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Objective:To investigate the relationship between serum uric acid (SUA) and 3-month outcomes in patients with acute ischemic stroke undergoing intravenous thrombolysis.Methods:A total of 386 patients with acute ischemic stroke received intravenous thrombolysis therapy from 1 January 2017 to 31 December 2019 in the Affiliated Hospital of Lianyungang, Xuzhou Medical University were enrolled prospectively. The National Institute of Health Stroke Scale (NIHSS) was used to evaluate the severity of stroke. The functional outcome was evaluated by the modified Rankin Scale at discharge or 3 months after onset. Pearson′s correlation was used to assess the relationship between SUA and NIHSS scores at baseline and discharge. Propensity score matching was used to balance confounding factors. Multivariate logistic regression model was used to identify the correlation between SUA and prognostic outcome after thrombolysis.Results:A total of 386 eligible patients were included. Two hundred and thirty patients (59.6%) had good outcomes in the follow-up after 3 months. The levels of SUA are negatively associated with the NIHSS score at discharge ( r=-0.171, P=0.003). A positive correlation was observed between the levels of SUA and the difference of NIHSS at baseline and discharge ( r=0.118, P=0.032). Patients were divided into three groups according to the quartile of SUA. Multivariate logistic regression analysis showed that high SUA levels were independently associated with good outcome three months after stroke ( OR=0.421, 95% CI 0.327-0.541, P<0.001). Conclusion:In patients with acute ischemic stroke, elevated SUA levels can predict better recovery and short-term outcomes in patients undergoing intravenous thrombolysis.
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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 correlation and predictive value of serum uric acid (SUA) and short-term clinical outcomes after intravenous thrombolysis in patients with acute ischemic stroke (AIS).Methods:Patients with AIS received intravenous thrombolysis in the First Affiliated Hospital of Kangda College of Nanjing Medical University from July 1, 2018 to March 31, 2022 were retrospectively enrolled. Fasting SUA, blood glucose and blood lipids were measured the next morning after admission. The modified Rankin Scale was used to evaluate the functional outcome at discharge. 0-2 points were defined as good outcome, and 3-6 points were defined as poor outcome. Multivariate logistic regression analysis was used to determine the independent risk factors for poor short-term outcome in patients with AIS after intravenous thrombolysis. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of SUA for poor short-term outcome after intravenous thrombolysis. Results:A total of 291 patients were enrolled during the study. Among them, 197 (67.70%) were male, aged 65.02±11.56 years. The median baseline National Institutes of Health Stroke Scale (NIHSS) score was 5 (interquartile range 3-11), and the SUA was 322.06±90.54 μmol/L. Univariate analysis showed that the age, proportions of patients with atrial fibrillation and cardiogenic embolism, baseline fasting blood glucose and NIHSS scores in the poor outcome group were significantly higher than those in the good outcome group, while the SUA after intravenous thrombolysis was significantly lower than that in the good outcome group (all P<0.05). Multivariable logistic regression analysis showed that higher SUA was independently associated with the good outcomes (odds ratio [ OR] 0.986, 95% confidence interval [ CI] 0.985-0.991; P<0.01), while older age ( OR 1.047, 95% CI 1.021-1.075; P<0.01) and baseline NIHSS score ( OR 1.155, 95% CI 1.063-1.254; P<0.01) were independently associated with the poor outcomes. ROC curve analysis showed that the area under the curve of poor outcome predicted by SUA was 0.642 (95% CI 0.552-0.732; P=0.002), the best cutoff value was 307.45 μmol/L, and the sensitivity and specificity of prediction were 57.7% and 68.0% respectively. Conclusion:Higher SUA is associated with the short-term outcome of patients with AIS after intravenous thrombolytic therapy, but its predictive value of the outcomes is limited.
