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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 FROM AUTHOR]

Feeding steel strip into molten steel is an effective technique for refining the solidification structure of steel, especially for high-alloy steel. This study experimentally and numerically investigated the effects of feeding strip on the solidification structure of super austenitic stainless steel S32654. The results revealed that feeding strip noticeably increased the proportion of equiaxed grains, refined the dendritic structure, and improved Mo segregation and the precipitation of σ phase. The relevant mechanism was clarified as follows. Firstly, feeding strip promoted the formation and survival of a large number of floating dendrites by cooling the molten steel. As the temperature decreased, these floating dendrites sharply increased their quantity by repeated splitting and then acted as nucleation particles. Numerous equiaxed grains grew around these floating dendrites, significantly refining the central dendritic structure. Meanwhile, the doubling of the equiaxed grains has two effects on Mo segregation. First, it prevented the growth of columnar grains and the movement of Mo segregation interface towards the center, thus reducing the Mo macrosegregation. On the other hand, it dispersed and refined the residual liquid phase (Mo segregation regions), thereby reducing the Mo microsegregation. Additionally, the reduced Mo segregation lowered the σ phase precipitation temperature, allowing it to form in solid austenite with a shortened growth duration. The lighter Mo segregation and slower Mo diffusion in solid austenite led to insufficient Mo supply for the σ phase growth. Moreover, dendritic refinement limited the growth space of the σ phase. Finally, less and finer σ phase particles precipitated in the S32654 steel fed with strip. The improvement of feeding strip on the solidification structure will reduce the temperature and time required for high-temperature homogenization, which is beneficial for the subsequent hot working. [Display omitted] • Feeding strip markedly improve dendritic structure, segregation, and precipitation. • Feeding strip noticeably promotes the formation of floating dendrites. • Floating dendrite acts as nucleation particles and refines the dendritic structure. • The refinement and proliferation of equiaxed grains reduce central Mo segregation. • Mo segregation reduction promotes the fine and dispersed precipitation of σ phase. [ABSTRACT FROM AUTHOR]

Ovarian endometriosis is a common gynecological disease, and one of its most significant symptoms is infertility. In patients with endometriosis, defects in endometrial decidualization lead to impaired endometrial receptivity and embryo implantation, thus affecting early pregnancy and women's desire to have children. However, the mechanisms underlying the development of endometriosis and its associated defective decidualization are unclear. We find that NEK2 expression is increased in the ectopic and eutopic endometrium of patients with endometriosis. Meanwhile, NEK2 interacts with FOXO1 and phosphorylates FOXO1 at Ser184, inhibiting the stability of the FOXO1 protein. Importantly, NEK2-mediated phosphorylation of FOXO1 at Ser184 promotes cell proliferation, migration, invasion and impairs decidualization. Furthermore, INH1, an inhibitor of NEK2, inhibits the growth of ectopic lesions in mouse models of endometriosis and promotes endometrial decidualization in mouse models of artificially induced decidualization. Taken together, these findings indicate that NEK2 regulates the development of endometriosis and associated disorders of decidualization through the phosphorylation of FOXO1, providing a new therapeutic target for its treatment. [ABSTRACT FROM AUTHOR]

The effects of Cr and Mo on the precipitation behavior and associated intergranular corrosion susceptibility of S32654 were investigated by microstructure characterization, thermodynamic calculation and electrochemical measurement. Increasing Cr and Mo contents significantly promoted the formation of σ phase and inhibited the precipitation of R, π phase and Cr 2 N. Mo has stronger promotion effect on the formation of σ phase than Cr. The effects of Cr and Mo on the precipitation behavior were mainly achieved by affecting the driving force for precipitation and the activity of elements. The specific influence mechanism has been fully discussed in this paper. Additionally, the promotion effect of Cr and Mo on precipitation further expanded the area of Cr- and Mo-depleted zones around various precipitates, enhancing the intergranular corrosion susceptibility of S32654. Unlabelled Image • Effects of Cr and Mo on driving force and element activity were clarified. • Increasing Cr and Mo contents significantly promotes the precipitation of σ phase. • Raising Cr and Mo contents remarkably enhances the intergranular corrosion susceptibility. • Mo has stronger promotion effect on precipitation and intergranular corrosion susceptibility. • Intergranular corrosion is mainly caused by Cr- and Mo-depleted zones around precipitates. [ABSTRACT FROM AUTHOR]

Abstract High-temperature oxidation behavior and the mechanism of hyper duplex stainless steel S32707 were investigated at 900, 1000, 1100 and 1200 °C in air. Some interesting oxidation characteristics were observed, and the corresponding oxidation mechanisms were proposed. At 900 °C, oxidation follows a linear rate law. The combined actions of MoO 3 volatilization, molten molybdate dissolution reaction and block-like σ phase and Cr 2 N precipitation cause catastrophic oxidation. When the temperature is raised to 1000 and 1100 °C, the deleterious effects of MoO 3 and molten molybdates are greatly enhanced. Moreover, undesirable air-nitriding occurs and further accelerates the oxidation. The synergistic effects of MoO 3 volatilization, molten molybdate dissolution reaction and air-nitriding strongly promote catastrophic oxidation. Surprisingly, the oxidation at 1200 °C follows a near-parabolic rate law. The disappearances of MoO 3 , molten molybdates and air-nitriding lead to the formation of a rather compact, complete and protective oxide layer. The oxidation resistance of the steel has been clearly improved. Graphical Abstract Unlabelled Image Highlights • High temperature oxidation behavior and mechanism of S32707 were investigated in air. • MoO 3 , molten molybdate and precipitate jointly cause catastrophic oxidation at 900 °C. • Air-nitriding plays an important role in accelerating oxidation at 1000 and 1100 °C. • Synergism of MoO 3 , molten molybdate and nitriding promotes catastrophic oxidation. • Disappearance of MoO 3 , molybdate and nitriding enhances oxidation resistance at 1200 °C. [ABSTRACT FROM AUTHOR]

Thermodynamic calculation as well as microstructure characterization was carried out to investigate the precipitation behavior of super austenitic stainless steel S32654 aged at 700–1100 °C. The corresponding precipitation characteristics and transformation mechanisms of secondary phases were proposed. The results demonstrate that σ phases with various morphologies formed during isothermal aging, and followed a sequence of intergranular, cellular and intragranular with aging temperature. The intergranular σ phase nucleated much faster than the intragranular one due to the lower nucleation energy and higher element diffusion rate at grain boundary. Most intragranular σ phase grew into needle-like shape because of the great difference in mobility of the interfaces formed around it. The cellular σ phase was firstly detected in S32654, and its growth process was successively controlled by intergranular diffusion and then by bulk diffusion of Cr and Mo. Both Cr and Mo bulk diffusion and large needle-like σ phase resulted in the incompleteness of cellular precipitation of σ phase. Another new phenomenon was found that σ phase could induce the precipitation of Cr 2 N ahead of cell boundary, between lamellar σ phases and at the σ/γ interfaces. Meanwhile, local parts of needle-like σ phase gradually transformed into Cr 2 N and R phase through Cr and Mo diffusion from the former to the latters. [ABSTRACT FROM AUTHOR]

The double loop electrochemical potentiokinetic reactivation method was modified and applied to detect the susceptibility to intergranular corrosion of super austenitic stainless steel S32654 aged at 1000 °C. The precipitation behavior was clarified, and the corresponding intergranular corrosion mechanism of aged S32654 was proposed. The microstructure demonstrated that σ phase, Cr 2 N and π phase nucleated at the initial stages of aging and gradually grew larger with increasing aging time. The degree of sensitization increased rapidly in the early stage of aging and then showed a slow increasing rate during long term aging stage, and no self-healing has been observed. Such modified double loop electrochemical potentiokinetic reactivation method could successfully characterize the relationship between microstructure evolution and intergranular corrosion susceptibility of S32654. The mechanism of intergranular corrosion was attributed to the Cr and Mo depletion adjacent to σ phase and π phase and the Cr depletion around Cr 2 N. [ABSTRACT FROM AUTHOR]

• A new insight of Y enhancing oxidation resistance of high-Mo stainless steel was proposed. • Y restrains the segregation and diffusion of Mo at GB, hindering MoO 3 volatilization. • Y promotes the segregation and diffusion of Cr at GB, accelerating Cr-rich oxide formation. A new insight into the mechanism of Y enhancing high-temperature oxidation resistance of high-Mo stainless steel was proposed from the influence of Y on the segregation and diffusion of Mo and Cr at grain boundary (GB). The results demonstrated that Y restrained the segregation and diffusion of Mo at GB and then hindered MoO 3 volatilization, remarkably reducing its damage to the oxide layer. Meanwhile, Y promoted the segregation and diffusion of Cr at GB and then accelerated the formation of Cr-rich oxides, thus improving the compactness and protectiveness of the oxide layer. Under the combined improvement of the two aspects, Y significantly enhanced the oxidation resistance of high-Mo stainless steel. [ABSTRACT FROM AUTHOR]

