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Objective:To explore the regulatory mechanism of α-synuclein in the degradation of autophagy-lysosome pathway(ALP) in Parkinson disease(PD) model cells after interference or overexpression of dynein heavy chain(Dynhc) gene.Methods:SH-SY5Y cells were divided into control group, PD group, Dynhc interference group, Dynhc overexpression group, and Dynhc interference+ rapamycin group according to experimental requirements.Using Western blot to detect Dynhc, α-synuclein, microtubule-associated protein l light chain 3 (LC3), lysosome-associated membrane protein 2 (LAMP2), tubulin, dynein activator protein p150, and kinesin KIF5B.Flow cytometry was used to detect the level of cell apoptosis.Immunoconfocal microscopy was used to observe the structure of tubulin and the co-localization of LC3 and LAMP.SPSS 23.0 software was used for statistical analysis.One-way ANOVA was used for inter group comparisons, and further pairwise comparisons were conducted by LSD- t test. Results:There were statistically significant differences in the expression of α-synuclein, autophagy-related proteins, microtubules, and microtubule-related proteins among cells in the 5 groups(all P<0.001). The protein expression levels of Dynhc, α-synuclein, LC3, LAMP2, p150, and KIF5B in the PD group were higher than those in the control group (all P<0.05). The protein levels of Dynhc, LAMP2, tubulin and p150 in the Dynhc interference group were lower than those in the PD group (all P<0.05), while the protein levels of α-synuclein, LC3 and KIF5B were higher than those in the PD group (all P<0.05). The protein levels of α-synuclein, LC3, and KIF5B in the Dynhc overexpression group were lower than those in the PD group (all P<0.05), while the protein levels of Dynhc, LAMP2 and p150 were higher than those in the PD group (all P<0.05). The protein level of LC3 in the Dynhc interference+ rapamycin group was higher than that in the Dynhc interference group ( P<0.05). There were no statistically significant differences in the protein levels of Dynhc, α-synuclein, LAMP2, microtubule protein, p150 and KIF5B compared to the Dynhc interference group (all P>0.05). Compared with the control group, the cell apoptosis rate in PD group increased((12.77±1.66)%, (7.64±1.45)%), the microtubule morphology remained unchanged, and autophagosomes fused more with lysosomes. Compared with the PD group, the cell apoptosis rate of Dynhc overexpression group decreased, and there was no significant change in microtubule structure, and there was more fusion between autophagosomes and lysosomes.Compared with the PD group, the cell apoptosis rat of Dynhc interference group increased((18.45±1.91)%), and the microtubule morphology was sparse, and there was less fusion between autophagosomes and lysosomes. Compared with the PD group, the Dynhc overexpression group showed a decrease in cell apoptosis rate ((9.95±1.56)%), no significant changes in microtubule structure, and more fusion between autophagosomes and lysosomes.Compared with the Dynhc interference group, the Dynhc interference+ rapamycin group showed no significant changes in cell apoptosis rate ((19.05±2.46)%), microtubule morphology, and fusion of autophagosomes and lysosomes. Conclusion:Dynhc can reduce cell apoptosis by enhancing cell ALP function, increasing the degradation of α-synuclein and maintaining of microtubule structure integrity.
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Ischemic stroke can cause severe brain damage in the short term after an ischemic attack. ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13) is a von Willbrand factor lyase that can affect both thrombosis and inflammation. It plays an important role in the occurrence, development, and outcome of ischemic stroke. In recent years, research on ADAMTS13 and ischemic stroke has gradually increased and there are some new developments. This article reviews the role of ADAMTS13 in the onset, outcome, and treatment of ischemic stroke.
