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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 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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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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Objective:To investigate the therapeutic efficacy of Golimumab in the treatment of children with refractory juvenile dermatomyositis(JDM).Methods:The clinical data of a child diagnosed with JDM in the Department of Allergy, Immunology and Rheumatology of Guangzhou Women and Children′s Medical Center in February 2019 were collected.The treatment effect was studied and literature review was conducted.Results:The patient was a 7-year-old boy with subacute onset of the disease.The illness protracted, and main manifestations included skin rashes, limb weakness, and swallowing dysfunction.Physical examination showed heliotropic rashes, Gottron papules, positive Gower, proximal limb muscle strength grade Ⅲ-Ⅳ, distal limb muscle strength grade Ⅳ, and a choking cough when swallowing fluid food.Laboratory tests revealed alanine aminotransferase (ALT) of 36 U/L, aspartate aminotransferase (AST) of 115 U/L, alkaline phosphatase of 69 U/L, lactate dehydrogenase of 941 U/L, creatine kinase of 974 U/L, hypersensitive C-reactive protein of 26 mg/L and an erythrocyte sedimentation rate (ESR) of 52 mm/1 h. Antinuclear antibody spectra were negative.Electromyography suggested myogenic damage.Thigh magnetic resonance imaging indicated diffuse abnormal signal shadows in the subcutaneous fat, muscles and muscle spaces of both hips, thighs and knee joints.The child was diagnosed with JDM, and given standardized treatment of Methylprednisolone, intravenous immunoglobulin, Methotrexate and Hydroxychloroquine sulfate.However, after the treatment, the facial rashes were still red, proximal limb muscle strength and swallowing dysfunction did not improve, the choking cough symptom still existed, and a Cushing face appeared.Recheck results showed ALT of 24 U/L, AST of 32 U/L, alkaline phosphatase of 56 U/L, lactate dehydrogenase of 216 U/L, creatine kinase of 527 U/L, hypersensitive C-reactive protein of 8 mg/L and an ESR of 15 mm/1 h. Refractory JDM was considered.After negotiating with the patient′s family members, they agreed to treat the patient with Golimumab 50 mg by subcutaneous injection once a month.Then tapered prednisone gradually, stopped Hydroxychloroquine sulfate tablets and continued to give the patient oral Methotrexate.After two doses of Golimumab 50 mg, proximal limb muscle strength and swallowing function improved markedly.After the third subcutaneous injection of Golimumab, proximal limb muscle strength improved to grade Ⅳ-Ⅴ, and he was able to go up and down stairs, squat and stand up after squatting.Besides, dysphagia and the choking cough disappeared, and skin rashes improved.Recheck results suggested a normal ESR and creatine kinase levels.Magnetic resonance imaging of thighs indicated no muscle inflammation.Conclusions:Golimumab works well in the treatment of refractory JDM and can effectively improve muscle strength.Therefore, it can be used as a treatment option for refractory JDM.
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Objective To evaluate the effect of propofol on the expression of programmed death-ligand-1 (PD-L1) in pancreatic cancer cells and the relationship with NMDA/Ca2+/calmodulin-dependent protein kinase Ⅱ (CaMK Ⅱ)/hypoxia-inducible factor-1α (HIF-1α) pathway.Methods Human pancreatic cancer cells were divided into 5 groups (n=16 each) by a simple random sampling method:control group (group C),propofol group (group P),KN93 (CaMK Ⅱ inhibitor) group,MK801 (NMDA receptor antagonist) group and propofol plus rapastinel (NMDA receptor agonist) group (group PR).Cells were cultured in DMEM supplemented with 10％ fetal bovine serum in group C.Cells were incubated for 8 h with 50 μmol/L propofol in group P.Cells were incubated for 8 h with 10 μmol/L KN93 in group KN93.Cells were incubated for 8 h with 500 μmol/L MK801 in group MK801.Cells were incubated for 8 h with 50 μmol/L propofol and 20 μmol/L rapastinel in group PR.After the end of treatment in each group,the cell viability was measured using CCK8 assay,the expression of PD-L1,HIF-1α,CaMK Ⅱ and phosphorylated CaMK Ⅱ (p-CaMK Ⅱ) was detected by Western blot,and intracellular calcium concentrations were determined by Fluo3/AM probe.Results Compared with group C,the cell viability was significantly decreased,the expression of PD-L1,HIF-1α and p-CaMK Ⅱ was down-regulated,and intracellular calcium concentrations were decreased in P,KN93 and MK801 groups (P＜0.05),and no significant change was found in group PR (P＞0.05).Compared with group P,the cell viability was significantly enhanced,the expression of PD-L1,HIF-1α and p-CaMK Ⅱ was up-regulated,and intracellular calcium concentrations were increased in group PR (P＜0.05).Conclusion The mechanism by which propofol inhibits the malignant potential of pancreatic cancer cells may be related to inhibiting NMDA/CaMK Ⅱ/HIF-1α pathway and down-regulating PD-L1 expression.
