Search

Background Cancer patients with financial toxicity experience psychological distress and often miss medical appointments and quit treatments early, which could be a barrier to the effective management of oral chemotherapy drugs at home. This study explores whether financial toxicity predicts symptoms and unplanned healthcare utilization among cancer patients taking oral chemotherapy at home, which will contribute to the safe management of oral chemotherapy. Methods Data in this study was from a prospective observational study, which was conducted between October 2018 and December 2019. 151 patients completed the Comprehensive Score for Financial Toxicity at discharge and completed the MD Anderson Symptom Inventory and unplanned healthcare utilization questionnaires after finishing one cycle of oral chemotherapy at home. Regression analyses were conducted to explore the associations of financial toxicity with symptoms and unplanned healthcare utilization. Results Among 151participants, 88.08% reported severe or moderate financial toxicity, 43.05% reported symptom interference, and 31.79% reported unplanned healthcare utilization while taking oral chemotherapy at home. Patients between the age of 45-60y (p = 0.042) have higher financial toxicity, while those living in urban areas (p = 0.016) have lower financial toxicity. Patients with worse financial toxicity suffered increased symptoms of fatigue, emotional distress, disturbed sleep, and lack of appetite. Consequently, their mood and personal relation with other significant suffered. However, no statistical differences in unplanned healthcare utilization were found among patients with different levels of financial toxicity. Conclusion Middle-aged adults and those living in suburban or rural areas experienced worse financial toxicity than other groups. Patients with worse financial toxicity experienced more severe psychological symptoms (e.g., fatigue, distress, disturbed sleep, and lack of appetite) and affective interference (e.g., mood and relations with others). Identifying at-risk patients is necessary to offer tailored support for psychological symptom management.

Acute myeloid leukemia (AML) is a hematological malignancy characterized by cytogenetic and genomic alterations. Up to now, combination chemotherapy remains the standard treatment for leukemia. However, many individuals diagnosed with AML develop chemotherapeutic resistance and relapse. Recently, it has been pointed out that leukemic stem cells (LSCs) are the fundamental cause of drug resistance and AML relapse. LSCs only account for a small subpopulation of all leukemic cells, but possess stem cell properties, including a self-renewal capacity and a multi-directional differentiation potential. LSCs reside in a mostly quiescent state and are insensitive to chemotherapeutic agents. When LSCs reside in a bone marrow microenvironment (BMM) favorable to their survival, they engage into a steady, continuous clonal evolution to better adapt to the action of chemotherapy. Most chemotherapeutic drugs can only eliminate LSC-derived clones, reducing the number of leukemic cells in the BM to a normal range in order to achieve complete remission (CR). LSCs hidden in the BM niche can hardly be targeted or eradicated, leading to drug resistance and AML relapse. Understanding the relationship between LSCs, the BMM, and the generation and evolution laws of LSCs can facilitate the development of effective therapeutic targets and increase the efficiency of LSCs elimination in AML.

Atrial fibrillation (AF) is a common atrial arrhythmia for which there is no specific therapeutic drug. Quercetin (Que) has been used to treat cardiovascular diseases such as arrhythmias. In this study, we explored the mechanism of action of Que in AF using network pharmacology and molecular docking. The chemical structure of Que was obtained from Pubchem. TCMSP, Swiss Target Prediction, Drugbank, STITCH, Pharmmapper, CTD, GeneCards, DISGENET and TTD were used to obtain drug component targets and AF-related genes, and extract AF and normal tissue by GEO database differentially expressed genes by GEO database. The top targets were IL6, VEGFA, JUN, MMP9 and EGFR, and Que for AF treatment might involve the role of AGE-RAGE signaling pathway in diabetic complications, MAPK signaling pathway and IL-17 signaling pathway. Molecular docking showed that Que binds strongly to key targets and is differentially expressed in AF. In vivo results showed that Que significantly reduced the duration of AF fibrillation and improved atrial remodeling, reduced p-MAPK protein expression, and inhibited the progression of AF. Combining network pharmacology and molecular docking approaches with in vivo studies advance our understanding of the intensive mechanisms of Quercetin, and provide the targeted basis for clinical Atrial fibrillation treatment.

