Mesoporous Cubic Nanocages Assembled by Coupled Monolayers With 100% Theoretical Capacity and Robust Cycling.

High capacity and long cycling often conflict with each other in electrode materials. Despite extensive efforts in structural design, it remains challenging to simultaneously achieve dual high electrochemical properties. In this study, we prepared brand-new completely uniform mesoporous cubic-cages assembled by large d-spacing Ni(OH)2 coupled monolayers intercalated with VO4 3- (NiCMCs) using a biomimetic approach. Such unique mesoporous structural configuration results in an almost full atomic exposure with an amazing specific surface area of 505 m2/g and atomic utilization efficiency close to the theoretical limit, which is the highest value and far surpasses all of the reported Ni(OH)2. Thus, a breakthrough in simultaneously attaining high capacity approaching the 100% theoretical value and robust cycling of 10,000 cycles is achieved, setting a new precedent in achieving double-high attributes. When combined with high-performance Bi2O3 hexagonal nanotubes, the resulting aqueous battery exhibits an ultrahigh energy density of 115 Wh/kg and an outstanding power density of 9.5 kW/kg among the same kind. Characterizations and simulations reveal the important role of large interlayer spacing intercalation units and mesoporous cages for excellent electrochemical thermodynamics and kinetics. This work represents a milestone in developing "double-high" electrode materials, pointing in the direction for related research and paving the way for their practical application.

Risk Factors and Prognosis of Perioperative Atrial Fibrillation in Elderly Patients Undergoing VATS Lung Surgery: A Retrospective Cohort Study.

Background: Atrial fibrillation (AF) has become the most common postoperative arrhythmia of thoracic surgery. This study aimed to investigate the risk factors and complications of perioperative atrial fibrillation (PoAF) in elderly patients who underwent video-assisted thoracoscopic surgery (VATS). Methods: Data were collected from patients who underwent VATS between January 2013 and December 2022 at Peking Union Medical College Hospital (PUMCH). Univariable analyses and multivariable logistic regression analyses were used to determine the factors correlated with PoAF. Receiver operating characteristic (ROC) curve was used to evaluate the discrimination of the indicators to predict PoAF. Results: The study enrolled 2920 patients, with a PoAF incidence of 5.2% (95% CI 4.4%-6.0%). In the logistic regression analyses, male sex (OR=1.496, 95% CI 1.056-2.129, P=0.024), left atrial anteroposterior dimension (LAD) ≥40 mm (OR=2.154, 95% CI 1.235-3.578, P=0.004), hypertension (HTN) without regular treatment (OR=2.044, 95% CI 0.961-3.921, P=0.044), a history of hyperthyroidism (OR=4.443, 95% CI 0.947-15.306, P=0.030), surgery of the left upper lobe (compared to other lung lobes) (OR=1.625, 95% CI 1.139-2.297, P=0.007), postoperative high blood glucose (BG) (OR=2.482, 95% CI 0.912-5.688, P=0.048), and the time of chest tube removal (per day postoperatively) (OR=1.116, 95% CI 1.038-1.195, P=0.002) were found to be significantly associated with PoAF. The area under the ROC curve was 0.707 (95% CI 0.519-0.799). 86.9% patients were successfully converted to sinus rhythm. Compared with the non-PoAF group, the PoAF group had significantly greater risks of prolonged air leakage, postoperative acute coronary syndrome, longer ICU stays, and longer hospital stays. Conclusion: Male sex, LAD≥40 mm, HTN without regular treatment, a history of hyperthyroidism, surgery of the left upper lobe, postoperative BG, and the time of chest tube removal were associated with PoAF. These findings may help clinicians identify high-risk patients and take preventive measures to minimize the incidence and adverse prognosis of PoAF.

Revolutionizing thoracic surgery education: a bibliometric analysis of the past decade's literature.

OBJECTIVES: Thoracic surgery is a complex field requiring advanced technical skills and critical decision-making. Surgical education must evolve to equip trainees with proficiency in new techniques and technologies. METHODS: This bibliometric analysis systematically reviewed 113 articles on thoracic surgery skills training published over the past decade, retrieved from databases including Web of Science. Publication trends, citation analysis, author and journal productivity, and keyword frequencies were evaluated. RESULTS: The United States contributed the most publications, led by pioneering institutions. Simulation training progressed from basic to sophisticated modalities and virtual reality emerged with transformative potential. Minimally invasive techniques posed unique learning challenges requiring integrated curricula. CONCLUSION: Ongoing investments in educational research and curriculum innovations are imperative to advance thoracic surgery training through multidisciplinary strategies. This study provides an evidentiary foundation to optimize training and address the complexities of modern thoracic surgery.

