ABSTRACT
Ischemic stroke stands as a prevalent neurological ailment, where a paucity of methodologies exists for the assessment of functional outcomes post-stroke. Our objective was the development of a WeChat applet for the evaluation of muscle strength and the subsequent evaluation of its validity in ischemic stroke patients experiencing motor dysfunction. The assessment encompassed Lovett and NIHSS, followed by muscle strength values (MSV) and muscle strength ratios (MSR). These metrics were then scrutinized in relation to NIHSS and Lovett, followed by examination of their interrelationships. We enrolled a cohort of 157 patients, with an average age of 65 years, consisting of 96 males and 61 females. Lovett scores in the range of 2-4 and NIHSS scores spanning from 0 to 3 were found to correspond to specific values of MSV and MSR, respectively. Upon conducting correlation analysis, we noted that both MSV and MSR exhibited significant positive correlations with Lovett scores and NIHSS. Remarkably, the correlation of MSR with Lovett scores or NIHSS surpassed that of MSV. The WeChat applet offers a means of digitization and visualization of muscle strength. It correlates well with Lovett score and NIHSS, especially MSR. This bears potential significance in guiding the rehabilitation of stroke patients.
Subject(s)
Brain Ischemia , Ischemic Stroke , Stroke , Male , Female , Humans , Aged , Severity of Illness IndexABSTRACT
To determine the possible risk factors for post-stroke depression in patients with mild and moderate acute strokes. A cross-sectional descriptive study was conducted involving 129 patients with mild and moderate acute strokes. The patients were divided into post-stroke depression and non-depressed stroke groups according to the Hamilton Depression Rating Scale for Depression-17 item and Patient Health Questionnaire-9 item assessments. All participants were evaluated based on clinical characteristics and a battery of scales. Patients with post-stroke depression had an increased stroke frequency, severe stroke symptoms and poor performance in activities of daily living (ADL), cognitive function, sleep quality, interest in pleasurable activities, negative life events, and utilization of social support compared to stroke patients without depression. The Negative Life Event Scale (LES) score was significantly and independently associated with an increased probability of depression in stroke patients. Negative life events were shown to be independently associated with the incidence of depression in patients with mild and moderate acute strokes, likely mediating the influence of other predictors of depression, such as a history of stroke, decreased ADL ability, and utilization of support.
Subject(s)
Activities of Daily Living , Stroke , Humans , Cross-Sectional Studies , Depression/epidemiology , Depression/etiology , Risk Factors , Stroke/complicationsABSTRACT
Septic acute kidney injury (AKI) is commonly associated with renal dysfunction and high mortality in patients. Owing to the rapid and violent occurrence of septic AKI with inflammation, there are no effective therapies to clinically treat it. Embelin, a natural product, has a potential regulatory role in immunocytes. However, the role and mechanism of embelin in septic AKI remains unknown. This study aimed to elucidate the role of embelin in macrophage regulation in lipopolysaccharide (LPS)-induced septic AKI. Embelin was intraperitoneally administered to mice after LPS injection. And bone marrow-derived macrophages (BMDMs) were subsequently isolated from the mice to explore the immunomodulatory role of embelin in macrophages. We found that embelin attenuated renal dysfunction and pathological renal damage in the LPS-induced sepsis mouse model. Molecular docking predicted that embelin could bind to phosphorylated NF-κB p65 at the ser536 site. Embelin inhibited the translocation of NF-κB p65 via phosphorylation at ser536 in LPS-induced AKI. It also reduced the secretion of IL-1ß and IL-6 and increased the secretion of IL-10 and Arg-1 of BMDMs and mice after LPS stimulation, indicating that embelin suppressed macrophage M1 activation in LPS-induced AKI. Therefore, embelin attenuated LPS-induced septic AKI by suppressing NF-κB p65 at ser536 in activated macrophages. This study preclinically suggests a therapeutic role of embelin in septic AKI.
