Fusion variations of neurotrophic receptor tyrosine kinase (NTRK) are oncogenic drivers in various solid tumors such as breast cancer, salivary gland carcinoma, infant fibrosarcoma, etc. Gene rearrangements involving NTRK1/2/3 lead to constitutive activation of the tropomyosin receptor kinase (TRK) domain, and the expressed fusion proteins drive tumor growth and survival. NTRK fusions are estimated to occur at a frequency of approximately 0.1% to 1% in non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) mutations are prevalent in NSCLC, but the frequency of EGFR G719A mutation is relatively low (about 2%), and EGFR mutations are typically mutually exclusive with NTRK fusion variants. The study presented the first documented case of lung adenocarcinoma harboring both EGFR G719A mutation and LMNA-NTRK1 fusion. A review of the literature was conducted to elucidate the role of NTRK fusion mutations in NSCLC and their relationship with EGFR mutations, aiming to enhance the understanding of NTRK fusion mutations in NSCLC.
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Humans ; Adenocarcinoma/genetics* ; Adenocarcinoma of Lung ; ErbB Receptors/genetics* ; Lamin Type A/genetics* ; Lung Neoplasms/genetics* ; Mutation ; Oncogene Proteins, Fusion/genetics* ; Receptor, trkA/metabolism*

Autoimmune disease is a kind of heterogeneous disease caused by the loss of immune tolerance to autoantigens.In recent years,antibody drug has become an important choice for the treatment of autoimmune diseases.Monoclonal antibodies are limited by their large relative molecular mass and difficult to penetrate solid tissues,while nanobodies,the smallest antibody fragment known to date with intact antigen recognition,have gained much attention in the treatment of autoimmune diseases due to their ease of modifi-cation,high penetration,and ability to target more cryptic epitopes.The review focuses on the application of nanobodies in the treat-ment of diseases such as rheumatoid arthritis,acquired thrombotic thrombocytopenic purpura,systemic lupus erythematosus,psoria-sis,and looks forward to the prospect of nanobodies in the treatment of autoimmune diseases.

The development, progression, and curative efficacy of head and neck squamous cell carcinoma (HNSCC) are influenced by complex interactions between epithelial and immune cells. Nevertheless, the specific changes in the nature of these interactions and their underlying molecular mechanisms in HNSCC are not yet fully understood. Cuproptosis, a form of programmed cell death that is dependent on copper, has been implicated in cancer pathogenesis. However, the understanding of cuproptosis in the context of HNSCC remains limited. In this study, we have discovered that cuproptosis-related long non-coding RNAs (CRLs) known as JPX play a role in promoting the expression of the oncogene urokinase-type plasminogen activator (PLAU) by competitively binding to miR-193b-3p in HNSCC. The increased activity of the JPX/miR-193b-3p/PLAU axis in malignant epithelial cells leads to enhanced cell proliferation, migration, and invasion in HNSCC. Moreover, the overexpression of PLAU in tumor epithelial cells facilitates its interaction with the receptor PLAUR, predominantly expressed on macrophages, thereby influencing the abnormal epithelial-immune interactome in HNSCC. Notably, the JPX inhibitor Axitinib and the PLAU inhibitor Palbociclib may not only exert their effects on the JPX/miR-193b-3p/PLAU axis that impacts the malignant tumor behaviors and the epithelial-immune cell interactions but also exhibit synergistic effects in terms of suppressing tumor cell growth and arresting cell cycle by targeting epidermal growth factor receptor (EGFR) and cyclin-dependent kinase (CDK4/6) for the treatment of HNSCC.
Humans ; MicroRNAs/metabolism* ; RNA, Long Noncoding/metabolism* ; Head and Neck Neoplasms/metabolism* ; Cell Proliferation ; Squamous Cell Carcinoma of Head and Neck/genetics* ; Urokinase-Type Plasminogen Activator/genetics* ; Cell Movement ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Carcinoma, Squamous Cell/genetics* ; Neoplasm Invasiveness

Objective:To evaluate the teaching effectiveness of independent experimental design from students' active learning behavior, and further provide the basis for advancing the reform of functional experimental teaching and teaching quality.Methods:In June 2019, 186 undergraduates (5-year-programme and 8-year-programme) of Xiangya School of Medicine were included in the teaching research. Self-administered questionnaires were applied to characterize students' active learning behavior in independent experimental design education. Spearman rank correlation analysis and Logistic regression analysis were used in the study. SPSS 23.0 was used for descriptive analysis of the data.Results:During the independent experimental design, 85.0%(158/186) of the students thought it was necessary and important to conduct independent experimental design education; 72.6%(135/186) of the students tentatively raised new scientific questions; 97.8%(182/186) of the students actively searched literature; 77.4%(144/186) of the students participated in reply positively. The value of correlation coefficient of actively learning behavior "tentatively raising new science questions" and teaching effectiveness "improving the ability of scientific thinking" was 0.81. And only 42.5%(79/186) of the students agreed that students needed to summarize after reporting.Conclusion:Independent experimental design education is welcomed and widely accepted by students, which has effectively improved the capacity for scientific research and innovation spirit of students. Whether students' active learning behavior can be fully mobilized in the education practice is closely related to the teaching effect. And the cultivation of leadership and leading consciousness still need to be improved.

OBJECTIVETo investigate the feasibility of urinary ortho-cresol levels as a biological monitoring indicator for toluene exposure.

METHODSEstablish pre-column derivation HPLC method to detect ortho-cresol levels in urine of human body. Ortho-cresol levels in urine of workers non-exposed and exposed to toluene was examined using this pre-column derivation HPLC method, and exposure assessment was conducted.

RESULTSIt was shown that urinary ortho-cresol level in exposed workers was (2.61 +/- 1.94) mg/L, higher than those of control group [(0.32 +/- 0.23) mg/L, P < 0.001]. Urinary ortho-cresol level in exposed workers at the end of a workshift was higher than those before exposure to toluene, and also was correlated with the concentration of toluene to which individual exposed(r = 0.6295, P < 0.01).

CONCLUSIONUrinary ortho-cresol as a biological monitoring indicator for toluene exposure is feasible.

Chromatography, High Pressure Liquid ; Cresols ; urine ; Environmental Monitoring ; methods ; Humans ; Occupational Exposure ; Toluene ; metabolism

Objective:To study on GFW-inducing tumor apoptosis and to find the experimenting basis for utilizing GFW in cancei theiapy.Methods:S180 mouse sarooma model was used to detect inhibiting effects of GFW on tumor grouth in viro,Morphological changes were observed by electron microscopy and flow cytometer was used for determination apoptosis.The protein expression of p21 and the mRNA expression of Survivin were evaluated by immunohistochemistry and in situ hybridization.Results:For S180 sarcoma ,the inhibiting rate of GFW was 38.93%.Apoptosis was 17.79% detected by flow cytomety.Typical apoptotic cells and apoptotic bodies were observed through electron microscope. Chromatin was found gathering as aggregates in nucleus or under nucleus membrane and the nuclear body formed at the same time. Survivin mRNA decreased markedly in the GFW group when compared with the model group(P