Objective To explore the relationship between circadian rhythm genes and the occurrence, development, prognosis, and tumor microenvironment (TME) of lung adenocarcinoma (LUAD). Methods The Cancer Genome Atlas data were used to evaluate the expression, copy number variation, and somatic mutation frequency of circadian gene sets in LUAD. Gene ontology, Kyoto encyclopedia of genes and genomes, and gene set enrichment analysis were used to explore the potential mechanisms by which circadian rhythm genes affected LUAD progression. Cox regression, least absolute shrinkage and selection operator regression, support vector machine recursive feature elimination, and random forest screened circadian genes and established prognostic models, and on this basis constructed nomogram to predict patients’ 1-, 3-, and 5-year survival rates. Kaplan-Meier survival curves, receiver operating characteristic (ROC) curves, and time-dependent ROC curves were drawn to evaluate the predictive ability of the model, and the external dataset of GEO further verified the prognostic value of the prediction model. In addition, we evaluated the association of the prognostic model with immune cells and immune checkpoint genes. Single cell RNA sequencing (scRNA-seq) analysis was used to explore the molecular characteristics between prognostically relevant circadian genes and different immune cell populations in TME. Results Differentially expressed circadian rhythm genes were mainly enriched in biological processes related to cGMP-PKG signaling pathway, lipid and atherosclerosis, and JAK-STAT signaling pathway. Seven circadian rhythm genes: LGR4, CDK1, KLF10, ARNTL2, RORA, NPAS2, PTGDS were screened out, and a RiskScore model was established. According to the median RiskScore, samples were divided into a high-risk group and a low-risk group. Compared with patients in the low-risk group, patients in the high-risk group showed a poorer prognosis (P<0.001). Immunological characterization analysis showed that there were differences in the infiltration of multiple immune cells between the low-risk group and high-risk group. Most immune checkpoint genes had higher expression levels in the high-risk group than those in the low-risk group, and RiskScore was positively correlated with the expression of CD276, TNFSF4, PDCD1LG2, CD274, and TNFRSF9, and negatively correlated with the expression of CD40LG and TNFSF15. The scRNA-seq analysis showed that RORA and KLF10 were mainly expressed in natural killer cells. Conclusion The prognostic model based on seven feature circadian rhythm genes has certain predictive value for predicting survival of LUAD patients. Dysregulated expression of circadian genes may regulate the occurrence, progression as well as prognosis of LUAD through affecting TME, which provides a possible direction for finding potential strategies for treating LUAD from the perspective of mechanism by which circadian disorder affects immune cells.

Objective To determine the prognostic biomarkers and new therapeutic targets of the lung adenocarcinoma (LUAD), based on which to establish a prediction model for the survival of LUAD patients. Methods An integrative analysis was conducted on gene expression and clinicopathologic data of LUAD, which were obtained from the UCSC database. Subsequently, various methods, including screening of differentially expressed genes (DEGs), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene Set Enrichment Analysis (GSEA), were employed to analyze the data. Cox regression and least absolute shrinkage and selection operator (LASSO) regression were used to establish an assessment model. Based on this model, we constructed a nomogram to predict the probable survival of LUAD patients at different time points (1-year, 2-year, 3-year, 5-year, and 10-year). Finally, we evaluated the predictive ability of our model using Kaplan-Meier survival curves, receiver operating characteristic (ROC) curves, and time-dependent ROC curves. The validation group further verified the prognostic value of the model. Results The different-grade pathological subtypes' DEGs were mainly enriched in biological processes such as metabolism of xenobiotics by cytochrome P450, natural killer cell-mediated cytotoxicity, antigen processing and presentation, and regulation of enzyme activity, which were closely related to tumor development. Through Cox regression and LASSO regression, we constructed a reliable prediction model consisting of a five-gene panel (MELTF, MAGEA1, FGF19, DKK4, C14ORF105). The model demonstrated excellent specificity and sensitivity in ROC curves, with an area under the curve (AUC) of 0.675. The time-dependent ROC analysis revealed AUC values of 0.893, 0.713, and 0.632 for 1-year, 3-year, and 5-year survival, respectively. The advantage of the model was also verified in the validation group. Additionally, we developed a nomogram that accurately predicted survival, as demonstrated by calibration curves and C-index. Conclusion We have developed a prognostic prediction model for LUAD consisting of five genes. This novel approach offers clinical practitioners a personalized tool for making informed decisions regarding the prognosis of their patients.

