A combined diagnostic model based on circulating tumor cell in patients with solitary pulmonary nodules.

BACKGROUND: Although many prediction models in diagnosis of solitary pulmonary nodules (SPNs) have been developed, few are widely used in clinical practice. It is therefore imperative to identify novel biomarkers and prediction models supporting early diagnosis of SPNs. This study combined folate receptor-positive circulating tumor cells (FR+ CTC) with serum tumor biomarkers, patient demographics and clinical characteristics to develop a prediction model. METHODS: A total of 898 patients with a solitary pulmonary nodule who received FR+ CTC detection were randomly assigned to a training set and a validation set in a 2:1 ratio. Multivariate logistic regression was used to establish a diagnostic model to differentiate malignant and benign nodules. The receiver operating curve (ROC) and the area under the curve (AUC) were calculated to assess the diagnostic efficiency of the model. RESULTS: The positive rate of FR+ CTC between patients with non-small cell lung cancer (NSCLC) and benign lung disease was significantly different in both the training and the validation dataset (p < 0.001). The FR+ CTC level was significantly higher in the NSCLC group compared with that of the benign group (p < 0.001). FR+ CTC (odds ratio, OR, 95% confidence interval, CI: 1.13, 1.07-1.19, p < 0.0001), age (OR, 95% CI: 1.06, 1.01-1.12, p = 0.03) and sex (OR, 95% CI: 1.07, 1.01-1.13, p = 0.01) were independent risk factors of NSCLC in patients with a solitary pulmonary nodule. The area under the curve (AUC) of FR+ CTC in diagnosing NSCLC was 0.650 (95% CI, 0.587-0.713) in the training set and 0.700 (95% CI, 0.603-0.796) in the validation set, respectively. The AUC of the combined model was 0.725 (95% CI, 0.659-0.791) in the training set and 0.828 (95% CI, 0.754-0.902) in the validation set, respectively. CONCLUSIONS: We confirmed the value of FR+ CTC in diagnosing SPNs and developed a prediction model based on FR+ CTC, demographic characteristics, and serum biomarkers for differential diagnosis of solitary pulmonary nodules.

Age-dependent genomic characteristics and their impact on immunotherapy in lung adenocarcinoma.

BACKGROUND: The incidence of lung cancer tends to be younger, and adenocarcinoma is the main histological type. Even patients with the same tumor type may have significant differences in clinical features, tumor microenvironment and genomic background at different ages. Immune checkpoint inhibitors (ICIs) have been shown to improve clinical outcomes in patients with lung adenocarcinoma (LUAD). However, differences in ICI efficacy between older and younger patients are unknown. Our study aimed to explore the relationship between age and immunotherapy in LUAD. METHODS: In our study, 1313 resected LUAD patients in our hospital were divided into young (age ≤ 50) and old groups (age > 50), and the clinical characteristic differences between them were analyzed. Of these, next-generation sequencing (NGS) was performed on the 311 cases. In addition, immune-related signatures of 508 LUAD patients were analyzed by TCGA RNA expression data. Then, we validated genomic and clinical information of 270 LUAD samples in the MSKCC cohort. RESULTS: ERBB2 and EGFR gene mutations were significantly different between the two groups, and the gene mutation number in the old group was significantly higher than that in the young group. In addition, immune-related signatures of LUAD patients were analyzed by TCGA RNA expression data, which indicated that the patients in the old group might have a better immune microenvironment. Then, we validated the MSKCC cohort and found that the TMB of the old group was significantly higher than that of the young group, and the OS of immunotherapy was longer in the old group. CONCLUSION: Our study was the first to analyze the differences in the genomic landscape and immune-related biomarkers between the young and old groups of LUAD patients and found that the old group had a better efficacy of immunotherapy, providing a reference for the study design and treatment of patients with LUAD.

[Efficacy of sublingual immunotherapy in children with allergic rhinitis].

OBJECTIVE: To evaluate the efficacy of sublingual immunotherapy with dermatophagoides farina drops on children with allergic rhinitis. METHOD: This was retrospective study analyzing the efficacy of dermatophaguides farinae drops SLIT in 110 patients (aged 4-14 years old) with house dust mites induced allergic rhinitis (without asthma). All the patients were divided into the SLIT group (n = 60) and drug group (n = 50). Patients in SLIT group received sublingual immunotherapy combined with symptomatic medication, and patients in drug group only received symptomatic medication. We recorded and evaluated the total nasal symptom scores (TNSS), total medication scores (TMS) and visual analogue scale (VAS) of the 2 groups at three time points, before the treatment, and the treatment for 1-year and 2-year. RESULT: After 1-year and 2-year treatment, compared with drug group, TMS, TNSS and VAS in SLIT group decreased significantly (P < 0.01). When compared with baseline, we got the similar result as compared with drug group. Besides, the TMS of drug group increased significantly after treatment (P < 0.01). And no significant difference was observed in TNSS and VAS. In addition, there was significant difference in the Proportion of patients withdrawing symptomatic medication in SLIT group and drug group (68.33%,16.00%, respectively; P < 0.01). There were 4 local adverse reactions occurred during the treatment and no serious adverse events occurred. CONCLUSION: Sublingual immunotherapy with Dermatophagoides farinae drops showed significant clinical efficacy in children with allergic rhinitis comparing with pharmacotherapy.