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Objective:To investigate the predictive value of systemic immune-inflammatory index (SII) for hemorrhagic transformation (HT) and symptomatic intracranial hemorrhage (sICH) after intravenous thrombolysis in patients with acute ischemic stroke (AIS).Methods:Patients with AIS received intravenous thrombolysis in the Department of Neurology, Huai’an First People’s Hospital from July 2019 to July 2022 were included retrospectively. The head CT was performed at 24 h after intravenous thrombolysis and determined whether HT existed. sICH was defined as brain parenchymal hematoma, and the National Institutes of Health Stroke Scale (NIHSS) scores increased by ≥4 compared with the baseline, or the patient died within 36 h after onset. Multivariate logistic regression analysis was used to determine the independent correlation between SII and HT and sICH after intravenous thrombolysis. The receiver operating characteristics (ROC) curve was used to evaluate the predictive value of SII for HT and sICH after intravenous thrombolysis. Results:A total of 352 patients with AIS received intravenous thrombolysis were enrolled, including 240 males (68.1%), aged 66.46±12.00 years. The median baseline NIHSS score was 8 (interquartile range, 5-13), and the median SII is 531.91×10 9/L (interquartile range, 351.20-896.91×10 9/L). HT occurred in 62 patients (17.6%) and sICH occurred in 27 patients (7.7%). Univariate analysis showed that the SII of the HT group was significantly higher than that of the non-HT group ( Z=–2.731, P=0.006), and the SII of the sICH group was significantly higher than that of non-sICH group ( Z=–4.125, P<0.01). Multivariate logistic regression analysis showed that the increased SII was the independent risk factor for HT (odds ratio [ OR] 1.001, 95% confidence interval [ CI] 1.000-1.001; P=0.004) and sICH ( OR 1.001, 95% CI 1.001-1.002; P<0.01). ROC curve analysis shows that the area under curve of SII predicting HT was 0.610 (95% CI 0.535-0.686; P=0.006), and the best cutoff value was 488.48×10 9/L. The corresponding sensitivity and specificity were 69% and 47% respectively. The area under the curve of SII predicting sICH was 0.739 (95% CI 0.636-0.842; P<0.01), and the best cutoff value was 846.56×10 9/L, the corresponding sensitivity and specificity were 70% and 77% respectively. Conclusion:The increased SII at admission can predict the risks of HT and sICH in patients with AIS after intravenous thrombolysis.
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Objective:To investigate the predicting value of eosinophil-to-neutrophil ratio (ENR) for outcomes at 3 months after intravenous thrombolysis in patients with acute ischemic stroke (AIS).Methods:Patients with AIS received intravenous thrombolysis in the Department of Neurology, Huai'an First People's Hospital from July 2019 to July 2022 were included retrospectively. Multivariate logistic regression model was used to determine the independent correlation between ENR and outcomes at 3 months after intravenous thrombolysis. The receiver operating characteristics (ROC) curve was used to evaluate the predictive value of ENR levels for poor outcomes at 3 months after intravenous thrombolysis. Results:A total of 352 patients with AIS receiving intravenous thrombolysis were enrolled, including 240 men (68.1%), age 66.46±12.00 years old. The median National Institutes of Health Stroke Scale score was 8 (interquartile range, 5-13). At 3 months after onset, 215 patients (61.0%) had good outcomes, 137 (38.9%) had poor outcomes. Univariate analysis showed that the median ENR×10 2 level of the poor outcome group was significantly lower than that of the good outcome group ( Z= –7.305, P<0.01). Multivariate logistic regression analysis showed that lower ENR×10 2 was an independent risk factor for poor outcomes at 3 months after intravenous thrombolysis (odds ratio 0.619, 95% confidence interval 0.514-0.745; P<0.01). ROC curve analysis showed that the area under the curve for ENR×10 2 predicting the poor outcomes after intravenous thrombolysis was 0.731 (95% confidence interval 0.678-0.784; P<0.01). The optimal cutoff value was 0.625 and the corresponding sensitivity and specificity were 94% and 40%, respectively. Conclusion:Lower ENR before intravenous thrombolysis in patients with AIS is independently associated with the poor outcomes at 3 months.
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Endovascular therapy has been proved to be the best treatment for acute ischemic stroke caused by large vessel occlusion, but its efficacy is closely associated with time, so it is of great significance to obtain biomarkers that can predict its outcome early. Blood cells can reflect inflammatory reaction, which is very low cost and easy to obtain. This article expounds the predictive value of blood cells on the outcomes of acute ischemic stroke after endovascular therapy.