Background Lung carcinoma is a common geriatric disease. The development of genotype-targeted therapies greatly improved the management of lung carcinoma. However, the treatment for old patients can be more complex than that for young individuals. Results To investigate the benefits of genetic detection for older patients with lung carcinoma, we explored the genomic profiling of 258 patients with more than 55 years using a targeted next generation sequencing, and some of these patients were treated with targeted therapies based on the results of genomic detection. KRAS codon 61 mutations were found in 15.2% KRAS-mutated patients, which tend to be co-existing with other classical activating mutations other than codons 12/13. Acquired EGFR C797S mutations were identified in 2 cases and ERBB2 amplification was identified in 1 case. All these 3 cases developed resistance to EGFR tyrosine kinase inhibitors and showed expected results of their followed therapies. The median progression-free survival and median overall survival of patients treated with molecular targeted therapies were better than those of patients treated with chemoradiotherapy alone. Conclusions Our findings revealed the specific genomic profiles of patients older than 55 years with lung carcinoma and suggested that these old patients have been benefit from the genetic detection, which helped identify druggable mutations and distinguish resistance mechanisms.

Strain engineering is proposed to be an effective technology to tune the properties of two-dimensional (2D) transition metal dichalcogenides (TMDCs). Conventional strain engineering techniques (e.g., mechanical bending, heating) cannot conserve strain due to their dependence on external action, which thereby limits the application in electronics. In addition, the theoretically predicted strain-induced tuning of electrical performance of TMDCs has not been experimentally proved yet. Here, a facile but effective approach is proposed to retain and tune the biaxial tensile strain in monolayer MoS2 by adjusting the process of the chemical vapor deposition (CVD). To prove the feasibility of this method, the strain formation model of CVD grown MoS2 is proposed which is supported by the calculated strain dependence of band gap via the density functional theory (DFT). Next, the electrical properties tuning of strained monolayer MoS2 is demonstrated in experiment, where the carrier mobility of MoS2 was increased by two orders (∼ 0.15 to ∼ 23 cm2·V−1·s−1). The proposed pathway of strain preservation and regulation will open up the optics application of strain engineering and the fabrication of high performance electronic devices in 2D materials.

Background Shen-ling-bai-zhu-san (SLBZS) regulates inflammation and gut microbiota which are associated with Streptococcus pneumoniae (Spn)-induced pneumonia. So, we studied the therapeutic effect of SLBZS and evaluated whether gut microbiota is associated with the effects of SLBZS in improving Spn-induced pneumonia. Methods Spn-induced pneumonia NIH mice were treated by SLBZS and cefixime. A CT scan was performed and Myeloperoxidase (MPO) activity in lung homogenates was determined using the MPO Colorimetric Assay Kit. Inflammation levels in lung homogenates were measured using ELISA. Bacterial load was coated on a TSAII sheep blood agar. Intestinal gut microbiota information was analyzed according to sequencing libraries. Results SLBZS decreased bacterial load, reduced wet/dry weight ratio, inhibited myeloperoxidase activity, reduced the neutrophils count, and ameliorated lung injury. Furthermore, SLBZS inhibited interleukin (IL)-1β, IL-6, tumor necrosis factor-α, IL-2, IL-8, IL-12, and interferon-γ secretion and enhanced IL-10 secretion. These results suggest that SLBZS ameliorates lung injury in mice with Spn-induced pneumonia. Moreover, SLBZS reduced inflammatory cytokine levels in a concentration-dependent manner and increased gut microbiota abundance and diversity. After SLBZS treatment, bacteria such as Epsilonbacteraeota, Bacteroidetes, Actinobacteria, Proteobacteria, and Patescibacteria were significantly reduced, while Tenericutes and Firmicutes were significantly increased. Conclusion SLBZS ameliorates inflammation, lung injury, and gut microbiota in mice with S. pneumoniae-induced pneumonia.

Plant trials were carried out to compare multiphase flow using a conventional ladle shroud (CLS) and a trumpet-shaped ladle shroud (TLS) in a steelmaking tundish. Steel splashing, slag exposure, smoke and flame were recorded to investigate the fluid flow during both transient and steady casting. A large eddy simulation model was employed to visualize the flow structure and obtain detailed flow information. The results showed that the TLS outperformed the CLS in relieving steel splashing during ladle change due to the braking effect of the TLS on the jet. During steady casting, a relatively calm melt bath was achieved with less exposed steel using the TLS, which is attributed to the reduced turbulence in the tundish. An eccentric tundish open eye was observed using the CLS, which is related to the misaligned flow pattern when the slide gate is partially open.

