Search

Background Antibody-drug conjugates (ADCs) have been the preferred regimens for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) after trastuzumab. Unfortunately, there is little data showing which ADCs should be chosen for those patients whose treatment with tyrosine kinase inhibitors (TKIs) failed. This study aims to analyze the efficacy and safety between novel anti-HER2 ADCs and trastuzumab emtansine (T-DM1) for those with TKIs failure. Materials and methods HER2-positive MBC using ADCs from January 2013 to June 2022 were included, and all of them were treated with TKIs. The primary study endpoint was progression-free survival (PFS), and the secondary study endpoints were objective response rate (ORR), clinical benefit rate (CBR), and safety. Results A total of 144 patients with 73 patients in the novel anti-HER2 ADCs group and 71 patients in the T-DM1 group. In these novel ADCs, 30 patients received trastuzumab deruxtecan (T-Dxd), 43 patients receive other novel ADCs. The median PFS in the novel ADCs group and T-DM1 group were 7.0 months versus 4.0 months, respectively, and ORR was 54.8% versus 22.5%, CBR was 65.8% versus 47.9%, respectively. In subgroups analysis, the PFS were both significantly improved in patients receiving T-Dxd and other novel ADCs compared with T-DM1. The most common grades 3-4 adverse events in the novel anti-HER-2 ADCs group were neutropenia (20.5%) and thrombocytopenia (28.1%) in the T-DM1 group. Conclusions In patients with HER2-positive MBC previously treated with TKIs, both T-Dxd and other novel anti-HER2 ADCs yielded statistically significant better PFS than T-DM1 did, with tolerable toxicities.

Purpose: we used the real-world data of Chinese patients to describe clinicopathological characteristics of patients with breast cancer brain metastases (BCBM) and to investigate survival after diagnosis of brain metastases (BM). Methods: The clinicopathological characteristics of 700 patients with BCBM at the fifth Medical Center of Chinese PLA General Hospital between 2003 and 2021 were retrospectively reviewed. Information was collected from the electronic medical records, including patient demographics, tumor characteristics, and dates of diagnosis of original breast carcinoma and subsequent metastases. Sites and number of metastatic lesions were also recorded, along with data on treatments and outcomes. The prognostic and predictive effects of these clinicopathological variables in BCBM were analyzed. Results: The median age at diagnosis of primary breast cancer was 44 years (range, 22-80 years) and all patients were female. Among the 700 patients with BCBM, 30.0%, 49.7%, 18.9%, 1.4% had Luminal, HER2 positive, triple-negative and unknown subtypes, respectively. Based on available clinical information, the proportions of extracranial metastasis at diagnosis included bone (63.7%), lymph nodes (61.6%), lung (55.1%), liver (50.1%), the soft tissues of the thoracic wall (26.1%) and bone marrow (4.9%).The median time from the diagnosis of breast cancer to the development of BM was 52.0 months [95% confidence interval (CI), 44.3-59.7], 36.0 months (95%CI, 31.9-40.1), and 29.0 months (95%CI, 22.4-35.6) for patients with Luminal, HER2 positive and triple-negative, respectively (p Table 1.patient characteristics (n=700)Parametern (%)Mean age, y, at diagnosis (range)44(22-80)Stage at initial diagnosis of cancerI89(12.7)II342(48.9)III167(23.9)IV69(9.9)unknown33(4.7)Molecular subtypesLuminal A/B211(30.0)HER2-positive347(49.7)TNBC132(18.9)Unknown10(1.4)Site of first metastasisBrain128(18.3)Others572(81.7)Number of BM at time of BM diagnosis1189(27.0)248(6.9)≥3454(64.9)Unknown9(1.3)Visceral metastases at diagnosis of BMliver351(50.1)lung386(55.1)bone446(63.7)lymph nodes431(61.6)the soft tissues of the thoracic wall183(26.1)bone marrow34(4.9) Citation Format: Tao Wang, Huiqiang Zhang, Feng Li, Xia Wu, Jinmei Zhou, Shao hua Zhang, Li Bian, Ze fei Jiang. The real word study on clinical features and prognostic factors of Chinese breast cancer patients with brain metastasis [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-21-04.

