Objective To study the role of ERK signal pathway in the endochondral ossification of bone mesenchymal stem cells ,and to explore the mechanism of ERK signal pathway in persistent enhanced FGFR2 function on development of mice BMSCs by a knock‐in mouse model with the FGFR2S252W/+ .Methods Mice with neo‐FGFR2 gain‐of‐function mutation were mated with EII‐Cre mice .The genotype of generation mice were identified by PCR and divided into wild type group and mutant type group ac‐cording to their genotype .6 week‐old mice were sacrificed to receive bone mesenchymal stem cells .The western blot was used to compare the level of P‐ERK and ERK and the RT‐PCR was applied to detect the genes of Col2 ,Col10 ,OC ,OP in chondrogenic dif‐ferentiation medium of BMSCs .Then ,treatment of cultured BMSCs with PD98059 ,compare the changes of genes and utilize the in vitro culture of long bones detect the role of ERK signal pathway in the endochondral ossification by FGFR2 mutant .Results We successfully derive BMSCs from FGFR2S252W/+ mutant mice and found the activity of ERK signal pathway of FGFR2S252W/+ was en‐hanced .After been cultured in chondrogenic differentiation medium ,the expressions of the BMSCs mRNA of Col2 ,Col10 from mu‐tant group were decreased ,while the expressions of OC ,OP were increased .Those OC ,OP genes levels showed an increased treated by PD98059 .Using in vitro culture of long bones ,we found the retardation of total length growth of long bones has been rescued by PD98059 treatment ,suggesting that ERK signal pathways was responsible for the retarded long bone development in FGFRS252W/+mice .Conclusion The results indicate these effects are mediated by the ERK signal pathway .Furthermore ,the retardation of long bones has been recued by PD98059 treatment ,suggesting that ERK signal pathway is responsible for the retarded long bone devel‐opment in FGFR2S252W/+ mice .

Objective To investigate the effect of mitogen activated protein kinase / extracellular signal-regulated kinase (MEK / ERK)1 / 2 signaling pathway on early brain injury (EBI)following experimental subarachnoid hemorrhage (SAH)in rats. Methods Sixty male SD rats were randomly divided into a control group and a 1,6,12,24,48,or 72 h group after SAH modeling. SAH + MEK inhibitor U0126 was used to intervene the 24,48,and 72 h groups (a total of 10 groups;n = 6 in each group). In
addition to the control group,blood was injected into the cisterna magna of the rats to induce a SAH model in another 9groups. The blood samples were taken from infraorbital venous plexus. Enzyme-linked immune sorbent assay (ELISA)was used to detect the levels of interleukin-6 (IL-6),IL-1β,and tumor necrosis factor α(TNF-α)in each group. Evans blue content in brain tissue was used to evaluate the blood-brain barrier damage. Western blot was used to detect the levels of phosphorylated extracellular signal-regulated kinase (p-ERK1/ 2)and matrix metalloproteinase-9 (MMP-9)proteins in basilar artery tissue,and compared them. Results Compared with the control group at the same time points,there were significant differences in the levels of IL-6 and IL-1β at 6,12,24,48,and 72h after modeling in the SAH group (all P <0. 05). At 12,24, 48,and 72 h after modeling,the expression levels of p-ERK1/ 2 protein of the basilar artery tissue of the SAH group were 0. 73 ± 0. 09,0. 85 ± 0. 12,0. 94 ± 0. 09,and 0. 96 ± 0. 09,respectively,they were significantly higher than those of the control group (all P < 0. 05). At 48 and 72 h after modeling in the SAH group,the level of MMP-9 protein was significantly higher than that in the control group (1. 27 ± 0. 15 vs. 0. 68 ± 0. 08,2. 41 ± 0. 11 vs. 0. 71 ± 0. 14). At 72 h after modeling,the Evans blue content in brain tissue of the SAH group was significantly higher than that of the control group (15. 3 ± 2. 2 μg/ g vs. 2. 7 ± 0. 4 μg/ g). After giving the MEK inhibitor U0126 intervention,the levels of serum IL-6,IL-1β,and TNF-α at 24,48, and 72 h after modeling,and the expression levels of p-ERK1 / 2 and MMP-9 proteins at 48 and 72 h (p-ERK1 / 2:0. 76 ± 0. 07,0. 81 ± 0. 06;MMP-9:0. 92 ± 0. 14,1. 79 ± 0. 16),and the Evans blue content (8. 9 ± 1. 7 μg / g)in brain tissue at 72 h after modeling were significantly lower than those of the SAH group (P < 0. 05). Conclusion The MEK/ ERK1/ 2 signal pathway may be closely associated with the inflammatory reaction and blood-brain barrier damage after SAH,which suggests that the intervention of the MEK/ ERK1 / 2 signal pathway may be a potential target for the prevention of early brain injury after SAH.

