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OBJECTIVE: To design and apply a novel puncture method, named P TO P technique, and to evaluate its efficacy and safety. METHOD: The data of patients treated with PVA in medical institution from January 2020 to December 2022 were reviewed and analyzed. The degree of pain relief and recovery from daily activities were evaluated using VAS and LAS scores, and radiological parameters were evaluated using local kyphosis angle and excellent cement distribution. Complications such as cement leakage and recurrent vertebral fractures were also recorded. RESULTS: 157 patients with thoracolumbar OVCF were successfully treated with novel puncture techniques. All postoperative clinical and radiological parameters significantly decreased in all patients, except for an increase in local kyphosis angle at the last follow-up compared to postoperative. All other above indicators remained statistically significant at the last follow-up compared to postoperative improvement. Except for 2 patients with poor cement distribution, the remaining 155 patients successfully achieved satisfactory results in unilateral puncture and bilateral cement distribution, achieving an excellent rate of 98.73%. In addition, 18 cases (11.46%) of cement leakage occurred during the operation, fortunately none of them were uncomfortable. During the postoperative follow-up period, 4 cases (2.55%) of recurrent fractures occurred. No other serious complications such as neurologic or named vascular injuries occurred. CONCLUSION: The application of P TO P technology in thoracolumbar OVCF patients is safe and effective. It can not only reduce pain and quickly recover daily activities, but also achieve the perfect effect of unilateral puncture and bilateral cement filling.
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Cimentos Ósseos , Fraturas por Compressão , Vértebras Lombares , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Vértebras Torácicas , Vertebroplastia , Humanos , Feminino , Fraturas por Compressão/cirurgia , Fraturas por Compressão/diagnóstico por imagem , Masculino , Fraturas da Coluna Vertebral/cirurgia , Fraturas da Coluna Vertebral/diagnóstico por imagem , Estudos Retrospectivos , Vértebras Torácicas/lesões , Vértebras Torácicas/cirurgia , Vértebras Torácicas/diagnóstico por imagem , Fraturas por Osteoporose/cirurgia , Fraturas por Osteoporose/diagnóstico por imagem , Vértebras Lombares/cirurgia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/lesões , Idoso , Vertebroplastia/métodos , Pessoa de Meia-Idade , Cimentos Ósseos/uso terapêutico , Resultado do Tratamento , Idoso de 80 Anos ou mais , SeguimentosRESUMO
Objectives: The metabolic syndrome in patients with schizophrenia has consistently been a challenge for clinicians. Previous studies indicate that individuals with schizophrenia are highly prone to developing type 2 diabetes mellitus (T2DM). In recent years, a continuous stream of new observational studies has been reported, emphasizing the pressing need for clinicians to gain a more precise understanding of the association between schizophrenia and T2DM. The objective of this meta-analysis is to integrate new observational studies and further explore the potential link between schizophrenia and the risk of T2DM. Methods: We conducted a comprehensive search of PubMed, Cochrane Library, Embase, and Web of Science using medical subject headings (MeSH) and relevant keywords. The risk of bias in cohort studies and case-control studies was assessed using the Newcastle-Ottawa Scale (NOS), while cross-sectional studies were evaluated using the Agency for Healthcare Research and Quality scale (AHRQ), scoring was based on the content of the original studies. A fixed-effects model was employed if P > 0.1 and I2 ≤ 50%, indicating low heterogeneity. Conversely, a random-effects model was utilized if I2 > 50%, indicating substantial heterogeneity. Publication bias was assessed using funnel plots and Egger's test. Statistical analyses were carried out using Stata statistical software version 14.0. Results: This meta-analysis comprised 32 observational studies, involving a total of 2,007,168 patients with schizophrenia and 35,883,980 without schizophrenia, published from 2004 to 2023. The pooled analysis revealed a significant association between a history of schizophrenia and an increased risk of T2DM (Odds Ratio [OR] = 2.15; 95% Confidence Interval [CI]: 1.83-2.52; I2 = 98.9%, P < 0.001). Stratified by gender, females with schizophrenia (OR = 2.12; 95% CI: 1.70-2.64; I2 = 90.7%, P < 0.001) had a significantly higher risk of T2DM than males (OR = 1.68; 95% CI: 1.39-2.04; I2 = 91.3%, P < 0.001). Regarding WHO regions, EURO (OR = 2.73; 95% CI: 2.23-3.35; I2 = 97.5%, P < 0.001) exhibited a significantly higher risk of T2DM compared to WPRO (OR = 1.72; 95% CI: 1.32-2.23; I2 = 95.2%, P < 0.001) and AMRO (OR = 1.82; 95% CI: 1.40-2.37; I2 = 99.1%, P < 0.001). In terms of follow-up years, the >20 years subgroup (OR = 3.17; 95% CI: 1.24-8.11; I2 = 99.4%, P < 0.001) showed a significantly higher risk of T2DM than the 10-20 years group (OR = 2.26; 95% CI: 1.76-2.90; I2 = 98.6%, P < 0.001) and <10 years group (OR = 1.68; 95% CI: 1.30-2.19; I2 = 95.4%, P < 0.001). Conclusions: This meta-analysis indicates a strong association between schizophrenia and an elevated risk of developing diabetes, suggesting that schizophrenia may function as an independent risk factor for T2DM. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023465826.
