ObjectiveTo explore the mechanism through which Banxia Baizhu Tianmatang ameliorates cognitive impairment in epileptic rats induced by lithium chloride-pilocarpine by regulating the neuroinflammatory reaction mediated by NOD-like receptor protein 3 （NLRP3） inflammasomes. MethodsSixty male SD rats were randomly allocated into blank， model， carbamazepine （0.125 g·kg^-1·d^-1）， Banxia Baizhu Tianmatang （1.04 g·kg^-1·d^-1）， and carbamazepine （0.125 g·kg^-1·d^-1） + Banxia Baizhu Tianmatang （1.04 g·kg^-1·d^-1） groups （n=12）. After the modeling of epilepsy， rats were administrated with corresponding agents by gavage for 12 weeks. At the 6th and 12th week of the intervention， the rats’ hyper-excited behavior was evaluated by the stylus experiment， and at the 12^th week of intervention， the cognitive function was evaluated by Barnes maze. At the same time， the seizure frequency and severity grade （Racine score） were recorded. The serum and hippocampus tissue samples were collected after anesthesia for the following tests. Nissl staining was used to evaluate the degree of neuronal damage in the hippocampal CA1 area. The content of malondialdehyde （MDA） in the hippocampus was determined by the thiobarbituric acid （TBA） method. Serum levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-18 （IL-18） were quantified by enzyme-linked immunosorbent assay （ELISA）. Immunohistochemical method was adopted to detect the expression of apoptosis-associated speck-like protein containing a card （ASC） in the hippocampus. Western blot was employed to quantitatively analyze the protein levels of NLRP3， cysteinyl aspartate-specific proteinase-1 （Caspase-1）， and brain-derived neurotrophic factor （BDNF） in the hippocampus. ResultsThe model group showed increased stylus scores at the 6th and 12^th week after modeling， a decreased Barnes maze strategy score at the 12^th week， a prolonged incubation period （P<0.05）， elevated serum levels of inflammatory factors （P<0.05）， decreased neurons with scattered arrangement and large gaps in the hippocampus， increased content of MDA in the hippocampus （P<0.05）， an increased positive expression of ASC， and up-regulated protein levels of Caspase-1， NLRP3， and BDNF （P<0.05）. Compared with the model group， the intervention with Banxia Baizhu Tianmatang for 12 weeks was accompanied by a decreased stylus score， epileptic seizures with a decreased score， a decreased number， and shortened duration， an increased Barnes maze strategy score， shortened escape latency （P<0.01）， declined serum levels of inflammatory factors （P<0.05）， regular morphology of hippocampal neurons， reduced MDA content in the hippocampus （P<0.05）， a decreased positive expression of ASC， and down-regulated protein levels of Caspase-1， NLRP3， and BDNF （P<0.05， P<0.01）. In addition， compared with the carbamazepine group， Banxia Baizhu Tianmatang + carbamazepine showed improved performance in controlling the seizure， improved the cognitive behavior score and morphology of hippocampal neurons， alleviated the oxidative stress products， lowered the levels of inflammatory factors， reduced the positive expression of ASC in the hippocampus， and down-regulated the expression of Caspase-1， NLRP3 and BDNF， with no significant differences. ConclusionBanxia Baizhu Tianmatang may reduce neuroinflammation， control epileptic seizures， and ameliorate cognitive impairment by inhibiting the expression of NLRP3 inflammasomes.

Objective To analyze the target,signal pathway and potential mechanism of Banxia Baizhu Tianma Decoction in the treatment of epilepsy based on network pharmacology,and to verify it by molecular docking technology and animal experiments.Methods The active ingredients and drug targets of Banxia Baizhu Tianma Decoction were screened by BATMAN and other databases.The targets of epilepsy-related diseases were obtained by GeneCards and other databases,and the intersection targets were taken.Constructing'drug-ingredient-target-disease'network and PPI network to screen the core targets.The core active ingredients were screened according to GO,KEGG functional enrichment analysis and'pathway-target-active ingredient'network.Molecular docking was used to verify the core targets and core active ingredients.In the animal experiment,the rat model of epilepsy was induced by lithium chloride-pilocarpine,and 40 Wistar rats were divided into normal control group,model control group,carbamazepine group and Banxia Baizhu Tianma Decoction group.The seizures were observed by behavior.Nissl staining was used to observe neuronal damage in hippocampus.Immunohistochemistry was used to detect the expression of BAX,BCL-2 and Caspase-3 protein.Results A total of 1072 targets of Banxia Baizhu Tianma Decoction were screened,1046 disease targets of epilepsy were screened,and 220 intersection targets of Banxia Baizhu Tianma Decoction in the treatment of epilepsy were screened.The core targets AKT1,ALB,ACTB,INS and TNF of PPI network were obtained.KEGG pathway mainly involves TNF signaling pathway,IL-17 signaling pathway,cAMP signaling pathway,pathways of neurodegeneration-multiple diseases,serotonergic synapse and Dopaminergic synapse.The core active ingredients with the highest correlation in the'pathway-target-active component'network were Betulin,Ephedrine,Ergotamine and Thymol.Results of molecular docking indicated that the core target had satisfactory affinity with those active ingredients.Animal experiments showed that Banxia Baizhu Tianma Decoction could effectively reduce epileptic seizures in rats,improve hippocampal neuronal damage in rats,significantly reduce the percentage of neuronal apoptosis,significantly down-regulate the expression of pro-apoptotic proteins BAX and Caspase-3,and up-regulate the expression of anti-apoptotic protein BCL-2.Conclusion Banxia Baizhu Tianma Decoction has the characteristics of multi-component,multi-target and multi-pathway in the treatment of epilepsy.Inhibiting neuronal apoptosis and reducing hippocampal neuronal damage may be one of the important mechanisms for its treatment of epilepsy.

