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Ethanol is one of the most widely used and abused psychoactive substances in the world. Long-term and excessive intake of alcohol can damage the central nervous system and lead to impairment of its function. As an important component of the central nervous system, cerebellum is one of the main target organs damaged by ethanol. Acute and chronic ethanol intake can damage human motor coordination, motor learning and some cognitive functions. Its damage mechanism is generally believed to be caused by the abnormal function of cerebellar cortical neural circuit caused by ethanol intake. Combined with recent studies on the mouse model of long-term ethanol intake, this article reviews the cerebellar neural network mechanism of long-term ethanol intake from various aspects, with a view to providing research and development in behavioral movement, motor coordination, cognitive function, depression, and offers new ideas with the rise of precision medicine for treatment. People are increasingly interested in exploring the mechanism of long-term ethanol intake on the cerebellar neural network. How to improve or block the corresponding mechanism based on the mechanism of action found in existing research is an important proposition in future research.
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Objective:To investigate the effect of long-term alcohol intake on sensory information synaptic transmission of mossy fiber-granular cells in the cerebellar cortex of mice.Methods:Twenty healthy male ICR mice aged 6 to 8 weeks were divided into normal saline group(control group) and alcohol intake group(alcohol group) according to random number table, with 10 mice in each group. The mice in alcohol group were injected intraperitoneally with 20% alcohol and the mice in control group were injected with the same amount of saline for 28 days.After the injection, the scalp, muscle tissue and skull were removed in turn, and the dura mater was removed to fully expose the crus II area of cerebellum. The mice were stimulated by air blowing at 30 mm of the ipsilateral tentacle pad with a gas jet device.When the the maximal response site was determined, the NMDA receptor antagonist (D-APV), metabolic glutamate receptor 1 antagonist (JNJ16259685) and N-methyl-D-aspartic acid (NMDA) were perfused on the brain surface of mice. Each drug was perfused for 20 minutes and ACSF was used between the two drugs until the waveform was recovered. Patch clamp amplifier was used to record the changes of potential waveform in mouse cerebellar granule layer. The data were analyzed by the softwares of Clampfit 10.3 and SPSS 22.0.Results:After exposure to wind stimulation, the latency of field potential response in granular layer of mice in alcohol group (11.8±0.7)ms was significantly longer than that in the control group (10.1±0.2)ms ( t=-8.041, P<0.05), and the amplitude of N1 (1.2±0.1) MV was significantly lower than that in the control group (0.6±0.1) MV ( t=-12.728, P<0.05). Compared with the control group, the rise time of P1 waveform((4.4±0.2)ms, (3.2±0.2)ms), duration ((12.1±0.5)ms, (10.3±0.2)ms), extinction time((7.8±0.2)ms, (6.9± 0.2)ms), volume under waveform ((7.3±0.2)ms, (4.3±0.2)ms) were significantly increased in the alcohol group ( t=16.100, - 11.840, -11.673, -35.576, all P<0.05). There were no significant differences in the amplitude, half width, rise time and decay time of Roff wave between the two groups ( t=-1.909, -0.910, -0.789, 1.462, all P>0.05). When JNJ16259685 was perfused on the brain surface of mice in alcohol group, the amplitude of field potential evoked by five blowing stimuli had no significant difference compared with that before administration (all P>0.05). When D-APV was perfused into the brain surface of mice in the alcohol group, the amplitude of P1 ((42.3±1.5) Mv)was significantly lower than that before administration ((101.1±0.9)mV) and after elution ((100.1±2.2) mV) ( t=106.762, - 69.605, both P<0.05), and the area under waveform of P1 ((42.6±1.3)%) was also significantly lower than that before administration ((100.6±1.6)%) and after elution ((97.6±2.2)%) ( t=88.862, -67.791, both P<0.05).The ratio of N2 / N1 (0.3±0.1) was significantly lower than that before administration (0.4±0.1) and after elution (0.3±0.1) ( t=2.242, 2.121, both P<0.05). When NMDA was perfused on the brain surface of mice in the control group, compared with before administration and after elution, the amplitude of P1 ((110.7±3.2) mV, (100.1±0.9) mV, (102.0±1.7) mV, t=-10.173, 7.669, both P<0.05), the area under the waveform of P1 ((127.9±3.5)%, (100.0±3.1)%, (115.0±5.3)%, t=-18.698, 6.447, both P<0.05), the ratio of N2 / N1 ((0.5±0.1), (0.3±0.1), (0.3±0.1), t=-5.669, 5.669, both P<0.05) were all significantly increased. When D-APV was perfused on the brain surface of mice in control group, the field potential evoked by blowing stimuli had no significant difference compared with that before administration and after elution (all P>0.05). Conclusion:Long-term alcohol intake significantly suppresses the synaptic transmission of excitatory glutamate in MF-GC, and enhances the inhibitory response mediated by GABAA receptor in cerebellar cortex. The inhibitory component is enhanced by NMDA receptor, but not by type 1 metabolic glutamate receptor.
