The 2025 European Lung Cancer Congress (ELCC) convened in Paris, France, centering on the optimization and innovation of immunotherapy for non-small cell lung cancer (NSCLC). Key topics at the congress included the application strategies for perioperative immunotherapy, breakthroughs in combination therapy models for advanced NSCLC, and the emerging roles of biomarkers in predicting diverse treatment outcomes. This paper integrates data from several key pivotal studies to systematically analyze the clinical value of neoadjuvant therapy within the perioperative setting, the potential of targeted combination regimens, and the challenges of managing drug resistance, thus offering new directions for clinical practice.

MRGPRX2 antagonists possess the potential for the treatment of allergic rhinitis, atopic dermatitis, and chronic urticaria. Previously, we identified a class of diaryl urea (DPU) MRGPRX2 antagonists with sub-micromolar IC₅₀ values in vitro. However, the structure-activity relationship remains unclear. Herein, we adopted a "relative symmetry with electronegativity of different key-groups" strategy for further modification of DPUs to achieve a promising MRGPRX2 antagonist with higher activity and safety. Electrostatic potential energy analysis and biological evaluation revealed that B-1023 and B-5023, that possess relatively symmetric electron-withdrawing substituents, remarkable inhibited mast cell degranulation at a sub-micromolar IC₅₀ in vitro and alleviated anaphylactic symptoms. Furthermore, B-1023, mitigated antigen-induced pulmonary inflammation (AIPI) in mice and competitively bonded to MRGPRX2. In summary, the "relative symmetry with electronegativity of different key-groups" strategy provided a drug design pattern for MRGPRX2 antagonists and identified promising antiallergic precursors for AIPI treatment.

The cooccurrence of NPM1, FLT3-ITD, and DNMT3A mutations (i.e., triple mutation) is related to dismal prognosis in patients with acute myeloid leukemia (AML) receiving chemotherapy alone. In this multicenter retrospective cohort study, we aimed to identify whether allogeneic hematopoietic stem cell transplantation (allo-HSCT) could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut AML across four transplant centers in China. Fifty-three patients with triple-mutated AML receiving allo-HSCT in complete remission were enrolled. The 1.5-year probabilities of relapse, leukemia-free survival, and overall survival after allo-HSCT were 11.9%, 80.3%, and 81.8%, respectively. Multivariate analysis revealed that more than one course of induction chemotherapy and allo-HSCT beyond CR1 were associated with poor survival. To our knowledge, this work is the largest study to explore the up-to-date undefined role of allo-HSCT in patients with triple-mutated AML. Our real-world data suggest that allo-HSCT could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut in AML.
Humans ; Nucleophosmin ; Leukemia, Myeloid, Acute/mortality* ; Hematopoietic Stem Cell Transplantation/methods* ; Male ; Female ; DNA Methyltransferase 3A ; Adult ; China ; Retrospective Studies ; DNA (Cytosine-5-)-Methyltransferases/genetics* ; Middle Aged ; Prognosis ; fms-Like Tyrosine Kinase 3/genetics* ; Mutation ; Young Adult ; Transplantation, Homologous ; Nuclear Proteins/genetics* ; Adolescent ; Aged