Objective To analysis the effects of Ang-(1-7) on the blood brain barrier permeability after subarachnoid hemor-rhage .Methods SAH-rats were produced by two times injection of blood into cisterna magna .Evans blue was used to detect the the permeability of SAH-rats brains and brain water content .RT-PCR and Western blot were performed to measure the expression of adhesion protein ICAM-1 and VCAM-1 in brains of SAH-rats .The artificial hemorrhagic cerebrospinal fluid (BCSF) was used to stimulate vascular endothelial cells (HBMEC) ,and the proliferation and apoptosis of HBMEC cell were analyzed .Results Ang-(1-7) reduced the content of Evans blue and brain water in brains of SAH-rats in dose and time dependent manner with the most sig-nificant change under the treatment of 10 - 5 mol/L Ang-(1-7) for 24 h (P< 0 .05) .Under the above condition ,the mRNA and pro-tein levels of ICAM-1 and VCAM-1 in brains of SAH-rats were significantly up-regulated (P< 0 .05) ,while the content of Evans blue in HBMEC cells stimulated by BCSF was obviously reduced .Besides ,Ang-(1-7) was observed to increase the expression of ICAM-1 and VCAM-1 in BCSF-stimulated HBMEC cells ,enhance the proliferation of HBMEC cells but reduce their apoptosis . Conclusion Ang-(1-7) plays a protective role in the blood-brain barrier damage induced by subarachnoid hemorrhage .

Objective Although multiple lines of evidence suggested that serum lipid is related to Parkinson's disease ( PD) , it has been controversial. The aim of this study is to conduct a systematic review and meta-analysis to analyse the relationship between serum lipid levels and PD risk. Methods Pertinent studies were identified by a search in Pubmed, Medline, Web of Science, Cochrane Library, Wanfang data-base, the Wiper database and China National Knowledge Infrastructure (CNKI) up to July, 2018. All sta-tistical analyses were conducted using STATA version 12. 0. Results Eleven related articles met our selec-tion criteria and a total of 1424 PD patients and 7250 healthy controls were included in further analysis. Through meta-analysis, low triglyceride ( TG) level appeared to increase risk of developing PD [ standard-ised mean difference (SMD) = -0. 31, 95％ CI ( -0. 40, -0. 21), P=0. 318, I2 =14. 7％], while no significant association was identified between total cholesterol ( TC) [ SMD= -0. 09, 95％ CI ( -0. 40, 0. 22), P=0. 000, I2 =94. 0％], low density lipoprotein cholesterol (LDL-C) [SMD= -0. 10, 95％ CI ( -0. 40, 0. 19), P=0. 000, I2 =92. 3％] and high density lipoprotein cholesterol (HDL-C) [SMD=-0. 09, 95％ CI ( -0. 22, 0. 05), P=0. 103, I2 =45. 5％] with PD. The similar conclusion was ob-tained by subgroup analysis in both Asian and non-Asian. Conclusions Our results indicate that TG were associated with the risk of PD, while TC, LDL-C and HDL-C maybe not associated with the risk of PD. However, this conclusion needs further confirmation.