To investigate the relationship between serum lipid level and cognitive function in middle-aged and elderly patients with type 2 diabetes mellitus(T2 DM).A cross-sectional study was implemented in 2017 to explore the correlation between lipid level and cognitive function in middle-aged and elderly diabetic patients. A random sample of 1526 middle-aged and elderly people were recruited from 2 communities in Beijing. Fasting blood samples were collected for blood lipid level detection, and the cognitive function of the subjects was assessed by the Montreal Cognitive Assessment Scale(MoCA). Logistic regression model was used to analyze the correlation between serum lipid levels and mild cognitive impairment(MCI) in elderly and T2 DM patients and control group.Compared with the control group, there were significant differences in blood lipid levels in T2 DM group. The levels of total cholesterol(TC) and high density lipoprotein cholesterol(HDL-C) in T2 DM group were lower than those in the control group, while triglyceride(TG) and low density lipoprotein cholesterol(LDL-C) were higher than those in the control group. Logistic regression analysis showed that high level of TC was a risk factor for MCI in patients with T2 DM, while high level of LDL-C was a protective factor, but no association was observed in the control population.Phenotype of T2 DM may affect the relationship between lipid level and cognitive function in middle-aged and elderly people.

With the continuous exploitation of coal resources, human safety has been seriously threatened during the mining process. Therefore, it is of great significance to establish an efficient human infrared image recognition system. In this paper, three classes of infrared image data of the human body are collected by a thermal imager, namely Human, Human others and None. According to the characteristics of downhole infrared images, a distributed channel feature extraction module (DCFE) is designed, and DCA-Net is proposed based on this module. The experimental results show that the recognition rate of the network reaches 98%. Compared with other networks, this network has better recognition performance. Among them, the recognition rate of DCA-Net50 reaches 98.214%, the amount of parameters and calculations are relatively small, and the cost-effectiveness is the highest. It is suitable for the human body infrared image recognition system that requires high accuracy and high real-time performance.

At present, local therapy, such as surgery and radiotherapy, is the mainstay treatment for brain metastasis and anti-human epidermal growth factor receptor type 2 (HER2)-targeted therapy has been shown to be efficacious for HER2This retrospective, observational study collected data from 79 HER2The intracranial ORRs were 48.6% in Group A and 20.5% (9/44) in Group B (P=0.015). The intracranial CBRs were 80.0% in Group A and 65.9% in Group B. The median intracranial PFS times (IC-PFS) were 15.0 months and 9.0 months in Group A and Group B, respectively (P=0.385). There was no statistically significant difference in OS between the 2 groups (95.0Pyrotinib combined with radiotherapy is recommended for HER2

The combustion of combustible gaseous mixture with/without oil droplet is studied based on a rapid compression machine under conditions comparable with the state at the end of compression in SI-eng...

