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Objectives: Post-stroke epilepsy (PSE) is associated with increased morbidity and mortality. This study aimed to develop and validate a novel prediction model combining clinical factors and radiomics features to accurately identify patients at high risk of developing PSE after intracerebral haemorrhage (ICH). Methods: Researchers performed a retrospective medical chart review to extract derivation and validation cohorts of patients with first-ever ICH that attended two tertiary hospitals in China between 2010 and 2020. Clinical data were extracted from electronic medical records and supplemented by tele-interview. Predictive clinical variables were selected by multivariable logistic regression to build the clinical model. Predictive radiomics features were identified, and a Rad-score was calculated according to the coefficient of the selected feature. Both clinical variables and radiomic features were combined to build the radiomics-clinical model. Performances of the clinical, Rad-score, and combined models were compared. Results: A total of 1571 patients were included in the analysis. Cortical involvement, early seizures within 7 days of ICH, NIHSS score, and ICH volume were included in the clinical model. Rad-score, instead of ICH volume, was included in the combined model. The combined model exhibited better discrimination ability and achieved an overall better benefit against threshold probability than the clinical model in the decision curve analysis (DCA). Conclusions: The combined radiomics-clinical model was better able to predict ICH-associated PSE compared to the clinical model. This can help clinicians better predict an individual patient's risk of PSE following a first-ever ICH and facilitate earlier PSE diagnosis and treatment. Key Points: • Radiomics has not been used in predicting the risk of developing PSE. • Higher Rad-scores were associated with higher risk of developing PSE. • The combined model showed better performance of PSE prediction ability. [ABSTRACT FROM AUTHOR]

The nuclear pore complex (NPC) is the bidirectional gate that mediates the exchange of macromolecules or their assemblies between nucleus and cytoplasm1–3. The assembly intermediates of the ribosomal subunits, pre-60S and pre-40S particles, are among the largest cargoes of the NPC and the export of these gigantic ribonucleoproteins requires numerous export factors4,5. Here we report the cryo-electron microscopy structure of native pre-60S particles trapped in the channel of yeast NPCs. In addition to known assembly factors, multiple factors with export functions are also included in the structure. These factors in general bind to either the flexible regions or subunit interface of the pre-60S particle, and virtually form many anchor sites for NPC binding. Through interactions with phenylalanine-glycine (FG) repeats from various nucleoporins of NPC, these factors collectively facilitate the passage of the pre-60S particle through the central FG repeat network of the NPC. Moreover, in silico analysis of the axial and radial distribution of pre-60S particles within the NPC shows that a single NPC can take up to four pre-60S particles simultaneously, and pre-60S particles are enriched in the inner ring regions close to the wall of the NPC with the solvent-exposed surface facing the centre of the nuclear pore. Our data suggest a translocation model for the export of pre-60S particles through the NPC.We report the cryo-electron microscopy structure of native pre-60S particles trapped in the channel of the yeast nuclear pore complex, suggesting a translocation model for the export of pre-60S particles through the complex. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the value of tumour-to-muscle (T/M) ratios and Patlak Ki images extracted from whole-body dynamic 18F-fluoromisonidazole (FMISO) PET/CT Patlak multi-parameter imaging for evaluating the early radiosensitizing effect of oleanolic acid (OA). Twenty-four rats with C6 gliomas were divided into 4 groups and treated with OA (group B), radiotherapy (group C), both (group D) or neither (group A). Whole-body dynamic 18F-FMISO PET/CT scans were performed for 120 min before treatment and 24 h following the treatment course. The tumour samples were dissected for hematoxylin and eosin staining, and HIF-1α, Ki-67 and GLUT-1 immunohistochemical staining. PET images were analysed using kinetic modelling (Patlak Ki) and static analysis (T/M ratios), and correlated with immunohistochemical results. The changes in T/M ratios, Ki values and tumour volume before treatment and 24 h following the treatment course were compared, and the survival time of tumour-bearing rats was recorded. Kaplan–Meier analysis showed that OA combined with radiotherapy can inhibit tumour growth and prolong the survival time of tumour-bearing rats. Whole-body dynamic 18F-FMISO PET/CT showed that the Ki values in group D were significantly lower than those in group C, whilst there was no significant difference in T/M ratios between groups C and D. The Pearson correlation coefficient analysis showed that Ki values were significantly related to immunohistochemical results. Our study suggests that Patlak Ki images may add value to PET/CT static images for evaluating the early radio-sensitizing effect of OA. [ABSTRACT FROM AUTHOR]