Under the state's key surveillance, petrochemical industries are considered polluting enterprises. Even though large-scale petrochemical enterprises follow the complete treatment of combustion waste gas, process waste gas, and volatile organic waste gas pollutants, the impact of pollutant emissions on the regional air quality is unclear. This study used the atmospheric chemical transport model and adopted the subtraction method to simulate the impacts of air pollutant emissions from four typical petrochemical enterprises on regional air quality of the North China Plain. Results indicated that emissions from petrochemical enterprises on surface PM2.5, SO2, and NO2 concentrations mainly contributed to the nearby area, particularly SO2 and NO2. The pollution can be controlled within the boundaries of the petrochemical plants. Petrochemical enterprises had a small SO2 and NO2 contribution with a maximum of up to 4.65% within a 9 km distance. Emissions from petrochemical enterprises contributed less to surface PM2.5 concentrations (less than 0.5%) within a 9 km distance. Surface O3 concentrations driven by petrochemical enterprises did not show near-source distribution characteristics, which were closely related to its complex precursors and secondary reactions. Contributions of petrochemical enterprises to local pollution decreased significantly with the increase in distance. The SO2 and NO2 pollution contributions to the North China Plain remained around 0.1–0.2%, with the maximum contribution occurring in January and July. The maximum contribution of PM2.5 in this region was in April (0.42%) while it was below 0.1% for other months. The pollutant emission from the four typical petrochemical enterprises in the North China Plain had little impact on the concentration of air pollutants in the North China Plain. However, it had a significant impact on the ambient air quality in the region near the enterprise. This study can be useful in analyzing and refining the influence of enterprises on the region. [ABSTRACT FROM AUTHOR]

Abstract: Dry deposition is an important path for pollutants entering soil and water. In this study, dustfall samples were collected at four representative sampling sites in the southeastern suburb of Beijing from March, 2005 to January, 2006, with a frequency of about once per month, and were analyzed for 16 USEPA priority PAHs using GC/MS. Results showed that the levels of ∑16PAHs in dustfall samples were 0.72–40.45 µg g−1. The levels of PHE and DahA were the highest and lowest among the 16 PAH compounds, with annual mean values of 2.07 µg g−1 and 0.009 µg g−1, respectively. Two and three ring PAH compounds were the dominant ones in dustfall samples. The distribution patterns of PAH compounds in different rings in dustfall were different from those in TSP and gas phase. Annual average fluxes of dustfall and PAHs were 1 296.67 mg m−2 d−1 and 5.14 µg m−2 d−1, respectively. There were about 423387.6 t dustfall and 1.7 t PAHs depositing onto the surface of Tongzhou District in 2005. Impacts of ground dust, meteorologic parameters, air pollution indexes and deposition velocities on PAHs deposition were discussed. Correlation analysis showed that the fluxes of 2–3 ring PAH compounds had significant positive correlation with the concentrations of 2–3 ring PAH compounds in TSP, and the fluxes of 4 ring PAH compounds had significant positive correlation with those in both TSP and gas phase, while no significant correlation existed between the fluxes of 5–6 ring PAH compounds and the concentrations of 5–6 ring PAH compounds in TSP or gas phase. A regression model was established to estimate the PAH fluxes. [Copyright &y& Elsevier]

Developing the prediction model of the end‐point carbon content of the electric arc furnace (EAF) is an effective way to reduce the adjustment frequency of liquid steel composition and shorten the smelting time. Previous data‐driven models lack effective handling of the missing values in EAF production data. This may be the main reason why model accuracy is difficult to improve. This article proposes a novel modeling method based on the CatBoost algorithm with two‐stage optimization. In the preprocessing session, empirical and empirical‐cumulative‐distribution‐based outlier detection (ECOD) methods are utilized to extract input features and reject outliers. The end‐point carbon content prediction model is built based on CatBoost. The generative adversarial imputation nets (GAIN) method is used in the first optimization stage to handle the missing values. In the second optimization stage, recursive feature elimination (RFE) is used to select the final features, and whale optimization algorithm (WOA) is used to optimize the parameters of the CatBoost model. After verification with actual production data, the two‐stage optimized CatBoost model demonstrates excellent performance compared with other methods, with an R2 of 0.903, mean absolute error of 0.021, root mean squared error of 0.043, and 90.34% hit ratio within ±0.05% error range. [ABSTRACT FROM AUTHOR]

• Hot corrosion mechanisms of S31254 were investigated at 400–1000 °C. • Mixed salt state was calculated and its effect on the corrosion was clarified. • Solid mixed salts do not corrode the sample at 400 °C. • Molten chloride salts accelerate corrosion via "electrochemical + chlorine-active corrosion" at 600 °C. • Molten chloride salts, sulfates and precipitates jointly cause catastrophic corrosion above 800 °C. Chloride- and sulphate-induced hot corrosion mechanisms of super austenitic stainless steel S31254 were investigated at 400–1000 °C under dry gas environment. The mixed salts melted with the temperature increasing, gradually deteriorating the corrosion resistance of the steel. Starting at 600 °C, molten chloride salts accelerated corrosion following a two-stage mechanism "electrochemical corrosion + chlorine-active corrosion". Above 800 °C, molten sulfates dissolved and destroyed corrosion layer via "basic fluxing" mechanism, causing serious internal and intergranular corrosion. Additionally, numerous precipitates formed and promoted element diffusion, further accelerating molten salt corrosion. Jointly deteriorated by molten salts and precipitates, the samples suffered catastrophic corrosion. [ABSTRACT FROM AUTHOR]

We have previously identified a panel of autoantibodies (AABs), including p53, GAGE7, PGP9.5, CAGE, MAGEA1, SOX2 and GBU4-5, that was helpful in the early diagnosis of lung cancer. This large-scale, multicenter study was undertaken to validate the clinical value of this 7-AABs panel for early detection of lung cancer in a Chinese population. Two independent sets of plasma samples from 2308 participants were available for the assay of AABs (training set = 300; validation set = 2008). The concentrations of AABs were quantitated by enzyme-linked immunosorbent assay (ELISA), and the optimal cutoff value for each AAB was determined in the training set and then applied in the validation set. The value of the 7-AABs panel for the early detection of lung cancer was assessed in 540 patients who presented with ground-glass nodules (GGNs) and/or solid nodules. In the validation set, the sensitivity and specificity of the 7-AABs panel were 61% and 90%, respectively. For stage I and stage II non-small cell lung cancer (NSCLC), the sensitivity of the 7-AABs panel was 62% and 59%, respectively, and for limited stage small cell lung cancer (SCLC) it was 59%; these sensitivity values were considerably higher than for traditional biomarkers (including CEA, NSE and CYFRA21-1). Importantly, the combination of the 7-AABs panel and low-dose computed tomography (CT) scanning significantly improved the diagnostic yield in patients presenting with GGNs and/or solid nodules. In conclusion, our 7-AABs panel has clinical value for early detection of lung cancer, including early-stage lung cancer presenting as GGNs. [ABSTRACT FROM AUTHOR]

Background: This study used next‐generation sequencing (NGS) to investigate the genetic profiles in cerebrospinal fluid (CSF), plasma, and tumor tissue to explore alternative detection methods for anaplastic lymphoma kinase (ALK) rearrangement status and potential resistance mechanisms to ALK inhibitors. Methods: From January 2016 to January 2021, 19 non‐small cell lung cancer (NSCLC) patients with brain metastases (BMs) and ALK‐positive primary tumors were enrolled at Beijing Chest Hospital. CSF, plasma, and primary tumor samples from patients with BMs of NSCLC were tested using NGS with a 168‐gene panel. The intracranial response and prognosis were also investigated. Results: The study included 19 patients, seven females and 12 males, aged between 29 and 68 (median age 44). CSF cytology was negative in all cases. NGS results showed ALK fusion genes detected in 26.3% (5/19) of CSF cfDNA samples, 78.9% (15/19) of plasma samples, and 89.5% (17/19) of tumor samples from ALK‐positive patients. ALK‐positive CSF samples had significantly higher allele fractions in CSF cfDNA compared with the other two sample types. In five patients with ALK‐positive in CSF, after receiving ALK inhibitors ± local treatment, one case achieved an intracranial complete response, and two had an intracranial partial response. In CSF samples, the intracranial median progression‐free survival was 8.0 and 18.0 months for ALK‐positive (n = 5) and ALK‐negative (n = 14), respectively (p = 0.077). Conclusion: CSF may serve as a liquid biopsy for ALK‐positive lung cancer with BMs by detecting cfDNA within CSF to characterize driver and resistant genes. [ABSTRACT FROM AUTHOR]

