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Hydrogen energy plays an increasingly vital role in global energy transformation. However, existing electric–hydrogen coupled integrated energy systems (IESs) face two main challenges: achieving stable operation when integrated with large-scale networks and integrating optimal dispatching code with physical systems. This paper conducted comprehensive modeling, optimization and joint simulation verification of the above IES. Firstly, a low-carbon economic dispatching model of an electric–hydrogen coupled IES considering carbon capture power plants is established at the optimization layer. Secondly, by organizing and selecting representative data in the optimal dispatch model, an electric–hydrogen coupled IES planning model considering the integration of wind, photovoltaic (PV), diesel and storage is constructed at the physical layer. The proposed electric–hydrogen coupling model mainly consists of the following components: an alkaline electrolyzer, a high-pressure hydrogen storage tank with a compressor and a proton exchange membrane fuel cell. The IES model proposed in this paper achieved the integration of optimal dispatching mode with physical systems. The system can maintain stable control and operation despite unpredictable changes in renewable energy sources, showing strong resilience and reliability. This electric–hydrogen coupling model also can integrate with large-scale IES for stable joint operation, enhancing renewable energy utilization and absorption of PV and wind power. Co-simulation verification showed that the optimized model has achieved a 29.42% reduction in total system cost and an 83.66% decrease in carbon emissions. Meanwhile, the simulation model proved that the system’s total harmonic distortion rate is controlled below 3% in both grid-connected and islanded modes, indicating good power quality.

Abstract A randomized double-blind phase 3 trial (CHOICE-01, NCT03856411) demonstrated that combining toripalimab with chemotherapy substantially improves progression-free survival (PFS) in advanced non-small cell lung cancer (NSCLC) patients without pretreatment. This study presents the prespecified final analysis of overall survival (OS) and biomarkers utilizing circulating tumor DNA (ctDNA) and tissue-based sequencing. Additionally, the analysis revealed a higher median overall survival (OS, 23.8 months) in the toripalimab group than that in the control group (17.0 months). (HR = 0.69, 95%CI: 0.57–0.93, nominal P = 0.01). This survival benefit was particularly notable in the non-squamous subgroup. As the first phase 3 study to perform both baseline tissue whole-exome sequencing (WES) and peripheral blood ctDNA testing, we investigated efficacy predictive biomarkers based on both tissue and ctDNA, Genomic sequencing of ctDNA showed high concordance with tumor tissue independently confirmed that individuals exhibiting a high tumor mutational burden, as well as mutations in the FA-PI3K-Akt and IL-7 signaling pathways benefited more from the toripalimab treatment. Furthermore, a ctDNA response observed on cycle 3 day 1, was associated with improved clinical outcomes for patients treated with the combination therapy. In conclusion, Toripalimab plus chemotherapy yields significant improvements in OS as a first-line treatment. The study highlights the utility of ctDNA as a proxy for tumor tissue, providing novel prospects for predicting efficacy of immuno-chemotherapy through continuous ctDNA monitoring.

Human bone marrow mesenchymal stem cells (HBMSCs) can promote new bone formation. Previous studies have proven the ability of long non-coding RNAs (lncRNAs) to modulate the osteogenic differentiation of mesenchymal stem cells. However, the molecular mechanism modulated by lncRNAs in affecting the osteogenic differentiation of HBMSCs remains largely unknown. Thus, this study aims to reveal the role of lncRNA ubiquitin-specific peptidase 2 antisense RNA 1 (USP2-AS1) in regulating the osteogenic differentiation of HBMSCs and investigate its regulatory mechanism. Through bioinformatics analysis and RT-qPCR, we confirmed that USP2-AS1 expression was increased in HBMSCs after culturing in osteogenic differentiation medium (OM-HBMSCs). Moreover, we uncovered that knockdown of USP2-AS1 inhibited the osteogenic differentiation of HBMSCs. Further exploration indicated that USP2-AS1 positively regulated the expression of its nearby gene USP2. Mechanistically, USP2-AS1 recruited lysine demethylase 3A (KDM3A) to stabilize ETS proto-oncogene 1 (ETS1), transcription factor that transcriptionally activated USP2. Additionally, USP2-induced Wnt/β-catenin signalling pathway activation via deubiquitination of β-catenin protein. In summary, our study proved that lncRNA USP2-AS1 facilitates the osteogenic differentiation of HBMSCs by targeting KDM3A/ETS1/USP2 axis to activate the Wnt/β-catenin signalling pathway.

Abstract Background The initial randomized, double‐blinded, actively controlled, phase III ANEAS study (NCT03849768) demonstrated that aumolertinib showed superior efficacy relative to gefitinib as first‐line therapy in epidermal growth factor receptor (EGFR)‐mutated advanced non‐small cell lung cancer (NSCLC). Metastatic disease in the central nervous system (CNS) remains a challenge in the management of NSCLC. This study aimed to compare the efficacy of aumolertinib versus gefitinib among patients with baseline CNS metastases in the ANEAS study. Methods Eligible patients were enrolled and randomly assigned in a 1:1 ratio to orally receive either aumolertinib or gefitinib in a double‐blinded fashion. Patients with asymptomatic, stable CNS metastases were included. Follow‐up imaging of the same modality as the initial CNS imaging was performed every 6 weeks for 15 months, then every 12 weeks. CNS response was assessed by a neuroradiological blinded, independent central review (neuroradiological‐BICR). The primary endpoint for this subgroup analysis was CNS progression‐free survival (PFS). Results Of the 429 patients enrolled and randomized in the ANEAS study, 106 patients were found to have CNS metastases (CNS Full Analysis Set, cFAS) at baseline by neuroradiological‐BICR, and 60 of them had CNS target lesions (CNS Evaluable for Response, cEFR). Treatment with aumolertinib significantly prolonged median CNS PFS compared with gefitinib in both cFAS (29.0 vs. 8.3 months; hazard ratio [HR] = 0.31; 95% confidence interval [CI], 0.17‐0.56; P < 0.001) and cEFR (29.0 vs. 8.3 months; HR = 0.26; 95% CI, 0.11‐0.57; P < 0.001). The confirmed CNS overall response rate in cEFR was 85.7% and 75.0% in patients treated with aumolertinib and gefitinib, respectively. Competing risk analysis showed that the estimated probability of CNS progression without prior non‐CNS progression or death was consistently lower with aumolertinib than with gefitinib in patients with and without CNS metastases at baseline. No new safety findings were observed. Conclusions These results indicate a potential advantage of aumolertinib over gefitinib in terms of CNS PFS and the risk of CNS progression in patients with EGFR‐mutated advanced NSCLC with baseline CNS metastases. Trial registration ClinicalTrials.gov number, NCT03849768

Abstract Background Usage of immune checkpoint inhibitors (ICIs) has prolonged the overall survival (OS) of patients with extensive‐stage small‐cell lung cancer (ES‐SCLC). In clinical trials, males accounted for a large proportion, leading to the uncertainty of its efficacy in female patients. We therefore conducted this study to explore the efficacy and safety of using ICIs in female patients with ES‐SCLC. Methods We retrospectively enrolled female SCLC patients and subdivided them into two groups. Group A (n = 40) was defined as ES‐SCLC patients who received first‐line standard chemotherapy with or without ICIs. Group B (n = 47) included relapsed SCLC patients who were administered with second‐line therapies. Kaplan–Meier methodology was used to calculate survival analysis. Chi‐squared tests were used to analyze the incidence of adverse events (AEs). Results Median progression‐free survival (PFS) and median OS favored the ICI‐contained cohorts (Group A PFS: 8.3 vs. 6.1 months; OS: not reached vs. 11.3 months; Group B PFS: 15.1 vs. 3.3 months; OS: 35.3 vs. 8.3 months), especially in those patients who received second‐line immunotherapies. Patients who received immunotherapy had a slightly higher incidence rate of grade ≥3 AEs (Group A: 71.4% vs. 46.2%; Group B: 44.5% vs. 13.2%). Those who developed grade ≥3 AEs in first‐line ICIs cohort had a more favorable survival (PFS: 8.3 vs. 3.2 months; OS: not reached vs. 5.1 months). Conclusions Our study suggested that female ES‐SCLC patients treated with immunotherapy tended to achieve a relatively longer survival. The incidence of AEs (grade ≥3) was higher in women patients receiving ICIs, which requires monitoring more closely.

