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The LiCoO2 (LCO) cathode is foreseen for extensive commercial applications owing to its high specific capacity and stability. Therefore, there is considerable interest in further enhancing its specific capacity by increasing the charging voltage. However, single-crystal LCO suffers from a significant capacity degradation when charged to 4.5 V due to the irreversible phase transition and unstable structure. Herein, an ultra-small amount (0.5% wt. in the electrode) of multi-functional PIM-1 (a polymer with intrinsic microporosity) additive is utilized to prepare a kind of binder-free electrode. PIM-1 modulates the solvation structure of LiPF6 due to its unique structure, which helps to form a stable, robust, and inorganic-rich cathod-eelectrolyte interphase (CEI) film on the surface of LCO at a high voltage of 4.5 V. This reduces the irreversible phase transition of LCO, thereby enhancing the cyclic stability and improving the rate performance, providing new perspectives for the electrodes fabrication and improving LCO-based high-energy-density cathodes.
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Na-based layered transition metal oxides with an O3-type structure are considered promising cathodes for sodium-ion batteries. However, rapid capacity fading, and poor rate performance caused by serious structural changes and interfacial degradation hamper their use. In this study, a NaPO3 surface modified O3-type layered NaNi1/3 Fe1/3 Mn1/3 O2 cathode is synthesized, with improved high-voltage stability through protecting layer against acid attack, which is achieved by a solid-gas reaction between the cathode particles and gaseous P2 O5 . The NaPO3 nanolayer on the surface effectively stabilizes the crystal structure by inhibiting surface parasitic reactions and increasing the observed average voltage. Superior cyclic stability is exhibited by the surface-modified cathode (80.1% vs 63.6%) after 150 cycles at 1 C in the wide voltage range of 2.0 V-4.2 V (vs Na+ /Na). Moreover, benefiting from the inherent ionic conduction of NaPO3 , the surface-modified cathode presents excellent rate capability (103 mAh g-1 vs 60 mAh g-1 ) at 10 C. The outcome of this study demonstrates a practically relevant approach to develop high rate and durable sodium-ion battery technology.
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Nickel-rich layered oxide cathodes, such as LiNi0.5Co0.2Mn0.3O2 (NCM523), are prevalent in high-power batteries owing to their high energy density. However, these cathodes suffer from undesirable side reactions occurring at the cathode/liquid electrolyte interface, leading to inferior interface stability and poor cycle life. To address these issues, herein, an amphiphilic diblock copolymer poly(dimethylsiloxane)-block-poly(acrylic acid) (PDMS-b-PAA) along with lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) is utilized for modifying the electrode surface. This modification causes a thin and stable cathode-electrolyte interface (CEI) on the surface of NCM523 particles, as evidenced by XPS, TEM, and EIS analysis. The introduction of this modified interface successfully suppresses the capacity fading of NCM523. After 200 cycles at a rate of 1.0 C, the capacity of the modified NCM523 cathode is 108.7 mAh g-1, with a capacity retention of 82.8%, while the control samples without the polymer modification display a capacity retention of 72.7%. These results outline the distinct advantage of electrode surface modification with diblock copolymers/LiTFSI for the stabilization of Ni-rich layered oxide cathodes.
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BACKGROUND: We aimed to investigate the associations of macrophage migration inhibitory factor (MIF), toll-like receptors 2 and 4 (TLR2/4), and matrix metalloproteinase 9 (MMP9) with 3-month poor outcome, death, and malignant cerebral edema (MCE) in patients with large hemispheric infarction (LHI). METHODS: Patients with LHI within 24 h of onset were enrolled consecutively. Serum MIF, TLR2/4, and MMP9 concentrations on admission were measured. Poor outcome was defined as a modified Rankin Scale score of ≥ 3 at 3 months. MCE was defined as a decreased level of consciousness, anisocoria and midline shift > 5 mm or basal cistern effacement, or indications for decompressive craniectomy during hospitalization. The cutoff values for MIF/MMP9 were obtained from the receiver operating characteristic curve. RESULTS: Of the 130 patients with LHI enrolled, 90 patients (69.2%) had 3-month poor outcome, and MCE occurred in 55 patients (42.3%). Patients with serum MIF concentrations ≤ 7.82 ng/mL for predicting 3-month poor outcome [adjusted odds ratio (OR) 2.827, 95% confidence interval (CI) 1.144-6.990, p = 0.024] also distinguished death (adjusted OR 4.329, 95% CI 1.841-10.178, p = 0.001). Similarly, MMP9 concentrations ≤ 46.56 ng/mL for predicting 3-month poor outcome (adjusted OR 2.814, 95% CI 1.236-6.406, p = 0.014) also distinguished 3-month death (adjusted OR 3.845, 95% CI 1.534-9.637, p = 0.004). CONCLUSIONS: Lower serum MIF and MMP9 concentrations at an early stage were independently associated with 3-month poor outcomes and death in patients with LHI. These findings need further confirmation in larger sample studies.