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Binocular vision uses the parallax principle of the human eye to obtain 3D information of an object, which is widely used as an important means of acquiring 3D information for 3D reconstruction tasks. To improve the accuracy and efficiency of 3D reconstruction, we propose a 3D reconstruction method that combines second-order semiglobal matching, guided filtering and Delaunay triangulation. First, the existing second-order semiglobal matching method is improved, and the smoothness constraint of multiple angle directions is added to the matching cost to generate a more robust disparity map. Second, the 3D coordinates of all points are calculated by combining camera parameters and disparity maps to obtain the 3D point cloud, which is smoothed by guided filtering to remove noise points and retain details. Finally, a method to quickly locate the insertion point and accelerate Delaunay triangulation is proposed. The surface of the point cloud is reconstructed by Delaunay triangulation based on fast point positioning to improve the visibility of the 3D model. The proposed approach was evaluated using the Middlebury and KITTI datasets. The experimental results show that the proposed second-order semiglobal matching method has higher accuracy than other stereo matching methods and that the proposed Delaunay triangulation method based on fast point location requires less time than the original Delaunay triangulation.
Subject(s)
Imaging, Three-Dimensional/methods , Vision, Binocular , Algorithms , Computer Simulation , HumansABSTRACT
Option pricing problem is one of the central issue in the theory of modern finance. Uncertain currency model has been put forward under the foundation of uncertainty theory as a tool to portray the foreign exchange rate in uncertain finance market. This paper uses uncertain differential equation involved by Liu process to dispose of the foreign exchange rate. Then an American barrier option of currency model in uncertain environment is investigated. Most important of all, the authors deduce the formulas to price four types of American barrier options for this currency model in uncertain environment by rigorous derivation.
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BACKGROUND: Diabetes is a metabolic disorder that causes a heavy burden on healthcare systems worldwide. The aim of this study was to determine the prevalence of type 2 diabetes and prediabetes and its associated factors among eight communities in Nanchong, China. METHODS: This was an observational cross-sectional study conducted throughout eight communities in Nanchong, China. The participants were 53,288 individuals aged 45 years or older. The participants' characteristics, comorbidities, health behaviors, family history, and dietary intake were assessed. Multinomial logistic regression models were fitted to identify factors associated with type 2 diabetes and prediabetes. RESULTS: The prevalence of diabetes and prediabetes was 13.9% (95% confidence interval [CI], 13.6-14.2) and 3.1% (95% CI, 2.9-3.2) of the population, respectively. After adjusting for other risk factors, advanced age, overweight, obesity, abdominal obesity, comorbidities, smoking, a family history of diabetes, and Chinese cooking vegetable intake were associated with an increased risk of type 2 diabetes and prediabetes. CONCLUSION: The prevalence of type 2 diabetes in the Chinese population is rising compared with data from the past. The risk factors of type 2 diabetes and prediabetes identified in this study will aid the identification of individuals at a high-risk of diabetes and the implementation of effective health promotion programs and campaigns. CLINICAL TRIAL REGISTRY NUMBER: ChiCTR-HOC-17013200.
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As lifespans lengthen, age-related diseases such as cardiovascular disease and diabetes are becoming more prevalent. Correspondingly, the use of contrast agents for medical imaging is also becoming more common, and there is increasing awareness of contrast-associated acute kidney injury (CA-AKI). There is no specific treatment for CA-AKI, and clinicians currently focus on prevention, interventions that alter its pathogenesis, and identification of risk factors. Although the incidence of CA-AKI is low in the general population, the risk of CA-AKI can reach 20% to 30% in patients with multiple risk factors. Many models have been applied in the clinic to assess the risk factors for CA-AKI, enable identification of high-risk groups, and improve clinical management. Hypotonic or isotonic contrast media are recommended to prevent CA-AKI in high-risk patients. Patients with risk factors should avoid using contrast media multiple times within a short period of time. All nephrotoxic drugs should be stopped at least 24 h before the administration of contrast media in high-risk populations, and adequate hydration is recommended for all patients. This review summarizes the pathophysiology of CA-AKI and the progress in diagnosis and differential diagnosis; updates the risk factors and risk factor scoring systems; reviews the latest advances related to prevention and treatment; discusses current problems in epidemiological studies; and highlights the importance of identifying high-risk subjects to control modifiable risk factors and use of a rating scale to estimate the risk and implement appropriate prevention strategies.