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Objective To investigate the relationship between blood glucose levels and severity of coronary stenosis in hypertensive patients. Methods Blood pressure, fasting plasma glucose, 2 h plasma glucose, clinical features and coronary angiographic findings were analyzed retrospectively in 540 patients with essential hypertension. Acoording 2 h plasma glucose, patients were stratified into three group: group 1: 2h plasma glucose
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@# ObjectiveTo observe the effect of telmisartan on plasma levels of inflammatory cytokine in coronary artery disease (CAD) patients complicated with diabetes mellitus and hypertension after percutaneous coronary intervention.MethodsFifty CAD patients who just had undertook angioplasty and implanted stents were randomly divided into two groups, the test group (telmisartan group, n=25) and control group (perindopril group, n=25). After treatment, patients were followed-up for 6 months; plasma samples were collected from each patient before and after percutaneous coronary intervention. Then plasma levels of C-reactive protein (CRP), monocyte chemoattractant protein-1 (MCP-1) were measured by enzyme-linked immunoassay. The changes of cholesterol, fasting plasma glucose (FPG), insulin and insulin resistance index (IRI) were observed.ResultsAt the end of 6 months, plasma levels of CRP and MCP-1 of patients in the test group significantly declined (P<0.01), and showing a inversely correlation with FPG (P<0.01), and FPG, insulin and IRI also declined. In the control group, only CRP and MCP-1 declined (P<0.05). Meanwhile, the frequency of cardiovascular events in test group was significantly lower than that in the control group.ConclusionTelmisartan can decline plasma levels of CRP, MCP-1 and frequency of cardiovascular events as well as increasing insulin sensitivity and improving glucose metabolism to unstable angina patients.
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@#ObjectiveTo investigate the correlation of lipids and lipoproteins with cardiac function in patients with coronary heart disease (CHD).MethodsParameters of blood pressure, serum lipids and lipoproteins, clinical features, radionuclide ventriculographic and coronary angiographic findings were analyzed retrospectively in 584 CHD patients treated with standard treatment.ResultsThe left cardiac dysfunction of CHD patients was correlative positively with age, systolic blood pressure (SBP), diastolic blood pressure (DBP), blood glucose, body mass index (BMI), smoking, total cholesterol(TC) and low density lipoprotein cholesterol(LDL-ch) significantly(P<0.001), not correlative with high density lipoprotein-cholesterol (HDL-ch). The left ventricular ejection fraction (LVEF) and left ventricular peak filling rate (LVPFR) were decreased along with the levels of TC and LDL-ch increased (P<0.05～0.01).ConclusionTC and LDL-ch are positively correlative with left cardiac dysfunction in CHD patients. In order to reduce cardiac damage of CHD associated with hyperlipoidemia, more attention should be paid to the amelioration of coronary arteriosclerosis and the reduction of serum lipids and lipoproteins.
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Objective To observe the influence of atorvastatin on serum high sensitive C-reactive protein (hs-CRP) levels and arteriosclerosis plaque of coronary artery in patients with unstable angina. Methods Thirty subjects with arteriosclerosis plaque of coronary artery were given atorvastatin 20 mg qd for 12 months.The serum levels of hs-CRP were detected before and 12 months after treatment in all patients with helical computerized tomography. Results After 12 months administration of atorvastatin, The serum levels of hs-CRP reduced( P