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Diabetes Mellitus Tipo 2 , Esquizofrenia , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Estudos Observacionais como Assunto , Fatores de Risco , Esquizofrenia/epidemiologiaRESUMO
Background: To construct a diagnostic model for Bipolar Disorder (BD) depressive phase using peripheral tissue RNA data from patients and combining Random Forest with Feedforward Neural Network methods. Methods: Datasets GSE23848, GSE39653, and GSE69486 were selected, and differential gene expression analysis was conducted using the limma package in R. Key genes from the differentially expressed genes were identified using the Random Forest method. These key genes' expression levels in each sample were used to train a Feedforward Neural Network model. Techniques like L1 regularization, early stopping, and dropout layers were employed to prevent model overfitting. Model performance was then validated, followed by GO, KEGG, and protein-protein interaction network analyses. Results: The final model was a Feedforward Neural Network with two hidden layers and two dropout layers, comprising 2345 trainable parameters. Model performance on the validation set, assessed through 1000 bootstrap resampling iterations, demonstrated a specificity of 0.769 (95â¯% CI 0.571-1.000), sensitivity of 0.818 (95â¯% CI 0.533-1.000), AUC value of 0.832 (95â¯% CI 0.642-0.979), and accuracy of 0.792 (95â¯% CI 0.625-0.958). Enrichment analysis of key genes indicated no significant enrichment in any known pathways. Conclusion: Key genes with biological significance were identified based on the decrease in Gini coefficient within the Random Forest model. The combined use of Random Forest and Feedforward Neural Network to establish a diagnostic model showed good classification performance in Bipolar Disorder.
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BACKGROUND: Diabetic kidney disease (DKD), characterized by increased urinary microalbumin levels and decreased renal function, is the primary cause of end-stage renal disease. Its pathological mechanisms are complicated and multifactorial; Therefore, sensitive and specific biomarkers are needed. Urinary exosome originate from diverse renal cells in nephron segments and partially mirror the pathological changes in the kidney. The microRNAs (miRNAs) in urinary exosome are remarkably stable and highly tissue-specific for the kidney. AIM: To determine if urinary exosomal miRNAs from diabetic patients can serve as noninvasive biomarkers for early DKD diagnosis. METHODS: Type 2 diabetic mellitus (T2DM) patients were recruited from the Second Hospital of Hebei Medical University and were divided into two groups: DM, diabetic patients without albuminuria [urinary albumin to creatinine ratio (UACR) < 30 mg/g] and DKD, diabetic patients with albuminuria (UACR ≥ 30 mg/g). Healthy subjects were the normal control (NC) group. Urinary exosomal miR-145-5p, miR-27a-3p, and miR-29c-3p, were detected using real-time quantitative polymerase chain reaction. The correlation between exosomal miRNAs and the clinical indexes was evaluated. The diagnostic values of exosomal miR-145-5p and miR-27a-3p in DKD were determined using receiver operating characteristic (ROC) analysis. Biological functions of miR-145-5p were investigated by performing Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment. RESULTS: Urinary exosomal expression of miR-145-5p and miR-27a-3p was more upregulated in the DKD group than in the DM group (miR-145-5p: 4.54 ± 1.45 vs 1.95 ± 0.93, P < 0.001; miR-27a-3p: 2.33 ± 0.79 vs 1.71 ± 0.76, P < 0.05) and the NC group (miR-145-5p: 4.54 ± 1.45 vs 1.55 ± 0.83, P < 0.001; miR-27a-3p: 2.33 ± 0.79 vs 1.10 ± 0.51, P < 0.001). The exosomal miR-145-5p and miR-27a-3p positively correlated with albuminuria and serum creatinine and negatively correlated with the estimated glomerular filtration rate. miR-27a-3p was also closely related to blood glucose, glycosylated hemoglobin A1c, and low-density lipoprotein cholesterol. ROC analysis revealed that miR-145-5p had a better area under the curve of 0.88 [95% confidence interval (CI): 0.784-0.985, P < 0.0001] in diagnosing DKD than miR-27a-3p with 0.71 (95%CI: 0.547-0.871, P = 0.0239). Bioinformatics analysis revealed that the target genes of miR-145-5p were located in the actin filament, cytoskeleton, and extracellular exosome and were involved in the pathological processes of DKD, including apoptosis, inflammation, and fibrosis. CONCLUSION: Urinary exosomal miR-145-5p and miR-27a-3p may serve as novel noninvasive diagnostic biomarkers or promising therapeutic targets for DKD.