Subject(s)
Acute Kidney Injury , Contrast Media , Acute Kidney Injury/chemically induced , Acute Kidney Injury/epidemiology , Acute Kidney Injury/prevention & control , Contrast Media/adverse effects , Humans , Incidence , Risk Factors , Weights and MeasuresABSTRACT
Acute kidney injury (AKI) is a common complication of acute pancreatitis (AP) that is associated with increased mortality. Conventional assessment of AKI is based on changes in serum creatinine concentration and urinary output. However, these examinations have limited accuracy and sensitivity for the diagnosis of early-stage AKI. This review summarizes current evidence on the use of advanced imaging approaches and artificial intelligence (AI) for the early prediction and diagnosis of AKI in patients with AP. CT scores, CT post-processing technology, Doppler ultrasound, and AI technology provide increasingly valuable information for the diagnosis of AP-induced AKI. Magnetic resonance imaging (MRI) also has potential for the evaluation of AP-induced AKI. For the accurate diagnosis of early-stage AP-induced AKI, more studies are needed that use these new techniques and that use AI in combination with advanced imaging technologies.
Subject(s)
Acute Kidney Injury/diagnostic imaging , Acute Kidney Injury/etiology , Diagnostic Imaging/methods , Image Interpretation, Computer-Assisted/methods , Pancreatitis/complications , Acute Disease , Artificial Intelligence , Humans , Kidney/diagnostic imaging , Magnetic Resonance Imaging/methods , Tomography, X-Ray Computed/methods , Ultrasonography/methodsABSTRACT
Objectives: Paraquat (PQ) poisoning can induce mitophagy and pulmonary fibrosis. Cyclosporine A (CsA) is an inhibitor of mitophagy. This study aimed at investigating whether CsA could inhibit PQ-induced mitophagy and pulmonary fibrosis in rats.Materials and Methods: Male Sprague-Dawley (SD) rats were treated with vehicle saline (control), 50 mg/kg PQ by gavage alone, or together with different doses of CsA. At 14 days post-induction, the levels of pulmonary fibrosis and PTEN-induced putative kinase 1 (PINK1) and Parkin expression in individual rats and mitochondrial membrane potential (MMP) in lung cells were measured. Moreover, A549 cells were treated with PQ or PQ + CsA for 24 h and the levels of PINK1, Parkin, fibronectin, collagen I and LC3 I and II expression and MMP were examined. Finally, the impact of PINK1 overexpression on the PQ or PQ + CsA-modulated fibronectin and collagen I expression in A549 cells was tested.Results: PQ exposure significantly increased the levels of hydroxyproline and collagen I expression and collagen fiber accumulation in the lung of rats, which were mitigated by CsA treatment. Furthermore, treatment with CsA significantly improved the PQ-decreased MMP and abrogated PQ-upregulated PINK1 and Parkin expression in the lungs of rats. In addition, CsA treatment decreased the PQ-induced fibrosis and mitophagy and PQ-impaired MMP as well as PQ-upregulated PINK1 and Parkin expression in A549 cells. The later effect of CsA was abrogated by PINK1 overexpression in A549 cells.Conclusions: Therefore, CsA can inhibit the PQ-induced mitophagy and pulmonary fibrosis by attenuating the PINK1/Parkin signaling.
