Fan Li

Background: Lactylation, a recently identified post-translational modification, plays a critical role in tumor progression and immune regulation. However, its cellular heterogeneity and functional impact in lung adenocarcinoma (LUAD) remain poorly understood. This study was designed as exploratory biological research to characterize lactylation-associated patterns at the single-cell level and to propose a potential lactylation-related prognostic model. Methods: Single-cell transcriptomic data from LUAD and normal lung tissues were analyzed to quantify lactylation activity using AUCell based on 332 lactylation-related genes. Cell-cell communication was inferred using CellChat to identify ligand-receptor interactions among subpopulations. Candidate genes were selected by integrating ligand-receptor pair genes, marker genes from highly lactylated subtypes, and previously reported lactylation-related genes. A total of 101 machine learning model combinations were evaluated to construct the prognostic model. Selected genes were further validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR), and the potential relationship between ANGPTL4 expression and lactylation was examined. Immune characteristics were evaluated using multiple established computational approaches for estimating immune infiltration, dysfunction, and immunogenicity. Results: Lactylation activity was higher in tumor epithelial and stromal cells, with particularly elevated levels in specific epithelial subpopulations. A 12-gene signature was identified, comprising nine risk genes (e.g., ANGPTL4, SOD1, and VEGFC) and three protective genes. The random survival forest (RSF) model demonstrated strong predictive performance [area under the curve (AUC) =0.99 for training, 0.68 for testing], and qRT-PCR validation largely confirmed the predicted gene expression patterns. High-risk patients exhibited poorer survival, reduced immune infiltration, increased immune exclusion, and higher enrichment of immunosuppressive cells. Moreover, ANGPTL4 expression positively correlated with lactylation-associated indicators. Cell-cell communication analysis further highlighted signaling pathways involving the identified genes. Conclusions: This study presents a lactylation-based prognostic model for LUAD and uncovers potential immune-related mechanisms by which highly lactylated epithelial cells may contribute to immune evasion and tumor progression.

Background: The relationship between obesity and respiratory diseases has been widely explored. In this context, the Weight-Adjusted Waist Index (WWI) has emerged as a novel metric for assessing visceral fat. This study aims to evaluate the association between WWI and the risk of emphysema in the U.S. population, by utilizing data from the 2001–2018 National Health and Nutrition Examination Survey (NHANES). Methods: A cross-sectional study was conducted using NHANES data from 2001 to 2018. Logistic regression models were applied to assess the relationship between WWI and emphysema risk. Interaction and subgroup analyses were performed to explore effect modifiers. Results: Our study included a total of 44,949 American adults. The results of the multivariable logistic regression analysis revealed an association between WWI and the incidence of emphysema. In the fully adjusted model, the probability of developing emphysema was 1.5 times higher in the group with WWI > 10.46 compared to those with WWI ≤ 10.46, with an odds ratio of [1.5 (1.1, 1.9), p = 0.003]. Subgroup analysis showed stronger associations among males, non-Hispanic Whites, and individuals with hypertension. Furthermore, we used a two-piece linear regression model and found a nonlinear association between WWI and emphysema, with a breakpoint at 12.5. Conclusions: Our findings indicate a significant association between WWI levels and emphysema. Larger-scale prospective studies are needed to further explore the role of WWI in emphysema.

Original Article Integrative genomic profiling reveals characteristics of lymph node metastasis in small cell lung cancer Kangle Kong, Shan Hu, Jiaqi Yue, Ziheng Yang, Salma K. Jabbour, Yu Deng, Bo Zhao, Fan Li

Tumor metastasis is still an insurmountable obstacle in tumor treatment. Lung cancer represents one of the most common malignancies with high morbidity worldwide. hnRNPA1 has been reported to be involved in the regulation of tumor metastasis, while its specific role in tumor metastasis seems to be controversial and its molecular mechanism in lung cancer metastasis remains to be further elucidated. In this study, we confirmed that knockdown of the hnRNPA1 led to enhanced migration, invasion and EMT transition in lung cancer cells. Bioinformatics analysis of the GSE34992 dataset revealed that hnRNPA1 may regulate the alternative splicing (AS) of LAS1L exon 9. Further AGE assays and RIP assays revealed that hnRNPA1 can directly bind to the LAS1L pre-mRNA to inhibit the splicing of LAS1L exon 9. The RNA pull-down assays showed that hnRNPA1 can specifically bind to the two sites (UAGGGU(WT1) and UGGGGU(WT3)) of LAS1L Intron 9. Further Transwell assays indicated that the expression ratio of LAS1L-L/LAS1L-S regulated by hnRNPA1 can further promote the migration, invasion and EMT transition in lung cancer cells. Moreover, hnRNPA1 expression showed significant heterogeneity in lung cancer tissues, which may contain new research directions and potential therapeutic targets. Our results indicate that hnRNPA1 can affect the metastasis of lung cancer cells by modulating the AS of LAS1L exon 9, highlighting the potential significance of hnRNPA1 in lung cancer metastasis.