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Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease without early diagnostic and specific therapeutic approaches. Podocyte apoptosis and loss play important roles in the pathological process of DKD. This study aimed to explore whether urinary exosomes from type 2 diabetes patients with DKD could induce podocyte apoptosis and the underlying pathological mechanisms. The exosomes were isolated from the urine samples of patients with DKD (DKD-Exo). Later, they were taken up and internalized by MPC5 cells. MPC5 cells were co-cultured with DKD-Exo (45 µg/ml) for 24 h in the presence or absence of microRNA-145-5p (miR-145-5p) inhibitor, fasudil and pcDNA-Srgap2 transfection. MiR-145-5p and Srgap2 expression was evaluated using real-time quantitative PCR. The protein levels of Srgap2, Bcl-2, Bax, and cleaved caspase-3, as well as ROCK activity were determined using Western blotting. Cell apoptosis was measured using flow cytometry and the TUNEL assay. miR-145-5p expression in MPC5 cells exposed to DKD-Exo was markedly upregulated. miR-145-5p negatively regulated Srgap2 levels. Exposure of MPC5 cells to DKD-Exo reduced Srgap2 expression and activated ROCK, which was partly reversed by the presence of the miR-145-5p inhibitor or Srgap2 overexpression. The apoptosis of MPC5 cells exposed to DKD-Exo increased significantly, which was counteracted by the addition of the miR-145-5p inhibitor and fasudil. The results showed that urinary exosomal miR-145-5p from patients with DKD induced podocyte apoptosis by inhibiting Srgap2 and activating the RhoA/ROCK pathway, suggesting that urinary exosomal miR-145-5p is involved in the pathological process of DKD and could become a noninvasive diagnostic biomarker for DKD.
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Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Exossomos , MicroRNAs , Podócitos , Humanos , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/patologia , MicroRNAs/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Podócitos/patologia , Exossomos/metabolismo , Apoptose/genéticaRESUMO
Application of the 316 L stainless steel (SS) is limited by its relatively low wear resistance, insufficient strength, and poor corrosion resistance in special environments. To this end, effects of Mo particles addition on the microstructure, mechanical properties, and corrosion resistance of the laser powder bed fusion (LPBF) 316 L SS are investigated in this study. The results show that the addition of Mo particles from 0 wt.% to 10 wt.% can modify the crystal orientation and improve the strength, wear resistance, and corrosion resistance of LPBF 316 L SSs. Particularly, the LPBF 316 L SS forms a biphasic structure with a similar ratio of α-Fe to γ-Fe with 5 wt.% Mo addition. As a result, the corresponding samples possess both the excellent toughness of austenitic SSs and the high strength and corrosion resistance of ferrite SSs, which reaches a high tensile strength of about 830 MPa, together with a low friction coefficient of 0.421 µ. Since the Mo particles addition is beneficial to increase the content of Cr2O3 on the samples surface from 13.48% to 22.68%, the corrosion current density of 316 L SS decreases by two orders of magnitude from 569 nA to 6 nA, while the mechanical properties remain favorable. This study is expected to serve as a reference for the preparation of LPBF SSs with excellent integrated performance.