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INTRODUCTION: The prevalence of cerebral smallvessel disease (SVD) and vascular dementia according to workplace or domestic exposure to hazardous substances is unclear. METHODS: We included studies assessing occupational and domestic hazards/at-risk occupations and SVD features. We pooled prevalence estimates using random-effects models where possible, or presented a narrative synthesis. RESULTS: We included 85 studies (n = 47,743, mean age = 44·5 years). 52/85 reported poolable estimates. SVD prevalence in populations exposed to carbon monoxide was 81%(95% CI = 60-93%; n = 1373; results unchanged in meta-regression), carbon disulfide73% (95% CI = 54-87%; n = 131), 1,2-dichloroethane 88% (95% CI = 4-100%, n = 40), toluene 82% (95% CI = 3-100%, n = 64), high altitude 49% (95% CI = 38-60%; n = 164),and diving 24% (95% CI = 5-67%, n = 172). We narratively reviewed vascular dementia studies and contact sport, lead, military, pesticide, and solvent exposures as estimates were too few/varied to pool. DISCUSSION: SVD and vascular dementia may be associated with occupational/domestic exposure to hazardous substances. CRD42021297800.
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Doenças de Pequenos Vasos Cerebrais , Demência Vascular , Exposição Ocupacional , Humanos , Demência Vascular/epidemiologia , Exposição Ocupacional/efeitos adversos , Doenças de Pequenos Vasos Cerebrais/epidemiologia , Exposição Ambiental/efeitos adversos , Exposição Ambiental/estatística & dados numéricos , Substâncias Perigosas/efeitos adversos , PrevalênciaRESUMO
Duodenal perforation is the most serious complication of endoscopic retrograde cholangiopancreatography (ERCP), with an incidence of 0.09-1.67% but a high mortality rate of 8-23%. The Stapfer classification categorizes ERCP perforations into four types based on location: I) lateral/medial duodenal wall, II) perivaterian, III) distal bile duct related to instrumentation, IV) retroperitoneal air alone. While surgery is recommended for diagnosed perforations due to the mortality risk, there is no established treatment for resulting long-term retroperitoneal infections. We describe our experience managing such cases.
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BACKGROUND: Cerebrovascular reactivity (CVR) is inversely related to white matter hyperintensity severity, a marker of cerebral small vessel disease (SVD). Less is known about the relationship between CVR and other SVD imaging features or cognition. We aimed to investigate these cross-sectional relationships. METHODS: Between 2018 and 2021 in Edinburgh, we recruited patients presenting with lacunar or cortical ischemic stroke, whom we characterized for SVD features. We measured CVR in subcortical gray matter, normal-appearing white matter, and white matter hyperintensity using 3T magnetic resonance imaging. We assessed cognition using Montreal Cognitive Assessment. Statistical analyses included linear regression models with CVR as outcome, adjusted for age, sex, and vascular risk factors. We reported regression coefficients with 95% CIs. RESULTS: Of 208 patients, 182 had processable CVR data sets (median age, 68.2 years; 68% men). Although the strength of association depended on tissue type, lower CVR in normal-appearing tissues and white matter hyperintensity was associated with larger white matter hyperintensity volume (BNAWM=-0.0073 [95% CI, -0.0133 to -0.0014] %/mm Hg per 10-fold increase in percentage intracranial volume), more lacunes (BNAWM=-0.00129 [95% CI, -0.00215 to -0.00043] %/mm Hg per lacune), more microbleeds (BNAWM=-0.00083 [95% CI, -0.00130 to -0.00036] %/mm Hg per microbleed), higher deep atrophy score (BNAWM=-0.00218 [95% CI, -0.00417 to -0.00020] %/mm Hg per score point increase), higher perivascular space score (BNAWM=-0.0034 [95% CI, -0.0066 to -0.0002] %/mm Hg per score point increase in basal ganglia), and higher SVD score (BNAWM=-0.0048 [95% CI, -0.0075 to -0.0021] %/mm Hg per score point increase). Lower CVR in normal-appearing tissues was related to lower Montreal Cognitive Assessment without reaching convention statistical significance (BNAWM=0.00065 [95% CI, -0.00007 to 0.00137] %/mm Hg per score point increase). CONCLUSIONS: Lower CVR in patients with SVD was related to more severe SVD burden and worse cognition in this cross-sectional analysis. Longitudinal analysis will help determine whether lower CVR predicts worsening SVD severity or vice versa. REGISTRATION: URL: https://www.isrctn.com; Unique identifier: ISRCTN12113543.
