cortisol concentration of patients in two groups were compared before and after the intervention.Results The SAS score in the observation group after surgery was (33.76±4.62);the PSQI score was (8.28±1.54);the plasma cortisol concentration was (17.35±6.32) ng/mL, and they were all lower than the data in the control group. Repeated measurement anova showed that the differences of SAS score, PSQI score and plasma cortisol concentration in two groups at different time were significant ( Ftime=12.230,16.512,18.041;P<0.05) , and in a downward trend. The nursing effect in the observation group was superior than that in the control group.Conclusions The nursing model based on story theory could significantly improve the anxiety and sleep of LC patients, which was conducive to the rehabilitation of patients after surgery.

Objective To discuss the application of spiral CT angiography in postoperative re-examination of lower limb artery stent implantation. Methods During the period from March 2012 to March 2014 at the Affiliated Nanjing Hospital of Nanjing Medical University, CT angiography was carried out in 67 patients who had received stent implantation for arteriosclerotic occlusion of lower limb. The diseases involved 78 lower limbs, and a total of 85 stents were employed. The volume rendering (VR), maximum intensity projection (MIP), multi-planar reformation (MPR) and curved surface reconstruction (CSR) were performed to stereoscopically display the lesion’s anatomy as well as the implanted stents, and the imaging manifestations were compared with the clinical symptoms and DSA findings. Results Successful examination was accomplished in 65 patients (81 stents in total), and clear images were obtained. Of the 81 stents, no stenosis was seen in 43, Ⅱ - Ⅳ grade stenosis in 32 and complete occlusion in 6. The results were closely correlated with the clinical symptoms. The CT angiography manifestations in 31 patients (34 stents in total) were compared with their DSA performed in two weeks, and the results showed that the stenotic degrees of three stents judged by CT angiography were not consistent with those judged by DSA. The consistent rate of CT angiography was 91.2% when taking DSA as the standard. Conclusion Lower limb arterial CT angiography examination is a safe and non-invasive technique, it can clearly display the stent inner canal. Therefore, this technique is of great value in postoperative re- examination of lower limb artery stent implantation.

OBJECTIVETo compare the pharmcoknetic parameters of six major alkaloids in the two drug delivery system of Zuojin Wan, by LC-MS assaying the six major alkaloids plasma concentration.

METHODThe blood samples were collected at different time after transdermal administration. The plasma concentration of six major alkaloids were detected by LC-MS, then the concentration-time data are modulated by software WinNonlin.

RESULTTook the six alkaloids (berberine palmatine coptisine jateorhizine evodiamine rutecarpine) as index components, the relative bioavailability were 131%, 127%, 108%, 121%, 92%, 109%, respectively, the ratio of Ka were 10.5, 5.1, 3.7, 0.8, 1.8, 1.5, respectively.

CONCLUSIONThe LC-MS can be applied in the determination of six major alkaloids plasma concentration. The pharmcoknetic parameters indicated that Zuojin Wan microemulsion gel delivery system can accelerate the transdermal absorption rate of Zuojin Wan, compared with the hydrogel drug delivery system.

Alkaloids ; administration & dosage ; chemistry ; pharmacokinetics ; Animals ; Chromatography, Liquid ; Drug Delivery Systems ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; pharmacokinetics ; Emulsions ; Female ; Gels ; Hydrogels ; chemistry ; Male ; Mass Spectrometry ; Rats