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Objective:Based on the method of metabonomics, the intervention effect of Dingchuan decoction on neutrophilic asthma and its possible mechanism were analyzed from the changes of endogenous metabolites.Methods:Forty C57BL/6 mice were randomly divided into five groups: normal group (group A), neutrophilic asthma model group (group B), Dingchuan decoction low dose treatment group (group C), Dingchuan decoction medium dose treatment group (group D), and Dingchuan decoction high dose treatment group (group E), with 8 mice in each group.B/C/D/E group used ovalbumin (OVA) and complete Freund′s adjuvant (CFA) to induce sensitized mice to establish neutrophilic asthma model, and C/D/E group used Dingchuan decoction with different concentrations of crude drugs for intervention treatment.Buxco small animal lung function tester was used to evaluate the airway reactivity of mice; The total number of white blood cells in bronchoalveolar lavage fluid (BALF) was counted by counting plate, and the number was classified by cell smear staining; The pathological changes of lung tissue were observed by hematoxylin and eosin (HE) staining.The serum metabolites of mice in each group were detected by high performance liquid chromatography coupled with four pole time of flight mass spectrometry (UPLC-Q-TOF-MS/MS). The commonly used principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), orthogonal partial least squares discriminant analysis (OPLS-DA) models were used for statistical analysis of the metabolite profiles in serum. The intervention effect of Dingchuan decoction and its possible mechanism were reflected from the changes of endogenous metabolites.Results:(1) General behavior observation: except mice in group A, mice in other groups showed asthma symptoms of different degrees during the challenge period. The symptoms of mice in each treatment group (group C, D, E) of Dingchuan decoction were less than those in group B. (2) Airway reactivity: the airway reactivity of mice in group B to methacholine (MCh) increased with the inhalation concentration, and the airway resistance at each concentration of MCh was significantly higher than that in group A (all P<0.01); the airway reactivity in group C, D and E was lower than that in group B (all P<0.01); the airway reactivity in group D and E was lower than that in group C (all P<0.05). There was no significant difference in airway reactivity between group D and E ( P>0.05). (3) Airway inflammatory cell infiltration: the total number of white blood cells (WBC) and percentage of neutrophil in BALF of group B were significantly higher than those of group A (all P<0.01). The total WBC and percentage of neutrophil in group C, D and E were lower than those in group B (all P<0.01). The total number of WBC and percentage of neutrophil in group D and E were lower than those in group C (all P<0.01). There was no significant difference between group D and group E (all P>0.05). (4) Pathological changes of lung tissues: no pathological changes were observed in the lung tissues of group A mice. In group B, typical pathological changes such as bronchial lumen stenosis, intraluminal mucosal folds hyperplasia, epithelial cell exfoliation, swelling, mucous embolus, alveolar and lung tissue structure destruction, massive inflammatory cell infiltration around bronchus and blood vessels were observed, among which neutrophil and lymphocyte infiltration were the most obvious. The damage of lung tissue structure, bronchial mucosa edema and inflammatory cell infiltration in Dingchuan decoction treatment groups were significantly improved compared with group B, and the pathological changes of lung tissue in group D were relatively light. (5) Metabolomics analysis: PCA, PLS-DA and OPLS-DA analysis of serum metabolites in each group showed that serum metabolites in group A and group B were significantly different. The metabolic pathway analysis showed that Dingchuan decoction with different crude drug concentrations could improve the metabolic disorders caused by asthma in different degrees. Conclusions:Dingchuan decoction can effectively reduce airway inflammation and airway hyperresponsiveness in mice with neutrophil asthma, and effectively regulate metabolic abnormalities caused by neutrophil asthma.
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OBJECTIVE@#To investigate the effect and underlying mechanisms of Tiaoxin Recipe (a Chinese herbal formula) treatment on Alzheimer's disease (AD).@*METHODS@#Twelve-week-old APPswe/PS1ΔE9 (APP/PS1) double transgenic mice were used as a model of AD-afflicted mice. One group of mice was treated with Tiaoxin Recipe by gastrogavage for 12 weeks, while two other groups were given intraperitoneal injections of nicotinamide adenine dinucleotide or FK866 for 4 weeks. Morris water maze and thioflavin S staining tests were performed to evaluate cognitive impairment and amyloid plaque deposition, respectively. Serum amyloid-β1-42 (Aβ1-42) content was detected using an enzyme-linked immunosorbent assay, and quantitative reverse transcription-polymerase chain reaction was performed to examine the expression levels of microRNA-34a (miR-34a) in cortex and hippocampus samples of the study mice.@*RESULTS@#Compared with the normal control group, the memory and learning abilities of the APP/PS1 model group were found to be impaired (P < 0.01), as shown by the increased levels of senile plaque deposition in cortex and hippocampus (P < 0.01), miR-34a expression (P < 0.01) and serum Aβ1-42 content (P < 0.01). Treatment with Tiaoxin Recipe significantly reduced memory impairment (P < 0.01) by reducing amyloid plaque accumulation in cortex and hippocampus (P < 0.01), miR-34a expression (P < 0.01) and serum Aβ1-42 content (P < 0.01) in APP/PS1 mice.@*CONCLUSION@#Tiaoxin Recipe is a viable complementary or alternative therapeutic treatment that is capable of delaying the development of early-stage AD by inhibiting the expression of miR-34a.