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Doenças de Pequenos Vasos Cerebrais , Substância Branca , Masculino , Humanos , Idoso , Feminino , Estudos Transversais , Doenças de Pequenos Vasos Cerebrais/complicações , Imageamento por Ressonância Magnética/métodos , Cognição , Substância Branca/patologiaRESUMO
BACKGROUND: Hemorrhagic transformation (HT) is a common complication of acute ischemic stroke (AIS), and may develop into parenchyma hemorrhage (PH). We aimed to investigate the association between serum homocysteine levels and HT as well as PH in all AIS patients, and in those with and without thrombolysis by subgroup analysis. METHODS: AIS patients who were admitted within 24 h after onset were enrolled and categorized into the higher homocysteine level group (≥ 15.5 µmol/L) and the lower homocysteine level group (< 15.5 µmol/L). HT was determined by a second round of brain imaging within 7 days during hospitalization, and PH was defined as hematoma in the ischemic parenchyma. Multivariate logistic regression was used to investigate the associations between serum homocysteine levels and HT and PH, respectively. RESULTS: Of the 427 included patients (mean age 67.35 years, 60.0% males), 56 (13.11%) developed HT and 28 (6.56%) had PH. Serum homocysteine levels were significantly associated with HT (adjusted OR 1.029, 95%CI 1.003-1.055) and PH (adjusted OR 1.041, 95%CI 1.013-1.070). The higher homocysteine group was more likely to have HT (adjusted OR 1.902, 95% CI 1.022-3.539) and PH (adjusted OR 3.073, 95% CI 1.327-7.120) than the lower homocysteine group. Subgroup analysis of patients without thrombolysis also showed the significant differences in HT (adjusted OR 2.064, 95% CI 1.043-4.082) and PH (adjusted OR 2.926, 95% CI 1.196-7.156) between the two groups. CONCLUSION: Higher serum homocysteine levels are associated with an increased risk of HT and PH in AIS patients, especially in those without thrombolysis. Monitoring the serum homocysteine may be conducive to determining individuals at a high risk of HT.
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Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Masculino , Humanos , Idoso , Feminino , Acidente Vascular Cerebral/complicações , Isquemia Encefálica/complicações , AVC Isquêmico/complicações , Fatores de Risco , Hemorragia Cerebral/complicaçõesRESUMO
Ultrafine SnO2/Sn nanoparticles encapsulated into an adjustable meso-/macroporous carbon matrix have been successfully fabricated by the in situ SiOx sacrificial strategy. The control over the void space in the carbon matrix effectively improves the accessibility of the SnO2/Sn toward an electrolyte solution. More importantly, the void space also provides an efficient means to accommodate the mechanical stress caused by the volume change of the SnO2/Sn over cycles. As a result, the enhanced electrolyte accessibility and suppressed mechanical stress improve the electrochemical performance regarding reversible capacity, cyclic stability, and rate capability. A reversible capacity of 1105 mAh g-1 is still retained after 290 cycles at 200 mAg-1, and the capacity still can keep at 107 mAh g-1 at a high current density of 10 A g-1.