Bibliometric analysis of the top 100 highly cited articles on sublobectomy for non-small cell lung cancer.

OBJECTIVES: The goal of this research is to pinpoint the top 100 most frequently referenced studies on sublobectomy for non-small cell lung cancer. METHODS: We identified the top 100 most frequently referenced studies on sublobectomy for non-small cell lung cancer by searching the Web of Science database. We extracted key information from the selected studies, including the author, journal, impact factor, type of article, year of publication, country, organization, and keyword. RESULTS: To the best of our understanding, this is the inaugural bibliometric study on sublobectomy for non-small cell lung cancer. The publication years of the top 100 most frequently referenced studies span from 1994 to 2022, with citation counts ranging from 51 to 795. The majority of the included studies are original (93/100) and primarily retrospective studies (82/93). The United States leads in terms of published articles and citations, with the Annals of Thoracic Surgery being the most frequently sourced journal (n = 27). High-density keywords primarily originate from limited resection, lobectomy, survival, carcinoma, recurrence, randomized trial, radiotherapy, lung cancer, outcome, 2 cm, as revealed by CiteSpace analysis. CONCLUSIONS: Our research compiles and analyzes the top 100 most frequently referenced studies in the field of sublobectomy for non-small cell lung cancer. The United States has the most published and cited works on this topic. Currently, the hot keywords for sublobectomy research are gradually shifting towards prognosis and obtaining better evidence-based medical evidence to demonstrate its value in the treatment of non-small cell lung cancer.

Prognostic factors and nomogram for pulmonary resected high-grade neuroendocrine carcinomas: a 20-year single institutional real-world experience.

BACKGROUND: Pulmonary high-grade neuroendocrine carcinomas(pHGNEC) encompassing small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) are clinically aggressive tumors with poor prognosis. The role of surgery and prognostic factors guiding management remain unclear. We aimed to analyze prognosis following resection and identify predictive variables. METHODS: This retrospective study analyzed 259 patients undergoing pHGNEC resection from 2001-2023. Overall survival (OS) and disease-free survival (DFS) were evaluated using Kaplan-Meier curves. Prognostic factors were assessed with Cox regression and visualized using nomogram tools. RESULTS: Minimally invasive surgery was associated with better OS (p = 0.001) and DFS (p = 0.001). Higher T stage predicted worse OS (T2 p = 0.044, T4 p = 0.007) and DFS (T2 p = 0.020, T4 p = 0.004). Advanced TNM stage III (OS p = 0.018; DFS p = 0.015) and IV (OS p < 0.001; DFS p < 0.001) also correlated with poorer prognosis. In the SCLC subgroup, elevated preoperative CEA independently predicted worse OS (p = 0.012) and DFS (p = 0.004). T4 disease (OS p < 0.001; DFS p = 0.002) and advanced TNM staging (stage III OS p = 0.043; DFS p = 0.045; stage IV OS p < 0.001, DFS p < 0.001) were associated with worse outcomes. In LCNEC patients, VATS resection improved OS (p = 0.048) and DFS (p = 0.027) despite conversion. Prior malignancy predicted worse OS (p < 0.001). Advanced TNM disease (stage III OS p = 0.047; stage IV OS p = 0.003, DFS p = 0.005) were also negative prognostic factors. The prognostic nomogram incorporating above variables effectively stratified risk. Calibration plots revealed good correlation between predicted and actual survival. CONCLUSIONS: We identified minimally invasive surgery, early TNM stage, younger age, and normal preoperative CEA as positive prognostic factors following pHGNEC resection. Our study provides an applicable prognostic nomogram to facilitate personalized pHGNEC management.

[Application and Research Progress of Lung Cancer Organoid in Precision Medicine 
for Lung Cancer].

