The value of cardiopulmonary comorbidity in patients with acute large vessel occlusion stroke undergoing endovascular thrombectomy: a retrospective, observational cohort study.

BACKGROUND: Chronic lung and heart diseases are more likely to lead an intensive end point after stroke onset. We aimed to investigate characteristics and outcomes of endovascular thrombectomy (EVT) in patients with acute large vessel occlusion stroke (ALVOS) and identify the role of comorbid chronic cardiopulmonary diseases in ALVOS pathogenesis. METHODS: In this single-center retrospective study, 191 consecutive patients who underwent EVT due to large vessel occlusion stroke in neurological intensive care unit were included. The chronic cardiopulmonary comorbidities and several conventional stroke risk factors were assessed. The primary efficacy outcome was functional independence (defined as a mRS of 0 to 2) at day 90. The primary safety outcomes were death within 90 days and the occurrence of symptomatic intracranial hemorrhage(sICH). Univariate analysis was applied to evaluate the relationship between factors and clinical outcomes, and logistic regression model were developed to predict the prognosis of ALVOS. RESULTS: Endovascular therapy in ALVOS patients with chronic cardiopulmonary diseases, as compared with those without comorbidity, was associated with an unfavorable shift in the NHISS 24 h after EVT [8(4,15.25) versus 12(7.5,18.5), P = 0.005] and the lower percentage of patients who were functionally independent at 90 days, defined as a score on the modified Rankin scale of 0 to 2 (51.6% versus 25.4%, P = 0.000). There was no significant between-group difference in the frequency of mortality (12.1% versus 14.9%, P = 0.580) and symptomatic intracranial hemorrhage (13.7% versus 19.4%, P = 0.302) or of serious adverse events. Moreover, a prediction model showed that existence of cardiopulmonary comorbidities (OR = 0.456, 95%CI 0.209 to 0.992, P = 0.048) was independently associated with functional independence at day 90. CONCLUSIONS: EVT was safe in ALVOS patients with chronic cardiopulmonary diseases, whereas the unfavorable outcomes were achieved in such patients. Moreover, cardiopulmonary comorbidity had certain clinical predictive value for worse stroke prognosis.

Effects of Viscum coloratum (Kom.) Nakai on collagen-induced rheumatoid arthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Viscum coloratum (Kom.) Nakai has been traditionally used in China for nearly a thousand years to treat rheumatic diseases. However, its efficacy and mechanisms in treating rheumatoid arthritis (RA) have not been demonstrated. AIM OF THE STUDY: To investigate the anti-arthritic effects and molecular mechanisms of Viscum coloratum (Kom.) Nakai on collagen-induced arthritic mice through network pharmacology technology and experimental validation. MATERIALS AND METHODS: First, the main ingredients of the extract of Viscum coloratum (Kom.) Nakai (EVC) were identified through chemical composition characterization using Ultra Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS). Then, the collagen-induced arthritis (CIA) model was established in DBA/1 J mice and the ameliorative effects of EVC on the progression of CIA mice were evaluated by oral treatment with different doses of the EVC for 28 days. After that, cytokine antibody microarray assay was used to detect the levels of multiple inflammation-related cytokines and chemokines in each group, and performed Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) enrichment analysis. Subsequently, the potential target for the effective chemical components of EVC in treating RA was identified using various databases. Additionally, a drug-disease target protein-protein interaction network (PPI) was conducted using Cytoscape for visualization and clustering, while GO and KEGG enrichment analyses were performed with the Metascape database. Finally, identified phenotypes and targets by network pharmacology analysis were experimentally validated in vivo. RESULTS: Treatment with EVC significantly suppressed the severity of CIA with a dramatic reduction of paw swelling, arthritis index, levels of IgGs (IgG, IgG1, IgG2a, and IgG2b), multi-inflammation-related cytokines and chemokines on the progression of CIA. Histopathological examinations showed EVC could markedly inhibit inflammatory cell infiltration, tartrate-resistant acid phosphatase (TRAP) activity of osteoclast, and bone destruction. Furthermore, GO and KEGG enrichment analyses revealed that EVC could ameliorate RA by inhibiting osteoclast differentiation and regulating multiple signaling pathways including Osteoclast differentiation, IL-17, and TNF. PPI network analysis demonstrated that AKT1, MMP9, MAPK3, and other genes were highly related to EVC in treating RA. Finally, we proved that EVC could inhibit the expression of NFTAc1, MMP9, Cathepsin K, and AKT which were closely related to osteoclast activity. CONCLUSIONS: EVC could treat RA through multiple components, multiple targets, and multiple pathways. The present study demonstrated the therapeutic efficacy of EVC and its molecular mechanisms in treating RA, indicating that it would be a potent candidate as a novel botanical drug for further investigation.