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Objective@#To assess the relationship between hemoglobin A1c (HbA1c) and hemorrhagic cerebral infarction (HI) in patients with acute cerebral infarction.@*Methods@#From January 2014 to June 2016, in the Lianyungang Hospital Affiliated to Xuzhou Medical University, 426 patients with acute anterior circulation infarction were included. The blood sugar status before stroke was expressed by HbA1c. HbA1c and fasting blood glucose (FBG) were measured on the second day after admission. The National Institutes of Health Stroke Scale (NIHSS) was used to assess the severity of neurological function at admission. The modified Rankin scale (mRS) was used to evaluate the prognosis at discharge. CT or MRI/SWI examination was performed to determine whether there was HT. Logistic regression was used to evaluate the risk factors for HT and short-term prognosis after cerebral infarction.@*Results@#Of the 426 patients enrolled, 93 (21.8%) appeared HT, 60 (14.1%) had hemorrhagic cerebral infarction (HI) and 33 (7.7%) had parenchymal hemorrhage (PH). Multivariate analysis showed that HbA1c and infarct volume were independent predictor of HT. When patients were grouped according to fasting blood glucose (FBG<7.8 mmol/L or ≥ 7.8 mmol/L), the predictive effect of HbA1c on HT was found in both groups. In multiple Logistic regression analysis, HbA1c was also a predictor of poor prognosis after stroke (OR=1.482, 95% CI 1.228 -1.788).@*Conclusions@#In patients with ischemic stroke, elevated HbA1c is independently associated with post-infarction HT, and this result doesn′t change even in patients with well-controlled blood glucose. HbA1c is also a predictor of poor prognosis after stroke. These findings are important for blood glucose management in patients with diabetes and acute anterior circulation infarction.
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Objective To assess the relationship between hemoglobin A1c (HbA1c) and hemorrhagic cerebral infarction (HI) in patients with acute cerebral infarction.Methods From January 2014 to June 2016,in the Lianyungang Hospital Affiliated to Xuzhou Medical University,426 patients with acute anterior circulation infarction were included.The blood sugar status before stroke was expressed by HbA1c.HbA1c and fasting blood glucose (FBG) were measured on the second day after admission.The National Institutes of Health Stroke Scale (NIHSS) was used to assess the severity of neurological function at admission.The modified Rankin scale (mRS) was used to evaluate the prognosis at discharge.CT or MRI/SWI examination was performed to determine whether there was HT.Logistic regression was used to evaluate the risk factors for HT and short-term prognosis after cerebral infarction.Results Of the 426 patients enrolled,93 (21.8％) appeared HT,60 (14.1％) had hemorrhagic cerebral infarction (HI) and 33 (7.7％) had parenchymal hemorrhage (PH).Multivariate analysis showed that HbA1c and infarct volume were independent predictor of HT.When patients were grouped according to fasting blood glucose (FBG ＜ 7.8 mmol/L or ≥ 7.8 mmol/L),the predictive effect of HbA1c on HT was found in both groups.In multiple Logistic regression analysis,HbA1c was also a predictor of poor prognosis after stroke (OR =1.482,95％ CI 1.228-1.788).Conclusions In patients with ischemic stroke,elevated HbA1c is independently associated with post-infarction HT,and this result doesn't change even in patients with well-controlled blood glucose.HbA1c is also a predictor of poor prognosis after stroke.These findings are important for blood glucose management in patients with diabetes and acute anterior circulation infarction.
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Mesenchymal stem cells are a kind of pluripotent stem cells that play a role in stroke treatment mainly through paracrine mechanisms. Recent studies have shown that mesenchymal stem cell-derived exosomes play an important role in reducing post-stroke injury, promoting neural repair and angiogenesis. This article describes the research progress of bone marrow mesenchymal stem cell-derived exosomes in the treatment of stroke, and investigates the therapeutic mechanism and application prospects of exosomes bioactive substances represented by microRNAs.
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Exosomes are extracellular vesicles released from various cellular sources and are widely present in body fluids. Bioactive substances such as microRNAs, mRNAs, and proteins are encapsulated in exosomes, which can activate various signaling pathways and play important roles in early warning of stroke and neurovascular unit repair. This article reviews the signal transduction of exosomes in cerebral ischemia.
