关键词： Chorioallantoic membrane   Tumor   Cancer   Patient-derived xenograft  

摘要： A variety of in vivo experimental models have been established for the studies of human cancer using both cancer cell lines and patient-derived xenografts (PDXs). In order to meet the aspiration of precision medicine, the in vivomurine models have been widely adopted. However, common constraints such as high cost, long duration of experiments, and low engraftment efficiency remained to be resolved. The chick embryo chorioallantoic membrane (CAM) is an alternative model to overcome some of these limitations. Here, we provide an overview of the applications of the chick CAM model in the study of oncology. The CAM model has shown significant retention of tumor heterogeneity alongside increased xenograft take rates in several PDX studies. Various imaging techniques and data analysis have been applied to study tumor metastasis, angiogenesis, and therapeutic response to novel agents. Lastly, to practically illustrate the feasibility of utilizing the CAM model, we summarize the general protocol used in a case study utilizing an ovarian cancer PDX.

关键词： Acute myocardial infarction   basophil   cardiogenic shock   eosinophil   leukocyte   short-term outcome  

摘要： Background: Patients with cardiogenic shock (CS) complicating acute myocardial infarction (AMI) are at high risk of death. Inflammation is involved in both CS and AMI, and our present study aimed to investigate the changes of leukocyte and its subtypes as well as their prognostic value in patients with CS complicating AMI. Methods: Data of 217 consecutive patients with CS complicating AMI were analyzed. The primary endpoint was 30-day all-cause mortality. The secondary endpoint was the composite events of major adverse cardiovascular events (MACE) including 30-day all-cause mortality, ventricular tachycardia/ventricular fibrillation, atrioventricular block, gastrointestinal hemorrhage and nonfatal stroke. The association of leukocyte and its subtypes with the endpoints was analyzed by Cox regression analysis. Results: Leukocyte and its subtypes including neutrophil, eosinophil, lymphocyte, monocyte and basophil were all statistically significant between survivors and nonsurvivors (all P < 0.05). Among the leukocyte subtypes, eosinophil had the highest predictive value for 30-day all-cause mortality (AUC = 0.799) and the composite of leukocyte and its subtypes improved the predictive power (AUC = 0.834). The 30-day mortality and MACE K-M curves of leukocyte and its subtypes reveal a distinct trend based on the cut-off value determined by Youden Index (all log rank P < 0.001). After multivariable adjustment, high leukocyte (>11.6 x 10(9)/L) (HR 1.815;95%CI 1.134, 2.903;P = 0.013), low eosinophil (<0.3%) (HR 2.562;95%CI 1.412, 4.648;P = 0.002) and low basophil (<= 0.1%) (HR 1.694;95%CI 1.106, 2.592;P = 0.015) were independently associated with increased risk of 30-day mortality. Similarly, high leukocyte (>11.6 x 10(9)/L) (HR 1.894;95%CI 1.285, 2.791;P = 0.001), low eosinophil (<0.3%) (HR 1.729;95%CI 1.119, 2.670;P = 0.014) and low basophil (<= 0.1%) (HR 1.560;95%CI 1.101, 2.210;P = 0.012) were independently associated with increased risk of 30-day MACE. Conclusions: L

关键词： Epithelial-mesenchymal transition   Alternative splicing   RNA binding proteins   Tumor metastasis  

摘要： Alternative splicing is an essential mechanism of gene regulation, giving rise to remarkable protein diversity in higher eukaryotes. Epithelial-mesenchymal transition (EMT) is a developmental process that plays an essential role in metazoan embryogenesis. Recent studies have revealed that alternative splicing serves as a fundamental layer of regulation that governs cells to undergo EMT. In this review, we summarize recent findings on the functional impact of alternative splicing in EMT and EMT-associated activities. We then discuss the regulatory mechanisms that control alternative splicing changes during EMT.

关键词： Acute kidney injury   acute respiratory distress syndrome   mortality   red cell distribution width  

