Quantitative evaluation of endobronchial ultrasound elastography in the diagnosis of benign and malignant mediastinal and hilar lymph nodes.

OBJECTIVE: To compare the diagnostic value of different quantitative methods of endobronchial ultrasound elastography in benign and malignant mediastinal and hilar lymph nodes. METHODS: This retrospective study included patients who underwent endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for mediastinal and hilar lymph node enlargement in our hospital between January 2019 and August 2022. We compared different quantitative elastography parameters [red area ratio (RAR, lymph node red area/lymph node area), green area ratio (GAR, lymph node green area/lymph node area), blue area ratio (SAR, lymph node blue area/lymph node area), mixed area ratio (MAR, lymph node green area/lymph node area), blue-green lymph node area/lymph node area), strain rate ratio (SR), strain rate in the target lymph node (LPA), ratio of blue area to total lymph node area outside the center of the target lymph node (PAR), and average grey value (MGV)], in order to find the best quantitative evaluation method. RESULTS: A total of 244 patients (346 lymph nodes) were included in this study. All quantitative elastography parameters were statistically significant for the differentiation of benign and malignant lesions except the average grey value of the target lymph nodes. The area under the receiver operating characteristic curve of SAR was 0.872 (95% confidence interval: 0.83-0.91), the cutoff value was 0.409, and the sensitivity, specificity, positive and negative predictive values were 85.4%, 78.0%, 80.4%, and 83.4%, respectively. CONCLUSION: Compared with other types of quantitative analysis, SAR has a higher predictive significance for benign and malignant lymph nodes.

Quantitative analysis of endobronchial elastography combined with serum tumour markers of lung cancer in the diagnosis of benign and malignant mediastinal and hilar lymph nodes.

Purpose: In malignant tumours, elastography and serum tumour markers have shown high diagnostic efficacy. Therefore, we aimed to quantitatively analyse the results of endobronchial elastography combined with serum tumour markers of lung cancer to accurately distinguish benign and malignant mediastinal and hilar lymph nodes. Methods: Data of patients who underwent endobronchial ultrasound-guided transbronchial needle aspiration for mediastinal lymph node enlargement in our hospital between January 2018 and August 2022 were retrospectively collected. The characteristics of quantitative elastography and serum tumour markers were evaluated. Results: We enrolled 197 patients (273 lymph nodes). In the differential diagnosis of benign and malignant mediastinal and hilar lymph nodes, the stiffness area ratio (SAR), strain ratio (SR), and strain rate in lymph nodes were significant, among which SAR had the highest diagnostic value (cut-off value, 0.409). The combination of the four tumour markers had a high diagnostic value (AUC, 0.886). Three types of quantitative elastography indices combined with serum tumour markers for lung cancer showed a higher diagnostic value (AUC, 0.930; sensitivity, 83.5%; specificity, 89.3%; positive predictive value, 88.1%; negative predictive value, 85%) (p < 0.05). In the differential diagnosis of pathological types of lung cancer, different quantitative elastography indicators and serum tumour markers for lung cancer have different diagnostic significance for the differential diagnosis of lung cancer pathological types. Conclusion: The quantitative analysis of endobronchial ultrasound elastography combined with tumour markers can improve the diagnosis rate of benign and malignant mediastinal and hilar lymph nodes, help guide the puncture of false negative lymph nodes, and reduce the misdiagnosis rate.

Risk factors for acute exacerbation of interstitial lung disease during chemotherapy for lung cancer: a systematic review and meta-analysis.

Purpose: The aim of this study was to investigate the risk factors for acute exacerbation (AE) of interstitial lung disease caused by chemotherapy for lung cancer. Methods: We searched PubMed, Embase, and The Cochrane Library databases from the establishment of each database to April 2023. Eligible studies were included, and the data on risk factors related to AE caused by chemotherapy in interstitial lung disease were extracted. Results: A total of 878 articles were retrieved and 21 met the inclusion criteria. The studies included 1,275 patients with lung cancer combined with interstitial lung disease. The results of the meta-analysis showed four significant risk factors for AE of interstitial lung disease, namely age < 70 years (odds ratio [OR]: 1.98, 95% confidence interval [CI]: 1.05-3.72), forced vital capacity (FVC) (MD=-9.33, 95% CI: -13.7-4.97), usually interstitial pneumonia (UIP) pattern on computed tomography (CT) (OR: 2.11, 95% CI: 1.43-3.11), and serum surfactant protein D (SP-D) (SMD: 0.35, 95% CI: 0.03-0.67). Conclusion: When patients with lung cancer complicated with interstitial lung disease are aged < 70 years, have a UIP pattern on CT, have lower FVC values, and have higher serum levels of SP-D, chemotherapy should be carried out with care.