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OBJECTIVE: Anxious behaviors often occur in individuals who have experienced early adversity. Anxious behaviors can bring many hazards, such as social withdrawal, eating disorders, negative self-efficacy, self-injurious thoughts and behaviors, anxiety disorders, and even depression. Abnormal behavior are is closely related to changes in corresponding circuit functions in the brain. This study investigated the relationship between brain circuits and anxious behaviors in maternal-deprived rhesus monkey animal model, which mimic early adversity in human. METHODS: Twenty-five rhesus monkeys (Macaca mulatta) were grouped by two different rearing conditions: 11 normal control and mother-reared (MR) monkeys and 14 maternally deprived and peer-reared (MD) monkeys. After obtaining images of the brain areas with significant differences in maternal separation and normal control macaque function, the relationship between functional junction intensity and stereotypical behaviors was determined by correlation analysis. RESULTS: The correlation analysis revealed that stereotypical behaviors were negatively correlated with the coupling between the left lateral amygdala subregion and the left inferior frontal gyrus in both MD and MR macaques. CONCLUSION: This study suggests that early adversity-induced anxious behaviors are associated with changes in the strength of the amygdala-prefrontal connection. The normalization of the regions involved in the functional connection might reverse the behavioral abnormality. It provides a solid foundation for effective intervention in human early adversity. SIGNIFICANCE STATEMENT: This study suggests that early adversity-induced anxious behaviors are associated with changes in the strength of the amygdala-prefrontal connection. The higher the amygdala-prefrontal connection strength, the less stereotyped behaviors exhibited by monkeys experiencing early adversity. Thus, in the future, changing the strength of the amygdala-prefrontal connection may reverse the behavioral abnormalities of individuals who experience early adversity. This study provides a solid foundation for effective intervention in humans' early adversity.
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Ansiedade , Privação Materna , Humanos , Animais , Tonsila do Cerebelo/diagnóstico por imagem , Lobo Frontal/diagnóstico por imagem , Córtex Pré-FrontalRESUMO
Objective: To determine the changes in serum bone metabolism indexes and ultrasonic bone mineral density (BMD) in patients with diabetic nephropathy at different stages, and their effects on diabetic renal microvascular complications. Methods: This is a clinical comparative study. One hundred twenty two diabetic patients admitted to the Baoding No.1 Central Hospital from January 2020 to March 2022 were selected as subjects and divided into three groups according to their actual condition: the simple diabetes (Group-A, 40 cases), diabetic nephropathy with micro urinary protein (Group-B, 40 cases) and diabetic nephropathy with massive proteinuria (Group-C, 42 cases). Another 36 healthy subjects were selected as the control group. Differences in serum bone metabolism indexes and ultrasound BMD levels were compared. Results: Twenty five hydroxy-vitamin D, BGP, T-PINP and ultrasound BMD levels in the control group were > Group-A > Group-B > Group-C, PTH and ß-CTX in the control group were < Group-A < Group-B < Group-C, statistically significant differences (p<0.05). The urinary albumin to urinary creatinine ratio (ACR) value in Group-B was significantly lower than Group-C (p<0.05). Logistic regression analysis showed that 25-hydroxy-vitamin D, PTH, BGP, ß-CTX, T-PINP and ultrasound BMD were the influencing factors of diabetic renal microvascular complications (p<0.05). Conclusion: Bone metabolism indexes and ultrasound bone mineral density are abnormally expressed in patients with diabetic nephropathy at different stages, which are closely related to the urine protein of patients. They have important clinical value in the diagnosis of early diabetic nephropathy.