Abstract Background The modifiable mechanisms underlying the association between socioeconomic status (SES) and preterm birth remain unclear. This study aimed to investigate the relationship between preterm birth and maternal SES or gestational weight gain (GWG), as well as the role of GWG in mediating SES disparities in preterm birth. Methods Data was from a hospital-based sub-study of physical growth and development survey for Chinese newborns with various gestational ages. Singleton newborns aged from 24 to 42weeks’ gestation and their mothers were included. Using information from maternal questionnaire, a composite SES was constructed with parental education and family annual income. GWG as mediator was calculated by deducting pre-pregnancy weight from maternal weight at delivery. Logistic regression model was adopted to investigate the association of preterm birth with SES or GWG. Causal mediation analysis was performed to measure mediating effect of GWG on the pathway from SES to preterm birth. Results After controlling for potential confounders, risk of preterm birth was reduced by 12.4% (OR = 0.876, 95%CI:0.855–0.879) for per one-kilogram increase of GWG, and risk of preterm birth was reduced by 24% (OR = 0.760, 95%CI: 0.717–0.806) for per one-unit increase of SES score. Mediation analysis supported a significant association between higher SES and decreased risk of preterm partly through higher GWG, in which estimated proportion mediated by GWG was 13.04% (95%CI: 11.89–16.25). GWG also played a significant role as a mediator when socioeconomic status was indicated by maternal education, paternal education or family income. GWG mediated approximately 11.03% (95% CI: 8.56–18.25) of the total effect of SES on very preterm birth, which was greater than that for moderate preterm birth (6.72%, 95%CI: 2.72–31.52) and late preterm birth (9.04%, 95%CI: 5.24–24.04). A series of sensitive analysis confirmed the robustness of association of interest. Conclusion Increased GWG and higher socioeconomic status are strongly associated with a lower risk of preterm birth. GWG mediates socioeconomic disparities in preterm birth, most notably in very preterm birth. Understanding this mechanism will aid in the development of interventions and policy for maternal and child health care.

This paper presents a plume divergence angle prediction model for ion thruster. Firstly, an analytical model using Gaussian distribution for single grid hole plume is proposed. The parameters of this single hole model are obtained from the particle simulation results of ion optics which utilizes the immersed finite element Particle-in-cell Monte Carlo collision (IFE-PIC-MCC) method. Then, by the extension of the single hole model, a three-dimensional plume model for the whole ion optics is proposed. This plume model can be used to predict the divergence angle of ion thruster plume. Finally, a numerical example with the simulation of a 217-hole ion optics is provided to demonstrate the features of the proposed method.

Abstract The tensile properties of coal under dynamic loading are important mechanical characteristics of coal and are highly important for controlling coal rock stability under impact loading conditions, selecting blasting engineering parameters, and studying the mechanism of rockburst disasters. To investigate the dynamic tensile failure process of coal subjected to impact loading, this study used high-speed photography and digital image correlation technology to capture the dynamic tensile failure of coal under impact loading. The dynamic tensile evolution was quantitatively analyzed from the beginning of coal sample being loaded to failure. The captured images of the coal were processed, and the fractal dimension was used to quantitatively describe the evolution of the coal surface cracks under impact loading. The following conclusions were drawn from the experimental results: (1) An empirical formula was established to describe the dynamic tensile strength characteristics of coal under different loading rates. (2) Under impact loading, the maximum strain of a Brazilian disc coal sample first appeared at the contact end between the sample and the incident rod. (3) Under impact loading, a Brazilian disc coal sample cracked from the center of the sample outward, and the crack subsequently extended toward both ends. The fractal dimension of the crack exhibited a power function relationship with time, and the variation range of the fractal dimension of the crack was 1.05–1.39.

In this paper, we introduce a novel method to predict composite plate microstructures based on thermal expansion using deep learning. Traditional analysis methods are cumbersome and resource intensive. We created a detailed dataset from finite element simulations, capturing edge displacements during thermal expansion. This dataset feeds into our multilayer perceptron model, generating precise microstructure matrices. Our approach achieves high accuracy and efficiency, markedly reducing computational overhead. By combining deep learning with finite element analysis, we streamline predictions and enhance precision. This integrated approach serves as a potent tool for engineers and materials scientists, facilitating composite structure design and optimization.

Abstract Background As a potential target receptor tyrosine kinase, mesenchymal-epithelial transition factor (MET) exhibits high aberrant expression across various tumors. This study aimed to evaluated the safety, tolerability, efficacy and pharmacokinetics (PK) of BPI-9016M, a novel tyrosine kinase inhibitor (TKI) targeting c-MET, in c-MET overexpression or MET exon 14 skipping mutation patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC). Methods/design In this two-part multicenter phase Ib study, eligible patients with locally advanced or metastatic NSCLC harboring c-MET overexpression or MET exon 14 skipping mutation were enrolled into Part A (tested positive for c-MET overexpression [immunohistochemical staining score ≥ 2+]; 300 mg quaque die [QD], 450 mg QD and 600 mg QD cohorts) or Part B (tested positive for MET exon 14 skipping mutation; 400 mg bis in die [BID] cohort), respectively. The primary endpoints were safety, objective response rate (ORR) and disease control rate (DCR), the second endpoints were PK parameters, progression-free survival (PFS) and overall survival (OS). Results Between March 15, 2017 and September 18, 2021, 38 patients were enrolled (Part A, n = 34; Part B, n = 4). Of 38 patients, 32 (84.2%) patients completed the treatment protocol. As of the data cut-off date on January 27, 2022, all patients reported at least one treatment-emergent adverse event (TEAE). Ninety-two point one percent (35/38) of patients experienced treatment-related adverse events (TRAEs), and grade ≥ 3 TRAEs were observed in 11 (28.9%) patients. The most common TRAEs were elevated alanine aminotransferase (ALT, 14/38, 36.8%) and elevated aspartate aminotransferase (AST, 11/38, 28.9%). Only one (2.6%) patient had treatment-related serious adverse event (SAE) in 600 mg QD cohort due to thrombocytopenia. PK analysis showed BPI-9016M and its main metabolites (M1 and M2-2) reached steady state after seven days of continuous administration. At the dose of 300 mg QD and 450 mg QD, the exposure of BPI-9016M increased with increasing dose. Exposure of BPI-9016M was similar at 450 mg QD and 600 mg QD, which may exhibit a saturation trend. In all patients, ORR and DCR were 2.6% (1/38, 95% confidence interval [CI] 0.1–13.8%) and 42.1% (16/38, 95% CI 26.3–59.2%), respectively. Only one partial response (PR) patient was observed at a dose of 600 mg QD in Part A. In Part B, DCR was 75.0% (3/4, 95% CI 19.4–99.4%). The median PFS and OS in all 38 patients were 1.9 months (95% CI 1.9–3.7) and 10.3 months (95% CI 7.3–not evaluable [NE]), respectively. Conclusion BPI-9016M showed manageable safety profile in c-MET overexpression or MET exon 14 skipping mutation patients with locally advanced or metastatic NSCLC, but showed limited efficacy. Trial registration Clinicaltrials.gov NCT02929290 (11/10/2016).