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Objective To analyze the relationship between Notch signaling pathway and levels of lymphocytes and cytokines in children with juvenile idiopathic arthritis (JIA),and to explore its role in the pathogenesis of JIA.Methods Thirty-five pediatric patients with JIA [males 20 cases,females 15 cases;aged (6.5 ±4.0) years old,(0.83-15.00 years old)] and 15 healthy children [males 6 cases,females 9 cases;aged (5.0 ± 2.9) years old,(1.0-11.0 years old)] from November 2015 to February 2016 in Guangzhou Women and Children's Medical Center were included in the study.The JIA group were divided into the systemonset JIA(So-JIA) group (22 cases) and psoriatic JIA(p-JIA) group (13 cases,polyarthritis 7 cases and oligoarthritis 6 cases).The expressions of Notch signaling's receptor,ligand and target gene mRNA in peripheral blood monouclear cells (PBMC) from the JIA group and the control group were determined by quantitative real-time PCR.The levels of cytokines interleukin (IL)-1 β,IL-10,IL-6,IL-17,IL-4 and transforming growth factor-β (TGF-β) were detected by enzyme-linked immunosorbent assay.Results Compared with the healthy control group,the Notch2 receptors (1.6 ± 3.2 vs.0.4 ± 0.3) expression level,Jagged1 ligand (44.0 ± 79.0 vs.11.3 ± 1.2) expression levels and the levels of target gene HES1(0.4 ±0.3 vs.0.1 ± 0.1) mRNA in the JIA group showed a significant increase,and the differences were all statistically significant (all P ＜0.05).Compared with the healthy control group,the JIA group showed an increased level of IL-1β [(182.22 ± 309.13) ng/L vs.(54.71 ± 20.33) ng/L],IL-10 [(32.99 ± 34.28) ng/L vs.(22.68 ±4.56) ng/L],IL-6 [(100.48 ±305.57) ng/L vs.(13.98 ±2.78) ng/L],IL-17 [(9.11 ± 17.57) ng/L vs.(2.42 ±0.29) ng/L] and TGF-β [(14.37 ±9.33) ng/L vs.(5.49 ±4.49) ng/L],and there were statistically significant differences (all P ＜ 0.05).The expression level of HES1 mRNA was positively correlated with STAT3 mRNA in the So-JIA group (r =0.573,P ＜0.05).The expression level of HES1 mRNA was positively correlated with CD3 + T(r =0.528),CD19 + B (r =0.480),CD3 + CD4 + TH(r =0.457) and CD16 + CD56 + NK (r =0.598) cell absolute count in the So-JIA group (all P ＜0.05).The expression level of HES1 mRNA was positively correlated with CD3 + T cell absolute count in the p-JIA group (r =0.577,P ＜ 0.05).Conclusion Imbalance between Notch pathway and lymphocytes and cytokines in children with JIA may play an important role in the pathogenesis of JIA.
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Objective Macrophage activation syndrome (MAS) is a severe, potentially life-threatening clinical condition. The clinical features including precipitating events, clinical presentations, treatment strategies, outcome in systemic onset juvenile idiopathic arthritis (So-JIA) children with MAS were reviewed. Perforin A91V gene analysis was also performed. Methods Retrospective review of fourteen MAS cases with So-JIA from 2003 to 2008 from a collected database. Gene-specific polymerase chain reaction ( PCR) primers were used to analyze the perforin A91V gene polymorphism. Results Fourteen patients with age from 4 months to 12 years were considered to have evidence of MAS. Nine of them were boys. The primary diagnosis was systemic onset juvenile idiopathic arthritis. No medication was identified as trigger. Eleven of them had infections prior to MAS. Among them specific infectious agents were identified in four patients. High fever, new onset of hepatosplenomegaly, lymphadenopathy, liver function abnormality, abnormal lipid metabolism and hemophagocytosis were common clinical features. Two cases presented with acute respiratory distress syndrome (ARDS). Multiple organ failure (MOF) occurred in three cases. Three patients died. The variant form (NCBI: SNP rs35947132) of perforin A91V gene was detected in seven systemic onset juvenile idiopathic arthritis compolicated with MAS cases. However no mutation was detected. Clucocorticoid, intravenous immunoglobulin, immunoimpressive therapy were effective treatment of this condition. Plasmapheresis (HP) was successfully used in one case with severe MAS. Conclusions MAS is a rare and potentially fatal complication of childhood rheumatoid diseases such as systemic onset juvenile idiopathic arthritis. In this series, majority of them were male and most of them were preceded by infection. Bone marrow studies support the diagnosis. MOF may be a poor prognostic sign of So-JIA. Aggressive and early therapy is essential. There is no relationship between the variant form (NCBI: SNP rs35947132) of perforin A91V gene and So-JIA with MAS in this small sample's study. More research need to be done by increasing sample's numbers.