Promotion of non-small cell lung cancer tumor growth by FHL2 via inducing angiogenesis and vascular permeability.

Background: Antiangiogenetic therapy is one of the effective strategies for non-small cell lung cancer (NSCLC) treatment. Four-and-a-half LIM-domain protein 2 (FHL2) serves as a key function in cell growth and metastasis of multiple cancers, but the role of FHL2 in NSCLC angiogenesis has not been intensely examined. Methods: FHL2 expression in NSCLC tissues and cell lines and its correlation with patients prognosis were investigated by using The Cancer Genome Atlas (TCGA) database and quantitative polymerase chain reaction (qPCR). Cell Counting Kit-8 (CCK-8) assay, EdU (5-ethynyl-2'-deoxyuridine) assay, and a xenograft model were used to investigate the effects of FHL2 on NSCLC progression in vitro and in vivo. CCK-8, wound-healing, Transwell invasion, tube formation, and permeability assays were performed to determine the roles of FHL2 in angiogenesis and vascular permeability. Vascular endothelial growth factor A (VEGFA) enzyme-linked immunosorbent assay (ELISA) assay, Western blot analysis, and MK-2206 were used to investigate the specific mechanism mediated by FHL2. Results: We demonstrated that FHL2 was significantly upregulated in NSCLC tissues and cell lines and was associated with poor prognosis. FHL2 overexpression enhanced the cell viability of NSCLC cells, as well as the proliferation, migration, invasion, and tube formation of human umbilical vein endothelial cells (HUVECs). In addition, we determined that FHL2 activated the AKT-mTOR signaling pathway in HUVECs by promoting VEGFA secretion from NSCLC cells, thereby inducing angiogenesis and vascular leakiness. We further confirmed that FHL2 also promoted NSCLC tumor growth in vivo. Conclusions: Our study revealed the role of FHL2 in NSCLC and the mechanism by which FHL2 promotes NSCLC tumorigenesis, providing novel insights into targeted therapy for NSCLC.

Modified surgical incision suturing technique in uniportal video-assisted thoracoscopic pulmonary resection.

Background: In recent years, single-hole thoracoscopic surgery technology is widely used in major medical centers and chest-specialized hospitals for the treatment of lung diseases. However, the single-hole minimally invasive surgery method focuses on one incision, and all surgical instruments need to pass through the same hole, resulting in repeated extrusion and tissue damage of the surgical incision. Therefore, we have improved the suture method of conventional surgical incision in order to reduce the probability of wound infection and dehiscence, promote early healing, and reduce the severity of postoperative wound scar, thereby enhancing the postoperative rapid recovery of patients. The purpose of this study is to explore the clinical efficacy of a modified surgical incision suture technique applied to uniportal thoracoscopic pulmonary resection. Methods: This study retrospectively analyzed 151 patients who were admitted to the Department of Thoracic Surgery and underwent pulmonary resection from January 2019 to October 2021 in the North District of Suzhou Municipal Hospital. The patients were divided into two groups according to the different surgical incision suture methods: a modified group and a conventional group. The postoperative general clinical indexes, incision infection rate, secondary suture rate, postoperative incision pain score, and the severity of postoperative incision scar were compared and analyzed between the two groups. Results: There were no statistically significant differences between the two groups in terms of chest tube duration or postoperative drainage and postoperative incision pain scores; the incision infection rate (1.3% vs. 6.7%, P<0.05), secondary suture rate (2.6% vs. 9.4%, P<0.05), and postoperative scar score (4.853 vs. 5.543, P=0.03) were better in the modified group than in the conventional group, and the differences between the two groups were statistically significant. Conclusions: Our modified suture method reduces the chance of infection and splitting and the severity of postoperative incision scar formation, promoting early healing. It can be safely and effectively applied to the incision suture of uniportal thoracoscopic pulmonary resection, enhancing the rapid postoperative recovery of patients.

Mebendazole induces apoptosis and inhibits migration via the reactive oxygen species-mediated STAT3 signaling downregulation in non-small cell lung cancer.

Background: The incidence and mortality of non-small cell lung cancer (NSCLC) are extremely high. Previous research has confirmed that the signal transducer and activator of the transcription 3 (STAT3) protein critically participate in the tumorigenesis of NSCLC. Mebendazole (MBZ) has exerts a larger number of pharmacological activities and has anticancer effects in lung cancer, but its mechanism of action remains unclear. This study thus aimed to clarify the impacts of MBZ on NSCLC cell. Methods: Cell proliferation, migration, and apoptosis were investigated via cell counting kit 8 (CCK-8) assay, Transwell assay, colony formation assay, wound-healing assay, and flow cytometry. Reactive oxygen species (ROS) were detected with a multifunctional microplate reader. Markers of cell migration and apoptosis were detected with Western blotting. The transcriptional activity of STAT3 was detected via luciferase assay. ROS scavenger N-acetylcysteine (NAC) was used to determine the effect of MBZ on NSCLC via ROS-regulated STAT3 inactivation and apoptosis. A xenograft model was constructed in vivo to investigate the role of MBZ in NSCLC tumor growth. Results: The findings demonstrated that MBZ inhibited NSCLC cell proliferation and migration while promoting apoptosis through triggering ROS generation. In addition, the Janus kinase 2 (JAK2)-STAT3 signaling pathway was abrogated with the treatment of MBZ. NAC could distinctly weaken MBZ-induced apoptosis and STAT3 inactivation. Moreover, MBZ inhibited the tumor growth of NSCLC in vivo. Conclusions: In summary, MBZ inhibited NSCLC cell viability and migration by inducing cell apoptosis via the ROS-JAK2-STAT3 signaling pathway. These data provide a theoretical basis for the use of MBZ in treating NSCLC.

