Glioblastoma (GBM) is among the most treatment-resistant solid tumors and often recurrs after resection. One of the mechanisms through which GBM escapes various treatment modalities is the overexpression of anti-apoptotic Bcl-2 family proteins (e.g., Bcl-2, Bcl-xl, and Mcl-1) in tumor cells. Small-molecule inhibitors such as ABT-263 (ABT), which can promote mitochondrial-mediated cell apoptosis by selectively inhibiting the function of Bcl-2 and Bcl-xl, have been proven to be promising anticancer agents in clinical trials. However, the therapeutic prospects of ABT for GBM treatment are hampered by its limited blood–brain barrier (BBB) penetration, dose-dependent thrombocytopenia, and the drug resistance driven by Mcl-1, which is overexpressed in GBM cells and further upregulated upon treatment with ABT. Herein, we reported that the Mcl-1-specific inhibitor A-1210477 (A12) can act synergistically with ABT to induce potent cell apoptosis in U87 MG cells, drug-resistant U251 cells, and patient-derived GBM cancer stem cells. We further designed a biomimetic nanomedicine, based on the apolipoprotein E (ApoE) peptide-decorated red blood cell membrane and pH-sensitive dextran nanoparticles, for the brain-targeted delivery of ABT and A12. The synergistic anti-GBM effect was retained after encapsulation in the nanomedicine. Additionally, the obtained nanomedicine possessed good biocompatibility, exhibited efficient BBB penetration, and could effectively suppress tumor growth and prolong the survival time of mice bearing orthotopic GBM xenografts without inducing detectable adverse effects.
The objective of this study was to define the threatened perception types of pregnant women during the COVID-19 pandemic and determine the correlations between the perception types and their demographic factors, their preventive knowledge of COVID-19 and their mental status in order to provide suggestions for pregnant women during pandemic. Methods Latent class analysis were used to explore the optimal numbers of clusters. Multinomial logistic regression and multiple correspondence analysis were used to analyze the demographic variables of the latent categories. MANOVA was used to analyze the difference of knowledge of COVID-19 obtained among clusters and their psychological status, and chisquare test was used determine the relationship between the latent clusters and the participant's COVID-19 worry level. Results Five clusters were found: the first cluster (n = 120, 39%) was unthreatened and confident. Cluster 2(n = 84, 28%) was unthreatened but not confident. Cluster 3 (n = 49, 17%) was threatened but confident. Cluster 4 (n = 25, 9%) was threaten, not confident and knowledgeable, and Cluster 5 (n = 20, 7%) was threatened, not confident and lacking knowledge. Three demographic variables were shown an effect on the classification, they were support from work, family support and intrapartum and postpartum complications. Conclusion This study can help assess the mental health risks of pregnant women during an epidemic. The results could be helpful for families, work units, communities and medical institutions to make targeted intervention decisions for pregnant women.
Rapid prototyping turns a three‐dimensional CAD drawing into an actual part that can be tested for form, fit, and function. Therefore, accuracy of the prototype is important. The goal of this research was to improve in‐plane dimensional accuracy for the Stratasys FDM 1650 rapid prototyping machine. The CHRISTMAS‐TREE™ test procedure developed by 3D Systems, Inc., was used to arrive at a new shrinkage compensation factor (SCF) for the Stratasys machine. It was found that an SCF of 1.010 will produce a 53% reduction in mean error of the dimensions. More test procedures could be implemented to further refine accuracy. © 1999 John Wiley & Sons, Inc. Comput Appl Eng Educ 7: 186–195, 1999
The identification of prognostic factors for multiple myeloma is important. This article focuses on the prognostic value of 1q21 gain in a Chinese population according to different treatment regimens and accompanying high‐risk factors.
Multidrug-resistant ( MDR ) Escherichia coli are responsible for difficult-to-treat infections. We sought to determine the prevalence and characteristics of MDR E. coli strains isolated from poultry and clinical patients in the same geographical region. Eighty-seven E. coli strains were isolated from poultry with perihepatitis lesions at different slaughterhouses, and 356 nonrepetitive E. coli strains were isolated from clinical patients. All samples were continuously collected from October to December 2017 in Tai'an, China. The presence of the mcr-1 gene in the strains was assessed by PCR. The genetic relationships of the polymyxin ( POL )-resistant E. coli strains were analyzed by pulsed-field gel electrophoresis and multilocus sequence typing. The results indicate that the POL resistance rate for the E. coli isolates from poultry was 31.03% (27 of 87), whereas the human-origin E. coli isolates were 100% sensitive to POL. The mcr-1 gene and extended-spectrum β-lactamase bla CTX-M-14 genes were identified in all 27 POL-resistant avian-origin E. coli isolates. Our pulsed-field gel electrophoresis analysis suggested that the 27 strains were represented by 14 pulsotypes, among which there were 3 strains each with A, E, I, and K pulsotypes, and 1 to 2 strains represented by the other 10 pulsotypes. Furthermore, multilocus sequence typing molecular typing identified 16 sequence types, including 4 ST156 strains, 3 ST533 strains, and 1 to 2 strains represented by the remaining 14 sequence types. In summary, the E. coli strains isolated in the Tai'an area all showed the MDR phenotype, the rate of which for poultry was higher than that for humans. No POL-resistant human-origin E. coli strains were identified in the clinical patients. Our study reveals that poultry-derived MDR mcr-1 –positive E. coli strains may pose a potential risk to humans, and the surveillance findings presented herein will be conducive to our understanding of the prevalence and characteristics of mcr-1 –positive E. coli strains in the Tai'an area.
Purpose This study aimed to assess the health‐related quality of life (HRQOL) of Chinese patients with different stages of multiple myeloma (MM) who received various treatments and identify the factors associated with a lower quality of life in China. Methods A cross‐sectional, anonymous questionnaire was distributed to adults with MM. The measures of quality of life included the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)‐C30, QLQ‐myeloma‐specific module 20 (MY20), and EuroQoL EQ‐5D. The data, including patient factors, difficulties experienced during the diagnosis and treatment processes, psychosocial factors and disease‐ or treatment‐related effects, were collected. Results Four hundred and thirty patients with MM were recruited from all 27 provinces of China, and their average age was 55.7 years. Many variables were significantly associated with the HRQOL of the patients with MM. In the multivariate analyses, performance status, psychosocial factors, disease phase, and an early diagnosis were significantly associated with the HRQOL. In the subgroup analysis, the HRQOL of the patients who underwent autologous stem cell transplantation (ASCT) was significantly higher than that of the non‐ASCT patients. Treatment‐related toxicities had a significant impact on the quality of life of the patients with MM, and 91.5% of the patients intended to stop the maintenance treatment. Conclusions The quality of life of patients with MM in China is affected by patient factors, difficulties experienced during the diagnosis and treatment processes, psychosocial factors, and disease‐ or treatment‐related effects. Efforts should be exerted to improve the overall quality of life of these patients in China.
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