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BACKGROUND: As currently defined, recent small subcortical infarcts (RSSI) do not have a lower size boundary, and the smallest diffusion-weighted imaging (DWI) infarcts, which we term acute subcortical cerebral microinfarcts (As-CMI) with lesion diameter less than 5 mm, might have clinical implications distinct from RSSI. We aimed to investigate the distinct characteristics of As-CMI as compared to the larger size of RSSI regarding vascular risk factors, clinical manifestation, radiological markers of SVD distribution, and outcomes. METHODS: In a consecutive cohort, patients were selected with a magnetic resonance DWI-confirmed RSSI between January 2010 and November 2020. We measured axial infarct diameter and classified patients into two groups: The As-CMI group (diameter < 5 mm) versus the Larger RSSI group (diameter 5-20 mm). Clinical variables, including vascular risk factors, clinical symptoms/signs, lesion locations, and radiological markers of cerebral small vessel disease (SVD) on MRI were analyzed between the two groups. Patients were followed up for 12 months and functional outcomes were measured by the modified ranking scale (mRS). RESULTS: In a total of 584 patients with RSSI, 23 (3.9%) were defined as As-CMI. The most common neurological deficits with As-CMI were hemiparalysis (n = 20), followed by central facial/lingual palsy (n = 10) and hemidysesthesia (n = 10). Most As-CMIs were located in the basal ganglia (n = 11), followed by the thalamus (n = 5) and centrum semiovale (n = 4). No different regional distributions and symptoms/signs frequencies were found between the two groups except for a lower percentage of dysarthria in the As-CMI group (p = 0.008). In a multivariate analysis, patients with As-CMI were independently associated with the presence of lacunes (adjusted odds ratio [aOR] 2.88; 95% confidence interval [CI] 1.21-6.84), multiple lacunes (aOR 3.5, CI 1.29-9.48) and higher total SVD burden (aOR 1.68, CI 1.11-2.53). Patients with As-CMI did not show a better functional outcome after 12 months of follow-up. CONCLUSIONS: Patients with As-CMI had a non-specific clinical profile but a higher burden of SVD, indicating As-CMI might be s sign of more severe small vascular injury. Whether its vascular features are associated with worse cognitive outcomes requires further investigation.
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Doenças de Pequenos Vasos Cerebrais , Acidente Vascular Cerebral , Biomarcadores , Infarto Cerebral/etiologia , Doenças de Pequenos Vasos Cerebrais/complicações , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética , Acidente Vascular Cerebral/complicaçõesRESUMO
Porous silicon-based anode materials have gained much interest because the porous structure can effectively accommodate volume changes and release mechanical stress, leading to improved cycling performance. Magnesiothermic reduction has emerged as an effective way to convert silica into porous silicon with a good electrochemical performance. However, corrosive HF etching is normally a mandatory step to improve the electrochemical performance of the as-synthesized silicon, which significantly increases the safety risk. This has become one of the major issues that impedes practical application of the magnesiothermic reduction synthesis of the porous silicon anode. Here, a facile HF-free method is reported to synthesize macro-/mesoporous silicon with good cyclic and rate performance by simply increasing the reduction temperature from 700 °C to 800 °C and 900 °C. The mechanism for the structure change resulting from the increased temperature is elaborated. A finite element simulation indicated that the 3D continuous structure formed by the magnesiothermic reduction at 800 °C and 900 °C could undertake the mechanical stress effectively and was responsible for an improved cyclic stability compared to the silicon synthesized at 700 °C.