Abstract Background Furmonertinib (AST2818) is a brain penetrant pan-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) targeting both EGFR sensitizing mutations and T790M mutation. We report the pooled central nervous system (CNS) efficacy data of furmonertinib in patients with EGFR T790M mutated non-small cell lung cancer (NSCLC) from two phase 2 studies. Methods This was a pooled, post-hoc analysis of two phase 2 studies (NCT03127449 [phase 2a study of furmonertinib], NCT03452592 [phase 2b study of furmonertinib]). In the phase 2a study, patients received furmonertinib 40 mg, 80 mg, 160 mg, or 240 mg orally once daily. In the phase 2b study, all patients received furmonertinib 80 mg orally once daily. CNS efficacy of furmonertinib was analyzed in patients with baseline CNS lesions by an independent review center per Response Evaluation Criteria in Solid Tumors version 1.1. Results A total of 132 patients with baseline CNS metastases were included in this analysis. In 52 patients with measurable CNS lesions, CNS objective response rates were zero (0/1), 65% (22/34), 85% (11/13), and 25% (1/4), and CNS disease control rates were zero (0/1), 97% (33/34), 100% (13/13), and 100% (4/4) in the 40 mg, 80 mg, 160 mg, and 240 mg orally once daily group, respectively. In patients with measurable or non-measurable CNS lesions, median CNS progression-free survival was 2.8 months (95% confidence interval [CI] 1.4–8.3), 11.6 months (95% CI 8.3–13.8), 19.3 months (95% CI 5.5-not available [NA]), and not reached (95% CI 2.8 months-NA) in the 40 mg, 80 mg, 160 mg, and 240 mg orally once daily group, respectively. Conclusions Furmonertinib showed promising CNS efficacy in doses of 80 mg orally once daily or higher in patients with EGFR T790M mutated NSCLC. Trial registration Both studies were registered on ClinicalTrial.gov. The phase 2a study was registered with NCT03127449 on April 25, 2017; The phase 2b study was registered with NCT03452592 on March 2, 2018.

Abstract Background The global Phase III IMpower132 study evaluating atezolizumab plus pemetrexed and carboplatin or cisplatin (APP) versus pemetrexed plus carboplatin or cisplatin (PP) for first‐line treatment of non‐squamous advanced non‐small cell lung cancer (NSCLC) met its co‐primary progression‐free survival (PFS) endpoint at the primary analysis in the intention‐to‐treat (ITT) population. Although the co‐primary overall survival (OS) endpoint was not met, numerical OS improvement favoring APP over PP was observed at the final analysis. We report primary results for Chinese patients in IMpower132. Methods Treatment‐naive Chinese patients with non‐squamous stage IV EGFR/ALK mutation‐negative NSCLC were randomized 1:1 to receive 4 or 6 cycles of APP or PP, followed by maintenance atezolizumab plus pemetrexed or pemetrexed. Co‐primary endpoints were investigator‐assessed PFS and OS. Results The ITT population included 163 Chinese patients (82 in the APP arm and 81 in the PP arm). At data cutoff (median follow‐up, 11.7 months), the median PFS in the APP and PP arms was 8.3 and 5.8 months, respectively; the unstratified hazard ratio (HR) was 0.73 (95% CI: 0.50, 1.08). At the interim OS analysis, median OS was not estimable in either arm; the unstratified HR was 0.70 (95% CI: 0.40, 1.24). No new safety signals were observed. Conclusion Among Chinese patients in IMpower132, PFS benefit was seen with APP versus PP. Though interim OS data were immature, there was a trend toward OS benefit favoring APP versus PP. The safety profile of the APP was consistent with the known risks of the individual treatment components. ClinicalTrials.gov: NCT02657434.

Abstract Background Early diagnosis of lung adenocarcinoma (LUAD), one of the most common types of lung cancer, is very important to improve the prognosis of patients. The current methods can’t meet the requirements of early diagnosis. There is a pressing need to identify novel diagnostic biomarkers. Secretory proteins are the richest source for biomarker research. This study aimed to identify candidate secretory protein biomarkers for early diagnosis of LUAD by integrated bioinformatics analysis and clinical validation. Methods Differentially expressed genes (DEGs) of GSE31210, gene expression data of early stage of LUAD, were analyzed by GEO2R. Upregulated DEGs predicted to encode secreted proteins were obtained by taking the intersection of the DEGs list with the list of genes encoding secreted proteins predicted by the majority decision-based method (MDSEC). The expressions of the identified secreted proteins in the lung tissues of early-stage LUAD patients were further compared with the healthy control group in mRNA and protein levels by using the UALCAN database (TCGA and CPTAC). The selected proteins expressed in plasma were further validated by using Luminex technology. The diagnostic value of the screened proteins was evaluated by receiver operating characteristic (ROC) analysis. Cell counting kit-8 assay was carried out to investigate the proliferative effects of these screened proteins. Results A total of 2183 DEGs, including 1240 downregulated genes and 943 upregulated genes, were identified in the GSE31210. Of the upregulated genes, 199 genes were predicted to encode secreted proteins. After analysis using the UALCAN database, 16 molecules were selected for further clinical validation. Plasma concentrations of three proteins, Midkine (MDK), WAP four-disulfide core domain 2 (WFDC2), and C-X-C motif chemokine ligand 14 (CXCL14), were significantly higher in LUAD patients than in healthy donors. The area under the curve values was 0.944, 0.881, and 0.809 for MDK, WFDC2, and CXCL14, 0.962 when combined them. Overexpression of the three proteins enhanced the proliferation activity of A549 cells. Conclusions MDK, WFDC2, and CXCL14 were identified as candidate diagnostic biomarkers for early-stage LUAD and might also play vital roles in tumorigenesis.

Abstract Background Treatment options for Chinese patients with locally advanced or metastatic squamous‐cell non‐small‐cell lung cancer (sqNSCLC) after failure of first‐line chemotherapy are limited. This study (ORIENT‐3) aimed to evaluate the efficacy and safety of sintilimab versus docetaxel as second‐line treatment in patients with locally advanced or metastatic sqNSCLC. Methods ORIENT‐3 was an open‐label, multicenter, randomized controlled phase 3 trial that recruited patients with stage IIIB/IIIC/IV sqNSCLC after failure with first‐line platinum‐based chemotherapy. Patients were randomized in a 1:1 ratio to receive either 200 mg of sintilimab or 75 mg/m2 of docetaxel intravenously every 3 weeks, stratified by the Eastern Cooperative Oncology Group performance status. The primary endpoint was overall survival (OS) in the full analysis set (FAS). Secondary endpoints included progression‐free survival (PFS), objective response rate (ORR), disease control rate (DCR), duration of response (DoR) and safety. Results Between August 25, 2017, and November 7, 2018, 290 patients were randomized. For FAS, 10 patients from the docetaxel arm were excluded. The median OS was 11.79 (n = 145; 95% confidence interval [CI], 10.28‐15.57) months with sintilimab versus 8.25 (n = 135; 95% CI, 6.47‐9.82) months with docetaxel (hazard ratio [HR]: 0.74; 95% CI, 0.56‐0.96; P = 0.025). Sintilimab treatment significantly prolonged PFS (median 4.30 vs. 2.79 months; HR: 0.52; 95% CI, 0.39‐0.68; P < 0.001) and showed higher ORR (25.50% vs. 2.20%, P < 0.001) and DCR (65.50% vs. 37.80%, P < 0.001) than the docetaxel arm. The median DoR was 12.45 (95% CI, 4.86‐25.33) months in the sintilimab arm and 4.14 (95% CI, 1.41‐7.23) months in the docetaxel arm (P = 0.045). Treatment‐related adverse events of grade ≥ 3 were reported in 26 (18.1%) patients in the sintilimab arm and 47 (36.2%) patients in the docetaxel arm. Exploratory biomarker analysis showed potential predictive values of expression levels of two transcription factors, including OVOL2 (HR: 0.35; P < 0.001) and CTCF (HR: 3.50; P < 0.001)，for sintilimab treatment. Conclusions Compared with docetaxel, sintilimab significantly improved the OS, PFS, and ORR of Chinese patients with previously treated locally advanced or metastatic sqNSCLC.

