[Research Progress on Localization of Pulmonary Nodules].

With the widespread adoption of low-dose computed tomography (LDCT) and advancements in computed tomography image resolution, the detection rate of pulmonary nodules, especially smaller ones, has significantly improved. The risk of developing malignant tumors increases with the pulmonary nodule diameter. Video-assisted thoracoscopic surgery (VATS) stands out as the preferred surgical method. The accurate localization of pulmonary nodules is crucial for the success of VATS and remains a significant challenge for thoracic surgeons. Currently, commonly employed localization methods include CT-guided percutaneous positioning, bronchoscope-guided positioning, intraoperative ultrasound positioning, augmented reality (AR), and 3D print-assisted positioning. This review explores recent research progress, highlights the strengths and weaknesses of various pulmonary nodule localization methods. The aim is to provide valuable insights for clinical applications and guide future developments in this field.

Co-treatment of betulin and gefitinib is effective against EGFR wild-type/KRAS-mutant non-small cell lung cancer by inducing ferroptosis.

Clinical trials suggest that non-small-cell lung cancer (NSCLC) patients with KRAS mutations and wild-type EGFR have reduced benefits from gefitinib treatment. Ferroptosis is a new form of cell death that plays an important role in mediating the sensitivity of EGFR-TIKs. Here, we explored the antitumor ability of gefitinib in combination with betulin to overcome drug resistance through ferroptosis in wild-type EGFR/KRAS-mutant NSCLC cells. A549 and H460 cells were treated with gefitinib and betulin, and cell viability, apoptosis, and migration ability were assessed using the CCK-8 assay, flow cytometry, and wound-healing assay, respectively. Several cell death inhibitors were used to study the form of cell death. Ferroptosis-related events were detected by performing reactive oxygen species (ROS) and iron level detection, malondialdehyde (MDA) assay, and glutathione (GSH) assay. EMT-associated proteins and ferroptosis-related proteins were detected by using western blotting. A xenograft model was constructed in vivo to investigate the role of the combination treatment of betulin and gefitinib in NSCLC tumor growth. Gefitinib in combination with betulin exhibited antagonistic effects on cellular viability and induced cell apoptosis. It also induced ROS accumulation, lipid peroxidation, and GSH depletion and induced ferroptosis-related gene expression. Moreover, ferroptosis inhibitors, but not inhibitors of other forms of cell death, abrogated the effect of gefitinib in combination with betulin. Moreover, it also inhibited the tumor growth of NSCLC in vivo. Our findings suggest that gefitinib in combination with betulin is a novel therapeutic approach to overcome gefitinib resistance in EGFR wild-type/KRAS-mutant NSCLC cells by inducing ferroptosis.

Retrovirus-Mediated Transfection of the Tissue-type Plasminogen Activator Gene Results in Increased Thrombolysis of Blood Clots.

Tissue-type plasminogen activator (tPA) is involved in the lysis of blood clots. In this study, we attempted to target thrombolysis and enhance blood clot lysis by generating a construct (pLEGFP-N1-tPA) to integrate tPA gene into the genome of different cell lines. pLEGFP-N1-tPA construct was generated and used to target the tPA gene in different cell lines. The thrombolytic effects mediated by the supernatant from transfected HeLa cells and Linx cells were assessed using plasma thrombus plates. Furthermore, enhanced green fluorescent protein (EGFP), which was fused to the tPA gene in the pLEGFP-N1-tPA construct, was analyzed under the fluorescent microscope to assess tPA localization. We also monitored tPA activity and expression in the transfected cell lines. As part of the study, we successfully generated the pLEGFP-N1-tPA construct. The sequence of this construct was verified and the construct was subsequently used to generate the PT67/pLEGFP-N1-tPA cell line. The pLEGFP-N1-tPA construct was also used to transfect HeLa cells and Linx cells. We observed that supernatants from transfected cells were capable of lysing thrombi. In addition, tPA activity and tPA concentration were elevated in the latter supernatants and tPA was rapidly and stably expressed in the transfected cell lines. These results reveal a potentially important thrombolytic role for tPA-targeted gene therapy following cardiac valve replacement.

microRNA-206 is involved in survival of hypoxia preconditioned mesenchymal stem cells through targeting Pim-1 kinase.

