The effects of axial profile parameters on the main bearing performance of the engine were investigated through the numerical method based on elasto-hydrodynamic lubrication theory, average flow, and ...asperity contact model. Results show that quadratic profile significantly improves the bearing performance, and the influence of profile varies with its width-to-height ratio. The performance is most improved when the ratio is between 0.8 and 2. An artificial neural network fitting model was developed to predict bearing performance, and multiobjective optimum analyses were performed using genetic algorithm and particle swarm optimization. The optimization goals are average peak asperity contact pressure and average total friction loss. The obtained Pareto front roughly includes three groups, and solutions in group 1 achieve a balance of the two goals, with a width-to-height ratio of 1.5–2. Finally, bearing friction tests were conducted on four profiled bearings to verify the simulation model and optimization results.
It is the aim of this work to reduce friction power loss of main bearings by optimization. To this purpose, elastohydrodynamic (EHD) model is used for EHD calculations for different main bearings. BP ...neural network is implemented to establish the approximation model for bearings. Then, multi-objective optimization of bearings using genetic algorithm is formulated and conducted. It is found that a more compliant bearing profile can provide hydrodynamic lift during film lubrication while bearing profiles have more significant impact on lubrication performance in comparison to other key parameters. The results of the BP network model using the genetic algorithm agree closely with the calculated value based on EHD-MBD model. The presented approach allows reliably to conduct the optimization of bearings. After optimization, the friction power loss is significantly reduced while the minimum oil film thickness increases and the total pressure drops.
The brain is the most common metastatic site of lung adenocarcinoma; however, the mechanism of this selective metastasis remains unclear. We aimed to verify the hypothesis that exposure of tumor ...cells to the brain microenvironment leads to changes in their gene expression, which promotes their oriented transfer to the brain. A549 and H1299 lung adenocarcinoma cells were exposed to human astrocyte-conditioned medium to simulate the brain microenvironment. Microarray analysis was used to identify differentially expressed genes, which were confirmed by quantitative real-time PCR and western blotting. Knockdown experiments using microRNAs and the overexpression of genes by cell transfection were performed in addition to migration and invasion assays. In vitro findings were confirmed in clinical specimens using immunohistochemistry. We found and confirmed a significant increase in insulin-like growth factor binding protein-3 (IGFBP3) levels. Our results also showed that the up-regulation of IGFBP3 promoted A549 cell epithelial-mesenchymal transition, migration, and invasion, while the knockdown of IGFBP3 resulted in decreased cell motility. We also found that Transforming growth factor-β (TGF-β)/Mothers against decapentaplegic homolog 4 (Smad4)-induced epithelial-mesenchymal transition was likely IGFBP3-dependent in A549 cells. Finally, expression of IGFBP3 was significantly elevated in pulmonary cancer tissues and intracranial metastatic tissues. Our data indicate that up-regulation of IGFBP3 might mediate brain metastasis in lung adenocarcinoma, which makes it a potential therapeutic target.
More clinical practice need to be performed to verify the toxicity of the hypofractionated radiotherapy (HFRT) combined with PD-1 blockade in lung cancer. This phase I study aimed to investigate the ...safety and efficacy of nivolumab combined with HFRT in patients with progressive advanced lung cancer following multiline treatment.
We enrolled 31 patients with advanced lung cancer pathologically confirmed to have progressive disease and treated with first-line or a higher therapy. Selected lesions were treated using HFRT, and nivolumab was administered within 7 days subsequently. Nivolumab was administered once a month following partial remission. Peripheral blood was collected before and after 1 month of treatment to evaluate relevant cytokines between nivolumab responders and non-responders.
Overall, 23 patients who completed the treatment were evaluated. Of them, 9 and 14 patients underwent hypofractionated brachytherapy with 30 Gy in a single fraction
percutaneous interstitial implantation of (192)Ir and 40-50 Gy in 5 fractions
stereotactic body radiation therapy, respectively. The median follow-up period was 11 months. At the 1-year follow-up, no patient developed grade ≥ 3 pneumonitis. The overall objective response and complete remission rates were 39.13% and 13.04%, respectively. The 1-year overall survival and median progression-free survival were 60.9% and 6 months, respectively. The plasma levels of interleukin IL-6, IL-10, and IL-17A were significantly reduced after treatment in nivolumab responders.