The continuous advancement of molecular detection technology has greatly propelled the development of precision medicine for lung cancer. However, tumor heterogeneity is closely associated with tumor metastasis, recurrence, and drug resistance. Additionally, different lung cancer patients with the same genetic mutation may exhibit varying treatment responses to different therapeutic strategies. Therefore, the development of modern precision medicine urgently requires the precise formulation of personalized treatment strategies through personalized tumor models. Lung cancer organoid (LCO) can highly simulate the biological characteristics of tumor in vivo, facilitating the application of innovative drugs such as antibody-drug conjugate in precision medicine for lung cancer. With the development of co-culture model of LCO with tumor microenvironment and tissue engineering technology such as microfluidic chip, LCO can better preserve the biological characteristics and functions of tumor tissue, further improving high-throughput and automated drug sensitivity experiment. In this review, we combine the latest research progress to summarize the application progress and challenges of LCO in precision medicine for lung cancer.
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Real-world efficacy of adjuvant therapy for totally resected stage I lung adenocarcinoma patients with pathological high-risk factors: propensity score analysis.

BACKGROUND: We investigated the real-world efficacy of adjuvant therapy for stage I lung adenocarcinoma patients with pathological high-risk factors. METHODS: Study participants were enrolled from November 1, 2016 and December 31, 2020. Clinical bias was balanced by propensity score matching. Disease-free survival (DFS) outcomes were compared by Kaplan-Meier analysis. The Cox proportional hazards regression was used to identify survival-associated factors. p ≤ 0.05 was the threshold for statistical significance. RESULTS: A total of 454 patients, among whom 134 (29.5%) underwent adjuvant therapy, were enrolled in this study. One hundred and eighteen of the patients who underwent adjuvant therapy were well matched with non-treatment patients. Prognostic outcomes of the treatment group were significantly better than those of the non-treatment group, as revealed by Kaplan-Meier analysis after PSM. Differences in prevention of recurrence or metastasis between the targeted therapy and chemotherapy groups were insignificant. Adjuvant therapy was found to be positive prognostic factors, tumor size and solid growth patterns were negative. CONCLUSIONS: Adjuvant therapy significantly improved the DFS for stage I lung adenocarcinoma patients with high-risk factors. Larger prospective clinical trials should be performed to verify our findings.

Clonal expansion of shared T cell receptors reveals the existence of immune commonality among different lesions of synchronous multiple primary lung cancer.

The increase in the detection rate of synchronous multiple primary lung cancer (MPLC) has posed remarkable clinical challenges due to the limited understanding of its pathogenesis and molecular features. Here, comprehensive comparisons of genomic and immunologic features between MPLC and solitary lung cancer nodule (SN), as well as different lesions of the same patient, were performed. Compared with SN, MPLC displayed a lower rate of EGFR mutation but higher rates of BRAF, MAP2K1, and MTOR mutation, which function exactly in the upstream and downstream of the same signaling pathway. Considerable heterogeneity in T cell receptor (TCR) repertoire exists among not only different patients but also among different lesions of the same patient. Invasive lesions of MPLC exhibited significantly higher TCR diversity and lower TCR expansion than those of SN. Intriguingly, different lesions of the same patient always shared a certain proportion of TCR clonotypes. Significant clonal expansion could be observed in shared TCR clonotypes, particularly in those existing in all lesions of the same patient. In conclusion, this study provided evidences of the distinctive mutational landscape, activation of oncogenic signaling pathways, and TCR repertoire in MPLC as compared with SN. The significant clonal expansion of shared TCR clonotypes demonstrated the existence of immune commonality among different lesions of the same patient and shed new light on the individually tailored precision therapy for MPLC.

Enhanced Survival with Lymphadenectomy in Early-Stage Metachronous Second Primary Lung Cancer: A Retrospective Analysis.