Apigenin Enhanced Antitumor Effect of Cisplatin in Lung Cancer via Inhibition of Cancer Stem Cells.

Cancer stem cell theory has been proposed to explain tumor heterogeneity and the carcinogenesis process. Highly tumorigenic lung cancer stem cells develop resistance to cisplatin (CDDP), a common chemotherapy drug. Herein, we attempted to clarify whether apigenin (API) can improve the antitumor efficiency of CDDP in lung cancer using cancer stem cells. Lung cancer stem cells were identified as CD 133 positive cancer cells in non-small cell lung cancer (NSCLC) A549, H1299 cells and CDDP-resistant NSCLC A549R cells. The cytotoxic effect of API was measured in CDDP-treated A549, H1299, and A549R cells. API repressed CD 133 positive cells and enhanced the antitumor effect of CDDP in A549, H1299, and A549R cells. The synergistic antitumor effect of API and CDDP was blocked by addition of the p53 inhibitor Pifithrin-α, and siRNA targeting the p53 gene in A549R cells. Furthermore, API eliminates CDDP-induced CSC via p53, since A549R cells lacking p53 and Pifithrin-α addition derepressed the decrease in CD 133 positive cells after API treatment in CDDP-treated A549 and A549R cells. The findings indicate that API might eliminate cancer stem cells and enhance the antitumor effects of CDDP in NSCLC via p53.

The roles of synovial hyperplasia, angiogenesis and osteoclastogenesis in the protective effect of apigenin on collagen-induced arthritis.

Apigenin (API) is a plant flavone that is known to exert a protective effect in rheumatoid arthritis (RA), which is a chronic autoimmune disease. However, the molecular mechanism for API's protective effect against RA is still unclear. Here, a collagen-induced arthritis (CIA) mouse model was used to assess the protective effect of API on RA. Histomorphological studies, immunohistochemistry, RT-PCR, and western blot were conducted to elucidate the roles of synovial hyperplasia, angiogenesis, and osteoclastogenesis in the protective effect of API on RA. Fibroblast-like synoviocytes (FLSs) were isolated to measure the effect of API on FLS proliferation and apoptosis. API exhibited a significant protective effect in CIA mice in a dose- and time-dependent manner. An increase in apoptosis and decrease in proliferation were observed after the API treatment in FLSs, suggesting that API might inhibit synovial hyperplasia. Moreover, CIA angiogenesis was repressed by API via down-regulation of VEGF and VEGFR. Furthermore, API regulated the osteoclastogenesis-associated RANKL/RANK/OPG system in CIA mice. Therefore, API inhibits CIA by repressing synovial hyperplasia, angiogenesis, and osteoclastogenesis. This suggested that API might be a putative low toxicity candidate drug for RA treatment.

Gain-of-function KCNH2 mutations in patients with Brugada syndrome.

BACKGROUND: Brugada syndrome (BrS) is an inherited disease characterized by right precordial ST segment elevation on electrocardiograms (ECGs) that predisposes patients to sudden cardiac death as a result of polymorphic ventricular tachyarrhythmia or ventricular fibrillation (VF). In BrS patients, except for SCN5A, mutations in other responsible genes are poorly elucidated. METHODS AND RESULTS: We identified 4 KCNH2 mutations, T152I, R164C, W927G, and R1135H, in 236 consecutive probands with BrS or Brugada-like ECG. Three of these mutation carriers showed QTc intervals shorter than 360 milliseconds and 1 experienced VF. We performed patch-clamp analyses on I(Kr) reconstituted with the KCNH2 mutations in Chinese hamster ovary cells and compared the phenotypes of the patients with different genotypes. Three mutations, R164C, W927G, and R1135H, increased I(Kr) densities. Three mutations, T152I, R164C, and W927G, caused a negative shift in voltage-dependent activation curves. Only the R1135H mutant channel prolonged the deactivation time constants. We also identified 20 SCN5A and 5 CACNA1C mutation carriers in our cohort. Comparison of probands' phenotypes with 3 different genotypes revealed that KCNH2 mutation carriers showed shorter QTc intervals and SCN5A mutation carriers had longer QRS durations. CONCLUSIONS: All KCNH2 mutations that we identified in probands with BrS exerted gain-of-function effects on I(Kr) channels, which may partially explain the ECG findings in our patients.