NSCLC (non-small-cell lung cancer) is an aggressive form of lung cancer and accompanies high morbidity and mortality. This study investigated the function and associated mechanism of MMP10 during radiotherapy of NSCLC. MMP10 expression in patients and their overall survival rate were assessed through GEPIA. Protein expression was tested by western blotting. Radioresistance was detected in vitro by apoptosis and clonogenic assay. The extent of DNA damage and repair was revealed by the comet test and γH2AX foci test. High MMP10 levels in specimens of lung adenocarcinoma were related to poor patient outcomes. Clonogenic and apoptosis assays revealed that MMP10 knockdown in A549 cells initiated radiosensitization. Furthermore, MMP10 siRNA increased damage to the DNA in NSCLC cells, while MMP10 was observed to participate in DNA damage repair post-ionizing radiation. Thus, after irradiation, MMP10 plays an essential role in NSCLC through the repair pathway of DNA damage; regulating MMP10 for NSCLC radiosensitivity might have potential treatment implications in radiotherapy of NSCLC.

The role of TLR4 (toll like receptor 4), a key molecule of the classical innate immune pathway, in individual tumors requires further exploration. In this study, numerous databases and tools, such as TCGA, GTEx, cBioportal, GSCALite, and GDSC, were utilized to systematically analyze the prognostic and immunological potential of TLR4 in tumors. The expression levels and mutational dynamics of TLR4 in pan-cancer were investigated. The prognostic potential of TLR4 was analyzed using Kaplan-Meier (KM) analysis. Results showed the levels of TLR4 in tumor tissues were significantly lower as compared to those in normal tissues in most cancers and were strongly correlated with the patient’s outcomes. The mutant genes associated with TLR4 were mainly enriched in the PI3K-AKT pathway. This could be a potential pathway for radiotherapy to activate the tumor immune microenvironment via TLR4/MAP. In tumors, the TLR4 mutations were closely associated with the M1/M2 polarization of macrophages. TLR4 and its ligand CD14 were significantly negatively associated with immunosuppressed MDSCs and TAM M2. The intervention of TLR4-dependent signaling pathways might be a promising strategy to reduce tolerance to ICB treatment in the post-immune era. In conclusion, this study expands the potential of TLR4 as an immune target in tumor therapy.

Background. The correct surgical position is very important in the treatment of peroral endoscopic myotomy (POEM) for achalasia, which can make the procedure safer and more efficient. Currently, there are two commonly used positions: the supine position with the right shoulder raised and the left lateral position. This study aims to evaluate the differences in the safety and efficacy of these two positions. Methods. We conducted a retrospective study of 702 patients with achalasia undergoing POEM from December 2010 to December 2020. These patients were divided into the supine position with the right shoulder raised group ( n = 579 ) and the left lateral position group ( n = 123 ). The efficacy of POEM and adverse events were analyzed. Results. The clinical characteristics were similar in both groups, and there were no significant differences between the two groups in the Eckardt score change, lower esophageal sphincter (LES) basal pressure or residual pressure after POEM (all p > 0.05 ). The mean operative time in the supine position with the right shoulder raised group was significantly shorter than that in the left lateral position group (43.5 min vs. 54.6 min, respectively, p < 0.001 ). In addition, the differences between the two groups in terms of gas-related complications, such as pneumoperitoneum, pneumomediastinum, and subcutaneous emphysema were statistically significant (all p < 0.05 ). Conclusions. The efficacy of POEM was comparable between the two groups. However, the supine position with the right shoulder raised significantly reduced the operative time and the rate of procedure-related adverse events, especially gas-related complications.