[Effect of okam on inflammation and remodeling of airway of mice with ovalbumin induced asthma].

OBJECTIVE: To investigate the effect of okam on inflammation and remodeling of airway in mice with ovalbumin (OVA) induced asthma. METHODS: Thirty-two mice of Kunming strain were divided into four groups randomly: model group, glucocorticoid inhalation group, okam group and control group, with 8 mice in each group. The asthmatic mice model was reproduced by combined injection and aerosol inhalation of OVA. The mice in model group received normal saline (0.3 ml) gavage daily. The mice in glucocorticoid inhalation group received budesonide (0.4 ml, 200 mug) and normal saline (3.6 ml) inhalation. The mice in okam group were gavaged with okam daily (50 mg/kg). The controls were given normal saline instead of OVA sensitization. All mice were sacrificed 42 days later, followed by lavage of tracheo-bronchial tree of the right lung, and the right lung was saved for pathological examination. The total cell number and differentiation in bronchoalveolar lavage fluid (BALF) were counted under microscope. The expression of interferon-gamma (IFN-gamma), interleukin-4 (IL-4) in BALF were assessed by enzyme linked immunosorbent assay (ELISA). The histological changes in the bronchi and alveoli were evaluated after hematoxylin and eosin (HE) staining. The expression of matrix metalloproteinase-9 (MMP-9) as well as the tissue inhibitor of metalloproteinase-1 (TIMP-1) were determined by immunohistochemistry. RESULTS: Compared with the model group, the total cell count and IL-4 level in BALF, and the score of pathological changes in the broncho-alveolar tissue in okam group or glucocorticoid inhalation group were lower significantly, and the IFN-gamma level elevated markedly (all P<0.01). The MMP-9, TIMP-1 expression in glucocorticoid inhalation group and the TIMP-1 expression in okam group were decreased greatly (P<0.05 or P<0.01). All of above indexes showed marked differences between control group and okam group (P<0.05 or P<0.01). There were significant changes in the total cell count, IFN-gamma, pathological changes, MMP-9 and TIMP-1 between the glucocorticoid inhalation group and the okam group (P<0.05 or P<0.01). CONCLUSION: Okam may alleviate inflammation of the bronchial and degrade the development of airway remodeling to some degree.

[Values of impulse oscillometry for pulmonary function and adhesion molecules in childhood asthma].

OBJECTIVE: Impulse oscillometry (IOS) is a novel technique for the evaluation of pulmonary function. Soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) are definitive indicators for the severity of asthma. This study aimed to explore the relationship of IOS pulmonary function with sICAM-1 and sVCAM-1, and their values in childhood asthma. METHODS: IOS via Master Screen System for pulmonary function was performed in 40 children with acute asthma and 25 healthy children. Twenty-three of 40 children with acute asthma were re-tested for IOS pulmonary function at remission. sICAM-1 and sVCAM-1 levels were measured in 23 children with acute asthma, 20 asthmatic children at remission and 16 healthy children. RESULTS: The parameters of IOS pulmonary function, R5, R20, R5-R20, X5, Fres and Zrs in children with acute asthma were significantly higher than in asthmatic children at remission and in normal controls (q= 2.91-15.61, P < 0.01 or 0.05). There were significant differences in R5, R5-R20, Fres and Zrs between the asthmatic children at remission and normal controls (q= 3.08- 9.19, P < 0.01 or 0.05). sICAM-1 and sVCAM-1 levels in children with acute asthma were significantly higher than in asthmatic children at remission and in normal controls (q= 6.23-26.15, P < 0.01). The asthmatic children at remission had higher levels of sICAM-1 and sVCAM-1 than the normal controls (q=16.86, 12.46, P < 0.01). R5-R20 positively correlated with sICAM-1 and sVCAM-1 in children with acute asthma (r=0.45, 0.57, P <0.05). CONCLUSIONS: IOS for pulmonary function and sICAM-1 and sVCAM-1 may be used to evaluate the severity and therapeutic effects of childhood asthma. A correlation exists between IOS pulmonary function and sICAM-1 and sVCAM-1.