Objective To investigate the effects of Xiaoyukang capsule on neuroinflammation and neuronal apoptosis after Intracerebral hemorrhage(ICH)in rats by regulating JNK/c-JUN signaling pathway.Methods Adult male SD rats were intrastriatally injected with bacterial collagenase Ⅶ to induce an ICH model and they were randomly divided into blank control group,model control group,Xiaoyukang capsule small dose group,medium dose group,and large dose group.Neurobehavioral tests,body mass measurements,hematoma volume statistics,hematoxylin-eosin(HE)staining,immunofluorescence,deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)staining,enzyme-linked immunosorbent assay(ELISA)and Western Blotting were performed after 3 and 5 days,respectively.Results Compared with the blank control group,the rats in the model control group had severe neurobehavioral defects and weight loss(P＜0.05).The arrangement of neurons in brain tissue was disordered,and there was microglia/macrophages activation,neutrophil infiltration,neuronal apoptosis(P＜0.05).The levels of pro-inflammatory factors TNF-α,IL-1β and the expression of p-JNK,p-c-JUN,Bax,Caspase-3 and Cleaved Caspase-3 protein around hematoma were significantly increased(P＜0.05),while the anti-inflammatory factor IL-10 and anti-apoptotic protein Bcl-2 were decreased(P＜0.05).Compared with the model control group,Xiaoyukang capsule large dose group significantly improved the neurobehavioral function of rats,promoted weight recovery and hematoma absorption(P＜0.05).Reduce the pathological injury of brain tissue,inhibition of microglia/macrophages activation,neutrophil infiltration and neuronal apoptosis(P＜0.05).In addition,the levels of pro-inflammatory factors TNF-α,IL-1β and the expression of p-JNK,p-c-JUN,Bax,Caspase-3,Cleaved Caspase-3 protein around hematoma were significantly decreased(P＜0.05),and the anti-inflammatory factor IL-10 and anti-apoptotic protein Bcl-2 were increased(P＜0.05).Conclusion Xiaoyukang capsule can improve neurobehavioral defects in ICH rats,promote body mass recovery and hematoma absorption,reduce pathological damage of brain tissue,inhibit microglia/macrophage activation and neutrophil infiltration,its mechanism may be achieved by inhibiting JNK/c-JUN-mediated neuroinflammation and neuronal apoptosis.

Objective To investigate the effects of Xiaoyukang capsule on neuroinflammation and neuronal apoptosis after Intracerebral hemorrhage(ICH)in rats by regulating JNK/c-JUN signaling pathway.Methods Adult male SD rats were intrastriatally injected with bacterial collagenase Ⅶ to induce an ICH model and they were randomly divided into blank control group,model control group,Xiaoyukang capsule small dose group,medium dose group,and large dose group.Neurobehavioral tests,body mass measurements,hematoma volume statistics,hematoxylin-eosin(HE)staining,immunofluorescence,deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)staining,enzyme-linked immunosorbent assay(ELISA)and Western Blotting were performed after 3 and 5 days,respectively.Results Compared with the blank control group,the rats in the model control group had severe neurobehavioral defects and weight loss(P＜0.05).The arrangement of neurons in brain tissue was disordered,and there was microglia/macrophages activation,neutrophil infiltration,neuronal apoptosis(P＜0.05).The levels of pro-inflammatory factors TNF-α,IL-1β and the expression of p-JNK,p-c-JUN,Bax,Caspase-3 and Cleaved Caspase-3 protein around hematoma were significantly increased(P＜0.05),while the anti-inflammatory factor IL-10 and anti-apoptotic protein Bcl-2 were decreased(P＜0.05).Compared with the model control group,Xiaoyukang capsule large dose group significantly improved the neurobehavioral function of rats,promoted weight recovery and hematoma absorption(P＜0.05).Reduce the pathological injury of brain tissue,inhibition of microglia/macrophages activation,neutrophil infiltration and neuronal apoptosis(P＜0.05).In addition,the levels of pro-inflammatory factors TNF-α,IL-1β and the expression of p-JNK,p-c-JUN,Bax,Caspase-3,Cleaved Caspase-3 protein around hematoma were significantly decreased(P＜0.05),and the anti-inflammatory factor IL-10 and anti-apoptotic protein Bcl-2 were increased(P＜0.05).Conclusion Xiaoyukang capsule can improve neurobehavioral defects in ICH rats,promote body mass recovery and hematoma absorption,reduce pathological damage of brain tissue,inhibit microglia/macrophage activation and neutrophil infiltration,its mechanism may be achieved by inhibiting JNK/c-JUN-mediated neuroinflammation and neuronal apoptosis.