Background: Iruplinalkib (WX-0593) is an anaplastic lymphoma kinase (ALK)/c-ros oncogene 1 (ROS1) tyrosine kinase inhibitor. Here we reported the single-arm, phase II study (INTELLECT) results of the efficacy and safety of iruplinalkib for ALK-positive crizotinib-resistant advanced non-small cell lung cancer (NSCLC) patients. Methods: ALK-positive crizotinib-resistant advanced NSCLC patients aged ≥18 years, with Eastern Cooperative Oncology Group performance status of 0–2 were eligible. Patients received iruplinalkib 180 mg orally once daily for a 21-day cycle with a 7-day lead-in phase at 60 mg orally once daily. The primary endpoint was the independent review committee (IRC)-assessed objective response rate (ORR). Results: From August 7, 2019, to October 30, 2020, 146 patients were included. As of the data cut-off date on November 30, 2021, the median follow-up time was 18.2 months (95% confidence interval [CI] 16.8–18.8). IRC-assessed ORR and disease control rate (DCR) were 69.9% (95% CI 61.7–77.2%) and 96.6% (95% CI 92.2–98.9%), respectively. Investigator-assessed ORR and DCR were 63.0% (95% CI 54.6–70.8%) and 94.5% (95% CI 89.5–97.6%), respectively. Investigator-assessed median duration of response and progression-free survival (the same as median time to progression) were 13.2 months (95% CI 10.4–17.7) and 14.5 months (95% CI 11.7–20.0), respectively. Corresponding IRC-assessed results were 14.4 months (95% CI 13.1–not evaluable [NE]), 19.8 months (95% CI 14.5–NE), and NE (95% CI 14.5–NE), respectively. Investigator-assessed intracranial ORRs were 46% (41/90, 95% CI 35–56%) in patients with central nervous system metastases and 64% (27/42, 95% CI 48–78%) in patients with measurable intracranial lesions. Overall survival data were immature. Treatment-related adverse events (TRAEs) occurred in 136/146 (93.2%) patients. The most common TRAEs were aspartate aminotransferase increased (63 [43.2%]), alanine aminotransferase increased (54 [37.0%]), and blood creatine phosphokinase increased (51 [34.9%]). Dose interruption, reduction, and discontinuation due to TRAEs occurred in 21 (14.4%), 16 (11.0%), and four (2.7%) patients, respectively. Conclusions: In this study, iruplinalkib (WX-0593) demonstrated favorable efficacy and manageable safety profiles in patients with ALK-positive crizotinib-resistant advanced NSCLC. Iruplinalkib could be a new treatment option for this patient population. Trial registration: Center for Drug Evaluation of National Medical Products Administration of China: CTR20190789, registered on April 28, 2019; ClinicalTrials.gov: NCT04641754, registered on November 24, 2020. [ABSTRACT FROM AUTHOR]

Super-austenitic stainless steel S32654 sheets with 2.4 mm thickness were successfully welded by friction stir welding (FSW) at the rotational speeds of 300 and 400 rpm with a constant traverse speed of 100 mm/min using W-Re tool. The sound joints with almost no nitrogen loss were successfully produced. The microstructure evolution was characterized by optical digital microscope (ODM), scanning electron microscopy with energy-dispersive spectroscopy (SEM-EDS), electron backscatter diffraction (EBSD) and transmission electron spectroscopy (TEM). The results suggest that the grain structure evolution in stir zone (SZ) is dominated by continuous dynamic recrystallization (CDRX). The strain rate plays a dominated effect on obvious grain refinement. The band structures containing W and Re are generated due to the wear between tool probe and steel in SZ. Furthermore, the microhardness measurements and transverse tensile tests indicate that the grain refinement combining with high density dislocations and substructures improves the hardness and strength, but greatly reduces the plastic deformation capacity of joints. The more suitable welding parameters are determined as 300 rpm and 100 mm/min for this steel. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR) mutations are the strongest response predictors to EGFR tyrosine kinase inhibitors (TKI) therapy, but knowledge of the EGFR mutation frequency on lung adenocarcinoma is still limited to retrospective studies. The PIONEER study (NCT01185314) is a prospective molecular epidemiology study in Asian patients with newly diagnosed advanced lung adenocarcinoma, aiming to prospectively analyze EGFR mutation status in IIIB/IV treatment-naïve lung adenocarcinomas in Asia. We report the mainland China subset results. Eligible patients (≥20 yrs old, IIIB/IV adenocarcinoma and treatment-naïve) were registered in 17 hospitals in mainland China. EGFR was tested for mutations by amplification refractory mutation system using biopsy samples. Demographic and clinical characteristics were collected for subgroup analyses. A total of 747 patients were registered. Successful EGFR mutation analysis was performed in 741, with an overall mutation rate of 50.2%. The EGFR active mutation rate is 48.0% (with 1.3% of combined active and resistance mutations). Tobacco use (>30 pack-year vs. 0–10 pack-year, OR 0.27, 95%CI: 0.17–0.42) and regional lymph nodes involvement (N3 vs. N0, OR 0.47, 95%CI: 0.29–0.76) were independent predictors of EGFR mutation in multivariate analysis. However, even in regular smokers, the EGFR mutation frequency was 35.3%. The EGFR mutation frequency was similar between diverse biopsy sites and techniques. The overall EGFR mutation frequency of the mainland China subset was 50.2%, independently associated with the intensity of tobacco use and regional lymph nodes involvement. The relatively high frequency of EGFR mutations in the mainland China subset suggest that any effort to obtain tissue sample for EGFR mutation testing should be encouraged. [ABSTRACT FROM AUTHOR]

The passivity and corrosion behavior of 254SMo stainless steel in aggressive oilfield environments containing both carbon dioxide (CO 2) and hydrogen sulfide (H 2 S) were investigated using weight-loss and surface analyses. The results indicated that the corrosion rate increased with the increase in temperature, CO 2 /H 2 S partial pressures, tensile stress and flow rate. Compressive stress led to a reduction in sulfide compound contents and promoted the formation of protective oxide films, while tensile stress had an opposite effect. Furthermore, a synergistic effect of stress and flow was observed. • The corrosion rate of 254SMo SS increased with the temperature, CO 2 /H 2 S pressures, tensile stress and flow rate. • Cr 2 O 3 were mainly distributed in inner layer, and outer layer was dominated by FeS or MoS 2. • Tensile stress and flow coupling have a promoting effect on the corrosion of 254SMo SS. • The synergistic effect of the compressive stress and flow on the corrosion of 254SMo SS could be neglected. • Significant inhibition of corrosion of 254SMo SS under compressive stress and flow coupling. [ABSTRACT FROM AUTHOR]

This work employed the "dissolution-diffusion-deposition" model to quantitatively describe the effect of N-Mo synergism on passivation process. The model was optimized by calibrating the ion concentration, calculating the equilibrium between H+ and OH−, as well as calculating the formation amount of passive film components. Through modelling studies, we visualized and quantified how N-Mo synergy promoted passivation process. Results demonstrate that N-Mo synergy enhanced corrosion resistance by suppressing acidification of solution, increasing Cr 2 O 3 content and improving cation-selectivity of passive film. The mutual promotion between hydrolysis of NH 3 and transpassive dissolution of Mo oxides played a critical role in improving corrosion resistance. [Display omitted] • The "dissolution-diffusion-deposition" model was optimized to improve reliability. • N-Mo synergy significantly enhanced the corrosion resistance of stainless steel. • Formation processes of passive film on stainless steels with different N and Mo contents were quantitatively studied. • Mutual promotion between NH 3 and MoO 4 2− played a critical role in strengthening passive film. [ABSTRACT FROM AUTHOR]

In this work, the effect of isothermal tempering time and temperature on microstructure and hardness of 3Cr5Mo2SiVN hot-work die steel was studied. The results indicated that with the increase of isothermal tempering time and temperature, the hardness significantly decreased, which corresponded to the microstructural recovery including the transformation of high angle grain boundaries (HAGBs), the precipitation and coarsening of precipitates, the annihilation and rearrangement of dislocations, the formation and coarsening of sub-grains, and the coarsening and coalescence of laths. The driving force of grain boundary transformation was provided by the dislocation- and heat-induced boundary migration. The increased density of HAGBs was induced by the coalescence of low-angle lath boundaries and low-angle sub-boundaries that continuously absorbed dislocations. In addition, the formation and coarsening of sub-grains were the results of dislocation rearrangement with dislocation cells acting as the core. Moreover, the V-rich M(C, N), Fe-rich M 3 C, (Fe, Cr)-rich M 7 C 3 and M 23 C 6 formed by the desolvation of alloying elements exhibited an obvious coarsening, decreasing the pinning effect of dislocations and then resulting in the hardness loss. This study offered a systematically revelation into the softening mechanism of hot-work die steel. • Dislocation- and heat-induced boundary migration transformed grain boundaries. • Sub-boundaries absorbed adjacent dislocations and transformed into HAGBs. • The coalescence of low-angle lath boundaries increased HAGBs density. • V-rich M(C, N) carbonitride exhibited an obvious Ostwald ripening law. [ABSTRACT FROM AUTHOR]