Subject(s)
Cyclosporine/pharmacology , Lung/drug effects , Mitophagy/drug effects , Paraquat/poisoning , Protein Kinases/metabolism , Pulmonary Fibrosis/prevention & control , Ubiquitin-Protein Ligases/metabolism , A549 Cells , Animals , Disease Models, Animal , Humans , Hydroxyproline/metabolism , Lung/metabolism , Lung/pathology , Male , Membrane Potential, Mitochondrial/drug effects , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/metabolism , Pulmonary Fibrosis/pathology , Rats, Sprague-DawleyABSTRACT
OBJECTIVE: To analyze the risk factors of dyslipidemia of adult residents in Shunqing District of Nanchong City. METHODS: A five-stage stratified cluster sampling method was used to select adult residents from 9 communities in the urban area of Shunqing District of Nanchong City from January 2013 to April 2018 for questionnaires survey,physical measurement and laboratory test. Univariate analysis and multivariate logistic regression analysis were used to study the influencing factors of dyslipidemia. RESULTS: A total of 105 956 people was investigated,and the prevalence rate of dyslipidemia was 34.2% (36 272 cases). Among them, the prevalence rate of male was 38.11%, and 31.91% for female ( P<0.01). The proportion of dyslipidemia with hypertension, diabetes, and coronary heart disease was 13.46%, 5.74%, and 0.39%, respectively. The proportion of hypertension with diabetes was 2.79%. Multivariate logistic regression analysis showed that gender (odds ratio ( OR)=1.276, P<0.001), body mass index ( OR=1.052, P<0.001), education level (set ≤elementary school as reference, high school OR=1.094, P<0.001, ≥graduated OR=1.185, P<0.001), smoking history ( OR=1.124, P<0.001), coronary heart disease ( OR=1.189, P<0.001), hypertension ( OR=1.148, P<0.001),sdiabetes ( OR=1.967, P<0.001), and family history of dyslipidemia ( OR=1.760, P<0.001) were the influencing factors of dyslipidemia in residents of this region. Conclusions The dyslipidemia of urban residents in Nanchong area is highly concerned with hypertension, diabetes, and coronary heart disease. Male, obesity, high education level, smoking, coronary heart disease, hypertension, diabetes, and family history of dyslipidemia are risk factors for dyslipidemia in urban residents of Nanchong area. It is necessary to actively target the above risk factors and high-risk groups.
Subject(s)
Dyslipidemias , Adult , China/epidemiology , Diabetes Mellitus/epidemiology , Dyslipidemias/epidemiology , Female , Humans , Hypertension/epidemiology , Male , Obesity/epidemiology , Prevalence , Risk FactorsABSTRACT
Glutathione (GSH) has been studied for its neuroprotection value in several diseases, but the effect of GSH on intracerebral hemorrhage (ICH) is unclear. In this study, we examined the protective effects of GSH in an experimentally induced ICH model and investigated the relative mechanisms. Adult male C57BL/6j mice were randomized into Sham, ICH and GSH treatment groups. GSH was injected with the dose of 50, 100 or 200â¯mg/kg once per day for 3â¯days, starting immediately after operation. The results revealed a GSH-mediated improvement of neurological deficits score (NDS), motor and sensory functions impairment in a dose-dependent manner three days post ICH (pâ¯<â¯0.01, GSH 200 vs ICH. Sham, nâ¯=â¯12; ICH, nâ¯=â¯9; GSH 50, nâ¯=â¯10; GSH 100, nâ¯=â¯10; GSH 200, nâ¯=â¯11) in addition to significantly reduced mortality rate (pâ¯=â¯0.2632, GSH 200 vs ICH. nâ¯=â¯12 per group) and damage volume (pâ¯<â¯0.05, GSH 200 vs ICH. nâ¯=â¯12 per group). GSH treatment also attenuated injury measured by decreased brain edema (pâ¯<â¯0.05, GSH 200 vs ICH. Sham, nâ¯=â¯10; ICH, nâ¯=â¯10; GSH 200, nâ¯=â¯12), blood-brain barrier disruption (pâ¯<â¯0.05, GSH 200 vs ICH. Sham, nâ¯=â¯10; ICH, nâ¯=â¯10; GSH 200, nâ¯=â¯12), and histopathological damage (pâ¯<â¯0.05, GSH 200 vs ICH. Sham, nâ¯=â¯6; ICH, nâ¯=â¯6; GSH 200, nâ¯=â¯8) 72â¯h after ICH. In addition, GSH treatment also decreased cell apoptosis (pâ¯<â¯0.01, GSH 200 vs ICH. Sham, nâ¯=â¯6; ICH, nâ¯=â¯6; GSH 200, nâ¯=â¯8) and resulted in up-regulated protein expression of complex I (pâ¯<â¯0.01, GSH 200 vs ICH. Sham, nâ¯=â¯6; ICH, nâ¯=â¯6; GSH 200, nâ¯=â¯8), which was consistent with an overall up-regulation of complex I function in mitochondria using Oxygraph-2â¯K high resolution respirometry (pâ¯<â¯0.05, GSH 200 vs ICH. Sham, nâ¯=â¯4; ICH, nâ¯=â¯5; GSH 200, nâ¯=â¯6). In conclusion, GSH effectively improved the prognosis of ICH mice by attenuating neurological impairment, decreasing neural damage, and inhibiting apoptosis. The neuroprotection by GSH resulted from the up-regulation of mitochondrial oxidative respiration function. The results of our study suggest that GSH can be a potential therapeutic agent for ICH.