Copper-based metal–organic frameworks (MOF) and multi-walled carbon nanotubes (HKUST-1-MWCNTs) composite were synthesized by one-step hydrothermal method, and PDA-enzyme-HKUST-1-MWCNTs composite was prepared by one-pot method for the construction of glucose biosensors, which realized the sensitive amperometric detection of glucose at 0.7 V (vs. SCE). The sensitivity of the sensor for glucose detection was 178 μA mM−1cm−2 in the wide linear range of 0.005 ~ 7.05 mM, the detection limit was 0.12 μM and the corresponding RSD was 3.8%. Its high performance is mainly benefitted from the high porosity and large specific surface area of HKUST-1, the good conductivity of MWCNTs, and the excellent adhesion and dispersion of PDA. The strategy of combining PDA and MWCNTs to improve the dispersion and conductivity of MOF is expected to achieve a wider application of MOF-based materials in the electrochemical biosensing field. [ABSTRACT FROM AUTHOR]

Blood–brain barrier (BBB) disruption has been recognized as an early hallmark of multiple sclerosis (MS) pathology. Our previous studies have shown that 2-(2-Benzofuranyl)-2-imidazoline (2-BFI) protected against experimental autoimmune encephalomyelitis (EAE), a classic animal model of MS. However, the potential effects of 2-BFI on BBB permeability have not yet been evaluated in the context of EAE. Herein, we aimed to investigate the effect of 2-BFI on BBB permeability in both an animal model and an in vitro BBB model using TNF-α to imitate the inflammatory damage to the BBB in MS. In the animal model, 2-BFI reduced neurological deficits and BBB permeability in EAE mice compared with saline treatment. The Western blot results indicated that 2-BFI not only alleviated the loss of the tight junction protein occludin caused by EAE but also inhibited the activation of the NR1-ERK signaling pathway. In an in vitro BBB model, 2-BFI (100 μM) alleviated the TNF-α-induced increase in permeability and reduction in expression of occludin in monolayer bEnd.3 cells. Similar protective effects were also observed after treatment with the NMDAR antagonist MK801. The Western blot results showed that the TNF-α-induced BBB breakdown and increase in NMDAR subunit 1 (NR1) levels and ERK phosphorylation could be blocked by pretreatment with 2-BFI or MK801. However, no additional effect was observed on BBB permeability or the expression of occludin and p-ERK after pretreatment with both 2-BFI and MK801. Our study indicates that 2-BFI alleviates the disruption of BBB in the context of inflammatory injury similar to that of MS by targeting NMDAR1, as well as by likely activating the subsequent ERK signaling pathway. These results provide further evidence for 2-BFI as a potential drug for the treatment of MS. [ABSTRACT FROM AUTHOR]

Background: Approximately two-thirds of patients with newly diagnosed epilepsy become seizure-free after antiepileptic drug (AED) treatment. A crucial issue for these patients and their families, especially after a long period of seizure freedom, is when to stop their medications.Objective: The aim of this study was to identify the optimal timing of AED withdrawal in adults with focal epilepsy who had been seizure-free for ≥ 2 years.Methods: Adults with focal epilepsy who had been seizure-free for ≥ 2 years were recruited. Based on their decision to discontinue (withdrawal) or continue (non-withdrawal) AED treatment, patients were assigned to withdrawal or non-withdrawal subgroups according to the length of remission (2 to < 3 years, 3 to < 4 years, 4 to < 5 years and ≥ 5 years). The relapse risks of the withdrawal and corresponding non-withdrawal subgroups were compared, and the relative relapse risks were assessed in a Cox proportional hazard regression model.Results: A total of 213 eligible patients began to withdraw from AED treatment; 70 had been seizure-free for 2 to < 3 years, 62 had been seizure-free for 3 to < 4 years, 37 had been seizure-free for 4 to < 5 years and 44 had been seizure-free for ≥ 5 years. The figures for the corresponding non-withdrawal subgroups were 463, 334, 251 and 182, respectively. There was a significantly higher risk of seizure relapse in patients withdrawing from AEDs after 2 to < 5 years of seizure freedom than in the corresponding non-withdrawal controls, and the relative relapse risk was 3.052 (95% confidence interval [CI] 2.126-4.381; p < 0.001) for the seizure-free period of 2 to < 3 years, 3.617 (95% CI 2.384-5.488; p < 0.001) for 3 to < 4 years and 2.644 (95% CI 1.456-4.799; p = 0.001) for 4 to < 5 years. However, for patients who were seizure-free for ≥ 5 years, AED withdrawal did not significantly increase the risk of seizure relapse compared with that of patients continuing treatment (hazard ratio [HR] 1.362, 95% CI 0.634-2.926, p = 0.428). Compared with a seizure-free period of 2 to < 3 years, the relative relapse risk after AED withdrawal was significantly reduced only after being seizure-free for ≥ 5 years (HR 0.441, 95% CI 0.233-0.834; p = 0.012).Conclusion: Overall, for adults with focal epilepsy, withdrawal from AEDs significantly increased the risk of seizure relapse after being seizure-free for 2 to < 5 years, but might not increase the risk if the seizure-free period was ≥ 5 years. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is an endocrine and metabolic disease characterized by high blood glucose. Diabetic nephropathy (DN) is one of the most typical diabetic complications. Cornus officinalis is a type of traditional Chinese medicine that replenishes the liver and kidney. Morroniside is one of the main characteristic components of C. officinalis. In this study, an in vitro model for simulating DN damage was established by stimulating rat glomerular mesangial cells by the advanced glycation end products. The protective mechanism and effect of morroniside in regulating receptor for advanced glycation end products signaling pathway in DN was investigated to provide experimental evidence for the prevention and treatment of DN. [ABSTRACT FROM AUTHOR]