The survival rate of patients with lung adenocarcinoma (LUAD) is low. This study analyzed the correlation between the expression of long noncoding RNA (lncRNA) and epigenetic alterations along with the investigation of the prognostic value of these outcomes for LUAD. Differentially expressed lncRNAs were identified based on multiomic data and positively related genes using DESeq2 in R, differentially histone-modifying genes specific to LUAD based on histone modification data, gene enhancers from information collected from the FANTOM5 (Function Annotation Of The Mammalian Genome-5) (fantom.gsc.riken.jp/5) human enhancer database, gene promoters using the ChIPseeker and the human lincRNAs Transcripts database in R, and differentially methylated regions (DMRs) using Bumphunter in R. Overall survival was estimated by Kaplan-Meier, comparisons were performed among groups using log-rank tests to derive differences between sample subclasses, and epigenetic lncRNAs (epi-lncRNAs) potentially relevant to LUAD prognosis were identified. A total of seven dysregulated epi-lncRNAs in LUAD were identified by comparing histone modifications and alterations in histone methylation regions on lncRNA promoter and enhancer elements, including H3K4me2, H3K27me3, H3K4me1, H3K9me3, H4K20me1, H3K9ac, H3K79me2, H3K27ac, H3K4me3, and H3K36me3. Furthermore, 69 LUAD-specific dysregulated epi-lncRNAs were identified. Moreover, lncRNAs-based prognostic analysis of LUAD samples was performed and explored that seven of these lncRNAs, including A2M-AS1, AL161431.1, DDX11-AS1, FAM83A-AS1, MHENCR, MNX1-AS1, and NKILA (7-EpiLncRNA), showed the potential to serve as markers for LUAD prognosis. Additionally, patients having a high 7-EpiLncRNA score showed a generally more unfavorable prognosis compared with those which scored lower. Seven lncRNAs were identified as markers of prognosis in patients with LUAD. The outcomes of this research will help us understand epigenetically aberrant regulation of lncRNA expression in LUAD in a better way and have implications for research advances in the regulatory role of lncRNAs in LUAD.

Background. Glycolysis is closely associated with tumor progression, but the roles of lncRNAs in glycolysis have not been comprehensively investigated in lung adenocarcinoma (LUAD). This study is aimed at studying the possible mechanisms of glycolysis‐related lncRNAs in tumor development and providing a guidance for targeted therapy. Methods. Unsupervised consensus clustering was used to identify molecular subtypes. Gene enrichment analysis was applied to screen important pathways involved in tumor progression. A series of immune analysis was performed to assess immune infiltration. Critical transcription factors (TFs) interacting with lncRNAs were selected by Pearson correlation analysis. A first‐order partial correlation analysis was implemented to identify critical lncRNAs with prognostic significance. Results. Three molecular subtypes (C1, C2, and C3) were identified with distinct overall survival. Three subtypes showed differential immune infiltration, and C3 subtype was the optimal for immunotherapy treatment. Ten lncRNA‐TF pairs among four glycolysis‐related lncRNAs (FTX, LINC00472, PSMA3‐AS1, and SNHG14) and six TFs (FOXP1, SP1, MYC, FOXM1, HIF1A, and FOS) were involved in tumor progression. We identified four critical glycolysis‐related lncRNAs significantly associated with prognosis. Conclusions. This study identified three molecular subtypes that could guide personalized therapy. The four‐lncRNA prognostic model can serve as an indicator for predicting prognosis or early screening of lung adenocarcinoma patients. The current results improve the understanding of the relation between lncRNAs and glycolysis.

To compare the perioperative and follow-up outcomes of patients with myasthenia gravis (MG) receiving subxiphoid-subcostal or unilateral thoracoscopic thymectomy and to identify the factors affecting MG prognosis. From January 2013 to December 2019, a total of 137 consecutive MG patients received subxiphoid-subcostal thoracoscopic thymectomy (STT, n = 65) or conventional unilateral thoracoscopic thymectomy (UTT, n = 72). The primary outcomes of this study were perioperative complications, duration and expenses of hospitalization, VAS score and complete stable remission (CSR). The patients receiving STT had significantly shorter drainage duration and postoperative hospital stay and lower hospitalization expenses (P < 0.01). Pain scores on postoperative Days 1, 3, 7 and 14 were significantly lower in patients undergoing STT (P < 0.01). The average follow-up was 54.3 ± 24.18 months, with a CSR rate of 30.6% and an overall effective rate of 87.3%. Through uni- and multivariable analyses, shorter symptom duration and Myasthenia Gravis Foundation of America (MGFA) class I were independent predictors for CSR in MG patients receiving thymectomy. The present study not only showed that STT was a safe and feasible technique for MG, with a potentially faster postoperative recovery, lower hospitalization expenses, less postoperative pain and equivalent remission rate, but also revealed that shorter symptom duration and MGFA class I were favourable prognostic factors for CSR.