INTRODUCTION: Lymphadenectomy is a cornerstone in the surgical management of resectable primary lung cancer. However, its prognostic significance in early-stage metachronous second primary lung cancer (MSPLC) remains poorly understood. This retrospective study aimed to evaluate the prognostic impact of lymphadenectomy in these patients using data from the Surveillance, Epidemiology, and End Results (SEER) Database. METHODS: A retrospective cohort study was conducted using data from the SEER Database for patients surgically treated for stage I MSPLC between 2004 and 2015. Propensity score-matching was employed to create comparable cohorts, and the Cox proportional hazards model was utilized to estimate the hazard ratio (HR) for overall survival after lymphadenectomy compared to non-lymphadenectomy. Survival analysis was performed using Kaplan-Meier curves and the log-rank test. RESULTS: Among 920 identified patients with MSPLC, 574 (62.4%) underwent lymphadenectomy. Propensity score-matching yielded 255 patients in both the lymphadenectomy and non-lymphadenectomy groups. Over a median follow-up of 38 months, the 5-year overall survival probability after a diagnosis of MSPLC was 58.7% in the lymphadenectomy group and 43.9% in the non-lymphadenectomy group (HR: 0.76; 95% confidence interval 0.64-0.90; p = 0.002). CONCLUSION: In this population-based study, lymphadenectomy is associated with prolonged overall survival in patients with stage I MSPLC. These findings suggest the potential benefit of incorporating lymphadenectomy into the surgical management of MSPLC, providing valuable guidance for thoracic surgeons in clinical decision-making.

Artificial dermis combined with negative pressure wound therapy and platelet-rich plasma to treat traumatic wounds: a retrospective study.

OBJECTIVE: The reconstruction of complex soft tissue defects with exposure of bones and tendons represents an increasing challenge in wound care, especially in large extremity wounds. The aim of this study was to detect the clinical efficacy of combined use of negative pressure wound therapy (NPWT), artificial dermis (ADM), platelet-rich plasma (PRP) and split-thickness skin grafting (STSG) in the reconstruction of large traumatic extremity skin defects. METHOD: In this study, eight cases were treated with combined therapies for repairing complex extremity wounds and the results were reviewed retrospectively. After surgical debridement, all wounds received ADM, PRP and delayed STSG, which were all aided with NPWT. RESULTS: The patients consisted of five males and three females, with a mean age of 44 years. A total of six lower extremity wounds were located at the foot/ankle, with exposed tendon in five, bone exposure in three and both in two. Of the group, two patients had exposed tendon on arm/hand wounds. The size of wounds and ADM averaged 126cm2 and 42.3cm2, respectively. ADM was used to cover the exposed bone or tendon, the granulation and muscular tissue were covered with vacuum sealing drainage (VSD) directly, for NPWT. The survival rate of ADM averaged 98.9%. The average time for survival of ADM was 12.8 days and the mean uptake of autologous skin graft was 93.5%. Only one patient received repeated skin grafts. All patients achieved successful healing and reported no complications. The mean length of hospital stay was 36.1 days. CONCLUSION: Our study revealed that ADM in conjunction with NPWT, PRP and STSG could be used for repairing large traumatic extremity wounds. Wound closure was achieved without flaps, the aesthetic and functional outcomes were acceptable, and only one patient developed a 35% loss of skin graft. DECLARATION OF INTEREST: This work was supported by grants from the Natural Science Foundation of Hubei Province (grant no. 2020CFB464) and Youth Foundation of Wuhan Municipal Health Commission (grant no. WX20Q15). The authors have no conflicts of interest to declare.

Adjuvant Osimertinib in Patients With Stage IB to IIIA EGFR Mutation-Positive NSCLC After Complete Tumor Resection: ADAURA China Subgroup Analysis.

Introduction: In Chinese patients with NSCLC, prevalence of EGFR-mutated (EGFRm) disease is high. In the global phase 3 ADAURA study (NCT02511106), adjuvant osimertinib was found to have a statistically significant and clinically meaningful improvement in disease-free survival (DFS) versus placebo in resected stage IB to IIIA EGFRm NSCLC. We present efficacy and safety data from a subgroup analysis of 159 Chinese patients enrolled in the People's Republic of China from ADAURA. Methods: In ADAURA, patients with completely resected stage IB to IIIA EGFRm (exon 19 deletion/exon 21 L858R) NSCLC were randomized 1:1 to receive osimertinib (80 mg once daily) or placebo for 3 years or until disease recurrence/discontinuation. Adjuvant chemotherapy was permitted before randomization, per physician/patient choice. Primary end point was investigator-assessed DFS in stage II to IIIA disease; secondary end points included DFS in stage IB to IIIA (overall population), overall survival, health-related quality of life (HRQoL), and safety. Results: Of 682 patients enrolled globally, 159 patients in the People's Republic of China were included in this subgroup analysis (osimertinib n = 77; placebo n = 82). Baseline characteristics were balanced across the treatment arms. At data cutoff, stage II to IIIA DFS hazard ratio (HR) was 0.23 (95% confidence interval [CI]: 0.13-0.42; maturity 59%); stage IB to IIIA DFS HR was 0.29 (95% CI: 0.17-0.48; maturity 42%). At 13% maturity (21 deaths), HR for overall survival in the stage IB to IIIA population was 0.51 (95% CI: 0.21-1.20). HRQoL was maintained from baseline, and safety was consistent with the global population. Conclusions: In this population of Chinese patients from ADAURA, adjuvant osimertinib was found to have a clinically meaningful improvement in DFS versus placebo, with maintained HRQoL and a safety profile consistent with the global study population.