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Objective:To investigate the effect of interfering S-phase kinase associated protein 1 (SKP1) gene on apoptosis in Parkinson's disease(PD) cell model induced by 1-methyl-4-phenyl-pyridine ion (MPP+ ) and the mechanism of ubiquitin proteasome system degradation of α-synuclein (α-syn) influence.Methods:SH-SY5Y cells were divided into control group, MPP+ group, SKP1 interference group, and SKP1 interference+ MG132(UPS inhibitor) group.The cells in the control group were cultured normally. The cells in the latter three groups were incubated with MPP+ (0.5 mmol/L) for 24 h as PD model cells.The cells in SKP1 interference group were transfected with lentivirus SKP1-siRNA, and the cells in SKP1 interference+ MG132 group were transfected with lentivirus SKP1 siRNA and added with MG132 (0.5 μmol/L) for 24 h. The protein levels and mRNA levels of SKP1, microtubule-associated protein light chain 3 (LC3), lysosome-associated membrane protein (LAMP), α-syn, ubiquitin activating enzyme E1 (UBE1), parkin, and p27 in cells were detected by Western blot and RT-PCR.Flow cytometry was used to detect cell apoptosis and cycle level, and CCK-8 method was used to detect cell proliferation level.Co-immunoprecipitation method was used to explore the interaction between SKP1 and p27. SPSS 23.0 software was used for statistical analysis. One-way ANOVA was used for comparison among groups, and LSD test was used for further pairwise comparison.Results:RT-PCR and Western blot results showed that the mRNA levels and protein levels of autophagy related proteins and ubiquitin related proteins LC3, LAMP2, α-syn, UBE1, parkin and p27 in the four groups were statistically significant(mRNA: F=99.155, 43.028, 138.464, 28.200, 22.009, 28.147, all P<0.05; F=245.517, 157.634, 315.920, 2 336.472, 477.429, 2 350.201, all P<0.05). The mRNA and protein levels of LC3, Lamp2, α-syn and p27 in SKP1 interference group were lower than those in MPP+ group (all P<0.05), while the mRNA and protein levels of UBE1 and parkin were higher than those in MPP+ group (all P<0.05). The mRNA and protein levels of LC3, α-syn and p27 in SKP1 interference+ MG132 group were higher than those in SKP1 interference group (all P<0.05), and the mRNA and protein levels of UBE1 and parkin were lower than those in SKP1 interference group (all P<0.05). The results of flow cytometry and CCK-8 method showed that the apoptosis rate and cell inhibition rate among the four groups were significantly different( F=2 749.420, 171.508, both P<0.05). The apoptosis rate of SKP1 interference group was lower than that of MPP+ group ((8.22±0.25)%, (15.30±0.21)%, P<0.05), while the cell inhibition rate of SKP1 interference group was lower than that of MPP+ group((26.31±3.73)%, (55.05±3.84)%, P<0.05). The apoptosis rate of SKP1 interference+ MG132 group ((9.49±0.07)%) was higher than that of SKP1 interference group, and the cell inhibition rate ((36.06±2.85)%) was higher than that of SKP1 interference group (both P<0.05). The results of immunoprecipitation method showed that P27 decreased after SKP1 immunoprecipitation. Conclusion:After SKP1 gene was interfered, the autophagy function of PD cells decreased, which may be related to parkin promoting α-syn ubiquitination, activating UBE1/ Parkin-mediated UPS pathway to degrade α-syn, and mediating P27 to inhibit apoptosis.
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Objective:To investigate the regulation of Parkin-dependent mitophagy mediated by calcyclin-binding protein and Siah-1 interacting protein (CacyBP/SIP) on apoptosis and cycle of dopaminergic (DA) neurons.Methods:SH-SY5Y cells were divided into model group, control group and CacyBP/SIP group; cells in the model group were treated with 1-methyl-4-phenylpyridine (MPP +, 0.5 mmol/L) for 24 h, and cells in the control group and CacyBP/SIP group were transfected with empty lentivirus or CacyBP/SIP-sgRNA lentivirus on the basis of MMP +(0.5 mmol/L) treatment for 24 h, respectively. Western blotting was used to detect the protein expression levels of CacyBP/SIP, microtubule-associated protein l light chain 3 (LC3), lysosome-associated membrane protein 2 (LAMP2), phosphatase and tensin homolog ten induced kinase 1 (Pink1), Parkin, P53, Bcl-2, and Bax; flow cytometry was used to detect the cell apoptosis and cycle; immunofluorescent single staining was used to detect the expressions of LC3 and LAMP2; immunofluorescent double staining was used to detect the coexpressions of CacyBP/SIP and Parkin. Results:As compared with the model group and control group, the CacyBP/SIP group had significant reduction in protein expressions of CacyBP/SIP, LAMP2, Pink1, and Parkin, LC3-II/I ratio, immunofluorescent staining intensities of LC3-II and LAMP2, and Bcl-2 protein expressions ( P<0.05). As compared with the model group and control group, the CacyBP/SIP group had significantly increased Bax protein expression, significantly decreased Bcl-2/Bax ratio, significantly increased apoptosis rate, significantly increased P53 protein expression, significantly increased proportion of cells at G1 phase, and significantly decreased immunofluorescent intensity of CacyBP/SIP and Parkin co-expressions ( P<0.05). Conclusion:After knocking out CacyBP/SIP gene, the decrease of Parkin protein leads to cell cycle being arrested at G1 stage, and mediates the decrease of Parkin-dependent mitochondrial autophagy, thereby leading to increased cell apoptosis.
