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1.
Tuberculosis (Edinb) ; 146: 102496, 2024 May.
Article in English | MEDLINE | ID: mdl-38401266

ABSTRACT

BACKGROUND: Tuberculosis (TB) is not only related to infection but also involves immune factors. This study explores the changes in T-lymphocyte subsets in children with TB who are human immunodeficiency virus (HIV)-negative and examines their relationship using chest computed tomography (CT) scans. Additionally, the study identifies risk factors for severe TB (STB) in children and establishes relevant risk prediction models. METHODS: We recruited 235 participants between 2018 and 2022, comprising 176 paediatric patients with TB who were HIV-negative and 59 age-matched children with bacterial community-acquired pneumonia (CAP). We quantitatively analysed and compared T-lymphocyte subsets between the two groups and among different types of TB infection. Both univariate and multivariate analyses of clinical and laboratory characteristics were conducted to identify independent risk factors for STB in children and to establish a risk prediction model. RESULTS: The absolute counts of CD3, CD4 and CD8 T-cells in children with TB infection decreased significantly compared with bacterial CAP. The percentage of CD8 T-cells increased, whereas the percentage of CD4 T-cells did not change significantly. The absolute count of CD3, CD4 and CD8 T-cells in extrapulmonary TB (EPTB) was significantly higher than in extra-respiratory TB, with unchanged subset percentages. According to chest CT lesion classification, CD4 T-cell counts decreased significantly in S3 compared with S1 or S2, with no significant change in CD3 and CD8 T-cell counts and percentages. No significant differences were observed in lymphocyte subset counts and percentages between S1 and S2. Univariate analyses indicated that factors such as age, symptom duration, white blood cell count, platelet count, neutrophil-to-lymphocyte ratio (NLR), erythrocyte sedimentation rate, prealbumin level, albumin level, globulin level, albumin/globulin (A/G) ratio, high-sensitivity C-reactive protein (Hs-CRP) level and CD4 and CD8 T-cell counts are associated with STB. Multivariate logistic regression analysis revealed that age, Hs-CRP level, NLR, symptom duration and A/G ratio are independent risk factors for STB in children. Increased age, Hs-CRP levels and NLR, along with decreased A/G, correlate with increased susceptibility to STB. A nomogram model, based on these independent risk factors, demonstrated an area under the receiver operating characteristics curve of 0.867 (95% CI: 0.813-0.921). Internal verification confirmed the model's accuracy, with the calibration curve approaching the ideal and the Hosmer-Lemeshow goodness-of-fit test showing consistent results (χ2 = 12.212, p = 0.142). CONCLUSION: In paediatric patients with TB, the absolute counts of all lymphocyte subsets were considerably reduced compared with those in patients with bacterial CAP. Clinicians should consider the possibility of EPTB infection in addition to respiratory infections in children with TB who have higher CD3, CD4 and CD8 T-cell counts than the ERTB group. Furthermore, CD4 T-cell counts correlated closely with the severity of chest CT lesions. Age, symptom duration, A/G ratio, Hs-CRP level and NLR were established as independent risk factors for STB. The nomogram model, based on these factors, offers effective discrimination and calibration in predicting STB in children.


Subject(s)
Globulins , HIV Infections , Latent Tuberculosis , Mycobacterium tuberculosis , Tuberculosis , Humans , Child , C-Reactive Protein , T-Lymphocyte Subsets , Tuberculosis/diagnosis , Risk Factors , Lymphocyte Subsets , Lymphocyte Count
2.
Oncotarget ; 8(18): 30252-30264, 2017 May 02.
Article in English | MEDLINE | ID: mdl-28415819

ABSTRACT

Tamoxifen is still the most commonly used endocrine therapy drug for estrogen receptor (ER)-positive breast cancer patients and has an excellent outcome, but tamoxifen resistance remains a great impediment to successful treatment. Recent studies have prompted an anti-tumor effect of aspirin. Here, we demonstrated that aspirin not only inhibits the growth of ER-positive breast cancer cell line MCF-7, especially when combined with tamoxifen, but also has a potential function to overcome tamoxifen resistance in MCF-7/TAM. Aspirin combined with tamoxifen can down regulate cyclinD1 and block cell cycle in G0/G1 phase. Besides, tamoxifen alone represses c-myc, progesterone receptor (PR) and cyclinD1 in MCF-7 cell line but not in MCF-7/TAM, while aspirin combined with tamoxifen can inhibit the expression of these proteins in the resistant cell line. When knocking down c-myc in MCF-7/TAM, cells become more sensitive to tamoxifen, cell cycle is blocked as well, indicating that aspirin can regulate c-myc and cyclinD1 proteins to overcome tamoxifen resistance. Our study discovered a novel role of aspirin based on its anti-tumor effect, and put forward some kinds of possible mechanisms of tamoxifen resistance in ER-positive breast cancer cells, providing a new strategy for the treatment of ER-positive breast carcinoma.


Subject(s)
Aspirin/pharmacology , Breast Neoplasms/metabolism , Cyclin D1/metabolism , Drug Resistance, Neoplasm/drug effects , Proto-Oncogene Proteins c-myc/metabolism , Receptors, Estrogen/metabolism , Tamoxifen/pharmacology , Antineoplastic Agents, Hormonal/pharmacology , Biomarkers , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Synergism , Female , Humans , Hydroxytestosterones/pharmacology
3.
Asian Pac J Trop Med ; 6(2): 150-2, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23339919

ABSTRACT

OBJECTIVE: To explore the expression of Annexin II and its relationship with the cell differentiation, proliferation in lung cancer. METHODS: RT-PCR and Western blot assays were used to detect the expression of Annexin II in lung cancer tissues and cell lines. RESULTS: Annexin II was significantly up-regulated in lung cancer tissues, and in lung cancer cell lines, Annexin II had higher mRNA and protein expressions. CONCLUSIONS: Annexin II is up-regulated in lung cancer, suggesting that the Annexin II has a potential value in the human lung cancer.


Subject(s)
Annexin A2/biosynthesis , Lung Neoplasms/metabolism , Aged , Analysis of Variance , Annexin A2/analysis , Annexin A2/genetics , Annexin A2/metabolism , Blotting, Western , Cell Differentiation/physiology , Cell Growth Processes/physiology , Cell Line, Tumor , Female , Humans , Lung Neoplasms/chemistry , Lung Neoplasms/pathology , Male , Middle Aged , RNA, Messenger/analysis , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain Reaction , Up-Regulation
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