摘要： Objectives: To determine the association of red cell distribution width (RDW) at admission with frequency of acute kidney injury (AKI) and 28-day mortality in acute respiratory distress syndrome (ARDS) patients. Methods: Two hundred fifty-eight ARDS patients were investigated in retrospective and prospective studies. The primary outcome was frequency of AKI. The secondary outcome was 28-day mortality. Results: The retrospective study included 193 ARDS patients, of which 67 (34.7%) were confirmed AKI and 76 (39.4%) died within 28 days. The RDW level in the AKI group was significantly higher than in the non-AKI group ([15.15 +/- 2.59]% vs. [13.95 +/- 1.89]%). Increased RDW was a significant predictor of frequency of AKI (odds ratio: 1.247, 95% confidence interval [CI]: 1.044, 1.489). The area under the receiver operating characteristic curve of RDW for predicting AKI was 0.687 (95%CI: 0.610, 0.764) and the cut-off value was 14.45 (sensitivity, 56.7%;specificity, 72.8%). In addition, the proportion of patients with RDW >= 14.45% in the non-survival group was notably higher compared with the survival group (48.7% vs. 29.1%). Furthermore, cox regression analysis revealed that RDW >= 14.45% was associated with 28-day mortality (hazard ratio: 1.817, 95%CI: 1.046, 3.158), while Kaplan-Meier analysis showed patients with RDW >= 14.45% had a significantly lower survival rate than those with RDW < 14.45%. The prospective study, on the other hand, included 65 ARDS patients, with frequency of AKI and 28-day mortality in the RDW >= 14.45% group significantly higher than in RDW Conclusion: RDW was a significant, independent predictor for frequency of AKI and 28-day mortality in ARDS patients.

关键词： Atrophy   autophagy   neuregulin-1 beta   sepsis   skeletal muscle  

摘要： Background: Several studies have shown that excessive protein degradation is a major cause of skeletal muscle atrophy induced by sepsis, and autophagy is the main pathway participating in protein degradation. However, the role of autophagy in sepsis is still controversial. Previously, we found that neuregulin-1 beta (NRG-1 beta) alleviated sepsis-induced diaphragm atrophy through the phosphatidylinositol-3 kinase signaling pathway. Akt/mechanistic target of rapamycin (mTOR) is a classic signaling pathway to regulate autophagy, which maintains intracellular homeostasis. This study aimed to investigate whether NRG-1 beta could alleviate sepsis-induced skeletal muscle atrophy by regulating autophagy. Methods: L6 rat myoblast cells were differentiated using 2% fetal bovine serum into myotubes, which were divided into four groups: Con group treated with normal serum;Sep group treated with septic serum to form a sepsis cell model;septic serum + NRG-1 beta (SN) group treated with septic serum for 24 h followed by injection with NRG-1 beta and incubation for another 48 h;and serum+NRG-1 beta+LY294002 group, in which the PI3K inhibitor LY294002 was added 30 min before NRG-1 beta, and other treatments were similar to those in SN group. Effects of NRG-1 beta were also evaluated in vivo using Sprague-Dawley (SD) rats, in which sepsis was induced by cecal ligation and puncture (CLP). Results: In L6 myotubes treated with septic serum, the expression of autophagy-related proteins UNC-51 like kinase 1, p-Beclin-1, and Beclin-1, and the ratio of LC3B II/I were highly increased, while protein p62 expression was decreased, indicating that autophagy was excessively activated. Moreover, NRG-1 expression was decreased, as detected by confocal immunofluorescence and western blotting. Upon exogenous addition of NRG-1 beta, autophagy was inhibited by the activation of Akt/mTOR signaling pathway, and cell viability was also increased. These effects disappeared in the presence of LY294002. In

关键词： glucocorticoids   intra-articular injection   low disease activity   remission   rheumatoid arthritis  

摘要： Background/Objective This study aimed at investigating whether a single intra-articular (IA) injection of triamcinolone acetonide (TA) could facilitate to achieve clinical remission in patients with rheumatoid arthritis (RA) exhibiting low disease activity (LDA). Methods This longitudinal study included 22 patients with RA exhibiting LDA involving wrist arthritis at our institution between April 2016 and March 2019. A single IA injection of 20 mg TA was administered into the symptomatic wrist joint. Efficacy was assessed by the primary end point of proportion of patients reaching clinical remission. Secondary end points included Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), Health Assessment Questionnaire Disability Index, adverse events, and ultrasonographic assessment of the injected wrist joints. Results Remission rates were 40% and 50% at weeks 4 and 12, respectively, and were maintained at approximately 50% until week 24. The secondary outcomes of CDAI, SDAI, and Health Assessment Questionnaire Disability Index were improved significantly at week 4, and the improvements in CDAI and SDAI continued up to week 24. Ultrasonography showed that synovial hypertrophy, power Doppler signals, and the combined score were significantly reduced at weeks 4, 12, and 24 compared with the baseline. No patient developed severe, irreversible adverse events. Conclusions Approximately half of the patients with RA exhibiting LDA who received a single IA injection of TA into the wrist joints achieved clinical remission without serious adverse events in the midterm period, suggesting that IA injection of TA might be considered as an alternative intervention to achieve remission in patients with RA exhibiting LDA.