Background: Pain is a fearful yet common symptom among lung cancer patients. This multicenter, cross‐sectional study was conducted to examine the current status of pain prevalence and management in lung cancer patients in northern China. Methods: A total of 18 hospitals across northern China were selected. Patients with primary lung cancer who visited the outpatient clinic or were admitted in the wards on a preplanned day were invited to complete a questionnaire. Meanwhile, physicians who had experience of treating primary lung cancer patients were also surveyed. Results: A total of 533 patients and 197 physicians provided valid responses to the survey, of which 45.4% (242/533) of patients reported pain during the course of disease and 24.2% (129/533) of patients had experienced pain within the past 24 h. The mean average pain intensity by the brief pain inventory was 3.47 ± 1.55. The binary logistic regression analysis showed female gender and stage IV disease were significantly associated with the presence of pain. A total of 74.4% (96/129) of patients reporting pain within 24 h were taking analgesics. The most common reason for patients not using analgesics was that the pain was tolerable (48.2%), while the most common barriers to prescribing opioids as reported by physicians were fear of adverse reactions (43.7%) and fear of addiction (43.1%). Conclusion: Despite recognition of the importance of pain control by most physicians and an improvement in cancer pain management, inadequate treatment of cancer pain still exists in lung cancer patients in northern China. High‐quality pain education for both patients and physicians is needed in the future. [ABSTRACT FROM AUTHOR]

CD155 is an immune checkpoint protein expressed in tumor cells that interacts with its ligand TIGIT, and inhibition of this point presents a new and novel way for cancer therapy. At present, whether the expression of CD155 affects the response to anti(α)-PD1 treatment in non-small cell lung cancer (NSCLC) patients is unclear. This observational study characterizes the expression of CD155 in NSCLC patients and its responses to PD1 inhibitors. We retrospectively detected the expression of CD155 and tumor-infiltrated lymphocyte (TIL) TIGIT by immunohistochemistry in advanced NSCLC patients who had received αPD1 therapy. The patients with CD155 positive had a significantly worse response to αPD1 therapy compared with CD155-negative patients (ORR: 25.6% vs 54.8%, P < 0.01; median PFS: 5.1 vs 7.1 months, HR = 2.322; 95% CI 1.396–3.861, P = 0.001). This effect is more prominent in PD-L1 positive patients. In PD-L1-positive patients, CD155 expression is associated with a poor response to αPD1 therapy in both LUAC (lung adenocarcinoma) and LUSC (lung squamous cell carcinoma); meanwhile, the expression of CD155 was associated with a poor response to the first-line αPD1 therapy, posterior-line αPD1 therapy, and αPD1 combination therapy. Furthermore, the expression of TIGIT was not correlated with the therapeutic effect of αPD1. Our pilot study suggests that CD155 expression attenuates the therapeutic effect of αPD1 therapy and is associated with a higher risk of progression. The CD155 pathway may be a promising immunotherapeutic target and simultaneously targeting CD155/TIGIT and PD1/PD-L1 can improve the effect of immunotherapy. CD155 impairs anti-PD1 therapy response in non-small cell lung cancer. CD155 positive patients had shorter PFS, lower ORR and 6-month response rate. [ABSTRACT FROM AUTHOR]

Lung adenocarcinoma is the most common form of lung cancer, accounting for 60% of non-small cell lung cancer (NSCLC) cases in Asian patients. Importantly, nearly half of these patients have epithelial growth factor receptor (EGFR) mutations. Though EGFR-tyrosine kinase inhibitors (EGFR-TKIs) are recommended as the first-line therapy for NSCLC patients, the development of resistance reduces their efficiency and limits their application. As the complicated and heterogeneous mechanism of acquired resistance among individuals, the efficiency of anti-angiogenesis therapy, immune checkpoint inhibitors, or chemo-radiotherapies is rather less promising. In this research, we investigated the role of the tumor stem cell marker DCLK1 in EGFR-TKI resistance of lung adenocarcinoma. We discovered that DCLK1 was critical in maintaining the stemness of tumor cells through the Wnt/β-Catenin pathway, which was conducive to the development of EGFR-TKI resistance. Inhibiting DCLK1 activity restored the sensitivity of TKI-resistant tumor cells and organoids. Moreover, our study showed that DCLK1 inhibitor had a synergistic effect in controlling tumor growth when combined with EGFR-TKIs. Overall, our study provides new insights into EGFR-TKI resistant lung adenocarcinoma through inhibition of DCLK1 expression. [ABSTRACT FROM AUTHOR]

A new type of high nitrogen hot-work die steel 3Cr5Mo2SiVN based on the idea of substituting C with N, proper Mo addition, and proper Si and V subtraction was designed, exhibiting higher microstructure and hardness stability than the frequently-used H13 steel. The results showed that the softening mechanism consisted of the coarsening and decomposition of laths, the formation and coarsening of precipitates, the annihilation and rearrangement of dislocations and the formation of sub-grains. The superior thermal stability of 3Cr5Mo2SiVN steel could be attributed to the low precipitate and dislocation recovery. First, the higher activation energy inhibited the diffusion of alloying elements, thus delaying the formation and coarsening of precipitates. Second, the undissolved M(C, N) exhibited a higher solid solution temperature than the undissolved MC, and M 3 C had a stronger heat absorption ability. In addition, the nano‑carbonitride M(C, N) exhibited lower lattice disregistry and interface energy than the nano-carbide MC. Hence, the undissolved M(C, N), M 3 C and nano‑carbonitride M(C, N) showed a higher precipitate stability. Third, in terms of dislocation evolution, the higher stability of lattice constant and solid solution of interstitial atoms as well as the smaller carbide size and lower precipitation content significantly inhibited the dislocation recovery. The preservation of prior austenite grain boundaries and lath boundaries effectively hindered the dislocation migration. After isothermal tempering at 580, 600 and 620 °C for 96 h, the hardness decreased to 41.1, 35.4 and 31.7 HRC with softening rate 4.6, 8.5 and 10.0 for 3Cr5Mo2SiVN steel, and 35.2, 29.3 and 28.1 HRC with softening rate 7.2, 11.2 and 11.5 for H13 steel. The difference in hardness and softening rate at 600 °C was the most prominent, attaining respective values of 6.1 HRC and 2.7, respectively. • 3Cr5Mo2SiVN steel achieves excellent microstructure and hardness stability. • The lath, precipitate, dislocation and sub-grain recovery affect stability. • M 3 C, undissolved and nano-scale M(C, N) exhibit high thermal stability. • High C, N contents in matrix and small carbides inhibit dislocation recovery. • Preservation of austenite and lath boundaries hinder dislocation migration. [ABSTRACT FROM AUTHOR]

The evidence of anaplastic lymphoma kinase (ALK) inhibitor for non-small cell lung cancer (NSCLC) harbouring sperm antigen with calponin homology and coiled-coil domains 1-like (SPECC1L)-ALK fusion was limited. In a previous case report, a Chinese, 44-year-old, female non-smoker with stage IV NSCLC harbouring SPECC1L-ALK fusion was treated with crizotinib ± bevacizumab for 23 months (from October 2017 to September 2019) and second-generation ALK inhibitor iruplinalkib for 2.5 months (from October 2019 to January 2020). The present study is an updated case report of subsequent follow-up of this patient. The patient participated in the phase II INTELLECT study and received iruplinalkib 180 mg once daily with a 7-day lead-in phase at 60 mg once daily. Systemic partial response was achieved 1 month later. Intracranial complete response was achieved nearly 5 months after iruplinalkib treatment initiation. Systemic and intracranial responses continued as of cut-off date (February 2023). The progression-free survival reached 39.3 months, with right censoring (progression did not occur during follow-up). Grade 3 hypertriglyceridaemia complicated with grade 2 hypercholesterolaemia recovered after fenofibrate treatment. The other adverse events were not noteworthy. Iruplinalkib demonstrated promising systemic and intracranial efficacy for NSCLC harbouring SPECC1L-ALK gene, with acceptable and manageable adverse events (for example, grade 3 hypertriglyceridaemia or grade 2 hypercholesterolaemia). Iruplinalkib may be an ideal option for patients with rare ALK fusions. [ABSTRACT FROM AUTHOR]

Background: There was no standard treatment for patients who acquired resistance to osimertinib mediated by epidermal growth factor receptor (EGFR) T790M‐cis‐C797S. The aim of this study was to investigate the association between different therapeutic strategies and survival outcomes among these patients. Methods: This retrospective cohort study analyzed 46 patients with metastatic lung adenocarcinoma and EGFR T790M‐cis‐C797S after osimertinib progression from January 1, 2017 to October 31, 2020. Among them, 13 patients received brigatinib‐based therapy, 23 patients received chemotherapy in combination of anti‐angiogenics or not, and 10 patients received other targeted treatments like dacomtinib, bevacizumab, or a combined therapy of osimertinib and other targeted drugs. Results: Compared to other targeted therapy, brigatinib‐based therapy (median progression‐free survival [mPFS]: 4.40 vs. 1.63 months, hazard ratio [HR] = 0.39, 95% confidence interval [CI]: 0.21–0.73, p = 0.001) and chemotherapy‐based treatment (mPFS: 4.70 vs. 1.63 months, HR = 0.18, 95% CI: 0.06–0.50, p < 0.001) presented a better survival outcome and there was no significant difference between brigatinib‐based therapy and chemotherapy‐based treatment (mPFS: 4.40 vs. 4.70 months, HR = 1.24, 95% CI: 0.57–2.67, p = 0.58). Chemotherapy combined with anti‐angiogenics achieved a better efficacy than only chemotherapy (mPFS: 5.50 vs. 1.03 months, HR = 0.30, 95% CI: 0.11–0.83, p = 0.02). Patients carrying EGFR exon 19 deletion mutation had a longer PFS than those who harboring EGFR exon 21 p.L858R mutation (4.57 vs. 1.03 months, HR = 0.18, 95% CI: 0.06–0.54, p = 0.001), no matter they received brigatinib‐based therapy (mPFS: 5.00 vs. 3.23 months, HR = 0.19, 95% CI: 0.01–0.96, p = 0.05) or chemotherapy‐based treatment (mPFS: 7.23 vs. 1.03 months, HR = 0.05, 95% CI 0.01–0.49, p < 0.001). Conclusion: Brigatinib‐based therapy and chemotherapy plus anti‐angiogenics could be considered beyond progression from osimertinib therapy. For patients harboring EGFR exon 19 deletion/T790M/cis‐C797S mutation, the clinical efficacy was superior to patients harboring EGFR exon 21 p.L858R/T790M/cis‐C797S mutation. [ABSTRACT FROM AUTHOR]

