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Objective To investigate the neuroprotective effects of exosomes derived from human umbilical cord mesenchymal stem cells(HUCMSCs) in cerebral palsy (CP) mice. Methods The exosomes from HUCMSCs were verified by transmission electron microscopy (TEM), nanoparticle tracking analyzer(NTA) and Western blot. The animals were randomly divided as sham operation group (sham group, n=8), model group[CP group, n=8, hypoxic induction after unilateral common carotid artery ligation combined with lipopolysaccharide(LPS) infection] and model exosome group (CP-Exo group, n=8, 125 μg exosomes was injected intravenously). Neuromotor function, the ability of grasping and balance were evaluated by Longa score, grid test and pole climbing test. The pathological lesion in brain tissue was observed with hematoxylin-eosin (HE) staining, the synaptic structure of neurons was observed by TEM, the survival of neurons was detected by toluidine blue staining, and the expression levels of PSD-95 and synaptophysin (SYP) were detected by Western blot. Results The exosomes isolated were spherical and double-membrane vesicles with an average particle size of 123nm, which expressed TSG101 protein. In animal behavior tests, Longa score in CP group was significantly higher than sham group(P＜0.01) and CP-Exo group (P＜ 0.05). There was no plaque necrosis found in exosome group and the incidence of nerve fiber demyelination in the white matter area was significantly reduced than in the CP group (P＜0.01). The synaptic structure of the sham group was relatively normal, while the other two groups showed varying degrees of pathological changes. The general trend of pathological changes was CP group＞CP-Exo group＞ sham group. The number of Nissl bodies in hippocampal pyramidal cells in CP group was significantly less than that in sham group(P＜0.01), however, which was also less than that in CP-Exo group (P＜ 0.01). The expression of PSD-95 and SYP in CP group was significantly lower than that in sham group (P＜0.01), and the levels PSD-95 and SYP in CP-Exo group was significantly higher than those in CP group(P＜0.01). Conclusions HUCMSCs exosomes can promote the recovery of neural function of cerebral palsy mice, reduce synaptic damage and protect neuron cells by increasing the expression of PSD-95 and SYP.

Exosomes secreted by mesenchymal stem cell(MSC-EXOs)carry lipids,proteins,nucleic acids and other signaling substances, which play an important role in intercellular communication, immune regulation and vascular regeneration. MSC-EXOs in pulmonary hypertension, pulmonary fibrosis and other lung diseases can improve the function of the lung tissue and treat lung diseases by regulating different signaling pathways, reducing cell inflammatory reaction, regulating immune function, improving the function of mitochondria, promoting angiogenesis, reducing pulmonary vascular remodeling and etc.,which provides new ideas for the treatment of refractory lung diseases in the future.

Background and purpose: The incidence of ductal carcinoma in situ (DCIS) has increased annually with the popularity of mammography screening. However, current treatment strategies are mostly based on the results of prospective randomized clinical trials in western countries. This study aimed to explore the clinical characteristics, recurrence patterns and prognostic factors of Chinese DCIS patients, hoping to optimize clinical decision-making. Methods: Medical records of 1 185 DCIS patients treated in Fudan University Shanghai Cancer Center from January 2008 to January 2017 were retrospectively analyzed. The local recurrence-free survival (LRFS) rate, disease-free survival (DFS) rate and overall survival (OS) rate were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the COX proportional hazards regression model. Results: With a median follow-up of 61 months, 50 treatment failure events were observed, including 16 locoregional recurrences, 30 contralateral breast cancer events and 4 distant metastases. The 5-year OS rate, LRFS rate and DFS rate were 99.9%, 98.7% and 96.6%, respectively. In the multivariate analysis, the positive status of human epidermal growth factor receptor 2 (HER2) was related to higher risk of local recurrence and the LRFS rate was poor (P=0.029). Conclusion: The patient with DCIS was associated with favorable prognosis. HER2 positivity was the risk factor for poor LRFS.

