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Background Comprehensive genomic analysis and optimal treatment for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor ( EGFR ) G719X + S768I co-mutations remain limited. This study aimed to elucidate the genetic landscape and the clinical effectiveness of EGFR tyrosine kinase inhibitors (EGFR-TKIs) in this subset. Methods A total of 645 EGFR -mutant NSCLC patients were retrospectively screened, with 142 patients harbored EGFR G719X + S768I co-mutations. Among these patients, next-generation sequencing was performed in 126 patients, and the efficacy of first-line EGFR-TKIs was evaluated in 96 patients with stage IV disease. Impacts of variant allele frequency (VAF) and concurrent TP53 mutations were also analyzed. Results Among G719X variants, G719C was most prevalent (69.8%), followed by G719A (19.0%) and G719S (8.7%). The most common co-existing mutation was TP53 (38.0%), followed by ALK and PIK3CA (6.3% each). For first-line EGFR-TKIs, the overall objective response rate (ORR) reached 68.8%, with a median progression-free survival (mPFS) of 21.4 months (95% CI: 18.2–24.6). Afatinib showed a significantly better response compared to both first- and third-generation EGFR-TKIs (1st vs. 2nd vs. 3rd generations, ORR: 35.7% vs. 76.8% vs. 61.5%, P  = 0.01; mPFS: 17.2 vs. 23.4 vs. 17.4 months, P  = 0.008). VAF and TP53 mutation status did not affect outcomes ( P  > 0.05), but patients with metastases in the brain and liver experienced notably shorter mPFS. Brain metastases patients had an ORR of 70.5% without additional benefit from third-generation TKIs. Conclusions This study delineates the genomic profile of EGFR G719X + S768I co-mutated NSCLC and highlights the superior effectiveness of second-generation EGFR-TKIs, particularly afatinib. These findings provided valuable insights to guide clinical decision-making and facilitate the development of tailored therapeutic strategies for this subset.

Background Programmed cell death protein 1 (PD-1) inhibitor is widely utilized in advanced-stage carcinomas including hepatocellular carcinoma (HCC), while its neoadjuvant application plus transarterial chemoembolization (TACE) in HCC remains unexplored. Thereby, the current study aimed to investigate the efficacy and safety of TACE plus PD-1 inhibitor as neoadjuvant therapy bridging to surgical resection in intermediate-stage HCC patients. Methods Twenty intermediate-stage HCC (China Liver Cancer (CNLC) stage II) patients treated with neoadjuvant TACE plus PD-1 inhibitor (camrelizumab or sintilimab) bridging to surgery were consecutively enrolled. Results The objective response rate (ORR) and disease control rate (DCR) to neoadjuvant therapy were 75.0% and 100.0%, respectively; meanwhile, alpha-fetoprotein (AFP) was decreased after the neoadjuvant therapy ( P  < 0.001). Moreover, 14 (70.0%) patients had successful downstaging (patients converted to CNLC stage I). Neither median disease-free survival (DFS) nor median overall survival (OS) was reached; additionally, the 1-year accumulating DFS rate was 86.6%; meanwhile, the 1-year and 2-year accumulating OS rates were 100.0% and 76.4%, separately. Moreover, patients with successful downstaging had a prolonged DFS ( P  = 0.014) compared to patients with failed downstaging; meanwhile, this trend was also observed in assessing accumulating OS ( P  = 0.067) (without statistical significance). Main adverse events included pain (50.0%), fever (25.0%), neutropenia (25.0%), nausea and vomiting (25.0%), fatigue (25.0%), peripheral neuropathy (20.0%), anemia (15.0%), thrombopenia (15.0%), diarrhea (15.0%), anorexia (15.0%), and rash (15.0%). Conclusion Neoadjuvant TACE plus PD-1 inhibitor realizes a satisfying downstaging rate, acceptable survival profile, and tolerance in intermediate-stage HCC patients.