Abstract Objective Kirsten rat sarcoma viral oncogene homolog (KRAS) is an important driver gene of non‐small cell lung cancer (NSCLC). Despite a rapid progress achieved in the targeted therapy, chemotherapy remains the standard treatment option for patients with KRAS‐mutant NSCLC. This study aimed to assess real‐world data of Chinese patients with KRAS‐mutant NSCLC undergoing chemotherapy and/or immunotherapy. Methods KRAS mutational status was analyzed using next‐generation sequencing of 150,327 NSCLC patients from the Lung Cancer Big Data Precise Treatment Collaboration Group (LANDSCAPE) project (Cohort I). Treatment data were collected and analyzed retrospectively from 4348 NSCLC patients who were admitted to the Peking University Cancer Hospital and Institute between January 2009 and October 2020 (Cohort II). Results In Cohort I, 18,224 patients were detected with KRAS mutations (12.1%) of whom G12C (29.6%) was the most frequent subtype, followed by G12D (18.1%) and G12V (17.5%). In case of concomitant mutations, TP53 had the highest incidence of 33.6%, followed by EGFR (11.6%), STK11 (10.4%), KEAP1(6.2%), and CDKN2A (6.0%). Cohort II included 497 patients (11.4%) with KRAS mutations. In the first‐line chemotherapeutic analysis of Cohort II, patients benefited more from the pemetrexed/platinum (PP) regimen than the gemcitabine/platinum (GP) or taxanes/platinum (TP) regimen (median progression‐free survival [PFS], 6.4 vs. 4.9 vs. 5.6 months, hazard ratio [HR] = 0.65, 95% confidence interval [CI] 0.48–0.88, p = 0.033 and HR = 0.69, 95% CI 0.47–1.00, p = 0.05, respectively), with no significant difference when combined with bevacizumab. Regarding patients who received immune checkpoint inhibitors (ICIs), the objective response rate was 26% for a median PFS of 9.6 months (95% CI 6.16–13.03). Patients who received ICIs combined with chemotherapy had a significantly longer survival than monotherapy (median PFS, 13.9 vs. 5.2 months, HR = 0.59, 95% CI 0.35–0.99, p = 0.049). Conclusion KRAS is an important driver gene in NSCLC, compromising 12.1% in this study, and G12C was noted as the most common subtype. Patients with KRAS‐mutant NSCLC could benefit from pemetrexed‐based chemotherapy and ICIs.

ABSTRACT Recently, microbiota dysbiosis in lung cancer has attracted immense attention. Studies on lung microbes are mostly based on sequencing, which has left the potentially functional bacteria with extremely low abundance uncovered. In this study, we characterized and compared the lung and oral cavity microbiotas using culturomics and 16S rRNA gene sequencing. Of the 198 bacteria identified at the species level from bronchoalveolar lavage fluid (BALF) samples, Firmicutes was predominant (39.90%). Twenty bacterial species isolated from BALF samples were present in at least half of the patients and were also highly abundant in oral samples. Of all isolated strains, Streptococcus and Veillonella were highly dominant. The abundance of Prevotella and Veillonella decreased from the oral cavity to the lung, whereas that of Pseudomonas increased. Linear discriminant analysis effect size demonstrated that Prevotella was more abundant in the healthy samples than in the cancerous ones, which is in accordance with the isolation of Prevotella oralis only from the healthy group using culturomics. Moreover, Gemella sanguinis and Streptococcus intermedius were isolated only from the non-small-cell lung cancer (NSCLC) group, and 16S rRNA gene sequencing showed that they were higher in the NSCLC than in the small-cell lung cancer group. Furthermore, while Bacillus and Castellaniella were enriched in lung adenocarcinoma, Brucella was enriched in lung squamous cell carcinoma. Overall, alterations were observed in the microbial community of patients with lung cancer, whose diversity might be site and pathology dependent. Using culturomics and 16S rRNA gene amplicon sequencing, this study has provided insights into pulmonary and oral microbiota alterations in patients with lung cancer. IMPORTANCE The relationship between lung microbiota and cancer has been explored based on DNA sequencing; however, culture-dependent approaches are indispensable for further studies on the lung microbiota. In this study, we applied a comprehensive approach combining culturomics and 16S rRNA gene amplicon sequencing to detect members of the microbiotas in saliva and BALF samples from patients with unilateral lobar masses. We found alterations in the microbial community of patients with lung cancer, whose diversity might be site and pathology dependent. These features may be potential bacterial biomarkers and new targets for lung cancer diagnosis and treatment. In addition, a lung and oral microbial biobank from lung cancer patients was established, which represents a useful resource for studies of host-microbe interactions.

ObjectivesIn order to reveal the mechanism of perforated fixed and floating structure through-type flow fields in local high turbulence, breaking waves and fluid separation, three types of typical active/passive perforated structures (gushing floating breakwater, forced rolling flooded compartment in calm water and international standard model DTMB 5415 damaged ship) are used to study the coupled/uncoupled problem of through-type flow field and motion in perforated structures. MethodsVolume force technology is introduced, the dynamic overset grid method based on the unsteady and incompressible Navier-Stokes equation is adopted, and the k-ε turbulence model is combined to establish a calculation model of the gushing floating breakwater inflow and outflow in waves, and a calculation model of the transient inflow and steady-state sloshing of a forced rolling empty flooded compartment in calm water and a prediction model of nonlinear damaged ship motion in waves. The numerical simulation of active/passive perforated fixed and floating structure through-type turbulent flow fields is carried out. ResultsThe results show that the simulated rolling, flooded compartment wave elevations and rolling motion response of a damaged ship are consistent with the relevant experimental data, which verifies the feasibility and accuracy of typical perforated structure through-type flow and motion coupled/uncoupled calculation models. Conclusions The numerical simulation of the through-type turbulent flow fields of different structures provides new technical support for the safe navigation and survivability assessment of damaged ships, and the development of gushing breakwater.