BACKGROUND: Fibroblast activation protein (FAP) is one of the surface markers of cancer-associated fibroblasts (CAFs) and is closely related to the malignant characterization of CAFs. SP13786 is a specific micromolecule inhibitor of FAP and this study is to investigate the effects and mechanism of SP13786 on the migration and invasion of A549 cells through regulating exosomes of CAFs. METHODS: CAFs and paracancerous fibroblasts (PTFs) were isolated and subcultured from freshly resected lung adenocarcinoma tissues and paracancerous normal tissues separately. MTT assay was used to detect the proliferation of CAFs incubated by different concentrations of SP13786; PTFs-exo, CAFs-exo and CAFs+SP13786-exo were extracted by polymer precipitation method. The A549 cells were divided into Ctrl group, PTFs group, CAFs group and SP13786 group and each group was incubated with DMEM, PTFs-exo, CAFs-exo and CAFs+SP13786-exo separately. Laser confocal microscope was used to observe the endocytoses of exosomes by A549 cells. The expression of alpha-smooth muscle actin (α-SMA) and FAP in PTFs and CAFs and the expression of E-cadherin, N-cadherin, Slug, Stat3 and P-Stat3 in A549 cells were detected by immunofluorescence, immunohistochemistry and Western blot. The migration and invasion ability of A549 cells were detected by cell scratch and transwell methods. RESULTS: α-SMA and FAP were expressed much higher in CAFs than that in PTFs which indicate that CAFs and PTFs were successfully obtained from lung adenocarcinoma and paracancerous tissues (P<0.05). MTT showed that the 50% inhibitory concentration (IC50) of SP13786 for CAFs was about 3.3 nmol/L. In addition, SP13786 can significantly decrease the expression of α-SMA and FAP in CAFs which means that targeted inhibition of FAP could reduce the malignant characteristics of CAFs (P<0.05). Laser confocal microscope found that exosomes from CAFs could be taken up by A549 cells and scratch and transwell tests showed that the endocytosed CAFs-exo could promote the migration and invasion of A549 cells (P<0.001), while FAP inhibitor SP13786 could inhibit the effects of CAFs-exo on A549 cells (P<0.05). Furthermore, Immunofluorescence and Western blot showed that CAFs-exo could promote EMT by decreasing E-cadherin expression and increasing N-cadherin, Slug expression in A549 cells while FAP inhibitor SP13786 could significantly supress CAFs-exo-induced epithelial-mesenchymal transition (EMT) of A549 cells (P<0.05). Moreover, the expression of P-Stat3 was obviously increased in A549 cells of CAFs group and significantly down-regulated in SP13786 group (P<0.05) whereas there was no significant difference in total Stat3 between CAFs and SP13786 groups (P>0.05). Finally, WP1066 (a specific inhibitor of Stat3) was used to comfirm whether SP13786 could influence EMT of A549 cells by inhibiting Stat3 phosphorylation via CAFs-Exo. The results showed that when the phosphorylation of Stat3 in CAFs group was inhibited by WP1066, SP13786 could not influence the P-Stat3 expression and EMT of A549 cells anymore (P>0.05). CONCLUSIONS As a specific micromolecule inhibitor of FAP, SP13786 indirectly inhibits the migration and invasion of A549 cells by affecting exosomes of CAFs. The possible mechanism is to inhibit the phosphorylation of Stat3 and thus affect the EMT of A549 cells.

As an effective training method in improving the team cooperation and communication of medical workers,constructing the patient safety culture and improving the medical quality,team resource management (TRM),was widely applied and promoted in medical and clinical treatment. The conception and application of TRM at home and abroad were reviewed in this paper,to demonstrate that,in complex and volatile environment,TRM could promote the team cooperation and communication,reduce clinical errors,improve the prognosis of patients and the medical quality,and provide basis for the improvement,construction and development of medical safety culture.