KHSRP combines transcriptional and posttranscriptional mechanisms to regulate monocytic differentiation.

RNA-binding proteins (RBPs) are widely involved in the transcriptional and posttranscriptional regulation of multiple biological processes. The transcriptional regulatory ability of RBPs was indicated by the identification of chromatin-enriched RBPs (Che-RBPs). One of these proteins, KH-type splicing regulatory protein (KHSRP), is a multifunctional RBP that has been implicated in mRNA decay, alternative splicing, and miRNA biogenesis and plays an essential role in myeloid differentiation by facilitating the maturation of miR-129. In this study, we revealed that KHSRP regulates monocytic differentiation by regulating gene transcription and RNA splicing. KHSRP-occupied specific genomic sites in promoter and enhancer regions to regulate the expression of several hematopoietic genes through transcriptional activation and bound to pre-mRNA intronic regions to modulate alternative splicing during monocytic differentiation. Of note, KHSRP had co-regulatory effects at both the transcriptional and posttranscriptional levels on MOGOH and ADARB1. Taken together, our analyses revealed the dual DNA- and RNA-binding activities of KHSRP and have provided a paradigm to guide the analysis of other functional Che-RBPs in different biological systems.

pH and Magnetism Dual-Responsive Pickering Emulsion Stabilized by Dynamic Covalent Fe3O4 Nanoparticles.

Herein, we describe pH and magnetism dual-responsive liquid paraffin-in-water Pickering emulsion stabilized by dynamic covalent Fe3O4 (DC-Fe3O4) nanoparticles. On one hand, the Pickerinfigureg emulsions are sensitive to pH variations, and efficient demulsification can be achieved by regulating the pH between 10 and 2 within 30 min. The dynamic imine bond in DC-Fe3O4 can be reversibly formed and decomposed, resulting in a pH-controlled amphiphilicity. The Pickering emulsion can be reversibly switched between stable and unstable states by pH at least three times. On the other hand, the magnetic Fe3O4 core of DC-Fe3O4 allowed rapid separation of the oil droplets from Pickering emulsions under an external magnetic field within 40 s, which was a good extraction system for purifying the aqueous solution contaminated by rhodamine B. The dual responsiveness enables Pickering emulsions to have better control of their stability and to be applied more broadly.

METTL3 preferentially enhances non-m6A translation of epigenetic factors and promotes tumourigenesis.

METTL3 encodes the predominant catalytic enzyme to promote m6A methylation in nucleus. Recently, accumulating evidence has shown the expression of METTL3 in cytoplasm, but its function is not fully understood. Here we demonstrated an m6A-independent mechanism for METTL3 to promote tumour progression. In gastric cancer, METTL3 could not only facilitate cancer progression via m6A modification, but also bind to numerous non-m6A-modified mRNAs, suggesting an unexpected role of METTL3. Mechanistically, cytoplasm-anchored METTL3 interacted with PABPC1 to stabilize its association with cap-binding complex eIF4F, which preferentially promoted the translation of epigenetic factors without m6A modification. Clinical investigation showed that cytoplasmic distributed METTL3 was highly correlated with gastric cancer progression, and this finding could be expanded to prostate cancer. Therefore, the cytoplasmic METTL3 enhances the translation of epigenetic mRNAs, thus serving as an oncogenic driver in cancer progression, and METTL3 subcellular distribution can assist diagnosis and predict prognosis for patients with cancer.

Eight undescribed steroidal saponins including an unprecedented 16, 26-epoxy-furostanol saponin from Solanum xanthocarpum and their cytotoxic activities.

Eight undescribed steroidal saponins named solasaponins A-H were isolated from the fruits of Solanum xanthocarpum, including an unusual 16,26-epoxy-furostanol saponin, two furostanol saponins, three isospirostanol saponins, two pseudo-spirostanol saponins. The structures of all compounds were elucidated by extensive spectroscopic data analyses (1D, 2D NMR, and HRESIMS) combined with physico-chemical analysis methods (acid hydrolysis, optical rotation, and IR). The cytotoxicities of all compounds in vitro against two human cancer cell lines (A-549 and HepG2) were evaluated by CCK-8 assay.

pH-Responsive Nanoemulsions Based on a Dynamic Covalent Surfactant.