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OBJECTIVE: To study the relationship between cerebral small vessel disease (CSVD) and hematoma volume in mixed-location intracerebral hemorrhage (ICH), and non-mixed ICH (hypertensive arteriopathy/cerebral amyloid angiopathy-related ICH). METHODS: We consecutively collected patients with primary ICH with MRI. Mixed-location ICH was defined as having ICH or cerebral microbleeds (CMBs) in both lobar and deep regions. CSVD markers including lacunes, white matter hyperintensities (WMH), CMBs, and enlarged perivascular spaces (EPVS) were assessed on brain MRI during hospitalization. Multivariable binary logistic regression (≥30 ml vs. <30 ml) and linear regression analyses (log-transformed hematoma volume as dependent variable) were implemented to explore the association between CSVD and hematoma volume. RESULTS: Of the 167 included patients, 69 (41.3%) had mixed-location ICH, with higher prevalence of lacune, more CMB count, higher WMH score and total CSVD score than those with non-mixed ICH (all p < .001). Higher WMH score was associated with lower risk of hematoma volume ≥30 ml (adjusted OR 0.521, 95% CI 0.299-0.908, p = .021) in patients with mixed-location ICH. Also, multivariable linear regression showed the association of smaller hematoma volume with higher CSVD burden, especially in mixed-location ICH (ß = -0.349, p = .019 for CMB ≥ 5; ß = -0.183, p < .001 for WMH score; ß = -0.456, p = .002 for EPVS>20 in basal ganglia and/or centrum semiovale; ß = -0.256, p = .002 for CSVD score), while these relationships were not observed in non-mixed ICH. CONCLUSIONS: Higher CSVD burden is associated with smaller hematoma volume in mixed-location ICH, but not in non-mixed ICH, which is novel and needs further studies with larger sample size to confirm our results and explore the underlying mechanisms.
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Doenças de Pequenos Vasos Cerebrais , Hemorragia Intracraniana Hipertensiva , Angiopatia Amiloide Cerebral , Hemorragia Cerebral/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Hematoma/diagnóstico por imagem , Humanos , Imageamento por Ressonância MagnéticaRESUMO
Silicon anodes have attracted much attention owing to their high theoretical capacity. Nonetheless, an inevitable and enormous volumetric expansion of silicon in the lithiated state restrained the development of the silicon anode for lithium-ion batteries. Fortunately, the utilization of the high-performance binder is a promising and effective way to overcome such obstacles. Herein, a polymer of intrinsic microporosity (PIM) is applied as the binder for the silicon anode, which is composed of a rigid polymer backbone, an intrinsic porous structure, and active carboxyl groups (PIM-COOH). Compared to the traditional binder, both the long-term stability and rate performance of the electrode using PIM-COOH as the binder are significantly improved. The mechanism responsible for the enhanced performance is investigated. The PIM-COOH binder provides stronger adhesion toward the current collector than the conventional binders. The unique rigid polymer backbone and porous structure of the PIM-COOH binder enable a good capability to withstand the volume change and external stress generated by the Si anode. The porous structure of the PIM-COOH binder enhances lithium-ion transportation compared to the SA binder, which improves rate performance of the silicon anode. This work provides a unique insight into design, synthesis, and utilization of the binders for lithium-ion batteries.
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BACKGROUND: It is unclear whether non-high-density lipoprotein cholesterol (Non-HDL-C) is associated with haemorrhagic transformation (HT) after acute ischaemic stroke (AIS). We aimed to explore the association between Non-HDL-C and HT, as well as compare the predictive values of Non-HDL-C and low-density lipoprotein cholesterol (LDL-C) for HT. METHODS: We consecutively enrolled AIS patients within 7 days of stroke onset. Participants were divided into four categories according to quartiles of Non-HDL-C. HT was assessed by follow-up brain imaging. We assessed the association between Non-HDL-C, LDL-C and HT in multivariate logistic regression analysis. RESULTS: A total of 2043 patients were included, among whom 232 were identified as HT. Compared with the highest quartiles, the first, second and third quartiles of Non-HDL-C were associated with increased risk of HT (adjusted odds ratios [ORs] 1.74 [95% confidence interval [CI] 1.09-2.78], 2.01[95% CI 1.26-3.20], and 1.76 [95% CI 1.10-2.83], respectively, P for trend = 0.024). Similar results were found for LDL-C. There was significant interaction between Non-HDL-C and age (P for interaction = 0.021). The addition of Non-HDL-C and LDL-C to conventional factors significantly improved predictive values [Non-HDL-C, net reclassification index (NRI) 0.24, 95%CI 0.17-0.31, P < 0.001; LDL-C, NRI 0.15, 95%CI 0.08-0.22, P = 0.03]. CONCLUSIONS: Low Non-HDL-C was associated with increased risks of HT. In addition, Non-HDL-C has similar effects as LDL-C for predicting HT.