Abstract Background This study was set to investigate the correlation between square dance and musculoskeletal system of early postmenopausal Chinese women. Methods Chinese postmenopausal women, who had been without menstruation for 1–10 years from the onset of menopause were recruited from community centers for this study. A standardized structured face-to-face interview was performed to collect demographic information, life styles, personal medical history, diet and menstrual status. Subjects who had been practicing regular square dance without participated in other sports activities for more than 2 years and over 4 h per week (usually more than 45 min per time and more than 5 times per week) were assigned to square dance group. Those postmenopausal women who had not participated in regular exercises (no more than 0.5 h per week) were recruited as the sedentary control group. Bone mineral density (BMD) of spine, total hip and femoral neck was measured by using dual-energy X-ray absorptiometry. Lower limb muscle strength was measured for the non-dominant leg, body flexibility was measured by a simple trunk bend-and-reach test, and body balance was evaluated using a single-stance test for the non-dominant leg. Independent two-tailed Student’s t-test was used for data analysis. Results 152 subjects from community centers were selected for this study and divided into square dance group (n = 74) and control group (n = 78). The square dance subjects had higher lumbar spine BMD (p = 0.01) and total hip BMD (p = 0.02) than control subjects, but there was no significant difference of femoral neck BMD (p = 0.48) between these two groups. Functional testing indicated that square dance subjects had higher lower limb muscle strength (p

Abstract Background A single‐agent of anti programmed cell death 1/programmed cell death ligand 1 (anti‐PD‐1/PD‐L1) therapy has been explored for resectable lung cancer before surgery. However, the effectiveness and safety of neoadjuvant programmed cell death 1 (PD‐1) blockade combined with chemotherapy have not been published. Methods Twenty‐one consecutive patients with potentially resectable squamous cell carcinoma of the lung who received neoadjuvant therapy followed by surgery in Beijing Cancer Hospital were included in this study. Eight patients received two cycles of neoadjuvant platinum‐based doublet chemotherapy combined with anti‐programmed cell death 1 (anti‐PD‐1) therapy, while 13 patients received two cycles of neoadjuvant platinum‐based doublet chemotherapy only. Chest computed tomography was repeated before neoadjuvant treatment and surgery. Adverse events were monitored. The major pathological response (MPR) rate was determined after surgery. Selected specimens were sent for immunohistochemical and multiplex immunofluorescence analyses, and T‐cell receptor DNA sequencing. Results Compared with neoadjuvant chemotherapy alone, the combination of PD‐1 blockade and chemotherapy increased the pathological complete response rate (37.5% vs. 7.69%) and MPR rate (50% vs. 38.46%). The pathological and radiological evaluations are not consistent. No unknown adverse effects were reported for all the patients. More tumor infiltrating lymphocytes were observed in patients who received PD‐1 blockade. No unknown pathological features associated with PD‐1 blockade were found. Immune suppression in the peritumoral spaces around the residual tumor cells was observed. The amino acid sequences of the T‐cell receptors are not significantly shared among the patients. Conclusions The combination of neoadjuvant chemotherapy and PD‐1 blockade is safe and feasible, and might indicate an increased MPR and pathological complete response rate. More investigations are needed for the best combination of the neoadjuvant therapy.

Abstract Background Lipusu is the first commercialized liposomal formulation of paclitaxel and has demonstrated promising efficacy against locally advanced lung squamous cell carcinoma (LSCC) in a small‐scale study. Here, we conducted a multicenter, randomized, phase 3 study to compare the efficacy and safety of cisplatin plus Lipusu (LP) versus cisplatin plus gemcitabine (GP) as first‐line treatment in locally advanced or metastatic LSCC. Methods Patients enrolled were aged between 18 to 75 years, had locally advanced (clinical stage IIIB, ineligible for concurrent chemoradiation or surgery) or metastatic (Stage IV) LSCC, had no previous systemic chemotherapy and at least one measurable lesion as per the Response Evaluation Criteria in Solid Tumors (version 1.1) before administration of the trial drug. The primary endpoint was progression‐free survival (PFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety profiles. To explore the possible predictive value of plasma cytokines for LP treatment, plasma samples were collected from the LP group at baseline and first efficacy evaluation time and were then subjected to analysis by 45‐Plex ProcartaPlex Panel 1 to detect the presence of 45 cytokines using the Luminex xMAP technology. The correlation between treatment outcomes and dynamic changes in the levels of cytokines were evaluated in preliminary analyses. Results The median duration of follow‐up was 15.4 months. 237 patients in the LP group and 253 patients in the GP group were included in the per protocol set (PPS). In the PPS, the median PFS was 5.2 months versus 5.5 months in the LP and GP group (hazard ratio [HR]: 1.03, P = 0.742) respectively. The median OS was 14.6 months versus 12.5 months in the LP and GP group (HR: 0.83, P = 0.215). The ORR (41.8% versus 45.9%, P = 0.412) and DCR (90.3% versus 88.1%, P = 0.443) were also similar between the LP and GP group. A significantly lower proportion of patients in the LP group experienced adverse events (AEs) leading to treatment interruptions (10.9% versus 26.4%, P < 0.001) or treatment termination (14.3% versus 23.1%, P = 0.011). The analysis of cytokine levels in the LP group showed that low baseline levels of 27 cytokines were associated with an increased ORR, and 15 cytokines were associated with improved PFS, with 14 cytokines, including TNF‐α, IFN‐γ, IL‐6, and IL‐8, demonstrating an overlapping trend. Conclusion The LP regimen demonstrated similar PFS, OS, ORR and DCR as the GP regimen for patients with locally advanced or metastatic LSCC but had more favorable toxicity profiles. The study also identified a spectrum of different cytokines that could be potentially associated with the clinical benefit in patients who received the LP regimen.

Background: Small cell lung cancer (SCLC) transformation had previously been reported mainly in epidermal growth factor receptor (EGFR) mutant adenocarcinoma. However, the underlying genomic profile remains unclear. Our study aimed to find the evolution and genotypic characteristic of SCLC transformation. Methods: Thirty-one SCLC transformation patients who were initially diagnosed as non-small cell lung cancer (NSCLC) patients were included. Whole exome sequencing (WES) of both primary and transformed re-biopsy lesions was conducted on 12 patients. Clinical characteristics were analyzed using R software (v.3.6.1). Results: Our study included 31 patients, of whom, three had lung squamous cell carcinoma, 6 patients did not carry EGFR mutations, and 30 patients received chemotherapy for SCLCs. The disease control rate (DCR) was 96.7%, and the median progression-free survival (PFS) was 4.03 months. The median time to transformation was 33.07 months, and the median overall survival (OS) was 62.08 months. Somatic mutation analysis showed that besides TP53, RB1, and EGFR, there was a high occurrence of mutations to CSMD3 and ADAMTS19, especially in the EGFR-wild type (EGFR-wt) group. Concerning mutational signature, the EGFR-mutant (EGFR-mut) transformed group favored an apolipoprotein B (APOBEC) mRNA editing catalytic polypeptide-like-associated mutation pattern (P = 0.16). DNA damage repair (DDR)-related signatures were significantly enriched in the EGFR-wt transformed group (P = 0.034). Additionally, clonal evolution analysis revealed that all patients had the same main trunk genes in the phylogenetic tree. Transformed SCLCs are not sensitive to immunotherapy, possibly due to increased tumor heterogeneity. Conclusions: Our results indicate that the EGFR-wt patients could also transform to SCLCs, but they have different genetic features with EGFR-mut patients. SCLC-transformed patients respond to classical chemotherapy and have a better prognosis than those with classical SCLCs.

In response to the challenge of low accuracy in node trust evaluation due to the high dynamics of entry and exit of drone cluster nodes, we propose a hierarchical blockchain-based trust measurement method for drone cluster nodes. This method overcomes the difficulties related to trust inheritance for dynamic nodes, trust re-evaluation of dynamic clusters, and integrated trust calculation for drone nodes. By utilizing a multi-layer unmanned cluster blockchain for trusted historical data storage and verification, we achieve scalability in measuring intermittent trust across time intervals, ultimately improving the accuracy of trust measurement for drone cluster nodes. We design a resource-constrained multi-layer unmanned cluster blockchain architecture, optimize the computing power balance within the cluster, and establish a collaborative blockchain mechanism. Additionally, we construct a dynamic evaluation method for trust in drone nodes based on task perception, integrating and calculating the comprehensive trust of drone nodes. This approach addresses trusted sharing and circulation of task data and resolves the non-inheritability of historical data. Experimental simulations conducted using NS3 and MATLAB demonstrate the superior performance of our trust value measurement method for unmanned aerial vehicle cluster nodes in terms of accurate malicious node detection, resilience to trust value fluctuations, and low resource delay retention.