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Objective To explore the relationship between different dimensions of infectious disease-specific health literacy scale in China.Methods Structural equation model (SEM) was employed to assess the psychometric properties of the infectious disease-specific health literacy scale.Based on the database from a randomly selected sample of 4 499 adult residents in three provinces in China,from March to May 2015.AMOS 21.0 software was used to build the SEM for data analyses.Results SEM analyses showed a good model fit of data,with the following satisfied parameters:goodness-of-fit index was 0.969,adjusted goodness-of-fit index was 0.962,root mean square residual was 0.038,root mean square error of approximation was 0.038,standardized root mean square residual was 0.032,Tacker-Lewis index/non-normed fit index was 0.926,comparative fit index was 0.934,normed fit index was 0.925,relative fit index was 0.915,incremental fit index was 0.934,parsimony goodness-of-fit index was 0.782,parsimony-adjusted normed fit index was 0.817,parsimony-adjusted comparative fit index was 0.825 and critical N was 702.The established SEM showed that the total influence path coefficient of "infectious disease-related knowledge and values" on the "infectious disease prevention","management or treatment of infectious diseases" and "identification of infection sources" were 0.771,0.744 and 0.843,respectively.The total influence path coefficients of "identification of infection sources","infectious disease prevention" on "management or treatment of infectious diseases" were 0.164 and 0.535,respectively.The effect of "infectious disease-related knowledge and values" on "management or treatment of infectious diseases" appeared the greatest (55.4％),followed by "infectious disease prevention" (28.6％) and "identification of infection sources" (2.7％).Conclusion This SEM could be optimistically used for planning and evaluation of health education and promotion programs on infectious diseases prevention.
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Objective: To explore the relationship between different dimensions of infectious disease-specific health literacy scale in China. Methods: Structural equation model (SEM) was employed to assess the psychometric properties of the infectious disease-specific health literacy scale. Based on the database from a randomly selected sample of 4 499 adult residents in three provinces in China, from March to May 2015. AMOS 21.0 software was used to build the SEM for data analyses. Results: SEM analyses showed a good model fit of data, with the following satisfied parameters: goodness-of-fit index was 0.969, adjusted goodness-of-fit index was 0.962, root mean square residual was 0.038, root mean square error of approximation was 0.038, standardized root mean square residual was 0.032, Tacker-Lewis index/non-normed fit index was 0.926, comparative fit index was 0.934, normed fit index was 0.925, relative fit index was 0.915, incremental fit index was 0.934, parsimony goodness-of-fit index was 0.782, parsimony-adjusted normed fit index was 0.817, parsimony-adjusted comparative fit index was 0.825 and critical N was 702. The established SEM showed that the total influence path coefficient of "infectious disease-related knowledge and values" on the "infectious disease prevention" , "management or treatment of infectious diseases" and "identification of infection sources" were 0.771, 0.744 and 0.843, respectively. The total influence path coefficients of "identification of infection sources" , "infectious disease prevention" on "management or treatment of infectious diseases" were 0.164 and 0.535, respectively. The effect of "infectious disease-related knowledge and values" on "management or treatment of infectious diseases" appeared the greatest (55.4%), followed by "infectious disease prevention" (28.6%) and "identification of infection sources" (2.7%). Conclusion: This SEM could be optimistically used for planning and evaluation of health education and promotion programs on infectious diseases prevention.