关键词： COVID-19   Myocarditis   Vaccination  

摘要： The COVID-19 vaccine is now approved for individuals greater than 5 years of age, but vaccination rates remain lower than expected in the pediatric age group. Misinformation and widespread reporting of vaccine-related myocarditis are contributing to vaccine hesitancy. When compared to severe cardiac complications that are associated with COVID-19, vaccine-related myocarditis has a milder presentation, is easily treated, and has a good prognosis. Acute COVID-19 has been associated with higher rates of myocarditis and myocardial injury. Multisystem inflammatory syndrome in children occurs weeks after initial infection with SARS-CoV-2 and can be associated with severe cardiovascular complications and death. Cardiac complications associated with acute COVID-19 and MIS-C are more severe and occur more frequently than myocarditis after mRNA COVID-19 vaccination. Furthermore, some of the academic and social disruptions caused by the pandemic expect to be eased by widespread vaccination. For all these reasons, COVID-19 vaccination is strongly recommended for all eligible age groups.

关键词： delta PKC   Drp1   fission   inflammation   macrophage   mitochondria  

摘要： Background: Recent studies have demonstrated that alterations in mitochondrial dynamics can impact innate immune function. However, the upstream mechanisms that link mitochondrial dynamics to innate immune phenotypes have not been completely elucidated. This study asks if Protein Kinase C, subunit delta (delta PKC)-mediated phosphorylation of dynamin-related protein 1 (Drp1), a key driver of mitochondrial fission, impacts macrophage pro-inflammatory response following bacterial-derived lipopolysaccharide (LPS) stimulation. Methods: Using RAW 264.7 cells, bone marrow-derived macrophages from C57BL/6J mice, as well as human monocyte-derived macrophages, we first characterized changes in delta PKC-mediated phosphorylation of Drp1 following LPS stimulation. Next, using rationally designed peptides that inhibit delta PKC activation (delta V1-1) and delta PKC-Drp1 interaction (psi Drp1), we determined whether delta PKC-mediated phosphorylation of Drp1 impacts LPS-induced changes in mitochondrial morphology, mitochondrial function, and inflammatory response. Results: Our results demonstrated that delta PKC-dependent Drp1 activation is associated with increased mitochondrial fission, impaired cellular respiration, and increased mitochondrial reactive oxygen species in LPS-treated macrophages. This is reversed using a rationally designed peptide that selectively inhibits delta PKC phosphorylation of Drp1 (psi Drp1). Interestingly, limiting excessive mitochondrial fission using psi Drp1 reduced LPS-triggered pro-inflammatory response, including a decrease in NF-kappa B nuclear localization, decreased iNOS induction, and a reduction in pro-inflammatory cytokines (IL-1 beta, TNF alpha, IL-6). Conclusion: These data suggest that inhibiting Drp1 phosphorylation by delta PKC abates the excessive mitochondrial fragmentation and mitochondrial dysfunction that is seen following LPS treatment. Furthermore, these data suggest that limiting delta PKC-dependent Drp1 activation decreases

关键词： Neurological manifestations   Pediatrics   SARS-CoV-2   Child development  

摘要： Background: Our objective was to characterize the frequency, early impact, and risk factors for neuro-logical manifestations in hospitalized children with acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or multisystem inflammatory syndrome in children (MIS-C). Methods: Multicenter, cross-sectional study of neurological manifestations in children aged <18 years hospitalized with positive SARS-CoV-2 test or clinical diagnosis of a SARS-CoV-2-related condition be-tween January 2020 and April 2021. Multivariable logistic regression to identify risk factors for neuro-logical manifestations was performed. Results: Of 1493 children, 1278 (86%) were diagnosed with acute SARS-CoV-2 and 215 (14%) with MIS-C. Overall, 44% of the cohort (40% acute SARS-CoV-2 and 66% MIS-C) had at least one neurological mani-festation. The most common neurological findings in children with acute SARS-CoV-2 and MIS-C diag-nosis were headache (16% and 47%) and acute encephalopathy (15% and 22%), both P < 0.05. Children with neurological manifestations were more likely to require intensive care unit (ICU) care (51% vs 22%), P < 0.001. In multivariable logistic regression, children with neurological manifestations were older (odds ratio [OR] 1.1 and 95% confidence interval [CI] 1.07 to 1.13) and more likely to have MIS-C versus acute SARS-CoV-2 (OR 2.16, 95% CI 1.45 to 3.24), pre-existing neurological and metabolic conditions (OR 3.48, 95% CI 2.37 to 5.15;and OR 1.65, 95% CI 1.04 to 2.66, respectively), and pharyngeal (OR 1.74, 95% CI 1.16 to 2.64) or abdominal pain (OR 1.43, 95% CI 1.03 to 2.00);all P < 0.05. Conclusions: In this multicenter study, 44% of children hospitalized with SARS-CoV-2-related conditions experienced neurological manifestations, which were associated with ICU admission and pre-existing neurological condition. Posthospital assessment for, and support of, functional impairment and neuro-protective strategies are vitally needed. (c) 2021 Elsevier Inc

ISBN: (纸本)9787559841681