Re-exploration of prognosis in type B thymomas: establishment of a predictive nomogram model.

OBJECTIVE: To explore the risk factors for disease progression after initial treatment of type B thymomas using a predictive nomogram model. METHODS: A single-center retrospective study of patients with type B thymoma was performed. The Cox proportional hazard model was used for univariate and multivariate analyses. Variables with statistical and clinical significance in the multivariate Cox regression were integrated into a nomogram to establish a predictive model for disease progression. RESULTS: A total of 353 cases with type B thymoma were retrieved between January 2012 and December 2021. The median follow-up was 58 months (range: 1-128 months). The 10-year progression-free survival (PFS) was 91.8%. The final nomogram model included R0 resection status and Masaoka stage, with a concordance index of 0.880. Non-R0 resection and advanced Masaoka stage were negative prognostic factors for disease progression (p < 0.001). No benefits of postoperative radiotherapy (PORT) were observed in patients with advanced stage and non-R0 resection (p = 0.114 and 0.284, respectively). CONCLUSION: The best treatment strategy for type B thymoma is the detection and achievement of R0 resection as early as possible. Long-term follow-up is necessary, especially for patients with advanced Masaoka stage and who have not achieved R0 resection. No prognostic benefits were observed for PORT.

[Relationship between Bacteria in the Lower Respiratory Tract/Lung Cancer 
and the Development of Lung Cancer as well as Its Clinical Application].

Due to the advancement of 16S rRNA sequencing technology, the lower respiratory tract microbiota, which was considered non-existent, has been revealed. The correlation between these microorganisms and diseases such as tumor has been a hot topic in recent years. As the bacteria in the surrounding can infiltrate the tumors, researchers have also begun to pay attention to the biological behavior of tumor bacteria and their interaction with tumors. In this review, we present the characteristic of the lower respiratory tract bacteria and summarize recent research findings on the relationship between these microbiota and lung cancer. On top of that, we also summarize the basic feature of bacteria in tumors and focus on the characteristic of the bacteria in lung cancer. The relationship between bacteria in lung cancer and tumor development is also been discussed. Finally, we review the potential clinical applications of bacterial communities in the lower respiratory tract and lung cancer, and summarize key points of sample collection, sequencing, and contamination control, hoping to provide new ideas for the screening and treatment of tumors.
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GOLM1 Promotes Pulmonary Fibrosis through Upregulation of NEAT1.

Idiopathic pulmonary fibrosis (IPF) is a lethal progressive disease with elusive molecular mechanisms and limited therapeutic options. Aberrant activation of fibroblasts is a central hallmark of lung fibrosis. Here, we report that Golgi membrane protein 1 (GOLM1, also known as GP73 or GOLPH2) was increased in the lungs of patients with pulmonary fibrosis and mice with bleomycin (BLM)-induced pulmonary fibrosis. Loss of GOLM1 inhibited proliferation, differentiation, and extracellular matrix deposition of fibroblasts, whereas overexpression of GOLM1 exerted the opposite effects. Similarly, worsening pulmonary fibrosis after BLM treatment was observed in GOLM1-knock-in mice, whereas BLM-treated Golm1-knockout mice exhibited alleviated pulmonary fibrosis and collagen deposition. Furthermore, we identified long noncoding RNA NEAT1 downstream of GOLM1 as a potential mediator of pulmonary fibrosis through increased GOLM1 expression. Depletion of NEAT1 inhibited fibroblast proliferation and extracellular matrix production and reversed the profibrotic effects of GOLM1 overexpression. Additionally, we identified KLF4 as a downstream mediator of GOLM1 signaling to NEAT1. Our findings suggest that GOLM1 plays a pivotal role in promoting pulmonary fibrosis through the GOLM1-KLF4-NEAT1 signaling axis. Targeting GOLM1 and its downstream pathways may represent a novel therapeutic strategy for treating pulmonary fibrosis.