HFRT could increase the responsivity to nivolumab and reduce its administration frequency. This combination treatment is well tolerated with acceptable toxicity and thus merits further trials to validate benefits.
http://www.chictr.org.cn/index.aspx, identifier ChiCTR-1900027768.
Purpose
This retrospective study aimed to investigate
18
F-fluorodeoxyglucose (
18
F-FDG)-positron emission tomography/computed tomography (PET/CT) as a predictor of response to hypofractionated ...radiotherapy (HFRT) combined with programmed cell death-1 (PD-1) blockade for lung cancer.
Methods
We included 41 patients with advanced non-small cell lung cancer (NSCLC) in this study. PET/CT was performed before (SCAN-0) and one month (SCAN-1), three months (SCAN-2), and six months (SCAN-3) after treatment. Using the European Organization for Research and Treatment of Cancer 1999 criteria and PET response criteria in solid tumors, treatment responses were classified as complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), or progressive metabolic disease (PMD). Patients were further categorized as those with metabolic benefits (MB; SMD, PMR, and CMR) and those without MBs (NO-MB; PMD). We analyzed the prognosis and overall survival (OS) of patients with new visceral/bone lesions during treatment. Based on the findings, we generated a nomogram to predict survival. Receiver operating characteristics and calibration curves were used to evaluate the accuracy of the prediction model.
Results
The mean OS based on SCANs 1, 2, and 3 was significantly higher in patients with MB and those without new visceral/bone lesions. The prediction nomogram for survival had a high area under the curve and a high predictive value based on the receiver operating characteristics and calibration curves.
Conclusion
18
FDG-PET/CT has the potential to predict the outcomes of HFRT combined with PD-1 blockade in NSCLC. Therefore, we recommend using a nomogram to predict patient survival.
The purpose of this study was to develop a novel drug delivery system for a sustained and targeted delivery of honokiol (HK) to the nasopharyngeal carcinoma (NPC) HNE-1 cell lines, since the folate ...receptor (FR) is over-expressed on their surface. Emulsion solvent evaporation was used to develop the active targeting nanoparticles-loaded HK (ATNH) using copolymerpoly (ɛ-caprolactone)-poly (ethyleneglycol)-poly (ɛ-caprolactone) (PCEC), which was modified with folate (FA) by introducing Polythylenimine (PEI). ATNH characterization, including particle size distribution, morphology, drug loading, encapsulation efficiency and drug release, was performed. Transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FTIR) were employed to evaluate the shape and construction, respectively. MTT assay, cell uptake study and apoptosis test were assayed to detect the antitumor properties and targeting uptake by HNE-1 cells in vitro. Cell-cycle redistribution,
18
F-FDG PET/CT and immunohistochemistry were performed in vivo. The ATNH we developed were successfully synthesized and showed a suitable size distribution, high encapsulation efficiency, gradual release, and targeting uptake by the cells in vitro. Moreover, ATNH significantly inhibited tumor growth, metabolism, proliferation, micro-vessel generation, and caused cell-cycle arrest at G
1
phase. Thus, these nanoparticles we developed might represent a novel formulation for HK delivery and a promising potential therapy in the treatment of cancer.
The high cycle fatigue behaviour of the Al–Si alloy extracted from a cylinder head is investigated through experiments and finite element simulations. Due to the complexity of the structure and the ...differences in cooling rates and local melt flow, the microstructure characteristics of the cylinder head studied exhibit high spatial heterogeneity. The scatter of the fatigue life of the alloy is high, which is significantly affected by the microstructure, especially by crack nucleation pores. The characteristics of the nucleation pores have a great effect on the dissipated inelastic energy (Wp) around the pores, which is used as the indicator for crack nucleation. Wp has the highest sensitivity to pore shape, followed by pore location and pore size. The nonlinear empirical relationship between Wp and pore characteristics is established with high reliability and accuracy, and the crack nucleation model is modified by considering pore characteristics. Based on the multistage fatigue model and the modified crack nucleation model, the fatigue life of cast Al–Si alloy extracted from cylinder heads can be predicted accurately within a feasible scatter band.
Background and Purpose
Currently, there is no optimal dose recommendation for a 120-h continuous infusion of 5-fluorouracil
via
arterial cannulation for advanced T-stage nasopharyngeal carcinoma ...(NPC). Thus, the aim of this study was to determine the maximum tolerated dose (MDT), along with the efficacy, late adverse events, and 10-year survival outcome of 5-fluorouracil administered continuously for 120 h combined with cisplatin
via
the superficial temporal artery in patients with advanced T-stage NPC.