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Purpose The aim was to examine c-MET,ALK,ROS1 variants in advanced non-small cell lung cancer (NSCLC) patients,and to analysis the association of c-MET,ALK,ROS1 variants with the clinical and pathological features.Methods The c-MET,ALK,ROS1 were detected by fluorescence in situ hybridization (FISH) in the 91 cases of NSCLC specimens.The correlation of c-MET gene amplification with clinicopathological features and the ALK,ROS1 fusions was analyzed.Results The positive rate of c-MET gene amplification was 8.79％ (8/91),the positive rates on male and female were 1.82％ and 19.4％,respectively.In ＜ 60-years-old and ≥60-years-old NSCLC patients,the positive rates were 7.5％ and 8.89％,resepectively.The positive rate was higher in stage Ⅲ than stage Ⅳ (9.62％ vs 7.69％),the c-MET gene amplification was detected in 9.2％ adenocarcinoma patients but none in squamous carcinoma patients.The detection rates of ALK fusions and ROS1 fusions were 10％ and 13.3％,respectively.One patient was detected the coexistence of MET with ROS1 fusion.Conclusion The c-MET gene amplification is correlated with gender,but not with age,histological types and clinical stages.C-MET amplification,ALK fusions and ROS1 fusions are almost no coexistence,but not completely mutually exclusive.To they knowledge,this is the first case report the coexistence of MET amplification with ROS1 fusion in NSCLC.
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AIM:To study the influence of lithium chloride (LiCl) on the neuronal differentiation of rat bone marrow mesenchymal stem cells (MSCs), and to explore whether autophagy was involved in this process .METHODS:MSCs were isolated and cultured in vitro.The cells were divided into LiCl group and control group .MSCs were treated withβ-mercaptoethanol as an inducer for triggering the cells to differentiate into neurons .The expression of neuronal markers-neuron specific enolase (NSE) and microtubule-associated protein-2 (MAP-2), and autophagic marker-microtubule-associ-ated protein 1 light chain 3 ( LC3) were measured by immunofluorescence method and Western blot .An autophagy activator rapamycin and autophagy inhibitor 3-methyladenine (3-MA) were applied to modulate the autophagy in the LiCl treated-cells.The protein expression of NSE and MAP-2 were determined by Western blot .RESULTS: After induction, the ex-pression of NSE and MAP-2 were increased .The percentage of NSE-and MAP-2-positive cells and the expression of NSE and MAP-2 in the LiCl group were greater than those in control group (P<0.05).After induction, the number of LC3-positive dots and the expression of LC3-Ⅱin LiCl group were greater than those in control group (P<0.05).The expres-sion of NSE and MAP-2 increased when the autophagy was modulated by rapamycin in LiCl treated -cells, and on the contra-ry, the expression of NSE and MAP-2 were inhibited as autophagy was modulated by 3-MA.CONCLUSION: Lithium chloride may promote the neuronal differentiation of rat bone marrow mesenchymal stem cells by modulating autophagy .
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OBJECTIVE@#To study the effect of atorvastatin on atherosclerotic rabbits.@*METHODS@#A total of 60 New Zealand male rabbits were randomly divided into the normal group, model group and atorvastatin group. The replication rabbit atherosclerotic model with immune injury combined with a high fat diet feeding was used. All rabbits were sacrificed after 3 months. TLR4 and NF-κB p65 were observed by HE staining, immunohistochemistry and western blotting.@*RESULTS@#The expression of TLR4, NF-κB p65 were significantly increased in the model group compared with the normal group. The expression of TLR4 and NF-κB p65 decreased significantly in the atorvastatin group, and there was no difference compared with the normal group.@*CONCLUSIONS@#The effect of atorvastatin on atherosclerosis may be achieved by the inhibition of the expression of TLR4 and NF-κB p65.