AZD9291 (osimertinib) is the third-generation EGFR-TKI treat for EGFR mutated NSCLC patients. Despite its encouraging efficacy in clinical, acquired resistance is still inevitable. The mechanism of drug resistance needs to be further explored. In a previous study, we established an AZD9291-resistant cell strain named HCC827/AZDR. We found that insulin-like growth factor binding protein 7 (IGFBP7) expression was markedly increased in HCC827/AZDR cells and AZD9291-resistant patients by RNA sequencing and immunohistochemical analysis, respectively. Reduced IGFBP7 in HCC827/AZDR cells by si-RNA interference recovered the sensitivity to AZD9291 partially and increased AZD9291-induced cell apoptosis. Enhancing IGFBP7 expression in EGFR -mutated non-small cell lung cancer (NSCLC) cells using lentiviruses infection reduced their sensitivity to AZD9291. This study is the first to discover that high IGFBP7 expression could occur following treatment with AZD9291. This might be one of the mechanisms underlying AZD9291 resistance and a potential therapeutic target following AZD9291 resistance. • IGFBP7 expression was markedly increased in AZD9291-resistant cells and patients. • Reduced IGFBP7 in AZD9291-resistant cells partially recovered the sensitivity to AZD9291. • IGFBP7 helps AZD9291-resistant cells survive by promoting cell proliferation and inhibiting apoptosis. • IGFBP7 may become the next therapeutic target to solve the problem of osimertinib resistance. [ABSTRACT FROM AUTHOR]

Thermodynamic calculations, time–temperature–transformation diagram construction, microstructural characterization and precipitation kinetics analyses were conducted to investigate the effect of N content on the precipitation behavior of hyper duplex stainless steel S32707. The results demonstrate that the nose time of 3% σ phase precipitation gradually increases with increasing N content. Increasing the N content substantially reduces the quantity of the σ phase at δ/γ interfaces. Within the first 5 min of aging, the growth rate of the σ phase decreased in the order N0.35, N0.45 and N0.56. Between 5 min and 48 h, the growth rates were essentially the same. The mechanism by which N inhibits the σ phase is attributed to three aspects: (i) N reduces the quantity of favorable nucleation sites by increasing the fraction of δ/γ interfaces with low Kurdjumov–Sachs orientation relationship deviation angles; (ii) N diminishes the tendency of Cr and Mo to diffuse from the δ to γ phase by decreasing the natural partitioning coefficients; and (iii) N decreases the σ phase nucleation driving force and Cr activity. Raising the N content promotes Cr 2 N precipitation only after long-term aging. The role of N in promoting Cr 2 N is generalized in two aspects: first, N increases the diffusion rate of Cr and N in austenite based on its increased diffusion coefficient with increasing N content; second, N increases the Cr 2 N nucleation driving force and N activity. • Increasing N content significantly inhibits the precipitation of σ phase. • Raising N content promotes Cr 2 N precipitation only after long term aging. • N reduces Cr and Mo diffusion trend, Cr activity, nucleation site and driving force of σ phase. • N raises Cr and N diffusion rate, N activity and driving force of Cr 2 N. [ABSTRACT FROM AUTHOR]

Background: Cancer treatment decision-making often needs to balance benefits, harms, and costs. This study sought to identify the differences in cancer treatment preference among oncologists, patients and their family members in China. Methods: A semi-structured face-to-face qualitative interview was conducted among oncologists, patients and their family members recruited in four tertiary hospitals in China. The interview guide was developed based on literature review and expert consultation. Participants were asked to indicate their preferences when making lung cancer treatment decisions. All interviews were audio-taped, transcribed verbatim, and thematic analyzed. The preferences were compared among three groups of participants. Results: A total of 17 participants (5 oncologists, 6 dyads of patients and family members) were interviewed between June and July 2019. Five themes, namely, survival benefit, adverse effect/symptom, treatment process, treatment cost, and the impact on daily life were identified. The oncologists and family members gave highest priority on survival benefit, while the patients are concerned most about treatment cost and quality of life. Conclusion: This study reveals different preferences for cancer treatment among oncologists, patients and their family members in China. Education is needed to empower patients and family members and promote share decision-making in this country. [ABSTRACT FROM AUTHOR]

Background: ALK rearrangement is a very rare subset of squamous cell carcinoma (SCC) and one of the clinical features in patients is lack of data. Here, we report eight patients diagnosed with SCC of the lung harboring ALK rearrangement. Methods: We collected primary NSCLC samples at the Beijing Chest Hospital between January 2012 and December 2018 for Ventana (D5F3) immunohistochemical detection. Among the 148 patients was diagnosed ALK‐rearranged non small cell lung cancer (NSCLC), only eight cases was SCC. We collected patients information from electronic patent records (EPRs). Results: The eight cases of SCC were diagnosed by immunohistochemistry (IHC). Two were given crizotinib as second‐line therapy. One patient had stable disease (SD) and progression‐free survival (PFS) of six months. The other patient had progressive disease (PD) but PFS was only one month. The side effects were tolerable. This report identified 31 cases of ALK rearrangement in SCC patients from a literature search (including the eight patients in this study). These fusion genes are often seen in a younger age group (mean age: 55.6 years) and non‐smokers (18/31, 58.1%). A total of 20 cases received an ALK inhibitor as first‐ or second‐line treatment which included 11 with a partial response (PR), four with SD, and five with PD. The DCR and ORR was 75.0% (15/20) and 55.0% (11/20), respectively. The median duration time of therapy was 6.4 ± 4.4 months. Conclusions: Patients with ALK‐rearranged SCC obtained clinical benefit from ALK‐inhibitor therapy, especially those who were non‐smokers and whose tumors had been identified by IHC+/FISH+. [ABSTRACT FROM AUTHOR]

The precipitation of Cr- and Mo-rich σ phases will seriously deteriorate the corrosion resistance and mechanical property of super austenitic stainless steel S31254. The precipitation of σ phase in S31254 containing B and Ce can be effectively inhibited by heat treatment to regulate trace elements. In this study, slow cooling combined low-temperature diffusion treatment (SCLDT) was adopted in S31254 containing B and Ce. Furthermore, the role of Ce was explored by comparing the precipitation behavior of samples with different Ce content. The results show that this new heat treatment strategy can better exert the inhibition effect of B and Ce on the precipitation of σ phase, and the inhibition effect is more obvious when the content of Ce is higher. It was found that the distribution of elements in the adjacent area of Ce at the GBs was almost the same as that in the matrix, which indicated that Ce could inhibit the formation of the precipitates along the GBs, and thus resulting in the precipitates distributed discontinuously. Besides, the B element was soluble in Mo-rich precipitates, and the B-containing precipitates was distributed in serrated pattern at GBs. In the 50Ce samples, serrated precipitates are more likely to form at the GBs, and the amount of precipitates was significantly reduced and discontinuities increased. Due to the homogeneous distribution of Cr in the serrated precipitates and their adjacent matrix zones, the phase interface has better resistance to intergranular corrosion. [Display omitted] • The slow cooling, low-temperature diffusion treatment and aging treatment were used to promote the segregation of B and Ce elements at grain boundaries in S31254. • The segregation of Ce at grain boundaries can obviously delay the formation of precipitates. • The Cr content in the adjacent region of the serrated B-containing and Mo-rich precipitate is similar to that in the matrix. • The increase of Ce content can further improve the corrosion resistance of the material. [ABSTRACT FROM AUTHOR]