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Isquemia Encefálica/complicações , LDL-Colesterol/sangue , Colesterol/sangue , Lipoproteínas/sangue , Acidente Vascular Cerebral/complicações , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
BACKGROUND: Emergency endoscopic retrograde cholangiopancreatography (ERCP) for ascending acute cholangitis in patients with severe comorbidities is challenging. Here, we evaluated the efficacy and safety of one-stage ERCP in such patients by performing a retrospective study. METHODS: We included all patients with ascending acute cholangitis and undergoing ERCP between January 2017 and March 2019. In total, we recruited 212 patients: 74 and 138 with and without severe comorbidities, respectively. We collected and analyzed data related to basal characteristics, ERCP, and clinical outcomes. RESULTS: Elderly age (76.20 ± 9.99 years vs. 66.52 ± 8.16 years, P = 0.000), higher levels of leukocyte count (15.86 ± 2.47 × 109/ml vs. 13.49 ± 1.65 × 109/ml, P = 0.000), and serum bilirubin (3.11 ± 1.29 mg/dl vs. 1.94 ± 0.90 mg/dl, P = 0.000) were present in patients with severe comorbidities. A significantly higher proportion of these patients were severe cases (32.4% vs. 6.5%, P = 0.000), American Society of Anesthesiologists (ASA) stage V status (37.8% vs. 10.1%, P = 0.000) and had undergone general anesthesia (56.8% vs. 18.8%, P = 0.000). Successful biliary cannulation and complete stone clearance in one session were achieved in 207 and 202 patients, respectively. Mean length of hospital stay was 8.02 ± 2.71 days. Forty-three patients required ICU stay with the mean length of 3.26 ± 3.51 days. In-hospital mortality occurred in seven patients; all these patients had severe comorbidities. ERCP details, including urgent and early ERCP, biliary cannulation, complete stone clearance in one session, stent insertion, and complications were not significantly different between the two groups. Patients with severe comorbidities had a longer in-hospital stay (9.39 ± 3.15 days vs. 7.29 ± 2.11 days, P = 0.000), a higher proportion of ICU admission (45.9% vs. 6.5%, P = 0.000), and a longer ICU stay length (4.88 ± 4.37 days vs. 1.44 ± 0.52 days, P = 0.000). Our data also revealed that early diagnosis is an important predictor associated with clinical outcomes. CONCLUSIONS: One-stage ERCP is safe and effective for ascending acute cholangitis caused by choledocholithiasis. Early diagnosis is a significant predictor of clinical outcomes.
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Colangiopancreatografia Retrógrada Endoscópica/métodos , Colangite/cirurgia , Coledocolitíase/cirurgia , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Colangite/etiologia , Coledocolitíase/complicações , Coledocolitíase/epidemiologia , Comorbidade , Emergências , Feminino , Mortalidade Hospitalar/tendências , Hospitalização , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: Hemorrhagic transformation (HT) is a common complication of acute ischemic stroke (AIS), and inflammation has been found to play an important role in the occurrence of HT. We aimed to investigate the impact of lymphocyte-to-monocyte ratio (LMR), a maker of inflammatory status, on HT in patients with AIS. METHODS: Consecutive AIS patients within 7 days from stroke onset were enrolled between January 2016 and October 2017. LMR was calculated according to lymphocyte and monocyte counts obtained within 24 h on admission. Patients were categorized into three groups according to LMR tertiles. HT was detected by follow-up computed tomography (CT) or magnetic resonance imaging (MRI) during hospitalization. The multivariate logistic analysis was used to evaluate the independent relationship between LMR and HT. RESULTS: A total of 1005 patients were finally included. HT was observed in 99 (9.9%) patients, with 51 (5.1%) hemorrhagic infarction (HI) and 48 (4.8%) parenchymal hematoma (PH). After adjustment for potential confounders, the odds ratio (OR) of HT was 0.523 (95% confidence interval [CI] 0.293-0.936, P = 0.029) for the highest LMR tertile compared with the lowest tertile. Multiple-adjusted spline regression model showed a nonlinear approximately L-shaped relationship between LMR levels and HT (P for nonlinear trend = 0.030). There was no significant association of baseline LMR with PH (OR 0.562, 95% CI 0.249-1.268, P = 0.165). CONCLUSION: Lower LMR was independently related to higher risk of HT in patients with AIS. Admission LMR may be used as one of the predictors for HT. Further prospective multicenter studies are needed to validate our findings.
