Objective To explore the dynamic changes of inflammatory cytokines and C-reactive protein(CRP)in patients with acute cerebral hemorrhage and its prognostic value.Methods TNF-α, IL-1β, IL-6, IL-8 and CRP were measured in 120 healthy persons and 120 patients after the onset of acute cerebral hemorrhage at 24 h, 3, 7 and 14 d.Correlation analyzes were performed respectively between bleeding quantity or serious degree in patients with acute cerebral hemorrhage and the above indicators.Receiver operating characteristic curve was emploied to analysis its clinical prediction significance to the deterioration of acute cerebral hemorrhage.Results Different periods of serum TNF-α,IL-1β, IL-6, IL-8, and CRP in patients with acute cerebral hemorrhage were higher than those in healthy controls(P<0.05).There was a positive correlation between brain bleeding quantity or severity and the contents of TNF-α, IL-1β, IL-6, IL-8, and CRP in patients with acute cerebral hemorrhage(P<0.05).The inflammatory cytokines and CRP in the patients had its clinical prediction significance to the deterioration of acute cerebral hemorrhage.Conclusion The serum levels of inflammatory cytokines and CRP is involved in cerebral hemorrhage in the pathophysiological process,and these indicators have important predictive value for patients.

Objective To observe the curative effect of nicergoline in the treatment of chronic cerebral circulation insufficiency ( CC-CI) . Methods 160 cases with CCCI were randomly divided into the treatment group which were administered 10 mg of oral Nicergoline, three times per day for one month,and the control group which were given 20 mg of oral nimodipine,three times per day for one month. The clinical effective rate and the transcranial Doppler ultrasound ( TCD) between the two groups before and after treatment were observed. Results There were significant difference in clinical effective rate and TCD index assessment between the two groups(P<0. 05). Conclu-sion Nicergoline is an effective and safe treatment for chronic cerebral circulation insufficiency.

Objective To investigate the effect of blood pressure control for early enlargement of hypertensive intracerebral hemorrhage.Methods A total of 96 patients were divided randomly into intensive blood pressure lowering group (n = 48 )and standard antihypertensive group(n=48).Patients were checked head CT and was evaluated defect of nerve function score immedi-ately when they arrive at hospital and after 24 hours.Then the clinical curative effect was evaluated.Results The defect of nerve function score in intensive blood pressure lowering group was lower than that of the standard antihypertensive group(P <0.05 ). The hematomas volume within 24 hours of admission and the rate of hematoma enlargement of intensive blood pressure lowering group were sharply smaller than those of standard antihypertensive group(P <0.05).Conclusion Controlling blood pressure ac-tively could decrease ratio early enlargement of hematoma and defect of nerve function score in patients with hypertensive cerebral hemorrhage.

Objective To investigate the effect of mild hypothermia on the expression of small ubiquitin-like modifier-specific proteases 3 (SENP3) in the brain tissues during cerebral ischemia-reperfusion (I/R) in mice.Methods Ninety-six male C57/BL6 mice,aged 10-12 weeks,weighing 22-30 g,were randomly divided into 3 groups (n =32 each) using a random number table:sham operation group (group S),group I/R,and mild hypothermia group (group H).Cerebral I/R was produced by occlusion of bilateral common carotid arteries for 15 min followed by reperfusion.The surface cooling was started immediately after reperfusion,and the rectal temperature was maintained at 32-34 ℃ for 3 h.At 6,12,24 and 72 h of reperfusion,8 mice were selected from each group and sacrificed.The hippocampi were removed for examination of the pathological changes (with light microscope) and for determination of cell apoptosis (using TUNEL) and expression of SENP3 (by Western blot).The apoptosis rate was calculated.Results Compared with group S,the apoptosis rate in hippocampal CA1 region was significantly increased,and the expression of SENP3 was significantly up-regulated at each time point of reperfusion in group I/R (P＜0.05).Compared with group I/R,the apoptosis rate in hippocampal CA1 region was significantly decreased,and the expression of SENP3 was significantly down-regulated at each time point of reperfusion (P＜0.05),and the pathological changes were significantly reduced in group H.Conclusion The mechanism by which mild hypothermia reduces cerebral I/R injury is associated with inhibition of SENP3 expression in the brain tissues of mice.