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OBJECTIVE: This study was designed to compare the effects of levosimendan and dobutamine on hemodynamics and clinical efficacy in patients with severe septic cardiomyopathy (left ventricular ejection fraction [LVEF] ≤35%). DESIGN: A prospective, single-blind, randomized controlled study. SETTING: In Baoding, China. PARTICIPANTS: Thirty patients with severe septic cardiomyopathy treated in the authors' hospital's Department of Critical Medicine from September 2018 to September 2021 were enrolled in this study. INTERVENTIONS: These patients were divided randomly into the levosimendan group and dobutamine group. The LVEF, cardiac index (CI), stroke volume index (SVI), systemic vascular resistance index, heart rate, norepinephrine dose, and lactate at the time of enrollment and the 24th hour were compared, along with myocardial injury markers on the third day, C-reactive protein, mechanical ventilation time, length of intensive care unit (ICU) stay, cost, and 28-day mortality. The primary outcome was 28-day mortality. MEASUREMENTS AND MAIN RESULTS: At the 24th hour after treatment, CI, LVEF, SVI, and fluid volume were found to be higher in the levosimendan group than in the dobutamine group, whereas the dose of norepinephrine was lower in the former rather than the latter group. On the third day of treatment, cardiac troponin I in the levosimendan group was lower than that in the dobutamine group. Although the differences in 28-day mortality, ICU stay, and ICU treatment cost between the groups were not statistically significant, the ventilator application time of the levosimendan group was significantly shorter than that of the dobutamine group. CONCLUSIONS: Compared with dobutamine, levosimendan was more effective at improving cardiac function, reducing myocardial injury, and reducing mechanical ventilation time in patients with severe septic cardiomyopathy.
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Cardiomiopatias , Piridazinas , Sepse , Choque Séptico , Humanos , Simendana , Dobutamina/uso terapêutico , Volume Sistólico , Estudos Prospectivos , Método Simples-Cego , Hidrazonas/uso terapêutico , Piridazinas/uso terapêutico , Choque Séptico/tratamento farmacológico , Função Ventricular Esquerda , Norepinefrina/farmacologia , Norepinefrina/uso terapêutico , Cardiomiopatias/tratamento farmacológico , Cardiotônicos/uso terapêuticoRESUMO
BACKGROUND: Delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) is a severe complication that can arise from acute carbon monoxide poisoning (ACOP). This study aims to identify the independent risk factors associated with DEACMP and to develop a nomogram to predict the probability of developing DEACMP. METHODS: The data of patients diagnosed with ACOP between September 2015 and June 2021 were analyzed retrospectively. The patients were divided into the two groups: the DEACMP group and the non-DEACMP group. Univariate analysis and multivariate logistic regression analysis were conducted to identify the independent risk factors for DEACMP. Subsequently, a nomogram was constructed to predict the probability of DEACMP. RESULTS: The study included 122 patients, out of whom 30 (24.6%) developed DEACMP. The multivariate logistic regression analysis revealed that acute high-signal lesions on diffusion-weighted imaging (DWI), duration of carbon monoxide (CO) exposure, and Glasgow Coma Scale (GCS) score were independent risk factors for DEACMP (Odds Ratio = 6.230, 1.323, 0.714, p < 0.05). Based on these indicators, a predictive nomogram was constructed. CONCLUSIONS: This study constructed a nomogram for predicting DEACMP using high-signal lesions on DWI and clinical indicators. The nomogram may serve as a dependable tool to differentiate high-risk patients and enable the provision of personalized treatment to lower the incidence of DEACMP.
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Encefalopatias , Intoxicação por Monóxido de Carbono , Humanos , Intoxicação por Monóxido de Carbono/complicações , Intoxicação por Monóxido de Carbono/diagnóstico por imagem , Intoxicação por Monóxido de Carbono/terapia , Estudos Retrospectivos , Nomogramas , Encefalopatias/diagnóstico por imagem , Encefalopatias/etiologia , Imagem de Difusão por Ressonância MagnéticaRESUMO
Objectives: To investigate the evaluation of bone mineral density (BMD) in patients with gestational diabetes mellitus (GDM) by ultrasonic bone mineral density measurement combined with Vitamin-D deficiency and its influencing factors. Methods: A total of 100 patients with gestational diabetes mellitus (GDM) admitted to our hospital from January 2017 to December 2020 were selected as the GDM group, and another 100 pregnant volunteers who underwent physical examination in our hospital were selected as the healthy control group. The levels of triacylglycerol (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), glycated hemoglobin (HbA1c), fasting insulin (FINS), C-peptide, procollagen, parathyroid hormone (PTH), serum calcium, 25-hydroxyvitamin-D3 (25-OH-D) and ultrasonic BMD Z-score were determined and compared between the two groups. Moreover, the effects of different levels of 25-OH-D on the above indexes were compared, and multivariate logistic regression analysis was performed. Results: Compared with the healthy reference group, the levels of TG, TC, LDL-C, PTH, HbA1c, FINS and C-peptide of GDM group were significantly increased (P < 0.05), while BMD Z-score and 25-OH-D levels were significantly decreased. In the GDM group, the lower the 25-OH-D levels, the higher the FPG, HbA1c and FINS levels and the lower the serum calcium level and BMD Z-score, with statistically significant differences (P < 0.05). Multivariate logistic regression analysis showed that 25-OH-D was an independent risk factor affecting BMD in patients with GDM (P<0.05). Conclusions: Patients with GDM have lower BMD and 25-hydroxyVitamin-D3 levels. Measurement of BMD and 25-hydroxyVitamin-D3 levels can help assess the progression of GDM. BMD has a close bearing on Vitamin-D deficiency in patients with GDM.
