In recent years,immunotherapy has become an important part of the treatment for advanced non-small cell lung cancer (NSCLC).Tumor cells can escape from the body's immune system by mediating various immune escape mechanisms,among which programmed death-1/programmed death ligand-1 (PD-1/ PD-L1) mediated immune escape plays an important role.Currently,chemotherapy,radiotherapy and molecular targeted therapy have certain limitations in the treatment of advanced NSCLC.Recent studies have found that the combined application of PD-1/PD-L1 inhibitor and other treatment methods has certain synergistic effect,thus enhances the anti-tumor effect and further prolongs the survival of patients.Immunotherapy brings not only changes in the treatment patterns of NSCLC,but also challenges in the screening of target population and the management of treatment-related adverse reactions.Summarizing the research progress on immune checkpoint inhibitors in the comprehensive treatment of advanced NSCLC can provide reference for the best treatment of NSCLC.

Objective To discuss the clinical value of tumor components of renal angiomyolipoma(AML)in predicting the efficacy of selective arterial embolization(SAE).Methods The clinical data of 20 patients with AML,who received SAE treatment at the General Hospital of Ningxia Medical University of China between August 2019 and April 2023,were retrospectively analyzed.The pre-SAE and post-SAE total tumor volume,fat volume(FV),non-fat volume(NFV),proportion of FV,proportion of NFV were calculated.Pearson correlation analysis was used to analyze the relationship between the initial volume of each tumor component and the tumor volume reduction rate.Multiple linear regression analysis was used to analyze the factors affecting the tumor volume reduction rate.Results The postoperative tumor volume,FV,and NFV were all significantly reduced when compared with their preoperative values(all P＜0.01).The postoperative proportion of FV was increased,and the postoperative proportion of NFV was decreased(P＜0.05).The postoperative tumor volume reduction value was closely correlated with the volume of tumor components and the presence of rupture(P＜0.05).Multivariate regression analysis revealed that the proportion of NFV was the independent risk factor for reduced tumor size.Conclusion After SAE,the proportion of NFV in AML is decreased.The preoperative measurement of this index can help clinicians to predict the postoperative tumor volume reduction ratio and to evaluate the postoperative efficacy of patients.

Microglia play a pivotal role in clearance of Aβ by degrading them in lysosomes, countering amyloid plaque pathogenesis in Alzheimer's disease (AD). Recent evidence suggests that lysosomal dysfunction leads to insufficient elimination of toxic protein aggregates. We tested whether enhancing lysosomal function with transcription factor EB (TFEB), an essential regulator modulating lysosomal pathways, would promote Aβ clearance in microglia. Here we show that microglial expression of TFEB facilitates fibrillar Aβ (fAβ) degradation and reduces deposited amyloid plaques, which are further enhanced by deacetylation of TFEB. Using mass spectrometry analysis, we firstly confirmed acetylation as a previously unreported modification of TFEB and found that SIRT1 directly interacted with and deacetylated TFEB at lysine residue 116. Subsequently, SIRT1 overexpression enhanced lysosomal function and fAβ degradation by upregulating transcriptional levels of TFEB downstream targets, which could be inhibited when TFEB was knocked down. Furthermore, overexpression of deacetylated TFEB at K116R mutant in microglia accelerated intracellular fAβ degradation by stimulating lysosomal biogenesis and greatly reduced the deposited amyloid plaques in the brain slices of APP/PS1 transgenic mice. Our findings reveal that deacetylation of TFEB could regulate lysosomal biogenesis and fAβ degradation, making microglial activation of TFEB a possible strategy for attenuating amyloid plaque deposition in AD.
Alzheimer Disease ; metabolism ; pathology ; Amyloid beta-Peptides ; metabolism ; Amyloid beta-Protein Precursor ; genetics ; metabolism ; Animals ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; chemistry ; genetics ; metabolism ; Brain ; metabolism ; Cells, Cultured ; Chloride Channels ; genetics ; metabolism ; Disease Models, Animal ; HEK293 Cells ; Humans ; Lysosomes ; genetics ; metabolism ; Mice ; Mice, Transgenic ; Microglia ; cytology ; metabolism ; Mutagenesis, Site-Directed ; Peptides ; analysis ; chemistry ; Protein Binding ; RNA Interference ; Sirtuin 1 ; antagonists & inhibitors ; genetics ; metabolism