Objective To evaluate the effects of selective brain hypothermia on the expression of miR-484 during cerebral ischemia-reperfusion ( I/R) in rats. Methods A total of 120 clean-grade healthy male Sprague-Dawley rats, aged 8-10 weeks, weighing 250-300 g, were divided into 4 groups ( n=30 each) using a random number table method: sham operation group ( group S) , cerebral I/R group ( group I/R) , hypothermia group ( group H) and normothermia group ( group N) . Blood vessels were only separa-ted and ligated without blockade in group S. In the other three groups, cerebral I/R was induced by inser-ting a nylon thread with rounded tip into the right internal carotid artery, and the middle cerebral artery was occluded for 2 h followed by reperfusion. In group H, 4℃ normal saline was infused for 15 min at a rate of 80 ml·kg-1 ·h-1 through the internal carotid artery immediately after removing the nylon thread. In group N, 37 ℃ normal saline was infused in the same way. Neurological deficit scores were evaluated at 6, 24 and 48 h after reperfusion. Animals were then sacrificed, the cerebral cortex of the ischemic penumbra was removed for determination of nerve cell apoptosis ( by TUNEL method) , expression of mitochondrial fission protein 1 ( Fis1) ( by Western blot) and expression of miR-484 ( quantitative real-time polymerase chain re-action) . The apoptotic rate was calculated. Results Compared with group S, the neurological deficit score and apoptotic rate of nerve cells were significantly increased, and the expression of Fis1 was up-regulated at each time point in the other three groups, the expression of miR-484 was significantly down-regulated in I/R and N groups, and the expression of miR-484 was significantly up-regulated in group H ( P＜0. 05 or 0. 01) . Compared with group I/R and group N, the neurological deficit score and apoptotic rate of nerve cells were significantly decreased, and the expression of Fis1 was down-regulated, and the expression of miR-484 was up-regulated at each time point in group H ( P＜0. 05 or 0. 01) . Conclusion The mechanism by which se-lective cerebral hypothermia attenuates cerebral I/R injury is associated with up-regulating miR-484 expres-sion and thus down-regulating Fis1 expression in rats.

In the present work, we studied the structure-activity relationship (SAR) of tautomycetin (TMC) and its derivatives. Further, we demonstrated the correlation between the immunosuppressive fuction, anticancer activity and protein phosphatase type 1 (PP1) inhibition of TMC and its derivatives. We have prepared some TMC derivatives via combinatorial biosynthesis, isolation from fermentation broth or chemical degradation of TMC. We found that the immunosuppressive activity was correlated with anticancer activity for TMC and its analog compounds, indicating that TMC may home at the same targets for its immunosuppressive and anticancer activities. Interestingly, TMC-F1, TMC-D1 and TMC-D2 all retained significant, albeit reduced PP1 inhibitory activity compared to TMC. However, only TMC-D2 showed immunosuppressive and anticancer activities in studies carried out in cell lines. Moreover, TMC-Chain did not show any significant inhibitory activity towards PP1 but showed strong growth inhibitory effect. This observation implicates that the maleic anhydride moiety of TMC is critical for its phosphatase inhibitory activity whereas the C1-C18 moiety of TMC is essential for the inhibition of tumor cell proliferation. Furthermore, we measured in vivo phosphatase activities of PP1 in MCF-7 cell extracts treated with TMC and its related compounds, and the results indicate that the cytotoxicity of TMC doesn't correlate with its in vivo PP1 inhibition activity. Taken together, our study suggests that the immunosuppressive and anticancer activities of TMC are not due to the inhibition of PP1. Our results provide a novel insight for the elucidation of the underlying molecular mechanisms of TMC's important biological functions.
Cell Line ; Cell Proliferation ; Fermentation ; Furans ; Lipids ; Maleic Anhydrides ; MCF-7 Cells ; Structure-Activity Relationship

BACKGROUND AND PURPOSE: This study investigated the contribution of white-matter hyperintensities (WMH) and lacunar infarcts (LI) to the risk of Alzheimer's disease (AD) in an elderly cohort in China. METHODS: Older adults who were initially cognitively normal were examined with MRI at baseline, and followed for 5 years. WMH were classified as mild, moderate, or severe, and LI were classified into a few LI (1 to 3) or many LI (≥4). Cognitive function was assessed using the Mini Mental State Examination and the Activities of Daily Living scale. RESULTS: Among the 2,626 subjects, 357 developed AD by the end of the 5-year follow-up period. After adjusting for age and other potential confounders, having only WMH, having only LI, and having both WMH and LI were associated with an increased risk of developing AD compared with having neither WMH nor LI. Moderate and severe WMH were associated with an increased risk of developing AD compared with no WMH. Furthermore, patients with many LI had an increased risk of developing AD compared with no LI. CONCLUSIONS: Having moderate or severe WMH and many LI were associated with an increased risk of developing AD, with this being particularly striking when both WMH and LI were present.
Activities of Daily Living ; Adult ; Aged* ; Alzheimer Disease* ; China* ; Cognition ; Cohort Studies ; Follow-Up Studies ; Humans ; Magnetic Resonance Imaging ; Strikes, Employee ; Stroke, Lacunar*