Background: Neoadjuvant therapy is a standard treatment for patients with large, nonmetastatic breast cancer and may allow breast-conserving surgery after tumor downsizing while decreasing the risk of subsequent relapse. Dynamic changes of circulation tumor cells (CTCs) have a role in predicting treatment efficacy of breast cancer. However, the relationship between CTC enumeration before neoadjuvant therapy and pathologic complete response rate is still uncertain.Methods: The study was exploratory. A total of 50 breast cancer patients were enrolled in a phase II clinical study of neoadjuvant therapy for HER-2-positive early breast cancer. They were enrolled for blood draws before and after neoadjuvant therapy. We used two methods (CellSearch and Tumor-Fisher) to detect tumor cells in bloodstream. We compared the sensitivity of the two CTC detection systems and investigated the correlation of the enumeration on baseline CTCs with the diagnosis, the prognosis, and the efficacy of the neoadjuvant therapy of the patients with HER-2-positive early breast cancer. We also explored the dynamic change of CTCs after the neoadjuvant therapy in enrolled patients. Results: The sensitivity of CTCs detection by the Tumor-Fisher (27/50) method was significantly higher than that of the CellSearch system (15/50, p=0.008). The CTC levels detected by the two detection systems were not significantly correlated with lymph node status, clinical stage, ki-67 level and hormone receptor status. Patients with ≥1 CTC before neoadjuvant therapy measured by the Tumor-Fisher system had a significant high pCR rate (74.1% vs. 39.1%, p = 0.013); However, CTC levels detected by the CellSearch system did not show a predictive value for pCR (73.3% vs. 51.4%, P = 0.15). Patients with a decrease in CTCs enumeration after neoadjuvant therapy were more likely to achieve pCR than those with no change or increase in CTCs enumeration (87.5% vs 50.0%, P = 0.015) by the Tumor-Fisher method, whereas no predictive effect on pCR by CellSearch system. Unfortunately, there was no predictive value of CTC enumeration for EFS before and after neoadjuvant therapy by two methods. Conclusions: Our study demonstrates that the new CTC detection method Tumor-Fisher system has a higher CTC detection rate in early breast cancer than the CellSearch system, and shows the opportunity of CTC enumeration as a novel assistant biomarker to predict the response of neoadjuvant therapy in patients with HER-2-positive early breast cancer.

In the increasingly complex electromagnetic environment of modern battlefields, how to quickly and accurately identify radar signals is a hotspot in the field of electronic countermeasures. In this paper, USRP N210, USRP-LW N210, and other general software radio peripherals are used to simulate the transmitting and receiving process of radar signals, and a total of 8 radar signals, namely, Barker, Frank, chaotic, P1, P2, P3, P4, and OFDM, are produced. The signal obtains time-frequency images (TFIs) through the Choi–Williams distribution function (CWD). According to the characteristics of the radar signal TFI, a global feature balance extraction module (GFBE) is designed. Then, a new IIF-Net convolutional neural network with fewer network parameters and less computation cost has been proposed. The signal-to-noise ratio (SNR) range is −10 to 6 dB in the experiments. The experiments show that when the SNR is higher than −2 dB, the signal recognition rate of IIF-Net is as high as 99.74%, and the signal recognition accuracy is still 92.36% when the SNR is −10 dB. Compared with other methods, IIF-Net has higher recognition rate and better robustness under low SNR.

Acoustic characteristics of a thrust chamber with quarter-wave resonators are numerically studied based on the unsteady Reynolds-averaged Navier-Stokes (URANS) method. Organized pressure disturbance model and constant-volume bomb model are applied as artificial disturbances to excite pressure oscillations in the chamber. Eigenfrequencies and amplitudes of acoustic modes of the chamber are obtained by fast fourier transform (FFT) analysis, while damping characteristics are evaluated by the half-power bandwidth method. Predicted damping capacities of the chamber with and without quarter-wave resonators agree well with experimental results. Pressure oscillations can be controlled by a quarter-wave resonator mainly through reducing the amplitude of target acoustic mode, rather than increasing damping capacity of the chamber. Major damping mechanism of the resonator is cutting down pressure peak of target acoustic mode and raising up its pressure trough (CPRT); therefore the amplitude of target acoustic mode is reduced significantly. Moreover, acoustic energy can be dissipated by vortex at the orifice and by viscosity on the surface of a resonator, which increase damping capacity of the chamber slightly. Under the condition with multi-modes pressure oscillations, a resonator can still suppress pressure oscillations of target acoustic mode through CPRT. However, it may enhance pressure oscillations of other modes due to redistribution of oscillation energy among all acoustic modes.

