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*

V-Raf murine sarcoma viral oncogene homolog B(BRAF)alteration is one of the most essential driver genes of non-small cell lung cancer(NSCLC).BRAF encodes serine/threonine protein kinases,and its mutations typically lead to protein compositional activation,thereby activating the mitogen-activated protein kinase kinase(MEK)signaling pathway.A promising new approach for the treatment of mutated BRAF and/or downstream MEK may provide customized treatment op-portunities for BRAF driven NSCLC patients.However,combination therapy is necessary to overcome the difficulties such as short duration of benefit,poor therapeutic effect of non-V600 BRAF mutations and susceptibility to drug resistance.This article reviewed the progress in structural characteristics,related signaling pathways,mutation types of BRAF gene,and the clinical pathological relationship between BRAF mutations and NSCLC,as well as the therapy,in order to provide more evidences for clinical doctors to make treatment decisions.

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 investigate the improvement effects and mechanism of imperatorin on cachexia model mice. METHODS Fifteen male C57BL/6J mice were randomly divided into blank control group， model group and imperatorin group， with 5 mice in each group. Except for blank control group， the remaining mice were inoculated with LLC cell suspension subcutaneously on the dorsal surface， and the drug was administered by gavage daily from the 7th day of inoculation. The imperatorin group was gavaged with imperatorin suspension （0.5% sodium carboxymethylcellulose solution as solvent） at 60 mg/kg； blank control group and model group were given an equal volume of 0.5% sodium carboxymethylcellulose solution， for 13 d of continuous administration. During the administration period， food intake and body mass of mice were recorded daily and regularly， tumor long and short diameters were measured every two days， and tumor volume was calculated. The skeletal muscle mass and tumor mass of each group were weighed and the tumor-free body weight was calculated； the pathological changes of skeletal muscle were observed and the cross-sectional area of skeletal muscle fibers was calculated； the phosphorylation levels of signal transduction and activator of transcription 3 （STAT3） （measured as p-STAT3/STAT3 ratio）， muscle atrophy box F gene （MAFbx）， myostatin （Myog）， B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， Caspase3 protein and mRNA expression were all detected. RESULTS Compared with blank control group， body mass and skeletal muscle mass of model group were decreased significantly （P＜0.05）， and reduced food intake， loose arrangement of skeletal muscle， large cell space were observed； the cross-sectional area of skeletal muscle fiber was significantly reduced， while p-STAT3/STAT3 ratio， protein and mRNA expressions of MAFbx， Bax and Caspase3 were somo_amour@163.com increased significantly （P＜0.05）. The protein and mRNA expressions of Myog and Bcl-2 were significantly reduced （P＜ 0.05）. Compared with model group， body weight， tumor-free weight and skeletal muscle weight were increased significantly in imperatorin group （P＜0.05）； food intake increased， while the expressions of tumor weight and volume were decreased significantly （P＜0.05）； the expressions of above proteins and genes were improved significantly （P＜0.05）. CONCLUSIONS Imperatorin can improve the tumor cachexia state， the mechanism of which may be related to the regulation of ubiquitin-proteasome pathway and anti-apoptosis.

Objective:To summarize the application rules of acupuncture and moxibustion in the clinical trials for dysmenorrhea and endometriosis.Methods:The relevant articles of clinical research on acupuncture and moxibustion for the treatment of dysmenorrhea in endometriosis were retrieved electronically from CNKI, Wanfang, VIP, PubMed and Cochrane Library (Retrieved from database establishment until 31 October 2021). The clinical literatures that met the inclusion criteria were included into the database (Microsoft Office Excel 2019), and the main table and sub-table were established through Microsoft Office Excel 2019. Descriptive statistic analysis was performed by using SPSS 26.0 software. StataSE15 (64-bit) software was used to analyze the correlation between the combinations of acupoints with single acupoint frequency>5.Results:A total of 40 clinical studies were included. Of them, the top 3 acupuncture methods according to the frequency were acupuncture (11 times), moxibustion (11 times), and electro-acupuncture (8 times), the top 3 acupuncture points used according to the frequency were Guan Yuan (34 times), San Yin Jiao (26 times), and Zhong Ji (25 times), the top 3 meridians of the body acupuncture points according to the frequency were Ren Meridian (36 times), Spleen Meridian (32 times), and Stomach Meridian (22 times). According to the correlation analysis, body points of Guan Yuan, San Yin Jiao, Uterus, Qi Hai and Zhong Ji were stronge related.Conclusion:Acupuncture can effectively treat EMT dysmenorrhea with less adverse reactions. The methods are mainly acupuncture, moxibustion and electroacupuncture, mostly local acupoints, intersection acupoints and empirical acupoints.