MALT1 regulates immunity and inflammation in multiple ways, while its role in rheumatoid arthritis (RA) is obscure. This study aimed to investigate the relationship of MALT1 with disease features, treatment outcome, as well as its effect on Th1/2/17 cell differentiation and underlying molecule mechanism in RA. Totally 147 RA patients were enrolled. Then their blood Th1, Th2, and Th17 cells were detected by flow cytometry. Besides, PBMC MALT1 expression was detected before treatment (baseline), at week (W) 6, W12, and W24. PBMC MALT1 in 30 osteoarthritis patients and 30 health controls were also detected. Then, blood CD4 T cells were isolated from RA patients, followed by MALT1 overexpression or knockdown lentivirus transfection and Th1/2/17 polarization assay. In addition, IMD 0354 (NF-κB antagonist) and SP600125 (JNK antagonist) were also added to treat CD4 T cells. MALT1 was increased in RA patients compared to osteoarthritis patients and healthy controls. Meanwhile, MALT1 positively related to CRP, ESR, DAS28 score, Th17 cells, negatively linked with Th2 cells, but did not link with other features or Th1 cells in RA patients. Notably, MALT1 decreased longitudinally during treatment, whose decrement correlated with RA treatment outcome (treatment response, low disease activity, or disease remission). In addition, MALT1 overexpression promoted Th17 differentiation, inhibited Th2 differentiation, less affected Th1 differentiation, activated NF-κB and JNK pathways in RA CD4 T cells; while MALT1 knockdown exhibited the opposite effect. Besides, IMD 0354 and SP600125 addition attenuated MALT1's effect on Th2 and Th17 differentiation. MALT1 regulates Th2 and Th17 differentiation NF-κB and JNK pathways, as well as correlates with disease activity and treatment outcome in RA.

The species holds substantial ecological value and economic potential, particularly in the realms of rehabilitating barren mountain landscapes and advancing urban greening endeavors. However, inadequate attention has been given to research endeavors exploring the genetic diversity and morphological characteristics of , a deficiency that could potentially hinder its development, utilization, and conservation of genetic resources. To rectify the shortage of existing basic morphological data, a morphological analysis was conducted in this study on 180 germplasm resources sourced from five provenances. Key traits explored included growth characteristics, overall morphology, branch/leaf features, and seed traits. This will facilitate the evaluation of genetic diversity in . The findings reveal a considerable level of phenotypic variation (PVC of 16.9%) and genetic diversity (1.97 index) in germplasm resources. The phenotypic differentiation is observed to be 48% between provenances and 52% within provenances, primarily attributed to variation originating from individual provenances. Based on these morphological characteristics, the germplasm resources have been categorized into four distinct groups: Ecological Restoration Planting, Secondary Reserve Forest, Urban Greening, and Timber Forest. Interestingly, the pattern of variation observed within these groups is irregular, exhibiting no significant correlation with their respective provenances. Furthermore, conifer trees sharing similar growth characteristics tend to display comparable patterns of random variation, suggesting potential underlying genetic mechanisms. This study significantly enriches the phenotypic dataset within the genetic variation research of , facilitating development and utilization for ecological construction, timber breeding, and horticultural greening.