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Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico por imagem , Humanos , Linfócitos , Monócitos , Fatores de Risco , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagemRESUMO
BACKGROUND: Accurate prediction of malignant brain edema (MBE) after stroke is paramount to facilitate close monitoring and timely surgical intervention. The Enhanced Detection of Edema in Malignant Anterior Circulation Stroke (EDEMA) score was useful to predict potentially lethal malignant edema in Western populations. We aimed to validate and modify it to achieve a better predictive value for MBE in Chinese patients. METHODS: Of ischemic stroke patients consecutively admitted in the Department of Neurology, West China Hospital between January 2010 and December 2017, we included patients with anterior circulation stroke, early signs of brain edema on computed tomography within 24 h of onset, and admission National Institutes of Health Stroke Scale (NIHSS) score ≥ 8. MBE was defined as the development of signs of herniation (including decrease in consciousness and/or anisocoria), accompanied by midline shift ≥ 5 mm on follow-up imaging. The EDEMA score consisted of five parameters: glucose, stroke history, reperfusion therapy, midline shift, and cistern effacement. We created a modified score by adding admission NIHSS score to the original EDEMA score. The discrimination of the score was assessed by the area under the receiver operating characteristics curve (AUC). Calibration was assessed by Hosmer-Lemeshow test and calibration plot. We compared the discrimination of the original and modified score by AUC, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Clinical usefulness of the two scores was compared by plotting net benefits at different threshold probabilities in the decision curve analysis. RESULTS: Of the 478 eligible patients (mean age 67.3 years; median NIHSS score 16), 93 (19%) developed MBE. The EDEMA score showed moderate discrimination (AUC 0.72, 95% confidence interval [CI] 0.67-0.76) and good calibration (Hosmer-Lemeshow test, P = 0.77). The modified score showed an improved discriminative ability (AUC 0.80, 95% CI 0.76-0.84, P < 0.001; NRI 0.67, 95% CI 0.55-0.78, P < 0.001; IDI 0.07, 95% CI 0.06-0.09, P < 0.001). Decision curves showed that the modified score had a higher net benefit than the original score in a range of threshold probabilities lower than 60%. CONCLUSIONS: The original EDEMA score showed an acceptable predictive value for MBE in Chinese patients. By adding the admission NIHSS score, the modified score allowed for a more accurate prediction and clinical usefulness. Further validation in large cohorts of different ethnicities is needed to confirm our findings.
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Edema Encefálico/epidemiologia , Regras de Decisão Clínica , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/terapia , Idoso , Idoso de 80 Anos ou mais , Glicemia/metabolismo , Edema Encefálico/etiologia , Edema Encefálico/mortalidade , Edema Encefálico/cirurgia , China/epidemiologia , Técnicas de Apoio para a Decisão , Craniectomia Descompressiva , Encefalocele/etiologia , Feminino , Humanos , Hipertensão Intracraniana/etiologia , AVC Isquêmico/complicações , AVC Isquêmico/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Trombectomia , Terapia Trombolítica , Tomografia Computadorizada por Raios XRESUMO
Exosome-derived miRNAs are regarded as biomarkers for the diagnosis and prognosis of many human cancers. However, its function in clear cell renal cell carcinoma (ccRCC) remains unclear. In this study, differentially expressed miRNAs from urinal exosomes were identified using next-generation sequencing (NGS) and verified using urine samples of ccRCC patients and healthy donors. Then, the exosomes were analysed in early-stage ccRCC patients, healthy individuals and patients suffering from other urinary system cancers. Thereafter, the target gene of the miRNA was detected. Its biological function was investigated in vitro and in vivo. The results showed that miR-30c-5p could be amplified in a stable manner. Its expression pattern was significantly different only between ccRCC patients and healthy control individuals, but not compared with that of other urinary system cancers, which indicated its specificity for ccRCC. Additionally, the overexpression of miR-30c-5p inhibited ccRCC progression in vitro and in vivo. Heat-shock protein 5 (HSPA5) was found to be a direct target gene of miR-30c-5p. The depletion of HSPA5 caused by miR-30c-5p inhibition reversed the promoting effect of ccRCC growth. In conclusion, urinary exosomal miR-30c-5p acts as a potential diagnostic biomarker of early-stage ccRCC and may be able to modulate the expression of HSPA5, which is correlated with the progression of ccRCC.