BACKGROUND: Overexpression of Pim-1 in stem/progenitor cells stimulated cell cycling and enhanced cardiac regeneration in vivo. We proposed that hypoxic preconditioning could increase survival of bone marrow mesenchymal stem cells (MSCs) via upregulation of Pim-1 and aimed to determine the microRNAs that modulate the expression of Pim-1. METHODS AND RESULTS: MSCs were subjected to hypoxia exposure. The expression of Pim-1 in MSCs was enhanced in a time-dependent manner, detected by quantitative PCR and western blot. miR-206 is predicted as one of the potential microRNAs that target Pim-1. The expression of miR-206 was decreased in hypoxic MSCs and reversely correlated with Pim-1 expression. Luciferase activity assay further confirmed Pim-1 as a putative target of miR-206. In addition, gain and loss-of-function studies with miR-206 mimics and inhibitors showed that inhibition of miR-206 in hypoxic MSCs promoted the migration ability of the cells, prevented cell apoptosis, and protected membrane potential of mitochondria, while the benefits were all blocked by Pim-1 inhibitor. In an acute model of myocardial infarction, transplanted hypoxic MSCs showed a significantly improved survival as compared with hypoxic MSCs overexpressing miR-206. CONCLUSIONS: Hypoxic preconditioning could increase short-term survival of bone marrow MSCs via upregulation of Pim-1, and miR-206 was one of the critical regulators in this process.

Pretreatment of Cardiac Stem Cells With Exosomes Derived From Mesenchymal Stem Cells Enhances Myocardial Repair.

BACKGROUND: Exosomes derived from mesenchymal stem cells (MSCs) were proved to boost cell proliferation and angiogenic potency. We explored whether cardiac stem cells (CSCs) preconditioned with MSC exosomes could survive and function better in a myocardial infarction model. METHODS AND RESULTS: DiI-labeled exosomes were internalized with CSCs. They stimulated proliferation, migration, and angiotube formation of CSCs in a dose-dependent manner. In a rat myocardial infarction model, MSC exosome-preconditioned CSCs had significantly better survival, enhanced capillary density, reduced cardiac fibrosis, and restored long-term cardiac function. MicroRNA profiling analysis revealed that a set of microRNAs were significantly changed in CSCs after MSC exosome treatment. CONCLUSIONS: Pretreatment of CSCs with MSC exosomes provided a promising strategy to improve survival and angiogenic potency of CSCs.

Preoperative ejection fraction determines early recovery of left ventricular end-diastolic dimension after aortic valve replacement for chronic severe aortic regurgitation.

BACKGROUND: In patients with chronic severe aortic regurgitation (AR), aortic valve replacement (AVR) has been proved to promote left ventricular (LV) remodeling, especially LV end-diastolic dimension (LVEDD) reduction. However, there is little research whether postoperative LVEDD could return to normal parameter after AVR. The objective of this study was to determine predictors for the recovery of dilated LVEDD early after AVR. METHODS: The echocardiographic data of 105 patients, who underwent AVR for chronic pure AR between January 2005 and December 2011, were analyzed at the preoperative (3-7 d), early (6-8 mo), and late (2-y) postoperative stages, retrospectively. According to the baseline level, LVEDD >70 mm or LV end-systolic dimension (LVESD) >50 mm or LVESD index >25 mm/m(2) were defined as severe LV dilation. Patients were then categorized into two groups (group 1: severe LV dilation; group 2: nonsevere LV dilation). RESULTS: In all patients, four-fifth of the reduction in LV dimension occurred at early (6-8 mo) postoperative stage. The patients in both groups had significant decreases in the LVEDD and LVESD early after AVR, with an additional but insignificant reduction at late postoperative stage. The ejection fraction (EF) in both groups significantly increased at either early or late stage. However, the LVEDD and LVESD in group 1 were larger than those in group 2, and the EF in group 1 was lower than that in group 2 at early postoperative stage. By multivariate analysis, we found that the preoperative EF was a good predictor for the recovery of dilated LVEDD early after AVR (P = 0.009). Receiver-operating characteristics analysis showed that EF >52% was the best cut-off value for the recovery of LVEDD. CONCLUSIONS: In patients with chronic pure AR, preoperative EF may be a good predictor for successful recovery of dilated LVEDD early after AVR.