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Animals , Male , Rabbits , Anticholesteremic Agents , Pharmacology , Aorta , Metabolism , Atherosclerosis , Blood , Drug Therapy , Metabolism , Atorvastatin , Cholesterol, HDL , Blood , Cholesterol, LDL , Blood , Disease Models, Animal , Gene Expression , Heptanoic Acids , Pharmacology , Histocytochemistry , Pyrroles , Pharmacology , Random Allocation , Toll-Like Receptor 4 , Transcription Factor RelAABSTRACT
<p><b>OBJECTIVE</b>To understand the incidence rates of agricultural profession-related injuries and the relationship to alcohol consumption.</p><p><b>METHODS</b>A multistage sample of 2366 villagers was selected from Minority Nationality Villages, Heilongjiang province. Face-to-face interviews were conducted by trained interviewers during May 2008. 2198 (92.9%) of the eligible questionnaires were available.</p><p><b>RESULTS</b>Incidence rate of agricultural profession-related injury rate was 11.8% (260/2198) from May 2007 to April 2008. Higher proportions of injuries were seen for males, 30 - 49 year olds, farmers and among those people working on farms for 10 years or more, smoking during farm work, with sleeping disorder, using motor vehicles, and those using agricultural machinery. Rate of alcohol drinking was 29.1% (640/2198) in the month prior to the investigation. Results from logistic regression models showed that alcohol consumption patterns and other alcohol-related behavior were examined in separate logistic models because of collinearity by controlling the variables that were associated with agricultural profession-related injury including sex, age, years of farm work, driving a motor vehicle, and agricultural machinery use etc. In each model, the reference group was those villagers who did not drink in the past month. The odds of injury among villagers with history of past month drinking, who drank distilled spirits, and alcohol drinking at breakfast and lunch were 1.80 (95%CI: 1.24 - 2.62), 2.09 (95%CI: 1.38 - 3.15), 2.15(95%CI: 1.43 - 3.22) respectively. The odds of agricultural injury also significantly increased with greater average amounts of pure alcohol per day, with increased frequency of drinking per week, and reported years of drinking.</p><p><b>CONCLUSION</b>Intervention efforts should include increasing awareness about alcohol drinking as a major risk factor causing agricultural injuries as well as controlling alcohol drinking, improving knowledge about driving motor vehicle and using agricultural machinery.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Accidents, Occupational , Agriculture , Alcohol Drinking , Epidemiology , Alcoholic Intoxication , Epidemiology , China , Epidemiology , Incidence , Logistic Models , Minority Groups , Risk Factors , Rural Population , Surveys and QuestionnairesABSTRACT
OBJECTIVE@#To investigate the effect of probucol and losartan on the prevention of restenosis after balloon angioplasty in hypercholesterolaemic rabbits, and to examine the expression of growth factors.@*METHODS@#Forty male New Zealand white rabbits were randomly divided into high cholesterol diet group, probucol group, losartan group and combined drugs group. After one week of diet, all rabbits were injured on iliac arteries with balloon. Four weeks after the injury, the morphology of the iliac arteries of the rabbits were observed, and the insulin-like growth factor-I receptor (IGF-IR) and vascular endothelial growth factor (VEGF) were examined by immunohistochemical methods.@*RESULTS@#Compared with the high cholesterol diet group, the lumen areas of the probucol group, losartan group and combined drugs group were larger (P < 0.01), the intimal areas were smaller (P < 0.05), and the expression of IGF-IR and VEGF significantly decreased (P < 0.05). There was no statistically significant difference among the three groups.@*CONCLUSION@#Probucol and losartan can prevent the restenosis of rabbits' iliac artery from balloon injury, and inhibit the expression of IGF-IR and VEGF. There is no statistical difference between combined drugs and single drug administration.
Subject(s)
Animals , Male , Rabbits , Angioplasty, Balloon , Anticholesteremic Agents , Pharmacology , Therapeutic Uses , Coronary Restenosis , Drug Therapy, Combination , Hypercholesterolemia , Therapeutics , Losartan , Pharmacology , Therapeutic Uses , Probucol , Pharmacology , Therapeutic Uses , Random Allocation , Receptor, IGF Type 1 , Genetics , Vascular Endothelial Growth Factor A , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To explore the affecting factors on coronary heart disease among people over 40 years of age in Guangxi area, China.</p><p><b>METHODS</b>Baseline data was gathered through the Third National Blood Pressure Survey in 1991 in China. A total number of 11 818 adults over 40 years old had been studied in Guangxi province. Data of morbidity and mortality of coronary heart disease was obtained.</p><p><b>RESULTS</b>Cardiovascular events were related to systolic blood pressure, diastolic blood pressure, pulse pressure, smoking, BMI regardless of their myocardial infarct (MI) history. Cox regression analysis showed that the relative risk for cardiovascular events increased by 21 [95% confidence interval (CI): 9.06-48.44] times for those people having MI history. When pulse pressure, systolic blood pressure, diastolic blood pressure increased by every 10 mm Hg, the relative risk for cardiovascular events increased by 1.29 (95% CI: 1.11-1.49), 1.18 (95% CI: 1.02-1.22), 1.13 (95% CI: 1.05-1.28) respectively. There was 1.23 (95% Cl: 1.05-1.45) times higher in smoker than non-smoker on relative risk for cardiovascular events. When BMI increasing 1, the relative risk for cardiovascular events would increase 1.03 (95% CI: 1.01-1 .05) times.</p><p><b>CONCLUSION</b>Hypertension, smoking, increase of BMI were the risk factors of coronary heart disease among people who were over 40 years of age.</p>