Adjuvant crizotinib treatment selected by patient-derived organoids in a patient with stage IIIA adenocarcinoma with novel LRRTM4-ALK fusion: a case report.

Background: Over 90 different anaplastic lymphoma kinase (ALK) fusions have been reported, and patients with different ALK fusion partners exhibit different responses to targeted therapy. Patient-derived organoid (PDO), a kind of 3-dimensional culture, is a promising model for drug-sensitivity testing for personalized treatment decision-making. It further has the potential to provide treatment strategy for patients with novel mutations, rare mutations, and concomitant mutations, serving as a supplement to evidence-based medicine. Case Description: We report a case in which a man with stage IIIA adenocarcinoma had pleural effusion 1 month after surgery. A novel leucine-rich repeat transmembrane neuronal protein 4 (LRRTM4)-ALK fusion was unveiled by next-generation sequencing (NGS), and PDOs were used in drug-sensitivity testing to select a proper adjuvant therapy for this patient. We chose crizotinib based on result of the test and drugs' availability in China and helped the patient achieve a more than 3-year-long disease-free survival (DFS). Higher variant allele frequencies (VAFs) of the driver mutation were also found in PDOs and their waste culture medium, indicating that the PDO model could filter out cells with driver genes or stemness and help us to identify the critical cancer cell colony in treatment decision-making. Conclusions: For the first time, we report the case of a LRRTM4-ALK fusion. The patient achieved a more than 3-year long-term DFS under crizotinib treatment, which was selected by an emerging PDO drug-sensitivity test model. We also discovered the enrichment of a low-abundance driver mutation in PDO and its waste culture medium, providing a new direction for future research.

Preliminary analysis of immune-related markers in thymic carcinoid.

The immune-related microenvironment of thymic carcinoid has rarely been reported. We analyzed the expression of PD-L1 and VISTA, and the distribution of CD4+ T cells, CD8+ T cells and CD68+ macrophages in the thymic carcinoid by immunohistochemical staining, and showed the correlation between these markers and clinical survival, indicating the potential therapeutic prospects.

Influence of treatment-related lymphopenia on the efficacy of immune checkpoint inhibitors in lung cancer: a meta-analysis.

Background: Treatment-related lymphopenia (TRL) is common in patients with lung cancer, particularly in those with radiotherapy. However, the influence of TRL on the efficacy of immune checkpoint inhibitors (ICIs) for patients with lung cancer remains poorly understood. We performed a systematic review and meta-analysis to investigate the influence of TRL on survival of lung cancer patients on ICIs. Methods: In order to accomplish the aim of the meta-analysis, a comprehensive search was conducted on databases including PubMed, Embase, Cochrane Library, and the Web of Science to identify observational studies with longitudinal follow-up. The Cochrane Q test was employed to evaluate heterogeneity among the included studies, while the I2 statistic was estimated. Random-effects models were utilized to merge the results, considering the potential impact of heterogeneity. Results: Ten cohort studies with 1130 lung cancer patients who were treated with ICIs were included. Among them, 427 (37.8%) had TRL. Pooled results showed that compared to patients without TRL, patients with TRL were associated with poor progression-free survival (hazard ratio [HR]: 2.05, 95% confidence interval [CI]: 1.62 to 2.60, p < 0.001; I2 = 22%) and overall survival (HR: 2.69, 95% CI: 2.10 to 3.43, p < 0.001; I2 = 0%). Sensitivity analysis limited to patients with non-small cell lung cancer showed similar results (HR: 2.66 and 2.62, both p < 0.05). Moreover, subgroup analyses according to the diagnostic criteria of TRL, regression analysis model (univariate or multivariate), and indications of ICIs (for locally advanced or advanced lung cancer) showed consistent results (p for subgroup difference all > 0.05). Conclusion: TRL was associated with poor survival of lung cancer patients who were treated with ICIs.

SUMOylation-triggered ALIX activation modulates extracellular vesicles circTLCD4-RWDD3 to promote lymphatic metastasis of non-small cell lung cancer.