Objective : The study provided evidence for clinical prevention of colorectal cancer by analyzing the characteristics of recurrence after colorectal polypectom． Methods : According to the number of polyps during the second colonoscopy，patients were divided into multiple recurrence group ( ≥3) and non-multiple recurrence group (＜3) ．The characteristics and risk factors of polyp recurrence were analyzed. Results : The clinical data of 370 patients who underwent two colorectal polypectomy were retrospectively analyzed．In univariate statistical analysis， polyp size (P = 0. 033) ，polyp site (P = 0. 002) ，and polyp color (P = 0. 032) were the risk factors for multiple polyp recurrence．In multivariate regression analysis，the number of polyps detected at the first colonoscopy (P = 0. 001) and the polyp site (P = 0. 001) were independent risk factors for multiple recurrence． Conclusion Multi- ple polyps on the first colonoscopy and polyps in the distal colon indicate an increased risk of multiple recurrence.

Objective To explore the relationship between iodine and fluoride content in drinking water and the incidence of adult thyroid nodules in Cangzhou,Hebei.Methods According to the previous reports on iodine and fluoride levels in drinking water in Cangzhou,from November 2016 to January 2017,Cangzhou was divided into high iodine,low iodine,normal iodine and fluorine,low iodine and high fluorine,high iodine and high fluorine areas,and according to the different contents of iodine and fluorine in drinking water,high iodine and high fluorine area was further divided into high iodine and high fluorine 1 (iodine:743.30 μg/L,fluorine:4.27 mg/L),2 (iodine:119.31μg/L,fluorine:4.67 mg/L) and 3 (iodine:105.30 μg/L,fluorine:1.64 mg/L) subareas.Subjects who lived for 20 or more years and aged 30 or older,without serious disease and not taken iodized salt were selected.Palpation was used to examine the size,texture,mass,tenderness and mobility of the thyroid gland.The boundary,internal echo,blood flow and quantity of nodules were observed and recorded by color Doppler.Results The prevalence difference of thyroid nodules [36.8％ (629/1 710),32.8％ (636/1 938),25.1％ (427/1 700)] in high iodine,low iodine and normal iodine and fluorine areas was statistically significant (x2 =55.597,P ＜ 0.05).The prevalences of thyroid nodules in both high iodine and low iodine areas were higher than that of normal iodine and fluorine area (P＜ 0.016 7).The prevalence difference of thyroid nodules [43.3％ (749/1 730),39.8％ (712/1 790),34.9％ (623/1 785)] in high iodine and high fluorine 1,2 and 3 subareas was statistically significant(x2 =26.220,P ＜ 0.05).Compared with low iodine area,the prevalence of thyroid nodules [41.2％ (735/1 785)] in low iodine and high fluorine area was increased (x2 =6.288,P ＜ 0.05).Conclusions Both high iodine and low iodine can induce thyroid nodules.In water source areas with high iodine content,both high iodine and high fluorine are the factors inducing thyroid nodules.The prevalence of thyroid nodules in low iodine and high fluorine area is significantly higher than that of low iodine area.

OBJECTIVETo evaluate the efficacy and metabolic safety of long-term treatment with ethinyl oestradiol/cyproteroneand desogestrel/ethinyl oestradiol tablets in women with polycystic ovary syndrome (PCOS).