Subject(s)
Adult , Humans , China , Health Literacy , Models, Theoretical , Psychometrics , Surveys and Questionnaires摘要
OBJECTIVE:To investigate therapy efficacy of large-dose of methylprednisolone plus therapy for acute myelitis, and it effects on nerve function recovery,pyramidal tract conduction function and sensory disturbance. METHODS:A total of 116 patients with acute myelitis were randomly divided into observation group and control group,with 58 cases in each group. Both group received conventional treatment. Control group was additionally given Dexamethasone sodium phosphate injection 0.4 mg/(kg·d)intravenously,once a day;7 d later,they were given Methylprednisolone tablet 60 mg,orally,qd,gradually decreasing to 5 mg/d. Observation group was given Methylprednisolone sodium succinate injection 1000 mg intravenously,once a day;7 d lat-er,they were given Methylprednisolone tablet 60 mg,orally,qd,gradually decreasing to 5 mg/d. The treatment course in eaeh group was 1 month. The nerve function recovery time,pyramidal tract conduction function,sensory disturbance scores,clinical ef-ficacy and ADR were compared between 2 groups. RESULTS:After treatment,the response rate of observation group was signifi-cantly higher than that of control group(93.10% vs. 79.31%);the time of muscle strength improvement≥grade 2,walking down the ground,urination and defecation function recovery in observation group were all significantly shorter than control group,with statistical significance(P0.05). CONCLUSIONS:Based on conventional treatment,large-dose of methylprednisolone plus therapy shows good efficacy in the treatment of acute myelitis,which can helps to improve pyramidal tract conduction function of patients with acute myelitis,ease sensory disturbance,promote the nerve functional recovery with good safety.
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Objective To evaluate the clinical efficacy of microwave ablation and surgical resection for the treatment of early primary hepatocellular carcinoma (HCC).Methods The Cochrane Library, Medline,PubMed, Web of Science, China National Knowledge Infrastructure, Wanfang database, VIP database were searched with the key words of tumor, liver cancer, primary hepatic carcinoma, hepatocellular carcinoma, HCC,surgery, surgical, surgical resection, liver resection, hepatic resection, thermal ablation, percutaneous thermal ablation, microwave coagulation, microwave ablation, 肝癌, 原发性肝癌, 肝细胞癌, 手术, 切除, 手术切除, 肝切除, 微波, 热消融, 微波治疗, 微波凝固, 微波消融 between the database establishment and February 2015.Chinese and English literatures on microwave ablation and surgical resection for the treatment of early primary HCC were retrieved, and data were extracted and analyzed by 2 independent researchers.All the patients were divided into the microwave ablation group and the surgical resection group.Measurement data were represented by the standardized mean difference (SMD) and 95％ confidence interval (CI), and count data were represented by the odds ratio (OR) and 95％ CI.Heterogeneity of the publication was analyzed using the I2 test.Results Seven literature including 6 retrospective cohort studies and 1 randomized controlled trial were retrieved, and total sample size were 993 patients including 648 in the microwave ablation group and 345 in the surgical resection group.There were significant differences in the volume of blood loss and duration of postoperative hospital stay between the2groups (SMD=-5.03,-1.74, 95％ CI:-6.21-3.85,-2.21--1.28, P＜0.05).There were no significant difference in the incidence of postoperative complications, 1-, 3-year overall survival rates, 1-, 3-year tumor-free survival rates and 1-, 2-, 3-year recurrence rates between the 2 groups (OR =1.57, 1.10, 1.20,0.77, 1.23, 1.32, 2.31, 1.39, 95％CI: 0.25-9.78, 0.43-2.86, 0.70-2.06, 0.19-3.12, 0.54-2.81,0.62-2.80, 0.96-5.55, 0.47-4.14, P ＞ 0.05).Conclusions The safety, feasibility and clinical efficacy of microwave ablation for the treatment of early primary HCC is comparable to surgical resection, and microwave ablation has the advantages of lesser blood loss and shorter duration of hospital stay.