Assuntos
Biomarcadores Tumorais/urina , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/urina , Exossomos/genética , Proteínas de Choque Térmico/genética , Neoplasias Renais/genética , Neoplasias Renais/urina , MicroRNAs/urina , Adulto , Idoso , Animais , Sequência de Bases , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Progressão da Doença , Chaperona BiP do Retículo Endoplasmático , Feminino , Regulação Neoplásica da Expressão Gênica , Proteínas de Choque Térmico/metabolismo , Humanos , Neoplasias Renais/patologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Pessoa de Meia-Idade , Adulto JovemRESUMO
Gliotoxin, one of the most toxic metabolites produced during the growth of Aspergillus fumigatus, can cause direct damage to the immune system and results in infection and spread of Aspergillus, or even leads to invasive aspergillosis. Accurate, rapid, and sensitive detection of the disease-specific marker gliotoxin, particularly in serum, urine, or other body fluids, is therefore an important approach to achieving early and rapid diagnosis of Invasive Aspergillus Fumigatus Infection (IAFI). In this study, aptamers that specifically bind to gliotoxin were successfully obtained using immobilization-free GO-SELEX technology. Furthermore, the performance of the aptamer, including binding affinity, targeting specificity, and structural stability, was further improved by optimizing through truncation and mutation. Finally, the optimized aptamer APT8T1M was used to develop a novel fluorescently labeled aptamer structure-switching assay (FLASSA) for the detection of gliotoxin. The method exhibited a good linear range from 0.1 nM to 100 nM of gliotoxin, with a lower detection limit of 0.05 nM. Moreover, FLASSA was applied to the detection of gliotoxin in spiked serum and urine samples. A good mean recovery of 98.76-110.85% and a low coefficient of variation (5.45-14.59%) were obtained, indicating a high degree of selectivity for gliotoxin, good reproducibility, and stability. These results show that the developed FLASSA has significant potential and offers an alternative to the traditional analytical methods for the rapid, sensitive, and efficient detection of gliotoxin, thus, providing an effective tool for the early and rapid diagnosis of IAFI.
Assuntos
Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/metabolismo , Corantes Fluorescentes/química , Gliotoxina/análise , Aptâmeros de Nucleotídeos/genética , Sequência de Bases , Gliotoxina/sangue , Gliotoxina/metabolismo , Gliotoxina/urina , Humanos , Limite de Detecção , Fatores de TempoRESUMO
BACKGROUND: Cell division cycle 42 (CDC42), an important member of the Rho family, is overexpressed in various human cancers. However, its expression and role in pancreatic cancer (PC) are not well understood. AIM: The present study was designed to investigate the expression patterns and underlying cellular mechanisms of CDC42 in PC. METHODS: First, immunohistochemical analysis, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were performed to detect CDC42 expression in clinical pancreatic carcinoma and adjacent tissues. Second, differential expression of CDC42 between PC cells and normal cells was evaluated by qRT-PCR and Western blotting. Third, the correlation between CDC42 expression as well as clinicopathological characteristics and patient survival was analyzed. Finally, CDC42 was knocked down to examine its role both in vivo and in vitro. RESULTS: The results showed significantly increased CDC42 expression in pancreatic tumor tissues compared with adjacent normal tissues, as revealed by qRT-PCR, Western blotting and immunostaining. Compared to PanC-1 cells, CDC42 expression was downregulated in HPDE6-C7 cells as shown by qRT-PCR and Western blotting. High CDC42 expression was observed in 69.2% (83/120) of pancreatic adenocarcinoma patients and was significantly associated with tumor differentiation (p = 0.013), median tumor size (p = 0.005), tumor infiltration (pT stage, p = 0.04), lymph nodal status (pN stage, p = 0.044) and TNM staging (p = 0.003). Multivariate Cox regression analysis revealed CDC42 expression to be an independent predictor of survival of PC patients (HR 3.0, 95% CI 1.60-5.61, p = 0.001). Finally, we found that CDC42 promoted the proliferation of PanC-1 cells both in vivo and in vitro. CONCLUSIONS: Our findings reveal that CDC42 might play an important role in promoting PC development, and the findings suggest that CDC42 might serve as a potential prognostic indicator of PC.