Subject(s)
Cerebral Hemorrhage/drug therapy , Glutathione/pharmacology , Mitochondria/drug effects , Neuroprotection , Neuroprotective Agents/pharmacology , Acute Disease , Animals , Apoptosis/drug effects , Brain Edema/drug therapy , Brain Edema/etiology , Cerebral Hemorrhage/complications , Glutathione/administration & dosage , Male , Mice , Mice, Inbred C57BL , Mitochondria/metabolism , Neuroprotective Agents/administration & dosageABSTRACT
High-pressure phase stability of gallium phosphide was explored under different hydrostatic environments up to 40.0 GPa in a diamond anvil cell. Two irreversible phase transitions from the semiconductor to metal to an amorphous state appear at 19.8 and 31.5 GPa and as well as 22.6 and 35.3 GPa under nonhydrostatic and hydrostatic environments, respectively. Furthermore, the hysteresis effect of the high-pressure phase transition of a sphalerite-structure compound under a hydrostatic environment was disclosed. All of the obtained results can provide new insight into the underlying structural evolution and electrical transport characteristics for the semiconducting compound at different hydrostatic environments.
ABSTRACT
The structural, vibrational, and electronic characteristics in orpiment were performed in the diamond anvil cell (DAC), combined with a series of experimental and theoretical research, including Raman spectroscopy, impedance spectroscopy, atomic force microscopy (AFM), high-resolution transmission electron microscopy (HRTEM), and first-principles theoretical calculations. The isostructural phase transition at ~25.0 GPa was manifested as noticeable changes in the compressibility, bond lengths, and slope of the conductivity, as well as in a continuous change in the pressure dependence of the unit cell volume. Furthermore, a pressure-induced metallization occurred at ~42.0 GPa, accompanied by reversible electrical conductivity. We also determined the metallicity of orpiment at 45.0 GPa by first-principles theoretical calculations, and the results were in good agreement with the results of the temperature-dependent conductivity measurements. The HRTEM and AFM images of the recovered sample confirmed that orpiment remains in the crystalline phase with an intact layered structure and available crystal-shaped clusters. These high-pressure behaviors of orpiment present some crucial information on the structural phase transition, metallization, amorphization and superconductivity for the A2B3-type of engineering materials at high pressure.
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In this study, the vibrational and electrical transport properties of molybdenum diselenide were investigated under both non-hydrostatic and hydrostatic conditions up to â¼40.2 GPa using the diamond anvil cell in conjunction with Raman spectroscopy, electrical conductivity, high-resolution transmission electron microscopy, atomic force microscopy, and first-principles theoretical calculations. The results obtained indicated that the semiconductor-to-metal electronic phase transition of MoSe2 can be extrapolated by some characteristic parameters including abrupt changes in the full width at half maximum of Raman modes, electrical conductivity and calculated bandgap. Under the non-hydrostatic condition, metallization occurred at â¼26.1 GPa and it was irreversible. However, reversible metallization occurred at â¼29.4 GPa under the hydrostatic condition. In addition, the pressure-induced metallization reversibility of MoSe2 can be revealed by high-resolution transmission electron and atomic force microscopy of the recovered samples under different hydrostatic conditions. This discrepancy in the metallization phenomenon of MoSe2 in different hydrostatic environments was attributed to the mitigated interlayer van der Waals coupling and shear stress caused by the insertion of pressure medium into the layers.