METHODSWomen with PCOSfrom West China Second Hospital of Sichuan University enrolled between September, 2011 and August, 2013 were randomlyallocated to receive either ethinyl oestradiol/cyproterone tablets (Group A, =355) or desogestrel/ethinyl oestradiol tablets(Group B, =357) for a prospective observation period of 6 months. Women with insulin resistance also received metformin. Atbaseline, 3 months, and 6 months, the patients were evaluated for menstruation, acne score, body mass index (BMI), waist-tohip ratio (WHR), plasma levels of sex hormones, fasting blood glucose (FPG), HOMA-insulin resistance index (HOMA-IR), serum lipid, ovarian volume, and the number of ovarian follicles.

RESULTSAll the patients had a regular menstrual cycle aftertreatments. Testosterone level, acne score, LH/FSH, ovarian volume, and the number of follicles decreased significantly afterthe treatments without significant differences between the two groups. Significant increases were noted in TG, TCh, LDL, HDL, and AIP, and HDL level in group A as compared with group B ( < 0.001). FPG decreased in both groups, and wassignificantly lower in group B at 6 months ( < 0.05). BMI and WHR decreased in all the patients with insulin resistance aftercombination treatment with metformin ( < 0.05), but increased significantly in patients without insulin resistance ( < 0.05). Ingroup A, HOMA- IR significantly increased in patientswithout insulin resistance at 3 months ( < 0.05), whereas asignificant increase was not observed until 6 months ingroup B ( < 0.05).

CONCLUSIONSBoth ethinyl oestradiol/cyproterone tablets and desogestrel/ethinyl oestradioltablets can relieve the symptoms of PCOS, but it isadvisable to assess the risk of cardiovascular diseasebefore the treatments.

Objective To investigate the inhibitory effect of rhIFN-γ on human chronic myeloid leukemia cell line K562,and the impaction on the expression of CD123.Methods MTT method was used to test cell relative viability with rhIFN-γ at different concentrations.The expression of CD123 on K562 ceils was detected by flow cytometry.Results The relative inhibition of K562 cells proliferation was hampered when the cells were treated with rhIFN-γ for 72 h at the concentration of 5 x 10P ～ 108 U/L,respectively.However,rhIFN-γ at 2 x 105 U/L was benefit to K562 cells proliferation.After treatment with rhIFN-γ at 0,2 x 105 U/L and 107 U/L,the percentages of CD123 expression on K562 cells were (4.10 ± 1.46) ％,(7.2 ± 2.50) ％ as well as (21.6 ± 1.17) ％,respectively.Compared with the control group,107 U/L rhIFN-γ significantly increased the expression of CD123 on K562 cells (P＜0.05).Conclusion The effect of rhIFN-γ on the growth of K562 cells has two aspects (inhibition or proliferation),and it can increase the expression of CD 123.

The estrogen related receptor family member Esrrb (Estrogen related receptor β) is a gene that expresses in the early stage of embryo and plays an important role in the core pluripotent network. Its function has been analyzed in human and mouse, although no report so far related to pig. Therefore, to explore its mechanism of transcriptional regulation and expression pattern, we cloned a 3.3 kb pig ESRRB promoter by PCR and constructed the green fluorescence protein (GFP) reporter vector pE3.3. We used these vectors to study the ESRRB expression pattern in 293T, Hela and C2C12. Sequence was analyzed for regulatory elements that share homology to known transcription factor binding sites by TFSEARCH and JASPER program. Some pluripotency related genes such as SMAD, STAT3, MYC, KLF4 and ESRRB have been found within the 3.3 kb sequence by co-transfected pig ESRRB promoter and these potential regulators. We found that ESRRB only expressed in 293T and SMAD could activate ESRRB expression obviously. To determine the core promoter region, a series of ESRRB promoter fragments with gradually truncated 5'-end were produced by PCR and inserted into pGL3-Basic vector. After transient transfection into 293T, dual luciferase assay was used to measure these promoter activities. The result suggested that the core promoter of pig ESRRB located within -25 bp to -269 bp region. These results suggest that these transcription factor binding sites and the core promoter region may be essential for transcriptional regulation of pig ESRRB gene.
Animals ; Binding Sites ; Cloning, Molecular ; Estrogen Receptor beta ; genetics ; Genetic Vectors ; HeLa Cells ; Humans ; Mice ; Promoter Regions, Genetic ; Swine ; genetics ; Transcription Factors ; Transfection