Developing solid-free nanoemulsions with pH responsiveness is desirable in enhanced oil recovery (EOR) applications. Here, we report the synthesis of an interfacial activity controllable surfactant (T-DBA) through dynamic imine bonding between taurine (T) and p-decyloxybenzaldehyde (DBA). Instead of macroemulsions, nanoemulsions can be prepared by using T-DBA as an emulsifier. The dynamic imine bond of T-DBA enables switching between the active and inactive states in response to pH. This switching of interfacial activity was used to gate the stability of nanoemulsions, thus enabling us to turn the nanoemulsions off and on. Using such dynamic imine bonds to govern nanoemulsion stability could enable intelligent control of many processes such as heavy oil recovery and interfacial reactions.

Myocardial extracellular volume fraction quantification in an animal model of the doxorubicin-induced myocardial fibrosis: a synthetic hematocrit method using 3T cardiac magnetic resonance.

BACKGROUND: Visualization of diffuse myocardial fibrosis is challenging and mainly relies on histology. Cardiac magnetic resonance (CMR), which uses extracellular contrast agents, is a rapidly developing technique for measuring the extracellular volume (ECV). The objective of this study was to evaluate the feasibility of the synthetic myocardial ECV fraction based on 3.0 T CMR compared with the conventional ECV fraction. METHODS: This study was approved by the local animal care and ethics committee. Fifteen beagle models with diffuse myocardial fibrosis, including 12 experimental and three control subjects, were generated by injecting doxorubicin 30 mg/m2 intravenously every three weeks for 24 weeks. Short-axis (SAX) and 4-chamber long-axis (LAX) T1 maps were acquired for both groups. The association between hematocrit (Hct) and native T1blood was derived from 9 non-contrast CMR T1 maps of 3 control beagles using regression analysis. Synthetic ECV was then calculated using the synthetic Hct and compared with conventional ECV at baseline and the 16th and 24th week after doxorubicin administration. The collagen volume fraction (CVF) value was measured on digital biopsy samples. Bland-Altman plots were used to analyze the agreement between conventional and synthetic ECV. Correlation analyses were performed to explore the association among conventional ECV, synthetic ECV, CVF, and left ventricular ejection fraction (LVEF). RESULTS: The regression model synthetic Hct = 816.46*R1blood - 0.01 (R2=0.617; P=0.012) was used to predict the Hct from native T1blood values. The conventional and synthetic ECV fractions of experimental animals at the 16th and 24th week after modeling were significantly higher than those measured at the baseline (31.4%±2.2% and 36.3%±2.1% vs. 22.9%±1.7%; 29.9%±2.4% and 36.1%±2.6% vs. 22.0%±2.4%; all with P<0.05). Bland-Altman plots showed a bias (1.0%) between conventional and synthetic ECV with 95% limits of agreement of -2.5% to 4.4% in the per-subject analysis (n=21) and a bias (1.0%) between conventional and synthetic ECV with 95% limits of agreement of -2.4% to 4.3% in the per-segment analysis (n=294). Conventional and synthetic ECV were well correlated with CVF (r=0.937 and 0.925, all with P<0.001, n=10). CONCLUSIONS: Our study showed promising results for using synthetic ECV compared with the conventional ECV for providing accurate quantification of myocardial ECV without the need for blood sampling.

Diagnostic accuracy of coronary CT angiography: comparison of filtered back projection and iterative reconstruction with different strengths.

PURPOSE: To investigate the diagnostic accuracy of coronary computed tomographic (CT) angiography (CCTA) using filtered back projection (FBP) and sinogram-affirmed iterative reconstruction (SAFIRE) of different strength factors with invasive coronary angiography as the reference standard. MATERIALS AND METHODS: Fifty consecutive patients (32 men and 18 women) prospectively underwent electrocardiogram-triggered CCTA on a dual-source CT system. The acquisition window was set depending on the heart rate (HR): HR of less than 60 beats per minute (bpm) at the 70% RR interval, 61 to 80 bpm at 30% to 80% RR interval, and greater than 80 bpm at 30% to 50% RR interval; 100 kV and 359 to 377 mA s for patients with a body mass index of less than 24 kg/m, and 410 to 438 mA s at 120 kV for patients with a body mass index of 24 kg/m or greater. Image data were reconstructed using both FBP and SAFIRE. Sinogram-affirmed iterative reconstruction series were reconstructed using 3 different strength factors. Two blinded observers independently assessed the image quality and image impression of each coronary segment using a 4-point scale (1, non-diagnostic; and 4, excellent). Image noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were measured. Filtered back projection and all SAFIRE series were independently evaluated for coronary artery stenosis (>50%), and their diagnostic accuracy was compared with invasive coronary angiography. RESULTS: Statistically significant increases in SNR and CNR were obtained when higher strength factors were used. The highest SNR and CNR were found with the highest SAFIRE strength factor of 5; however, this strength also resulted in a more unfamiliar, "plasticlike" image appearance. Imaging quality scores of FBP and different SAFIRE strengths were 3.37 ± 0.49, 3.41 ± 0.47, 3.52 ± 0.30, and 3.48 ± 0.35, respectively (P < 0.001). The diagnostic accuracies were 92.91%, 93.76%, 95.28%, and 94.94% on per-segment level, respectively (P = 0.993). A tendency toward higher diagnostic performance was observed with SAFIRE strength factor 3 on per-segment analysis, albeit without reaching statistical significance. The effective radiation dose equivalent was 5.7 ± 1.6 mSv. CONCLUSION: Sinogram-affirmed iterative reconstruction provides significant improvements in image noise, SNR, and CNR compared with FBP, which are progressive with increasing SAFIRE strength factors. Sinogram-affirmed iterative reconstruction strength factor 3 or 5 is recommended for use with CCTA.