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OBJECTIVE: To construct a prediction model for the risk of ischemic stroke (IS) by classification tree model, and evaluate its application value. METHODS: By cluster sampling, 858 IS patients with perfect clinical data from January to December 2017 in the Affiliated Hospital of Guilin Medical College (IS group) were enrolled, and 844 health checkups matched with the gender and age of IS patients in the same period were enrolled as controls (healthy control group). The metabolic characteristics of the two groups were compared and analyzed. The classification tree model was used to construct the prediction model of the risk of IS, and the gain diagram, index chart, risk value of misclassification probability and receiver operating characteristic curve (ROC) were used to evaluate the application value of the model. RESULTS: Compared with the healthy control group, body mass index (BMI), fasting blood glucose (FPG), triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) in IS group were significantly increased [BMI (kg/m2): 25.34±3.70 vs. 24.24±3.10, FPG (mmol/L): 6.79±2.89 vs. 5.73±1.17, TG (mmol/L): 1.62±1.06 vs. 1.44±1.06, TC (mmol/L): 4.70±2.73 vs. 4.35±0.79, LDL-C (mmol/L): 3.18±0.94 vs. 2.73±0.73, all P < 0.01], high density lipoprotein cholesterol (HDL-C) was significantly decreased (mmol/L: 1.12±0.33 vs. 1.35±0.36, P < 0.01), and the proportion of hypertension, smoking and drinking were significantly increased (69.0% vs. 41.9%, 23.1% vs. 16.8%, 19.2% vs. 13.4%, all P < 0.01). By assigning values to each factor [IS: No = 0,Yes = 1; BMI: < 24.0 kg/m2 = 0, ≥ 24.0 kg/m2 = 1; FPG: < 7.0 mmol/L = 0, ≥ 7.0 mmol/L = 1; TG: < 2.26 mmol/L = 0, ≥ 2.26 mmol/L = 1; TC: < 6.22 mmol/L = 0, ≥ 6.22 mmol/L = 1; LDL-C: < 4.14 mmol/L = 0, ≥ 4.14 mmol/L = 1; HDL-C: < 1.04 mmol/L = 0, ≥ 1.04 mmol/L = 1; hypertension: No = 0,Yes = 1; smoking: No = 0,Yes = 1; drinking: No = 0,Yes = 1], a classification tree model was established to analyze the risk factors of IS. The classification tree model consisted of 4 layers and 17 nodes: the first layer was hypertension, the second layer was FPG and HDL-C, the third layer was HDL-C and FPG, and the fourth layer was LDL-C and smoking. There were five explanatory variables screened out in the model, including hypertension, FPG, HDL-C, LDL-C and smoking. The first layer of the tree showed that the incidence of IS in hypertensive population (62.6%) was significantly higher than that in non-hypertensive population (35.2%). The second layer of the tree showed that the incidence of IS in people with hypertension with HDL-C ≥ 1.04 mmol/L (53.6%) was lower than that in people with HDL-C < 1.04 mmol/L (78.5%). However, in the population without hypertension, the probability of IS occurrence in the population with FPG ≥ 7.0 mmol/L (71.1%) was significantly higher than that in the population with FPG < 7.0 mmol/L (28.3%). The third layer of the tree showed that the IS incidence of HDL-C ≥ 1.04 mmol/L (21.8%) was lower than that of HDL-C < 1.04 mmol/L (48.7%) in the population without hypertension and FPG < 7.0 mmol/L. However, in the population with hypertension and HDL-C ≥ 1.04 mmol/L, the probability of IS occurrence in the population with FPG ≥ 7.0 mmol/L (78.6%) was significantly higher than that in the population with FPG < 7.0 mmol/L (46.7%). The fourth layer of the tree showed that the IS incidence of people with LDL-C ≥ 4.14 mmol/L (53.8%) was higher than that of people with LDL-C < 4.14 mmol/L (19.0%) in the population without hypertension, FPG < 7.0 mmol/L and HDL-C ≥ 1.04 mmol/L. In the population without hypertension, the incidence of IS in smokers (76.9%) was higher than that in non-smokers (39.1%) of people with FPG < 7.0 mmol/L and HDL-C < 1.04 mmol/L. In the population with hypertension, the probability of IS occurrence in the population with LDL-C ≥ 4.14 mmol/L (72.5%) was higher than that in the population with LDL-C < 4.14 mmol/L (44.4 %) of people with HDL-C ≥ 1.04 mmol/L and FPG < 7.0 mmol/L. The gain diagram of IS classification tree model shown that the gain value increased rapidly from 0% to 100% and then tended to be stable. The index chart shown that the index value kept stable in the moving direction from above 100% and then dropped rapidly to 100%, indicating the model was very well. The risk value of misclassification probability of the classification tree model was 0.291, and the correct rate of risk factor for IS patients was 70.90%. The area under ROC curve (AUC) was 78.0% [95% confidence interval (95%CI) = 75.9%-79.9%, P < 0.001], the sensitivity was 62.5% (95%CI = 59.1%-65.7%) and the specificity was 79.4% (95%CI = 76.5%-82.1%). CONCLUSIONS: Classification tree model can properly predict the risk factor of IS, and the most important risk factors are hypertension, hyperglycemia, high LDL-C and smoking.