Objective To explore the mechanism of long non-coding RNA fibroblast activation inhibitory factor 1(FAIF1)regulates the proliferation,activation,and fibrosis of human cardiac fibroblasts induced by advanced glycation end products(AGEs).Methods Human cardiac fibroblasts were assigned to control group,AGE group,FAIF1 recombinant lentivirus(Lv-FAIF1)+AGE group or control lentivirus(Lv control)+AGE group.The expression levels of miRNA-424-5p,FAIF1,and Smad7 in myocardial fibroblasts induced by AGEs were detected by quantitative polymerase chain reaction(qPCR)and Western blotting.Bioinformatics analysis was used to predict the interactions between miRNA-424-5p,FAIF1,and Smad7;and luciferase reporter assays were used for verification.Cell proliferation activity was measured by cell counting kit 8 assay,the expression and secretion of collagen Ⅰ/Ⅲ were observed by immunofluorescence staining,and the effect of Lv-FAIF1 on cell activation markers α-smooth muscle actin(α-SMA)and migration proteins matrix metalloproteinase 9(MMP9)induced by AGEs was evaluated by qPCR.Results qPCR and Western blotting results showed that AGEs significantly reduced the expression of FAIF1 and Smad7 in myocardial fibroblasts and upregulated the level of miRNA-424-5p(compared with the control group,all P＜0.05).Bioinformatics analysis revealed that the 3'-untranslated region of Smad7 mRNA contained a binding site for the miRNA-424-5p seed sequence"UGCUGCU",and FAIF1 sequence contained 3 identical binding sites.Luciferase assays showed that miRNA-424-5p inhibited the expression of Smad7,while FAIF1 competed with miRNA-424-5p for binding,thereby relieving the inhibitory effect of miRNA-424-5p on Smad7 mRNA.Functional experiments showed that Lv-FAIF1 significantly inhibited AGEs-induced cell proliferation,collagenⅠ/Ⅲ expression and secretion,as well as α-SMA and MMP9 expression(compared with AGE group,all P＜0.01);and it promoted the expression of Smad7(compared with AGE group,P＜0.01).Conclusion miRNA-424-5p can inhibit the expression of Smad7,and FAIF1 effectively suppresses AGEs-induced over-activation of cardiac fibroblasts by regulating the miRNA-424-5p/Smad7 axis,which provides a new molecular target for the prevention and treatment of diabetic cardiomyopathy.

Objective To investigate the inhibitory effect of morin on the cell cycle progression and prolif-eration ability of lung adenocarcinoma cells by regulating the transforming growth factor β1(TGF-β1)/Smads signaling pathway.Methods Human lung adenocarcinoma cell line A549 was used for in vitro experiments.Different concentrations of morin(0,30,90,150 μg/mL)were used to treat human lung adenocarcinoma cell line A549.Cell survival rate was detected by CCK-8 method,cell cycle distribution was detected by Hoechst 33342 staining method,cell proliferation ability was detected by clone formation assay,cell invasion ability was detected by Transwell invasion assay,cell apoptosis was detected by TUNEL staining method,and the expres-sion levels of TGF-β1/Smads signaling pathway related proteins were analyzed by Western blot.Results CCK-8 experimental results showed that the survival rate of A549 cells in the morin-treated group significantly decreased with the increase in morin concentration(P＜0.05).The results of Hoechst 33342 staining showed that the proportion of G1 phase cells in the morin-treated group significantly increased,and the proportion of S phase and G2/M phase cells significantly decreased(P＜0.05).The results of the colony formation assay showed that the number of colonies formed in the morin-treated group was significantly less than that in the control group,and the colony formation rates in the 90 μg/mL and 150 μg/mL groups were reduced by approximately 50％and 70％respectively(P＜0.05).Transwell invasion assay results showed that the number of invasive cells in the morin-treated group was significantly reduced(P＜0.05).TUNEL staining results showed that the proportion of apoptotic cells in the morin-treated group significantly increased(P＜0.05).Western blot results showed that the expression levels of TGF-β1 and p-Smad2/3 in the morin-treated group were significantly reduced(P＜0.05),and the expression level of Smad7 was significantly in-creased(P＜0.05).Conclusion Morin blocks A549 cells in the G1 phase by regulating the TGF-β1/Smads signaling pathway,thereby inhibiting cell proliferation,reducing cell invasion ability,and inducing cell apopto-sis.This indicates that morin has potential application value in the treatment of lung adenocarcinoma.