Metal structural plates are extensively used in various engineering structures due to their high strength, high-temperature resistance, toughness, and plasticity. However, they are susceptible to damage from external loads and impacts over time. The current Lamb wave detection methods suffer from dispersion and multimodal effects, leading to ineffective identification of damage information. In this paper, we investigate Lamb wave propagation in steel structure plates with flat-bottomed holes using a sinusoidal modulation five-peak wave signal. Finite element numerical models are developed, and an experimental platform is constructed using steel and aluminum boards. Experimental data is collected using a Scanning Laser Doppler Vibrometer (SLDV, PSV-500, Polytec Inc., Baden-Württemberg, German). The results demonstrate that, under the same frequency, the damage reflection energy for different modes is distinct. By fusing the data from the two modes, more accurate damage imaging results are obtained in the frequency-wavenumber (f-k) domain compared to single-mode imaging. Furthermore, experiments are conducted to locate damage in a steel board with a through hole and an aluminum plate with double flat-bottomed holes, confirming the feasibility of the proposed algorithm in isotropic plates.

Traditional methods for detecting damage in engineering structures often use offline static damage detection. To enable the real-time and precise identification of dynamic damage while maintaining symmetry in engineering structures, this study primarily concentrates on isotropic plate structures widely employed in engineering. Moreover, fiberglass board composite plates were opted as a specific research object. By utilizing the weak S0 mode signals generated by low-frequency ultrasonic Lamb waves, the non-stationary A0 wave signals in the composite symmetry plate structure are collected using the non-contact SLDV (Scanning Laser Doppler Vibrometer) technique. The frequency characteristic parameters in the vibration signals are obtained through HHT (Hilbert–Huang Transform) analysis, followed by filtering and noise reduction. Finally, the circular trajectory intersection method is employed to accurately locate dynamic damage sources in plate structures with different material properties, thereby validating the positioning effect of contact sensors in detecting impacts caused by random impulses.

Abstract The delegating computation has become an irreversible trend, together comes the pressing need for fairness and efficiency issues. To solve this problem, we leverage game theory to propose a smart contract-based solution. First, according to the behavioral preferences of the participants, we design an incentive contract to describe the motivation of the participants. Next, to satisfy the fairness of the rational delegating computation, we propose a rational delegating computation protocol based on reputation and smart contract. More specifically, rational participants are to gain the maximum utility and reach the Nash equilibrium in the protocol. Besides, we design a reputation mechanism with a reputation certificate, which measures the reputation from multiple dimensions. The reputation is used to assure the client’s trust in the computing party to improve the efficiency of the protocol. Then, we conduct a comprehensive experiment to evaluate the proposed protocol. The simulation and analysis results show that the proposed protocol solves the complex traditional verification problem. We also conduct a feasibility study that involves implementing the contracts in Solidity and running them on the official Ethereum network. Meanwhile, we prove the fairness and correctness of the protocol.

Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. The systemic antitumor therapy of advanced NSCLC has undergone renovations of chemotherapy, targeted therapy and immunotherapy, which results in greatly improved survival for patients with advanced NSCLC. Immune checkpoint inhibitors (ICIs), especially targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1), has changed the treatment paradigm of NSCLC. ICIs have become the standard treatment for advanced NSCLC without epidermal growth factor receptor(EGFR) mutation or anaplastic lymphomakinase(ALK) translocation in the first- or second-line setting, and for locally advanced NSCLC following concurrent radiotherapy and chemotherapy. ICIs are also promising in adjuvant/neoadjuvant therapy. More and more ICIs have been approved domestically for the treatment of NSCLC. Led by the NSCLC expert committee of Chinese Society of Clinical Oncology (CSCO), this consensus was developed and updated based on thoroughly reviewing domestic and foreign literatures, clinical trial data, systematic reviews, experts’ discussion and the consensus(2019 version). This consensus will aid domestic clinicians in the treatment of NSCLC with ICIs.

Abstract Background Although advanced non-squamous non-small cell lung cancer (NSCLC) patients have significantly better survival outcomes after pemetrexed based treatment, a subset of patients still show intrinsic resistance and progress rapidly. Therefore we aimed to use a blood-based protein signature (VeriStrat, VS) to analyze whether VS could identify the subset of patients who had poor efficacy on pemetrexed therapy. Methods This study retrospectively analysed 72 advanced lung adenocarcinoma patients who received first-line pemetrexed/platinum or combined with bevacizumab treatment. Results Plasma samples from these patients were analysed using VS and classified into the Good (VS-G) or Poor (VS-P) group. The relationship between efficacy and VS status was further investigated. Of the 72 patients included in this study, 35 (48.6%) were treated with pemetrexed plus platinum and 37 (51.4%) were treated with pemetrexed/platinum combined with bevacizumab. Among all patients, 60 (83.3%) and 12 (16.7%) patients were classified as VS-G and VS-P, respectively. VS-G patients had significantly better median progression-free survival (PFS) (Unreached vs. 4.2 months; P

Abstract Background The five-year cumulative incidence rate in patients diagnosed with stage I small-cell lung cancer (SCLC) who were instructed to undergo surgery was from 40 to 60%.The death competition influence the accuracy of the classical survival analyses. The aim of the study is to investigate the mortality of stage I small-cell lung cancer (SCLC) patients in the presence of competing risks according to a proportional hazards model, and to establish a competing risk nomogram to predict probabilities of both cause-specific death and death resulting from other causes. Methods The study subjects were patients diagnosed with stage I SCLC according to ICD-O-3. First, the cumulative incidence functions (CIFs) of cause-specific death, as well as of death resulting from other causes, were calculated. Then, a proportional hazards model for the sub-distribution of competing risks and a monogram were constructed to evaluate the probability of mortality in stage I SCLC patients. Results 1811 patients were included in this study. The five-year probabilities of death due to specific causes and other causes were 61.5 and 13.6%, respectively. Tumor size, extent of tumor, surgery, and radiotherapy were identified as the predictors of death resulting from specific causes in stage I SCLC. The results showed that surgery could effectively reduce the cancer-specific death, and the one-year cumulative incidence dropped from 34.5 to 11.2%. Like surgery, chemotherapy and radiotherapy improved the one-year survival rate. Conclusions We constructed a predictive model for stage I SCLC using the data from the SEER database. The proportional sub-distribution models of competing risks revealed the predictors of death resulting from both specific causes and other causes. The competing risk nomogram that we built to predict the prognosis showed good reliability and could provide beneficial and individualized predictive information for stage I SCLC patients.