Background After the coronavirus disease 2019 (COVID-19) pandemic, no studies on bacterial and atypical pathogens were conducted in primary care. We aimed to describe the etiological composition of acute respiratory tract infections (ARTIs) presenting to primary care with limited resources after the pandemic. Methods 1958 adult patients with ARTIs from 17 primary care clinics were recruited prospectively from January 2024 to March 2024. 17 and 62 pathogens in throat swab samples were tested using polymerase chain reaction (PCR) and targeted next-generation sequencing (tNGS), respectively. We analyzed the pathogen spectrum and co-infectious pattern of viral, bacterial or atypical pathogens. Then, the associations between clinical characteristics and pathogens were investigated. Results In PCR test, the positive rate of any pathogens was 80.3%, consisting of 60.2% for viruses, 41.8% for bacteria and 21.7% for viral-bacterial co-infection. In tNGS test, the positive rate was 89.1%, consisting of 64.7% for viruses, 55.2% for bacteria and 30.9% for viral-bacterial co-infection. Influenza virus B (18.2%), influenza virus A (16.8%) and severe acute respiratory syndrome coronavirus 2 (14.1%) were the three leading viral pathogens, and H. influenzae (36.1%), S. anginosus (15.7%) and S. pneumoniae (8.4%) were the three leading bacterial pathogens. Few M. pneumoniae (1.6%) were detected. The mixed bacterial or mixed viral-bacterial co-infections were the most common co-infectious patterns. The mixed bacterial or mixed viral-bacterial co-infections were the most common co-infectious patterns. Overall, patients with viral infection or viral-bacterial co-infection had more clinical symptoms, and patients with bacterial infection had higher inflammatory indicators. Conclusions After the COVID-19 pandemic, the main viral pathogens of ARTIs were unevenly distributed, and less bacterial and atypical pathogens were detected in primary care. The microbiological evidences can optimize the precision diagnosis and treatment of ARTIs in primary care with limited resources.

The dual-bell nozzle is a kind of altitude adaptive nozzle for improving the performance of space launchers as well as future reusable launch vehicles. Numerical investigations have been conducted on a planar dual-bell nozzle to illustrate the flow characteristics at sea level, “sneak” transition, and altitude modes, respectively. Findings from computational fluid dynamics have been contrasted with experimental data from the open literature. The normalized pressure distributions along the dual-bell nozzle wall for different turbulence models are compared to the pressure measurements taken during the experiment by fixing the nozzle pressure ratio (NPR) at 29.8. The NPR value gradually rises across a large range from 6 to 55 to explore the evolution of the flow characteristics. The pressure distributions along the nozzle wall and shock position have been investigated. The hysteretic behaviors occur in dual-bell nozzles close to the contour inflection. The wall pressure and hysteresis behaviors have been expounded in detail.

Transverse secondary gas injection into an axisymmetric supersonic nozzle under standard atmosphere pressure is investigated to get the performance of thrust vectoring control. An analytical model was established based on the transverse injection flow. Three-dimensional CFD methods were performed with different transverse secondary injection models. To validate the ability of the numerical model, numerical results were compared with the analytical and experimental results. Overall pressure distributions show quite good match with the analytical and experimental results. The Mach number contours in different injection positions were obtained. Reflection of the bow shock occurred for x j / L = 0.6 , not for x j / L = 0.9 . Nozzle pressure ratio is also the key factor for shock vector control. Based on this data, thrust vectoring efficiency and system thrust ratio have been considered. Finally, the pressure distributions in different momentum flux ratios were studied in CFD and analytical models. The separating point of boundary layer is moving upstream with the increasing of momentum flux ratio. The result will provide the reference to the further development of shock vector control.

Dual-mode scramjet has become a viewpoint in the research fields of propulsion systems of aeronautics and astronautics. The key operating process of the dual-mode scramjet is from a started situation to an unstarted situation. The operating process composes of three phases. The first phase is when the pseudo shock wave is in the combustor. The second phase is when the pseudo shock wave is in the isolator. The last phase is when inlet unstart happens. In this study, two-dimensional numerical model has been made to replicate the process before inlet unstart. The location of pseudo shock wave has been determined in according to the location of the plug. As the throat area of the plug is decreasing, pseudo shock wave goes upstream. The prediction of inlet unstart has been focused in terms of the throat area ratio. The transition point of throat area ratio just before inlet unstart has been indicated. The transition points of throat area ratio in steady simulation and unsteady simulation are different. This is because the transition information needs time to spread from the plug to upstream location. The difference could be used for predicting the inlet unstart.