Subject(s)
Brain Ischemia/diagnosis , Decision Trees , Mass Screening/methods , Stroke/diagnosis , Case-Control Studies , Cholesterol, HDL , Cholesterol, LDL , Humans , Risk FactorsABSTRACT
The electrical transport properties of undoped and yttrium-doped strontium titanate (Sr(Ti1 - x Y x )O3 - δ , x = 0, 0.02) under high pressure were investigated with in situ impedance spectroscopy measurements. A pressure-induced conductivity switching for undoped and 2 mole% Y-doped strontium titanate is observed at around ~10.0 and 7.0 GPa respectively, which are caused by a cubic to tetragonal I4/mcm phase transition. The decrease of the phase transition point of 2 mole% Y-doped strontium titanate can be attributed to larger Y(3+) atoms occupying the B-site and the creation of more oxygen vacancies, which lead to octahedra tilting and symmetry breaking. The results of the voltage-bias dependence of grain-boundary impedance of undoped and 2 mole% Y-doped strontium titanate at different pressures revealed that Schottky-type potential barriers formed at grain boundaries are the key factor for the accumulation of oxygen vacancy at the interface under pressure.
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OBJECTIVE: CC-chemokine receptor 5 (CCR5) plays a pivotal role in reperfusion after stroke. This study assessed and confirmed the effects of CCR5 in experimental stroke via regulation of ROCK/P-MLC pathway. METHODS: Male Sprague Dawley (SD) rats were randomly divided into sham group, ischaemia-reperfusion group (I/R group) and DAPTA group (I/R + CCR5 antagonist group). The rats of the I/R group were subjected to transient middle cerebral artery occlusion (tMCAO) for 2 hours, followed by 24 hours of reperfusion. Animals were measured for neurologic deficit, cerebral infarct volume, TUNEL and hematoxylin-eosin (HE) staining. The protein expressions of ROCK2 and P-MLC2(Ser19) were determined by western blot. RESULTS: Pre-treatment with DAPTA displayed significantly improved neurological functional outcome and reduced cerebral lesion compared with the I/R group animals (p < 0.05); HE staining showed that the I/R group had severe neuronal damage in the ischaemia core and penumbral; Compared with the I/R group, ROCK2 and P-MLC2(Ser19) protein expression in the DAPTA group was reduced (p < 0.05). CONCLUSIONS: The data demonstrate that CCR5 is correlated with up-regulation of the expression of ROCK2 and P-MLC2(Ser19) in the ischaemia cortex. Treated with CCR5 antagonist protects the brain against focal cerebral ischaemia-reperfusion injury in rats.