The potential advantages of rotating detonation combustion are gradually approved, and it is becoming a stable and controllable energy conversion way adopted to the propulsion devices or ground-engines. This study focuses on the rotating detonation-based turboshaft engine, and the architecture is presented for this form of engine with compatibility between the turbomachinery and rotating detonation combustor being realized. The parametric performance simulation model for the rotating detonation-based turboshaft engine are developed. Further, the potential performance benefits as well as their generation mechanism are revealed, based on the comprehensive performance analysis of the rotating detonation-based turboshaft engine. Comparisons between the rotating detonation turboshaft engine and the conventional one reveal that the former holds significant improvements in specific power, thermal efficiency, and specific fuel consumption at lower compressor pressure ratios, and these improvements decrease with the increase of compressor pressure ratio and increase as turbine inlet temperature increases. The critical compressor pressure ratio corresponding to the disappearance of specific power improvement is higher than that corresponding to the disappearance of thermal efficiency and specific fuel consumption. These critical compressor pressure ratios are positively correlated with flight altitude and negatively correlated with flight velocity. The conductive research conclusion is guidable for the design and engineering application of rotating detonation-based engines.

An efficient and reliable flight Mach controller is specially needed for an aircraft. A Flight mach fuzzy controller based on modern fuzzy control theory is designed for an unmanned aerial vehicle (UAV) using a turbojet engine. The theory and process of designing control law are introduced and its control performance is optimized by changing the scale factors. In order to evaluate the control performance, a mathematical simulation system and a hardware-in-the-loop (HIL) simulation platform are built. The mathematical simulation and HIL simulation are carried out respectively, and the simulation results are compared. The evaluation shows good control performance to stabilize the UAV flight Mach number to the target one quickly by controlling the engine work condition.

In this paper, an extended state observer (ESO) is established for the linear model of aircraft with small disturbance, considering wind disturbance, structural disturbance, model uncertainty and measurement noise. The real-time estimation and compensation of the system state are carried out. The nonlinear feedback control law is designed to complete the design of aircraft attitude controller. The simulation results show that the attitude controller with extended state observer and nonlinear control law has better control quality than the traditional attitude control correction network method. In the case of large unknown measurement noise, the system has better filtering characteristics and robustness.

A configuration for a dual-duct rotating detonation aero-turbine engine (DRDATE) is proposed. With the isolator and mixer arranged upstream and downstream from the rotating detonation combustor (RDC) respectively, the compatibility between turbomachinery and RDC can be realized. The conventional single annular RDC is replaced with a multi-annular RDC to expand the stable operation range of the RDC. A low-order analytical model of the rotating detonation process is presented, and comparisons between the results calculated by this model and the CFD solvers show reasonable agreement. Thereafter, a performance simulation model of the DRDATE is established, and further the variations in the overall performances with design parameters under three different flight conditions are investigated. The results demonstrate that, there exists an optimum compressor pressure ratio π opt that maximizes the specific thrust and an optimum pressure ratio π opt ′ that maximizes the thermal efficiency for the DRDATE. With an increase in the compressor and turbine polytropic efficiency and turbine inlet temperature, both π opt and π opt ′ increase monotonically. Comparisons between the DRDATE and conventional turbine engine reveal that, the former exhibits a major improvement in overall performance at low compressor pressure ratios, while the improvement decreases continuously with an increase in the pressure ratio. Moreover, as the turbine inlet temperature increases, the specific thrust improvement increases and the fuel consumption performance improvement decreases monotonically.

In this research, n-hexane flashing jets discharged from two-hole GDI injectors were studied numerically with different superheat levels and inter-hole angles. The mutual interaction between under-expanded flashing jets was discussed in terms of its effect and mechanism. It was found that under certain conditions, the jets deflected towards each other and merged into one jet which moved along the central axis, indicating the occurrence of spray collapse. The spray collapse is ascribed to the pressure drop in the central area between the two jets, which is an effect of the low-pressure cores within individual jets. The pressure drop in the central area is mainly determined by two effects, i.e. the intensity and volume of the low-pressure cores in individual jets, and the formation of the secondary cell which protects the central area from being affected by the ambience. In the transitional stage from non-collapse to fully-collapse, the pressure drop was enhanced with the rise of superheat level or the decrease of inter-hole angle, and the extent of spray collapse increased. Besides, unique shock structures similar to those of under-expanded gaseous twin-jets were formed at high superheat levels, which consist of two primary cells and a secondary cell.

