Parkinson′s disease(PD)is a common disease caused by multiple factors and characterized by pathological degen?eration in the dopaminergic neural system. Based on its pathogenic factors,PD can be divided into several subtypes,so it is essential to develop therapeutic agents based on the main pathogenic factor of each subtype of PD. Recently it is confirmed that the mutation of leucine-rich repeat kinase 2(LRRK2)gene leads to increased activity of the LRRK2 notably,and then causes neurodegeneration. Thus developing LRRK2 inhibitors to modulate the kinase activity will be a novel therapy for the PD subtype which is caused by LRRK2 gene mutation. LRRK2,either a kinase or a GTPase,has two drug binding sites. Therefore,two types of LRRK2 inhibitors are being studied,one is the kinase inhibitor and the other is GTPase inhibitor. This paper summarizes the recent progress in the dis?covery and development of LRRK2 inhibitors.

Objective To investigate the effect of CDT1 gene over-expression on the apoptosis and cell cycle distribution in liver cells with a characteristic of genomic instability induced by radiation(GIR).Methods Lentivirus particles were transferred into liver cells of GIR to up-regulate the expression of CDT1 gene.The apoptosis and the cell cycle were detected by flow cytometry (FCM).The expression changes of p53,ATM,ATR,Bcl-2,and Caspase-3 genes were analyzed by real-time fluorescence quantitative PCR.Results CDT1 gene was efficiently increased by the gene transfection(t =15.56,P ＜ 0.05).In the CDT1 over-expressed cells,while the apoptosis ratio was increased (t =4.19,P ＜ 0.05),the expressions of p53 and Bcl-2 gene were decreased (t =-4.21,-2.06,P ＜ 0.05),but the expression of ATM,ATR and Caspase-3 changed with no significant difference compared with control.Conclusions Over-expression of CDT1 could regulate genomic instability through apoptosis pathway and checkpoint independent of p53.

AIM:To explore the change of antithrombin Ⅲ( AT-Ⅲ) in the patients with atherosclerotic cere-bral infarction .METHODS:Chromogenic substrate assay was used to measure the activity of AT-Ⅲ in 55 patients with atherosclerotic cerebral infarction and 55 healthy controls , and the correlation analysis was applied to determine the AT-Ⅲactivity with the severity of damage in central nervous system and general biochemical parameters .The levels of TNF-αand IL-6 in the plasma were detected by ELISA .Immunocomplex in the plasma was measured by enzyme immunoassay (EIA). The number and phenotype of the monocytes in peripheral blood were analyzed by flow cytometry .ELISA was also applied to determine the secretion of TNF-αand IL-6 from the monocytes after the stimulation of immunocomplex .The expression of AT-Ⅲin human brain vascular endothelial cells after the stimulation of TNF-αand IL-6 was observed by Western blotting . RESULTS:The activity of AT-Ⅲsignificantly decreased in the patients with atherosclerotic cerebral infarction , and nega-tively correlated with the damage degree of nervous system function , systolic pressure , diastolic pressure , glucose , choles-terol, triglyceride, low-density lipoprotein cholesterol and homocysteine , while positively correlated with high-density lipo-protein.In addition, the plasma levels of TNF-αand IL-6 increased significantly , accompanied with the enhancement of immunocomplex level .The numbers of CD14 + CD16 + and CD14 + CD32 + monocytes in peripheral blood were not changed , while CD14 +CD64 +monocytes increased obviously .The secretion of TNF-αand IL-6 by monocytes were signifi-cantly enhanced after stimulated with immunocomplex , while the protein expression of AT-Ⅲ in the human brain vascular endothelial cells was down-regulated after co-incubated with TNF-αor IL-6.CONCLUSION:Decreased AT-Ⅲactivity in the patients with atherosclerotic cerebral infarction is one of the risk factors of cerebral infarction , and related with the dis-ease severity .The production of pro-inflammatory cytokines through immunocomplex from CD 14 +CD64 +monocytes may be involved in the mechanism .Improvement of AT-Ⅲactivity may protect against cerebral ischemia .

Objective To investigate the relationship between inflammation and blood coagulation function in the patients with acute exacerbation of chronic cor pulmonale (AECCP) and discuss the potential mechanism and influence on the patients. Methods The present study was based on 30 healthy controls and 141 cases of AECCP in our hospital from January 2011 to June 2014.Levels of white blood cell (WBC), neutrophil (NEUT), high-sensitivity C-reactive protein (hs-CRP, Complement 3 (C3), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB) and thrombin time (TT) in the patients were determined. Results Compared with the healthy controls, the patients had higher levels of WBC, NEUT, hs-CRP, PT, APTT, FIB, TT (all P < 0.001) and lower level of C3 (P < 0.001). Significant positive correlations were found between the levels of WBC, NEUT and FIB (r = 0.196 and r = 0.199, both P < 0.05); hs-CRP and APTT, FIB(r = 0.234, P < 0.01 and r = 0.466, P < 0.001); C3 and FIB(r = 0.466, P < 0.001), and significant negative correlations were observed between the levels of C3 and PT, APTT, TT (r=-0.258, P<0.01;r=-0.279, P < 0.01 and r = -0.168, P < 0.05, respectively). Compared with the survival patients, the cases of death had higher levels of WBC and NEUT (both P < 0.01). The area under receiver operating characteristic curve of WBC and NEUT, predicting the prognosis, was 0.666 (95% CI 0.552, 0.780; P < 0.01) and 0.695 (95% CI 0.558, 0.801; P = 0.001) respectively. Conclusions Inflammation and blood coagulation function disorder usually coexist in the patients with AECCP, and are closely associated with the severity. Levels of both WBC and NEUT can be used as prognosis predictors for the patients.

OBJECTIVE: To compare the effects of ~(56)Fe~(17+),~(12)C~(6+)ion beams and~(60)Co γ rays on chromosome aberration in human lymphoblastoid cells. METHODS: The human lymphoblastoid cells were divided into 0. 1,0. 3,0. 5,0. 7,1. 0,2. 0 Gy irradiated groups and 0. 0 Gy control group. They were separately exposed to ~(56)Fe~(17+)ion beams( linear energy transfer was 400. 0 ke V/μm),~(12)C~(6+)ion beams( linear energy transfer was 26. 0 ke V/μm) and~(60)C γ rays. Chromosome specimens were harvested 48 hours after irradiation. The effects of different radiation on dicentric plus centric ring( “d + r”) aberration rate and chromosome aberration in human lymphoblastoid cells were detected by light microscope with artificial counting. RESULTS: The “d + r”aberration rates induced by 0. 3-2. 0 Gy ~(12)C~(6+)ion beams were significantly higher than those of ~(56)Fe~(17+)ion beams and~(60)Co γ rays at the same dose( P < 0. 017). Chromosome aberration cell rates of 0. 1-2. 0 Gy ~(12)C~(6+)ion beams were significantly higher than those of ~(56)Fe~(17+)ion beams and~(60)C γ rays at the same dose( P < 0. 017). At the dose range of 0. 0-2. 0 Gy,chromosome aberration effects of three kinds of radiations were gradually increased( P < 0. 01). The relative biological effectiveness of ~(56)Fe~(17+)ion beams was lower than that of ~(12)C~(6+)ion beams.CONCLUSION: The chromosome aberration induced by ~(12)C~(6+)ion beams was more serious than that of~(60)Co γ rays and ~(56)Fe~(17+)ion beams.