Materials and Methods
Fifty-one patients with histologically confirmed advanced T-stage NPC were eligible for inclusion in this clinical trial. The patients received induction chemotherapy consisting of cisplatin (20 mg/m
2
/d for 1–5 d) and 5-fluorouracil, administered continuously for 120 h at different dose gradients
via
a superficial temporal artery. To identify the MTD of 5-fluorouracil infused arterially, we employed a 3 + 3 design during study phase I. The initial dose administered was 200 mg/m
2
/d, which then was gradually escalated by 50 mg/m
2
/d until the MTD was reached. Following two cycles of induction chemotherapy, current radical chemoradiotherapy commenced. We assessed the efficacy, survival, toxicity, and quality of life of patients following treatment.
Results
The overall response (complete response + partial response) rates following induction chemotherapy in the primary mass and lymph nodes were 100% and 100%, respectively. All 51 (100%) patients achieved T-category down-staging after intra-arterial chemotherapy. The MTD was 450 mg/m
2
/d for 120 h. No late neurological toxicities, such as brain stem injury, temporal lobe necrosis, and spinal cord injury, were observed. The 5- and 10-year overall survival (OS) rates were 78.0% and 71.7%, respectively, with a median OS of 131 months.
Conclusion
Continuous infusion of 5-fluorouracil combined with cisplatin
via
the superficial temporal artery showed promising survival benefits and few toxicities in patients with advanced T-stage NPC.
The aim of this study was to evaluate whether a patented single‐channel applicator, which was modified from the traditional tandem applicator and wrapped with an oval‐shield alloy around the source ...channel, has the same clinical efficacy and safety as the standard Fletcher‐type applicator in high dose rate (HDR) brachytherapy for carcinoma of the cervix. Between December 2011 and February 2017, 299 patients with pathologically confirmed International Federation of Gynecology and Obstetrics (2009) stage Ib2‐IVa cervical cancer were recruited to the trial and finished the allocated intervention. Of the first 151 patients, 71 were allocated to the Fletcher group and 80 to the single‐channel group, satisfying the criteria for a preliminary analysis. All but 3 patients were treated with concurrent cisplatin chemotherapy and external beam radiotherapy followed by HDR brachytherapy. The 2‐year overall survival, progression‐free survival, and locoregional failure‐free survival was 80.3%, 77.5%, and 78.9%, respectively, for the Fletcher group, and 86.3%, 82.5%, and 83.8%, respectively, for the single‐channel group. The seriousness of acute treatment‐related toxicities was similar in the 2 groups. The cumulative rate of late rectal complications of grade 3‐4 in the Fletcher group and the single‐channel group was 2.8% and 2.5%, respectively. The cumulative rate of grade 3 bladder complications was 2.8% for the Fletcher group and 1.3% for the single‐channel group. The preliminary results of our study show that the patented single‐channel intracavitary applicator might be able to provide protection for the rectum and bladder and seems to have the same clinical efficacy as the standard Fletcher‐type 3‐channel applicator in HDR brachytherapy for carcinoma of the cervix. This trial was registered with the Chinese Clinical Trial Registry (registration no. ChiCTR‐TRC‐12002321).
Preliminary results show that a patented single‐channel intracavitary applicator might be able to provide protection for the rectum and bladder and seems to have the same clinical efficacy as the standard Fletcher‐type 3‐channel applicator in high dose rate brachytherapy for carcinoma of the cervix.
Objective To explore the dose of template-assisted 192Ir source hypofractionated stereotactic brachytherapy (SABT) for peripheral lung cancer. Methods We retrospectively analyzed the dose parameters ...of GTV and OARs of 28 peripheral lung cancer patients treated with template-assisted 192Ir-source hypofractionated SABT, and compared the dose parameters between SABT with virtual SBRT. Results The Dmean and V150 for the GTV in the SABT plan were significantly higher than those in the SBRT plan (all P<0.01). For OARs, all dosimetric parameters in the SABT plan were significantly lower than those in the SBRT plan (all P<0.01), except for the D1000cm3 and D1500cm3 for the lung (P>0.05). Conclusion Template-assisted 192Ir source hypofractionated SABT ensures high dose in the gross tumor volume and reduces the dose in organs at risk in the treatment of peripheral lung cancer.
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