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Phase separation phenomena in high-entropy alloys (HEAs) have attracted much attention since their discovery, but little attention has been given to the dynamics of the deformation mechanism of this kind of HEA during uniaxial tension, which limits their widespread and practical utility. In this work, molecular dynamics simulation was used to study the effect of phase separation on the mechanical properties of an HEA under uniaxial tensile loading. Moreover, the associated deformation behavior of the Co-Cr-Cu-Fe-Ni HEA was investigated at the nanoscale. Models with Cu-rich grain boundaries or grains were constructed. The results showed that Cu-rich grain boundaries or grains lowered the strength of the Co-Cr-Cu-Fe-Ni HEA, and Cu-rich grain boundaries significantly reduced ductility. This change of mechanical properties was closely associated with a deformation behavior. Furthermore, the deformation behavior was affected by the critical resolved shear stress of Cu-rich and Cu-depleted regions and the uneven stress distribution caused by phase separation. In addition, dislocation slipping and grain boundary sliding were the main mechanisms of plastic deformation in the Co-Cr-Cu-Fe-Ni HEA.
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INTRODUCTION: This study is to analyze the neuroprotective effects of long-term metformin (Met) preconditioning on rats with ischemic brain injuries and the related mechanisms. METHODS: Twenty-five Sprague-Dawley rats were randomly divided into 5 groups: sham group, middle cerebral artery occlusion (MCAO) group, normal saline + MCAO group, pre- Met + MCAO group, and 3-MA + Met + MCAO group. Pathological changes of brain were observed by hematoxylin-eosin staining. Neurobehavior scores were calculated. Infarct area was assessed by 2,3,5-triphenyltetrazolium chloride staining. Apoptosis of neurons was detected by TdT-mediated dUTP Nick-End Labeling (TUNEL). Western blot tested the expression of LC3 (microtubule-associated protein 1 light chain 3), Beclin-1, adenosine 5'-monophosphate ([AMP]-activated protein kinase [AMPK]), and p-AMPK in hippocampal CA1 region. RESULTS: Compared with the sham group, the MCAO group induced severe pathological changes in the brain. The neurobehavior scores and infarct area in the brain were increased in the MCAO group than in the sham group. The apoptosis level in the MCAO group was also higher than in the sham group. However, after pretreatment with Met, the pathological changes in the brain were attenuated. Compared with the MCAO group, the pre-Met + MCAO group also had decreased neurobehavior scores and infarct area in the brain. Additionally, the apoptosis level in the pre-Met + MCAO group was lower than in the MCAO group. Moreover, the MCAO group had increased levels of LC3 and Beclin-1 than in the sham group. In the pre-Met + MCAO group, their levels were decreased than in the MCAO group. The p-AMPK level in the pre-Met + MCAO group was also increased than in the MCAO group, suggesting activation of p-AMPK by Met. CONCLUSION: Long-term Met pretreatment has neuroprotective effect on ischemic brain injury, which may be related to the regulation of autophagy-related protein expression and apoptosis.
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Lesões Encefálicas , Isquemia Encefálica , Metformina , Fármacos Neuroprotetores , Animais , Apoptose , Isquemia Encefálica/tratamento farmacológico , Humanos , Infarto da Artéria Cerebral Média/tratamento farmacológico , Metformina/farmacologia , Fármacos Neuroprotetores/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
With the rapid development of MEMS, the demand for metal microstructure is increasing. Micro electrochemical milling technology (MECM) is capable of manufacturing micro metallic devices or components based on the principle of electrochemical anode dissolution. To improve the capacity of MECM, this paper presents a compound method named ultrasonic vibration-assisted micro electrochemical milling technology (UA-MECM). Firstly, the simulation and mathematical model of UA-MECM process is established to explain the mechanism of ultrasonic vibration on micro electrochemical milling. Then, the effects of ultrasonic parameters, electrical parameters and feedrate on machining localization and surface quality are discussed considering sets of experiments. The surface roughness was effectively reduced from Ra 0.83 to Ra 0.26 µm with the addition of ultrasonic vibration. It turns out that ultrasonic vibration can obviously improve machining precision, efficiency and quality. Finally, two- and three-dimensional microstructures with good surface quality were successful fabricated. It shows that ultrasonic vibration-assisted electrochemical milling technology has excellent machining performance, which has potential and broad industrial application prospects.