Objective To systematically review the efficacy and safety of traditional Chinese patent medicines for tonifying lung and kidney combined with conventional Western medicine in the treatment of stable chronic obstructive pulmonary disease(COPD)by network Meta-analysis.Methods PubMed,Embase,Web of Science,Cochrane Library,CNKI,WanFang Data,VIP and SinoMed databases were electronically searched to collect randomized controlled trials(RCTs)of traditional Chinese patent medicines for tonifying lung and kidney to intervene in the stable phase of COPD from inception to June 25,2024.Two reviewers independently screened the literature,extracted data,and assessed the risk of bias in the included studies.Meta-analysis was performed by using RevMan 5.4 software.The network Meta-analysis was then performed using Stata 15.0 software.Results A total of 74 studies were included,involving 7 kinds of traditional Chinese patent medicines and 3 738 patients.The results of direct Meta-analysis showed that Chinese patent medicines combined with conventional Western medicine were superior to conventional Western medicine(P＜0.001).The network Meta-analysis results showed that,Huanglong Kechuan capsules combined with conventional Western medicine had the best effect in improving the overall clinical efficacy.Heche Dazao capsules combined with conventional Western medicine had the best effect in improving FEV1.Yifei capsules combined with conventional Western medicine had the best effect in improving FVC.Jinshuibao capsules combined with conventional Western medicine had the best effect in improving FEV1/FVC.Jinshuibao capsules combined with conventional Western medicine had the best effect in increasing 6MWD.Yifei capsules combined with conventional Western medicine had the best effect in reducing COPD scores.Compared with conventional Western medicine,traditional Chinese patent medicines for tonifying lung and kidney combined with conventional Western medicine did not increase the occurrence of adverse drug reactions.Conclusion Different traditional Chinese patent medicines for tonifying the lung and kidney combined with conventional Western medicine have their advantages in the intervention of COPD in the stable stage,and have a better safety profile.Due to the limited quality and quantity of the included studies,more high-quality studies are needed to verify the above conclusion.

Objective To systematically review the efficacy and safety of traditional Chinese patent medicines for tonifying lung and kidney combined with conventional Western medicine in the treatment of stable chronic obstructive pulmonary disease(COPD)by network Meta-analysis.Methods PubMed,Embase,Web of Science,Cochrane Library,CNKI,WanFang Data,VIP and SinoMed databases were electronically searched to collect randomized controlled trials(RCTs)of traditional Chinese patent medicines for tonifying lung and kidney to intervene in the stable phase of COPD from inception to June 25,2024.Two reviewers independently screened the literature,extracted data,and assessed the risk of bias in the included studies.Meta-analysis was performed by using RevMan 5.4 software.The network Meta-analysis was then performed using Stata 15.0 software.Results A total of 74 studies were included,involving 7 kinds of traditional Chinese patent medicines and 3 738 patients.The results of direct Meta-analysis showed that Chinese patent medicines combined with conventional Western medicine were superior to conventional Western medicine(P＜0.001).The network Meta-analysis results showed that,Huanglong Kechuan capsules combined with conventional Western medicine had the best effect in improving the overall clinical efficacy.Heche Dazao capsules combined with conventional Western medicine had the best effect in improving FEV1.Yifei capsules combined with conventional Western medicine had the best effect in improving FVC.Jinshuibao capsules combined with conventional Western medicine had the best effect in improving FEV1/FVC.Jinshuibao capsules combined with conventional Western medicine had the best effect in increasing 6MWD.Yifei capsules combined with conventional Western medicine had the best effect in reducing COPD scores.Compared with conventional Western medicine,traditional Chinese patent medicines for tonifying lung and kidney combined with conventional Western medicine did not increase the occurrence of adverse drug reactions.Conclusion Different traditional Chinese patent medicines for tonifying the lung and kidney combined with conventional Western medicine have their advantages in the intervention of COPD in the stable stage,and have a better safety profile.Due to the limited quality and quantity of the included studies,more high-quality studies are needed to verify the above conclusion.