Purpose This retrospective study aimed to investigate changes in pulmonary function among patients undergoing computed tomography (CT)-guided microwave ablation (MWA) for the treatment of pulmonary ground-glass nodules following lobectomy. Materials and methods Fifty-two patients with pulmonary ground-glass nodules (GGN) who underwent lobectomy and were subsequently diagnosed with non-small cell lung cancer (NSCLC) were included in the study. Pulmonary function tests (PFTs) were conducted at baseline and again 1 month after microwave ablation (MWA). The assessed parameters included vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1 percentage (FEV1%), peak expiratory flow (PEF), maximal voluntary ventilation (MVV), and maximum mid-expiratory flow (MMEF). The measurements obtained 1-month post-MWA were compared to the baseline values. Results The mean values for VC, FVC, FEV1, FEV1%, MMEF, PEF, and MVV at baseline and 1-month post-MWA for all patients were as follows: VC (3.01 ± 0.68vs. 2.88 ± 0.67, P  = 0.348), FVC (3.07 ± 0.75 vs. 2.95 ± 0.69, P  = 0.430), FEV1 (2.29 ± 0.61 vs. 2.14 ± 0.55, P  = 0.228), FEV1% (74.26 ± 7.70 vs. 72.41 ± 9.40, P  = 0.316), MMEF (1.88 ± 0.81 vs. 1.74 ± 0.72, P  = 0.410), PEF (5.03 ± 1.62 vs. 4.54 ± 1.53, P  = 0.179), and MVV (77.69 ± 22.21 vs. 73.15 ± 17.63, P  = 0.286). For the eight patients who underwent ablation of two or more lesions simultaneously, the mean values for VC, FVC, FEV1, FEV1%, MMEF, PEF, and MVV at baseline and 1 month post-MWA were as follows: VC (2.67 ± 0.90vs. 3.05 ± 0.97, P  = 0.341), FVC (2.82 ± 0.94vs. 3.10 ± 0.92, P  = 0.430), FEV1 (1.97 ± 0.69vs. 2.07 ± 0.69, P  = 0.709), FEV1% (70.01 ± 7.24 vs. 66.27 ± 4.47, P  = 0.082), MMEF (1.28 ± 0.80 vs. 1.35 ± 0.58, P  = 0.777), PEF (4.43 ± 1.44 vs. 3.87 ± 1.40, P  = 0.074), and MVV (65.22 ± 16.50 vs. 72.26 ± 12.28, P  = 0.222). No significant differences were observed in the PFT results before and 1 month after MWA. Conclusions MWA is a localized treatment that spares lung parenchyma. The pulmonary function 1 month after MWA did not statistically differ from baseline levels, suggesting that MWA may not adversely affect pulmonary function.

The dual-mode scramjet is a prime candidate for air-breathing propulsion engines given its broad speed range and high efficiency. The detailed structure of the pseudo-shock wave in the isolator is worth investigating. Therefore, the present study investigates the effect of isolator length on the pseudo-shock wave. We replicate the experimental work of the reference paper with a two-dimensional numerical model. Pressure distribution on the body surface is applied in the numerical validation. The numerical result is in good agreement with that of the existing experimental work. We simulate the thermal choking condition with a throttling device. As the throat area of throttling device decreases, the back pressure continues increasing and the pseudo-shock wave moves upstream. Avoiding unstart phenomenon is a key objective in the operation of dual-mode scramjet. Therefore, we investigate the critical condition shortly before unstart phenomenon occurs. The pseudo-shock wave structure is described by pressure distribution. Our main objective is to explore the effect of isolator length on the dual-mode scramjet. The optimal isolator length depends on the maximum back pressure and total pressure loss in the critical condition shortly before the unstart phenomenon occurs. The maximum back pressure in the critical condition is higher when the isolator length ranges from 8.7 to 20.7. The total pressure loss in the critical condition decreases at the beginning and then increases when the isolator length ranges from 8.7 to 20.7.