To observe the effect of curcumin on a C57BL/6J mouse liver cancer model induced by N-nitrosodiethylamine (DEN) combined with carbon tetrachloride (CCl4), and to explore its mechanism. METHODS: Forty young male C57BL/6J mice were intraperitoneally injected with DEN (25 mg/kg) 14 d after birth and randomly divided into the following 4 groups at the 4th week (10 in each group) : model control group and curcumin (100, 200 and 400 mg/ kg) groups. Ten male mice of the same age were used as normal control group. The mice in model group and curcumin groups were gavaged with 10% CCl4 (5 mL/kg) twice a week from the 8th week on. At the same time, the mice in curcumin groups were gavaged with curcumin, and the mice in normal control group were gavaged with the same volume of distilled water once a day for 14 weeks. After administration, the mice were sacrificed, the liver surface was observed, and the number of tumor nodules was compared. The activity of alanine aminotransferase ( ALT) and aspartate aminotransferase (AST) in serum was detected by an automatic biochemical instrument. The pathological changes of liver tissues were observed by HE staining. The mRNA expression levels of heme oxygenase-1 (HO-1) and NAD(P)H-quinone oxidoreductase 1 (NQO1) were detected by RT-qPCR, and the protein expression levels of HO-1, NQO1 and Ki67 were detected by Western blot and immunohistochemistry. RESULTS: Compared with normal control group, the body weight of the mice in model group was decreased significantly (P<0. 01), the liver index was increased significantly (P<0. 01), and the serum levels of ALT and AST were increased obviously (P<0. 01). There was no significant difference in the mRNA expression levels of HO-1 and NQO1 (P>0. 05), the protein levels of HO-1 and NQO1 were increased distinctly (P<0. 05), and the positive expression rate of Ki67 was increased significantly (P<0. 05). After curcumin treatment, the body weight of the mice was significantly increased (P<0. 01), the liver index was not changed (P>0. 05), and the number of tumor nodules in the liver was decreased significantly (P<0. 05 or P<0. 01). The serum level of AST was decreased significantly (P< 0. 01), the mRNA and protein expression levels of HO-1 and NQO1 were decreased significantly (P<0. 05), and the positive expression rate of Ki67 was decreased significantly (P<0. 05). CONCLUSION: Curcumin significantly protects against liver cancer in a C57BL/6J mouse model induced by DEN combined with CCl4, and its mechanism may be related to the inhibition of HO-1 and NQO1 expression. [ABSTRACT FROM AUTHOR]

Objective: This project is designed to explore the potential role of cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) in cardiac electrical remodeling induced by pacing at different ventricular positions in dogs., Methods: An animal model by implanting the pacemakers in beagles was established. According to the different pacing positions, the animals were divided into 4 groups:conditional control group (n=6), left ventricle pacing group (n=6), right ventricle pacing group (n=6) and bi-ventricle pacing group (n=6). Cardiac and electrical remodeling were observed by echocardiography, electrocardiogram and plasma BNP. Myocardial pathology and protein expression of extracellular regulated protein kinases1/2 (ERK1/2), P38 mitogen activated protein kinases (P38 MAPK) and CREB were examined at 4 weeks post pacing., Results: Cardiac structure and plasma BNP level were similar among 4 groups (all P>0.05). Electrocardiogram derived Tp-Te interval was significantly prolonged post pacing (92±11, 91±10, and 79±13 ms vs. 60±12 ms), and the Tp-Te interval in bi-ventricle pacing group was shorter than in left or right ventricle pacing group (P < 0.05). Western blot results showed that the expression of p-ERK1/2 in left ventricular myocardium of left ventricle pacing group, right ventricular myocardium of right ventricle pacing group and bi-ventricular myocardium of bi-ventricle pacing group was 2.7±0.4, 2.4±0.2, 1.7±0.1 and 1.9±0.2, respectively, the expression of p-P38 MAPK was 1.9±0.3, 1.7±0.2, 0.8±0.1 and 1.1±0.1, respectively, and the expression of p-CREB was 2.1±0.2, 2.0±0.2, 2.7±0.4 and 2.6±0.3, respectively. The p-ERK1/2 and p-P38 MAPK expression of bi-ventricle pacing group was lower,but the p-CREB expression was higher compared to the other pacing groups (P < 0.05)., Conclusions: Ventricular pacing could induce electrical remodeling evidenced by prolonged Tp-Te interval and increased phosphorylation of ERK1/2 and p38 MAPK and reduced phosphorylation of CREB. Compared with single ventricle pacing, bi-ventricle pacing could attenuate electrical remodeling in this model.