Photoelectrocatalysis (PEC) produces high-efficiency electron-hole separation by applying a bias voltage between semiconductor-based electrodes to achieve high photocatalytic reaction rates. However, using PEC to treat polluted gas in a gas-phase reaction is difficult because of the lack of a conductive medium. Herein, we report an efficient PEC system to oxidize NO gas by using parallel photoactive composites (TiO

Nitrous oxide fuel blend propellants have great potential to be used in rocket engine, and investigations on the fundamental combustion characteristics of such propellants are therefore necessary to control flashback and develop their chemical kinetics mechanism. Laminar burning velocities (LBVs) of C2H4/N2O flames are measured by using spherical expansion flames in this paper at 0.5–2.0 atm and 280 K. The present method for upper and lower limits of effective flame radius is reasonable for the experimental stretched flame speeds can be fitted very well with the flame stretch rates. The LBVs of C2H4/N2O flames are smaller than those of C2H4/N2/O2 flames (same N/O ratio as N2O) at conditions near stoichiometric ratio, while they are larger than those at other conditions especially at fuel-rich side. The LBVs of C2H4/N2O flames are not sensitive to the pressure in the measured range. Two kinds of sub-mechanisms are applied for detailed chemical kinetics mechanisms of C2H4/N2O reactions, which are USC Mech II-2 for hydrocarbon reactions as well as GRI 3.0 mechanism and San Diego mechanism for nitrogen oxide reactions respectively. Eight key elementary reactions are chosen based on the sensitivity analysis, and the effects of their available rate constants from literatures on the LBVs are tested. Modified mechanisms for C2H4/N2O reactions are therefore proposed by replacing the rate constants of these key elementary reactions, which predicts well for LBVs of hydrocarbon/N2O flames. Sensitivity analyses are performed for C2H4/N2O flames at different equivalence ratios, it is found that the N2O decomposition is a dominant reaction in conditions near stoichiometric ratio, while it is the codominant and nondominant reaction in fuel-lean and fuel-rich conditions respectively. Furthermore, the reaction pathways of oxidizers consumption in C2H4/N2O flames and C2H4/N2/O2 flames are analyzed, and the observations on the LBVs of these two flames in the experiment can be well explained through the reaction pathways and their relative changes under fuel-lean, stoichiometric and fuel-rich conditions.

Pulsating instabilities in hydrogen/air double-flame partially premixed counterflow flames are numerically investigated with detailed chemistry and transport. The whole stability map on the equivalence ratio-strain rate plane is obtained. With the increase of the equivalence ratio or strain rate, there are two transitions for combustion patterns from stable to unstable, and to stable again. For the one transition presented at the smaller equivalence ratio and strain rate, it is similar to that in the pure premixed flame. After this transition, the flames do not extinguish with the increase of equivalence ratio or strain rate, but transit from unstable to stable. For the second transition appeared at the larger equivalence ratio and strain rate, the effects of equivalence ratio and strain rate on the pulsating instability are completely contrary to those in pure premixed flames. The effective activation energy of the premixed flame of partially premixed flame predicted by a new method is applied to calculate the Zeldovich number. Then the first transition is proved to satisfy Sivashinsky-like criterion, but the critical value is larger than that for pure premixed flame due to the heat transfer between premixed and non-premixed flames. It means that the pulsating instability is more difficult to happen in partially premixed flames. From the first transition to the second transition along the equivalence ratio or strain rate, though the premixed flame becomes weaker, the increase degree of heat transfer from non-premixed flame to premixed flame is much larger than the decrease degree of max heat release of the premixed flame due to decrease of distance and increase of temperature difference of two flames, which induces the premixed flame stable again. The second transition is therefore controlled by the heat transfer between two flames.