Transforming growth factor β-activated kinase-1 (TAK1) is a key upstream kinase in cell signaling during inflammation, which regulates the expression of inflammatory mediators. Small interfering RNA (siRNA) against TAK1 offers promise as a potential therapeutic strategy in immune-mediated inflammatory disorder including rheumatoid arthritis. Here, we are to evaluate the therapeutic effects of intra-articular administration of adenoviral-mediated siRNA against TAK1 (ad-siRNA-TAK1) on collagen-induced arthritis (CIA) in mice. Ad-siRNA-TAK1 was constructed. The murine RAW 264.7 macrophages were infected with ad-siRNA-TAK1, and the silencing specificity of TAK1 was assessed by quantitative polymerase chain reaction (PCR) and western blot. DBA/1 mice were injected intra-articularly with ad-siRNA-TAK1. Development and severity of arthritis was assessed histologically. Synovial inflammation and bone destruction were determined by hematoxylin and eosin (HE) staining. Articular and serum concentrations of tumor necrosis factor-α, interleukin-1, and interleukin-6 were determined using enzyme-linked immunosorbent assay. Levels of phosphorylated p38, c-Jun N-terminal kinase (JNK), and extracellular-signal-regulated kinase (ERK) were detected by western blot. In vitro, ad--siRNA-TAK1 efficiently inhibited the expression of TAK1 at both mRNA and protein levels. In vivo, intra-articular injection of ad-siRNA-TAK1 efficiently alleviated joint inflammation, decreased the expression of pro-inflammatory mediators, and suppressed JNK pathways. Our results demonstrate the efficiency of ad--siRNA-TAK1 in controlling joint inflammation of CIA, which is associated with the suppression of the expression of pro-inflammatory cytokines and JNK activation.

Slag entrainment in a continuous casting mold is one of the major causes of macro nonmetallic inclusions in continuous casting steel products. Stabilizing the level fluctuation is an important factor to improve steel quality. A new type of submerged entry nozzle (SEN) named self-braking SEN was designed. In the current study, water modeling experiments were performed to study the effect of self-braking SEN on level fluctuation in a continuous casting slab mold. The level position and the root mean square value of level fluctuation were analyzed through the online detection data. The results showed that the flow in the mold was more symmetrical and the tracer dispersion was more uniform. Moreover, the meniscus was also more uniform than the conventional nozzle with the self-braking SEN, especially at high casting speed.

To replace nickel-based stainless steel, a nitrogen-bearing stainless steel was produced to lower the production cost stemming from the shortage of nickel recourses. Thermodynamic model to calculate the saturated nitrogen content in the stainless steel was developed and the model was validated by experimental measurements performed with a high temperature induction furnace. Nitrogen gas under constant pressure was injected into the molten steel with a top lance. Thus, the nitrogen was transferred to the molten stainless steel. The effects of chemical composition, temperature, superficial active elements and nitrogen flow rate on the transfer of nitrogen to the steel were investigated and discussed. The results showed that the dissolution rate of nitrogen in the molten steel increases with a higher temperature and larger nitrogen flow rate but decreases significantly with an increase in the content of surface-active elements. Alloying elements such as chromium and manganese having a negative interaction coefficient can increase the dissolution of nitrogen in the molten steel. It was also proposed that the primary factor affecting the final saturated nitrogen content is temperature rather than the dissolved oxygen content.

Copper-tungsten films were deposited on Si and Al2O3 substrates by magnetron sputtering and then in situ annealed in vacuum chamber at different temperatures. X-ray diffraction (XRD), scanning electron microscopy (SEM), and the polarization phase shift technique were used to characterize the microstructure, surface morphology, and residual stress of Cu–W films. The results indicated that there are two successive but distinctive stages of phase transition with the change of annealing temperatures. The evolution of surface morphology of Cu–W thin films shows a significant effect on the distribution of in-plane stresses. A strategy of integrating discrete wavelet transform and fractal geometry concepts was developed to analyze the anisotropy of surface structure of Cu–W thin films. The correlation between the anisotropy of surface morphology and the stress distribution of thin films was constructed. It is found that the stress distribution of the thin films is sensitive to the variations of the anisotropy of the surface structure with annealing temperature. The variation in the uniformity of in-plane stress distribution with the evolution of surface structure of thin films is independent of the choice of substrate materials.