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The present study aimed to investigate the relationship between an increase in the pre- and post-operative neutrophil-lymphocyte ratio (NLR) and superficial femoral artery in-stent restenosis (ISR) rate. We recruited 199 patients that underwent superficial femoral artery stenting for lower extremity arteriosclerosis obliterans at our hospital from March 2015 to July 2018. Patients were divided into two groups according to the occurrence of ISR within 1 year (group 1, ISR and group 2, Non-ISR). The after NLR (NLRafter) and NLR change ratio (NLRratio) (P<0.001) were significantly higher in group 1. A NLRafter > 4.3 was associated with an odds ratio of 1.946 (95% CI [1.51-2.50]; P<0.001) for the presence of ISR. A NLRratio > 37.5% was associated with an odds ratio of 3.6 (95% CI [2.03-6.36]; P<0.001) for occurrence of ISR. A NLRafter level > 4.3 had 75% sensitivity and 76% specificity for the prediction of ISR, as identified by the ROC curve. A NLRratio level > 37.5% predicted ISR with 77% sensitivity and 60% specificity. Multivariate logistic regression analysis demonstrated that NLRratio was the strongest independent predictor of ISR (P<0.001). In conclusions, NLRratio could be used as a prognostic marker in superficial femoral artery stents.
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Angioplastia com Balão/efeitos adversos , Arteriosclerose Obliterante/cirurgia , Artéria Femoral/cirurgia , Oclusão de Enxerto Vascular/epidemiologia , Linfócitos , Neutrófilos , Idoso , Idoso de 80 Anos ou mais , Angiografia , Angioplastia com Balão/instrumentação , Arteriosclerose Obliterante/sangue , Arteriosclerose Obliterante/diagnóstico , Feminino , Artéria Femoral/diagnóstico por imagem , Oclusão de Enxerto Vascular/sangue , Oclusão de Enxerto Vascular/diagnóstico , Oclusão de Enxerto Vascular/etiologia , Humanos , Extremidade Inferior/irrigação sanguínea , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Período Pós-Operatório , Valor Preditivo dos Testes , Período Pré-Operatório , Prognóstico , Curva ROC , Medição de Risco/métodos , Fatores de Risco , Stents/efeitos adversosRESUMO
In previous studies, Ti-based bulk metallic glasses (BMGs) free from Ni and Be were developed as promising biomaterials. Corresponding amorphous coatings might have low elastic modulus, remarkable wear resistance, good corrosion resistance, and biocompatibility. However, the amorphous coatings obtained by the common methods (high velocity oxygen fuel, laser cladding, etc.) have cracks, micro-pores, and unfused particles. In this work, a Ti-based Ti47Cu38Zr7.5Fe2.5Sn2Si1Nb2 amorphous coating with a maximum thickness of about 100 µm was obtained by laser surface remelting (LSR). The in-situ formation makes the coating dense and strongly bonded. It exhibited better corrosion resistance than the matrix and its corrosion mechanism was discussed. The effects of LSR on the microstructural evolution of Ti-based prefabricated alloy sheets were investigated. The nano-hardness in the heat affected zone (HAZ) was markedly increased by 51%, meanwhile the elastic modulus of the amorphous coating was decreased by 18%. This demonstrated that LSR could be an effective method to manufacture the high-quality amorphous coating. The in-situ amorphous coating free from Ni and Be had a low modulus, which might be a potential corrosion-resistant biomaterial.