In this paper, n-hexane flashing jets discharged from a single-hole gasoline direct injector (GDI) were studied numerically with the adoption of diffuse Eulerian framework and the homogeneous relaxation model (HRM). The fuel temperature ranged from 30 to 130 °C, and the ambient pressure varied from 20 to 101 kPa. The results showed that considerable vaporization started at the counter bore and a liquid core existed near the nozzle exit. Due to drastic vaporization, the pressure within the liquid core increased so the two-phase flow became under-expanded. Violent expansion then occurred and a low-pressure region was formed, which is believed as the origin of the spray collapse under flashing conditions for multi-hole GDI injectors. At high superheat levels, shock wave structures similar to those in highly under-expanded gaseous jets were identified. However, the transonic position located at some distances from the nozzle rather than at the throttle. Besides, vapor fraction played the dominant role in the onset of expansion, while the expansion was ended by the pressure difference between the two sides of the Mach disk.

A lower combustor inlet Mach number is desirable in order to design a compact, lightweight combustor and boost the overall performance of the scramjet engine. In this study, a thrust control strategy is proposed for a hydrogen-fueled scramjet taking into account the operating limitations, which is called the minimum combustor inlet Mach number rule since the combustor inlet Mach number is used as the control variable. By scheduling the fuel supply and modifying the intake geometry, the combustor inlet Mach number can be minimized while ensuring a certain thrust output within the operation constraints. In this manner, the scramjet engine can be operated with high specific thrust and low fuel consumption throughout the flight envelope. The thrust control strategy is further applied to a hydrogen-fueled scramjet in the hypersonic flight regime. Because the combustor inlet Mach number varies with flight conditions, the thrust strategy can be applied in practice by monitoring the following aerothermodynamic parameters in different flight regimes instead: (1) combustor outlet Mach number, (2) combustor inlet static temperature, and (3) combustor outlet static temperature. Furthermore, the effects of the thrust output on the division of flight regime are investigated, and the overall performance of the hydrogen-fueled scramjet engine obtained from applying the thrust control strategy is discussed in detail.

The present study was designed to explore the neuroprotective effects of docosahexaenoic acid (DHA) and/or vitamin E (VE) in vitro. The PC12 cells were pretreated with DHA and/or VE for 4 h, followed by 50 μmol L-1 Aβ25-35 treatments for another 48 h. The cells were then collected and used for the measurements of oxidative stress parameters. Real time-PCR and western blot were applied to measure fatty acid transporters, Nrf2 and its downstream antioxidant targets' gene and protein expression. Our results indicated that the Aβ25-35 treatment inhibited cellular growth, increased intracellular ROS generation and decreased the mitochondrial membrane potential. The Aβ25-35 treatment decreased the total antioxidant capacity (T-AOC), whereas it increased the MDA levels in neuron cells. Pretreatment of cells with VE or DHA could antagonize the Aβ25-35-mediated cell growth inhibition and mitochondrial membrane potential decline. Activation of the Nrf2 signaling pathway and regulation of CD36, SRB1 and FABP5 expression were observed in DHA- and DHA + VE-pretreated cells. Our results indicated a synergistic effect of DHA and VE in antagonizing the oxidative damage caused by Aβ25-35 in the PC12 cells. The results of the present study will shed light on the application of nutritional intervention for DHA and VE in preventing neuronal damage-related diseases.

In the field of electronic countermeasure, the recognition of radar signals is extremely important. This paper uses GNU Radio and Universal Software Radio Peripherals to generate 10 classes of close-to-real multipulse radar signals, namely, Barker, Chaotic, EQFM, Frank, FSK, LFM, LOFM, OFDM, P1, and P2. In order to obtain the time-frequency image (TFI) of the multipulse radar signal, the signal is Choi–Williams distribution (CWD) transformed. Aiming at the features of the multipulse radar signal TFI, we designed a distinguishing feature fusion extraction module (DFFE) and proposed a new HRF-Net deep learning model based on this module. The model has relatively few parameters and calculations. The experiments were carried out at the signal-to-noise ratio (SNR) of −14 ∼ 4 dB. In the case of −6 dB, the recognition result of HRF-Net reached 99.583% and the recognition result of the network still reached 97.500% under −14 dB. Compared with other methods, HRF-Nets have relatively better generalization and robustness.