Background: ROS1 gene fusion represents a specific subtype of non‐small cell lung cancer (NSCLC). Crizotinib is recommended for ROS1‐positive NSCLC due to its favorable outcome in published clinical trials. However, due to the low incidence of ROS1‐positive NSCLC, there is limited information on real‐world clinical outcomes in patients treated with either crizotinib or platinum‐based doublet chemotherapy. Methods: Outcomes were recorded in 102 patients with stage Ⅲb or Ⅳ NSCLC who were treated at four Chinese hospitals between April, 2010 and June, 2019. Results: Of the 102 patients followed, 71.6% were females, 81.4% were non‐smokers, and 98.0% had adenocarcinoma. First‐line treatment with crizotinib achieved a significantly longer median progression‐free survival (PFS) compared with platinum‐based chemotherapy (14.9 months vs 8.5 months, respectively; P <.001). Next‐generation sequencing (NGS) identified 61 patients who had ROS1 fusion variants, including CD74 (n = 33) and non‐CD74 (n = 28) variants. In patients harboring CD74 fusion variants, the median PFS with first‐line crizotinib treatment was significantly longer than in those harboring non‐CD74 fusion variants (20.1 months vs 12.0 months, respectively; P =.046). However, in patients treated with platinum‐based chemotherapy, there was no significant difference in PFS between the CD74 and non‐CD74 variant groups (8.6 months vs 4.3 months, respectively; P =.115). Overall survival (OS) was not reached. Conclusions: First‐line therapy with crizotinib is more beneficial than platinum‐based chemotherapy in patients with advanced NSCLC with different ROS1 fusion variants. Patients harboring CD74 fusion variants appear to respond better to crizotinib. [ABSTRACT FROM AUTHOR]

To evaluate the correlation between the changes in serum concentrations of cluster of differentiation-147 (scCD147) and chemotherapy outcome in patients with NSCLC and evaluate the combination of scCD147 with serum matrix metalloproteinase-9 (scMMP-9) levels in the prediction of chemotherapy response, eighty-two patients with advanced LC were enrolled. Newly diagnosed cases were treated with platinum-based chemotherapy. We measured scCD147 protein levels in LC cases by ELISA and used receiver operating characteristic (ROC) curves to analyze the results. Four time points were chosen to examine the association between the changes in scCD147 and chemotherapy outcome: before chemotherapy and 21 days after the start of the first, second, and fourth chemotherapy cycles. We assessed the combination of scCD147 and scMMP-9 serum levels in predicting the chemotherapy response. scCD147 was higher in LC cases than that in healthy volunteers (HVs). scCD147 was associated with distant metastases and TNM stage. scCD147 and scMMP-9 appeared to be independent predictive factors for chemotherapy outcomes after the first and second chemotherapy cycles for patients with NSCLC. Multivariable analysis also demonstrated that variations in scCD147 and scMMP-9 could be independent factors for monitoring chemotherapy outcome for patients with NSCLC. Furthermore, when scCD147 and scMMP-9 are combined into a new risk model, it has a markedly better prediction of chemotherapy outcomes than each protein alone. scCD147 and MMP-9 are potential predictive biomarkers for efficacy, and their combination significantly improves the predictive power for chemotherapy response in patients with NSCLC. [ABSTRACT FROM AUTHOR]

To evaluate the correlation between the changes in serum concentrations of cluster of differentiation-147 (scCD147) and chemotherapy outcome in patients with NSCLC and evaluate the combination of scCD147 with serum matrix metalloproteinase-9 (scMMP-9) levels in the prediction of chemotherapy response, eighty-two patients with advanced LC were enrolled. Newly diagnosed cases were treated with platinum-based chemotherapy. We measured scCD147 protein levels in LC cases by ELISA and used receiver operating characteristic (ROC) curves to analyze the results. Four time points were chosen to examine the association between the changes in scCD147 and chemotherapy outcome: before chemotherapy and 21 days after the start of the first, second, and fourth chemotherapy cycles. We assessed the combination of scCD147 and scMMP-9 serum levels in predicting the chemotherapy response. scCD147 was higher in LC cases than that in healthy volunteers (HVs). scCD147 was associated with distant metastases and TNM stage. scCD147 and scMMP-9 appeared to be independent predictive factors for chemotherapy outcomes after the first and second chemotherapy cycles for patients with NSCLC. Multivariable analysis also demonstrated that variations in scCD147 and scMMP-9 could be independent factors for monitoring chemotherapy outcome for patients with NSCLC. Furthermore, when scCD147 and scMMP-9 are combined into a new risk model, it has a markedly better prediction of chemotherapy outcomes than each protein alone. scCD147 and MMP-9 are potential predictive biomarkers for efficacy, and their combination significantly improves the predictive power for chemotherapy response in patients with NSCLC. [ABSTRACT FROM AUTHOR]

Background: The expression of PD‐L1 and its regulation in tumors remains unclear. The importance of IFN‐γ in upregulating the PD‐L1 expression in various tumors, and the effects of other essential cytokines in the tumor microenvironment (TME), need to be further elucidated. Methods: Constitutive expression of PD‐L1 and CD137L in all 13 lung cancer cell lines were tested by flow cytometry. CD137L mRNA of lung cancer cell lines was detected by RT‐PCR. PD‐L1 expression rates following stimulation with these cytokines (IFN‐γ, TNFα and IL2) were measured. After coculture of cells expressing CD137L (lung cancer cells or 293FT cells transfected with CD137L plasmid) with T cells, the PDL1 expression of lung cancer cells and IFN‐γ in supernatant was detected. Results: Our data revealed that adenocarcinoma and squamous cell carcinoma cells had the highest positive expression rate. IFN‐γ was the core‐inducing factor for enhancing the PD‐L1 expression. CD137L was also widely expressed in the lung cancer cell lines at the mRNA level, whereas its expression was generally low at the protein level. However, the low expression of CD137L protein was still enough to induce T cells to produce IFN‐γ, which subsequently increased the PD‐L1 expression by lung cancer cells. The CD137 signal induces IFN‐γ secretion by T cells, which stimulates high‐level of PD‐L1 expression in cancer cells; this negative immune regulation may represent a mechanism of immune escape regulation. Conclusions: CD137L mRNA was widely expressed in lung cancer cell lines whereas levels of protein expression were generally low. The low level of CD137L protein was still enough to induce T cells to produce IFN‐γ that subsequently increased PD‐L1 expression. The CD137L‐induced negative immune regulation may represent a mechanism of immune escape. [ABSTRACT FROM AUTHOR]

A novel high nitrogen hot-work die steel 3Cr5Mo2SiVN was manufactured by pressurized induction melting, possessing excellent hardness-strength-toughness balance under conventional heat treatment process. The results indicated that 3Cr5Mo2SiVN steel exhibited better hardness-toughness synergy compared with H13 steel. Meanwhile, its impact energy and elongation were improved by ca. 50% and 13% compared with H13 steel with similar hardness. The achievement of superior toughness of 3Cr5Mo2SiVN steel could be attributed to the following reasons: firstly, the higher fraction of operators 1 and 2, more uniform and refined close-packets and Bain groups as well as smaller effective grain size obtained a higher ratio of high angle grain boundaries, which resulted in the more changes of crack propagation direction and thus an increase of energy absorption. Secondly, the smaller size and number density of undissolved M(C, N) carbonitrides distributed along the prior austenite grain boundaries required greater tensile stress and then reduced grain boundary brittleness. For the strengthening mechanism, the precipitation strengthening increment was mainly provided by M(C, N) carbonitrides and M 3 C carbides for 3Cr5Mo2SiVN steel, and MC carbides for H13 steel, respectively. The smaller effective grain size and higher interstitial atom (C and N) content in the martensitic laths of 3Cr5Mo2SiVN steel were crucial factors in enhancing its strength. • 3Cr5Mo2SiVN steel achieves excellent hardness-strength-toughness balance. • A higher ratio of high angle grain boundary effectively hinders crack deflection. • Smaller size and number density of M(C, N) reduce grain boundary brittleness. • Smaller effective grain and higher interstitial atoms content enhance the strength. [ABSTRACT FROM AUTHOR]

Background: Tyrosine kinase inhibitors (TKIs) can significantly prolong overall survival for patients with advanced non‐small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR)‐mutation or anaplastic lymphoma kinase (ALK)‐rearrangement. However, the real‐world evaluation status of ALK/EGFR in China remains unclear. Methods: We conducted a prospective study including 1134 patients with cytologically or histologically confirmed advanced NSCLC (stage IIIb–IV) at 12 Chinese hospitals. Results: The most common evaluation methods were amplification‐refractory mutation system for EGFR status and immunohistochemistry targeting D5F3 for ALK status. Among patients with non‐squamous, the EGFR mutation rate was 44.1% and the ALK rearrangement rate was 10.0%. Among patients with squamous cell carcinoma, the EGFR mutation rate was 8.3% and the ALK rearrangement rate was 3.7%. Among all patients, gender (HR = 1.7, 95%CI = 1.2–2.4, P = 0.006), smoking history (HR = 1.8, 95%CI = 1.3–2.7, P = 0.001), histology (HR = 5.0, 95%CI = 2.4–10.1, P < 0.001), and brain metastases (HR = 1.5, 95%CI = 1.1–2.2, P = 0.017) were independent predictors of EGFR mutation, while age (HR = 2.6, 95%CI = 1.7–4.1, P < 0.001) was an independent predictor of ALK rearrangement. The median time from tumor diagnosis to EGFR or ALK status confirmation was 7 and 5 days, respectively. Targeted therapy rate was 73.8% in EGFR‐positive patients and 51.4% in ALK‐positive patients. There was a negative correlation between the first‐line targeted therapy rate and the EGFR mutation detection period (r = −0.152, P = 0.02), while no significant correlation among patients with ALK rearrangement (r = −0.179, P = 0.076). Conclusion: Squamous NSCLC patients should also be routinely tested to determine their EGFR/ALK statuses. The first‐line targeted therapy rate remains low in Chinese patients with NSCLC. [ABSTRACT FROM AUTHOR]