Improved image quality in dual-energy abdominal CT: comparison of iterative reconstruction in image space and filtered back projection reconstruction.

OBJECTIVE: The purpose of this study is to investigate whether an iterative reconstruction in image space (IRIS) algorithm improves the image quality of dual-energy CT abdominal examinations performed during the hepatic arterial phase. MATERIALS AND METHODS: Seventy patients with suspected liver masses underwent contrast-enhanced multiphase abdominal examination and were enrolled in the study. A dual-energy CT protocol was performed in the hepatic arterial phase (parameters: tube A, 140 kV and 90 mA; tube B, 80 kV and 382 mA; automatic tube current modulation on; and collimation, 14 × 1.2 mm). The reconstructions were performed with filtered back projection (FBP) and IRIS algorithms at a slice thickness of 3 mm and kernels of B30 and I30. The image noise was measured on the liver, aorta, and subcutaneous fat on the FBP and IRIS fusion images (m = 0.3) at the same position. The image noise and diagnostic acceptability of all images were scored by two radiologists. RESULTS: The image noise using the IRIS algorithm was lower than that using the standard FBP algorithm on the liver, aorta, and subcutaneous fat, respectively. The signal-to-noise ratio and contrast-to-noise ratio of images reconstructed with the IRIS algorithm also were significantly higher than for those reconstructed with the FBP algorithm. The diagnostic acceptability score using the IRIS algorithm was higher than that using the FBP algorithm at the same dose level (1.20 ± 0.40 vs 1.37 ± 0.57; p < 0.05). CONCLUSION: Compared with standard FBP reconstruction, an IRIS algorithm enables significant reduction of image noise and improvement of image quality and has the potential to decrease radiation exposure during contrast-enhanced dual-energy CT abdominal examination.

Low dose prospective ECG-gated delayed enhanced dual-source computed tomography in reperfused acute myocardial infarction comparison with cardiac magnetic resonance.

PURPOSE: To determine whether prospective electrocardiogram (ECG)-gated delayed contrast-enhanced dual-source computed tomography (DCE-DSCT) can accurately delineate the extension of myocardial infarction (MI) compared with delayed enhanced cardiac MR (DE-MR). MATERIAL AND METHODS: Eleven patients were examined using dual-source CT and cardiac MR in 2 weeks after a first reperfused MI. DCE-DSCT scan protocol was performed with prospective ECG-gating sequential scan model 7 min after contrast administration. In a 17-model, infarcted myocardium detected by DE-MR was categorized as transmural and subendocardial extension. Segment of infarcted location and graded transmurality were compared between DCE-MDCT and DE-MR. RESULTS: In all eleven patients, diagnostic quality was obtained for depicting delayed enhanced myocardium. Agreement between DCE-DSCT and MR was good on myocardial segment based comparison (kappa=0.85, p<0.001), and on transmural and subendocardial infarction type comparison (kappa=0.82, p<0.001, kappa=0.52, p<0.001, respectively). CT value was higher on infarcted region than that of normal region (100.02±9.57 HU vs. 72.63±7.32 HU, p<0.001). Radiation dose of prospectively ECG-gating protocol were 0.99±0.08 mSv (0.82-1.19 mSv). CONCLUSIONS: Prospective ECG-gated DCE-DSCT can accurately assess the extension and the patterns of myocardial infarction with low radiation dose.