Objective To discover the mechanism by which miR-1287-5p affects the sensitivity of human esophageal cancer cell line KYSE30 to paclitaxel.Methods KYSE30 cells were divided into control group,group of transfected with miR-1287-5p mimic and inhibitor groups.RT-qPCR was used to detect the transfection rate.A paclitaxel-resistant cell line was established and cell viability and half inhibitory concentration(IC50)were detected by CCK-8 assay.The scratch test,Transwell chamber test and TUNEL method were used to evaluate the migration,invasion and apoptosis of cells.Western blot and immunocytochemistry(ICC)were used to detect the expression and localization of Akt and GSK-3β in cells.Results The expression level of miR-1287-5p in the miR-1287-5p mimic group was significantly higher than that in the miR-NC group and control group(P＜0.05),while the ex-pression level of the miR-1287-5p inhibitor group was significantly lower than that in miR-NC group and control group(P＜0.05).The cell survival rate of the miR-1287-5p mimic group was higher than that of the miR-NC group and the miR-1287-5p inhibitor group(P＜0.05).The cell migration rate and number of invasive cells in the miR-1287-5p mimic group were higher than those of the miR-NC group(P＜0.05),and the apoptosis rate was lower than that of the miR-NC group(P＜0.05).While in miR-1287-5p,the cell migration rate was lower and invasive cells were less in the inhibitor group and the apoptosis rate was increased as compared to the miR-NC group(P＜0.05).The expression of Akt and GSK-3β in the miR-1287-5p mimic group was significantly increased than in the miR-NC group(P＜0.05),while the expression in the miR-1287-5p inhibitor group was significantly inhibited than in miR-NC group(P＜0.05).Conclusions Up-regulation of miR-1287-5p can promote the migration and invasion of paclitaxel-resistant cell lines,inhibit cell apoptosis and thereby promote the development of paclitaxel resistance.

ObjectiveTo investigate the correlation between the color， odor and volatile components of Paeoniae Radix Alba（PRA） and its processed products， and to examine the effects of different processing methods on the odor and color formation of PRA. MethodThe odor and chromaticity information of PRA， honey chaff-fried PRA and honey bran-fried PRA were identified by electronic nose and colorimeter， and the volatile components in the different processed products of PRA were identified and relatively quantified by headspace gas chromatography-mass spectrometry（HS-GC-MS）， and analyzed using principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）， then the differential key flavor components among the three were screened according to the principles of variable importance in the projection（VIP） value>1 and relative odor activity value（ROAV）≥1. Pearson correlation analysis was used to investigate the association between the differential flavor components and the colorimetric values and electronic nose sensors， respectively. ResultAfter being fried with honey chaff and honey bran， the lightness value（L^*） of PRA decreased， and red-green value（a^*） and yellow-blue value（b^*） increased significantly（P<0.05， P<0.01）. The odor differences were mainly reflected in the S1， S2， S4， S5， S6， S8 and S11 sensors， and the results of PCA of the electronic nose indicated that the odor differences among PRA， honey chaff-fried PRA and honey bran-fried PRA were obvious， among which the overall odor intensity of honey bran-fried PRA was higher than that of honey chaff-fried PRA. A total of 47 volatile components were identified from PRA and its processed products， including 21 for PRA， 36 for honey chaff-fried PRA， and 37 for honey bran-fried PRA. Odor analysis revealed that 12， 24 and 22 volatile components may be the key flavor components in PRA， honey chaff-fried PRA and honey bran-fried PRA， respectively. Correlation analysis showed that the L^* of the decoction pieces was negatively correlated with the content of the Maillard reaction products， the a^* and b^* were positively correlated with the content of the Maillard reaction products， the S1 and S8 sensors were negatively correlated with the content of the Maillard reaction products， and the S2， S4， S5， S6 and S11 sensors were positively correlated with the Maillard reaction products. ConclusionThe color of PRA is deepened after being stir-fried with honey chaff and honey bran， and 5-hydroxymethylfurfural， furfural and other components are generated at the same time， which is in line with the theory of burning aroma strengthens the spleen of stir-fried with honey chaff and honey bran. Honey bran-fried PRA has a stronger Maillard reaction than honey chaff-fried PRA， which makes honey bran-fried PRA with a burnt flavor and a dark yellow color， while honey chaff-fried PRA has a sweet flavor and a bright yellow color.