Abstract Objective Recently, a low frequency of de novo T790M mutations existing in tumor tissues before TKIs therapy has been reported. However, the origin of T790M and its impact on clinical outcomes is still being debated. This study aimed to use highly sensitive methods to detect T790M before and after TKIs therapy and investigated the correlation of T790M with clinical prognosis. Patients and methods Matched tumor samples before and after treatment were collected from 61 lung adenocarcinoma (LAC) patients in Beijing Chest Hospital between June 2014 to October 2017. Presence of the T790M mutation was simultaneously detected using amplification refractory mutation system-PCR (ARMS-PCR) assay and droplet digital PCR (ddPCR) assay. Results Of the 61 enrolled patients, 46 were candidates for and received TKIs treatment based on their EGFR mutation status. When these samples were assayed, ddPCR identified significantly more T790M mutations than ARMS-PCR (before TKIs treatment: 19.6% (9/46) vs. 2.2% (1/46), P = 0.040; after TKIs treatment: 78.3% (36/46) vs. 50% (23/46), P < 0.001, respectively). Patients with first-line TKIs treatment harboring de novo T790M mutations showed a shorter PFS compared to those without de novo T790M mutations (median, 7.0 months vs. 11.7 months, p = 0.013). In multivariate analyses, de novo T790M mutation was an independent predictor of PFS in EGFR-mutant patients who received TKIs treatment (p = 0.031, HR 0.310, 95% CI: 0.107-0.900). Conclusion The ddPCR assay is an ultra-sensitive method to detect a minor amount of de novo T790M mutations in tumor samples. The de novo T790M mutation is a relatively unfavorable prognosis factor for patients receiving first-line TKIs treatment. [ABSTRACT FROM AUTHOR]

The aim of the present study was to develop a procedure for the isolation of circulating tumor cells (CTCs), and to evaluate its application in the detection of epidermal growth factor receptor (EGFR) mutations, and potential heterogeneity in patients with non-small-cell lung cancer (NSCLC). Peripheral blood samples were collected from 91 patients with lung cancer, 10 patients with benign disease and 10 healthy volunteers. CTCs were enriched by positive immunomagnetic separation, detected by immunocytochemistry, and processed for single-cell capture. Pure CTC DNA was amplified, and the EGFR gene was analyzed using the amplification refractory mutation system (ARMS) and digital polymerase chain reaction (dPCR). The CTC capture rate in patients with lung cancer was 61.5% (56/91), whereas no CTCs were detected in patients with benign lung disease or in healthy volunteers. The CTC-positive detection rates were 69.3% (52/75) and 25.0% (4/16) in patients with TNM stage III and IV disease, respectively. Markedly more CTCs were captured from patients with small-cell lung cancer compared with patients with other types of cancer. In patients who were positive for EGFR mutations, the detection rate of these mutations was low (16.67%, 2/12), at the single CTC level. The sensitivity increased as the number of CTCs per sample increased. A total of four patients displayed consistent detection of EGFR mutations at the 10-cell level, and one patient exhibited a clear, inconsistent and rare mutation (G719×) between CTCs. A simplified technique for isolating CTCs from blood was established, though multiple CTCs were required to sensitively detect mutations in these cells. The detection of EGFR mutations in CTCs and tissue specimens was generally homogeneous, and therefore, the CTC-level mutation analysis may potentially contribute to the discovery of heterogeneous mutations. [ABSTRACT FROM AUTHOR]

The CAPTRA‐Lung study (NCT03334864) is a prospective observational study that will capture real‐world data of patients with advanced or metastatic non‐small cell lung cancer (NSCLC) across China. The study aims to complement the results from current therapeutic regimens to improve the standard of diagnosis and treatment, evaluate the effectiveness and safety of systemic therapy, and determine the factors influencing the outcomes and responses to treatment. From January 2018 to December 2023, eligible patients with advanced or metastatic NSCLC who are receiving treatment and participating in follow‐up at 16 institutions in China, will be enrolled. The demographic, clinical, laboratory, and treatment characteristics and responses to treatment will be recorded in a case report form and transcribed into an electronic data capture system. Overall survival, progression‐free survival, overall response rate, and incidence of adverse events will be calculated from the time of initial enrolment until progression evaluated by physicians, last contact, date of death, or analysis cutoff date, respectively. Based on the disease characteristics and treatment strategies, four sub‐cohorts will also be established. This study cohort could serve as a pool of patients with advanced or metastatic NSCLC to support further research. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Pressurized metallurgy remarkably enhanced N content in martensitic stainless steel. • Increasing N content firstly decreased then increased the content of precipitates. • With increasing N content, main precipitates were converted from M 23 C 6 to M 2 N. • High nitrogen martensitic stainless steels exhibited excellent corrosion resistance. • Excess nitrogen deteriorated corrosion resistance of martensitic stainless steel. Abstract Effect of nitrogen on microstructure and corrosion behaviour of high nitrogen martensitic stainless steels manufactured by pressurized metallurgy was investigated by microscopy, electrochemical and spectroscopy analyses. Results indicated that increasing nitrogen content significantly enhanced the corrosion properties of martensitic stainless steels, while excess nitrogen deteriorated the corrosion resistance. The impacts of increased nitrogen content could be summarized as three aspects: the change of precipitation content and conversion of main precipitates from M 23 C 6 to M 2 N; the enhanced protection performance of passive film by enrichment of Cr, especially Cr 2 O 3 and CrN; the improved repassivation ability by increased nitrogen content in solid solution. [ABSTRACT FROM AUTHOR]

Background: Before tyrosine kinase inhibitor (TKI) therapy can be administered in patients with advanced non‐small cell lung cancer (NSCLC), EGFR mutation testing is required. However, few studies have evaluated the extent of EGFR testing in real‐world practice in China. Methods: A multicenter, observational study of EGFR testing in NSCLC patients in North China was conducted. Treatment‐naïve patients or those with postoperative recurrent stage IIIB/IV NSCLC were enrolled. The primary objective was EGFR testing rate. Secondary objectives included EGFR mutation status, EGFR testing methods and specimens, factors associated with EGFR testing, and overall survival with or without EGFR testing. Results: Overall, 2809 patients with stage IIIB/IV NSCLC were enrolled; 90.78% had adenocarcinoma. The EGFR screening rate was 42.54%. EGFR testing rates were higher in tumor samples obtained by lymph node puncture, and in patients with urban medical insurance, adenocarcinoma, non‐smokers, or those located in developed cities (all P < 0.001). The EGFR mutation rate was 46.44%. The most commonly used specimens for EGFR testing were biopsy tumor samples (67.53%). PCR‐based methods (72.05%), Sanger sequencing (5.36%), and Luminex liquid chip (5.10%) were the most frequently used testing platforms. Similar positive EGFR mutation rates were achieved with different platforms. TKI therapy was the first‐line treatment administered to most EGFR‐positive patients (56.22%), and chemotherapy in EGFR‐negative patients (84.88%). Overall survival was higher in EGFR‐tested than in untested patients (27.50 vs. 19.73 months; P = 0.007). Conclusion: Real‐world EGFR testing rates for NSCLC in North China were relatively low because of clinical and social factors, including medical insurance coverage. [ABSTRACT FROM AUTHOR]

Purpose: AZD9291 is an irreversible, small-molecule inhibitor which has potency against mutant EGFR- and T790M-resistant mutation. Despite the encouraging efficacy in clinical, the acquired resistance will finally occur. Further study will need to be done to identify the acquired resistance mechanisms and determine the next treatment.Methods: We established an AZD9291-resistant cell line (HCC827/AZDR) from parental HCC827 cell line through stepwise pulsed selection of AZD9291. The expression of EGFR and its downstream pathways were determined by western blot analysis or immunofluorescence assay. The sensitivity to indicated agents were evaluated by MTS.Results: Compared with parental HCC827 cells, the HCC827/AZDR cells showed high resistance to AZD9291 and other EGFR-TKIs, and exhibited a mesenchymal-like phenotype. Almost complete loss of EGFR expression was observed in HCC827/AZDR cells. But the activation of downstream pathway, MAPK signaling, was found in HCC827/AZDR cells even in the presence of AZD9291. Inhibition of MAPK signaling had no effect on cell viability of HCC827/AZDR and could not reverse AZD9291 resistance because of the subsequent activation of AKT signaling. When treated with the combination of AKT and MAPK inhibitor, HCC827/AZDR showed remarkable growth inhibition.Conclusions: Loss of EGFR could be proposed as a potential acquired resistance mechanism of AZD9291 in EGFR-mutant NSCLC cells with an EMT phenotype. Despite the loss of EGFR, the activation of MAPK pathway which had crosstalk with AKT pathway could maintain the proliferation and survival of resistant cells. Blocking MAPK and AKT signaling may be a potential therapeutic strategy following AZD9291 resistance. [ABSTRACT FROM AUTHOR]