Abstract Background This study aimed to establish a novel nomogram prognostic model to predict death probability for non-small cell lung cancer (NSCLC) patients who received surgery.. Methods We collected data from the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute in the United States. A nomogram prognostic model was constructed to predict mortality of NSCLC patients who received surgery. Results A total of 44,880 NSCLC patients who received surgery from 2004 to 2014 were included in this study. Gender, ethnicity, tumor anatomic sites, histologic subtype, tumor differentiation, clinical stage, tumor size, tumor extent, lymph node stage, examined lymph node, positive lymph node, type of surgery showed significant associations with lung cancer related death rate (P

Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer, most NSCLC patients are at advanced stage at the time of diagnosis. For patients without sensitive driven-oncogene mutations, chemotherapy is still the main treatment at present, the overall prognosis is poor. Improving outcomes and obtaining long-term survival are the most urgent needs of patients with advanced NSCLC. In recent years, immunotherapy has developed rapidly. Immune checkpoint inhibitors (ICIs), especially targeting programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1), have made a breakthrough in the treatment of NSCLC, beneficial to patients’ survival and changed the treatment pattern for NSCLC. It shows more and more important role in the treatment of NSCLC. Led by NSCLC expert committee of Chinese society of clinical oncology (CSCO), relevant experts in this field were organized. On the basis of referring to domestic and foreign literature, systematically evaluating the results of Chinese and foreign clinical trials, and combining the experiences of the experts, the experts group reached an agreement to develop this consensus. It will guide domestic counterparts for better application of ICIs to treat NSCLC.

Lung cancer is the second most common cancer worldwide and the leading cause of cancer death in the world. Therefore, there is an urgent need to develop new and effective biomarkers for diagnosis and treatment. Under this circumstance, human endogenous retroviruses (HERVs) were recently introduced as novel biomarkers for cancer diagnosis. This study focused on the correlation between lung cancer and HERV-K (HML-2) transcription levels. At the cellular level, different types of lung cancer cells and human normal lung epithelial cells were used to analyze the transcription levels of the HERV-K (HML-2) gag, pol, and env genes by RT–qPCR. At the level of lung cancer patients, blood samples with background information from 734 lung cancer patients and 96 healthy persons were collected to analyze the transcription levels of HERV-K (HML-2) gag, pol, and env genes. The results showed that the transcriptional levels of the HERV-K (HML-2) gag, pol, and env genes in lung cancer cells and lung cancer patient blood samples were significantly higher than those in the healthy controls, which was also verified by RNAScope ISH technology. In addition, we also found that there was a correlation between the abnormal transcription levels of HERV-K (HML-2) genes in lung cancer patients and the clinicopathological parameters of lung cancer. We also identified the distribution locations of the gag, pol, and env primer sequences on each chromosome and analyzed the function of these loci. In conclusion, HERV-K (HML-2) genes may be a potential biomarker for the diagnosis of lung cancer.

In this paper, the limitations of two-dimensional magnetic field configuration for an annular ion thruster are analyzed theoretically and numerically. The two-dimensional magnetic field, which is commonly used in traditional ion thrusters, has been proved to be a very effective way for the confinement of primary electrons and ions. Hence, the confinement characteristics of primary electrons and ions in an annular ion thruster with the two-dimensional magnetic field configuration are first analyzed theoretically. Then, according to the analysis, a two-dimensional magnetic field for an annular ion thruster is designed. On this basis, the limitations of the two-dimensional magnetic field configuration are analyzed and discussed by a three-dimensional (3D) Particle-in-cell Monte Carlo collision (PIC-MCC) model. The results show that if the collision process is not considered, a uniform distribution of primary electrons can be achieved theoretically. However, when considering the collision process, the atom forms a significant impedance to the circumferential motion of primary electrons, thus greatly increasing the loss rate of primary electrons. Finally, it is found that, since primary electrons are not guided and constrained in the circumferential direction under the two-dimensional magnetic field, the discharge uniformity cannot be improved only by increasing the magnetic field intensity.

Introduction: Pembrolizumab plus chemotherapy significantly improved survival outcomes versus placebo plus chemotherapy in patients with previously untreated metastatic squamous NSCLC in the randomized, double-blind, phase 3 KEYNOTE-407 study. We present the results of Chinese patients enrolled in the KEYNOTE-407 global and China extension studies. Methods: Patients enrolled from mainland China in the KEYNOTE-407 global (NCT02775435) and China extension studies (NCT03875092) were randomized 1:1 to 35 cycles of pembrolizumab or placebo plus four cycles of carboplatin and paclitaxel or nab-paclitaxel. Dual primary end points were overall survival (OS) and progression-free survival (PFS) (based on the Response Evaluation Criteria in Solid Tumors version 1.1 by blinded independent central review). Results: A total of 125 patients were randomized (pembrolizumab–chemotherapy, n = 65; placebo–chemotherapy, n = 60). As of September 30, 2020, median (range) study follow-up was 28.1 (25.1‒40.9) months. Pembrolizumab–chemotherapy improved OS (hazard ratio [HR] = 0.44, 95% confidence interval [CI]: 0.28–0.70) and PFS (HR = 0.35, 95% CI: 0.24–0.52) versus placebo–chemotherapy. Two-year OS and PFS rates for pembrolizumab–chemotherapy versus placebo–chemotherapy were 56.9% versus 31.7% and 24.2% versus 3.3%, respectively. Treatment-related grade 3 to 5 adverse events occurred in 81.5% and 81.7%, respectively. Relative to baseline, pembrolizumab–chemotherapy improved global health status/quality of life scores at week 18 versus placebo–chemotherapy (difference in least squares means = 7.6, 95% CI: 1.5–13.7) and prolonged time to deterioration in cough, chest pain, or dyspnea (HR = 0.50, 95% CI: 0.28–0.89). Conclusions: Pembrolizumab–chemotherapy prolonged survival versus placebo–chemotherapy with manageable toxicity and preserved or improved health-related quality of life in Chinese patients with metastatic squamous NSCLC. These findings support pembrolizumab–chemotherapy as first-line therapy in this population.

A healthy lifestyle is related to metabolic syndrome (MetS), but the mechanism is not fully understood. This study aimed to examine the association of components of MetS with lifestyle in a Chinese population and potential mediation role of serum uric acid (SUA) in the association between lifestyle behaviors and risk of components of MetS. Data were derived from a baseline survey of the Shaanxi urban cohort in the Regional Ethnic Cohort Study in northwest China. The relationship between components of MetS, healthy lifestyle score (HLS), and SUA was investigated by logistic or linear regression. A counterfactual-based mediation analysis was performed to ascertain whether and to what extent SUA mediated the total effect of HLS on components of MetS. Compared to those with 1 or less low-risk lifestyle factors, participants with 4-5 factors had 43.6% lower risk of impaired glucose tolerance (OR = 0.564; 95%CI: 0.408~0.778), 60.8% reduction in risk of high blood pressure (OR = 0.392; 95%CI: 0.321~0.478), 69.4% reduction in risk of hypertriglyceridemia (OR = 0.306; 95%CI: 0.252~0.372), and 47.3% lower risk of low levels of HDL cholesterol (OR = 0.527; 95%CI: 0.434~0.641). SUA mediated 2.95% (95%CI: 1.81~6.16%) of the total effect of HLS on impaired glucose tolerance, 14.68% (95%CI: 12.04~18.85%) on high blood pressure, 17.29% (95%CI: 15.01~20.5%) on hypertriglyceridemia, and 12.83% (95%CI: 10.22~17.48%) on low levels of HDL cholesterol. Increased HLS tends to reduce risk of components of MetS partly by decreasing the SUA level, which could be an important mechanism by which lifestyle influences MetS. [ABSTRACT FROM AUTHOR]