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Objective To evaluate the relationship between short-term blood pressure variability and poor outcome and hemorrhagic transformation after intravenous thrombolysis in patients with acute ischemic stroke.Methods The Databases such as Wanfang,CNKI,Cochrane,Pubmed,EMBASE,and Web of Science were retrieved.The randomized controlled trials,cohort studies and case-control studies about blood pressure monitoring after intravenous thrombolytic therapy in patients with acute ischemic stroke and calculation and analysis of blood pressure variability were enrolled.The deadline for retrieval was December 2017.STATA 13.0 software was used to conduct Meta-analysis.Results A total of 9 non-randomized controlled trials with 19 161 patients were included.Four of them were prospective studies and 5 were retrospective studies.The relationship between short-term blood pressure variability and poor outcome (defined as a modified Rankin scale score ＞2) were investigated in 8 studies (a total of 19 045 patients).The relationship between short-term blood pressure variability and hemorrhagic transformation were investigated in 6 studies (with 18 456 patients).The results of Meta-analysis showed that short-term systolic blood pressure variability (every 10 mmHg change;1 mmHg =0.133 kPa) and poor outcome (odds ratio [OR] 1.55,95％ confidence interval [CI] 1.22-1.86;P ＞0.001),hemorrhagic transformation (OR 2.39,95％ CI 1.71-3.35;P =0.025),and symptomatic intracranial hemorrhage (OR 2.49,95％ CI 1.39-4.39;P =0.048) had significant correlations.Conclusion The increased short-term blood pressure variability after intravenous thrombolysis in patients with acute ischemic stroke is associated with poor outcome,hemorrhagic transformation,and symptomatic intracranial hemorrhage.
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Objective To explore the effects of extracellular regulated protein kinase 1/2 (ERK1/2) signal pathway on cardiomyocyte apoptosis and tumor necrosis factor-α (TNF-α) expression at different glucose-lowing rates,and the influence of glucose-lowing rate on cardiomyocyte injury and inflammatory secretion function,as well as its mechanism.Methods Cardiomyocytes of Wistar neonate rat were maintained in medium supplemented with 25 mmol/L glucose for 72 h.Then the medium was changed to different concentrations of glucose and all cells were divided into five groups.Group A was control group whose medium supplemented with 25 mmol/L glucose.Medium of group B,C,D,E was supplemented with 20,15,10,5 mmol/L glucose (glucose-lowing rate was 5,10,15,20 mmol/L) respectively.Survival rate of cardiomyocyte was measured by CCK8 kit.Cardiomyocyte apoptosis was measured by flow cytometry instrument and laser confocal microscope after Annexin V-PI.TNF-α was measured by ELISA.ERK1/2 protein and phosphorylation were measured by Western blot.Cardiomyocyte apoptosis and TNF-α levels were measured again after U0126 was added.Results At the same time point,along with the glucose-lowing rate increased,survival rate of cardiomyocyte in group A was increased and those in group C,D,E were decreased (P＜ 0.05).TNF-α concentration was increased in group B,C,D and decreased in group E.After 24 h,apoptosis rate decreased in group B and increased in group C,D,E (P＜0.05).ERK1/2 phosphorylation level increased in group B,D,and E(P＜0.05).The ERK1/2 phosphorylation level in group B was the lowest.After U0126 was added,survival rates of cardiomyocyte in all groups were increased (P＜0.01) while TNF-α concentrations were decreased (P＜0.05).In every group,survival rate of eardiomyocyte after 48 h was lower than that after 3 h and 24 h,while TNF-α concentration was higher (P＜0.05).Conclusion Influence of glucose-lowering rate for cardiomyocyte apoptosis and TNF-o is caused by ERK1/2 pathway.In the glucose-lowering course,ERK1/2 pathway promotes cardiomyocytes apoptosis and TNF-α secretion is related with not only osmotic pressure,but also ERK1/2 signal pathway activation as well.
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One hundred and fifty-one type 2 diabetic patients with coronary heart disease ( T2 DMC) and 142 cases of type 2 diabetes mellitus were included for analyzing the influence of different glucose-lowering rates on MB isoenzyme of creatine kinase (CKMB) and muscle hemoglobin level changes to search for the rational glucose-lowering rate.The level of CKMB in type 2 deabetes mellitus group was significantly lower( P＜0.05 ) at follow-up than that before and after intensive therapy.In type 2 diabetes mellitus group,when the fasting or postprandial glucose-lowering rate was not greater than 6 mmol· L-1 · d-1,the level of CKMB and muscle hemoglobin were significantly lower at follow-up than that before intensive therapy ( P＜0.05 ).When the fasting glucose-lowering rate is greater than 6 mmol· L-1 · d-1,the level of CKMB is significantly higher after intensive therapy than that before glucose-lowering ( P＜0.05 ).In T2DMC group,when the fasting or postprandial glucose-lowering rate was not greater than 4 mmol· L-1 · d-1,the level of CKMB and muscle hemoglobin was significantly lower at follow-up than that before intensive therapy(P＜0.05 or P＜0.01 ),buthigher at follow-up when the fasting glucose-lowering rate was greater than 4 mmol· L-1 · d-1(P＜0.05).