Objective To analyze the target,signal pathway and potential mechanism of Banxia Baizhu Tianma Decoction in the treatment of epilepsy based on network pharmacology,and to verify it by molecular docking technology and animal experiments.Methods The active ingredients and drug targets of Banxia Baizhu Tianma Decoction were screened by BATMAN and other databases.The targets of epilepsy-related diseases were obtained by GeneCards and other databases,and the intersection targets were taken.Constructing'drug-ingredient-target-disease'network and PPI network to screen the core targets.The core active ingredients were screened according to GO,KEGG functional enrichment analysis and'pathway-target-active ingredient'network.Molecular docking was used to verify the core targets and core active ingredients.In the animal experiment,the rat model of epilepsy was induced by lithium chloride-pilocarpine,and 40 Wistar rats were divided into normal control group,model control group,carbamazepine group and Banxia Baizhu Tianma Decoction group.The seizures were observed by behavior.Nissl staining was used to observe neuronal damage in hippocampus.Immunohistochemistry was used to detect the expression of BAX,BCL-2 and Caspase-3 protein.Results A total of 1072 targets of Banxia Baizhu Tianma Decoction were screened,1046 disease targets of epilepsy were screened,and 220 intersection targets of Banxia Baizhu Tianma Decoction in the treatment of epilepsy were screened.The core targets AKT1,ALB,ACTB,INS and TNF of PPI network were obtained.KEGG pathway mainly involves TNF signaling pathway,IL-17 signaling pathway,cAMP signaling pathway,pathways of neurodegeneration-multiple diseases,serotonergic synapse and Dopaminergic synapse.The core active ingredients with the highest correlation in the'pathway-target-active component'network were Betulin,Ephedrine,Ergotamine and Thymol.Results of molecular docking indicated that the core target had satisfactory affinity with those active ingredients.Animal experiments showed that Banxia Baizhu Tianma Decoction could effectively reduce epileptic seizures in rats,improve hippocampal neuronal damage in rats,significantly reduce the percentage of neuronal apoptosis,significantly down-regulate the expression of pro-apoptotic proteins BAX and Caspase-3,and up-regulate the expression of anti-apoptotic protein BCL-2.Conclusion Banxia Baizhu Tianma Decoction has the characteristics of multi-component,multi-target and multi-pathway in the treatment of epilepsy.Inhibiting neuronal apoptosis and reducing hippocampal neuronal damage may be one of the important mechanisms for its treatment of epilepsy.

Objective To investigate the difference of the expression of estrogen receptor,progesterone receptor,human epidermal growth factor receptor 2 and Ki-67 protein between primary lesions of breast cancer and its synchronous ipsilateral lymph node metastasis,as well as its clinical implications.Methods Retrospectively analyze invasive breast cancer patients treated in Peking University First Hospital from January 2012 to May 2016.The IHC expressions of estrogen receptor,progesterone receptor,human epidermal growth factor receptor 2 and Ki-67 protein in both the primary and lymph node metastatic lesions are compared and analyzed statistically.The count data were represented as n(％),and comparsion between groups were evaluated using the McNemar test.Results One hundred and fifty-six patients were included,of which on 2 cases (1.3％),estrogen receptor status of primary lesions is different from that of lymph node metastases(P =0.500);on 10 cases (6.4％),progesterone receptor status of primary lesions is different from that of lymph node metastases (P =0.344);on 28 cases (18.0％),Ki-67 protein status of primary lesions is different from that of lymph node metastases (P =0.000 18);on 3 cases (1.9％),human epidermal growth factor receptor 2 status of primary lesions is different from that of lymph node metastases (P =1.000).Conclusion There may be difference between primary lesions and lymph node metastases in the expression of estrogen receptor,progesterone receptor,human epidermal growth factor receptor 2 and Ki-67 protein,which can provide a reference for individualized treatment of breast cancer patients.