Intubated general anesthesia and single-lung ventilation are considered mandatory for conventional thoracoscopic surgery. Non-intubated thoracoscopic thymectomy is technically challenging. The aim of this article was to present the initial results of non-intubated subxiphoid-subcostal thoracoscopic thymectomy (NI-STT) under LMA management for patients with thymic tumor or myasthenia gravis (MG) and to investigate the feasibility and safety of the procedure. A retrospective analysis of patients undergoing NI-STT for thymic tumor or MG at our department from January 2017 to January 2020 was performed. The clinical characteristics and perioperative outcomes of the patients were reviewed and analyzed. A total of 61 patients were received NI-STT in this analysis, of which 19 patients with MG undergone an extended thymectomy and the rest (n=42) undergone a partial thymectomy. The anesthetic induction duration, surgical duration and global operating room duration were 24.83±12.27 min, 118.75±32.49 min and 173.51±41.80 min, respectively. The lowest SpO2 and peak EtCO2 during operation were 96.15±2.93 mmHg and 41.79±7.53 mmHg, respectively. The mean duration of chest drainage and postoperative hospital stays were 1.87 days, and 2.91 days, respectively. Three cases had sore throat and irritable cough and two cases suffered nausea and vomiting occurred. one patient suffered from an atrial fibrillation, two patients experienced pneumonia, and one patient suffered wound infection, respectively. There were no phrenic nerve paralysis and mortality occurred in the study group. The postoperative pain was low on 1,3, 7, 14, 30, 90 and 180 postoperative days. NI-STT was a technically safe and feasible approach for treating thymic tumors or MG. It could be an alternative to intubated single-lung ventilation for thymectomy in selected patients.

Purpose: We aim to investigate the incidence, clinical course, and risk factors for developing postoperative hyphema after 23-gauge pars plana vitrectomy (PPV) for patients with proliferative diabetic retinopathy (PDR) without neovascularization of the iris or angles and neovascular glaucoma (NVG). Methods: This retrospective study included 155 consecutive eyes from 124 patients with at least three-month follow-up who underwent PPV for PDR without neovascularization of the iris or angles and NVG. Demographic data, surgery notes, postoperative hyphema assessment, intraocular pressure (IOP), and the surgical outcome were recorded. Results: Postoperative hyphema occurred in 18 of 155 eyes (11.6%), with 14 of those having hyphema on day 1, and 4 having hyphema on days 7– 20. Of the 18 eyes, only 3 (16.7%) had normal IOP, and immediate intraocular hypertension was observed in 15 (83.3%). Seven eyes required anterior chamber paracentesis and five needed anterior chamber irrigation. The average time for absorption of the hyphema was 13.1 days, and IOP was controlled in all cases. There was a significant correlation between membrane removal and the development of hyphema (OR = 5.65 and 95% CI: 1.190– 25.203; p = 0.013). No recurrence of hyphema was observed. In patients with hyphema, the final best corrected visual acuity (BCVA) was 1.75 ± 0.84 logMAR, which improved significantly compared to the initial BCVA of 2.20 ± 0.65 logMAR (t = 3.893; p = 0.001), and the final anatomic success rate was 100%. Conclusion: The development of hyphema is not uncommon after PPV for patients with PDR without neovascularization of the iris or angles and NVG, and membrane removal is a risk factor for postoperative hyphema. The timely management of hyphema ensures that hyphema does not affect the visual recovery or the final anatomical success.

Background. The widespread use of low-dose chest CT screening has improved the detection of early lung adenocarcinoma. Radical surgery is the best treatment strategy for patients with early lung adenocarcinoma; however, some patients present with postoperative recurrence and poor prognosis. Through this study, we hope to establish a model that can identify patients that are prone to recurrence and have poor prognosis after surgery for early lung adenocarcinoma. Materials and Methods. We screened prognostic and relapse-related genes using The Cancer Genome Atlas (TCGA) database and the GSE50081 dataset from the Gene Expression Omnibus (GEO) database. The GSE30219 dataset was used to further screen target genes and construct a risk prognosis signature. Time-dependent ROC analysis, calibration degree analysis, and DCA were used to evaluate the reliability of the model. We validated the TCGA dataset, GSE50081, and GSE30219 internally. External validation was conducted in the GSE31210 dataset. Results. A novel four-gene signature (INPP5B, FOSL2, CDCA3, RASAL2) was established to predict relapse-related survival outcomes in patients with early lung adenocarcinoma after surgery. The discovery of these genes may reveal the molecular mechanism of recurrence and poor prognosis of early lung adenocarcinoma. In addition, ROC analysis, calibration analysis and DCA were used to verify the genetic signature internally and externally. Our results showed that our gene signature had a good predictive ability for recurrence and prognosis. Conclusions. We established a four-gene signature and predictive model to predict the recurrence and corresponding survival rates in patients with early lung adenocarcinoma after surgery. These may be helpful for reforumulating post-operative consolidation treatment strategies.