Lymph node (LN) metastasis is one of the predominant metastatic routes of non-small cell lung cancer (NSCLC) and is considered as a leading cause for the unsatisfactory prognosis of patients. Although lymphangiogenesis is well-recognized as a crucial process in mediating LN metastasis, the regulatory mechanism involving lymphangiogenesis and LN metastasis in NSCLC remains unclear. In this study, we employed high-throughput sequencing to identify a novel circular RNA (circRNA), circTLCD4-RWDD3, which was significantly upregulated in extracellular vesicles (EVs) from LN metastatic NSCLC and was positively associated with deteriorated OS and DFS of patients with NSCLC from multicenter clinical cohort. Downregulating the expression of EV-packaged circTLCD4-RWDD3 inhibited lymphangiogenesis and LN metastasis of NSCLC both in vitro and in vivo. Mechanically, circTLCD4-RWDD3 physically interacted with hnRNPA2B1 and mediated the SUMO2 modification at K108 residue of hnRNPA2B1 by upregulating UBC9. Subsequently, circTLCD4-RWDD3-induced SUMOylated hnRNPA2B1 was recognized by the SUMO interaction motif (SIM) of ALIX and activated ALIX to recruit ESCRT-III, thereby facilitating the sorting of circTLCD4-RWDD3 into NSCLC cell-derived EVs. Moreover, EV-packaged circTLCD4-RWDD3 was internalized by lymphatic endothelial cells to activate the transcription of PROX1, resulting in the lymphangiogenesis and LN metastasis of NSCLC. Importantly, blocking EV-mediated transmission of circTLCD4-RWDD3 via mutating SIM in ALIX or K108 residue of hnRNPA2B1 inhibited the lymphangiogenesis and LN metastasis of NSCLC in vivo. Our findings reveal a precise mechanism underlying SUMOylated hnRNPA2B1-induced EV packaging of circTLCD4-RWDD3 in facilitating LN metastasis of NSCLC, suggesting that EV-packaged circTLCD4-RWDD3 could be a potential therapeutic target against LN metastatic NSCLC.

Physical activity and cancer risk: a dose-response analysis for the Global Burden of Disease Study 2019.

OBJECTIVE: Adopting a healthy lifestyle, including regular physical activity, is widely believed to decrease cancer risk. This study aimed to quantitatively establish the dose-response relationships between total physical activity and the risk of breast, colon, lung, gastric, and liver cancers. METHODS: A systematic review and dose-response analysis were conducted using PubMed and Embase from January 1, 1980 to March 20, 2023. Prospective cohort studies that examined the association between physical activity and the risks of any of the 5 outcomes were included. The search was confined to publications in the English language with a specific focus on human studies. Physical activity is standardized by using the data from US National Health and Nutrition Examination Surveys (NHANES) and the Global Burden of Disease 2019 database. RESULTS: A total of 98 studies, involving a combined population of 16,418,361 individuals, were included in the analysis. Among the included studies, 57 focused on breast cancer, 17 on lung cancer, 23 on colon cancer, 5 on gastric cancer, and 7 on liver cancer. Overall, elevated levels of physical activity exhibited an inverse correlation with the risk of cancer. The dose-response curve for lung cancer exhibited a non-linear pattern, with the greatest benefit risk reduction observed at 13,200 MET-minutes/week of physical activity, resulting in a 14.7% reduction in risk (relative risk 0.853, uncertainty interval 0.798 to 0.912) compared to the inactive population. In contrast, the dose-response curves for colon, gastric, breast, and liver cancers showed linear associations, indicating that heightened levels of total physical activity were consistently associated with reduced cancer risks. However, the increase in physical activity yielded a smaller risk reduction for colon and gastric cancers compared to breast and liver cancers. Compared to individuals with insufficient activity (total activity level < 600 MET-minutes/week), individuals with high levels of activity (≥ 8,000 MET-minutes/week) experienced a 10.3% (0.897, 0.860 to 0.934) risk reduction for breast cancer; 5.9% (0.941, 0.884 to 1.001) for lung cancer; 7.1% (0.929, 0.909 to 0.949) for colon cancer; 5.1% (0.949, 0.908 to 0.992) for gastric cancer; 17.1% (0.829, 0.760 to 0.903) for liver cancer. CONCLUSIONS: This study demonstrated a significant inverse relationship between total physical activity and the risk of breast, gastric, liver, colon, and lung cancers.