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Objective To identify the rate of hepatitis B virus (HBV) reactivation and potential risk factors in hepatitis B surface antigen negative/hepatitis B core antibody positive patients with lung cancer receiving adjuvant chemotherapy without concomitant antiviral prophylaxis.Methods The records of 3280 patients with lung cancer who received adjuvant chemotherapy were retrospectively reviewed from January 2003 to December 2011.Among these patients,367 hepatitis B surface antigen negative/hepatitis B core antibody positive patients were analyzed for the HBV reactivation in this study.The HBV serology marker and biochemical tests of the 367 patients were performed.The data were analyzed by chi square test.Results Among 367 hepatitis B surface antigen negative/hepatitis B core antibody positive patients with lung cancer,14 patients suffered HBV reactivation.Univariate analysis showed that age≥70 years(x2 =13.003,P=0.019),abnormal liver computed tomography findings (x2 =11.225,P =0.026) and the amount of corticost eroids≥ 150 mg(x2 =7.008,P =0.033)were associated with HBV reactivation.However,gender and adjuvant chemotherapy regimens were not related with HBV reactivation.Conclusion HBV reactivation occurs in a proportion of hepatitis B surface antigen negative/hepatitis B core antibody positive patients with lung cancer during adjuvant chemotherapy.
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Objective To investigate the association of C-reactive protein (CRP) gene polymorphisms and plasma hs-CRP level,and effect on the genetic susceptibility of ischemic stroke (IS).Methods A case-control study was conducted and 548 patients with acute ischemic stroke and 993 agematched controls from community-based population were included in this study.Epidemiological questionnaires were managed to collect for demographic information.Blood pressure was measured and blood glucose,triacylglycerol,cholesterol,and high sensitivity C-reaction protein (hs-CRP) were detected.Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for genotyping of CRP gene in all participants.Results The levels of plasma hs-CRP and the proportion of elevated plasma hs-CRP (≥3.0 mg/L) in the ischemic stroke patients (3.534 ± 3.484) mg/L (43.1％) were significantly higher than those of controls (1.957 ±2.344) mg/L (16.6％),t =9.475,P ＜ 0.01,x2 =128.326,P ＜ 0.01.The results of association analysis indicated that rs3093059 and rs3091244 of CPR gene presented statistical associations with ischemic stroke.After correction for confounding factors,ORs (95％ CI) of additive model and dominant model of rs3093059 were 0.697 (0.528-0.921),0.671 (0.487-0.923) respectively.ORs 95％ CI) of dominant model of rs3091244 was 0.728 (0.536-0.988).Further analysis indicated the polymorphism of rs876537,rs3093059,rs3091244 of CPR genotyping were significantly associated with plasma hs-CRP elevation (≥ 3.0 mg/L) both in ischemic stroke patients and in controls (P ＜0.05).Conclusion The CRP genetic polymorphisms were negatively associated with ischemic stroke,and positively corrleted with plasma hs-CRP elevation.However,plasma hs-CPP was positively correlated with ischemic stroke.These results suggested that the plasma hs-CRP levels might be accompanied by ischemic stroke.
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The clinical data and findings in MRI enhanced scanning of 16 patients with meningeal carcinomatosis were analyzed retrospectively.Meningeal carcinomatosis with subacute- or chronic-onset deteriorated progressively presenting the characteristics of intracranial hypertension and meningeal irritation.Fourteen out of 16 patients showed abnormal linear and strip signal enhancement of meninges by enhancement scanning.Meningeal carcinomatosis presented in diversified patterns and contrast-enhanced MRI is of referential value for the diagnosis of the disease.
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The concept of the health promoting hospital, a modern mode of medical service that has turned from the formerly unitary pattern of medical treatment to the health promoting and life quality improving pattern of medical treatment, prevention and health care, was proposed by modern medical institutions so as to keep up with the change in medical modes and medical socialization. In recent years, many countries in the world have adopted the advanced service ideas of the health promoting hospital and conducted active research on various specific subjects. The paper gives an account of the concept, basic theories, development history, and latest progress both at home and abroad of the health promoting hospital so as to give an impetus to health education and health promotion in China.
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Objective To investigate the feature of distribution of vesicular monoamine transporter(VMAT2) in human embryonic brains and their relationships with Parkinson disease.Methods The distribution of VMAT2 and tyrosine hydroxylase (TH) in substantia nigra pars compacta(SNC), ventral tegmental ares(VTA) and locus coeruleus(LC) were examined by immunohistochemical staining and Western blot in human spontaneous abortion embryonic brains of different gestational age.Results The distribution of VMAT2 in SNc was less than that in both VTA and LC(all P