In this work, time temperature transformation (TTT) diagram, thermodynamic calculations and microstructure observations were performed to investigate the precipitation behavior of hyper duplex stainless steel UNS S32707 aged at nose temperature for various aging time up to 48 h. The corresponding secondary phase transformation mechanisms were proposed. The results demonstrate that the precipitation kinetics of σ phase in UNS S32707 is very fast due to its higher Cr and Mo contents at nose temperature of 950 °C. At the initial stage of aging, σ phase preferentially formed along the α/α and α/γ phase boundaries and then penetrated into α phase, resulting from the eutectoid reaction α → γ 2 + σ. Meanwhile, a few σ phases nucleated at the γ/γ phase boundaries. With the aging time prolonging, some σ phases nucleated within γ phase due to the decomposition of the supersaturated γ phase. In addition, a cellular structure consisting of lamellar σ and γ 2 phase was detected during short term aging, and it gradually grew with aging time via cell boundary migration. After 30 min and 6 h aging, the lamellar σ phases in the cellular structure broke into small lamellas or into bending bars and evolved into blocky shapes. Most of rounded Cr 2 N particles formed at the σ/γ 2 interfaces and were surrounded by σ and γ 2 phase. A few rod-like Cr 2 N particles nucleate at γ/γ phase boundaries due to the low energy interfaces between Cr 2 N and γ phase. No Cr 2 N was detected in α phase, which was attributed to the fact that σ phase has much faster precipitation kinetics than that of Cr 2 N. [ABSTRACT FROM AUTHOR]

High temperature oxidation behavior and mechanisms for super-austenitic stainless steel S32654 were investigated at 900, 1000 and 1200 °C in air. The oxide layers were characterized by scanning electron microscopy with energy-dispersive spectroscopy (SEM-EDS), electron-probe microanalysis (EPMA), x-ray diffraction (XRD) and transmission electron spectroscopy (TEM). At 900 °C, oxidation follows parabolic law within the initial 10 h, and the external solid MnMoO 4 molybdate oxide layer and the internal spinel oxide layer prevent oxygen or metal cations diffusion. The parabolic law then changes to a linear law due to the molten MnMoO 4 -MoO 3 molybdate electrochemical reaction and oxide layer cracking. At 1000 and 1200 °C, oxidation follows linear law. The nitrogen in air plays a very important role in accelerating oxidation. The synergistic effects of the molten MnMoO 4 -MoO 3 molybdate electrochemical reaction and discontinuous Cr 2 N precipitation strongly promote catastrophic oxidation. [ABSTRACT FROM AUTHOR]

Background: The correlation between epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and EGFR sensitive mutation subtypes in advanced or metastatic non-small cell lung cancer (NSCLC) remains uncertain. We performed this meta-analysis to determine different clinical outcomes between patients with exon 19 deletion accepting EGFR-TKI therapy compared with those with exon 21 L858Rmutation. Methods: PubMed and Web of Science were analyzed for eligible trials. Raw data were extracted to give pooled estimates of the effect of EGFR-TKI therapy on objective response rate (ORR), one-year progression-free survival (PFS), and two-year overall survival (OS). Results: We identified 13 eligible trials involving 912 patients. Prospective metaanalysis demonstrated that theORRof the 19 deletion group was significantly higher than the 21 L858R mutation group (odds ratio [OR] 1.98, 95% confidence interval [CI] 1.18-3.33; P = 0.01), but no statistical significance between the one-year PFS rate of the 19 deletion and 21 L858R groups (OR 1.44, 95% CI 0.96-2.18; P = 0.08) was found. However, retrospective meta-analysis demonstrated that a significantly higher one-year PFS rate was associatedwith the 19 deletion group (OR 1.73,95% CI 1.17-2.56; P = 0.006).The two-year survival rate of the 19 deletion group was significantly higher than the 21 L858R group (OR 5.27, 95%CI 1.76-15.71; P = 0.003). Conclusions: In advanced NSCLC patients, an exon 19 deleton may provide superior ORR, PFS, and OS after EGFR-TKI treatment compared with an exon 21 L858R mutation. [ABSTRACT FROM AUTHOR]

Background To explore the efficacy and safety of crizotinib versus platinum-based double agent chemotherapy as the first-line treatment in patients with advanced anaplastic lymphoma kinase (ALK)-positive lung adenocarcinoma. Method We retrospectively analyzed data from 19 patients with advanced ALK-positive lung adenocarcinoma who had received no previous systemic treatment for advanced disease. Seven patients received oral crizotinib at a dose of 250 mg twice daily; 12 patients were administered standard chemotherapy (pemetrexed, paclitaxel, vinorelbine or gemcitabine plus either cisplatin or carboplatin) every three weeks for up to six cycles. The primary endpoint was overall response rate ( ORR), disease control rate ( DCR), and safety. Results The ORR was significantly higher with crizotinib than with chemotherapy (83.3% in the crizotinib vs. 25.0% in the chemotherapy group, P < 0.05); the DCRs were 100% and 75%, respectively ( P < 0.05). The common adverse events associated with crizotinib were visual abnormality and diarrhea, whereas those associated with chemotherapy were neutropenia and nausea. In the crizotinib group, liver aminotransferase elevation (adverse events grade 3 or 4) occurred in one patient (14.3%). In the chemotherapy group, the same grade neutropenia adverse event occurred in two patients (16.6%). The incidence of treatment-related grade 3 or 4 adverse events was similar in both groups. Compared with chemotherapy, crizotinib was associated with a greater reduction in lung cancer symptoms and a greater improvement in quality of life. Conclusion As a first-line treatment, crizotinib was superior to platinum-based double chemotherapy in patients with previously untreated advanced ALK-positive lung adenocarcinoma. Therefore, crizotinib is an optimal therapy as a first-line treatment in these patients. [ABSTRACT FROM AUTHOR]

Background: Icotinib is a small molecule targeting epidermal growth factor receptor tyrosine kinase, which shows non-inferior efficacy and better safety comparing to gefitinib in previous phase III trial. The present study was designed to further evaluate the efficacy and safety of icotinib in patients with advanced non-small-cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy. Methods: Patients with NSCLC progressing after one or two lines of chemotherapy were enrolled to receive oral icotinib (125mg tablet, three times per day). The primary endpoint was progression-free survival. The secondary endpoints included overall survival, objective response rate, time to progression, quality of life and safety. Results: From March 16, 2010 to October 9, 2011, 128 patients from 15 centers nationwide were enrolled, in which 124 patients were available for efficacy evaluation and 127 patients were evaluable for safety. The median progression-free survival and time to progression were 5.0 months (95%CI 2.9–6.6 m) and 5.4 months (95%CI 3.1–7.9 m), respectively. The objective response rate and disease control rate were 25.8% and 67.7% respectively. Median overall survival exceeded 17.6 months (95%CI 14.2 m-NA) according to censored data. Further follow-up of overall survival is ongoing. The most frequent treatment-related adverse events were rash (26%, 33/127), diarrhea (12.6%, 16/127) and elevation of transaminase (15.7%, 20/127). Conclusions: In general, this study showed similar efficacy and numerically better safety when compared with that in ICOGEN trial, further confirming the efficacy and safety of icotinib in treating patients with advanced NSCLC previously treated with chemotherapy. Trial Registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Background Epidermal growth factor receptor-tyrosine kinase inhibitors ( EGFR-TKIs) effectively treat advanced non-small cell lung cancer with EGFR-mutation. However, most patients develop acquired resistance without effective therapy subsequent to EGFR-TKI failure. We evaluated the efficacy of subsequent treatment strategies for EGFR-TKI resistance. Methods We retrospectively analyzed 240 patients with advanced lung adenocarcinoma with EGFR-TKI failure and following subsequent treatment. According to the first subsequent strategies after EGFR- TKI failure, patients were divided into groups of EGFR-TKI continuation (21 cases), EGFR-TKI continuation with chemotherapy (23 cases), chemotherapy alone (143 cases), and best supportive care ( BSC) (53 cases). Results Except for 53 cases of BSC, the disease control rates ( DCR) of the remaining 187 patients in the EGFR-TKI continuation, EGFR-TKI continuation with chemotherapy, and chemotherapy alone groups were 66.7%, 73.9%, and 44.8%, respectively. The median post-progression progression-free survival ( PFS) for the three groups was 3.0, 3.3, and 2.0 months, respectively. The DCR for the EGFR-TKI continuation with chemotherapy group was significantly higher than the chemotherapy alone group ( P = 0.006). The post-progression PFS of the EGFR-TKI continuation with chemotherapy group was significantly longer than the chemotherapy alone group ( P = 0.037). The median overall survival in the EGFR-TKI continuation, EGFR-TKI continuation with chemotherapy, chemotherapy alone, and BSC groups were 6.9, 11.6, 8.8, and 0.9 months, respectively. Compared to the BSC group, all groups achieved a survival benefit ( P < 0.001). Conclusions EGFR-TKI continuation with chemotherapy could provide benefits for patients with acquired resistance to EGFR-TKI. [ABSTRACT FROM AUTHOR]