Effects of preserving the bronchial artery on cough after thoracoscopic lobectomy.

BACKGROUND: The purpose of this prospective study was to explore the influence of both preoperative three-dimensional (3D) reconstruction and intraoperative preservation of the bronchial artery (BA) on postoperative cough after thoracoscopic lobectomy. METHODS: A total of 60 patients who had received a combination of thoracoscopic lobectomy and systematic lymph node dissection were included in this study. They were divided into two groups, namely the BA preservation group (Group A), and conventional surgical treatment group (Group B). In group A, we used Exoview software for 3D reconstruction of the BA before the operation and the BA was preserved during the operation. 3D reconstruction of the BA was not performed before surgery in group B. The incidence of postoperative cough, the Mandarin Chinese version of the Leicester cough questionnaire (LCQ-MC), physiological, psychological and social dimensions and total score of the two groups were compared and analyzed. RESULTS: The scores and total scores of LCQ-MC in group B were lower than those in group A one and two months after surgery. There were significant differences between the two groups in physiological and psychological dimensions and total scores (p < 0.05), but there was no significant difference in social dimension between the two groups (p > 0.05). The incidence of postoperative cough in group A (16.7%) was lower than that in group B (30%), while the difference was not statistically significant (p = 0.222). CONCLUSIONS: Preoperative 3D reconstruction and intraoperative preservation of the BA can reduce the severity of postoperative cough.

Utility of preoperative three-dimensional CT bronchography and angiography in uniportal video-assisted thoracoscopic anatomical lobectomy: a retrospective propensity score-matched analysis.

BACKGROUND: Personalized three-dimensional (3D) reconstruction can help surgeons to overcome technical challenges and variations of pulmonary anatomic structures in the performance of uniportal video-assisted thoracoscopic surgery (UVATS), thus improving the safety and efficacy of the procedure. This study aims to evaluate the utility of preoperative 3D-CT bronchography and angiography (3D-CTBA) with Exoview software in the assessment of anatomical variations of pulmonary vessels, and to analyze short-term surgical outcomes in patients undergoing UVATS lobectomy. METHODS: We retrospectively analyzed the data of 198 consecutive patients who underwent curative UVATS lobectomy between November 2019 and September 2020. The patients were divided into an "Exoview" group (n=53) and a "non-Exoview" group (n=145). We performed 1:1 propensity score matching and compared intraoperative and postoperative outcomes between the two groups. A subgroup analysis of 74 patients who underwent single-direction uniportal lobectomy was also conducted. Aberrant pulmonary vessel patterns related to the surgery were also examined. RESULTS: The operative time in the Exoview group was significantly shorter than that in the non-Exoview group, both before (145.7±33.9 vs. 159.5±41.6 minutes, P=0.032) and after (145.7±33.9 vs. 164.2±41.8 minutes, P=0.014) propensity score matching. The number of mediastinal lymph nodes dissected was higher in the Exoview group than in the non-Exoview group (8.19±6.89 vs. 5.78±3.3, P=0.024) after propensity score matching. Intraoperative blood loss showed a statistical difference between the Exoview and non-Exoview groups (60.4±45.4 vs. 100.8±83.9, P=0.009). Four types of arterial variations and 2 types of venous variations related to the surgery were observed among 8 patients (15%), which have rarely been reported before. CONCLUSIONS: Personalized preoperative 3D-CT bronchography and angiography helped to clearly visualize the pulmonary anatomical structures and could contribute to the safe and efficient performance of UVATS anatomical lobectomy.

Predictive factors of cough after uniportal video-assisted thoracoscopic pulmonary resection.

BACKGROUND: Cough is one of the shared complications after lung surgery. In this study, a prospective analysis was conducted for exploring the risk factors of persistent cough after uniportal video-assisted thoracoscopic pulmonary resection. METHODS: One hundred thirty-five patients with pulmonary nodules who underwent surgical treatment in the same surgical group from November 2019 to January 2020 were enrolled in this prospective study. The severity of cough and its impact on patients' quality of life before and after surgery were assessed by the Mandarin Chinese version of the Leicester cough questionnaire (LCQ-MC), and postoperative cough was tested by the cough visual analog scale (VAS) and cough symptom score (CSS). Risk factors of cough after pulmonary resection (CAP) were determined by univariate and multivariate logistic regression analysis. RESULTS: The incidence of postoperative cough was 24.4% (33 of 135 patients). Univariate analysis showed that gender (female), the surgical site (upper right), the resection (lobectomy), subcarinal lymph node dissection, postoperative acid reflux, length of hospitalization contributed to the development of CAP resection. Multivariate logistic regression analysis showed that the resection (lobectomy) (OR 3.590, 95% CI: 0.637-20.300, P=0.017), subcarinal lymph node dissection (OR 4.420, 95% CI: 1.342-14.554, P=0.001), postoperative acid reflux (OR 13.55, 95% CI: 3.186-57.633, P<0.001) and duration of anesthesia (over 153 minutes, OR 0.987, 95% CI: 0.978-0.997, P=0.011) were independent risk factors for postoperative cough. CONCLUSIONS: The application of uniportal video-assisted thoracoscopic techniques to several types of lung surgery are conducive to enhanced recovery after surgery (ERAS). Postoperative cough is related to an ocean of factors, the resection (lobectomy), subcarinal lymph node dissection, postoperative acid reflux, and duration of anesthesia (over 153 minutes) are independent high-risk factors for CAP resection. TRIAL REGISTRATION: This study was registered on ClinicalTrials.gov (NCT04204148).