Objective: Sites of latest mechanical activation (SOLA) have been recognized as optimal left-ventricular (LV) lead positions for cardiac resynchronization therapy (CRT). This study was aimed to investigate SOLA in ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) patients with left bundle branch block (LBBB). Methods: Sixty-four consecutive LBBB patients (47 DCM, 17 ICM), who met the standard indications for CRT and underwent resting SPECT myocardial perfusion imaging (MPI), were selected. Phase analysis was used to assess LV dyssynchrony and SOLA. The Emory Cardiac Toolbox was used to measure perfusion defects. LV dyssynchrony and SOLA were compared between the DCM patients with wide (≥150 ms) and moderate (120-150 ms) QRS durations (QRSd). The relationship between SOLA and perfusion defects was analyzed in the ICM patients. Results: The DCM patients with wide QRSd had significantly more LV dyssynchrony than those with moderate QRSd. Lateral SOLA were significantly more frequent in the DCM patients with wide QRSd than those with moderate QRSd (96 % vs. 62 %, p = 0.010). In the ICM patients, SOLA were either in the scar segments (82 %) or in the segments immediately adjacent to the scar segments (18 %), regardless of QRSd. Conclusion: Lateral SOLA were more frequent in the DCM patients with wide QRSd than those with moderate QRSd. Such relationship was not observed in the ICM patients, where SOLA were associated with scar location rather than QRSd. These findings support the use of SPECT MPI to aid the selection of potential CRT responders and guide LV lead placement. [ABSTRACT FROM AUTHOR]

Bufadienolides, known ligands of the sodium pump, have been shown to inhibit the proliferation of several cancer cell types. However, their development to date as anticancer agents has been impaired by a narrow therapeutic margin resulting from their potential to induce cardiotoxicity. In the present study, we examined the effects of bilirubin, an endogenous antioxidant, on the cardiotoxicity of bufadienolides (derived from toad venom) in guinea-pigs. The results showed that bufadienolides (8 mg/kg) caused ventricular arrhythmias, conduction block, cardiac dysfunction and death in guinea-pigs. Pretreatment with bilirubin (75 and 150 mg/kg) significantly prevented bufadienolide-induced premature ventricular complexes, ventricular tachycardia, ventricular fibrillation and death. Bilirubin also markedly improved the inhibition of cardiac contraction in bufadienolide-treated guinea-pigs as evidenced by increases in left ventricular systolic pressure and decreases in left ventricular diastolic pressure in vivo. Furthermore, bilirubin significantly reduced the intracellular sodium content ([Na]) in ex vivo bufadienolide-stimulated guinea-pig ventricular myocytes loaded with the sodium indicator Sodium Green. An antitumor study showed that bilirubin did not compromise the ability of bufadienolides to inhibit gastric cancer cell MGC-803 proliferation. These results suggested that bilirubin can attenuate bufadienolide-induced arrhythmias and cardiac dysfunction in guinea-pigs by reducing elevated [Na] and may improve bufadienolide therapeutic index in cancer treatment. [ABSTRACT FROM AUTHOR]

A simple, efficient and accurate liquid chromatographic method was established to determine five flavonoid aglycones, 7-hydroxy flavonone, pinocembrin, 2′,4′-dihydroxy chalcone, 2′-hydroxy-4′-methoxy chalcone and pinostrobin in the whole plant powder of Oxytropis falcata Bunge. These five compounds were separated on an Agilent Zorbax Eclipse XDB-C8 column (150 × 4.6 mm, 5 μm). Mobile phases were composed of water containing 0.1% v/v formic acid and acetonitrile using gradient elution. The established method was validated for linearity, accuracy, precision, limit of detection and quantitation, repeatability and stability. [ABSTRACT FROM AUTHOR]