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N-acetylcysteine (NAC), a precursor for glutathione (GSH), causes permeable antioxidation protecting normal cells and disrupting cancer cells. In the present study, we found that a NAC-based medium can trigger a reversal response of human clear cell renal cell carcinoma (ccRCC). To further investigate the action of a NAC-based solution in ccRCC cell lines, 786-O and SN12C were incubated in a serum-free acid medium (low pH) in the presence of 2 mM NAC for 24 hours or in a serum-free medium (normal pH) as the control, and then a phenotypic and proteomic analyses were performed. To determine the reversal occurrence, we tested the phenotypic features associated with cancer cells. Under this premise, a systematic and in-depth analysis of NAC-solution-triggered protein alterations was carried out by quantitative proteomics in both cell lines. Among the paramount protein signature, we identified a large number of proteins associated with cancer features were downregulated, but other proteins in the KEGG pathways associated with recovery of the missing tumorigenicity, such as the p53 pathway and repair pathway, were significantly upregulated. Quantification of notable proteins was validated by messenger RNA (mRNA) and protein levels in the ccRCC cell line. Collectively, our data indicate that the NAC-based solution inhibits human ccRCC cell growth by decreasing cell proliferation and inducing apoptosis, limiting their migration by limiting cell motility and completely changing their metabolic mode. Thus, NAC-based solutions could be used for the prevention or treatment of ccRCC.
Assuntos
Acetilcisteína/farmacologia , Carcinoma de Células Renais/metabolismo , Marcação por Isótopo , Neoplasias Renais/metabolismo , Proteômica , Linhagem Celular Tumoral , Humanos , Anotação de Sequência Molecular , Reprodutibilidade dos Testes , Transdução de Sinais , SoluçõesRESUMO
The aim of the present study was to understand the possible role of the Dihydromyricetin (DHM) in Alzheimer's disease (AD) rat model through regulation of the AMPK/SIRT1 signaling pathway. Rats were divided into Sham group, AD group, AD + DHM (100 mg/kg) group and AD + DHM (200 mg/kg) group. The spatial learning and memory abilities of rats were assessed by Morris Water Maze. Then, the inflammatory cytokines expressions were determined by radioimmunoassay while expressions of AMPK/SIRT1 pathway-related proteins by Western blot; and the apoptosis of hippocampal cells was detected by TdT-mediated dUTP nick end labeling assay. AD rats had an extended escape latency with decreases in the number of platform crossings, the target quadrant residence time, as well as swimming speed, and the inflammatory cytokines in serum and hippocampus were significantly elevated but AMPK/SIRT1 pathway-related proteins were reduced. Meanwhile, the apoptosis of hippocampal cells was significantly up-regulated with decreased Bcl-2 and increased Bax, as compared with Sham rats (all P<0.05). After AD rats treated with 100 or 200 mg/kg of DHM, the above effects were significantly reversed, resulting in a completely opposite tendency, and especially with 200 mg/kg DHM treatment, the improvement of AD rats was more obvious. DHM exerts protective role in AD via up-regulation of AMPK/SIRT1 pathway to inhibit inflammatory responses and hippocampal cell apoptosis and ameliorate cognitive function.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Doença de Alzheimer/tratamento farmacológico , Cognição/efeitos dos fármacos , Flavonóis/farmacologia , Nootrópicos/farmacologia , Sirtuína 1/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/administração & dosagem , Animais , Apoptose , Cognição/fisiologia , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Injeções Intraperitoneais , Injeções Intraventriculares , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Memória/efeitos dos fármacos , Memória/fisiologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Fragmentos de Peptídeos/administração & dosagem , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/genética , Técnicas EstereotáxicasRESUMO
OBJECTIVE: To breed Aspergillus oryzae strains with high fructosyltransferase (FTase) activity using intraspecific protoplast fusion via genome-shuffling. RESULTS: A candidate library was developed using UV/LiCl of the conidia of A. oryzae SBB201. By screening for enzyme activity and cell biomass, two mutants (UV-11 and UV-76) were chosen for protoplast fusion and subsequent genome shuffling. After three rounds of genome recombination, a fusion mutant RIII-7 was obtained. Its FTase activity was 180 U g-1, approximately double that of the original strain, and RIII-7 was genetically stable. In fermentation culture, FTase activity of the genome-shuffled strain reached a maximum of 353 U g-1 using substrate-feeding method, and this value was approximately 3.4-times higher than that of the original strain A. oryzae SBB201. CONCLUSIONS: Intraspecific protoplast fusion of A. oryzae significantly enhanced FTase activity and generated a potentially useful strain for industrial production.