Subject(s)
Cardiac Myosins/metabolism , Infarction, Middle Cerebral Artery/metabolism , Myosin Light Chains/metabolism , Receptors, CCR5/metabolism , Reperfusion Injury/metabolism , rho-Associated Kinases/metabolism , Analysis of Variance , Animals , Brain Infarction/etiology , Disease Models, Animal , In Situ Nick-End Labeling , Infarction, Middle Cerebral Artery/prevention & control , Male , Neurologic Examination , Peptide T/therapeutic use , Rats , Rats, Sprague-Dawley , Serine/metabolismABSTRACT
It has been reported that remote ischemic postconditioning was able to protect from a harmful ischemia occurring in brain. In the present study, we investigated the role of p38 MAPK signal pathway in the process of neuroprotection and anti-apoptosis following remote limb ischemic postconditioning on rat focal cerebral ischemia/reperfusion (I/R) model. Male Sprague-Dawley rats were divided randomly into four groups: the sham-operated group, I/R group, limb ischemic postconditioning (LPostC) group, and LPostC+SB203580 (p38 MAPK inhibitor) group. Focal ischemia was induced by transient middle cerebral artery occlusion. Limb ischemic postconditioning was implemented by brief cycles of femoral artery occlusion. At 24h after modeling, we analyzed the neurological deficit score, assessed the cerebral tissue morphology by H-E staining, and evaluated neuronal apoptosis by TUNEL staining. The protein expression levels of p-p38 or p-ATF2 (phospho-activating transcription factor 2) in the penumbra region were detected by western blotting or immunohistochemical staining. Our findings revealed that LPostC relieved cerebral ischemia/reperfusion injury by decreasing neurological score, improving neuronal morphological changes in the ischemic penumbra area, and reducing neuronal apoptosis. In addition, LPostC or LPostC+SB203580 attenuated the increase in p-p38 and p-ATF2 levels in ischemia/reperfusion brain tissue. These results indicate that the protective effects of LPostC against cerebral I/R injury may be related to the attenuation of neuronal apoptosis and the suppression of p38 MAPK-ATF2 pathway.
Subject(s)
Brain Ischemia/enzymology , Hindlimb/blood supply , Ischemic Postconditioning/methods , MAP Kinase Signaling System/physiology , Reperfusion Injury/enzymology , Reperfusion Injury/prevention & control , Animals , Brain Ischemia/pathology , Imidazoles/pharmacology , MAP Kinase Signaling System/drug effects , Male , Pyridines/pharmacology , Rats , Rats, Sprague-Dawley , Reperfusion Injury/pathologyABSTRACT
A series of amino acid and dipeptide prodrugs of IMB-070593, a fluoroquinolone candidate discovered in our lab, were synthesized and evaluated for their water solubility and then antibacterial activity. Our results reveal that four amino acid prodrugs 4a,b,e,f and two dipeptide prodrugs 4k,l have much greater solubility (>85 mg/mL) than IMB-070593 mesylate (22.5 mg/mL). Compounds 4a and 4k show good in vivo efficacy against MSSA 12-1 (p.o./i.v., 5.32-7.68 mg/kg) and S. pneumoniae12-10 (p.o., 18.39-23.13 mg/kg) which is 1.19-1.50 fold more active than the parent drug.
Subject(s)
Anti-Bacterial Agents/pharmacology , Dipeptides/chemistry , Dipeptides/pharmacology , Oximes/chemistry , Piperidines/chemistry , Prodrugs/chemistry , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/chemistry , Chemistry Techniques, Synthetic , Injections, Intravenous , Methicillin-Resistant Staphylococcus aureus/drug effects , Mice , Microbial Sensitivity Tests , Prodrugs/chemical synthesis , Prodrugs/pharmacology , SolubilityABSTRACT
BACKGROUND AND OBJECTIVES: Fibroblast activation protein (FAP) expression has been detected in fibroblastic component of osteosarcomas. The aim of this study was to analyze the correlation of FAP expression with the clinicopathological features of osteosarcoma. METHODS: FAP mRNA and protein expression levels in human osteosarcoma tissues were, respectively detected by RT-PCR, Western blot, and immunohistochemistry assays. RESULTS: FAP mRNA and protein expression were both higher in osteosarcoma than in corresponding noncancerous bone tissues (both P < 0.001). In addition, the immunohistochemistry assay found that all patients showed positive FAP expression. Higher FAP expression was significantly correlated with advanced clinical stage (P = 0.006), high histological grade (P = 0.02), positive metastatic status (P = 0.01), shorter overall (P < 0.001), and disease-free (P < 0.001) survival in osteosarcoma patients. Furthermore, Cox multivariate analysis showed that FAP overexpression was an independent prognostic factor for predicting both overall and disease-free survival of osteosarcoma patients. CONCLUSION: Expression of FAP in osteosarcoma could be adopted as a candidate biomarker for the diagnosis of clinical stage, histological grade and metastasis, and for assessing prognosis, indicating for the first time that FAP may play an important role in tumor development and progression in osteosarcoma. FAP might be considered as a novel therapeutic target against this cancer.