Background Thymic carcinomas (TCs) are rare aggressive tumors with no standard first‐line treatment. This study was conducted to determine the optimal chemotherapy regimen for advanced TC. Methods This retrospective study included 67 patients treated for stage IV TC in 2006–2015. The primary endpoints were the objective response rate (ORR) and progression‐free survival (PFS) with different chemotherapy regimens. Multivariate Cox regression analysis was used to identify factors associated with PFS, including metastatic status, radiotherapy post‐chemotherapy, primary lesion resection before chemotherapy, and chemotherapy regimen. Results A total of 36 patients received a paclitaxel‐platinum regimen, 31 received a gemcitabine‐platinum regimen, 14 underwent primary lesion resection, and 33 underwent radiotherapy. ORR was 31% (11/36) and 29% (9/31) in the paclitaxel‐platinum and gemcitabine‐platinum groups, respectively (P = 0.890). Median PFS, one‐year PFS rate, and two‐year PFS rate were 7.0 months, 26%, and 6% with paclitaxel‐platinum treatment and 12 months, 48%, and 24% with gemcitabine‐platinum treatment (log‐rank P = 0.030). Median PFS, one‐year PFS rate, and two‐year PFS rate were 18.0 months, 57%, and 33% with surgical resection and 7.3 months, 31%, and 7% without resection (log‐rank P = 0.030). Median PFS, one‐year PFS rate, and two‐year PFS rate were 13.0 months, 52%, and 20% with radiotherapy and 4.3 months, 22%, and 7% without radiotherapy (log‐rank P = 0.001). In multivariate analysis, metastatic status (hazard ratio [HR], 0.33, P = 0.004), surgical resection (HR, 0.32; P = 0.004), and radiotherapy (HR, 0.32; P

Background Small‐cell lung cancer (SCLC) is one of the most aggressive types of lung cancer. The prognosis for SCLC patients depends on many factors. The intent of this study was to construct a nomogram model to predict mortality for extensive‐stage SCLC. Methods Original data was collected from the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute in the United States. A nomogram prognostic model was constructed to predict death probability for extensive‐stage SCLC. Results A total of 16 554 extensive‐stage SCLC patients from 2004 to 2014 in the SEER database were included in this study. Gender, race, age, TNM staging (including tumor extent, nodal status, and metastasis), and treatment (surgery, chemotherapy, and radiotherapy) were identified as independent predictors for lung cancer‐specific death for extensive‐stage SCLC patients. A nomogram model was constructed based on multivariate models for lung cancer related death and other cause related death. Performance of the two models was validated by calibration and discrimination, with C‐index values of 0.714 and 0.638, respectively. Conclusion A prognostic nomogram model was established to predict death probability for extensive‐stage SCLC. This validated prognostic model may be beneficial for treatment strategy choice and survival prediction.

Background Primary tumors located in the right and left side have distinctive prognoses, but the details have not been fully identified in non‐small cell lung cancer (NSCLC). This study investigated the impact of primary tumor side on long‐term survival in NSCLC patients. Methods Data of 90 407 patients from the Surveillance, Epidemiology, and End Results (SEER) Program were analyzed. To avoid bias between groups, we used innovative propensity score matching (PSM) analysis. Results There was no significant distinction in overall survival (OS) between right (n = 53 496) and left (n = 36 911) side tumors (hazard ratio [HR] 0.993, 95% confidence interval [CI] 0.9756–1.011; P = 0.432). Left side was associated with superior five‐year cancer‐specific survival (CSS) compared to right side NSCLC (HR 0.977, 95% CI 0.9574–0.9969; P = 0.024). No significant difference was observed in OS (P = 0.689) or CSS (P = 0.288) after PSM analysis. In the 51 319 patients who underwent surgery, left side (n = 21 245) was associated with poor OS compared to right side (n = 30 074) NSCLC (HR 1.039, 95% CI 1.011–1.067; P = 0.006), while CSS was similar (HR 1.031, 95% CI 0.997–1.065; P = 0.069). In patients who underwent surgery, there was also no significant difference in OS (P = 0.986) or CSS (P = 0.979) after PSM analysis. Conclusion The prognosis between right and left side NSCLC in stage I–IIIA was similar regardless of whether patients underwent surgery. Primary tumor side cannot be considered a prognostic factor when choosing appropriate treatment.

So as to improve the reliability and accuracy of marine simulators, it is essential to predict ship heave and pitch motions in regular waves. The motions of two ships, the international standard model KVLCC2 and the first training ship, “Yukun”, of Dalian Maritime University, are simulated using a three-dimensional (3D) numerical wave tank based on the Unsteady Reynolds Averaged Navier–Stokes (URANS) equations. The free surface is captured by the volume of fluid (VOF) method, and an SST k-ω turbulence model is used to describe the turbulence flow. The numerical model is first validated for the standard KVLCC2 at three different speeds through a comparison with the published experimental data and the potential flow results. Then, numerical simulation is performed for the motion of the ship Yukun with different speeds under various sea conditions. The heave amplitude of the hull changes with the increase in the wavelength when the maximum value is reached. Upon comparing the RAOs of ship motions under different wave steepness conditions, it is apparent that the heave and pitch motions of ships nonlinearly decrease with an increase in wave steepness. The results were added to the database of the marine simulator to further improve the accuracy and realism of the simulator.

This paper proposes a fast multigrid algorithm to simulate the non-linear motion of ships in both intact and damaged conditions. The simulations of ship motions in waves are known to require much time to calculate due to the strong non-linear interactions between ship and waves. To improve the calculation efficiency while retaining the accuracy, a prediction-correction strategy was designed to accelerate the simulation through three sets of locally refined meshes. The flow field was first estimated in a coarse mesh and then mapped to a locally refine mesh for further higher-fidelity corrections. A partitioned radial basis function (PRBF) method is proposed to interpolate and reconstruct the flow field for the refined mesh. A new two-phase flow solver was developed with a fast multigrid algorithm based on the Reynolds-averaged Navier–Stokes equations (RANSE). The new solver was applied to study the non-linear behavior of a damaged ship in beam waves and the effect of damaged compartments on ship rolling motion. Validation against the solution with the original method of single set meshes and experimental data indicates that the proposed algorithm yields satisfactory results while saving 30–40% of the computational time.

Currently, there are limited treatment options for patients who developed resistance to osimertinib, a third-generation epidermal growth factor receptor (EGFR) inhibitor. Resistance to EGFR inhibitors is frequently associated with enhanced vascular endothelial growth factor (VEGF) levels. This multicenter, retrospective study aimed to evaluate the efficacy of the combination treatment with apatinib and osimertinib in 39 patients with EGFR-mutant non-small cell lung carcinoma (NSCLC) who developed osimertinib resistance. The patients received the combination of oral apatinib 250 mg qd and osimertinib 80 mg qd. The efficacy was evaluated after the first month then every 2 months thereafter. The primary endpoint was progression-free survival (PFS). The overall response rate (ORR) and the disease control rate (DCR) of the combination of apatinib and osimertinib was 12.8% (5/39) and 79.5% (31/39), respectively. The median PFS was 4 months [95% confidence interval (CI): 3.5–4.5 months]. Fourteen patients were administered with at least 6 months of combination therapy, and 11 of them remained on treatment programs. The 6-month PFS rate was 38%. Nine patients underwent biopsies after failing osimertinib treatment, and five of six patients with TP53 mutations had PFS of less than 3 months. The spectrum of resistance to osimertinib mechanisms included c-mesenchymal-epithelial transition factor (c-Met) amplification, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gain-of-function mutation, phosphatase and tensin homolog (PTEN) loss-of-function mutation, Erb-B2 receptor tyrosine kinase 2 (ERBB2) amplification, and insulin-like growth factor 1 receptor (IGF1R) mutation. The most common adverse events were hypertension (30.7%, 12/39), diarrhea (15.4%, 6/39), and proteinuria (12.8%, 5/39). The combination of apatinib and osimertinib improved the ORR and the DCR of patients with osimertinib-refractory EGFR-positive NSCLC, thus making it a reasonable treatment choice after the development of osimertinib resistance.