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Objective To compare the changes of high sensitive-C reactive protein (hs-CRP) and cardiac troponin Ⅰ ( cTn Ⅰ ) levels before and after intensive therapy in patients with type 2 diabetes,and to find out the reasonable glucose-lowering rate.Methods One hundred and thirty-two cases of type 2 diabetes( T2DM group) and 135 cases of type 2 diabetes with coronary heart disease( T2DM+CHD group) received intensive therapy.After testing hs-CRP and cTn Ⅰ levels,the variations were analyzed.Results The ranges of the change in cTn Ⅰ and hs-CRP levels were different under four glucose-lowering rates in the T2DM+CHD group( P＜0.05 ).cTn Ⅰ and hs-CRP levels were higher than those before intensive therapy in the T2DM+CHD group with glucose-lowering rate greater than 4.0mmol· L-1 · d-1.The other two subgroups with glucose-lowering rate less than 4.0 mmol· L-1 · d-1 showed decreased cTn Ⅰ and hs-CRP levels.While at the end of 3 months follow-up,cTn Ⅰ and hs-CRP levels were all significantly lower than those before intensive therapy in four subgroups ( P＜0.05 ).Conclusions The increase of cardiovascular events after intensive therapy may be due to excessively fast glucose-lowering rate.The reasonable glucose-lowering rate for patients with type 2 diabetes should depend on whether there is accompanying coronary heart disease.For type 2 diabetes with coronary heart disease,excessively fast glucose-lowering rate could lead to acute rise ofcTn Ⅰ and hs-CRP levels,which causes myocardial injury.The mechanism of myocardial injury resulted from excessively fast glucose-lowering rate may be due to activation of the inflammatory pathway.In type 2 diabetes with coronary heart disease,long-term good control of blood glucose could alleviate inflammatory response and cardiac damage resulted from excessively fast glucose-lowering rate.
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Objective To explore the influence of glucose-lowering rate on left ventricular function in patients with type 2 diabetes mellitus (T2DM). Methods One hundred and thirty-two cases of type 2 diabetes mellitus and 135 cases of type 2 diabetes mellitus with coronary heart disease (T2DM+CHD)received intensive glucose lowering therapy. Then, after measuring left ventricular ejection fraction (LVEF) and E/A ratio, the variation was analyzed. Results LVEF was significantly higher than that before intensive therapy in T2DMsubgroup with glucose-lowering rate less than 6 m mol · L-1 · d-1( P＜0.05 ). So was T2DM+CHD subgroup with glucose-lowering rate less than 4 mmol· L-1 · d-1 (P＜0.05). LVEF was significantly lower than that before intensive therapy in T2DM+CHD subgroup with glucose-lowering rate greater than 4 mmol · L-1 · d-1( P＜0. 05 ),while by the end of following up for 3 months, LVEF stepped up and no significant difference was observed between subgroups ( P ＞ 0. 05 ). The E/A ratio stepped up in both subgroups after intensive therapy ( P ＜ 0. 05 ).Conclusions For T2DM patients with coronary heart disease, excessively fast glucose-lowering rate may impair left ventricular function. Long-term good control of blood glucose restores the impaired left ventricular function causes by excessively fast glucose-lowering rate. After intensive therapy, left ventricular diastolic function finally improves in both subgroups regardless of the glucose-lowering rate and coronary heart disease.
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The difference in serum calcium levels between patients with typical hyperthyroidism and apathetic hyperthyroidism was analyzed. Serum calcium levels in patients with apathetic hyperthyroidism were higher than those in patients with typical hyperthyroidism, while bone-specific alkaline phosphatase levels were lower. The atypical manifestation of apathetic hyperthyroidism may be due to the significant elevation of serum calcium level.