There are different views on the theory of “spleen governs time”， which is still a hot spot in the study of Zangxiang （藏象） theory. Based on Zangxiang time-space view， it is found that the thinking mode of the spleen governing time theory follows space-time logic. It is believed that the different time views of the spleen governing time are all formed based on the space view that the spleen belongs to earth and resides in the center， and the zang time theory is developed with the unified time and space logic. Guided by Zangxiang time-space view， the origin of the spleen belonging to earth and residing in the center is traced， and the theoretical connotation and its clinical application of spleen governing time under different time-space logic are explored with reference to the four season and five zang theory， five season and five zang theory， six season and six zang theory， and eight season and eight zang theory.

Objective:To identify the influencing factors for community elderly health services provided by general practitioners (GPs) using the social ecological theory, for reference in improving their participation and satisfaction.Methods:According to the social ecological theory, an ecological model for GPs to carry out community elderly health services was constructed from four levels: public policy ecology, community health service ecology, interpersonal relationship ecology, and individual characteristics ecology of general practitioners. A survey questionnaire was designed with six latent variables: public health policy support, public health service and basic medical service supply, doctor-patient relationship, individual participation and individual satisfaction. The questionnaire was distributed to 220 GPs from 11 primary healthcare institutions in Jiangsu province, China, who were randomly selected between October and November 2021. Exploratory and confirmatory analyses of the model were conducted using AMOS 25.0.Results:A total of 207 valid questionnaires were collected, and all the KMO values of the six latent variables were greater than 0.7, while the composite reliability values and average variance extracted values greater than 0.7 and 0.5, respectively. Both the reliability and validity of the data met the analysis requirements. Exploratory analysis revealed that public health policy support had a direct positive effect on both public health service and basic medical service supply (both effect sizes being 0.37). Public health service had a direct positive effect on doctor-patient relationship, individual participation and individual satisfaction (effect sizes being 0.52, 0.22, and 0.31, respectively). The direct effect of basic medical service supply on doctor-patient relationship was not significant (effect size being 0.03), but it had a direct positive effect on public health service (effect size being 0.46). Doctor-patient relationship had a direct positive effect on individual participation (effect size being 0.51), but its direct effect on individual satisfaction was not significant (effect size being 0.06). Individual participation had a direct positive effect on individual satisfaction (effect size being 0.52). Conclusions:By optimizing the public policy ecosystem, community health service ecosystem, and interpersonal relationship ecosystem, the participation and satisfaction of general practitioners can be systematically improved.

Molecular knowledge of human gastric corpus epithelium remains incomplete. Here, by integrated analyses using single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and single-cell assay for transposase accessible chromatin sequencing (scATAC-seq) techniques, we uncovered the spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium. Specifically, we identified a stem/progenitor cell population in the isthmus of human gastric corpus, where EGF and WNT signaling pathways were activated. Meanwhile, LGR4, but not LGR5, was responsible for the activation of WNT signaling pathway. Importantly, FABP5 and NME1 were identified and validated as crucial for both normal gastric stem/progenitor cells and gastric cancer cells. Finally, we explored the epigenetic regulation of critical genes for gastric corpus epithelium at chromatin state level, and identified several important cell-type-specific transcription factors. In summary, our work provides novel insights to systematically understand the cellular diversity and homeostasis of human gastric corpus epithelium in vivo.
Humans ; Epigenesis, Genetic ; Gastric Mucosa/metabolism* ; Chromatin/metabolism* ; Stem Cells ; Epithelium/metabolism* ; Fatty Acid-Binding Proteins/metabolism*